Avenues for patient safety education.
\r\n\tThe main goal of this book is (1) prevention and treatment of life-related diseases and metabolic syndrome, (2) mechanism of lifestyle-related diseases and metabolic syndrome, (3) effective functional compounds, foods, and diet to lifestyle-related diseases and metabolic syndrome, (4) relationship between metabolic syndrome and various diseases such as cancer, allergy, and aging. This book hopes to bring an overview of the recent advances of metabolic syndrome, and thus we welcome both review chapters and original chapters.
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For example, intensive care unit (ICU) patients’ care is complex with multiple disciplines involved performing numerous activities and procedures that increase the potential risk of error [3]. A recent study reports that drug management (25%, 95% confidence interval 16% to 34%, I2=98%) and other therapeutic management incidents (24%, 21% to 30%, I2=98%), surgical procedures (23%, 9% to 38%, I2=98%) and healthcare infections (16%, 11% to 22%, I2=98%) are the leading causes of preventable patient harm [2, 4, 5]. Lastly, fear around reporting medical errors manifests strongly within the healthcare culture in numerous places around the world, and contributes to stunting advancement towards error prevention and patient safety [5].
Though patient safety is an essential principle of health care, yet many medical practices and risks related with healthcare are major challenges for patient safety. In high-income countries, one in 10 patients experiences an adverse event during their hospital stay [4]. In the United States, medical error is the third leading cause of death after cancer and heart disease, resulting in 250,000 deaths annually, and in the United Kingdom, a patient is reported to be harmed every 35 seconds [5, 6]. Low and middle-income countries fare far worse as one in four patients is estimated to be harmed, which results in 2.6 million yearly deaths [4].
Additionally, the cost of medical errors associated with poor care is an enormous economic burden. Unsafe practices which result in death or permanent disability have cost some countries between US $6 billion and US $29 billion per year [5]. Furthermore, the psychological cost to the patient and families associated with a loved one’s death or disability, and loss of trust in the healthcare system are immeasurable [5]. Studies report that annual global economic growth could be boosted by over 0.7% if harmful medical practices are eliminated [4].
The joint commission gathers new evidence on emerging patient safety issues to inform goals for every year. Below are the brief descriptions of common safety issues, its burden, and the steps that can be taken to improve each.
Medical errors are events that occur during medical care which can lead to adverse consequences to patients. It is the third leading cause of death in the United States behind heart disease and cancer; about 250,000 deaths can be attributed to medical errors, including medication errors [7, 8]. They can be related to events when a wrong action was taken (error of commission) or when an action was not taken (error of omission). Additionally, medical errors can have consequences to health care professionals and institutions due to negative financial outcomes [9]. Healthcare providers can experience negative psychological responses with fear of punishment, and therefore be hesitant to report errors. It has been suggested that acknowledging healthcare providers are fallible and promoting a culture that focuses on mental health can lead to improved care for patients [10].
Several aspects of medical care can lead to medical error, including misdiagnosis, procedures, medication and/or dosage, patient identification and billing. It is important to recognize why they occur, foster a culture that encourages quality improvement, and cautions against an environment of blame and punishment [11]. There is often multiple causes of medical error: insufficient training, responsibilities performed by inappropriate staff, rare diseases, complexity of illness, unsatisfactory testing, time restraints, patient’s age, and newer procedures, amongst others [7]. It is important for all members of the healthcare delivery team to be involved in all aspects of patient safety and improvement.
Diagnostic errors have been estimated to be associated with up to 40,000 to 80,000 deaths or injuries per year. These include situations when a diagnosis was an unintentional delay, incorrect, or overlooked, and can occur in all specialties over a wide range of diagnoses. Preventing errors in diagnosis is a multifaceted approach, ranging from ensuring awareness of conditions that are often misdiagnosed, acknowledging first impression bias, discussion with appropriate specialists, and clear communication and documentation. This includes a complete differential diagnosis, appropriate handoffs, if applicable, and knowing which patients are at higher risks of diagnostic error, such as those with multiple medical conditions, patients with language and socioeconomic barriers, and patients with poor follow-up and compliance. Interventions to reduce diagnostic errors should not only be at the individual level, but should ideally be focused at the systems based level. System related errors include technical and equipment problems, organizational failures, “no-fault” errors like unusual presentation or conditions, and patient-related issues, such as compliance and misrepresenting symptom concerns [12, 13, 14].
The COVID-19 pandemic brings to light the importance of medical errors, including diagnostic errors as it relates to learning a new disease entity, as well as compromised physical and psychological aspects of healthcare providers that can affect clinical reasoning [15]. Additionally, system-based factors, such as staffing, capacity of the healthcare facility, and new care delivery systems, could be prone to delayed diagnosis due to postponement in patients coming to seek evaluation of symptoms or preventive screenings. It has been suggested that strategies to mitigate diagnostic error during these challenging times can be helpful: decision support tools, electronic health record, triage protocol, optimized use of telemedicine and follow-up, encouraging patients to seek care, education on safety protocols, a strong healthcare leadership team, open door for concerns without fear of judgement, continued support for education of trainees, and opportunities for discussion among colleagues for challenging cases and situations [16].
Sepsis is a syndrome characterized by life-threatening organ dysfunction in response to an infection. It is frequently not diagnosed early enough to save a patient’s life. Because these infections are often resistant to antibiotics, patients are at high risk for complications and death and have higher health care costs [17].
In October 2015, the Centers for Medicare and Medicaid Services (CMS) began requiring U.S. hospitals to report compliance rates with the sepsis CMS core measure SEP-1 (Severe Sepsis and Septic Shock Management Bundle). It puts out guidelines for frontline hospital clinicians fighting sepsis. SEP-1 focuses on timely sepsis recognition and early intervention with lifesaving therapies [22]. Preliminary data from CMS indicate that the majority of SEP-1 cases nationally fail the measure and cases that fail have higher mortality rates than cases that pass [23]. E
Radiation therapy, consisting of targeting malignant cells with ionized radiation, is an increasingly important cancer therapy with approximately 50% of all cancer patients receiving radiation during their illness [25]. Toxicities and adverse side effects of this therapy are related to the dose of radiation given and therefore dose calculation and regulation is of concern with regards to patient safety.
Radiation therapy safety and regulation has been under scrutiny and overhaul following a New York Times article from 2010 describing several patient stories with devastating outcomes [26, 27]. Many of the errors described are related to patients receiving several times the intended dose of radiation or miscalculations of the field resulting in areas of the body receiving radiation which were not intended or planned. Unfortunately, these errors are caused by flaws in an exceedingly complicated series of calculations and considerations depending heavily on computers systems and software. In fact, data shows that in radiation oncology, 30% of errors occur in the planning phase of therapy and 29% of errors are discovered in the treatment step of therapy [27]. This may suggest that the planning phase needs a more robust universally standardized control system and many studies have attempted to elucidate areas of improvement regarding geometric discrepancies resulting in errors [28, 29, 30].
As medicine becomes increasingly more complex, so does error analysis. In the field of radiation oncology, the multidisciplinary team adds to this complexity. The specific skill sets that are required to plan and execute a radiation treatment cannot be expected of one provider and so several health care providers are needed to successfully implement a complex therapy, including a highly specialized physician, medical physicist, and radiation therapist/dosimetrist. This is no doubt overall beneficial in the big picture for patient outcomes, however, advanced software and multiple highly specialized providers means that the way providers consider their options when an image or patient is in front of them requires far more critical thinking than what may have been expected from an average physician 30 years ago. Each provider must critically look at the information in front of them and understand and accept that there are parts of the treatment plan and the method in which they were derived that they do not fully comprehend. This requires all the members of the treatment team to trust the computer systems and software, as well as other providers, which are all integral in planning of radiation therapy. At the same time, all involved must realize the limitations of technology and consider human error on the part of their colleagues. This makes error analysis in the field of radiation oncology intricate, and one might argue that a key consideration in the future may be cognitive biases among providers and need for structured training to minimize them [27].
Every year, millions of people undergo surgical treatment for various ailments and disease processes. Surgical interventions account for an estimated 13% of the world’s total disability-adjusted life years (DALYs). These procedures are intended to improve and save lives; however, unsafe surgical care can cause substantial harm. A modeling study, published in Lancet in 2008, estimated that 234 million operations are carried out every year across the world [31]. This translates to one operation for every 25 people, which is more than the number of children born worldwide each year. Current estimates of morbidity and mortality following surgery indicate that over 7 million people (about twice the population of Oklahoma) worldwide will suffer complications following surgery. One million of these people will die as a result. This correlates to an overall mortality rate of 0.5-5%. Complications in inpatient operations occur in up to 25% of our patients, which accounts for nearly half of all adverse events in hospitalized patients [31]. Regrettably, it is estimated that in at least half of the cases, in which surgery led to harm, were considered preventable. Several surgical societies and hospital administrations have put forth recommendations, and in many cases requirements, to help ensure our patients have a safe journey through our operating rooms.
On a global scale, the World Health Organization (WHO) is the leading authority on patient safety and has undertaken essential global and regional initiatives to address surgical safety. WHO established the Second Global Patient Safety Challenge, “Safe Surgery Saves Lives,” in 2007. This program proposed to improve the safety of surgical care around the world by defining a core set of safety standards which led to the Surgical Safety Checklist, a 19-item tool created by WHO in association with the Harvard School of Public Health. This safety checklist aims to decrease errors and adverse events by increasing communication and teamwork in surgery [32]. Improving teamwork and communication is one of the main goals of using a checklist. The checklist is a simple tool designed to improve the safety of surgical procedures by bringing together the whole operating team (surgeons, anesthesia providers and nurses) to perform key safety checks during vital phases of perioperative care: prior to the induction of anesthesia, prior to skin incision, and before the team leaves the operating room. Between October 2007 and September 2008, the effect of the Checklist was studied in eight hospitals in eight cities (Toronto, Canada; New Delhi, India; Amman, Jordan; Auckland, New Zealand; Manila, The Philippines; Ifakara, Tanzania; London, UK; and Seattle, USA) representing a wide variety of health-care settings, economic circumstances and diverse patient populations and demonstrated dramatic improvements in both processes and outcomes. The study showed use of the WHO Surgery Checklist, reduced the rate of deaths and surgical complications by more than one-third across all eight pilot hospitals. The rate of major inpatient complications dropped from 11% to 7%, and the inpatient death rate following major operations fell from 1.5% to 0.8% [33].
Many hospitals are already performing most of the items on the list but not reviewing them as a team. Good data has now proven that implementation of the 19-item checklist results in a significant reduction in both morbidity and mortality [33]. The WHO continues to develop patient safety action plans with an action-oriented framework to facilitate the implementation of strategic patient safety interventions at all levels of health systems. Because complications will strike, we must strive for perfection, by adhering to proven protocols, meticulously preparing, conducting, and caring for our surgical patients.
