Advantages, disadvantages, and side effects of P2Y12 inhibitors.
\r\n\tAbout 25 percent of all foods produced globally are lost due to microbial growth. L. monocytogenes is a microorganism ubiquitously present in the environment and affects animals and humans. L. monocytogenes can enter a factory and is able to survive in biofilms in the food processing environment. The use of adequate sanitation procedures is a prerequisite in risk prevention. Moreover, effective control measures for L. monocytogenes are very important to food operators.
\r\n\r\n\tThe safety and shelf life maximizing of food products to meet the demand of retailers and consumers is a challenge and a concern of food operators.
\r\n\r\n\tTo obtain food systems more sustainable, several developments are ongoing to ensure safe food products with an extended shelf life and a reduction of food loss and waste. The problem of antimicrobial resistance is also a great issue that must be taken into consideration.
\r\n\r\n\tThe implementation of natural antimicrobials, using food cultures, ferments, or bacteriophages, is one approach to control L. monocytogenes in food products that meet the consumer preference for clean label solutions.
\r\n\tThis book intends to provide the reader with a comprehensive overview of the current state-of-the-art about Listeria monocytogenes in terms of occurrence in humans, animals, and food-producing plants. Its control by more natural agents allows for more sustainable food systems and points future directions to transform challenges into opportunities.
The purpose of the foster care system in the United States is to provide for the well-being of children and youth who have been removed from their family of origin due to abuse, neglect, and/or other reasons: exposures collectively referred to as Adverse Childhood Experiences (ACEs) [1]. Meeting the physical and mental health needs of this population is an acute challenge, as children and youth typically enter the system with an array of significant social and medical issues and factors within the system, such as lack of access to care, compound the problem. Roughly 40% of children (ages 3–9) and youth (ages 10–17) in foster care have a serious mental health disorder, including PTSD; alcohol, nicotine, and other drug abuse; depression and anxiety; eating disorders; and social phobia [2]. They are also more likely to require treatment for physical conditions such as asthma, obesity, chronic pain, and other problems that may interfere with physical activity [3, 4, 5]. Unfortunately, national long-term health outcomes associated with foster care include high rates of chronic mental (54%) and physical (30%) health disorders among young adults exiting the foster care system [6].
As of 2017, 443,000 children and youth live in foster care in the United States. The average age of entry is 7, and the average duration in care is 20.1 months [7]. According to 2014 data, Florida is fifth in the nation in the number of children investigated per 1,000 children in the general population (70.6%) [8]. Since October 2013, the number of children and youth in out-of-home care statewide in Florida has risen from just over 17,000 to now almost 24,000 [9].
By 2005, the state of Florida had transitioned to a privatized system. Recent reviews have found this system to be in disarray, and despite some positive signs [10, 11], the state is failing to implement many recommendations related to the physical and mental healthcare needs of children and youth in the foster care system [10, 11]. While the percentage of children and youth in foster care who received some medical care over the previous 12 months has risen from 80% in 2011 to over 95% in 2017, the level of care available continues to fall short of demand Figure 1 [12]. Shows that less than 75% of foster children and youth are getting their mental, behavioral, physical, and dental needs met.
MyFLFamiles dashboard summary.
The information currently available indicates that children and youth with ACEs who remain untreated are at significant risk of suffering a 20-year difference in lifespan compared to their peers who are unaffected by ACEs, as well as increased risk for unemployment, poverty, homelessness, and more [13, 14]. Programs that provide these young people with skills and strategies to improve their health and well-being can mitigate the risk of chronic physical and mental illness [15].
Florida’s fractured and privatized child welfare system leads to significant deficits in foster child and youth education and physical and mental healthcare. These deficits directly translate to poor quality of life outcomes for Florida’s foster children and youth. The Wicked Problem Impact Project of underdog DREAMS was to identify strategies to improve the quality of life and well-being for Florida foster youth. Our work identified three key strategies essential for helping youth in foster care reach their potential:
Education
Mental and physical wellness
Access to innovative technology
The underdog Dreams team participating in the Clinical Scholars program consists of two clinical social workers (DS, SB), a family physician (AB), an adolescent psychiatrist (AD), and a clinical psychologist. The underdog DREAMS project engaged in a multi-faceted approach to support foster youth as well as the healthcare providers who play a role in the foster care system infrastructure. Thus, the team focused on clinical, research, and advocacy interventions for foster youth and on the development of the workforce that supports them through training on the impacts of trauma and poverty. The initial goals for the project were adjusted based on our research and investigative findings, particularly during phase one:
Phase two concentrated on
Figure 2 is a visual timeline representing the underdog DREAMS team’s approach and accomplishments and the next steps to be implemented.
underdog DREAMS Timeline.
Capitalizing on best practices in community-based engagement principles, our team partnered with foster youth so that their perspective served as a foundation for all later actions. Youth sources included foster youth enrolled in the First Star Central Florida Academy, the Job Readiness and Leadership Bootcamp, and other Central Florida area youth. Simultaneously the team conducted an in-depth literature review on this topic, including researching the current foster care environment in the State of Florida. The goal of this exercise was to figure out what had been or was being done in this arena and (more importantly) who seemed to be doing it effectively.
Team underdog DREAMS executed several engagement strategies which included:
An active partnership with foster care youth and other community partners;
A physical activity-based life skills intervention and collaboration entitled underdog DREAMS Foster Youth Physical Activity and Social Emotional Development Program with an organization called Move + Live + Learn;
Education to promote community awareness and advocacy;
Education directly tailored for foster youth and advocacy;
Foster youth mental and physical wellness; and
Technology solutions to support youth in foster care.
Youth in foster care are the most critical community partners, and thus the team emphasized building trust and engaging with them to build a positive and trusting relationship and to identify their physical, social, and emotional needs.
Team underdog DREAMS collaborated with Move + Live + Learn to develop, deliver, monitor, and evaluate an 8-week physical activity-based life skills program. The ongoing collaboration helped underdog DREAMS develop our three strategic categories for maximum impact on the lives of foster youth in Florida: education, mental and physical wellness, and technology. This program was designed to increase:
Physical activity levels;
Understanding of healthy eating behaviors;
Proficiency in practical life skills;
Proficiency in social–emotional skills such as emotional regulation, communication, and decision making; and
Understanding of how to make choices that enhance wellness.
