The frequency of presentation in the general population of the types of abdominal wall hernia.
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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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\r\n\tTropical plant species include some fruit, flowering plants, indoor and outdoor, climbers, and herbaceous plants including perennials, annuals, bulbous plants. Further, palms, ferns, and other plants are included in the list of tropical plant species. To successfully grow these plant species in orchards and gardens of tropical and subtropical regions, several factors need to be taken care of.
\r\n\r\n\tThis book aims to provide a broader platform to discuss how to grow fruit and ornamental plants for nutrition, nutraceuticals, and aesthetic values. Further, the issues, advancements in technologies, and solutions to the problems of these plant species will be discussed. Hence, the key features of the book that will broadly be, but not be limited to production of tropical fruit plant species and orchard management, production to industry management of tropical medicinal plant species and tropical ornamental plant species nursery and garden management (outdoor and indoor herbaceous plant species, tropical outdoor and indoor flowering plant species, and outdoor and indoor foliage plant species).
",isbn:"978-1-80356-075-5",printIsbn:"978-1-80356-074-8",pdfIsbn:"978-1-80356-076-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,hash:"5b101dfc7d68d23a0072d99987b029c6",bookSignature:"Prof. Muhammad Sarwar Khan",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11311.jpg",keywords:"Tropical Plants, Tropical Fruit Plants, Tropical Ornamental Plants, Biotechnology, In Vitro Culture, Plant Architecture, Plant Genealogy, Nursery Management, Orchard Development, Disease Management, Insect-Pest Management, Medicinal Plants and Nutraceuticals",numberOfDownloads:28,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 3rd 2021",dateEndSecondStepPublish:"December 24th 2021",dateEndThirdStepPublish:"March 1st 2022",dateEndFourthStepPublish:"May 20th 2022",dateEndFifthStepPublish:"July 19th 2022",remainingDaysToSecondStep:"5 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Well-established educationist, scientist, editor, and recipient of prestigious awards who has vastly published in high-impact journals, including Nature and Nature Biotechnology, and is an author of several books and book chapters.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"212511",title:"Prof.",name:"Muhammad Sarwar",middleName:null,surname:"Khan",slug:"muhammad-sarwar-khan",fullName:"Muhammad Sarwar Khan",profilePictureURL:"https://mts.intechopen.com/storage/users/212511/images/system/212511.jpg",biography:"Muhammad Sarwar Khan is a distinguished Plant Molecular Biologist who started his career as a Bachelor and Master student in horticulture. He earned his Ph.D. from the University of Cambridge, UK. Dr. Khan was awarded a prestigious fellowship to research at the Waksman Institute of Microbiology, Rutgers, The State University of New Jersey, by the Rockefeller Foundation. He has served as the founding Head of the Biotech Interdisciplinary Division at the NIBGE and is currently serving as the Director of the Center of Agricultural Biochemistry and Biotechnology (CABB), University of Agriculture, Faisalabad, Pakistan. Dr. Khan has supervised more than 100 Ph.D. candidates, MPhil students, and researchers. He has published several papers in high-impact journals, including Nature and Nature Biotechnology, and is the author of several book chapters and books. Dr. Khan has received several prestigious awards, including the President’s Medal for Technology, a Gold Medal in Agriculture from the Pakistan Academy of Sciences, a Performance Gold Medal, the Biotechnologist Award by the National Commission of Biotechnology, and the Best University Teacher Award by the Higher Education Commission of Pakistan. He is a fellow of the Cambridge Commonwealth Society, the Cambridge Philosophical Society, the Rockefeller Foundation, and the Cochran Foundation. 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Projections show dramatic increases in older population; approximately by 2030 there will be an estimated 8 million people who are 85 years or older [1-3]. Moreover, 25% of the population in USA will be age 65 years or older in 2050. The percentage over the age of 85 is expected to triple [4-7]. Europe has experienced the similar transition to an older population profile over the last century which reflects a world-wide demographic trend towards an ageing population. Department of Health reports that in Britain, the number of people aged over 65 years has doubled in the last 70 years and the number of people over 90 years is expected to double in the next 25 years [8]. Similarly D\'Astolfo et al state that older adults aged 65 plus, are the fastest growing segment of the Canadian population [9].
The European Union has identified the provision of health and social care for this population as a crucial challenge for the 21st century. In a shift away from merely extending life, ways of reducing morbidity and coping with disability, preventing incapacity, extending the quality of life and enhancing the functional independence of older people will be an important component of service provision [10,11]. Recent efforts have begun to concentrate on the predictors of successful aging, but age-based comparisons of the pain experience remain challenging due to the complexity and non-uniformity of the aging process [12]. Therefore, there is an urgent and growing need for interventions that are effective in decreasing pain, suffering, and pain-related disability in this group.
Although chronic pain is a highly prevalent and often disabling condition among older adults, the prevalence in the elderly is not properly defined. Some studies suggest that fifty percent of community dwelling adults aged 60 years or above have been found to experience pain and this number increases to 45–80% in the nursing home population with analgesics being used in 40% to 50% of residents [1,13-19]. Brown et al report higher percentage and state that more than 90% of the elderly living in the community experienced pain within the past month [6]. Given the prevalence of chronic pain, its impact on health, and its costs, which approach $100 billion annually, chronic pain represents a major public health issue [20].
While the existence of acute pain remains approximately the same across the adult life span, there is an age-related increase in the prevalence of chronic pain at least until the seventh decade of life [13,15]. Approximately 57% of older adults report experiencing pain for 1 or more years compared with less than 45% of younger people. Furthermore, long-term care data indicate that over 40% of patients, who were known to have pain at an initial assessment, had worsening or severe pain at the time of the second assessment 2–6 months later [21].
Chronic musculoskeletal pain (CMP) is the most common, non-malignant disabling condition that affects at least one in four older people [22,23]. The most musculoskeletal pain in the joints of the upper and lower extremities, especially hips, knees, and hands, is associated with the degenerative changes of osteoarthritis. Older adults may also develop tendonitis and bursitis, as well as inflammatory joint and muscle disease [24]. The most common painful musculoskeletal conditions among older adults are osteoarthritis, low back pain, fibromyalgia, chronic shoulder pain, knee pain, myofascial pain syndrome and previous fracture sites [7,23,25].
It is reported that the most common causes of pain identified in nursing home patients included arthritis and previous fractures. Arthritis alone affects well over 20 million Americans with an increase to 40 million expected by 2020. Twenty-nine percent of Medicare patients in nursing homes with a fracture in the prior 6 months suffer with daily pain [13]. Also surgical procedures are more frequently performed on older people. In the Medicare population in the United States for example, rates of total joint replacement surgery for patients with severe hip or knee osteoarthritis are more than doubled between 1988 and 1997. Over the same time period, rates of spine surgery in Medicare patients increased by 57% [23]. Chronic low back pain (CLBP) is one of the most common, poorly understood, and potentially disabling chronic pain conditions in older adults [26]. Many older adults remain quite functional despite CLBP, and because age-related co-morbidities often exist independently of pain, the unique impact of CLBP is unknown [27]. The Framingham Study (1992-1993) reported 63% of women pain in one or more regions, compared to 52% of men. Widespread CMP was more prevalent among women than men (15 versus 5%, respectively) [28].
Finding that CMP is linked with the subsequent development of severe mobility disability may have important public health implications for the rapidly aging population [29]. Among 898 nondisabled community-dwelling older adults, it was found that the risk of disability increases with the number of areas reported with CMP [30]. The results of the another study indicated that more than 90% of the elderly living in the community experienced pain within the past month, with 41% reporting discomforting, distressing, unbearable, or severe pain. CMP was found to be the most predominant pain, and inactivity was the most effective strategy used to lessen pain [6]. D\'Astolfo et al emphasized that CMP is a significant burden on the Canadian health care system. It is considered the third most expensive disorder in terms of spent health care dollars, surpassed only by cancer and heart disease [9].
The impact of CMP is a cycle of disuse and inactivity. This cycle in turn leads to a further reduction in function, accompanying psychological effects and decreased quality of life [7,31]. Interrelated problems caused by the inadequate treatment of pain in older adults have been highlighted by several authors. Consequences of poorly managed CMP in this population may include fear of movement, decreased ambulation, functional decline, functional dependence, disability, impaired posture, risk of pressure sores, muscle atrophy, increased subsequent exacerbation of frailty. Older adults may also have impaired appetite, malnutrition, impairment of excretory functions (bowel and bladder) and impaired memory, the impairment of enjoyable recreational activities, impaired dressing and grooming, sleep disturbance, behavioral problems, social isolation, depression, anxiety and even suicidal thoughts [7,10,14-16]. Furthermore, depression, behavioral changes, and cognitive impairment can complicate therapy and make assessment more difficult. Pain-induced decline in mobility and activity may further lead to increase the risk of trauma, particularly caused from falls [14].
Falls are one of the major causes of death among older adults and the most important cause of hospitalization and increased healthcare utilization and costs in this population [9]. CMP measured according to number of locations, severity, or pain interference with daily activities is associated with greater risk of falls in older adults [32-35]. Leveille et al conducted the population-based study. At baseline, 40% of participants reported polyarticular chronic pain, and another 24% reported chronic pain in only one joint area. A total of 1,029 falls were reported during 18 months of follow-up. The researchers found that patients who had chronic pain had higher rates of falls during follow-up than those who were pain-free [33]. In the another population based study, total of 605 participants aged 75 years and older, CMP was reported by 48% of the participants, of whom majority had moderate to severe pain in lower extremities or back. The participants with moderate to severe pain had more than twice (odds ratio 2.33, 95% confidence interval 1.44-3.76) the risk for impaired balance compared with those without pain. The researchers came up with a conclusion that there was a direct relationship between the moderate to severe CMP and impaired postural balance [36].
In spite of high prevalence and consequences of CMP among older adults, there have been relatively few studies in older populations with pain. Studies have indicated that less than 1% of the thousands of papers published on pain focus on the aging society [13,17]. Therefore, health care professionals remain ineffective in assessing and treating pain. Improving the health care professionals’ knowledge and skills related to pain assessment in older adults and adopting aggressive approaches to comprehensive pain assessment are crucial to improve older adult’s quality of life [15,37]. The study conducted recently reported that although CLBP was a common and debilitating problem in older adults, primary care physicians did not feel "very confident" in their ability to diagnose any of the contributors of CLBP listed (most items <40%). The results point to a need for more primary care physician education about CLBP in older adults [38].
Older people may not report pain, and nurses or caregivers may not enquire about it. Both older people and their caregivers can hold age related attitudes regarding pain and view pain as an expected consequence of the ageing process. Older adults may not report pain because they do not want to be a burden for their families and caregivers. It results mostly in lack of information by healthcare professionals about pain control of older people. Furthermore, extensive documentation requirement may deter health-care professionals from appropriately prescribing effective treatments [39,40]. Other factors such as inadequate reimbursement and financial incentives for pain management efforts, negative reinforcement in training programs for attending to pain while being rewarded for less important and more detailed interventions, lack of training for pain management skills, lack of recognition and interaction among various medical disciplines (and even among different pain groups), limited access to diagnostic or therapeutic facilities or experts, inadequate pharmacy services, insufficient staffing for proper pain assessment and interventions, inflexible access to medications based on formulary selections, and other restrictive policies may also contribute to failure in treatment of pain [4,40].
