The “
\r\n\tUnstoppable progress in the technologies of synthesis of diamond, graphene, and its compounds with stable parameters will provide materials for the industry of devices for integrated, radio, Opto- and quantum electronics and photonics.
\r\n\tIn most electronic and optical properties, diamond and graphene are superior to traditional and perspective semiconductors. It is safe to say that silicon and gallium arsenide are materials for electronics and optoelectronics of the past, gallium nitride and silicon carbide are high-tech today, and diamond and graphene are the future of electronics and photonics.
The United States (US) is in the midst of a mental health crisis [1, 2, 3, 4, 5, 6, 7]. More than one in four (26.2%) adults experience a diagnosable mental health disorder each year, and 46% of the population will do so in their lifetime [1, 2]. Collectively, mental disorders are a leading cause of disability, accounting for one-third of all years lived with disability and premature mortality [3].
Despite the heavy burden of disease, availability of mental health care services is inadequate. Available care services are often underutilized because mental health disorders impair one’s ability to seek and adhere to care, delaying the receipt of effective treatment. Screening, early detection, and effective ongoing treatment of mental health disorders can have a positive impact on the quality and quantity of life. Unfortunately, this often does not occur; many people experience their introduction to mental health treatment in emergency settings at a late stage in the course of the disease. Elements influencing mental health treatment-seeking behaviors include systemic factors, knowledge, beliefs, attitudes, and stigma [4].
More than 18% of people in the US who experience mental health morbidity are Black, but Black people account for only 12% of the population [4]. Black adults are more likely to have feelings of sadness, hopelessness, and worthlessness than are white adults [6]. Despite this higher morbidity, many Black Americans do not seek mental health care [4]. Multiple factors contribute to the higher burden of mental health morbidity in Black Americans and include, but are not limited to, racism and other forms of discrimination, stigma, distrust of the health care system, a perception of bias and lack of cultural sensitivity in the health care system in general, inadequate mental health literacy, and poverty.
Hankerson et al. cited individual and institutional racial discrimination as a risk factor for depression [8]. Institutional racism results from policies and practices within organizations that contribute to discrimination for a group of people [9]. Living with a plethora of discriminations that manifest as police brutality and other forms of racial harassment can result in racial stress and have a deleterious effect on the health and well-being of Black people. Racial stress often occurs as a result of repeated everyday discrimination known as micro-aggressions. Research shows that repeated acts of micro-aggression are a more consistent predictor of depressive symptoms than single instances of major discrimination [10, 11].
The persistent psychological assault of racial stressors culminates in the form of racial trauma. Racial trauma occurs when African Americans are surrounded by constant reminders of the dangers of being African American [12]. Washington called these reminders a form of Persistent Enslavement Systemic Trauma (PEST) [13]. PEST describes a specific dimension of the trans-generational trauma pervasive in all walks of Black American life. PEST is a systemic trauma that has residual effects on the daily activities of African/Black people and influences multiple aspects of their lives. Washington asserts PEST affects the entire psychological well-being of people of African descent, including their physical bodies, minds, perceptions of reality and themselves, relationships with themselves and others, and notions of what it means to be a person [13].
Stigma is a collection of attitudes, beliefs, and behaviors that assign shame to an individual who exhibits actions or traits outside of a perceived norm [14]. Connor et al. posited that both public stigma (negative attitudes held by the public) and internal stigma (negative attitudes held by stigmatized individuals about themselves) are important barriers to successful mental health treatment [15]. Their study found Black American adults as a whole tended to internalize the stigma of mental illness and sought treatment at half the rate of non-Hispanic white Americans [15]. Upon seeking treatment, Black people were reported to skip sessions and terminate treatment at higher rates than their white counterparts [15].
The history of deliberate medical and scientific mistreatment of Black people in the US is well-chronicled [8]. One of the most significant events was the 1932 Tuskegee Syphilis Experiment, in which Black men with syphilis were followed by the US Public Health Service to observe the course of the disease [16]. Researchers withheld treatment allowing the disease to progress and, in some cases, to infect wives and children of the subjects. The Tuskegee Experiment was one in a series of events throughout history that instilled social norms of medical mistrust in the Black community.