Led or participated in outreach experiences including training and ongoing reflective supervision to professionals, facilitating simulations, and presenting at conferences
Represented youth voices at Florida Baker Act Task Force for Adolescents
Served on Florida Child Welfare Advisory Board as an advocate for foster youth
Hosted the underdog DREAMS Foster Care Month Celebration and Fundraiser Event held at Topgolf Orlando, highlighting underdog DREAMS’ $42,000 sponsorship of First Star Central Florida Academy
Submitted an opinion piece to the American Academy of Family Physicians that included a call to action to create a formal initiative for Family Medicine around the child welfare system
Created underdog DREAMS Child Welfare Standard of Care Protocol
First Star Central Florida Academy: underdog DREAMS participated in the academy’s onsite summer program and monthly at their Saturday sessions.
underdog DREAMS Job Readiness and Leadership Boot Camp: The team created and facilitated a preparatory program for 18 Central Florida foster youth ages 16–17.
Experiential Learning Experiences: The team sponsored trips to North Carolina; Washington, DC; and Puerto Rico.
Student-led video development: Participants created a video to pitch concepts on how the Microsoft HoloLens can innovate the child welfare system and improve long-term outcomes.
In an effort to deliver continuity of mental healthcare and address the frequent turnover of medical providers foster youth must endure, we implemented evidence-based treatment rooted in Trauma-Focused Cognitive Behavioral Therapy (TF-CBT), utilizing telepsychiatry to ensure continuity of care and access to child and adolescent psychiatry.
We partnered with MOVE + LIVE + LEARN to create the underdog DREAMS Foster Youth Physical Activity and Social Emotional Development Program and evaluate a pilot intervention entitled underdog DREAMS: A physical activity program focused on life skills and social emotional health for deserving youth in foster care. Results of this mixed-methods research project are presented in the Notable Findings section of this chapter.
Telepsychiatry and our presence on-line and in social media contributed to the effectiveness of this project. We partnered with remote professionals to deliver innovative and engaging curriculum for youth in our underdog DREAMS Job Readiness and Leadership Boot Camp.
Notable Findings.
To support a more unifying approach to foster youth across the state, Team underdog DREAMS developed an evidence-based standard of care protocol outlining the necessary services that should be provided to every child entering the child welfare system. Ideally, this protocol would be legally mandated and utilized by the Community-Based Care (CBC) system to ensure all children and youth receive equal access and the highest caliber of treatment across the state.
There are 4 components to this protocol: Access, Assessment, Assistance, & Advocacy (see Figure 3).
underdog DREAMS Child Welfare Standard of Care Protocol.
At the end of year 2, underdog DREAMS implemented the underdog DREAMS Job Readiness and Leadership Boot Camp, a preparatory program for CBC Central Florida foster youth ages 16–17 who were embarking on summer employment opportunities. There were 18 participants who attended the 4-day program that included psychosocial education, life skill training, and experiential learning.
On the final day of the camp, the participants completed a survey that asked for in-depth feedback on different aspects of the program. One set of questions focused on satisfaction, specifically with the presentations, the training facilities, and the overall quality of the workshop. The results of these questions are illustrated in Figure 4.
underdog DREAMS Job Readiness and Leadership Boot Camp Program Results.
Feedback data was overwhelmingly positive, with 100% of participants being satisfied/very satisfied, stating the program met their expectations, and they would recommend it to others. Results were similar for participants’ views about instructional quality. Several youth attendees commented specifically on how much they liked learning with the use of video conference technology.
One theme that stood out among the positive comments from the foster youth was their enjoyment with interacting, hearing others’ thoughts, debating, group discussions, and “networking” with one another.
In the summer of 2019, Team underdog DREAMS launched an evidence-based youth physical and mental health program consisting of 24 sessions designed to increase physical activity levels and perceptions of physical activity; improve functional life skills (e.g., communication, nutrition education), and improve social emotional learning skills (e.g., coping strategies, decision making). Three group homes were partners in this project and transported youth to a central location for the twice weekly program throughout the summer. Trained coaches facilitated the lessons.
The underdog DREAMS team hypothesized that if the program proved to substantially improve the health (i.e., physical, mental, social, etc.) of youth in residential foster care, the successful elements of the program might be applicable in other residences. A mixed-methodology (quantitative and qualitative) evaluation occurred toward the end of and upon completion of the 8-week program. The quantitative assessments consisted of two previously validated instruments: the Survey (YES) 2.0 and the Life Skills Assessment (LSA) (Figures 5 and 6) [16, 17]. The qualitative analysis consisted of an opt-in participation focus group session so that participants’ voices could be heard. Program participants also completed an informational questionnaire (Google forms) in a guided opt-in focus group. All program participants completed “exit slips” that indicated the degree to which the learning objectives were met by the session.
Life skills assessment (LSA) observation tool findings of program participants, post participation. Legend: 1 = does not yet do; 2 = does with a lot of help; 3 = does with some help; 4 = does with little help; 5 = does independently.
Youth experience in sport (YES) 2.0 tool findings of program participants, post participation. Legend: 1 = not at all; 2 = a little; 3 = quite a bit; 4 = yes, definitely.
Challenges emerged related to consistency on the part of group home staff to transport youth to the programming. Thus, while underdog DREAMS planned for, recruited, and could accommodate approximately 60 youth for the program, a total of 13 youth attended all 24 sessions. While this reduced expected numbers, it allowed for the intervention to be piloted and points to the key role that transportation plays in intervention planning and design.
The Life Skills Assessment (LSA) is an observation tool completed by facilitators of the program for each youth who participated in the program. This tool provides a sense of where coaches feel youth are in terms of applying the social–emotional skills they were taught in the program. Coaches observed high ratings in the LSA skill areas in youth who had participated in the program.