Treatments for CMP are focused at decreasing pain, making it more tolerable and improving patients function. Considering the needs of individual older patients can better explain what their expectations are regarding pain treatment outcomes. Treating pain should be done individually as well as following some general principles. Multidisciplinary pain programs that combine several modes of pharmacological and non-pharmacological treatment have demonstrated efficacy for the management of chronic pain in older adults. However, those programs appear to be not being used effectively, because older patients are less likely to be offered this treatment in pain management clinics, and receive fewer treatment options when attending such clinics due to inadequate representation [12,41].
Pharmacological therapy for chronic musculoskeletal pain is the most effective when combined with non-pharmacological approaches: physical therapy (e.g., exercise program, TENS, application of heat or cold), psychological methods (e.g., relaxation, biofeedback, hypnosis, cognitive-behavioral therapy), educational programs, social interventions and complementary therapies (e.g., acupuncture) [14,16,37,41,]. In an older population, where the risk of adverse events is higher, the non-pharmacologic options will usually cost less and cause fewer side effects.
Although the high risk for adverse drug reactions in the older adults, pharmacologic interventions remain the primary modality for treating CMP in the geriatric population [20]. The management of CMP in older patients mostly consists of opioids, non-opioids and adjuvant analgesics.
Drug distribution usually is different in older patients as compared to younger patients because of changes in blood flow to organs, protein binding, and body composition that occur with aging [3]. In addition, many older adults continue to report substantial pain despite the regular use of analgesic medications. Polypharmacy, as well as inappropriate prescribing, for the older patients is a major problem and a challenge that contributes to costs, adverse drug events, confusion, compliance issues, and errors in management. [42-44] It is reported that CMP is one of the most common geriatric consultation and admission the hospital. Geriatric consultations increase the total number of medications and the cost of medications used by elderly patients. These restrictions have led to a need for effective non-pharmacological interventions to manage CMP [42].
According to American Geriatric Society (AGS) nonopioids are generally the first line of therapy for mild to moderate or “tolerable” CMP [16,23,43]. Acetaminophen (APAP) and nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common analgesics used to. APAP is usually the first choice because it is relatively safe for older people. It was reported that APAP treatment reduced pain behaviors associated with musculoskeletal pain in persons with dementia in community-dwelling [45,46]. Dosing of APAP should be limited to avoid liver toxicity, and topical analgesics are preferred for focal pain. The long-term use of NSAIDs should be avoided when possible because of their high frequency of adverse effects; e.g., risks of gastrointestinal bleeding and renal dysfunction which are significantly higher in older adults than in the younger population. The newer cyclooxygenese-2 (COX)-2 inhibitor NSAIDs are believed to be associated with a lower side effect profile in older adults [41]. COX-2 inhibitor NSAIDs has been linked to an increased incidence of acute coronary syndrome, although there is evidence that cardiovascular-related adverse events are not limited to the selective COX-2 inhibitors. Additionally, chronic use of either APAP or NSAIDs has been associated to elevations in blood pressure [47].
Data was collected from 428 patients aged ≥50 years with non-inflammatory musculoskeletal pain during a consultation with their general practitioner (GP). In cases, where a prescription is issued, this is more strongly influenced by previous NSAID prescriptions than the patient\'s pain level. Researchers concluded that GPs mostly adopt an individualized approach to the treatment of musculoskeletal pain in older adults [48]. A survey of inpatients’ drug knowledge showed that 66–90% of older adults did not know which of several medicines contained APAP, and only 7% knew the maximum daily dose. Therefore close monitoring of pain medication use is necessary in older patients, particularly those with cognitive impairment. According to the 2009 guidelines for pharmacologic management of persistent pain in older persons published by the AGS, NSAIDs should be used only with extreme caution in highly selected individuals once other safer therapies have failed. Absolute contraindications for NSAIDs use in older adults are chronic kidney disease, heart failure, and active peptic ulcer disease [16,46,49].
Worries connected to taking opioids and a reluctance to report pain have caused inefficient pain management with opioids in older patients. In reality, addiction risk with opioids is low (<0.1%) when analgesics are used for acute pain in patients who are not substance abusers [4]. Opioids are one of the pharmacologic classes recommended for treatment from moderate to severe pain in guidelines released in 2009 by the AGS. According to the AGS, opioids should be considered for patients who have pain related functional impairment or diminished quality of life due to pain [23,50].
Within this population, short-acting opioids can be used in treatment of patients with intermittent pain, whereas sustained-release opioids should be given for continuous pain (with short-acting preparations available for breakthrough pain). Once total daily dose requirements have been determined, a long acting agent may be used. Sustained-released opioids should be used for the treatment of continuous pain while using short-acting preparations for breakthrough pain. Both morphine and oxycodone are commonly used and available in both short-acting and sustained-release preparations. For patients who may not be able to take oral preparations periodically, opioids are available as parenteral, sublingual (buprenorphine hydrochloride), suppository (oxymorphone hydrochloride), and transdermal (eg, fentanyl patch) products. Long-acting opioids should seldom be initiated in opioid-naive older patients [7,46].
Patient-controlled analgesia (PCA), whether using oral or parenteral agents, can be most beneficial in a cognitively intact population, with the likelihood of the best pain control in conjunction with the least amount of opioid needed to control musculoskeletal pain [4].
An oral long-acting agent such as morphine (the oral dose required is usually about 3 to 4 times greater than the parenteral dose needed for the same duration) or oxycontin in conjunction with a similar short-acting agent can also be used. Some people will metabolize the medication more quickly, and if breakthrough pain occurs after 8 hours of adequate pain relief, therefore the solution would be to increase the frequency of dosing to every 8 hours from every 12 hours rather than to increase the 12-hour dosage. A controlled-release morphine or controlled-release oxycodone should never be prescribed more frequently than every 8 hours [4].
Meperidine hydrochloride should not be used because of the accumulation of a nephrotoxic metabolite. Benzodiazepines have also been used in the treatment of a variety of painful conditions, particularly muscle spasms related to pain crises. Transdermal fentanyl patches should generally be avoided as a first-line agent in older patients, because absorption is unpredictable, being affected by differences in body temperature and subcutaneous fat and water in older patients as compared with younger adults studied in clinical trials [23]. Trescot et al reported that long-term effectiveness of 6 months or longer use of opioids is variable with evidence ranging from moderate for transdermal fentanyl and sustained-release morphine with a Level II-2, to limited for oxycodone with a Level II-3, and indeterminate for hydrocodone and methadone with a Level III [51].
Although opioid therapies may have a lower risk for organ failure than other therapies, confusion, dizziness, nausea, sedation, constipation, impaired balance, falls and hip fractures, depression, and agitation are other potential related side effects that can affect this population in particular. Finally, older adults with CMP taking opioid analgesics should be reassessed for ongoing attainment of therapeutic goals, adverse effects, and safe and responsible medication use [46].
Adjuvant medications, while not classically categorized as analgesics, may be effective in treating certain CMP syndromes in older adults. Steroids, anticonvulsants, topical local anesthetics, and antidepressants are adjuvant agents. Depression/anxiety is often unnoticed in older patients and requires consideration when managing patients with pain [4,23,41]. The study of the relationship between depression and pain complaints in older patients has revealed that initial control of depression greatly facilitates pain management. If depression is not addressed aggressively, interventions to manage pain are unlikely to be successful [7]. Tertiary amines (e.g., amitriptyline, imipramine, trimipramine, doxepin, clomipramine, should be avoided in older patients because of greater anticholinergic side effects, including sedation, delirium, urinary retention, constipation, glaucoma exacerbation, and dizziness and, for amitriptyline, especially, the risk of cardiac arrhythmia. By contrast, secondary amines (nortriptyline, desipramine, protriptyline, amoxapine) tend to have better adverse event profiles in older patients [41].
Tramadol is another agent available to help control mild to moderate pain and, except in a substance-abuse population. It should have a low tolerance problem and may be beneficial in a variety of pain situations [23].
In about 90% of cases, additional adjuvant medications will be needed to control pain. Vitamin D is also likely to be helpful in some pain situations. Vitamin D and calcium have also been shown to decrease fracture rates, which are a source of pain themselves. Lower concentrations of 25(OH)D are associated with significant back pain in older women, but not men. Because vitamin D deficiency and CMP are fairly prevalent in older adults, these findings suggest it may be worthwhile to query older adults about their pain and screen older women with significant back pain for vitamin D deficiency [52]. Calcitonin has been shown in clinical trials to relieve pain associated with vertebral compression fractures. Topical agents are also available for site-specific pain. Also, topical treatments can be useful for patients who have difficulty swallowing pills and for patients taking multiple medications. The safety of topical lidocaine has been established as well. Topical capsaicin should be started at the lowest dose recommended. However the burning sensation associated with capsaicin application during the chemical desensitization phase makes for poor tolerability; many older patients are not able to endure the treatment long enough to achieve therapeutic effects [4,41,50].
Adverse drug reactions occur more than twice as frequently among older adults than younger ones and increase as the number of medications increases. On average, a 70-year-old takes seven different medications. A high prevalence of medication errors in older adults results from accumulation of factors that contribute to medication errors in all age groups, such as polypharmacy, polymorbidity, enrollment in several disease-management programs, and fragmentation of care [53]. The essential approach to treating older adults is not necessarily to find a set number of medications and try to stay below it, but to find the right medication at the right dosage and for the shortest possible duration on a case-by-case basis. This individualized approach to treating patients will provide a much safer and more effective means of practicing and will improve patients\' quality of life [54]. In general, as specific initial and titrating dosage regimens for the elderly are not readily available, the “start low and go slow” approach to drug prescribing in the elderly is particularly important as it applies to pain management (AGS 2002) [16,21,42].
Ideally, first-line interventions should directly address the source of pain in older adults with CMP. A comprehensive examination of the patient to identify impairments associated with the painful condition will direct those interventions. Physical therapy interventions reduce stress and correct malalignments of joint structures, correct muscle imbalances, and enhance the shock absorption capacity of tissue structures. Selection of appropriate treatments must include consideration of contraindications associated with the patient’s comorbid conditions (e.g., osteoporosis or osteopenia) [10,20,57].
Passive treatment modalities focused solely on temporarily decreasing pain symptoms (e.g., heat treatments, cryotherapy, transcutaneous electrical nerve stimulation [TENS]) should be used sparingly as part of the physical therapy intervention [1,2]. These modalities should be a means to an end, the end being decreasing pain to a sufficient extent to allow patients to participate in subsequent active treatments aimed at positively affecting functional abilities [20,50,55-57].
Superficial heating agents (e.g. hot packs, warm hydrotherapy, paraffin, fluidotherapy and infrared) or deep heating agents (e.g. short-wave and microwave diathermy, and ultrasound) can be used to increase blood flow, membrane permeability, tissue extensibility and joint range of motion in ways that can contribute to decreasing pain. Heat and cold alter both peripheral and central nervous system excitability, and can thus serve as a means of modulating pain [20,58].