Each day, life-saving blood transfusions are needed in hospitals and emergency treatment facilities across the United States. There are more than 13.2 million blood donors in the U.S., resulting in a total of 17.2 million transfused blood product units per year. Worldwide, approximately 118.5 million blood donations are collected [34]. How do we ensure safety with this staggering number? In the U.S., the federal agencies responsible for keeping our blood safe are the Centers for Disease Control (CDC), protecting health through investigations and surveillance [35]. The U.S. Food and Drug Administration (FDA) ensures safety of blood donations by protecting the health of donors. The National Institutes of Health (NIH) performs research on blood transfusion basic science, epidemiology, and clinical practices. Safety is also the responsibility of the blood centers and hospitals that collect and transfuse millions of units of blood each year. On the donor end, each donor is screened for risk of transmissible disease by questionnaire, which asks standard health questions to determine eligibility to donate. Additionally, each unit of donated blood in the U.S. is routinely screened for various infectious disease pathogens, using FDA approved assays [35]. The blood is then tested for blood type (ABO group) and Rh type (positive or negative). Prior to transfusion, the donor and blood unit are also tested for certain proteins (antibodies) that may cause adverse reactions in a person receiving a blood transfusion.
Presently, the most significant risk for a transfusion complication occurs due to noninfectious hazards from deficient processes [36]. The goal of providing safe transfusion therapy depends on a complex process that requires integration and coordination among multiple hospital services, including laboratory medicine, nursing, anesthesia, surgery, clerical support, and transportation. Most healthcare institutions in the United States have formed a multidisciplinary hospital-based transfusion committee to review blood transfusion practices and adverse outcomes. The Center for Medicare/Medicaid Services (CMS) requires such a process to receive payment for transfusion services. However, CMS does not require a specific committee be assigned to oversee the review process. This process must include a program of quality assessment and performance improvement, which is ongoing, hospital-wide, data-driven, reflects the complexity of the hospital’s organization and services, and involves all hospital departments and services (including those contracted) [37]. If a hospital elects not to receive payments from Medicare, it must still comply with applicable sections of the Code of Federal Regulations pertaining to transfusion services.
Venous thromboembolism (VTE) is a frequent complication of hospitalized patients and a leading cause of preventable hospital death and increased hospital length of stay in the United States and worldwide. Hospital-acquired VTE is defined as VTE occurring during or within 3 months after hospitalization and accounts for >50% of the population burden of VTE in the United States. Although, the precise number of people affected by VTE is unknown, it is estimated as many as 900,000 people are affected (1 to 2 per 1,000) each year in the United States, resulting in an estimated loss of 60,000-100,000 American lives. As one might expect, there is an exponential increase with age from 1 per 10,000 in young adults to 1 per 100 in the elderly. Data from two large U.S. studies place the estimated absolute risk of VTE after age 45 to be 8.1% overall, 10.9% in obese patients, 11.5% in blacks, 17.1% in those with factor V Leiden mutation, and 18.2% among blacks with sickle cell trait [38]. Of these patients, two-thirds will present with Deep Vein Thrombosis (DVT) only and the remaining presenting with Pulmonary Embolism (PE) as the first manifestation and primary cause of VTE related mortality.
Early data regarding COVID-19 patients developing VTE suggests substantial risk. Reports have ranged from 1.1% in non–intensive care unit (ICU) hospital wards to 69% in ICU patients. More data is necessary regarding the relationship between COVID-19 and increased risk of VTE. Currently, many of reports are from small sample sizes and retrospective in design. However, it seems prudent that all patients admitted to a hospital unit receive pharmacologic prophylaxis. The question of whether to administer full therapeutic dose versus prophylactic dose anticoagulant in critically ill patients is controversial and is actively being studied [39].
Venous thromboembolism remains one of the most preventable causes of hospitalized patients. Risk stratification and prophylactic measures have proven to be safe, cost effective, and most importantly, save lives. The data regarding VTE morbidity and mortality is not new yet, despite decades of solid evidence from multiple randomized clinical trials, thromboprophylaxis remains either underused or misused. The key is for health care providers to adhere to proven protocols and policies. Multiple policy statements have been published focusing efforts to eliminate unnecessary human death and suffering. Five major areas of policy guidance have put forth by the American Heart Association that they believe will lead to improved implementation, tracking and prevention of VTE events. They include assessment and reporting the level of VTE risk in all hospitalized patients, integrating preventable VTE as a benchmark for hospital comparison and pay-for-performance programs, supporting appropriation to improve public awareness of VTE, tracking VTE nationwide with the use of standardized definition and developing a centralized data steward for data tracking on VTE risk assessment, prophylaxis, and rates [40].
Diagnosis and defining exactly who should be screened remains challenging because the clinical features are often non-specific, and testing can be falsely negative or positive. Therefore, risk stratification scoring systems have been proposed and used widely. The Wells DVT and Wells PE scoring systems, as well as the Geneva PE score, have been adopted by many major medical centers in the U.S. and around the world. These scoring systems have been used in conjunction with objective diagnostic imaging, providing a high degree of accuracy in making the diagnosis of VTE. Some of these diagnostic testing modalities includes compression ultrasonography, computed tomography angiography, ventilation-perfusion scintigraphy or single-photon emission tomography, magnetic resonance angiography and echocardiography.
Another method of making healthcare administrator’s and medical practitioners take notice is by making them financially aware of the devasting avoidable cost to our healthcare industry. When factoring in the VTE-related morbidity of VTE, including post-phlebitic syndrome occurring in 30-50% of patients with proximal DVT, and chronic thromboembolic pulmonary hypertension occurring in 4% of patients within 2 years of PE survival, the estimated annual cost of preventable hospital acquired VTE is $7-10 billion per year [41]. Regardless of the method, it is our duty as healthcare providers to take on the challenge by educating our healthcare colleagues and soliciting the support of our administrators in establishing hospital wide protocols to prevent this devastating, albeit preventable, disease process.
Health-care associated infections (HCAIs) are infections acquired by patients 48 hours or more to within 30 days after receiving care from various health care settings, which include acute-care facility, long-term facility, family medicine clinics, ambulatory care and home care [42]. HCAIs are the most common complications of hospital care and one of the top 10 causes of mortality worldwide [42]. Numerous factors heighten the risk for developing HCAIs, such as increased age, immunosuppression, multiple underlying comorbidities, increased length of hospital stay, admission to the intensive care unit (ICU), mechanical ventilatory support, recent invasive procedures, indwelling devices, frequent visits to healthcare facilities, and infection-control practices at the healthcare facility [43]. Patients’ risk of developing antimicrobial resistance increases highly if they received intravenous antibiotics within 90 days of administration [43]. Even though $28-45 billion is spent annually in the United States, 90,000 deaths still occur due to HCAIs [42]. The World Health Organization (WHO) reports that 7 out of 100 hospital patients in high income countries and 10 out of 100 hospital patients in low-to-middle income countries will acquire HCAIs at any given time [44]. These statistics continue to highlight a major concern to patient safety worldwide.
Surgical site infections (SSIs), also known as wound infections, central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated pneumonia (VAP), hospital-acquired pneumonia (HAP) and
The most important practice to prevent and control HCAIs is effective hand hygiene [42, 49]. The World Health Organization (WHO) advocates education and training for all healthcare workers to encourage washing hands for at least 30 seconds before and after touching a patient or their environment, after body fluid exposure, and before and after aseptic procedures using soap and water or alcohol-based sanitizers [42, 49]. Widespread and consistent hand hygiene practices can decrease infection rates by 50% [49].
Personal protective equipment (PPE), for example, face masks, gloves, gowns, protective eyewear, and face shields, reduce transmission of microorganisms and body fluids between healthcare workers and patients [42]. Organisms transmitted through aerosols, such as influenza virus,
Cleanliness of equipment used by healthcare workers is also important to patient safety. A study found medical residents’ coat sleeves (50%), stethoscopes (36.3%), and pagers (36.3%) carried methicillin sensitive
The estimated number of inpatient falls in United States is between 700,000 to 1,000,000, with reported fall rates ranging from 1.3 to 8.9 per 1000 bed-days [54, 55]. In general, fall related injuries are the most common cause of accidental death among hospital patients over 65, resulting in 41 fall-related deaths per 100,000 people per year [54].
Per the World Health Organization, falls are defined as “inadvertently coming to rest on the ground, floor, or other lower level, excluding intentional change in position” and in the inpatient setting, they include slips, trips, faints, collapses and any patient found on the floor unwitnessed [56]. As of 2008, Centers for Medicare & Medicaid Services (CMS) does not reimburse hospital for certain types of traumatic injuries while patients are in the hospital, many of which occur after a fall [57].
Preventing falls in the hospital setting can be challenging. Hospital staff needs to treat patient for their acute condition, keep them safe and help patients maintain and recover physically and mentally. When an adverse event like a fall happens, it may result in high-impact outcomes for a patient, such as decline in function, increased length of hospital stays, and increased cost of health care services. Damage resulting from a fall can affect as many as 50% of patients, and about 44% of falls can result in serious injuries and even death [56]. About 1-3% of falls in hospitals results in fractures [58]. Even without injury, harm to patients, caregivers and hospital staff can manifest as psychological distress, including anxiety and depression, reduced physical activity, fear of future falls, prolonged hospital stay, increased use of restrains and sedating drugs, complaints, litigations, guilt, and dissatisfaction [55, 59]. Fall prevention often consists of managing patients’ underlying fall risk factors. Such risk factors include age, limited mobility, visual impairment, use of some classes of medications (especially psychotropics), medication side effects, change in medications, delirium, change in environment, frequent toilet needs, urinary incontinence, orthostatic hypotension, fall history, and fear of falling. In addition to the elderly, patients with recent diagnoses of stroke or cancer, and patients hospitalized in neurology and rehabilitation units are at increased risk of falls [60]. There are several fall-risk tools to help stratify patients at risk, but many of them are not validated due to their lack of sensitivity and specificity for clinical use. Three of these have been validated in multiple studies across the populations. These are the St Thomas’s Risk Assessment Tool in Falling Elderly Inpatients (STRATIFY), the Morse Fall Scale (MFS), and the Hendrich Fall Risk Model (HFRM). Based on the risk stratification, there is usually a multimodal intervention for inpatient fall prevention, and it can include patient education, bedside risk sign, staff education, alert wristband, footwear, toileting schedules, environmental modifications, movement alarms, bedrail review, hip protection, exercise, restrains, and a review after a fall to identify causes. High quality evidence shows that multicomponent intervention can reduce the risk of inpatient falls by up to 30% [61].
A common taxonomy is needed to standardize and track events to measure particularly when healthcare workers are working between and within different professional backgrounds. The core terms that are essential to know and understand are described below.
Near misses also may be referred to as close calls, near accidents, accident precursors, injury-free events and, in the case of moving objects, near collisions.
A near miss is often an error, with harm prevented by other considerations and circumstances.
The phrase "near miss" should not be confused with the phrase “nearly a miss” which would imply a collision.
A coordinated and practical strategy in which systemwide safety processes are applied across entire healthcare fields through collaboration among diverse stakeholders has been proven to provide the best outcomes. Risks are to be expected as healthcare is and will continue to be an ever evolving. Preventing harm and improving systems will not happen in a vacuum. It takes effort from frontline personnel, educators, trainers, and organizational leaders to create a systemwide approach. In the following section, we will discuss how we can prevent harm with our proactive attitude and build a capacity to improve patient safety when we try to conquer risks and errors spanning the myriad layers of healthcare.
The crucial step towards lowering errors and harms to the patients is educating healthcare professionals about patient safety. Since there is involvement of many individuals at different layers of the system in the delivery of health services, education and training also needs to be multidisciplinary and multi -professional. Education cannot be based on a linear or hierarchical educational model as medicine is often approached. Multimodal approach should be implemented at each level of health professional education.