The YES 2.0 tool was completed by participants following their participation in the program, and specifically referred to the underdog DREAMS physical activity program. Participants of the program stated that overall they had gained helpful skills centered around topics such as goal setting, effort, problem solving, time management, emotional regulation, positive relationships, managing stress, etc. at rates between
A stepwise linear regression analysis revealed that positive relationships among youth significantly predicted the observer’s overall assessment of the overall life skills of each participant. In other words, the higher someone reported that the program had a positive impact on their relationship with others, the higher the coaches rated their overall use of life skills during the program.
Qualitative data was collected through focus groups with participants. Analysis indicated that youth in the foster care system may respond better in a focus group with one other youth or in a one-on-one setting. Youth had to be continuously directed to refocus and did not share their experiences as much as we anticipated. Four primary themes emerged from the focus groups (Figure 7).
Focus group themes.
Overall, the data suggest that the time and resources designated to teach social emotional skills and functional life skills had a positive impact on those youth in foster care who were able to attend regularly. Participants indicated that the program primarily helped them with self-management and emotional regulation skills (e.g., dealing with conflict, knowing when to step back and walk away).
Youth in foster care rarely participate in studies on well-being related topics such as physical activity and social emotional skills. There are many reasons for this as highlighted by Quarmby and Pickering, who conducted a scoping review of barriers and policy related to physical activity behaviors of youth in foster care [18]. To illustrate the minimal literature on this topic, only seven research articles qualified for their 2016 review from an original pool of 576 potential articles. The criteria for the authors’ broad review included: published in English, published in a peer-reviewed article, published between 1989 and 2014, related to children and youth living in or leaving foster care (including residential homes), and referenced physical activity participation [19]. Thus, drawing comparisons from previous research on physical activity and social emotional learning programs for youth in foster care is difficult; this fact emphasizes the need for work such as our project to determine what types of programming best supports the well-being of youth in the foster care system.
The majority (n = 12) of total participants (n = 13) who participated in all 24 sessions of the physical activity life skills and social emotional program were adolescent girls. According to the 2018 US Report Card on Physical Activity for Children and Youth, only 18% of adolescent girls receive the recommended 60 minutes of moderate to vigorous physical activity daily, compared to 36% of adolescent boys [20]. Given that fact, it was promising to the underdog DREAMS team that something about this particular program kept 12 girls returning to the program. Perhaps it was the social component, the inclusive nature of the evidence-based physical activities provided, and/or the positive relationships established among participants and between participants and facilitators of the program. Choice is highlighted here as a potential motivating factor because previous researchers determined choice in physical activity is a predictor of self-determination [21]. Facilitators of the underdog DREAMS program reported that when participants informally communicated joy from particular activities, they were sure to revisit those activities in future settings, which may have contributed to the girls’ continued participation.
While the underdog DREAMS team celebrates that adolescent girl participants increased their physical activity levels and reported learning life skills, one should not assume that local boys in residential homes did not want to participate or that the program is not ideal for adolescent boys in foster care. In this program, two of the three sites with whom we formed partnerships failed to transport youth to the programming location. Decision makers of these group homes were on board for this programming, but group home staff lacked either the capacity or the motivation to transport youth on a consistent basis. Consistent transportation to an off-site venue may have yielded more male participants.
After several weeks of delivering the program to participants from one group home, we changed our program location to their group home property. We did this to reduce transportation needs for that group home and to increase the number of youth from that program participating. This increased participation in the second half of the program implementation.
Youth in this program completed exit slips after some of the sessions as a form of formal, formative assessment. Facilitators analyzed their responses and used them to guide future instruction accordingly. Applying best pedagogical practices to this program was important to the collaborative because this program was not just focused on increasing physical activity behaviors; it was also focused on equipping participants with the necessary social and emotional skills that are often learned from parents. Analyzing these exit slips was extremely promising for the collaborative because participants were able to demonstrate an understanding of the social emotional and life skills taught.
One particular methodological issue that presented itself during data collection was that participants did not share their experiences in detail during the qualitative focus groups program evaluation portion of the project. Even with qualitative research interview strategies such as probing and prompting, youth seemed reluctant to share information about their experiences in any detail. Fortunately, this evaluation was a mixed-methodology study and included a monitoring phase where participants were welcome to give informal feedback at any time. This informal feedback was critical and contributed to the program’s success.
Our results show a great deal of promise for the underdog DREAMS physical activity program, and communities are encouraged to replicate this program. Key successes of program planning and implementation include the following:
A
Program facilitators display
Future sites that implement this program can learn from our implementation and make every effort to increase participation by minimizing challenges to transportation. While we invested in partnerships with organizations and key decision makers, perhaps more time could have been spent with group home staff (i.e., those directly responsible for transporting the youth).
Future implementation of this program should consider giving youth a choice to record their answers individually rather than in a focus group and/or allowing youth to choose how many and which peers they feel most comfortable sharing their thoughts and experiences within a focus group setting. Youth may also be encouraged to write their responses rather than sharing them verbally.
Future sites should collaborate with the underdog DREAMS team to benefit from the body of research in this area. As the program is replicated it can continuously be monitored to measure the impact. It is critical to contribute to the literature as so few studies examine the influence of physical activity programming for youth in foster care [22].
Below are remarks from our team on our crucial leadership insights gained through the experience of serving as a Clinical Scholar.
As defined by the Robert Wood Johnson Foundation, “Health equity means that everyone has a fair and just opportunity to be as healthy as possible. This requires removing obstacles to health such as poverty, discrimination, and their consequences, including powerlessness and lack of access to good jobs with fair pay, quality education and housing, safe environments, and health care” [23]. Belief in this value should be the “north star” for your project and the foundation upon which to build a vision and culture and guide your efforts. In all that our underdog DREAMS team did, we asked ourselves, “does this advance health equity for foster youth?” For example, the underdog DREAMS Child Welfare Standard of Care Protocol is designed to require that
Social determinants of health (SDoH) are the conditions in the places where people live, learn, work, and play that affect a wide range of health risks and outcomes [24]. We recommend spending time understanding the SDoH affecting your target population and creating interventions to address them specifically. Foster youth living in group homes have limited accessibility to healthy food choices, are often responsible for making their own meals, and are unable to participate in sports or fitness activities due to lack of transportation. These were the SDoH identified and addressed in our project; other projects and work might address others.