Although thermal agents are frequently used in the physical therapy treatment of patients with pain, the literature on the effects of thermal agents on pain in older adults is limited. Thermal agents are commonly used in the self-management of chronic pain [55]. In a study of 235 (mean age of 82 years) community-dwelling adults, Acetaminophen, regular exercise, prayer, and heat and cold were the most frequently used pain management strategies (61%, 58%, 53%, and 48%, respectively). 272 community-dwelling older adults aged 73 years or older reported hot and/or cold modalities (28%) as a pain-reduction strategy [59]. Chatap et al conducted a study to determine the effects of hyperbaric CO(2) cryotherapy in older adults with pain whose origin was usually musculoskeletal (80.3%). They found that the pain scores decreased significantly after four sessions, from 45mm to 13mm on visual analog scale (P<0.001) in those with chronic pain. They concluded that hyperbaric CO(2) cryotherapy is an innovative tool that should be incorporated within the non-pharmacological armamentarium for achieving pain relief in older patients [60].
Although there is scant evidence on the use of joint mobilization and manipulation specifically for older adults, research has addressed the use of these treatments for knee and hip osteoarthritis (OA), conditions common in older adults [20]. A recent qualitative systematic review aimed to determine if manual therapy improves pain and/or physical function in people with hip or knee OA. Four RCTs were eligible for inclusion (280 subjects), three of which studied people with knee OA and one studied those with hip OA. There is silver level evidence that manual therapy is more effective than exercise for those with hip OA in the short and long-term. The researchers concluded that due to the small number of RCTs and patients, this evidence could be considered to be inconclusive regarding the benefit of manual therapy on pain and function for knee or hip OA [61].
A Cochrane systematic review concludes that manual therapy alone is insufficient in the management of persistent neck pain. However, there is strong evidence that either manipulation or mobilization combined with exercise is effective in reducing pain. This review also concluded that manual therapy with exercise improves function and the patients’ global perceived effect of treatment [62]. The Philadelphia Panel (2001) concluded that there were insufficient data for the general population to reach a conclusion about the effect of massage for low back pain, neck pain, and shoulder pain. A systematic review by Harris et al [63], determined that slow-stroke back massage and hand massage showed statistically significant improvements on physiological or psychological indicators of relaxation in older people. A limited number of studies on massage have been conducted exclusively with older individuals. Hawk et al compared the clinical outcomes of spinal manipulation and a non-manipulative mind-body approach (Bioenergetic Synchronization Technique) for patients with chronic musculoskeletal pain in older adults. They reported that for this particular group of patients, both groups demonstrated similar improvement scores on the Pain Disability Index [64].
Protective and supportive devices assist a decrease in pain and increase in function for patients with joint instability or malalignment. Therapeutic taping for patellar realignment is effective in reducing pain and improving function in patients with osteoarthritis of the knee. Recently introduced kinesiotaping method helps to increase blood circulation, decrease pain and relaxation on fascia, tendon and muscles regarding painful musculoskeletal conditions. Impact-absorbing shoes may help to relieve foot, ankle, knee and hip pain from osteoarthritis. Patients with metatarsalgia associated with rheumatoid arthritis experienced decreased pain using custom-fitted foot orthotics. Besides supportive and protective devices, ambulation devices like wheelchair, cane, crutch etc. can help to relieve stress from lower extremity especially during immobilization period after musculoskeletal injuries in older adult. Therefore appropriate device selection and measurements are important in order to improve efficiency. Decisions regarding the use of protective or supportive devices should therefore be individualized to the patient based on the information gained in the examination [20,57,58].
Despite positive conclusions regarding the use of transcutaneous electrical nerve stimulation (TENS), methodological weaknesses of published studies limit the ability to conclusively support the use of TENS for chronic pain conditions in older adults. High-frequency TENS appears to be the most effective TENS application for postsurgical pain and can be used with modulating frequencies to control neurologic accommodation. A recent systematic review of TENS for persistent pain concluded that an insufficient number of high-quality randomized clinical trials existed to evaluate the use of TENS for the management of persistent pain. To date, only a small number of studies have been found that examined the effect of TENS exclusively with older adults [57,58].
Most recently, van Middelkoop M et al found no difference in effectiveness of TENS and sham TENS and no difference between TENS and active treatments. The data provided low quality evidence for TENS versus sham-TENS and very low quality evidence that percutaneous electrical nerve stimulation (PENS)/acupuncture is more effective than TENS for post-treatment and short-term pain relief [65]. They concluded that application of TENS attenuates blood pressure and vasoconstrictor responses during exercise and metaboreflex activation, associated with improved sympatho-vagal balance in healthy young and older individuals [66]. A recent study by Weiner et al provides some support for the use of percutaneous electrical nerve stimulation (PENS) for low back pain in older adults. Subjects randomized to PENS plus physical therapy intervention had significantly greater reductions in pain intensity measures at the end of the 6 weeks (P<.001). These pain reduction effects were maintained at 3-month follow-up [67].
In evidence-based meta analysis by Zhang W et al in 2008, authors search recommendations for the management of hip and knee osteoarthritis (OA). Recommendations cover the use of 12 non-pharmacological modalities: education and self-management, regular telephone contact, referral to a physical therapist, aerobic, muscle strengthening and water-based exercises, weight reduction, walking aids, knee braces, footwear and insoles, thermal modalities, TENS and acupuncture [68]. Same author groups made similar meta-analysis in 2010 and reported that among non-pharmacological therapies, effect size for pain relief was unchanged for self-management, education, exercise and acupuncture. However, with new evidence the effect size for pain relief for weight reduction reached statistical significance [69].
Complementary and alternative medicine is most often used to treat painful musculoskeletal conditions as well as conditions that are comorbid with pain in older adults as a holistic therapy. [70]. Molton et al researched the pain coping strategies among older, middle-aged, and younger adults living with CMP. They reported older adults report a wider range of frequently used strategies and significantly more frequent engagement in activity pacing, seeking social support, and use of coping self-statements than did younger or middle-aged adults [71]. Self-management programs for pain have particular relevance for the field of geriatric pain management [56,71]. Despite their documented efficacy in young to middle aged samples cognitive-behavioral and self-management pain therapies have been little-studied in elderly populations. A variety of self-management programs aim to enhance the ability of patients to successfully self manage their pain, using a variety of techniques [72,73]. The most common behavioral modes of therapy include self-regulation strategies such as relaxation, biofeedback, hypnosis, imagery, and meditation. Although there are variations among these approaches, they share some or all of the following components: 1) education about pain and its consequences; 2) relaxation skills training (e.g., progressive muscle relaxation); 3) cognitive coping skills training; 4) problem solving (e.g., addressing problems with homework exercises or goals that are proposed to be met after each class); and 5) communication skills training (e.g., how to talk to physicians or health care providers about pain). In pain management, self management therapy serves to focus a patient’s attention to exercise control in decreasing sympathetic arousal [37,74]. Besides patient education caregiver education is especially important for caring in the elderly. Both one-on-one as well as group programs can be effective [3,7].
The American Psychological Association recognizes cognitive-behavioral therapy (CBT) as an empirically supported intervention in management of chronic musculoskeletal pain; including rheumatoid arthritis, osteoarthritis, fibromyalgia, and low back pain. Its foundation is the gate control theory integrating the sensory, affective, and cognitive components of pain. Cognitive processes are thoughts, self-statements, or evaluations about the pain and beliefs, interpretations, or attributions regarding this condition [37,75]. 10-session psychosocial (i.e. cognitive behavioral orientation) pain management program that was specifically designed for older adults was used in ninety-five community dwelling seniors with at least one chronic musculoskeletal pain condition. Although decreases in pain intensity were observed in both the treatment and wait-list control groups, the intervention was found to result in fewer maladaptive beliefs about pain and greater use of relaxation, which is considered to be an adaptive coping strategy [76]. Beissner et al reported if physical therapists incorporate CBT techniques (eg, relaxation, activity pacing) when treating older patients with chronic pain. Commonly used CBT interventions included activity pacing and pleasurable activity scheduling [75].
The National Center for Complementary and Alternative Medicine defines mind–body medicine in the following way: Mind-body medicine focuses on the interactions among the brain, mind, body, and behavior, and the powerful ways in which emotional, mental, social, spiritual, and behavioral factors can directly affect health. It regards as a fundamental approach that respects and enhances each person’s capacity for self-knowledge and self-care, and it emphasizes techniques that are grounded in this approach [72]. Morone et al conducted a structured review of eight mind–body interventions: biofeedback, progressive muscle relaxation, meditation, guided imagery, hypnosis, tai chi (TC), qi gong, and yoga for older adults with chronic nonmalignant pain. He reported that there is some support for the efficacy of progressive muscle relaxation plus guided imagery for osteoarthritis pain. There is limited support for meditation and TC for improving function or coping in older adults with low back pain or osteoarthritis. TC, yoga, hypnosis, and progressive muscle relaxation were significantly associated with pain reduction in these studies [72].
It is reported that prevalent coping strategies included analgesic medications (78%), exercise (35%), cognitive methods (37%), religious activities (21%), and activity restriction (20%) for older adults with chronic pain due to a musculoskeletal cause [77]. Reid et al suggested in their review (N = 27) that a broad range of self-management programs (yoga, massage therapy, TC, and music therapy) may provide benefits for older adults with CMP highlighting the need for research to establish the efficacy of the programs in different age and ethnic groups of older adults and identify strategies that maximize program reach long-term participation [74].
Biologically based therapies, one of the major categories of complementary and alternative therapies, according to the federal National Institutes of Health (NIH), involve supplementing a person’s normal diet with additional extracts, nutrients, herbs and/or certain foods. Among older adults, glucosamine sulfate and chondroitin sulfate are popular supplements used for the treatment of osteoarthritis and are among the most well studied biologic alternative medicines. Glucosamine and chondroitin are components of the extracellular matrix of articular cartilage; glucosamine is a substrate required to synthesize glycoproteins and glycosaminoglycans, components of synovial fluid, ligaments, and other cartilaginous joint structures, and chondroitin is a glycosaminoglycan that functions as a building block for joint matrix structure. Another commonly used biological agent for arthritis is S-adenosyl L-methionine (SAMe). This is a synthetic version of a naturally occurring coenzyme that is produced by the liver from methionine SAMe has been attributed with analgesic and antiinflammatory properties, and can stimulate articular growth [50].
In recent years exercise, which is one of the non-pharmacological approaches, is getting the most important component of CMP management. Regular exercise, interventions to increase physical activity, strengthening the muscles, accompanied with weight loss are effective methods in the management of CMP such as OA, low back pain etc. in older adults. Regular moderate level exercise training or increased physical activity does not aggravate pain and joint symptoms as expected in OA according to RCTs and elicit significant health benefits. But pain, swelling, fatigue and weakness during activity or lasting more than 1-2 hours after exercise should be always considered as sign of excessive stress. Any activity that worsens pain or the other symptoms, and in acute flare-up periods of rheumatoid arthritis should be discontinued [78,79].
The most studied CMP among older adults in literature belongs to knee OA. High and low-intensity aerobic exercises are equally effective in improving pain in persons with knee OA [80]. Specifically, aerobic exercise, water-based (aquatic) and land-based exercises, aerobic walking, quadriceps strengthening, and resistance exercise, physiotherapy-based exercise modalities reduce knee pain in older adults [80-84]. But a recent systematic review states that there are few RCTs recommending the use of exercise in reducing pain related to hip and knee OA and the content, duration and frequency of the exercise sessions is very heterogeneous [85].