Association of American Medical Colleges (AAMC) addressed Competency Based Education (CBE) in 2019 with suggestions for improvement for patient safety education. It acknowledges the importance of developing curricula based on competency at each level of learning- undergraduate, graduate, and continued education [62]. The same look but from a distinct perspective - as one accrues knowledge, they begin to see more clearly the finer aspects of how to prevent harm. Multiple avenues exist for formal coursework in patient safety education. Continued Medical Education (CME) is available by multiple formats such as lectures, testing, reading materials. It is the most pervasive patient safety education model; not only does updating clinical knowledge leads to improved outcomes but direct patient safety courses enhance its implementation. Certification courses are available, as well. In recent years there has been as rise in Master\'s degrees in patient safety and healthcare quality.
Several ongoing activities for trainees and experts, either directly or indirectly, enable patient safety education. Accreditation Council for Graduate Medical Education (ACGME) has mandated Quality Improvement (QI) projects in residency. They require pattern recognition for process improvement, inadvertently propelling involved parties to become educated on areas of patient harm. ACGME has appropriately made QI a requirement in physician training [63]. More informally, training occurs in the break rooms or during lunch when knowledge is shared openly, and indirect learning occurs from other’s experience. The table below provides list of some of the pros, cons, and growth opportunities for each educational setting (Table 1).
Type | Description | Pros | Cons | Potential sources of improvement |
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M&M conference | Healthcare teams thoroughly analyze a case often using the Ishikawa Diagram to discuss errors with an audience to educate and identify improvement |
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QI projects | Process improvement using the PDSA cycle |
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Case analysis | Experts reviewers who are familiar to the system and individuals find issues leading to patient harm |
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CME | Short formal sessions on specific topics on patient safety |
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Courses | Longer formal training on specific topics on patient safety |
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Multidisciplinary rounds | Involve multiple patient team member- such as provider, nurse, pharmacist, residents, fellows, etc to oversee patient care and provide increased oversight to prevent patient harm |
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Books/Articles/News | Dedicated books on/patient-oriented perspectiveopinions on patient safety |
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Avenues for patient safety education.
WHO has recognized the need for an international leader in patient safety education. In 2013, WHO published a Multi-professional Patient Safety Curriculum Guide for standardization of patient safety education, an update to its earlier Curriculum Guide for Medical Schools published in 2009 [64]. Additionally, during their 2021 assembly, the WHO adopted the first ever Global Patient Safety Action Plan 2021 – 2030, a global initiative to eliminate avoidable harm. Amongst other things, it will focus on involving patients and families for patient safety [44]. Smaller entities, such as Improvement for Healthcare Safety (IHI) or Patient Safety Network (PSNET), have perceived this necessity and invested in producing a concise platform for medical professionals as well [65, 66] attempting to innovate this field of learning.
Having recognized the need for such courses in medical educational infancy, the new trend has been to incorporate patient safety education across the globe [67]. By creating patient safety education early on, lifelong learners of patient safety can be made.
COVID-19 pandemic has provided fertile ground for medical errors as the medical system was stretched thin [68]. Much learning and teaching had internationally shifted to the virtual world. If this shift can be harnessed to standardize patient safety education as we continue to grapple with COVID as a reference, it may allow us to build a more robust patient safety instruction. Updating courses in medical school to incorporate patient safety is a new trend [69]. While each organization and individual will need to adapt proposed training, interactive learning curriculums improve student learning of difficult concepts such as patient safety and “just culture”. With the correct attitude, continually renewed educational offerings, and standardization of basics globally, we can navigate the complex and evolving nature of medicine better.
Effective leadership is necessary to lead an organization down the path to establishing a culture of safety. Primarily, the leadership needs to be persistent and well-balanced. Stable organizational leadership allows organizations to grow and transform successfully. According to the American College of Healthcare Executives and the Lucian Leape Institute, there are 6 key domains that healthcare leaders need to focus on to create a long-lasting organizational culture of safety [70]:
Establishing a compelling vision for safety
Build trust, respect, and inclusion
Select, develop, and engage your Board
Prioritize safety in the selection and development of leaders
Lead and reward a just culture
Establish organizational behavior expectations
These domains do not exist by themselves and must always be looked at as a cohesive unit.
To successfully lead an organization on its path to a safer patient experience, the leader must set clear priorities and communicate a sharp vision. A shared vision is a fundamental part of highly effective organizations, and this endeavor is no different. Because so much of patient safety initiatives involves voluntary reporting by staff, the role of leadership building trust amongst their employees and selecting managers who prioritize safety cannot be understated. Many staff members view patient safety reports as “snitching” and do not understand the fundamental importance of identifying these sentinel events. Leaders and managers leading by example in reporting events concerning them and by ensuring the principles of “just culture” are on display is necessary to ensuring the organization becomes a champion for patient safety.
The pairing of high-quality education and transformative leadership based on the 6 domains are two-parts to a successful, patient-focused organization. Neither will be successful alone and without coordination of educational programming and leadership efforts, they will not be successful either. Leaders will need to work with organization educational designers to create engage, transformative educational material that will motivate staff to focus on patient safety as a core value of the organization [71].
“Just Culture” refers to a system of shared accountability in which organizations are accountable for the systems they have designed and for responding to the behaviors of their employees in a fair and just manner. Employees are accountable for the quality of their choices and for reporting errors and system vulnerabilities. While the organization has a duty and responsibility to employees and to patients, all employees are held responsible for the quality of their choices [72].
Promoting a just culture is to implement a nonpunitive response to error in improving patient outcome and safety. Just culture encourages employee to focus on compliance and corrective actions instead of fear of punitive actions. Creating a safe and transparent environment encourages reporting of mistakes and hazards and improves the care provided to patients. Lack of reported information decreases the organization ability to proactively address patient-safety issues and improves the existing work infrastructure.
For health care systems to be successful in achieving the above goals of patient safety they need to foster a just culture [72].
These examples address an aspect of just culture that goes beyond ensuring that employees feel free to report errors. Exceptionally reliable organizations and industries promote mindfulness in their workers.
Weick and Sutcliffe describe mindfulness in terms of 5 components [73]:
A constant concern about the possibility of failure
Deference to expertise regardless of rank or status
Ability to adapt when the unexpected occurs
Ability to concentrate on a task while having a sense of the big picture
Ability to alter and flatten the hierarchy to fit a specific situation
Mindfulness throughout an organization considers moves beyond events and occurrences. Everyone in the organization is continually learning, adjusting, and redesigning systems for safety and managing behavioral choices.
A fair and just culture improves patient safety by empowering employees to proactively monitor the workplace and participate in safety efforts in the work environment. Improving patient safety reduces risk by its focus on managing human behavior (or helping others to manage their own behavior) and redesigning systems. In a just culture, employees are not only accountable for their actions and choices, but they are also accountable to each other, which may help some overcome the inherent resistance to dealing with incompetency [72].
Secondary benefits of a just culture include the ability to develop a positive patient safety profile to respond to outside auditors, such as The Joint Commission. When implemented, a just culture fosters innovation and cross-departmental communication. An example is the opportunity to revitalize the morbidity and mortality conference to cross specialty lines and develop a patient-centered focus. In a just culture, both the organization and its people are held accountable while focusing on risk, systems design, human behavior, and patient safety [72].
The process of implementing the just culture is not one that happens overnight. However, a health care organization can build an infrastructure to embed this methodology by achieving it through education and allocation of resources to training the employee.
“Engagement of patients and families resides at the core of the framework for safe, reliable, and effective care. In safe and reliable organizations, patients and families are as much members of the care team as clinicians and other health care staff” [74].
The joint commission mandated that healthcare organizations “encourage patient’s active involvement in their own care as a patient safety strategy”. Because of this action, hospitalized patients, as well as patients receiving care on outpatient basis, are routinely surveyed about their satisfaction with the care they received [75].
Studies in the in-patient setting have found that patients often report errors that were not detected through traditional mechanisms, such as chart review [75]. Unless patient involvement through surveys after service was considered, these errors would not have been detected. Therefore, patient engagement and involvement practices in the day-to-day functions of an organization is essential in ensuring a safe environment.
Some examples of safety targets in patient care that show patient outcome improvement and risk reduction through patient engagement in hospitals and outpatient settings include: improved anticoagulation management with reduction in risks of thromboembolic events and mortality, improved hypoglycemia management in diabetes, increased medication adherence, reduced medication administration errors, improved hospital readmissions rates, and reduced hospital acquired infections when patient education and engagement is optimized and encouraged [76].
With all the evidence demonstrating patient involvement and participation supporting positive outcome, the next step is for health care teams to partner with patients and caregivers to integrate effective patient engagement into clinical practice and health care systems.
The following elaborates on proposed methods to involve and engage patients in the care they receive from organizations to ensure patient satisfaction and safety outcomes [74]:
Patients should be included in decision making process. While it is the clinical team’s responsibility to provide key facts and advise to patients, the patients and/or their representatives should be given opportunity to have input in decision-making process. It is easier to reach a common goal when all parties are informed and well educated on real expectations. This will minimize unnecessary steps and reduced risks and negative outcomes associated with those steps.
Healthcare teams and organizations should provide a safe environment for patients to express concerns, questions, and ideas openly and without judgment. The clinical team should avoid negative reactions to foster more comprehensive and accurate information exchange between patients and organizations/healthcare teams. As a result, patients will be more forthcoming about their incompliances and will provide more accurate information. This process will help providers utilize factual data to come up with a plan of care that reduces unintentional harm to patients.
The Agency for Healthcare Research and Quality (AHRQ) is one of twelve agencies within US Department of Health and Human services (HHS). It is a lead federal agency charged with improving the quality and safety of America’s health system performance, offers practical and research-based tools with resources to support healthcare organizations, providers, hospital staff, patients and others that make care safer in healthcare settings. These organized tools and resources help staff in hospitals, emergency departments, long-term care facilities, and ambulatory settings to prevent avoidable complications of care. AHRQ contributes to forming a higher performing health system in three main ways: investing in research and evidence to improve safety and quality of healthcare, creating materials to teach and train healthcare professionals to catalyze the improvements in care, and generating measures and data used to track and evaluate progress of US healthcare [77].
AHRQ assists and provides various tools and resources by different settings, quality measures, reports and resources, engaging patients and families, education, and training, etc. Teams STEPPS, is one such teamwork system developed by AHRQ and Department of Defense (DoD) that offers a powerful solution to improving collaboration and communication among healthcare professionals [78]. There are many other quality improvement tools and information, including AHRQ Quality Indicators Hospital Toolkit, ambulatory clinical performance measures, and talking quality, to help staff build the knowledge and develop the skills that impact organizational culture and lead to sustained improvements in safety.
Since quality improvement is a driving force and is a vital part at every level of service delivery in healthcare, collecting and analyzing data are therefore central to the function of quality improvement at all levels. Data not only allows us to accurately recognize problems, it also supports to prioritize quality improvement initiatives, and qualifies objective assessment of whether change and improvement have indeed occurred. Making changes to improve quality is complex business, thus solid evidence in the form of data is required to support decision-making rather than isolated occurrences, assumptions, emotions, or politics.
Role of data in quality improvement is helpful in all five phases of quality improvement: project definition phase (what is the problem?), diagnosis phase (what can we improve?), intervention phase (how can we achieve improvement?), impact measurement phase (have we achieved improvement?), and sustainability phase (have we sustained improvement?) [79].