The underdog DREAMS team initially created and were subsequently guided by our vision: Utilizing the value of health equity, create and project a compelling and engaging vision. Our team recommends that others engaging in this work ground their own approach in a strong overarching vision, as indicated in the (Figure 8) below.
underdog DREAMS Vision Statement.
One of our greatest successes was the development of relationships with key stakeholders. Our relationship with the youth in foster care was most pivotal. By spending quality time engaging in conversation both formally in the classroom and informally through fun activities, we learned from the experts how best to make an impact in their lives. By consistently demonstrating our values of transparency and accountability along with hard work and dedication to this project, underdog DREAMS developed a reputation as trustworthy, knowledgeable team-players, thus allowing for these partnerships to form and grow.
Forms, additional charts and data can be accessed at the underdog DREAMS website.
U.S. Department of Health and Human Services Children’s Bureau
U.S. Department of Health and Human Services Child Welfare Information Gateway
Florida Department of Children and Families
Florida’s Child Welfare Statistics
Casey Family Programs
Center for Youth Wellness
American Academy of Pediatrics Health Foster Care America
National Youth in Transition Database (NYTD)
Tracking the United States Congress
Community-based Care Central Florida
Move Live Learn
University of Central Florida Foundation
First Start Central Florida Academy
UCF College of Community Innovation and Education
Orange County Parks and Recreation
Friends of Puerto Rico
Lo Cal Guest
Cavarocchi Ruscio Dennis Associates
A more comprehensive toolkit can be found at https://clinicalscholarsnli.org/community-impact.
Because of a global change in illness and death from infectious to noninfectious causes during the 20th century, life expectancy doubled and global population quadrupled [1]. Cardiovascular diseases (CVDs) have surpassed cancer as the main cause of mortality, with low- and middle-income countries bearing the brunt of the burden [2].
In 2015, the United States spent more than $200 billion on heart problems, including related medications and health-care services [3]. In 2017, the American Cardiology Association reported that more than 360,000 persons were diagnosed with coronary heart disease [4].
The principal therapy for preventing arterial thrombosis in CVD patients is platelet inhibitors [5, 6]. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard medical treatment for patients with acute coronary syndrome (ACS) and those undergoing percutaneous coronary intervention (PCI) with an intracoronary stent [6].
Every year, about 1.2 million patients get DAPT after receiving a drug-eluting stent (DES). DAPT is used for a variety of cardiologic, neurologic, and surgical indications where the need to prevent thromboembolic events outweighs the risk of bleeding [7, 8]. DAPT is widely used to treat thrombotic stroke, coronary artery disease (CAD), peripheral vascular diseases, and transient ischemic attack (TIA). When compared to aspirin alone, DAPT with aspirin and clopidogrel has been shown to enhance clinical outcomes in patients with acute coronary syndrome or PCI [9, 10].
Despite the effectiveness of DAPT in preventing primary and subsequent myocardial infarction (MI) and stroke, there is an increased associated risk of spontaneous intracerebral hemorrhage (ICH) [11]. Interestingly, in-hospital mortality is greater in patients with ICH who are on DAPT compared to other antiplatelet agents [12, 13]. The goal of achieving efficient antiplatelet activity while avoiding gastrointestinal (GI) injury and bleeding has become a key focus in the management of thrombotic disease patients. This chapter is meant to explore on dual antiplatelet therapy highlighting the current guidelines and recent evidences on the indications, dosing, and duration of treatment using dual antiplatelet therapy.
DAPT comprises of aspirin together with a P2Y12 inhibitor. These agents have different mechanisms of actions. This section will focus solely on the mechanism of action related to antithrombotic effects of dual antiplatelet therapy.
Aspirin is an anti-inflammatory drug, which possesses both anti-inflammatory and antioxidant properties [14]. The primary mechanism of action of aspirin is centered on the irreversible inhibition of cyclooxygenase (COX 1) enzyme, thus preventing the conversion of arachidonic acid into prostaglandin G2 and prostaglandin H2, subsequently inhibiting thromboxane A2 synthesis. Aspirin acetylates and forms a covalent bond with serine residues in COX active site at position 529, thus inhibiting cox 1 enzyme [15, 16]. Other activities of aspirin include mitochondrial oxidative phosphorylation and modulation of NF-KB signals [14].
P2Y12 inhibitors, otherwise known as P2Y12 antagonists, act by blocking P2Y12 adenosine diphosphate (ADP) receptors on platelet surface membrane, subsequently inhibiting thrombocyte activation/aggregation [17]. P2Y12 inhibitors can be classified into two groups: thienopyridines and nucleoside/nucleotide derivatives [16].
Thienopyridines are competitive and irreversible P2Y12 inhibitors [16]. Drugs in this class can be further subdivided into three generations: first-, second-, and third-generation thienopyridines.
Ticlopidine is a first-generation thienopyridines that was withdrawn due to major side effects such as GI disorders, cytopenia, and allergies. Clopidogrel is a prodrug of second-generation thienopyridine derivatives, which is a drug of first choice in DAPT. Clopidogrel active metabolite binds to P2Y12 receptor to form an irreversible covalent bond, which inhibits ADP-dependent platelet activation and aggregation [18]. Dual antiplatelet therapy with aspirin and clopidogrel has been associated with more than 3% platelet reactivity [19] and 10% ischemic occurrences after 12 months of treatment.
Third-generation thienopyridine (prasugrel) was developed with rapid absorption and higher bioavailability than clopidogrel [16, 18].
Some drugs in this class are mainly reversible P2Y12 inhibitors such as ticagrelor and cangrelor. Ticagrelor is a more potent, efficacious, and fast acting P2Y12 inhibitor when compared with other P2Y12 inhibitors such as clopidogrel and prasugrel [20]. Ticagrelor acts by binding to P2Y12 receptor site other than the ADP binding site. In addition, ticagrelor binds to equilibrative nucleoside transporter 1 (ENT 1) in platelets and red blood cells to block the reuptake of adenosine [21].