Regular exercise also as an important adjunct to other interventions (e.g. thermal agents, patient education, etc.) is the most frequently preferred pain management strategies after medication in some older adult populations [55,58].
Various forms of exercise can modulate pain either directly or indirectly. Passive or active exercise has a direct effect on pain through increasing input from joint mechanoreceptors. Indirect effects of exercise on pain may be related to increased blood flow, decreased edema, inhibition of muscle spasm, enhanced ROM, flexibility, strength and weight loss which may improve biomechanical factors and decrease joint stress, and provide [58,81,86,87]. Improved sleep, enhanced mood, relaxation, reduction in anxiety and general well-being following regular exercise also can alter pain sensitivity positively in same way. After a single exercise session pain tolerance increases significantly [58,88].
Another benefit of exercise is its effect on risk of falling among older adults with CMP. Older adults with CMP are at increased risk of falling because of pain related muscle weakness, increased body sway and impaired balance [33,89,90]. Primarily strengthening program and physical agents as an adjunct are recommended for joint pain management among this population [90]. The most effective physical therapy approach for the prevention of falls is a combination of balance and strength training [91] in addition to aerobic training such as walking, aerobic dance, circuit training, aquatics and active lifestyle [92]. RCTs are needed to learn whether pain reduction with exercise could affect fall risk in older adults with CMP.
An exercise program should address primer functional problems and impairments (pain, limited joint range of motion, muscle weakness) for functional independence. After relieving from these impairments or reducing them exercise program can begin [78]. A physical therapist has the primary responsibility to plan an exercise program accommodating pain or other disabilities [93]. Flexibility, strength and aerobic endurance are the basic components for exercise programs aiming to control pain. Time needed for adaptation to exercise stress may be 2 to 3 months for older arthritic adults with low physical capacity [78].
Exercise sessions should have three phases: The first phase, a warm-up period lasting 5-10 minutes, involves repetitive low-intensity range-of-motion exercises. The second phase, the training period, includes range of motion, strength, or aerobic capacity exercises, or a combination of these. The final phase, cool-down period lasting 5 minutes, involves flexibility exercises [78,94]. In addition the time of the exercise during the day can change according to the chronic condition. Older adults with OA better perform exercise in the morning, whereas older adults with rheumatoid arthritis may be better several hours after awakening. Low-impact, non-weight-bearing exercises and exercise machines distributing the load to all limbs usually recommended for artritic patients [79].
Flexibility exercise should begin at the beginning of an exercise program during the warm-up, preferably cool-down period. Static stretching is recommended during cool down period for the osteoartritic older adults at as full as possible pain-free range for the greatest improvements [95]. Stretching exercises must be modified when the joint is inflamed or painful. Painful joints should not be over stretched and superficial heat application, relaxation prior to stretching helps reduce pain [78]. Older adults tend to have some movement patterns and positioning, which causes joint movement limitation resulting in painful movement patterns. Consideration of the potential for future painful conditions also should be treated by stretching [96].
Stretching exercises should be performed at least 3 times per week or daily if the pain and stiffness are minimal or must be modified when the joint is inflamed or painful. The progression should be gradual from one stretching to 4-10 repetitions for each major muscle group. The stretch position should be hold 10-30 seconds. [78]. Effective stretching exercises require longer holding times with increasing age and loss of extensibility, so if there is no pain, 60 seconds is necessary for older adults to achieve a long-term effect. Four repetitions of a 60-second hold performed regularly, 5 to 7 days a week, appear to be most effective [96].
Aerobic exercise programs aiming improvement in strength and proprioception reduce pain in OA patients. Examples of aerobic exercise are bicycling (stationary bike, recumbent-type bike etc.), walking, dance, Tai-Chi and aquatic exercises such as swimming, Ai-Chi etc. Daily activities and some hobbies like walking the dog, mowing the lawn or playing golf, are also considered as aerobic exercise [78,92]. To prevent overuse of specific joints and to elicit long-term participation, activity selection for aerobic exercise is important and depends on the patient’s current disease state, joint stability, opportunities, individual’s preference and abilities [96].
There are few studies addressing effect of aerobic exercise on CMP in older adults [97, 98]. A 14-year prospective longitudinal study showed that regular aerobic exercise over the long period in physically active seniors was associated with about 25% less CMP than reported by more sedentary ones [97].
The aerobic exercise intensity should range between 50%-60% of HRmax (220 - age in years), 10-12 point in rating of perceived exertion (an ordinal scale, 6 to 20), or be positive on the “talk test” [78]. The talk test represents the ability to engage in a conversation during exercise. When the exerciser reaches an intensity at which he or she can “just barely respond in conversation,” the intensity is considered to be safe and appropriate for cardiovascular adaptation [96]. The initial intensity may be 9-11 point in rating of perceived exertion for frail and sedentary older adults [92]. A 2.5% increase in the intensity or volume weekly is appropriate for adaptation and prevention of musculoskeletal injuries among arthritic older adults [78].
The ideal volume for the beginner is 20 to 30 minutes per day but for sedentary, frailer or more deconditioned older adults, it would be easier to begin with one to five exercise bouts of 3-5 minutes in a day and gradually reach to ideal length. Totally 60 and 90 minutes of moderate level physical activity during a week is recommended by the ACSM (American Colleges of Sports Medicine) [78,92].
The initial frequency of exercise training is recommended 3 [78,92] and later maximum 4 days a week in order not to cause injury according to ACSM [78].
Joint pain can limit older adults from contracting multiple muscles to provide a cardiovascular stimulus during aerobic exercise and causes muscle weakness. In those cases and for frail older adults, it is sensible to add aerobic activity following strengthening and balance exercise to stabilize or support the joint and decrease pain followed by functional improvement [15,82,83,92,96]. Both high and low intensity resistive training significantly reduces pain [99]. A Cochrane systematic review showed that there was evidence for modest reduction in pain following progressive resistive training. It is also reported that there was no significant difference in reducing pain between progressive resistive training with functional, aerobic and flexibility training [100,101].
Because low articular pressures during isometric contractions can be well tolerated, isometric strengthening with a few repetition should be given if the joints are inflamed, unstable, swollen, painful or if it is initial phase of strengthening program [78,79]. Isometric strength training should target the major muscle groups. The intensity should gradually increase to 75% from approximately 30% of the maximal voluntary contraction; the number of repetitions to 8-10 from one; number of sessions to 5-10 from 2 times throughout the day. During a contraction held for maximum 6 seconds (20 seconds resting between contractions), older adults should keep on breathing. Contractions should be performed at different muscle lengths or joint angles, too [78]. As soon as possible, when it is tolerated, isotonic training involving 8-10 major muscle groups should begin to improve overall function maximum of 2 days a week. The intensity should gradually increase to 80% from 40% of 1RM (repetition maximum) for adaptation [78]. 1RM is the weight a person can lift one time with good form. The ACSM recommends no more than three trials with a 30- to 60-second rest between trials to find out the most accurate 1 RM, but older adults may have a better response with a multiple RM of 6 to 10 because they need experience to learn to generate that type of force. Elastic bands or tubing, cuff and hand weights, barbells, dumbbells, hand-held blades, fixed weights, medicine and stability balls etc. can be used as equipment [96,102].
For safety reasons, older adults especially those with cardiovascular problems adults should not perform more than two to three sets of a given exercise and repetition number must be carefully determined. For muscular endurance sets of 12-15 repetitions with lighter resistances, for strength development 8-12 repetitions with higher resistance should be used [78].
Another option for exercise is stabilization exercises, which target co-activation of specific muscles and provide joint stability based on the spine [103]. Increased strength and cross-sectional area of the vertebral muscles reduces CLBP by maintaining muscle balance [102].
Tai-Chi [TC], shortly defined as a traditional Chinese mind-body exercise, has recently become popular worldwide because more people with musculoskeletal problems are looking for complementary and alternative treatments [104,105]. TC gives emphasis to diaphragmatic breath, relaxation and composed of slow, gentle, smooth, harmonic and coordinated movements of different body parts, and weight shifting [104,106]. TC involves routines or “forms” ranging from the classic 109 postures to as few as 42 and now has multiple styles modified from the original form. In addition to physical benefits, the focus required to complete these routines elicits mental and cognitive benefits [96].
TC is a moderate-intensity exercise, so it is suitable for physically frail older adults. Besides reducing the pain, people practice TC for also improving physical condition, muscle strength, coordination, flexibility, balance, decreasing risk for falls, stiffness, fatigue, improving sleep, cardiovascular and respiratory function, mood, depression, anxiety, self-efficacy, health-related quality of life and overall wellness in both eastern and western populations [103,104,106,107]. The therapeutic benefits of TC for chronic conditions have been showed in researches recently.
TC is common in older adults especially those with OA, because it is shown to improve pain [103,108], although it is stated that the methodological quality of TC research is generally less than strength and aerobic training research [84]. The physical component of TC provides current recommendations for OA (strength, balance, flexibility, and aerobic cardiovascular exercise) and the mental component could contribute to chronic pain reduction by modulating complex factors of OA pain [104].
Significant pain-relieving effect is shown especially at knee rather than other joints like in the upper extremities where less weight-carrying activity involved in TC [109-111]. It is believed that weight-carrying TC footwork provides pain-relieving effects on knee OA [106]. TC also showed no significant difference in pain reduction of older adults with knee and hip OA compared to hydrotherapy, where there is less knee joint stress than TC [112].
A systematic review and meta-analysis suggested that TC had a small positive effect on pain in people with arthritis and the extent to which it benefits other forms of CMP is unclear but the review also reported that the studies included were low-quality [108]. However a more recent study indicates that water- or land-based exercise, aerobic walking, quadriceps strengthening, resistance exercise, and TC reduce pain and disability from knee OA with evidence rating of A category [80].
There is another discussion about TC that if its benefit increases when combined with the other exercise types or not. Yip YB et al showed that self-management exercise program including stretching, walking, and TC types of movement, had positive effect in reducing pain [113] but a recent systematic review concluded that TC based exercise programs elicited better outcomes than mixed ones but without clear differences [85].
Among different TC styles (Chen, Yang, Wu styles…ect.) the “Sun” style is the most studied one. Sun style TC requires higher stance with bending knees less than other types, so it is more comfortable. In fact in all styles the patient can prefer high or low stance [106]. Song R et al reported that a Sun-style TC exercise could be applied to OA patients in outpatient clinics or public health centers if they are not in acute inflammatory stage to reduce arthritic symptoms [114]. Simplified Yang-style TC is also shown to be effective in osteoartritic knee pain [115,116].
Beside osteoartritis, benefits of TC have been found in some other musculoskeletal problems such as fibromyalgia [6], rheumatoid arthritis [117] and nonspecific CLBP [118].
Aquatic exercise is another good option for the treatment of musculoskeketal problems because water is a safe exercise environment and its temperature provides analgesia for painful muscles and joints [78,119]. The water temperature is recommended between 85 and 90 Fahrenheit (29-32 Celsius) for artritic older adults [79].