With good data, we can access: current performance, identify performance gaps, identify problem steps, prioritize opportunities for improvements, establish clear objectives for improvement, prioritize most appropriate interventions, compare the benefits of alternative interventions and implementation strategies, assess impacts of interventions, demonstrate the success of improvement project to stakeholders, provide feedback to reinforce change, demonstrate benefits, identify problems in practice, and need for repeated intervention.
To get quality, unbiased data, one must use sound data collection techniques, appropriate tools, correct sampling techniques, ensure data validity, and confirm it is secured.
The dynamic nature of healthcare delivery where innovative technologies and approaches to care are incorporated constantly into the regular practice, new occasions for unsafe practices are continually created. An attitude of inclusivity for all care teams with necessary education, proper communication, just culture, and engaging leadership will lower errors and harms and improve patient safety. Besides these, proper collection and review of safety data can help serve as a catalyst for increased resources dedication to most needed facet of healthcare in that setup. Thus, if we integrate the science of safety into our daily healthcare practices, we are certain to lessen the magnitude and extent of harm and economic burden and improve patient safety.
In adult individuals, the mammary gland is composed of bilayered epithelial structures, forming a branched ductal tree within an adipocyte-rich stroma [1]. These tree-like structures consist of distinct epithelial cell populations that form secretory alveoli, organized into lobules and a branched network of ductal structures. Development of the mammary epithelial cell populations within these structures, occurs hierarchically through specific intermediates and coordinated expression of several lineage-specific markers [2, 3, 4]. Functionally these distinct cell populations are organized into an inner luminal epithelial (LE) cell layer and outer basal cell layer, the basal layer containing both mature myoepithelial (ME) and stem/progenitor cell populations [5]. These specific cell populations within the bilayered mammary epithelium can be distinguished by the expression of various markers, including the cytokeratin expression pattern [6].
The basal cell layer is responsible for the regenerative potential of the mammary epithelium due to the colonization of the mammary stem cells with multilineage potential, within this compartment [5, 7, 8]. Contractile ME cells, localized to the same cell layer, provide a niche for these stem cells. Additionally, ME cells have an important role in synthesizing and maintaining normal basement membrane (BM), controlling polarization and proliferation of the LE cells as well as directing branching and differentiation of the developing structures [9, 10]. Upon gestation, epithelial cell populations further undergo directed differentiation and proliferation, consequently leading to side-branching and formation of alveolar, lactating units within lobular clusters [11, 12, 13]. In such functionally mature mammary epithelial structures, the inner luminal cell population produces and secretes milk into the lumen [14, 15], whereas the outer, smooth muscle actin (α-SMA)-expressing myoepithelial cells provide contractile forces for milk ejection in response to oxytocin [14, 16, 17]. When lactation is over, the alveolar cells undergo programmed cell death and the epithelium is returned to its pregestational state [18, 19, 20].
Calcium is crucial for various physiological processes through activation of specific intracellular cascades and by modulating the integrity of cellular junctions [21, 22]. Alterations in the activity or expression levels of different Ca2+ channels, or factors involved in their regulation can therefore significantly change cellular responses to various cues that direct tissue homeostasis [23, 24]. Consequently, deregulation of calcium signaling is therefore associated with several pathological conditions, including cancers. In cancers, abnormal calcium signaling has been linked to high proliferation, inhibition of apoptosis and invasive migration through the epithelial-to-mesenchymal transition, EMT [25, 26]. As for any other tissue, calcium signaling is likewise crucial for the regulation of mammary epithelium, its various calcium-dependent intracellular functions, the integrity of the epithelial sheets and mammary tissue-specific task, lactation [27]. The functional maintenance of the bilayered mammary epithelium is importantly also guided by various hormones and growth factors, which may also cooperate with calcium-triggered pathways [28, 29, 30]. In this review, the role of TRPV, vanilloid subgroup of transient receptor potential family ion channels are discussed in respect of their significance in the regulation of normal mammary epithelial homeostasis and along breast cancer progression.
TRPV channel proteins belong to the transient receptor potential, TRP, the family of proteins [23]. This superfamily of proteins is formed by over 30 different cationic channel proteins, which are further divided into seven subfamilies: TRPV (vanilloid), TRPA (ankyrin), TRPC (canonical), TRPM (melastatin), TRPML (mucolipin), TRPN (NOMPC), and TRPP (polycystin) families [23, 31]. TRP proteins possess crucial functions in various tissues, in both non-excitable cells as well as in the cells of the nervous system [23, 31]. The members of this family display both structural and functional similarities and many of them are voltage- and temperature-sensitive for functioning as sensors in the peripheral and central nervous systems. Besides these, they can sense various other extracellular cues, both biochemical and physical ones, leading to their spatio-temporal activation, ion influx and adjustment of the downstream signaling cascades [32, 33].
The subfamily of TRPVs has six members, TRPV1-6 that can form both homo-and heterodimeric channels. Of these subfamilies, TRPV1-4 do not display high Ca2+-selectivity [34, 35, 36, 37]. On the opposite, TRPV5 and TRPV6 are highly selective for Ca2+ [38, 39, 40]. Most of these TRPV family members can sense and respond to various stimuli, consequently activating multiple intracellular signaling cascades [31, 41, 42]. TRPV1 is found in the plasma membrane and prominently expressed in sensory neurons but it is also clearly expressed in other cell types [43]. TRPV1 is involved in nociception and triggered by heat, pH and some compounds, including capsaicin [44, 45, 46]. TRPV2 is found in all tissues, and is highly expressed in sensory neurons. Its main localization in cells is not at the plasma membrane but in the intracellular membranes [47, 48, 49]. TRPV2 displays various physiological functions through its actions as a thermo-, lipid- and mechanosensor. Additionally, it can also respond to growth factors, hormones and cytokines [50, 51, 52], leading to a wide range of functions that play a role in healthy tissues and in pathophysiological conditions.
Both TRPV3 and TRPV4 are highly ubiquitous and they are noticeably expressed in epithelial tissues [35, 37, 53]. TRPV3 is a non-selective cation channel and is especially abundant in the skin keratinocytes [54]. It can sense temperature and plays a role in various tasks, including maintenance of the skin barrier function, wound healing, pain sensation and itch [53, 55]. Therefore, TRPV3 seems to be particularly important for the skin health. Like TRPV3, TRPV4 is an abundant cationic channel in the epithelial tissues and can trigger ion-influx upon various cues, such as mechanical stretching, osmolarity and heat [56, 57, 58, 59, 60]. The activity of TRPV4 has been associated with various physiological functions, it has an important role in cell volume regulation, homeostasis of the vasculature, central nervous system and as a mechanosensor in a wide array of tissues [37, 61, 62].
Unlike the other TRPVs, TRPV5 and its close relative TRPV6 are the only highly calcium-selective channels among TRPVs and the whole TRP superfamily [38, 39, 40]. TRPV5 is highly expressed in the kidney, while TRPV6 has a broad expression pattern in some different tissues. TRPV5 and TRPV6 constitute the apical Ca2+ entry mechanism for active calcium transport in the kidney and intestine, respectively. Their roles in the active Ca2+-reabsorption and maintenance of cellular Ca2+-homeostasis are essential, loss of these proteins leading to reduced bone thickness, defects in the intestinal calcium absorption, reduced fertility, and hypocalcemia [63, 64, 65, 66, 67]. Interestingly, TRPV5 and TRPV6 are under the regulation of 1,25-dihydroxyvitamin D3, and hormones, such as parathyroid hormone, estrogen, and testosterone may participate in fine-tuning the calcium-uptake [68, 69, 70, 71, 72, 73].
The hormonal regulation of TRPV channels has mainly concentrated on the role of sex hormones, which can impact the expression of ion channels either directly or indirectly through intracellular signaling [74, 75]. Progesterone, a steroid hormone, is known to elevate TRPV6 levels in mammary carcinoma cells [76]. In human mammary epithelium, progesterone receptor, PR, is expressed in both luminal and basal epithelial cell populations, and it promotes the proliferation of the basal mammary epithelial cells. Luminal PR may also promote the proliferation of neighboring cells through paracrine signaling mechanisms [77]. In addition to TRPV6, TRPV4 is under the control of progesterone receptors in the mammary gland, airways and smooth muscle cells of the vasculature [78]. In the case of TRPV4, progesterone was found to decrease both mRNA and protein levels of TRPV4, while silencing of PR led to increased level and activity of TRPV4 in the T47D mammary epithelial cell model [78]. In adult individuals, the PR-positive cells are usually also ERα positive [79] and estrogen acts through ERα to induce the expression of PR [80, 81]. This interconnection between the hormone receptors and specific TRPV channel proteins should be further assessed in future studies, as they may also play a role in the disease progression.
Calcium signaling is known to direct developmental processes and is also crucial for both structural and functional maintenance of the mammary epithelium [82]. Different TRP family proteins serve as important calcium influx routes in the mammary epithelium and may thus act as central players in the maintenance of the mammary epithelium through calcium homeostasis.
Among the TRPV family channel members, the TRPV4 channel is probably the most well studied in respect of its role in epithelial integrity through the regulation of adherens- and tight junction proteins [83, 84, 85, 86, 87, 88, 89, 90]. In a mouse mammary epithelial cell line, HC11, TRPV4 localizes at the basolateral membrane to regulate calcium influx and permeability [86]. This TRPV4-mediated Ca2+-intake is known to trigger activation of some calcium-dependent voltage-gated potassium channels, BK channels, that have a major role in tight junction regulation through at least claudin family proteins. Mechanistically, TRPV4-mediated calcium influx leads to two separate cellular events: A fast elevation in the transcellular conductance via the activation of apically-located large BK potassium channels and a slower increase in paracellular permeability for small soluble molecules. Associated with these alterations, down-regulation of several claudin family tight junction proteins was detected together with large break formation in the tight junction strands [86]. In contrast, studies by Islam et al. showed that TRPV4 can also positively affect the expression of tight junction proteins through X-box-binding protein 1, XBP1, in the mammary epithelial cells upon heat induction [89]. Besides TRPV4, also TRPV6 may play a role in the homeostasis of the mammary epithelium, both during differentiation and maintenance of the intact epithelial structures: Zinc finger homeobox 3 (ZFHX3) is a transcription factor that directs numerous cellular processes, including differentiation. ZFHX3 was found to regulate calcium homeostasis in the mammary epithelium through positive regulation of TRPV6, leading to differentiation of MCF10A mammary epithelial cells in the 3D environment [91]. These observations support the role of TRPV6-mediated calcium influx in the differentiation and maintenance of the mammary epithelium, downstream of ZFHX3. As ZFHX3 is also linked to the function of hormones, including progesterone which can upregulate TRPV6, it would be interesting to investigate the possible connection between them. Furthermore, TRPV6 seems to be important for the maintenance of the junctional integrity of the mammary epithelium [92]. TRPV6 was found to localize at the cell-cell junctions together with adherens junction protein E-cadherin and its depletion led to the loss of epithelial integrity as detected with both MCF10A and 184A1 mammary epithelial cell cultures, treated with TRPV6 siRNA. This could be at least partially through the regulation of peripheral actomyosin bundles that maintain junctional tension as TRPV6 depletion affected pathways upstream of actomyosin assembly [92]. While there is evidence for the role of TRPV4 and TRPV6 in the structural maintenance of the mammary epithelium, the possible role of the other TRPV channel family members have not been properly assessed in this respect, at least in the mammary epithelial model. Additionally, it may be that these channel proteins respond differently to distinct cues to regulate the junctional integrity in the epithelial sheets. At least in the case of TRPV4, there seems to be dual modulation depending on the initial cues.