The P2Y12 inhibitors have peculiar features, advantages and disadvantages, as well as adverse effects. These effects have been summarized in Table 1.
P2Y12 inhibitor | Advantages | Disadvantages | Adverse effects |
---|---|---|---|
Clopidogrel |
|
|
|
Ticagrelor |
|
|
|
Prasugrel |
|
|
|
Advantages, disadvantages, and side effects of P2Y12 inhibitors.
About 40% of patients with atrial fibrillation have a high risk of having CAD. DAPT prevents the risk of thrombotic complications in patients with atrial fibrillation that are undergoing percutaneous coronary intervention [24]. DAPT is preferable to triple therapy with an oral anticoagulant (OAC) due to low risk of bleeding and other thrombotic complications [24, 25, 26]. Clopidogrel is a drug of first choice; however, prasugrel and ticagrelor have been recently approved for treating patients with high ischemic risk and high risk of hemorrhage and stent thrombosis associated with clopidogrel [27].
However, prasugrel is contraindicated in patients undergoing treatment with aspirin and OAC due to the risk of hemorrhage [28].
DAPT can be prescribed for prevention of ACS and other adverse cardiovascular (CVS) events. A combination of aspirin and ticagrelor or prasugrel is commonly recommended for treating patients with ACS within 6–12 months [29, 30]. DAPT is recommended for treating patients with ACS and atrial fibrillation who are at a risk of developing coronary artery disease, which may necessitate PCI with stents [31]. Clopidogrel can be replaced with ticagrelor in rare cases [32, 33]. Cangrelor, a potent intravenous P2Y12 inhibitor with fast onset of action, can be indicated for treating unconscious ACS patients on emergency who are unable to absorb an oral P2Y12 inhibitor [34].
DAPT with aspirin and clopidogrel is recommended for patients with CAD in order to avert atherothrombotic events. In patients undergoing elective stent implantation, DAPT with aspirin and clopidogrel is usually recommended for 3–6 months [30, 35].
In previous years, DAPT with aspirin and clopidogrel or ticagrelor was formerly recommended for preventing recurrent stroke especially in patients with high risk of transient ischemic attack and noncardioembolic mild stroke [36]. However, DAPT has been found in previous studies to reduce the incidence of stroke and CVS-related death, thus making it effective for stroke prevention. Because DAPT reduces the risk of minor stroke and high transient ischemic attack in these patients, DAPT can be recommended in combination with aspirin and a P2Y12 inhibitor for acute treatment of patients with acute noncardioembolic minor ischemic stroke [37].
Novel and trending studies have compared the efficacy of other potent P2Y12 antagonist such as ticagrelor and prasugrel with clopidogrel especially in preventing nonfatal MI, ischemic CVS events, stroke, and other CVS-related death [38]. DAPT with aspirin and clopidogrel is also approved for treating patients with severe stenosis of the intracranial artery [39] and chronic symptomatic peripheral artery diseases (PADs) [40].
Dual antiplatelet therapy is indicated in patients on the line for transcatheter aortic valve implantation (TAVI) without high risk of hemorrhage for 3–6 months [17]. After revascularization, DAPT is usually indicated for 1–12 months in peripheral artery disease (PAD) patients [17]. It is worth to note that DAPT can be extended for more than 1 year in patients with atherosclerosis and mechanical prosthesis having high risk of coronary events [17].
DAPT can also be used in other nonconventional indications, which include diabetes, renal transplant, and carotid endarterectomy. In diabetes, DAPT consisting of aspirin and prasugrel or ticagrelor is indicated due to increased platelet reactivity [41]. DAPT administration reduces the risk of cardiovascular events in patients undergoing renal transplant. On the other hand, the risk of postoperative hemorrhage is increased with DAPT. Therefore, DAPT is strictly recommended for renal transplant patients with high risk of cardiovascular events [42]. DAPT can also be used for patients undergoing carotid endarterectomy [34].
Antiplatelet therapy is an important pharmacological component in preventing atherothrombotic events. Aspirin, a widely used antiplatelet drug, has been found to reduce the risk of recurrent major adverse cardiovascular events (MACE) by around one-fifth [43]. However, the combination of antiplatelets has been reported to achieve better outcomes than the use of aspirin alone [10]. DAPT refers to a therapy that includes aspirin and a P2Y12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor). When compared to single antiplatelet medication, DAPT has been found to prevent recurrent major ischemic episodes in patients with ACS or undergoing PCI at the cost of an unavoidable increased risk of major bleeding [10]. Below are guidelines on the effective use of DAPT across various indications.
Clinical trials have shown that all the patients receiving PCI require DAPT as it reduces risk of short- and long-term thrombotic events when compared to aspirin. Current guidelines recommend a 6-month DAPT for patients with stable symptoms and a 12-month DAPT for those who have had an ACS [29].
Except for patients who have received a bioabsorbable drug-eluting stent, the clinical setting in which it occurs—stable or unstable—and the patient’s bleeding risk are the two most important factors to consider when determining the DAPT duration following PCI. When feasible, extended (at least 12 months) and potent DAPT should be used for these individuals.
Platelet inhibition is critical for the treatment and prevention of short- and long-term thrombotic events. The cyclooxygenase-1 inhibitor aspirin and the platelet adenosine diphosphate P2Y12 receptor inhibitors clopidogrel, prasugrel, and ticagrelor are all available as oral antiplatelet medicines for secondary prevention in patients with CAD. The more recent powerful P2Y12 platelet receptor inhibitors prasugrel and ticagrelor have been tested in individuals with ACS, whereas aspirin and clopidogrel have been studied across the entire range of CAD [44].
A 6-month DAPT time is advised for individuals with stable illness following PCI; however, this might be decreased based on the patient’s bleeding risk or for safety considerations. The guidelines go beyond specifics and advocate for the use of metallic stents as a first-line therapy, even in patients who are only given a 1-month antiplatelet regimen for safety reasons [45, 46]. DAPT should be continued for 6 months in individuals who have had angioplasty with a drug-coated balloon. This guideline is based on the results of many clinical trials that employed empirical antiplatelet methods.