Qualitative studies show that some Black Americans today have a fear of being used as “guinea pigs” [16]. This fear drives decreased healthcare utilization, treatment compliance, and decreased willingness to participate in research and clinical trials [8, 17].
Some Black Americans identified the mental health system specifically as a stressor [15]. Many perceived that Black Americans had a more difficult time accessing mental health services and expressed frustration with the process of seeking care.
Multiple studies of the US health care system have documented implicit bias—thoughts and attitudes that exist outside conscious awareness. In one such study, Hall et al. examined 15 articles and used the Implicit Association Test to assess implicit bias. They concluded that most health care providers appear to have an implicit bias in terms of positive attitudes toward whites and negative attitudes toward people of color [18].
Several studies have shown Black Americans strongly prefer mental health providers of their same ethnic background [8, 15, 17]. However, Black people make up only 3.9% of psychologists [5] and 5% of physicians [17], a visible reminder of why Black Americans perceive the mental health system as being culturally insensitive.
An important factor related to seeking mental health support is mental health literacy, which is the “knowledge and beliefs about mental disorders which aid their recognition, management, or prevention” [19, 20]. In a 2010 study of Black Americans, participants were able to recognize their symptoms (trouble sleeping, excessive drinking, sadness, and fatigue) but did not relate them to depression [21]. Upon learning the relationship, a majority of participants believed they needed to deal with them on their own and were averse to the idea of seeking treatment. Many believed that treatment would be ineffective or feared the idea of taking medication [21]. Many Black people do not perceive a need for mental health care as shown in a 2017 study using data from the National Survey of Drug Use and Health (NSDUH). Only 9.4% of Black Americans reported a perceived need for mental health care compared with 17.9% of their white counterparts [14].
Economic challenges prevalent within the Black community also affect psychological well-being. Black adults living below poverty are two to three times more likely to report serious psychological distress than those living above poverty [6]. A 2013 review of depression in Black men found that higher-income served as a protective factor against depression, and job security correlated with a lower frequency of depressive episodes [22]. In a 2011 study of Black men, major depressive disorder (MDD) was associated with lower income, less education, and being unmarried [23].
Black men, in particular, have increased morbidity due to mental illness. Data from the US Department of Health and Human Services show Black men are 30% more likely than non-Hispanic white men to report having a mental illness [5]. Suicide attempts among Black males are 1.6 times higher than white males [5]. A 2017 Health and Human Services study found the death rate from suicide for African American men was more than four times greater than for African American women [6].
Racial stress contributes to the total burden of stress on Black men and impacts mental health outcomes. In a 2006 longitudinal prospective study of over 700 Black men, racial discrimination was strongly associated with poor physical and mental health [24]. A 2011 study using data from the National Survey of American Life found that Black American men below the age of 30 had greater depressive symptoms, experienced greater perceived discrimination, and had a lower perception of mastery than their counterparts above the age of 54 [11]. Belgrave & Brevard state African American boys have many potential stressors, even relative to African American girls, that negatively impact their psychological well-being throughout their lives [9].
A 2012 review analyzing beliefs of masculinity among men of color found an association between “machismo” or traditional masculinity beliefs and the inability or unwillingness to describe emotions - “taking it like a man” [25, 26]. Masculinity is often associated with certain expectations and standards a man must uphold. In a 2019 qualitative study, Black men reported endorsing the role of caretaker, someone who needs to display strength for their family [26]. Displays of emotion or vulnerability were perceived as a weakness and negatively affected mental health treatment-seeking behaviors [27, 28].
Research by Holden et al. showed Black men are more likely to struggle with describing depression and their emotional state [5], making acknowledging the need for care increasingly difficult. Even if Black men recognize the symptoms of depression, they are less likely than Black women to believe mental health treatment would be effective. Younger Black men were the least open to the idea of seeking mental health treatment as compared with older African American men and women of all ages [4]. Cook et al. and others have shown Black American men have lower rates of use of psychotropic medication than their white counterparts [8, 29].