In the course of gestation, the mammary gland and its epithelial structures undergo major architectural changes, leading to the formation of milk-producing alveolar structures. These morphological events are jointly guided by hormones and growth factors, alterations in the physical microenvironment as well as the paracrine signaling in between the mammary stroma and the bilayered epithelium [93, 94, 95]. Coinciding with the formation of alveoli, TRPV4 mRNA levels are known to be increased at the day 15 of gestation and to be downregulated immediately after lactation [89]. These findings suggest that at least TRPV4 could have a role in the pregnancy-linked developmental processes within the mammary gland. While other, TRPV channels are also responsive to hormones and changes in the mechanical microenvironment, their role along gestation-linked epithelial changes have not been assessed.
During lactation, the maternal calcium and magnesium homeostasis encounter significant alterations due to excessive need of the divalent cation Ca2+ in breast milk. Consequently, demineralization of the skeleton is observed together with changes in both renal and intestinal Ca2+ transport [96]. For this, several proteins, playing a role in the transcellular Ca2+ and Mg2+ transportation are upregulated along lactation. Vitamin D also contributes to this process by inducing intestinal hyperabsorption [97]. TRPV5 is highly expressed in the kidney epithelium, in the distal convoluted tubules and connecting tubules [98]. Structurally similar TRPV6 is more widely expressed but exhibits prominent expression in the intestine epithelium [99, 100]. Moreover, both TRPV5 and 6 are Ca2+-selective and also vitamin D-responsive [101], and in line with this connection to lactation-induced alterations in Ca2+-homeostasis, they are also upregulated in renal and intestinal epithelium upon lactation [97]. Furthermore, prolactin is known to regulate both vitamin D metabolism and induce TRPV6 levels to regulate calcium intake during lactation [102]. TRPV5 and TRPV6 thus participate to lactation by enabling the excessive need of calcium during this physiological phase.
Production of milk is triggered by heat as mammary epithelial cells can activate their milk generation at 39 degrees [103, 104]. Mammary epithelial cells also undergo heat-evoked proliferation and differentiation [105]. Interestingly, many TRP channels act in sensing heat and from the vanilloid subfamily of proteins, TRPV1-4 acts as major thermosensors [45, 106, 107, 108]. Upon heat-treatment, TRPV4 is also able to activate the expression of milk protein beta-casein and tight junction (TJ)-associated proteins, Zonula occludens-1 (ZO-1), Claudin 3 (Cldn3) and Occludin (Ocln) [89]. Permeability of TJs is known to be modulated upon milk production and immediately after parturition [109], and this feature may thus be dependent on TRPV4. Heat stress is also known to induce unfolded protein response, UPR [110] and UPR-associated transcription factor XBP1 plays a role in the differentiation of mammary epithelium together with the expression of milk protein beta-casein [104, 111]. Intriguingly, recent work by Islam et al. proposes that TRPV4 acts through XBP1 [89]. Besides heat, TRPV4 is activated by mechanical changes and stretching in the cell environment that are also known to take place along lactation. In addition to TRPV4, the TRPV2 channel can play a role in lactation as it localizes to oxytocinergic neurons [112].
After lactation is over, the milk-producing structures regress to the pre-pregnancy state in a complicated reverse action, involution [113]. Ca2+-dependent signaling may also impact this transfer from lactation to involution [14]. Whether any of the TRPV family members play a role in this process, remains to be studied.
The characterization of breast cancers is based on different criteria, including the histopathological evaluation, grading and staging as well as defining the expression of estrogen (ER), progesterone (PR), and epidermal growth factor (HER2) receptors [114]. Additionally, gene expression profiles can be used to determine the molecular subtypes, which can be Basal-like, HER2-enriched, Claudin-low, Luminal A, Luminal B, or Normal-like. The heterogeneity of breast cancer as a disease is well seen also on the differences in Ca2+-channel expression that vary greatly in between specific breast cancer subtypes. Often the levels or activity of plasma membrane-embedded calcium channels can also reflect the metastatic potential and prognosis of distinct mammary carcinomas [26]. Abnormal activity of the Ca2+-channels in breast cancers could potentially take place due to mutations, deregulation of the channel gating or changes in the expression levels, triggering Ca2+-influx in unfavorable patterns, both spatially and temporally. As several calcium channels can respond to a wide variety of biochemical and mechanical cues in their microenvironment, any alterations in such could lead to deregulated calcium channel activity to sustain an elevated or abnormally low calcium entry. Additionally, a variety of the plasma membrane-associated calcium channels could be deregulated at the same time, within similar cancer types, further cooperating in adverse processes along the course of neoplastic progression.
TRPV channel family, among the other TRP family members, has been linked to the progression of a variety of human cancers [115, 116]. These cationic channels can also mediate Ca2+-influx and have been shown to contribute to several hallmarks of cancers, including the potential to proliferate, resistance to apoptosis, angiogenesis, and invasion [117, 118]. Additionally, these channel proteins may have different roles, as either cancer promoters or suppressors, depending on the cancer type and its genetic background as well as the expression levels of distinct channel proteins. The primary Ca2+-triggered pathways that play a role in promoting these cancer-associated features through specific TRP channels, include CaMKII, NF-κB, calpains and calcineurin pathways [119, 120], but other less studied signaling cascades may as well be involved.
While the members of TRPV family channels are frequently deregulated in many cancers and associated with certain cancer-specific cellular features, their regulation along the breast cancer progression is still poorly understood. TRPV1 channel is often upregulated in breast cancers and its high expression correlates with the tumor grade [121]. Some studies have shown no differences in between distinct breast cancer sub-types and expression levels of TRPV1 [122, 123, 124]. Aggregated TRPV1 in the intracellular compartment has, however, been linked to poor prognosis in breast cancer patients [125]. TRPV2 expression also seems to display oncogenic activity in various cancers [126, 127]. In triple-negative breast cancers (TNBCs), TRPV2 levels are especially prominent but correlate interestingly with high relapse-free survival in this case [122, 128]. Additionally, the study by Elbaz et al. [128], proposed the therapeutic potential of high TRPV2 to elevate the uptake and efficacy of chemotherapeutic agents in patients with TNBC. The role of TRPV4 in cancer progression has been investigated by several labs and its expression in breast cancers is highest in the basal-like cancer subtype [122, 129]. High TRPV4 expression has also been detected in IHC stainings from the metastatic lesions of invasive ductal carcinomas and its levels correlate with the tumor grade and size [130].
TRPV6 channel is likewise overexpressed in various cancers, including cancers of the mammary tissue [76, 131, 132, 133, 134]. The levels of overexpressed TRPV6 vary a lot depending on the breast cancer subtype, and as with the TRPV4 channel also TRPV6 levels are highest in the basal-like breast cancers and HER2-enriched molecular subtypes [76, 135, 136]. In line with this, ER receptor-negative breast cancers and cancer cell lines with several overlapping features with the basal and HER2-enriched subtypes display significant amounts of TRPV6 [136]. High TRPV6 in the patients is also associated with lower survival in comparison to patients that express lower TRPV6 levels [136].
Of the TRPV family, TRPV3 and TRPV5 have been studied to less extent. TRPV3 is known to be expressed at low levels in different types of breast cancer subtypes and its possible association with cancer progression has not been well assessed [122]. Likewise, there are no reports on TRPV5 and its link to the progression of distinct breast cancer types [122]. While these two subtypes may not be important in respect of breast cancer progression, more studies are needed on the field to understand how the deregulation of the other TRPV forms takes place along cancer progression and whether for instance hormonal regulation or stromal changes could impact their expression and activity.
Various studies have shown the significance of calcium signaling in the uncontrolled proliferation of cancer cells [25, 137, 138]. Various plasma membrane-embedded calcium channels are acting as major sources of calcium for the regulation of such pathways that lead to elevated cell amounts [139, 140]. Among the TRP family, also TRPV channels contribute to these processes, related to malignant growth [120].
TRPV1 channel can mediate both Ca2+ and Na+-influx and trigger cell proliferation by two separate mechanisms: It can contribute to the activation of serine-threonine kinase Akt as well as to the activation of ERK1/2 downstream of the epidermal growth factor (EGFR) [141]. However, studies in the MCF-7 breast cancer cell line show that both agonists and antagonists of the TRPV1 channel can inhibit cell growth through yet unidentified mechanisms [142]. Thus, it may be that the balance in the expression of this protein is important for controlled cell proliferation through distinct intracellular pathways in a cell type-specific manner. MCF-7 cell line has also been utilized as a model to study TRPV2 in respect of cell proliferation. TRPV2 was shown to be responsive to insulin-like growth factor-I (IGF-I) [143] and tranilast, an anti-inflammatory agent, was reported to inhibit IGF-1-induced cell growth by blocking the calcium influx through TRPV2 [144]. Significant overexpression of TRPV4 is also linked to breast cancers and this seems to correlate with the tumor grade and size, leading to poor survival [122, 130, 145, 146]. However, evidence from studies performed with 4 T07, MDA-MB-231 and MDA-MB-468 breast cancer cell lines show that TRPV4 is dispensable for the proliferative potential of these specific breast cancer cell lines, since its silencing or pharmacological inhibition was not anti-proliferative [145, 147]. In contrast, high expression of TRPV6 is linked to the proliferation through Ca2+-triggered intracellular pathways and the high levels also act as prognostic factors together with potential resistance to chemotherapy [76, 134, 135]. Depletion of TRPV6 from the T47D breast cancer cell line, displaying high endogenous TRPV6, also decreases the proliferation of these cells [76, 136]. The precise mechanisms behind this are not understood but may involve PI3K/pAKT pathway that regulates cell proliferation, survival and therapeutic resistance in some breast cancer subtypes, including the HER2-enriched subtype. In line with this, depletion of TRPV6 was associated with lower levels of active, phosphorylated AKT in HCC-1569 breast cancer cells [148]. Studies in breast cancer cell lines, MCF-7 and MDA-MB-231, additionally showed the link in between TRPV6 and PI3K/Akt pathway as a functionally auto-inhibitory intramolecular interaction between S5 and S6 helices of TRPV6 was shown to contribute to TRPV6/PI3K association and the activation of PI3K/Akt/GSK-3β pathway [149].
TRPV6 activity and expression are known to be controlled by estrogen, progesterone, and 1,25-vitamin D that all play a role in the proliferation of breast cancer cells [76, 120]. Treatment of breast cancer cell line T47D with estrogen receptor antagonist, tamoxifen, also led to lower activity and expression of TRPV6 calcium channel protein. Further, the effect of tamoxifen on the functionality of TRPV6 was shown in EYFP-C1-TRPV6-transfected MCF7 breast cancer cells by Fura-2 calcium imaging [150]. Calcium levels in the transfected cells were found to be higher than in non-transfected cells and the calcium levels were lowered by 50% with tamoxifen-treatment. Interestingly, tamoxifen also played a role in TRPV6 inhibition in MDA-MB-231 cells that are estrogen receptor-negative [150], suggesting a direct impact on TRPV6-mediated Ca2+-influx. Besides tamoxifen, TRPV6 activity can also be negatively regulated by a protein called Numb1 [151]. Numb1 is maybe more known for its role in the stabilization of tumor suppressor protein p53 [152], affecting both cell cycle progression and apoptosis. Studies on the Numb1-TRPV6 link in MCF-7 breast cancer cells showed that Numb1-depleted cells displayed elevated TRPV6 expression and calcium influx as well as enhanced proliferation. TPV6 thus has interesting connections to the pathways of the major tumor suppressor protein as well as to hormones that play a role in breast cancer progression through the proliferative potential of the cells.