The buoyancy of water causes less impact or compressive forces on the joints and therefore allows pain-free motion without the biomechanical stress experienced on land [119]. Older adults with OA or history of surgery may benefit from aquatic exercise. Water resistance can be used for strengthening to progress to land-based exercise among older adults with arthritis. Moreover aquatic exercise, usually practiced with a group, motivates practitioners [78,96]. It is reported that among older adults class attendance is higher for hydrotherapy compared with TC [112] because it provides a playful environment, many social and psychological benefits for them [119]. It also should be considered that heart rate is lower than heart rates when performing at the same level of oxygen consumption on land. “Aquatic heart rate reduction” should be included in the formula while determining target heart rate or it is sensible to use rating of perceived exertion when determining aquatic exercise intensity [96,119].
Chronic pain has been found to be associated with difficulty in exercising regularly [120]. Motivation has a key role for older adults to participate in exercise willingly. Older adults’ outcome and self-efficacy expectations, negative sensations associated with physical activity, such as fear of pain especially back pain or falling influence motivation to engage in physical activities [121]. These negative sensations and related beliefs must be eliminated through facilitating appropriate use of pain medications before exercise or alternative measures such as heat/ice before or after exercise to relieve activity related pain, use of braces or straps, or isolating the damaged joint during exercise. Additionally positive reinforcement and self-management interventions including explaining to older adults how exercise will help reduce pain, cognitive-behavioral therapy, relaxation and distraction techniques and graded exposure to overcome fear of falling or pain can improve participation to exercise among older adults with arthritic pain. Even pain should be minimized in every way possible, the older adult may have to learn to tolerate some pain or discomfort [73,79,86,121].
The use of supervised exercise sessions such as classes in the initial exercise period followed by home exercises and calling patients back for intermittent consultations, or “refresher” group exercise classes may also assist long-term adherence [83]. Generally older adults are interested in self-managing their chronic pain but can’t find opportunity. Austrian et al indicated that 73% of the 68 patients (70 years of age and over with chronic pain) included in his study were willing to participate in an exercise program for pain management but 16% of them had this opportunity [40].
Most types of exercise with some evidence are frequently preferred for pain management in older adult populations with CMP especially for arthritis, mostly knee OA, and secondly CLBP. Exercise content, time and frequency are very heterogeneous in RCTs, so it is hard to determine the best exercise structure. At that point individualized approach to exercise prescription is required.
Because aging is an extremely variable process, older adults require more individualized management than younger individuals. Treatment decisions should weigh the risks of pain with the risks of treatment. In order to provide the most efficient and safest therapy approach in the older adults with musculoskeletal pain, the identification and frequent re-evaluation of the cause of the chronic pain and the impact on the patient\'s general medical state are crucial.
The high cost and adverse side effect profiles associated with many analgesic treatments, as well as the potential for drug-drug interactions, operate as significant barriers to the use of standard pharmacologic treatments in older adults [19,74]. Based on studies conducted to date, combined pharmacologic and non- pharmacologic therapies give the best results for pain relief. Regardless, alternative or complementary medical interventions should be recognized as options for older adults with chronic musculoskeletal pain [4,56]. While some studies have demonstrated that integrating complementary medicine into the care of older patients can yield promising results. Additionally, some of the challenges encountered with conventional pain management of older adults can be ameliorated by integrating complementary and alternative medicine approaches [56].
An obturator hernia (OH) is the protrusion of either an intraperitoneal or an extraperitoneal organ or tissue through the obturator canal [1]. The development of ossification of the ischium and pubis occurs between the 4th and 5th months of gestation, so perhaps it can be assumed that potential bone formation to fill the obturator foramen stops during this period. For anatomical purposes, the obturator foramen is a lacuna, and the obturator canal is the true foramen [2]. The obturator hole is an orifice located in the lower half of the iliac bone, below the acetabulum, limited by the pubis and the ischium (Figure 1). This orifice is almost completely blocked by the obturator membrane, a fibrous membrane in continuity with the periosteum of the margins of the foramen itself. This membrane consists of two layers and is covered by the internal and external obturator muscles that latch on it and the bone margin (Figure 2) [2].
Endopelvic view of the obturatory canal. 1: superficial epigastric vessels; 2: anastomosis between epigastric and obturator vessels; 3: obturator foramen; 4: ileo-psoas muscle; 5: obturator nerve; 6: obturator vessels; 7: internal obturator muscle. with permission from Ref. [
In vivo anatomy of the right obturator foramen. (with permission from Ref. [
The obturator membrane does not cover the entire foramen: upwards it leaves a passage between its upper edge and the lower border of the horizontal branch of the pubis. This path is the obturator canal: an osteo-fibrous duct 2–3 cm long, directed obliquely from the inside out, which connects the pelvic cavity with the pre-obturator space of the thigh, between the external obturator muscle dorsally and muscles long adductor, comb, ileo-psoas ventrally. Its upper wall is the lower face of the horizontal branch of the pubis and as a floor, the obturator membrane, reinforced by an internal ligament. The canal is crossed by the obturator artery, vein and nerve. The obturator canal inwards is closed by the peritoneum, which may have a dimple at this level (obturator dimple) (Figure 1), enough to explain the possibility of obturator hernias, which occur in the upper part of the inner thigh region [5]. The canal offers a passage to the obturator peduncle, where the nerve is located above the artery and vein, and which contains a portion of adipose tissue. The obturator nerve, originating from L2, L3 and L4, divides into two branches at the emergence of the obturator canal. The ventral branch innervates the pectinate and the adductors muscles and supplies sensory branches to the medial face of the thigh; the dorsal branch also innervates the adductors and ends at the knee joint level. This anatomical arrangement explains the Howship–Romberg sign: in case of compression of the obturator nerve by a strangulated hernia, it occurs obturator neuralgia exacerbated by extension, abduction and internal rotation of the thigh, resolved by flexion [6].
The obturator artery originates from the internal iliac artery and it is divided into two branches, medial and lateral, forming a circle around the perimeter of the obturator foramen, in the thickness of its musculoaponeurotic operculum.
There is an anastomosis between the obturator artery and inferior or superficial epigastric artery which crosses the horizontal branch of the pubis. There may be an aberrant obturator artery that can originate from the superficial epigastric artery or the external iliac artery. These arteries are accompanied by satellite veins. This vascular circle has been called “corona mortis”, due to the high risk of bleeding. An anatomic variant has also been reported in which a pubic branch of the epigastric artery descending into the obturator foramen can replace the obturator artery, and a larger pubic vein draining into the iliac vein may replace the obturator vein.
Arnaud de Ronsil in 1724 first described the obturator hernia, and then Henry Obre first successfully repaired it in 1851 [7].
Three anatomic stages in the formation of obturator hernia have been described. The first stage is the entrance of the pre-peritoneal fat tissue into the pelvic orifice of the obturator canal, forming a pilot fat plug. During the second stage, a peritoneal dimple develops through the canal and progresses to the formation of a peritoneal sac. The third stage consists of the onset of symptoms resulting from the herniation of the viscera into this sac [7, 8]. The formation of obturator hernia is favored by weight loss which involves the disappearance of the adipose tissue at the level of the obturator canal. This hernia is mainly formed in the elderly and thin women. In the beginning, the penetration of the extra-peritoneal tissue into the sub-pubic canal, then there is the formation of a dimple at the level of the peritoneum that covers it. Finally, a sac is formed with the risk of intestinal loops being inserted and their throttling due to the stiffness of the margins of the orifice. The sac can externalize directly through the exopelvic orifice of the canal, between the external obturator and pectineus muscles. However, it can also pass through the external obturator muscle or even fit between the two obturator muscles. The contents of the sac are usually the small intestine, more seldom an annex or ovary, bladder, appendix or epiploon. The narrowness of the orifice favors strangulation.
Obturator hernia is a rare pelvic hernia, accounting for the 0.5–1.4% of all hernias (Table 1) [9] that frequently causes bowel obstruction; the hernia passes through the obturator canal, bounded above by the obturator groove of the pubic bone, and below by the obturator membrane (Figures 3 and 4). The obturator canal is usually filled with fat and allows no space for hernia [3]. The fat disappears in patients who have had massive weight loss or are very thin indeed it is observed in elderly emaciated and multiparous women, so it’s also called “little old’s lady hernia” [10]. Right-sided OH is commoner than the left in the ratio of 2:1, as the left obturator foramen may be covered by the sigmoid colon [11], although an incidence of 6% bilateral hernias have been reported [12]. The hernia sac usually contains small bowel, rarely appendix, colon, Meckel diverticulum, or omentum [13]. A prompt diagnosis and treatment could avoid complications such as necrosis of the intestine that increases morbidity and mortality. Signs such as Howship–Romberg and Hannington–Kiff are aspecific and they should be associated with a CT-scan which is clearly the choice radiological exam. Symptoms such as the pain radiating from the inner parts of the thigh, the knee, or the hip could be confused with the dorso-lumbar intervertebral disc pathology or gonarthrosis [14, 15].
Hernia type | Percentage of presentation |
---|---|
Inguinal | 75% |
Incisional | 10–15% |
Femural | 5–10% |
Umbilical | |
Spigelian (at linea semilunaris) | |
Epigastric (linea alba) | |
Obturator | 0.5–1.6% |
The frequency of presentation in the general population of the types of abdominal wall hernia.
Depiction of strangulated obturator hernia. (with permission from Ref. [
Intraoperative findings: the small intestine is incarcerated in the obturator foramen. (with the permission from Ref. [
Obturator hernia poses a diagnostic challenge and the signs and symptoms are often aspecific, which makes a preoperative diagnosis difficult. Obturator hernia should be included in the differential diagnosis of intestinal obstruction of unknown origin, especially in emaciated elderly women with chronic disease. The almost exclusive incidence of obturatory hernia in women can be explained by the greater extension of the obturator foramen and from the different obliquity of the pelvis that exposes it to a direct action of abdominal pressure in women. More frequent symptoms are due to an intestinal obstruction like abdominal pain, distension, nausea, vomiting and constipation [16]. They may also have recurrent attacks of intestinal obstruction in the past with or without a palpable mass in the groin. On physical examination, it may be evident the Howship–Romberg sign: in case of compression of the obturatory nerve by a strangulated hernia, it occurs an obturator neuralgia exacerbated by extension, abduction and internal rotation of the thigh, resolved by flexion. It is considered pathognomonic and presents in 15–50% of cases. The Hannington–Kiff sign (absent adductor reflex and an intact patellar reflex) is reported as more specific [17]. It would be necessary to perform a computed tomography (CT) to make a diagnosis. The CT has an accuracy of 90% [18]. An emergency exploratory laparotomy is fundamental in patients presenting with an acute abdomen.
Abdominal plain radiograph shows aspecific signs of intestinal obstruction and very rarely may show a gas shadow in the area of obturator foramen, therefore, it is not an informative exam [19].
Herniography with the intraperitoneal injection of contrast material under local anesthesia was reported to be useful for demonstrating the hernial sac but it is not a reproducible examination in emergency conditions because it can be done only in elective cases [20].
Ultrasonography (US) is a noninvasive, cheap, and easily available diagnostic tool that can be used to diagnose OH accurately, especially in the emergency setup when patients present with the acute abdomen of uncertain cause, hence allowing early operative treatment. Using a high-frequency probe, the examiner could detect a hypoechoic mass corresponding to the dilated and edematous segment of the intestine posterior to the pectineus muscle [21]. The major advantages of US are that it is a non-invasive and allows for comparison with the asymptomatic side. Limiting factors are dependence on examiner experience (who may at times miss the diagnosis by not scanning the femoral region or may not recognize the hernia as it is small and found deep within the pelvic musculature) and the relatively long learning curve. Also, too much pressure on the transducer can reduce the sensitivity of detection of hernias [22].