The broad geographical area within the District of Columbia (DC) where the initiative operates is referred to as “Southeast DC” or “East of the Anacostia River”. The unemployment rate across DC is four times the national average with twice the rate of alcohol abuse, twice the rate of alcohol-related driving deaths, and 20 times the violent crime rate [30]. Most of these figures are driven by data from Southeast DC, the service area for the
Life expectancy in Southeast DC can be up to 10 years less than other neighborhoods three miles away, with limitations due to physical or emotional health more common. More than 10 times as many families as those who live in other areas of DC reside in poverty, and child poverty rates are as high as 47.1% compared with 20.3% nationally [31]. Additionally, one in five (20.3%) Southeast DC residents is unemployed.
In MHISTREET’s specific area of Ward 8 in Southeast DC, 92% of the population is Black, 30.7% of the population lives in poverty, and 85% completed high school [7]. Southeast DC is unfortunately emblematic of numerous disenfranchised communities in the US [32]. African Americans living here experience the highest rates of mental health disorders in DC [33]. Contributing factors include constant exposure to environmental factors such as discrimination, violence, limited health service access, and poverty [34, 35]. Each factor is a significant barrier to mental health service utilization and exists at multiple social-ecological levels including individual/interpersonal, provider/mental health system, community, and societal levels [33]. Devising effective systematic approaches for improving the mental health of Black men living in Southeast DC must reflect an understanding of the ecological and system perspective.
Wicked problems are unique in that they have no definitive formulation. They are interdependent, codependent, and symptoms of other wicked problems. Wicked problems have no true endpoints and no template to follow. As laid out in the introduction, poor mental health and wellbeing in Black Americans, particularly Black men, fit this description. It is an elusive, complex, “
The selection of poor mental health and well-being among African Americans in Southeast DC is based on the authors’ experiences at a medical clinic treating people living with HIV/AIDS. The clinic is located within the United Medical Center hospital, the only hospital in Southeast DC. United Medical Center operates as a safety-net hospital in the only designated mental health professional shortage area of the city. The authors surmised that the impact of negative social determinants (racism, discrimination, and underemployment) on the physical health of their predominantly Black and low-income patients was compounded by unaddressed mental health issues. Their patients who had mental health disorders (depression, anxiety, post-traumatic stress disorder) also had difficulty adhering to their care and treatment goals and consequently had poorer health outcomes. These outcomes also informed the authors’ view that improving access to and utilization of mental health services in Ward 8 of Southeast, DC should be a key priority, and the first step should be increasing mental health literacy in the community to reduce the barriers to treatment.
The project design changed dramatically over the first few months and continued to evolve over the course of the initiative. Project evolution was possible because the team drew from community-based participatory research (CBPR) principles [37, 38] and used an action research approach [39].
Use community settings and involve the community in the project design and implementation
Build on strengths and resources within the community
Focus on problems relevant to the community
Use an ecological perspective that attends to multiple determinants of health and disease
Openly address race, racism, ethnicity, and social class
Problem identification
Organization of plan of action
Data collection
Organization and analysis of data
Planning for future action
The initial proposal was to design a community hospital-based clinical support program at the patient, provider, and population levels. At the patient level, the plan was to screen primary care patients for mental health disorders and social needs and link them to mental health care and social services. For the providers, the intent was to support mental health education of Southeast DC private Medicaid primary care providers and share community mental health resources. Lastly, at the population level, the goal was to train community members on
The project became predominantly community-based and was implemented outside the traditional health care setting to have a wider reach and deeper resonance within the community. After many cycles of the action research process, the focus became African American men, and the core intervention became an educational program for barbers and community members to increase mental health using the culturally safe space of the barbershop to deliver “embedded education”.