Apoptosis can be characterized as a programmed cell death process, which leads to the fragmentation of DNA. This strictly controlled process can take place through cell death-receptors or through mitochondria-mediated apoptotic pathways [153]. Apoptosis is also controlled by calcium-dependent pathways [154, 155, 156]. Changes in intracellular Ca2+-levels are known to influence the two major apoptotic pathways through gene expression [157, 158, 159, 160, 161]. For instance, the calcium/calmodulin-dependent signaling cascades can affect the balance in between cell cycle progression and apoptosis [160].
TRPV1-triggered calcium influx has been shown to act as a determinator of the balance in between cell proliferation and apoptosis. TRPV1-mediated apoptosis can take place through the mitochondrial mechanism, while its proliferation-supportive actions usually involve other cell membrane receptors or specific intracellular signaling cascades [141]. Studies with MCF-7 breast cancer cell line have also shown that high TRPV1 sensitizes cells to programmed cell death, induced by TRPV1 activator capsaicin [162, 163]. Likewise, capsaicin is involved in the induction of cell death in breast cancer cell line, SUM149PT through TRPV1 activation [121].
The role of TRPV4 in apoptosis has as well been investigated during the past few years and these studies support the role of high TRPV4 expression in inducing cell death. In breast cancer cell lines, MDA-MB-468 and HCC1569, activation of TRPV4 by pharmacological compounds reduced the viability of the cells [147]. Both cell lines display high endogenous TRPV4 levels and its activation was able to promote cell death by apoptosis or oncosis, while the same phenomenon was not detected in breast cancer cell lines with low TRPV4 levels. Moreover, the studies by Peters et al. found that TRPV4 activation has therapeutical relevance in vivo and can inhibit the growth of tumors [147]. Similarly, to TRPV4, overexpression of TRPV2 and its pharmacological activation with cannabidiol have been linked to inducing cytotoxic impact in SUM159 and MDA-MB-231 breast cancer cells via doxorubicin-treatment [128]. In contrast, the TRPV6 calcium channel seems to act oppositely and its high levels are rather protecting from apoptosis: TRPV6 calcium channel is known to get transported to the plasma membrane in an Orai1-mediated mechanism to control the survival of the cancer cells [164]. On the other hand, TRPV6 depletion from breast cancer cells with high expression of this protein can be used for decreasing the viability of the cells, as shown by studies in T47D breast cancer cells [76].
The tissue microenvironment undergoes drastic alterations along breast cancer progression [165, 166, 167]. Besides stiffness and composition of the matrix, there are also changes for instance in the amount of growth factors and acidicity of the environment that may trigger specific calcium channels [168, 169]. How TRPV channels, among other ion channels on the plasma membrane, respond to such cancer-linked cues from the extracellular space, is poorly understood. Additionally, stromal cells, such as fibroblasts, immune cells, or adipocytes that also express channel proteins, may be functionally altered and contribute to abnormal signaling from the stroma.
At least TRPV4 and TRPV6 are known to be responsive to stromal stiffening [92, 170, 171, 172, 173] and could be triggered by cancer-associated mechanical changes in the extracellular space. Furthermore, TRPV4 has been shown to control the expression of some extracellular matrix proteins, in this way contributing itself to the stiffness of the environment [130]. Stiffening may impact various processes along cancer progression and one of these features is the growth of new vasculature, angiogenesis. The first evidence that TRPV4 could also be involved in angiogenesis along breast cancer progression was presented in the work by Fiorio Pla et al. [174]. The authors discovered the role of TRPV4 in mediating arachidonic acid (AA)-promoted migration of endothelial cells (ECs), derived from breast tumors. These endothelial cells displayed high endogenous TRPV4 and were enhancing the migration of ECs, a key step in the growth of new vessels. This step could be inhibited by antagonist or siRNAs against TRPV4 and the opposite was detected with TRPV4 stimulation [174].
Support for the role of TRPV4 in angiogenesis has also been shown in studies by Adapala et al. [170]. TRPV4 seems to control the mechanosensitivity of tumor endothelial cells (TECs), and the angiogenetic process all the way to the maturation of the vessels. Interestingly, the authors found that these TECs display lower TRPV4 levels than normal endothelial cells, leading to angiogenesis through the altered ability of the cells to sense the mechanical environment. Besides, they discovered that normalizing TRPV4 levels could be acting as an anti-angiogenetic therapy to normalize the vasculature and enhance drug efficiency. Moreover, studies by Thoppil et al. have shed light on the mechanisms that TRPV4 could utilize in the regulation of the angiogenetic process [175]. These studies also linked low TRPV4 levels of endothelial cells to enhanced migration and disturbed angiogenesis. This could be reversed by the treatment of cells with Rho kinase inhibitor, Y-27632, suggesting that TRPV4 action in angiogenesis involves modulation of mechanosensitivity of ECs via Rho pathway [175]. Based on these data, TRPV4 may therefore be a significant regulator of angiogenesis and this information could potentially be utilized in therapeutical approaches. TRPV4 thus has an important role in the modulation of tumor stroma by affecting both its mechanical features as well as the growth of new blood vessels in the stroma. Interestingly, TRPV4 is this far the only channel protein among the TRP superfamily that has been implicated in the growth of new vessels along cancer progression.
Abnormal expression of distinct TRPV channels has also been linked to invasive migration and metastasis. Several TRP channel family members are connected to Rho-pathway and display the potential to promote invasive migration through Rho-dependent cytoskeletal reorganization [174, 176]. Of the TRPV family members, at least TRPV2 appears to be under the control of Rho-kinase as the treatment of breast cancer cells with Rho-inhibitors lowers the levels of TRPV2 [177]. Another factor, known to impact cell migration through activation of TRPV2, is the antimicrobial peptide, LL-37. LL-37 can influence cancer progression through various ways, including its positive impact on cancer cell migration [178]. The expression of LL-37 correlates with the expression levels of TRPV2 in breast cancer cell lines and has been shown to promote invasive migration of MDA-MB-435, MCF-7 and MDA-MB-231 cells dependently on TRPV2 [179]. Mechanistically, LL-37 increases calcium influx through TRPV2 and enhances cell migration via PI3K/AKT signaling [180]. Activation of PI3/Akt pathway as such leads to recruitment of TRPV2 into pseudopodia, impacting the migration of specific breast cancer cell types [179].
TRPV4 has also been associated with invasive migration and has been linked to EMT and lower relapse-free survival in basal breast cancers with lymph node involvement [181]. In MDA-MB-468 breast cancer cells, TRPV4-mediated calcium-influx plays an important role in the EGF-triggered EMT: activation of TRPV4 by chemical compounds was able to drive the upregulation of various EMT markers in these cells [181]. In line with these results, TRPV4 depletion from a murine mammary cancer cell line, 4T07, lowered the migration capability and 3D invasion of these normally high TRPV4-expressing cells [145]. Furthermore, determining TRPV4 levels from database information of human clinical samples as well as phosphoproteomic analyses of xenograft-derived in vitro models, indicated the role of TRPV4 in breast cancer metastasis, high expression of TPV4 in basal breast cancers and its association with poor prognosis [145]. Additionally, TRPV4 KD decreased the levels of metastatic nodules in mouse xenografts [145].
Interestingly, TRPV4 also implies to determine the stiffness of cancer cells through actin dynamics, in this way affecting deformability and metastasizing potential of breast cancer cells [130, 145]. TRPV4 was regulating the compliance of cancer cells through Ca2+-mediated AKT-E-cadherin signaling [130]. Additionally, TRPV4 was involved in the expression of extracellular matrix proteins and the modeling of the matrix [130]. Knowing the mechanosensitive nature of TRPV4, there seems to be a functional feedback loop in between TRPV4 and its mechanical environment that plays a role along cancer progression. TRPV4 may therefore impact invasion and metastasis of breast cancer cells through various means.
Besides TRPV2 and -4, also TRPV6 has been linked to invasion and metastasis in breast cancers. Overexpression of TRPV6 is very common in breast carcinomas and TRPV6 levels have been shown to be very high in the invasive regions of the mammary carcinoma samples [76, 135]. The mechanisms of how TRPV6 could impact invasive progression, are not well understood. However, it seems to be linked to both actomyosin dynamics and the expression of EMT markers that could be critical along the development of invasive disease [92]. Further, inhibition of TRPV6-mediated calcium-influx by lidocaine, led to lower migration and invasion ability of the MDA-MB-231 breast cancer cells [182]. The exact molecular pathways, affecting TRPV6-mediated invasion in breast carcinomas, needs still to be further clarified.
TRPV channels have been indicated to function in nociception, the sensation of pain [41, 44]. Although, not directly linked to the function of the mammary gland, it plays a role in breast cancer progression in the form of bone pain as a consequence of bone metastasis formation.
One of the main TRPV channels, playing a role in nociception, is TRPV1 [44, 46]. Interestingly, the formation of a tumor within a bone is known to increase the expression of TRPV1 in a specific population of dorsal root ganglion neurons [183]. In addition, TRPV1 is important for both the development and maintenance of cancer pain [184]. Likewise, it has been observed that extracellular cues within the bone microenvironment, developed during the formation of breast cancer-derived metastasis, are contributing to the pain sensation via TRPV1 activation [185]. In line with these data, experiments with rat models have revealed that when mammary carcinoma cells are injected to the rat bones, TRPV1 expression is upregulated within the dorsal root ganglion cells [184, 186]. Further, MDA-MB-231 breast cancer cells have been shown to promote sensory neuronal growth and elevate sensitivity to active TRPV1 [187]. TRPV1 may therefore be important in the sensation of pain upon metastatic breast cancer and its pharmacological targeting has also been pursued for instance by blocking the capsaicin receptor [188].
The mechanisms through which TRPV1 is induced upon bone cancer and -metastasis have been studied as well: in a rat bone cancer-pain model, utilizing mammary carcinoma cells injected to the bone cavity, TRPV1 was upregulated and activated through induction of Insulin-like Growth Factor 1, IGF-1 [184]. Additionally, TGF-β1 is known to contribute to pain upon bone cancer via upregulation and sensitization of TRPV1 in sensory neurons [189, 190]. In conjunction with these observations, TGFβRI and TGFβRII are known to be upregulated in this rat bone cancer-pain model upon inoculation of rat mammary carcinoma cells [190]. Furthermore, lysophosphatidic acid, LPA, triggers TRPV1 through a PKCε-dependent signaling cascade in dorsal root ganglion neurons upon bone cancer formation in rats [191]. TRPV1 may thus be a central player along the pathways that are behind bone cancer pain in advanced breast cancers.
The emerging role of TRP channels in cancer progression has been widely admitted. Abnormal expression of several TRPV family members, along with the altered expression of other TRP family channels, direct various cancer-linked features, including proliferation, apoptotic control, angiogenesis, and invasive migration leading to distant metastasis [76, 122, 129, 133, 191] (see also Figure 1). For that, these calcium channel proteins can also serve as biomarkers and as attractive objectives for therapeutical targeting. The fact that these ion channels can be activated by small pharmacological compounds, also supports their potential for therapeutical approaches and several studies have been performed with potential modulators against the activity of these proteins to target cancer cells [191, 192, 193, 194, 195].