Barium enema fluoroscopy can demonstrate a hank of intestinal loops but is very time-consuming and not feasible in cases of acute abdomen. Also, retained barium in the bowel loop may increase the risk of subsequent complications, hence it is not routinely advocated [23].
Magnetic resonance is a comparable method to CT scan for diagnosis but is not always available in urgency or in most cases of obturator hernia presentation [24].
CT scan (Figure 5) is more sensitive and specific, showing a mass-like lesion between the obturator externus and pectineus muscles (Figure 6), it is useful to shorten the lapse of time from presentation to appropriate diagnosis and spontaneously subjecting a patient to definitive surgery, and thus also giving a choice in the surgical approach required [14].
CT scan, coronal: the arrow identifies the right obturator hernia sac; the small intestine is dilated. (with permission from Ref. [
CT scan transverse section. (with permission from Ref. [
Once the diagnosis is obtained or in the diagnostic suspicion of obturator hernia, therapy is exclusively surgical: in the presence of signs of intestinal obstruction or incarceration, surgical exploration is mandatory. The manual reduction of an incarcerated obturator hernia has been described in cases of patients considered unfit for surgery, but two aspects must be considered: the early recurrence and the impossibility to explore the incarcerated viscera in case of possible evolution to gangrene or bowel infarction. If the incarcerated obturator hernia is not treated, it can be fatal and in any case, should always be repaired both in case of urgency and in case of non-acute symptomatology attributable to the hernia; it should be remembered that symptoms may persist and then result in incarceration. The current trend is to repair the obturatory foramen with the use of prostheses primarily made of polypropylene; however, if the orifice is less than 1 cm, the approach could also consist of direct repair. Currently, there is no consensus on the repair technique but it is all based on the surgeon’s experience and preference. The different feasible surgical approaches are intraabdominal, inguinal extraperitoneal, obturator or crural, Cheatle–Henry retropubic and laparoscopic approach [24, 25, 26, 27].
In an emergency set-up usually, a midline incision by laparotomy is required to allow a wider exposure of the obturator ring, the pelvic floor and the lower abdomen, especially in the case of gangrenous bowel resection. Uncoiling the bowel discovers the dilated tract at the border with the strangulated one, usually with a lateral clamping: it is necessary to gently pull the bowel to reduce it in the abdomen avoiding rupture that would lead to septic contamination. The bowel is treated as in all cases of strangulation, preserving or resecting it depending on the degree of intestinal wall perfusion. Suturing the small orifice can be done with several techniques: simple direct closure with several stitches, two layers closure of peritoneum (Figure 7). For large defect: patching and plugging the canal with rib cartilage, peritoneal patch, periosteal patch, pectineal or adductor longus muscle flap with external oblique aponeurosis, greater omentum, round ligament, uterine fundus, ovary, urinary bladder wall, ox fascia, tantalum gauze, teflon cloth, marlex mesh, oxidized cellulose gauze (oxycel), polytetrafluoroethylene (PTFE), polypropylene mesh, Kugel patch, permacol patch plug [19] of mersilene, rolled up marlex mesh as a “cigar roll” plug and titanium alloy staples without mesh [24, 25, 26, 27, 28].
Trocars placement in obturator hernia laparoscopic repair.
The laparoscopic approach, both–trans-abdominal pre-peritoneal (TAPP) or total extraperitoneal (TEP) [29], is feasible in expert settings: the position of the trocars, patient and operators is similar to that of the TAPP and TEP repair for inguinal hernia (Figure 8) [30, 31, 32]. Placement of a double-layer prosthesis is not recommended in the same manner as in abdominal wall hernias because the peripheral anchorage is not safe due to the presence of vascular and nerve structures. It is necessary to proceed as in TAPP repair for inguinal hernia: the peritoneum is dissected above the inguinal dimples, the dissection is conducted lower than the orifice of the obturator canal, the sac is reduced in the abdomen, and the prosthesis is placed in the extraperitoneal space with an overlap of at least 3–4 cm. The peritoneum is sutured above the prosthesis.
The obturator orifice (A) is repaired with direct intra-abdominal suture (B). (with permission from Ref. [
The procedure is similar to the Stoppa inguinal hernia repair. Through a median or Pfannenstiel incision, the Retzius’ space is dissected, posterior to the pubic symphysis, the dissection is extended laterally to the antero-superior iliac spine. The peritoneum is detached from the anterior abdominal wall and the epigastric vessels are left attached. Once the sac is reduced in the abdomen, it is possible to place a large prosthesis covering the inguinal, femoral and obturator region attached to the transverse and rectus abdominis muscles medially and on the pubic symphysis inferiorly.
A 10-cm vertical incision is made on the medial margin of the femoral triangle medial to the femoral vessels and adductor muscles, passed by blunt dissection between the pectinate and middle adductor muscles. The sac can be resected and the orifice closed with a plug or direct suture. This approach is not the recommended one [3].
Other possible approaches can be performed via combined abdomino-crural, cruro-obturator, inguino-obturator, subcrural intraperitoneal [33, 34, 35]. The obturator dimple can be repaired using a direct suture (Figure 9), with a recurrence rate lower than 3%, or use a resorbable mesh or plug [36, 37]. Patches of peritoneum or omentum may be used in cases of small orifices [38, 39].
Primary laparoscopic repair by using non-absorbable suture. (with permission from Ref. [
Due to its rarity of presentation obturator hernia presents a diagnostic challenge and should be included in the differential diagnosis of intestinal obstruction of unknown origin, especially in emaciated elderly women with chronic disease; a prompt suspect based on aspecific symptoms is crucial for the diagnosis. CT scan has a major sensitivity than other radiological exams. Late diagnosis of obturator hernia can lead to ischemia and bowel necrosis with bowel perforation and then localized or generalized peritonitis as a life-threatening condition. Postoperative complications have been reported in 11.6% of patients as pneumonia, sepsis, wound infection [40, 41] and mesh migration which may be prevented with metal anchors [42, 43]. The resultant morbidity and mortality rates are around 38% and 12–70%, respectively. Surgical management depends on early diagnosis and it is the only possible treatment for this pathology [4].
This work has been funded by AUSL Piacenza, Unit of Research and Quality.
Dr. Conti conceived the book chapter; Dr. Conti and Dr. Bonfili wrote the chapter and processed the images. Dr. Baldini and Dr. Conti performed the surgery. Dr. Cattaneo, Dr. Grassi, Dr. Banchini and Dr. Capelli reviewed the literature. All authors reviewed and approved the chapter.
The authors declare no conflict of interest.
We would like to thank the physicians of the Acute Care Surgery team of AUSL Piacenza, Dr. Sonia Agrusti, Dr. Mauro Filosa, Dr. Luigi Percalli, Dr. Gabriele Regina, Dr. Giandomenico Arzu, Dr. Giancarlo Giannone and Dr. Antonio Caizzone for their contributions and expertise in the field of hernia surgery.
We would also like to thank the editor Elsevier-Masson, SAS Paris, for the kind permission to reuse the iconography from the EMC Surgical techniques book.
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Samim Al Azad and Slimane Ed-dafali",coverURL:"https://cdn.intechopen.com/books/images_new/11392.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10400",title:"The Application of Ant Colony Optimization",subtitle:null,isOpenForSubmission:!1,hash:"f4fdfd07ee1ab99fb7c740d6d0c144c6",slug:"the-application-of-ant-colony-optimization",bookSignature:"Ali Soofastaei",coverURL:"https://cdn.intechopen.com/books/images_new/10400.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"257455",title:"Dr.",name:"Ali",middleName:null,surname:"Soofastaei",slug:"ali-soofastaei",fullName:"Ali Soofastaei"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10915",title:"Leadership",subtitle:"New Insights",isOpenForSubmission:!1,hash:"0d72e79892f2a020cee66a52d09de5a4",slug:"leadership-new-insights",bookSignature:"Mário Franco",coverURL:"https://cdn.intechopen.com/books/images_new/10915.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"105529",title:"Dr.",name:"Mário",middleName:null,surname:"Franco",slug:"mario-franco",fullName:"Mário Franco"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10683",title:"Technological Innovations and Advances in Hydropower Engineering",subtitle:null,isOpenForSubmission:!1,hash:"7ce7ad8768bd2cad155470fe1fd883f4",slug:"technological-innovations-and-advances-in-hydropower-engineering",bookSignature:"Yizi Shang, Ling Shang and Xiaofei Li",coverURL:"https://cdn.intechopen.com/books/images_new/10683.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"349630",title:"Dr.",name:"Yizi",middleName:null,surname:"Shang",slug:"yizi-shang",fullName:"Yizi Shang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7102",title:"Pneumonia",subtitle:null,isOpenForSubmission:!1,hash:"9fd70142814192dcec58a176749f1b60",slug:"pneumonia",bookSignature:"Nima Rezaei",coverURL:"https://cdn.intechopen.com/books/images_new/7102.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9670",title:"Current Trends in Wheat Research",subtitle:null,isOpenForSubmission:!1,hash:"89d795987f1747a76eee532700d2093d",slug:"current-trends-in-wheat-research",bookSignature:"Mahmood-ur-Rahman Ansari",coverURL:"https://cdn.intechopen.com/books/images_new/9670.jpg",editedByType:"Edited by",publishedDate:"May 11th 2022",editors:[{id:"185476",title:"Dr.",name:"Mahmood-ur-Rahman",middleName:null,surname:"Ansari",slug:"mahmood-ur-rahman-ansari",fullName:"Mahmood-ur-Rahman Ansari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"213",title:"Neurobiology",slug:"life-sciences-neuroscience-neurobiology",parent:{id:"18",title:"Neuroscience",slug:"life-sciences-neuroscience"},numberOfBooks:10,numberOfSeries:0,numberOfAuthorsAndEditors:191,numberOfWosCitations:69,numberOfCrossrefCitations:73,numberOfDimensionsCitations:147,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"213",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10554",title:"Proprioception",subtitle:null,isOpenForSubmission:!1,hash:"e104e615fbd94caa987df3a8d8b3fb8b",slug:"proprioception",bookSignature:"José A. Vega and Juan Cobo",coverURL:"https://cdn.intechopen.com/books/images_new/10554.jpg",editedByType:"Edited by",editors:[{id:"59892",title:"Prof.",name:"José A.",middleName:null,surname:"Vega",slug:"jose-a.