The use of DAPT to inhibit platelet function after an acute coronary syndrome aims to reduce short- and long-term thrombotic consequences [47]. The stent protective effect of DAPT in the first weeks after percutaneous revascularization reduces the risk of stent thrombosis, a potentially fatal event caused by inflammation and endothelial damage associated with mechanical insult during PCI [48]. Long-term therapy has been demonstrated to reduce the risk of subsequent ischemia episodes caused not only by the culprit lesions/vessels, but also by the advancement of atherosclerosis, a phenomenon described as the “patient protective effect” [48].
Several antithrombotic medications have been proposed over time with the goal of offering the best thrombotic protection while minimizing hemorrhagic hazards. However, recent European guidelines advise the use of the two most modern and strong P2Y12 inhibitors (prasugrel and ticagrelor) in patients with or without PCI [49, 50]. The default DAPT length for patients with ACS treated with coronary stenting should be 12 months, while it may be fair to cut it to 6 months in patients with a high bleeding risk or to extend it to more than 12 months in certain cases. These choices should be made after a thorough assessment of the patients’ bleeding and ischemia risks. Although some criteria can aid in the identification of patients who will benefit the most, the requirement to validate surgical tools in clinical practice is well understood. This is especially essential if the DAPT is extended beyond 1 year. A longer dual antiplatelet duration may be considered for patients with this indication who have tolerated this length of DAPT without bleeding problems. In this sense, ticagrelor 60 mg twice daily is advised for patients with a history of myocardial infarction and a high ischemia risk.
According to recent
A higher reduction in thrombotic risk comes at the cost of an increase in significant bleedings, which occur in 1–8% of patients in the first year after starting DAPT [53, 54, 55]. Even less severe bleeding has been linked to an increased risk of death through indirect mechanisms such as unplanned hospitalization, the necessity for urgent operations, and the termination of DAPT [56]. Bleeding is reportedly linked to an increased risk of death and is also linked to the recurrence of ischemic events such myocardial infarction (MI) and stroke [57, 58].
The most significant DAPT-related adverse event is intracranial bleeding (ICB). With recurrence rates of more than 15% and 3%, respectively, ICB is classed as lobar (affecting the cerebral cortex and underlying white matter) or deep (affecting the basal ganglia, thalamus, and brainstem). Antiplatelet therapy on admission was linked with a greater 24-hour in-hospital [59] and 3-month death rate compared to naive patients in a recent study on patients with ICB [60].
Patients with ICB should be observed and managed in an intensive care unit or a dedicated stroke unit with a high level of skill in the acute environment. All the anticoagulant and antiplatelet medications should be stopped immediately.
GI hemorrhage is the most prevalent significant DAPT-related bleeding event following PCI [61, 62].
Owing to its direct suppression of cyclooxygenase-1, aspirin promotes GI bleeding by lowering the endothelium protective action of prostaglandins. P2Y12 inhibitors are thought to affect ulcer healing through limiting platelet aggregation, angiogenesis, and endothelial proliferation rather than being directly ulcerogenic. When compared to clopidogrel, ticagrelor and prasugrel have been linked to a greater incidence of GI bleeding [61].
Owing to its insidious nature, GI bleeding in patients with recent ACS and/or PCI poses a significant treatment challenge. The need to achieve hemostasis frequently necessitates the early termination of antithrombotic therapy. Furthermore, acute bleeding causes platelet activation, and the formation of a prothrombotic environment could explain why patients with GI bleeding who get DAPT after ACS have a higher risk of ischemic stroke [63].
Proton pump inhibitors (PPIs) should be prescribed alongside antiplatelet medication since gastrointestinal (GI) bleeding is the most prevalent major bleeding event [64]. PPIs are only recommended by the ACC/AHA for individuals who are at risk of bleeding (previous GI bleeding, advanced age, and concurrent use of warfarin, steroids, or nonsteroidal anti-inflammatory medicines); however, the ESC supports PPIs for all DAPT patients [7]. The disparity in recommendations stems from different interpretations of a big clinical research that found a pharmacokinetic interaction between clopidogrel and omeprazole, but no effect on cardiovascular events. Given the known cytochrome pharmacokinetic interaction, it is best to avoid co-prescribing clopidogrel with omeprazole/esomeprazole if at all possible [65]. However, there is no known interaction between PPIs and prasugrel.
Antiplatelet drugs commonly block glycoprotein receptors in ACS because they are required for platelet aggregation. Tranexamic acid (TXA) has been demonstrated to be an effective drug for reduce antiplatelet-related bleeding in a number of clinical scenarios, including trauma, and has a good safety profile [66]. TXA has specifically been shown to increase in vitro platelet activity among coronary artery bypass graft (CABG) patients taking antiplatelet medication as well as demonstrating a reduction in operational blood loss [67]. By enhancing platelet function, TXA can be regarded a potential strategy for reducing bleeding problems associated with antiplatelet monotherapy or DAPT.
Platelet concentrates (PCs) are sometimes infused to patients with ICH who are on antiplatelet medications to enhance primary hemostasis before neurosurgery. Platelet concentrates (PCs) are frequently given to patients on APT who develop ICH to overcome platelet inhibition induced by antiplatelet medications [68]. Preoperative transfusion of at least two PCs can enhance primary hemostasis in individuals who require decompression neurosurgery owing to ICH while on APT. Rebleeding could still be a concern especially in individuals with chronic ICH and those using P2Y12 inhibitors. Other options can be explored in the control of bleeding in patients on antiplatelet agents especially DAPT. The options include prothrombin complex concentrates [69] and fresh frozen plasma [70] although they are mostly used for bleeding associated with vitamin K antagonists and direct oral anticoagulants.
Antiplatelet agents have been widely utilized in patients with acute coronary syndrome for decades and are increasingly valued for their antithrombotic as well as anti-inflammatory characteristics. DAPT has been shown to be effective in improving the clinical outcomes of patients with ACS or PCI but is associated with high bleeding risk. Recent guidelines have been proposed not only to help reduce the tendency of bleeding in DAPT patients but also to ultimately improve patient overall quality of life.