The role of TRPV family members in the maintenance of normal mammary epithelium and in the induction of hallmarks of cancer. The connection of distinct TRPV family members to the structural and functional maintenance of the normal mammary epithelium as well as their connections to specific steps along breast cancer progression are summarized in this figure. The corresponding references are found within the brackets.
TRPV1 channel is activated by a natural compound, capsaicin, the primary pungent component of the chili pepper, and there is evidence for its potential anticancer activity and ability to induce apoptosis [196]. In breast cancer models, ectopic expression of TRPV1 combined with capsaicin-treatment, leads to mitochondrial Ca2+ accumulation and necrosis [197]. TRPV1 expression alone was able to stop cell proliferation and induce apoptosis via activation of caspase-3 activity in breast cancer cell lines [197]. As capsaicin, through its impact on TRPV1 activity, also causes pain sensation, it cannot be used as a therapeutical compound in high doses to induce apoptosis. However, a chemical compound, dihydropyridine derivative MRS1477, operates as a modulator of TRPV1 activity, and can be used together with capsaicin to promote apoptosis in breast cancer cells [163]. A study by Wu et al. investigated the mechanisms behind capsaicin-mediated apoptosis by utilizing a TRPV1-inducible MCF-7 breast cancer cell line [162]. They found that the cell death upon capsaicin-treatment was necrotic and linked to elevated levels of c-Fos and receptor-interacting serine/threonine kinase 3, RIP3 that plays a role in the inflammatory mode of cell death, necroptosis [162]. Additionally, an alkyl sulfonamide analogue of capsaicin, RPF151, shows potential for targeting breast cancer cells as shown by studies with MDA-MB-231 cells [198]. In this study, capsaicin analogue was found to downregulate p21, cyclins A, D1, and D3, subsequently leading to arrest in the S-phase and induction of apoptosis [198]. Furthermore, modulation of TRPV1 activity in sensory neurons by pharmacological compounds may also lead to an anti-tumoral immune response [199]. Systemic treatment with low-dose of capsaicin was shown to trigger an anti-inflammatory response against metastatic breast carcinomas and have potential as a therapy choice [199]. On the other hand, a synthetic antagonist against TRPV1, capsazepine, CPZ, has also been shown to possess anti-cancer effects in vivo through its impact on cell proliferation in several cancer cell types, including breast cancer cells [200]. Capsazepine and its analogues may thus act as potential therapeutic compounds in the future [200].
Besides capsaicin, another natural compound, cannabidiol, has an impact on the induction of apoptosis in MDA-MB-231 breast cancer cells through the TRPV1 channel [201]. These studies showed that besides inducing apoptosis through vanilloid transient receptor potential vanilloid type-1 receptors, cannabidiol can act in the induction of apoptosis via cannabinoid receptor type 2, CB2 and through cannabinoid/vanilloid receptor-independent mechanisms [201]. The interconnection between cannabinoid receptors and TRPV1 has also been investigated in another study that utilized MDA-MB-231 cells as a model. In this study, the role of these receptors in cancer cell invasion was assessed and the results linked activation of both CB1 and TRPV1 by agonist to reduced invasion capability of the MDA-MB-231 cells [202].
Intriguingly, it has also been noticed that some common chemotherapeutic agents interact with TRPV-dependent pathways: The combination of selenium and cisplatin operate through overlapping intracellular pathways and can also modulate TRPV1 activity to induce apoptosis in MCF-7 breast cancer cell line [203]. In addition, combination therapy with alpha-lipoic acid, ALA and cisplatin benefits from the activation of the TRPV1 channel to induce apoptosis in MCF-7 breast cancer cells [204]. Furthermore, in the same breast cancer cell line, chemotherapeutic agent 5-Fluorouracil induces mitochondrial cytotoxicity and apoptosis upon TRPV1 activation [205]. The effectiveness of chemotherapy, combined with the activation of transient receptor potential channel activity, has also been demonstrated with TRPV2: activation of TRPV2 with cannabidiol, CBD, sensitized aggressive triple-negative breast cancer (TNBC) cells to the chemotherapeutic drug, doxorubicin, consequently inhibiting tumor growth in
Besides induction of apoptosis and inhibition of cell proliferation, TRPV channels have been investigated as potential targets to block invasive migration. TRPV2 has been associated with the function of antimicrobial peptide hCAP18/LL-37, which stimulates both proliferation and migration of various cancer cell types, including breast cancer cells [206]. In line with these previous findings, TRPV2 silencing was found to diminish the LL-37-dependent migration of MCF-7 and MDA-MB-231 breast cancer cells [179]. As TRPV4 is involved in invasive migration as well, and modulation of its activity is possible through several compounds, the potential of targeting this protein should be assessed for reducing metastasis in breast cancer models. Several animal studies have already shown the effectiveness of TRPV4 antagonists as therapeutic agents for treating several other diseases [207, 208]. In addition, TRPV6 is overexpressed in breast cancers and could be targeted in estrogen receptor-negative subtype of mammary carcinomas [136]. Specific TRPV6-targeting compounds have been developed that could be used for manipulating TRPV6 activity and such compounds have also shown promising results in various cancer types, including breast cancer cells [209, 210, 211, 212]. While the utilization of TRPV modulators to induce apoptosis or inhibition of either cell proliferation or migration has shown very promising results, one should also consider the risk of other unwanted side-effects through toning of some critical signaling cascades. Such problems can be caused due to the unspecificity of certain antagonists and agonists against the ion channel proteins, leading to the deregulation of several channel protein types. In addition, the wide expression of many of the ion channel proteins throughout various tissues will create challenges in the modulation of ion channel activities at specific sites. For instance, TRPV1 is very widely expressed and most often linked to toxicity in the trials [213, 214]. The balance in the expression and activity of these proteins is though decisive for such a variety of cellular processes.
The mammary epithelium is strictly regulated by hormonal signaling, growth factors and cytokines that direct its development, growth and functional organization. In addition, the mammary epithelium is exposed to various physical alterations in the microenvironment that may be sensed by the plasma-membrane embedded structures, such as the ion channels in the mammary epithelial cell populations. Calcium ion pumps and influx through them play a central role in decoding many of the extracellular cues into intracellular signaling. Therefore, these channel proteins greatly impact all essential processes in the maintenance of normal mammary tissue and participate to the development of pathophysiological conditions.
TRPV channels, among the TRP superfamily, are abundantly expressed in discrete tissues, also in the mammary tissue. Of these channel proteins, at least TRPV4-6 have identified functions in the structural and functional maintenance of the normal mammary epithelium, both directly in the mammary epithelium or indirectly through the control of ion influx in other tissues that impact physiological functions of the mammary gland. Whether the other TRPV channels have importance in the structural maintenance of the mammary epithelium or along with lactation, remains to be studied.
Abnormal expression of TRPV channels is also abundantly found in human breast carcinomas and these channel proteins are involved in triggering many of the typical hallmarks of cancers. How TRPV channels are deregulated or aberrantly expressed along breast cancer progression, is still poorly understood. However, as these proteins are sensitive to any physical or biochemical changes in the microenvironment, it is more than likely that they would be affected by the cancer-associated changes in the stroma. This topic certainly requires more investigations in the future. As inducers of the cancer-linked features, such as proliferation, inhibition of apoptosis, invasive migration and angiogenesis, TRPV family members also act as attractive targets for therapeutical choices. A number of known natural and synthetic modulators of TRPV activity already exist and some of them have given promising results in the trials that aim for pharmacological intervention of breast cancers. However, as these proteins are upstream of numerous intracellular pathways that guide cellular functions, there are challenges in such attempts. Furthermore, one should consider the possible interplay in between distinct plasma-membrane embedded calcium channels, several of which may be deregulated along cancer development and impact overlapping intracellular pathways. Such a phenomenon creates a more complex picture on the role of specific ion channels in cancer progression and requires extensive studies in the future.
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Its effects on the economy (and also on the wider society) are well researched, yet still not completely. Corruption thus inhibits economic growth and affects business operations, employment and investments. It also reduces tax revenue and the effectiveness of various financial assistance programs. The wider society is influenced by a high degree of corruption in terms of lowering of trust in the law and the rule of law, education and consequently the quality of life (access to infrastructure, health care). There also does not exist an unambiguous answer as to how to deal with corruption. Something that works in one country or in one region will not necessarily be successful in another. This chapter tries to answer at least a few questions about corruption and the causes for it, its consequences and how to deal with it successfully.",book:{id:"6487",slug:"trade-and-global-market",title:"Trade and Global Market",fullTitle:"Trade and Global Market"},signatures:"Štefan Šumah",authors:[{id:"228073",title:"Mr.",name:"Stefan",middleName:null,surname:"Sumah",slug:"stefan-sumah",fullName:"Stefan Sumah"}]},{id:"55499",title:"Human Resources Management in Nonprofit Organizations: A Case Study of Istanbul Foundation for Culture and Arts",slug:"human-resources-management-in-nonprofit-organizations-a-case-study-of-istanbul-foundation-for-cultur",totalDownloads:2282,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The aim of this study is to investigate the efficiency and importance of human resources management in nonprofit organizations. The understanding was included to the literature as personnel management at the beginning of the twentieth century and it turned into an approach as human resources management in the 1980s. It could be observed that many organizations, which deem the human as the most critical stakeholder, adopt a traditional way of personnel management in operating human resources. The employees play a key role in the success of an organization. For this reason, subjects such as recruitment, training, development, career management, performance appraisal, occupational health, and safety are the fundamental functions of human resources management. The study examines to what extent these roles are evaluated through a case study. The subject matter of the study is the most powerful culture and art foundation in Turkey. Compared to many other nonprofit organizations, the foundation actively performs a variety of services within a year worldwide. The fact that the total number of employees might rise up to 800, including the field personnel, indicates the need of a good functioning human resources management. The human resources practices of the foundation are examined and evaluated within that scope.",book:{id:"5826",slug:"issues-of-human-resource-management",title:"Issues of Human Resource Management",fullTitle:"Issues of Human Resource Management"},signatures:"Beste Gökçe Parsehyan",authors:[{id:"189113",title:"Dr.",name:"Beste",middleName:null,surname:"Gokce Parsehyan",slug:"beste-gokce-parsehyan",fullName:"Beste Gokce Parsehyan"}]},{id:"59152",title:"Marketing Strategies for the Social Good",slug:"marketing-strategies-for-the-social-good",totalDownloads:1590,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Social network sites (SNS) have proven to be a good environment to promote and sell goods and services, but marketing is more than creating commercial strategies. Social marketing strategies can also be used to promote behavioral change and help individuals transform their lives, achieve well-being, and adopt prosocial behaviors. In this chapter, we seek to analyze with a netnographic study, how SNS are being employed by nonprofits and nongovernment organizations (NGOs) to enable citizens and consumers to participate in different programs and activities that promote social transformation and well-being. A particular interest is to identify how organizations are using behavioral economic tactics to nudge individuals and motivate them to engage in prosocial actions. By providing an understanding on how SNS can provide an adequate environment for the design of social marketing strategies, we believe our work has practical implications both for academicians and marketers who want to contribute in the transformation of consumer behavior and the achievement of well-being and social change.",book:{id:"6583",slug:"marketing",title:"Marketing",fullTitle:"Marketing"},signatures:"Alicia De La Pena",authors:[{id:"196878",title:"Dr.",name:"Alicia",middleName:null,surname:"De La Pena",slug:"alicia-de-la-pena",fullName:"Alicia De La Pena"}]}],onlineFirstChaptersFilter:{topicId:"4",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81785",title:"Social Distancing Disbanding Learner Groupings: A Case on Language Development",slug:"social-distancing-disbanding-learner-groupings-a-case-on-language-development",totalDownloads:1,totalDimensionsCites:null,doi:"10.5772/intechopen.104893",abstract:"Information sharing is a fundamental aspect in learning an unfamiliar, yet, an additional language, with specific regards to reading comprehension. Language teachers are faced with a task to monitor development, performance, and effectiveness in