-vega",fullName:"José A. Vega"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9347",title:"Neuroimaging",subtitle:"Neurobiology, Multimodal and Network Applications",isOpenForSubmission:!1,hash:"a3479e76c6ac538aac76409c9efb7e41",slug:"neuroimaging-neurobiology-multimodal-and-network-applications",bookSignature:"Yongxia Zhou",coverURL:"https://cdn.intechopen.com/books/images_new/9347.jpg",editedByType:"Edited by",editors:[{id:"259308",title:"Dr.",name:"Yongxia",middleName:null,surname:"Zhou",slug:"yongxia-zhou",fullName:"Yongxia Zhou"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6899",title:"Chronobiology",subtitle:"The Science of Biological Time Structure",isOpenForSubmission:!1,hash:"521dfb38a216470da6f8f7d02469832c",slug:"chronobiology-the-science-of-biological-time-structure",bookSignature:"Pavol Svorc",coverURL:"https://cdn.intechopen.com/books/images_new/6899.jpg",editedByType:"Edited by",editors:[{id:"169212",title:"Prof.",name:"Pavol",middleName:null,surname:"Svorc",slug:"pavol-svorc",fullName:"Pavol Svorc"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6907",title:"Feed Your Mind",subtitle:"How Does Nutrition Modulate Brain Function throughout Life?",isOpenForSubmission:!1,hash:"91a663d09b6d6e80db3a69fca11e5b68",slug:"feed-your-mind-how-does-nutrition-modulate-brain-function-throughout-life-",bookSignature:"Clémentine Bosch-Bouju, Sophie Layé and Véronique Pallet",coverURL:"https://cdn.intechopen.com/books/images_new/6907.jpg",editedByType:"Edited by",editors:[{id:"265901",title:"Dr.",name:"Clémentine",middleName:null,surname:"Bosch-Bouju",slug:"clementine-bosch-bouju",fullName:"Clémentine Bosch-Bouju"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6991",title:"Neurons",subtitle:"Dendrites and Axons",isOpenForSubmission:!1,hash:"696489f55e1077935f47087fa3829b5f",slug:"neurons-dendrites-and-axons",bookSignature:"Gonzalo Emiliano Aranda Abreu and María Elena Hernández Aguilar",coverURL:"https://cdn.intechopen.com/books/images_new/6991.jpg",editedByType:"Edited by",editors:[{id:"72314",title:"Dr.",name:"Gonzalo Emiliano",middleName:null,surname:"Aranda Abreu",slug:"gonzalo-emiliano-aranda-abreu",fullName:"Gonzalo Emiliano Aranda Abreu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6786",title:"Optic Nerve",subtitle:null,isOpenForSubmission:!1,hash:"b21864e6a0b3b316480d18efda1e18ee",slug:"optic-nerve",bookSignature:"Felicia M. 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Chaban",coverURL:"https://cdn.intechopen.com/books/images_new/6092.jpg",editedByType:"Edited by",editors:[{id:"83427",title:"Prof.",name:"Victor",middleName:null,surname:"Chaban",slug:"victor-chaban",fullName:"Victor Chaban"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5521",title:"Synaptic Plasticity",subtitle:null,isOpenForSubmission:!1,hash:"9eea3c7f926cd466ddd14ab777b663d8",slug:"synaptic-plasticity",bookSignature:"Thomas Heinbockel",coverURL:"https://cdn.intechopen.com/books/images_new/5521.jpg",editedByType:"Edited by",editors:[{id:"70569",title:"Dr.",name:"Thomas",middleName:null,surname:"Heinbockel",slug:"thomas-heinbockel",fullName:"Thomas Heinbockel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:10,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"59437",doi:"10.5772/intechopen.74318",title:"Music and Brain Plasticity: How Sounds Trigger Neurogenerative Adaptations",slug:"music-and-brain-plasticity-how-sounds-trigger-neurogenerative-adaptations",totalDownloads:2085,totalCrossrefCites:5,totalDimensionsCites:14,abstract:"This contribution describes how music can trigger plastic changes in the brain. We elaborate on the concept of neuroplasticity by focussing on three major topics: the ontogenetic scale of musical development, the phenomenon of neuroplasticity as the outcome of interactions with the sounds and a short survey of clinical and therapeutic applications. First, a distinction is made between two scales of description: the larger evolutionary scale (phylogeny) and the scale of individual development (ontogeny). In this sense, listeners are not constrained by a static dispositional machinery, but they can be considered as dynamical systems that are able to adapt themselves in answer to the solicitations of a challenging environment. Second, the neuroplastic changes are considered both from a structural and functional level of adaptation, with a special focus on the recent findings from network science. The neural activity of the medial regions of the brain seems to become more synchronised when listening to music as compared to rest, and these changes become permanent in individuals such as musicians with year-long musical practice. As such, the question is raised as to the clinical and therapeutic applications of music as a trigger for enhancing the functionality of the brain, both in normal and impaired people.",book:{id:"6092",slug:"neuroplasticity-insights-of-neural-reorganization",title:"Neuroplasticity",fullTitle:"Neuroplasticity - Insights of Neural Reorganization"},signatures:"Mark Reybrouck, Peter Vuust and Elvira Brattico",authors:[{id:"196698",title:"Prof.",name:"Mark",middleName:null,surname:"Reybrouck",slug:"mark-reybrouck",fullName:"Mark Reybrouck"},{id:"209976",title:"Prof.",name:"Elvira",middleName:null,surname:"Brattico",slug:"elvira-brattico",fullName:"Elvira Brattico"},{id:"209977",title:"Prof.",name:"Peter",middleName:null,surname:"Vuust",slug:"peter-vuust",fullName:"Peter Vuust"}]},{id:"67730",doi:"10.5772/intechopen.86822",title:"Circadian Rhythms of the Autonomic Nervous System: Scientific Implication and Practical Implementation",slug:"circadian-rhythms-of-the-autonomic-nervous-system-scientific-implication-and-practical-implementatio",totalDownloads:1074,totalCrossrefCites:8,totalDimensionsCites:12,abstract:"Circadian rhythms are omnipresent in almost any biosignal. In this chapter, we join them with the need for practical tools for screening in preventive settings and point out heart rate variability (HRV), a measure of autonomic nervous system activity, as a chronobiologic, unspecific index of mental and physical health. We discuss methods to calculate the circadian variation of HRV measures, particularly the cosinor procedure. We present reference values for circadian variation parameters of HRV and data concerning reproducibility. Furthermore, we show data giving first evidence of HRV as a comprehensive health index by showing altered circadian variation patterns of HRV depending on mental (trait dysthymia) as well as physical (inflammatory markers) health. Finally, we present examples of disturbed chronobiology of HRV in clinical and preventive settings and its practical application in medical consultation.",book:{id:"6899",slug:"chronobiology-the-science-of-biological-time-structure",title:"Chronobiology",fullTitle:"Chronobiology - The Science of Biological Time Structure"},signatures:"Marc N. Jarczok, Harald Guendel, Jennifer J. McGrath and Elisabeth M. Balint",authors:[{id:"289160",title:"Dr.",name:"Marc",middleName:"N",surname:"Jarczok",slug:"marc-jarczok",fullName:"Marc Jarczok"},{id:"289379",title:"Dr.",name:"Elisabeth",middleName:null,surname:"Balint",slug:"elisabeth-balint",fullName:"Elisabeth Balint"},{id:"299975",title:"Prof.",name:"Jennifer J",middleName:null,surname:"McGrath",slug:"jennifer-j-mcgrath",fullName:"Jennifer J McGrath"},{id:"304667",title:"Prof.",name:"Harald",middleName:null,surname:"Gündel",slug:"harald-gundel",fullName:"Harald Gündel"}]},{id:"57827",doi:"10.5772/intechopen.71165",title:"A Role for the Longitudinal Axis of the Hippocampus in Multiscale Representations of Large and Complex Spatial Environments and Mnemonic Hierarchies",slug:"a-role-for-the-longitudinal-axis-of-the-hippocampus-in-multiscale-representations-of-large-and-compl",totalDownloads:1397,totalCrossrefCites:6,totalDimensionsCites:12,abstract:"The hippocampus is involved in spatial navigation and memory in rodents and humans. Anatomically, the hippocampus extends along a longitudinal axis that shows a combination of graded and specific interconnections with neocortical and subcortical brain areas. Functionally, place cells are found all along the longitudinal axis and exhibit gradients of properties including an increasing dorsal-to-ventral place field size. We propose a view of hippocampal function in which fine-dorsal to coarse-ventral overlapping representations collaborate to form a multi-level representation of spatial and episodic memory that is dominant during navigation in large and complex environments or when encoding complex memories. This view is supported by the fact that the effects of ventral hippocampal damage are generally only found in larger laboratory-scale environments, and by the finding that human virtual navigation studies associate ventral hippocampal involvement with increased environmental complexity. Other mechanisms such as the ability of place cells to exhibit multiple fields and their ability to scale their fields with changes in environment size may be utilized when forming large-scale cognitive maps. Coarse-grained ventral representations may overlap with and provide multi-modal global contexts to finer-grained intermediate and dorsal representations, a mechanism that may support mnemonic hierarchies of autobiographical memory in humans.",book:{id:"6250",slug:"the-hippocampus-plasticity-and-functions",title:"The Hippocampus",fullTitle:"The Hippocampus - Plasticity and Functions"},signatures:"Bruce Harland, Marcos Contreras and Jean-Marc Fellous",authors:[{id:"210681",title:"Dr.",name:"Bruce",middleName:null,surname:"Harland",slug:"bruce-harland",fullName:"Bruce Harland"},{id:"210682",title:"Dr.",name:"Marco",middleName:null,surname:"Contreras",slug:"marco-contreras",fullName:"Marco Contreras"},{id:"210683",title:"Prof.",name:"Jean-Marc",middleName:null,surname:"Fellous",slug:"jean-marc-fellous",fullName:"Jean-Marc Fellous"}]},{id:"68423",doi:"10.5772/intechopen.88232",title:"Polyunsaturated Fatty Acid Metabolism in the Brain and Brain Cells",slug:"polyunsaturated-fatty-acid-metabolism-in-the-brain-and-brain-cells",totalDownloads:1128,totalCrossrefCites:8,totalDimensionsCites:10,abstract:"Dietary polyunsaturated fatty acids (PUFAs) have gained more importance these last decades since they regulate the level of long-chain PUFAs (LC-PUFAs) in all cells and especially in brain cells. Because LC-PUFAs, especially those of the n-3 family, display both anti-inflammatory and pro-resolution properties, they play an essential role in neuroinflammation. Neuroinflammation is a hallmark of neurological disorders and requires to be tightly controlled or at least limited otherwise it can have functional consequences and negatively impact the quality of life and well-being of patients. LC-PUFAs exert these beneficial properties in part through the synthesis of specialized pro-resolving mediators (SPMs) that are involved in the resolution of inflammation and to the return of homeostasis. SPMs are promising relevant candidates to resolve brain inflammation and to contribute to neuroprotective functions and lead to novel therapeutics for brain inflammatory diseases. Here we present an overview of the origin and accumulation of PUFAs in the brain and brain cells and their conversion into SPMs that are involved in neuroinflammation and how nutrition induces variations in LC-PUFA and SPM levels in the brain and in brain cells.",book:{id:"6907",slug:"feed-your-mind-how-does-nutrition-modulate-brain-function-throughout-life-",title:"Feed Your Mind",fullTitle:"Feed Your Mind - How Does Nutrition Modulate Brain Function throughout Life?"