The authors wish to thank the Provost, College of Pharmacy, Afe Babalola University, Professor Femi Oyewo and other lecturers for their support and outstanding encouragement during the course of writing this manuscript.
The authors declare no conflict of interest.
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Stuchlik",coverURL:"https://cdn.intechopen.com/books/images_new/6250.jpg",editedByType:"Edited by",editors:[{id:"207908",title:"Dr.",name:"Ales",middleName:null,surname:"Stuchlik",slug:"ales-stuchlik",fullName:"Ales Stuchlik"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6092",title:"Neuroplasticity",subtitle:"Insights of Neural Reorganization",isOpenForSubmission:!1,hash:"1003fc63680b1c04e9135f3dea18a8c3",slug:"neuroplasticity-insights-of-neural-reorganization",bookSignature:"Victor V. 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:3,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:2157,totalCrossrefCites:6,totalDimensionsCites:16,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:"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:1442,totalCrossrefCites:6,totalDimensionsCites:13,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:"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:1471,totalCrossrefCites:5,totalDimensionsCites:9,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"}]},{id:"57312",doi:"10.5772/intechopen.70854",title:"The Hippocampus as a Neural Link between Negative Affect and Vulnerability for Psychostimulant Relapse",slug:"the-hippocampus-as-a-neural-link-between-negative-affect-and-vulnerability-for-psychostimulant-relap",totalDownloads:1591,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"Psychostimulant dependence (including cocaine, amphetamine, and methamphetamine) is a chronic relapsing disorder with significant personal, health, and financial burdens. Attempts at abstinence produce a severe and protracted withdrawal syndrome characterized by stress hypersensitivity that can facilitate drug craving, anxiety, and dysphoria. These negative withdrawal symptoms can induce relapse, maintaining the addiction cycle. The hippocampus mediates cognitive, emotional, and endocrine responses to stressors. The ventral hippocampus is in a pivotal position to regulate the mesoaccumbal dopamine reward system, and interacts with serotonergic and glucocorticoid systems that mediate anxiety and stress responsiveness. Psychostimulant actions on the hippocampus induce long-term changes to these systems and impact the process of adult neurogenesis in the hippocampus, which may facilitate drug dependence by altering drug-cue learning and emotional regulation. Multiple studies indicate that psychostimulant-induced hippocampal neuroadaptations heighten hippocampal-mesoaccumbal activity to amplify drug- and drug-cue responses while persistent dysregulation of hippocampal emotional systems potentiate negative affect. Understanding how psychostimulants modulate the hippocampus to alter hippocampal-mesoaccumbal activity—and how hippocampal neurogenesis influences drug-related memories and reward—is important for identifying novel treatment strategies that can ameliorate negative affect and relapse vulnerability in psychostimulant addiction.",book:{id:"6250",slug:"the-hippocampus-plasticity-and-functions",title:"The Hippocampus",fullTitle:"The Hippocampus - Plasticity and Functions"},signatures:"Jeffrey L. Barr, Brenna Bray and Gina L. Forster",authors:[{id:"145620",title:"Dr.",name:"Gina",middleName:null,surname:"Forster",slug:"gina-forster",fullName:"Gina Forster"},{id:"219827",title:"Dr.",name:"Jeffrey",middleName:null,surname:"Barr",slug:"jeffrey-barr",fullName:"Jeffrey Barr"},{id:"219828",title:"BSc.",name:"Brenna",middleName:null,surname:"Bray",slug:"brenna-bray",fullName:"Brenna Bray"}]},{id:"54143",doi:"10.5772/67127",title:"Plasticity of Dendritic Spines. Not Only for Cognitive Processes",slug:"plasticity-of-dendritic-spines-not-only-for-cognitive-processes",totalDownloads:1384,totalCrossrefCites:0,totalDimensionsCites:6,abstract:"Excitatory synaptic transmission is associated with the input of “new” information at synaptic junctions established by dendritic spines. The role that each type of spine plays in the transmission of the synaptic impulses is different. Indeed, there is a close relationship between the shape of spines and the differential processing of the excitatory synaptic information that is relayed to them, influencing in turn the transmission of synaptic information related to several psychoneural processes.",book:{id:"5521",slug:"synaptic-plasticity",title:"Synaptic Plasticity",fullTitle:"Synaptic Plasticity"},signatures:"Ignacio González-Burgos, Dulce A. Velázquez-Zamora, David\nGonzález-Tapia, Nallely Vázquez-Hernández and Néstor I. Martínez-\nTorres",authors:[{id:"190521",title:"Dr.",name:"Ignacio",middleName:null,surname:"Gonzalez-Burgos",slug:"ignacio-gonzalez-burgos",fullName:"Ignacio Gonzalez-Burgos"},{id:"196267",title:"Dr.",name:"Dulce A",middleName:null,surname:"Velázquez-Zamora",slug:"dulce-a-velazquez-zamora",fullName:"Dulce A Velázquez-Zamora"},{id:"196269",title:"MSc.",name:"David",middleName:null,surname:"González-Tapia",slug:"david-gonzalez-tapia",fullName:"David González-Tapia"},{id:"196270",title:"MSc.",name:"Nallely",middleName:null,surname:"Vázquez-Hernández",slug:"nallely-vazquez-hernandez",fullName:"Nallely Vázquez-Hernández"},{id:"196271",title:"MSc.",name:"Nestor I",middleName:null,surname:"Martínez-Torres",slug:"nestor-i-martinez-torres",fullName:"Nestor I Martínez-Torres"}]}],mostDownloadedChaptersLast30Days:[{id:"58530",title:"Sleep Disorders in Multiple Sclerosis",slug:"sleep-disorders-in-multiple-sclerosis",totalDownloads:1208,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Patients with multiple sclerosis (MS) have multiple causes of poor sleep and potential triggers may relate to MS-related symptoms, co-morbidities and adverse effects from medication. Sleep