The authors were regular attendees of Ward 8 Health Council meetings, created by a former DC mayor to convene diverse stakeholders committed to improving the health of Ward 8 residents. The Council consists of stakeholders from local managed-care associations, hospitals, universities, community-based organizations, and DC residents, who meet monthly and share information and ideas. The issue of poor mental health in Ward 8 was a topic of frequent discussion. The authors were invited by the chair of the council to create a mental health sub-committee charged with promoting and enhancing policies and practices that increase access to mental and behavioral health services, decreasing stigma associated with mental health disorders, promoting mental health wellness, and improving mental health literacy and outcomes for individuals living in Ward 8. Sub-committee members reflected the diversity of the council and were influential in the decision to change the original project design.
Through the authors’ rigorous review of the literature and consultation with the mental health sub-committee and other community members, the program evolved into a community-based intervention. The authors strongly believed the intervention needed to reach residents who were not engaged with the traditional health system.
Myriad factors relate to and influence mental health treatment-seeking behaviors. One important factor is mental health literacy, the knowledge and beliefs about mental health disorders which aid their recognition, management, or prevention [19, 20]. Literacy is a significant determinant of mental health and has the potential to improve both individual and population health. Mental health literacy is conceptualized by Bjornsen et al. [40, 41, 42, 43] as having four domains:
understanding how to obtain and maintain good mental health
understanding mental health disorders and their treatments
decreasing stigma against mental illness and
enhancing help-seeking efficacy
Domains are consistent with the qualitative input collected from community partners and stakeholders about their concerns with stigma, misinformation, and misperceptions about mental health. Their experiences echoed research findings on stigma, medical mistrust, and cultural norms within the African American population.
As a result of strong community input and data collection, increasing mental health literacy became the goal of the intervention. Closing the existing literacy gap was determined to be essential to improve community mental health.
The authors’ understood that an anchor institution was critical to successful program implementation. The term “anchor institution” was coined by Michael Porter in 2002 [44] and is defined as a community-dependent resource which capitalizes on opportunities to create shared value and be a major economic force within the community by controlling important levers for community development [45]. In a review of outreach strategies directed at Black men, the highest yield was produced using personnel of the same ethnicity to conduct face-to-face outreach [17]. Results were amplified when the outreach came from within the Black community [21].
Emerging literature highlights the power and potential of universities, hospitals, and other institutions with long-term rooted investments in an area to transform neighborhoods, cities, and regions [46]. Originally, the authors thought the local hospital would serve as the anchor institution. However, that idea was abandoned based on community perceptions of the hospital and the team’s desire to reach individuals not currently engaged with the health care system.
The authors then considered the Black church, given its historical importance and service to the Black community. The team connected with an out-of-state program called PEWS (Promoting Emotional Wellness and Spirituality) at the Mental Health Association of New Jersey. PEWS trains faith leaders in mental health to address the need within their congregations. The authors explored replicating the PEWS model in Southeast DC with the Faith-Based Director of the local DC Department of Behavioral Health. However, a nascent program was already in place, and the committee advised that large segments of the population would not be reached through religious organizations.
After much discussion, with Black men as the primary focal point of the intervention, barbershops were selected as the anchor institution to implement mental health literacy programming. Unlike healthcare sites and religious organizations, barbershops are regarded as a trusted and equalizing space and barbers as trusted members of the community. In addition, barbershops are non-medical and non-religious settings with no “negative psychological baggage” [47].
The team conducted a systematic review of barbershop interventions to evaluate their effectiveness and seek best practices from several existing programs in the US and abroad. They consulted with the Lion’s Den in the United Kingdom, a barbershop mental health program recognized by former Prime Minister Theresa May and Prince William. In the US, the authors found several health-related programs in barbershops. The most robust and well known was The Confess Project led by Lorenzo Lewis. Mr. Lewis’s grassroots efforts in Arkansas and surrounding states were inspirational and confirmed the notion that the Black barbershop has long served an important social and cultural purpose.
Barbershops have historically been a safe gathering place for Black men, a place where people have received the news, registered to vote, and shared personal struggles. The barber often not only cuts hair but also serves as a confidant. The barber/client connection in Black communities places the barber in a unique position to be a strong partner and leader in increasing mental health literacy among Black men. In addition, the authors’ speculated the Black barbershops’ place in the community would enable interaction with women and children, so this health intervention could potentially impact families and the broader community.