},signatures:"Corinne Joffre",authors:[{id:"281107",title:"Dr.",name:"Corinne",middleName:null,surname:"Joffre",slug:"corinne-joffre",fullName:"Corinne Joffre"}]},{id:"61465",doi:"10.5772/intechopen.76603",title:"The Importance of Distinguishing Allocentric and Egocentric Search Strategies in Rodent Hippocampal-Dependent Spatial Memory Paradigms: Getting More Out of Your Data",slug:"the-importance-of-distinguishing-allocentric-and-egocentric-search-strategies-in-rodent-hippocampal-",totalDownloads:1419,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"While the brain works as a dynamic network, with no brain region solely responsible for any particular function, it is generally accepted that the hippocampus plays a major role in memory. Spatial memory operates through the hippocampus with communication with the prefrontal and parietal cortices. This chapter will focus on two separate reference frames involved in spatial memory, egocentric and allocentric, and outline the differences of these reference frames and associated search strategies with relevance to behavioural neuroscience. The importance of dissociating these search strategies is put forward, and steps researchers can take to do so are suggested. Neurophysiological and clinical differences between these spatial reference frames are outlined to further support the view that distinguishing them would be beneficial.",book:{id:"6250",slug:"the-hippocampus-plasticity-and-functions",title:"The Hippocampus",fullTitle:"The Hippocampus - Plasticity and Functions"},signatures:"Adrienne M. Grech, Jay Patrick Nakamura and Rachel Anne Hill",authors:[{id:"230389",title:"Dr.",name:"Rachel",middleName:null,surname:"Hill",slug:"rachel-hill",fullName:"Rachel Hill"},{id:"230394",title:"Ms.",name:"Adrienne",middleName:null,surname:"Grech",slug:"adrienne-grech",fullName:"Adrienne Grech"},{id:"230395",title:"Mr.",name:"Jay",middleName:null,surname:"Nakamura",slug:"jay-nakamura",fullName:"Jay Nakamura"}]}],mostDownloadedChaptersLast30Days:[{id:"64482",title:"Neurodegenerative Diseases and Their Therapeutic Approaches",slug:"neurodegenerative-diseases-and-their-therapeutic-approaches",totalDownloads:1324,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Alzheimer’s disease and Parkinson’s disease are characterized as a chronic and progressive neurodegenerative disorder and are manifested by the loss of neurons within the brain and/or spinal cord. In the present chapter, we would like to summarize the molecular mechanism focusing on metabolic modification associated with neurodegenerative diseases or heritable genetic disorders. The identification of the exact molecular mechanisms involved in these diseases would facilitate the discovery of earlier pathophysiological markers along with substantial therapies, which may consist (of) mitochondria-targeted antioxidant therapy, mitochondrial dynamics modulators, epigenetic modulators, and neural stem cell therapy. Therefore, all these therapies may hold particular assurance as influential neuroprotective therapies in the treatment of neurodegenerative diseases.",book:{id:"6991",slug:"neurons-dendrites-and-axons",title:"Neurons",fullTitle:"Neurons - Dendrites and Axons"},signatures:"Farhin Patel and Palash Mandal",authors:[{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal"}]},{id:"75762",title:"Structural and Biological Basis for Proprioception",slug:"structural-and-biological-basis-for-proprioception",totalDownloads:474,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The proprioception is the sense of positioning and movement. It is mediate by proprioceptors, a small subset of mechanosensory neurons localized in the dorsal root ganglia that convey information about the stretch and tension of muscles, tendons, and joints. These neurons supply of afferent innervation to specialized sensory organs in muscles (muscle spindles) and tendons (Golgi tendon organs). Thereafter, the information originated in the proprioceptors travels throughout two main nerve pathways reaching the central nervous system at the level of the spinal cord and the cerebellum (unconscious) and the cerebral cortex (conscious) for processing. On the other hand, since the stimuli for proprioceptors are mechanical (stretch, tension) proprioception can be regarded as a modality of mechanosensitivity and the putative mechanotransducers proprioceptors begins to be known now. The mechanogated ion channels acid-sensing ion channel 2 (ASIC2), transient receptor potential vanilloid 4 (TRPV4) and PIEZO2 are among candidates. Impairment or poor proprioception is proper of aging and some neurological diseases. Future research should focus on treating these defects. This chapter intends provide a comprehensive update an overview of the anatomical, structural and molecular basis of proprioception as well as of the main causes of proprioception impairment, including aging, and possible treatments.",book:{id:"10554",slug:"proprioception",title:"Proprioception",fullTitle:"Proprioception"},signatures:"José A. Vega and Juan Cobo",authors:[{id:"59892",title:"Prof.",name:"José A.",middleName:null,surname:"Vega",slug:"jose-a.-vega",fullName:"José A. Vega"},{id:"100648",title:"Dr.",name:"Juan",middleName:null,surname:"Cobo",slug:"juan-cobo",fullName:"Juan Cobo"}]},{id:"62564",title:"Inflammation and Autonomic Function",slug:"inflammation-and-autonomic-function",totalDownloads:1785,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Inflammation is generally a temporary and limited condition but may lead to a chronic one if immune and physiological homeostasis are disrupted. The autonomic nervous system has an important role in the short- and, also, long-term regulation of homeostasis and, thus, on inflammation. Autonomic modulation in acute and chronic inflammation has been implicated with a sympathetic interference in the earlier stages of the inflammatory process and the activation of the vagal inflammatory reflex to regulate innate immune responses and cytokine functional effects in longer processes. The present review focuses on the autonomic mechanisms controlling proinflammatory responses, and we will discuss novel therapeutic options linked to autonomic modulation for diseases associated with a chronic inflammatory condition such as sepsis.",book:{id:"6808",slug:"autonomic-nervous-system",title:"Autonomic Nervous System",fullTitle:"Autonomic Nervous System"},signatures:"Ângela Leal, Mafalda Carvalho, Isabel Rocha and Helder Mota-Filipe",authors:[{id:"227590",title:"Prof.",name:"Isabel",middleName:null,surname:"Rocha",slug:"isabel-rocha",fullName:"Isabel Rocha"},{id:"253537",title:"Ph.D.",name:"Ângela",middleName:null,surname:"Leal",slug:"angela-leal",fullName:"Ângela Leal"},{id:"253581",title:"MSc.",name:"Mafalda",middleName:null,surname:"Carvalho",slug:"mafalda-carvalho",fullName:"Mafalda Carvalho"},{id:"253701",title:"Prof.",name:"Hélder",middleName:null,surname:"Mota-Filipe",slug:"helder-mota-filipe",fullName:"Hélder Mota-Filipe"}]},{id:"62850",title:"Anatomy of the Human Optic Nerve: Structure and Function",slug:"anatomy-of-the-human-optic-nerve-structure-and-function",totalDownloads:2939,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"The optic nerve (ON) is constituted by the axons of the retinal ganglion cells (RGCs). These axons are distributed in an organized pattern from the soma of the RGC to the lateral geniculated nucleus (where most of the neurons synapse). The key points of the ON are the optic nerve head and chiasm. This chapter will include a detailed and updated review of the ON different parts: RGC axons, glial cells, connective tissue of the lamina cribrosa and the septum and the blood vessels derivate from the central retina artery and from the ciliary system. There will be an up-to-date description about the superficial nerve fibre layer, including their organization, and about prelaminar, laminar and retrolaminar regions, emphasizing the axoplasmic flow, glial barriers, biomechanics of the lamina cribrosa and the role of the macro- and microglia in their working.",book:{id:"6786",slug:"optic-nerve",title:"Optic Nerve",fullTitle:"Optic Nerve"},signatures:"Juan J. Salazar, Ana I. Ramírez, Rosa De Hoz, Elena Salobrar-Garcia,\nPilar Rojas, José A. Fernández-Albarral, Inés López-Cuenca, Blanca\nRojas, Alberto Triviño and José M. Ramírez",authors:null},{id:"68362",title:"Carbohydrates and the Brain: Roles and Impact",slug:"carbohydrates-and-the-brain-roles-and-impact",totalDownloads:1398,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Even if its size is fairly small (about 2% of body weight), the brain consumes around 20% of the total body energy. Whereas organs such as muscles and liver may use several sources of energy, under physiological conditions, the brain mainly depends on glucose for its energy needs. This involves the need for blood glucose level to be tightly regulated. Thus, in addition to its fueling role, glucose plays a role as signaling molecule informing the brain of any slight change in blood level to ensure glucose homeostasis. In this chapter, we will describe the fueling and sensing properties of glucose and other carbohydrates on the brain and present some physiological brain functions impacted by these sugars. We will also highlight the scientific questions that need to be answered in order to better understand the impact of sugars on the brain.",book:{id:"6907",slug:"feed-your-mind-how-does-nutrition-modulate-brain-function-throughout-life-",title:"Feed Your Mind",fullTitle:"Feed Your Mind - How Does Nutrition Modulate Brain Function throughout Life?"},signatures:"Xavier Fioramonti and Luc Pénicaud",authors:[{id:"281112",title:"Ph.D.",name:"Xavier",middleName:null,surname:"Fioramonti",slug:"xavier-fioramonti",fullName:"Xavier Fioramonti"},{id:"281113",title:"Dr.",name:"Luc",middleName:null,surname:"Pénicaud",slug:"luc-penicaud",fullName:"Luc Pénicaud"}]}],onlineFirstChaptersFilter:{topicId:"213",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},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:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,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:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{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"}}}},{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"}}}}]},series:{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:"May 15th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:27,editor:{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"}}},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:48,paginationItems:[{id:"81799",title:"Cross Talk of Purinergic and Immune Signaling: Implication in Inflammatory and Pathogenic Diseases",doi:"10.5772/intechopen.104978",signatures:"Richa Rai",slug:"cross-talk-of-purinergic-and-immune-signaling-implication-in-inflammatory-and-pathogenic-diseases",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81764",title:"Involvement of the Purinergic System in Cell Death in Models of Retinopathies",doi:"10.5772/intechopen.103935",signatures:"Douglas Penaforte Cruz, Marinna Garcia Repossi and Lucianne Fragel Madeira",slug:"involvement-of-the-purinergic-system-in-cell-death-in-models-of-retinopathies",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"81756",title:"Alteration of Cytokines Level and Oxidative Stress Parameters in COVID-19",doi:"10.5772/intechopen.104950",signatures:"Marija Petrusevska, Emilija Atanasovska, Dragica Zendelovska, Aleksandar Eftimov and Katerina Spasovska",slug:"alteration-of-cytokines-level-and-oxidative-stress-parameters-in-covid-19",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",subseries:{id:"18",title:"Proteomics"}}},{id:"81681",title:"Immunomodulatory Effects of a M2-Conditioned Medium (PRS® CK STORM): Theory on the Possible Complex Mechanism of Action through Anti-Inflammatory Modulation of the TLR System and the Purinergic System",doi:"10.5772/intechopen.104486",signatures:"Juan Pedro Lapuente",slug:"immunomodulatory-effects-of-a-m2-conditioned-medium-prs-ck-storm-theory-on-the-possible-complex-mech",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}}]},overviewPagePublishedBooks:{paginationCount:27,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science and Technology from the Department of Chemistry, National University of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013. She relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the National Institute of Fundamental Studies from April 2013 to October 2016. She was a senior lecturer on a temporary basis at the Department of Food Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is currently Deputy Principal of the Australian College of Business and Technology – Kandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI) Ambassador to Sri Lanka.",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. 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The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of 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.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",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.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, 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.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. Osma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDv7QAG/Profile_Picture_1626602531691",institutionString:null,institution:{name:"Universidad de Los Andes",institutionURL:null,country:{name:"Colombia"}}},{id:"69697",title:"Dr.",name:"Mani T.",middleName:null,surname:"Valarmathi",fullName:"Mani T. Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/361128",hash:"",query:{},params:{id:"361128"},fullPath:"/profiles/361128",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)}()