disorders may occur independently of demographic factors, gender and clinical condition. The real frequency of sleep disturbances in MS and their impact on the patients’ quality of life are unknown. The prevalence of sleep problems in the population with MS ranges between 47 and 62% and is more frequent in women, as well as having a higher risk of mortality. High psychological burden has been associated with poor sleep and with increased risk of co-morbid conditions such as heart disease, obesity, dyslipidemia and diabetes, which may have a profound impact on long-term health. The poor sleeping patients with MS were more likely to report fatigue and sleepiness. Insomnia is present in mood disorders, restless leg syndrome (RLS), pain, nocturia and obstructive sleep apnea (OSA), in patients with MS. All the symptoms are intermixed, and it is not possible to discern the precipitating factor or the perpetuating factor. Clinicians should routinely ask about sleep when forming a comprehensive care plan for patients with MS. Sleep specialty referrals should be considered for management of conditions that require polysomnography (PSG) diagnosis.",book:{id:"6092",slug:"neuroplasticity-insights-of-neural-reorganization",title:"Neuroplasticity",fullTitle:"Neuroplasticity - Insights of Neural Reorganization"},signatures:"Montserrat González Platas and María Yaiza Pérez Martin",authors:[{id:"202099",title:"Dr.",name:"Montserrat",middleName:null,surname:"Gonzalez Platas",slug:"montserrat-gonzalez-platas",fullName:"Montserrat Gonzalez Platas"},{id:"231355",title:"Dr.",name:"Maria Yaiza",middleName:null,surname:"Perez Martín",slug:"maria-yaiza-perez-martin",fullName:"Maria Yaiza Perez Martín"}]},{id:"53927",title:"GABAergic Synapse Dysfunction and Repair in Temporal Lobe Epilepsy",slug:"gabaergic-synapse-dysfunction-and-repair-in-temporal-lobe-epilepsy",totalDownloads:1668,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Severe medial temporal lobe epilepsy (mTLE) is often associated with pharmacoresistant seizures, impaired memory and mood disorders. In the hippocampus, GABAergic inhibitory interneuron dysfunction and other neural circuit abnormalities contribute to hyperexcitability, but the mechanisms are still not well understood. Experimental approaches aimed at correcting deficits in hippocampal circuits in mTLE include attempts to replace GABAergic interneurons through neural stem cell transplantation. Evidence from studies in rodent mTLE models indicates that transplanted GABAergic progenitor cells integrate into the hippocampus, form inhibitory synapses, reduce seizures and improve cognitive deficits. Here, we review current work in this field and describe potential molecular mechanisms underlying successful transplantation.",book:{id:"5521",slug:"synaptic-plasticity",title:"Synaptic Plasticity",fullTitle:"Synaptic Plasticity"},signatures:"Meghan A. Van Zandt and Janice R. Naegele",authors:[{id:"154904",title:"Prof.",name:"Janice",middleName:null,surname:"Naegele",slug:"janice-naegele",fullName:"Janice Naegele"},{id:"194530",title:"Ph.D. Student",name:"Meghan",middleName:null,surname:"Van Zandt",slug:"meghan-van-zandt",fullName:"Meghan Van Zandt"}]},{id:"54067",title:"Neuroplasticity in Bipolar Disorder: Insights from Neuroimaging",slug:"neuroplasticity-in-bipolar-disorder-insights-from-neuroimaging",totalDownloads:1630,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Background: Advances in neuroimaging techniques have produced evidence about disrupted frontolimbic circuits related to emotional regulation. These neuroimaging studies may suggest impairments in cellular plasticity in bipolar disorder (BD) patients. However, the long-term use of mood stabilizers may restore these dysfunctions by neurotrophic effects",book:{id:"5521",slug:"synaptic-plasticity",title:"Synaptic Plasticity",fullTitle:"Synaptic Plasticity"},signatures:"Marlos Vasconcelos Rocha, Fabiana Nery, Amanda Galvão-de-\nAlmeida, Lucas de Castro Quarantini and Ângela Miranda-Scippa",authors:[{id:"192139",title:"Ph.D.",name:"Marlos",middleName:"Vasconcelos",surname:"Rocha",slug:"marlos-rocha",fullName:"Marlos Rocha"},{id:"192876",title:"Dr.",name:"Fabiana",middleName:null,surname:"Nery-Fernandes",slug:"fabiana-nery-fernandes",fullName:"Fabiana Nery-Fernandes"},{id:"192877",title:"Prof.",name:"Ângela",middleName:null,surname:"Miranda-Scippa",slug:"angela-miranda-scippa",fullName:"Ângela Miranda-Scippa"},{id:"192878",title:"Prof.",name:"Lucas",middleName:null,surname:"De Castro Quarantini",slug:"lucas-de-castro-quarantini",fullName:"Lucas De Castro Quarantini"},{id:"192879",title:"Dr.",name:"Giovanna",middleName:null,surname:"Ladeia-Rocha",slug:"giovanna-ladeia-rocha",fullName:"Giovanna Ladeia-Rocha"},{id:"192880",title:"Prof.",name:"Amanda",middleName:null,surname:"Galvão-de Almeida",slug:"amanda-galvao-de-almeida",fullName:"Amanda Galvão-de Almeida"}]},{id:"59437",title:"Music and Brain Plasticity: How Sounds Trigger Neurogenerative Adaptations",slug:"music-and-brain-plasticity-how-sounds-trigger-neurogenerative-adaptations",totalDownloads:2155,totalCrossrefCites:6,totalDimensionsCites:16,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:"54566",title:"Introductory Chapter: Mechanisms and Function of Synaptic Plasticity",slug:"introductory-chapter-mechanisms-and-function-of-synaptic-plasticity",totalDownloads:2244,totalCrossrefCites:3,totalDimensionsCites:3,abstract:null,book:{id:"5521",slug:"synaptic-plasticity",title:"Synaptic Plasticity",fullTitle:"Synaptic Plasticity"},signatures:"Thomas Heinbockel",authors:[{id:"70569",title:"Dr.",name:"Thomas",middleName:null,surname:"Heinbockel",slug:"thomas-heinbockel",fullName:"Thomas Heinbockel"}]}],onlineFirstChaptersFilter:{topicId:"1175",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:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. 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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