The use of barbershops for health interventions dates to the 1980s. This model has been used to address Black American health issues such as hypertension, prostate cancer, and HIV/AIDS, but the MIHSTREET team found no published reports in peer-reviewed literature regarding its use for mental health interventions [48, 49, 50]. All intervention studies reviewed by the team found greater health improvement among those interacting with the barber [51, 52, 53, 54, 55]. The literature, composed of non-experimental studies, suggested that several common factors were present in successful barbershop interventions, including the training of the barber in health knowledge, referring clients to a healthcare provider (physician and/or primary care provider), and the use of a theoretical model to guide the intervention. These findings influenced the authors’ approach to project design and implementation, specifically the training of the barbers and the need for an immediate connection to services.
MHISTREET chose embedded education, a recognized public innovation in governance tool, to deliver mental health information [56]. Embedded education is the practice of educating people through everyday interpersonal encounters within organizations that exist for non-educational purposes [57]. Embedded education uses existing social relationships and trust between individuals and organizations or within social networks, to deliver content that learners can immediately use and share [58]. By using the existing trusting environment of the barbershop and minimal additional supplies, MHISTREET’s barbershop approach provides the potential to reach a mental health service-neglected population. As a client waits for or receives services, he becomes a learner in a health-related educational encounter. The encounter occurs between the barbers and their clients and/or between community residents/peer educators and the clients. The educational content is mental health information transmitted via conversations between barber and client or between a community resident/peer educator and clients.
With guidance from multi-disciplinary community partners on the Ward 8 sub-committee, the authors created a culturally relevant mental health education curriculum for embedded education in barbershops. The curriculum was based on the previous work of a collaborating partner, Dr. Kevin Washington, a professor of psychology, who had developed a mental health curriculum specifically designed for African American men. The final product was a six-module curriculum that incorporated pop-culture, race, and social justice themes, and used interactive lessons, music, video, and audio presentations.
The program structure for BEE involved training barbers on mental health and having them engage with and share resource information with interested clients. A pilot cohort of barbers received the initial training in 2018 and provided structured feedback. Specific feedback included comments such as, “This was great; I hear people’s problems all the time and I didn’t know how to help them!” and “I used to think peoples’ issues were too big to overcome and now I know there is help out there” and “I did not realize there is help out there for my brothers.” Participants also stated the training was beneficial but too long. It interfered with their work schedules, led to a loss of earnings, and financial incentives provided for attendance were not enough to counterbalance lost income.
Feedback from barbers and input from community advisors led to program modifications. The revamped MHISTREET program included not only barbers but also 40 community members. The inclusion of community members was modeled after an existing program, The Confess Project in Arkansas [58], led by community mental health advocate Lorenzo Lewis. Mr. Lewis shared his moving story of adversity and the benefit he received from mental health counseling. Through storytelling, he was increasing the mental health literacy of barbershop clients in Arkansas and surrounding states.
Storytelling is an evidence-based education method that increases the likelihood of behavior change based on the activation of neurotransmitters in the brain responsible for concentration, empathy, and connection [59]. Storytelling, particularly stories that resonate individually, has the ability to change one’s attitudes, beliefs, and behavior, and can be a powerful vehicle for change.
The authors used their original barber training to develop a program similar to The Confess Project [58]. The MHISTREET team hosted a one-day training event for the new iteration of the project. The authors then met monthly over six months with the new team affectionately referred to as the “BEE Squad”. The six BEE Squad members learned more about mental health, rehearsed their stories, and practiced facilitation of group discussions.
The logic model that the authors used as a framework to develop the Barbershop Embedded Education program. Provides the inputs, activities, outputs and outcomes related to the project (Table 1).
INPUTS → | ACTIVITIES → | OUTPUTS → | OUTCOMES |
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The “
The authors developed, administered, and analyzed a 200-patient mental health knowledge, behavior, and attitude survey in the only safety-net hospital in Southeast DC. Data showed that over 80% of respondents had some degree of knowledge about mental health but over half indicated significant stigma around using mental health services for themselves or loved ones.