learner reading proficiencies. This chapter aims to measure if disbanding learner groupings as per the social distancing protocols brought about by COVID-19 restrictions has any impact on language enhancement. Henceforth, there are limited suggestions by literature in relation to disbanding learner groupings, yet improved reading proficiency is one of the crucial language aspects to be mastered for one to be a successful scholar. Nonetheless, this chapter aims to provide teaching strategies applied by English language teachers to necessitate transmitted learning in accordance with information sharing as learners are dependent on one another for language enhancement, thus leading to academic achievement.",book:{id:"10912",title:"Psychosocial, Educational, and Economic Impacts of COVID-19",coverURL:"https://cdn.intechopen.com/books/images_new/10912.jpg"},signatures:"Bulelwa Makena and Thandiswa Mpiti"},{id:"82248",title:"Sustainability and Excellence: Pillars for Business Survival",slug:"sustainability-and-excellence-pillars-for-business-survival",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.105420",abstract:"The chapter presents an overview of management models starting with self-assessment (ISO 9004) and continuing with the European Foundation for Quality Management (EFQM) Excellence Model. Stakeholders’ analysis and their needs and expectations diagnostic are the baseline for building sustainable businesses. Sustainability and excellence are connected, and particular details of these approaches’ implementation are presented. Partnership development appears a key principle in the EFQM model. Based on companies’ strategies analysis, a simplified model may be proposed in order to support business survival in changing environments. Some guidelines to allow assessment of excellence fundamentals implementation are given. Based on experience and without seeing as exhaustive, a summary sheet of possible approaches and deployments is given. This may be used as a practical tool to connect actions implemented in organizations with the excellence model enablers, so as to facilitate assessment to explore the performance maturity level. The same sequence of Plan-Do-Check-Act relates approaches stated by ISO 26000 and sustainability initiatives. Embedding excellence and sustainability into business strategic objectives allows the management to define the framework for competitive continuous improvement.",book:{id:"11476",title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg"},signatures:"Irina Severin, Maria Cristina Dijmarescu and Mihai Caramihai"},{id:"82269",title:"CSR Reporting and Blockchain Technology",slug:"csr-reporting-and-blockchain-technology",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.105512",abstract:"Blockchain technology is a public ledger that stores data in a chain of blocks which can radically improve the quality of our records from “records that might be trustworthy” to “records that trust is absolute”. This chapter explores one area that blockchain technology can radically transform but has not yet received significant attention. We evaluate the suitability of applying blockchain technology for corporate social responsibility (CSR) reporting. We demonstrate that blockchain technology is suitable in the context of CSR reporting since there is a strong need for an immutable common database shared among various stakeholders with potential trust issues. We also argue that blockchain technology does not completely eliminate existing trusted third parties such as governments, international organizations that provide CSR reporting standards, major CSR reporting assurance companies and major CSR infomediaries. In particular, blockchain technology can be used as a platform that integrates all traditional trusted third parties, transforms their functions, and reduces their drawbacks for advancing CSR reporting. We also demonstrate that a permissionless public blockchain would be the most suitable structure.",book:{id:"11602",title:"Corporate Social Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11602.jpg"},signatures:"Pattarake Sarajoti, Pattanaporn Chatjuthamard, Suwongrat Papangkorn and Piyachart Phiromswad"},{id:"82270",title:"From Corporate Social Opportunity to Corporate Social Responsibility",slug:"from-corporate-social-opportunity-to-corporate-social-responsibility",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.105445",abstract:"During the early 2020s, business leaders have been faced with the confluence of multiple challenges, the likes of which they had never seen before: the Covid-19 pandemic, systemic racism and the continued escalation of the climate crisis. These challenges forced companies to search for new ways to create value for their investors and other stakeholders; these challenges forced business leaders to think differently about the role that their companies play in the broader society. As we think about how business leaders balance these short-term opportunities and long-term strategies, it is critical that they realize that he level of social responsibility expected by society has risen significantly in recent years. Companies need to move beyond seeing social dynamics as short-term opportunities and incorporate them into long-term strategies. In this study, we offer 6 rules for moving forward and for turning short-term social opportunities into long-term strategic value creations. Business leaders need to focus on offering products, services and relationships that help their stakeholders improve their lives. In doing this, we rely on both academic studies and case studies to show how moving beyond corporate social opportunity and towards value creation through social responsibility is the key to long-term corporate success.",book:{id:"11602",title:"Corporate Social Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11602.jpg"},signatures:"Brian Bolton"},{id:"82341",title:"Circular Economy - Recent Advances in Sustainable Construction Waste Management",slug:"circular-economy-recent-advances-in-sustainable-construction-waste-management",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.105050",abstract:"With time, construction waste is increasing massively and its dumping is a serious issue globally. Utilizing the waste in various products and construction projects is boosting, but still, the amount of waste is much higher. Transitions to more sustainable construction can assist in attaining the specific goal of slowing down natural resources depletion, reducing environmental damage by extracting and recycling new materials, and minimizing pollution from the processing, use, and disposal of materials once they complete their useful life period. An important way to do this is to improve efficiency and bring productivity in the utilization of resources. The circular economy is more productive and healthier, where raw materials are stored longer in the production cycle and can be recycled, thus producing less waste. Due to potential benefits through enhanced quality and productivity in the processes, the concept of circular economy is grabbing the attention of construction industry stakeholders to attain sustainable construction waste management. This chapter focuses on the significance of a circular economy for the attainment of sustainable waste management in the construction sector. Moreover, the impact of construction waste and its utilization through recent sustainable solutions which also impact the economy has also been highlighted.",book:{id:"11256",title:"Circular Economy - Recent Advances of Sustainable Waste Management",coverURL:"https://cdn.intechopen.com/books/images_new/11256.jpg"},signatures:"Muhammad Ali Musarat, Muhammad Irfan, Wesam Salah Alaloul, Ahsen Maqsoom, Muhammad Jamaluddin Thaheem and Muhammad Babar Ali Rabbani"},{id:"82344",title:"Supply Chain: A Modeling-Based Approach for Cyber-Physical Systems",slug:"supply-chain-a-modeling-based-approach-for-cyber-physical-systems",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.105527",abstract:"Within the frame of this chapter, the author focuses on the distribution processes of green supply chain solutions and describes a potential mathematical model, taking environmental aspects into consideration. The first part of the chapter includes a systematic literature review. Based on the identified research gap, a new mathematical model is described, which makes it possible to describe last-mile logistics processes from an environmental point of view. The functional model of the distribution system includes the potential of Industry 4.0 technologies, which makes it possible to gather real-time information from the distribution process and use real-time status information for a sophisticated design and operation. The mathematical model of this approach defines an NP-hard optimization problem; therefore, heuristic optimization algorithm is supposed to solve the design and operation tasks of the green distribution problem. As the computational results show, cyber-physical systems increase the performance of green supply chain solutions and have a great impact on operational cost. As the numerical example shows, the integrated approach resulted in a 5.3% cost reduction in transportation operations.",book:{id:"11263",title:"Supply Chain - Recent Advances and New Perspectives in the Industry 4.0 Era",coverURL:"https://cdn.intechopen.com/books/images_new/11263.jpg"},signatures:"Ágota Bányai"}],onlineFirstChaptersTotal:266},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:16,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:4,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"3",title:"Dentistry",doi:"10.5772/intechopen.71199",issn:"2631-6218",scope:"\r\n\tThis book series will offer a comprehensive overview of recent research trends as well as clinical applications within different specialties of dentistry. Topics will include overviews of the health of the oral cavity, from prevention and care to different treatments for the rehabilitation of problems that may affect the organs and/or tissues present. The different areas of dentistry will be explored, with the aim of disseminating knowledge and providing readers with new tools for the comprehensive treatment of their patients with greater safety and with current techniques. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This series of books will focus on various aspects of the properties and results obtained by the various treatments available, whether preventive or curative.
",coverUrl:"https://cdn.intechopen.com/series/covers/3.jpg",latestPublicationDate:"May 13th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:8,editor:{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:43,paginationItems:[{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:1,totalCrossrefCites:0,totalDimensionsCites:null,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82212",title:"Protein Prenylation and Their Applications",doi:"10.5772/intechopen.104700",signatures:"Khemchand R. Surana, Ritesh B. Pawar, Ritesh A. Khairnar and Sunil K. 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Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",institution:null}]},{type:"book",id:"6820",title:"Keratin",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6820.jpg",slug:"keratin",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Miroslav Blumenberg",hash:"6def75cd4b6b5324a02b6dc0359896d0",volumeInSeries:2,fullTitle:"Keratin",editors:[{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"7978",title:"Vitamin A",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7978.jpg",slug:"vitamin-a",publishedDate:"May 15th 2019",editedByType:"Edited by",bookSignature:"Leila Queiroz Zepka, Veridiana Vera de Rosso and Eduardo Jacob-Lopes",hash:"dad04a658ab9e3d851d23705980a688b",volumeInSeries:3,fullTitle:"Vitamin A",editors:[{id:"261969",title:"Dr.",name:"Leila",middleName:null,surname:"Queiroz Zepka",slug:"leila-queiroz-zepka",fullName:"Leila Queiroz Zepka",profilePictureURL:"https://mts.intechopen.com/storage/users/261969/images/system/261969.png",biography:"Prof. Dr. Leila Queiroz Zepka is currently an associate professor in the Department of Food Technology and Science, Federal University of Santa Maria, Brazil. She has more than fifteen years of teaching and research experience. She has published more than 550 scientific publications/communications, including 15 books, 50 book chapters, 100 original research papers, 380 research communications in national and international conferences, and 12 patents. She is a member of the editorial board of five journals and acts as a reviewer for several national and international journals. 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His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. 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He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}}]}},subseries:{item:{id:"27",type:"subseries",title:"Multi-Agent Systems",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11423,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. 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possibility to collaborate with more research groups interested in animal nutrition, leading to the development of new feeding strategies and food valuation while being more sustainable with the environment, allowing more readers to learn about the subject.",author:{id:"175967",name:"Manuel",surname:"Gonzalez Ronquillo",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",slug:"manuel-gonzalez-ronquillo",institution:{id:"6221",name:"Universidad Autónoma del Estado de México",country:{id:null,name:"Mexico"}}}},{id:"18",text:"It was great publishing with IntechOpen, the process was straightforward and I had support all along.",author:{id:"71579",name:"Berend",surname:"Olivier",institutionString:"Utrecht University",profilePictureURL:"https://mts.intechopen.com/storage/users/71579/images/system/71579.png",slug:"berend-olivier",institution:{id:"253",name:"Utrecht 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living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine"},{id:"8",title:"Bioinspired Technology and Biomechanics",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation"},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:{title:"Biomedical Engineering",id:"7"},selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 24th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:314,numberOfPublishedBooks:31,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/140915",hash:"",query:{},params:{id:"140915"},fullPath:"/profiles/140915",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()