The authors developed and administered a survey to six local Medicaid primary care providers on their knowledge and practices in mental health care. All of the providers reported that they were caring for many patients with mental health disorders and five of the six providers were interested in learning more about mental health and available services.
In partnership with George Washington University (GWU), the team collaborated on geographic “hotspot” mapping in Ward 8 to determine whether a correlation existed between emergency room use and mental health diagnoses. While informative about the overall prevalence of mental health disorders, the analysis did not show any particular “hotspots” for the high prevalence of mental health disorders within the Ward 8 boundaries.
The authors’ supervised eight GWU public health student projects. One project resulted in an inventory of Ward 8 mental health and social service resources as requested by stakeholders. Information from the inventory was incorporated into the BEE training curriculum.
Over the first two years, the authors built an active and engaged network of professionals from the Ward 8 Health Council, including several community-based leaders from around Washington, DC. The authors regard this as one of the project’s strengths and earliest successes.
The MHISTREET creation and leadership of the Mental Health Sub-Committee Advisory Group of the Ward 8 Health Council allowed access to the insight and knowledge of thought leaders. It generated active collaborations with local clinics, DC managed care organizations and mental health professionals in order to gain a deeper awareness of local strengths, resources, and needs.
The sub-committee members also convened three Southeast DC faith leaders and organizations from the local community and around the US for advice and guidance. Among the most prominent organizations was the Mental Health Association in New Jersey through their PEWS program (Promoting Emotional Wellness and Spirituality).
Other community engagement activities implemented included:
Convened a core group of five barbers to serve as an advisory team for the embedded education approach and curriculum development
Met with three local Core Service Agencies, which are the DC Department of Behavioral Health funded MH outpatient clinics, to introduce the program and gauge interest in partnerships
In 2018, the team piloted their curriculum with a cohort of five barbers (Table 2). Weekly 2-hour sessions were held for six weeks. Lunch, refreshments and $50 Visa gift card incentives were provided.
Element | Description |
---|---|
Existing relationships | |
Host | Barbershops |
Encounter |
|
Target Individuals | Black American Men (barbers, owners, clients) |
Community | Family and friends of the target population, barbershop visitors |
Embedded Education Practice | |
Content | Personal stories of mental health service use; positive accurate messaging on mental health |
Learning Objectives | 1. To increase mental health literacy 2. To increase knowledge of the local mental health resources in the Southeast, DC community, |
Anticipated Change | Knowledge, attitude, and behavior change around mental health; increased likelihood of seeking mental health services |
Pedagogy | Listening to peer educators, participatory interactive dialog |
Tools | Peer stories, barber discussions |
Activities | Connection to services if desired |
Educators | Non-medical community residents/peer educators trained by program staff |
The team developed a partnership consisting of the Confess Project, members of the original advisory committee, and the DC Commission for Fatherhood, Men, and Boys (DCFMB) to expand the project to include community members. The training was a one-day conference with 40 men from the community recruited with support of the DCFMB. Twelve men stated a willingness to share their stories in barbershops and connect people to resources. Two-hour, monthly training sessions for six months followed the conference.
The BEE Squad conducted the barbershop trainings, in pairs, over the course of three months. The attendance of customers at the barbershops was highly variable. Some shops had upward of 30 guests, while others had only 4 to 5 customers in the shop. The presentations were also highly variable due to the variance in presentation skills of the participants, as well as the layout of the shops, the time of day and the day of the week. In some cases, the presentations got curtailed due to distractions in the shop. Also, some of the presentations served refreshments. All of these factors influenced the learning environment of the embedded education sessions.
The team’s third area of activity was the development of a social media presence. The purpose was not only to promote the program but also to stimulate conversations around mental health. One of the authors attended a Social Entrepreneurship training with SeedSpot at Booz Allen Hamilton to develop an “elevator pitch” to market the program and also enrolled in a graduate-level social marketing course at a local university to gain a better understanding of social marketing. The team hired a consultant and developed a social media presence for MHISTREET and the Barbershop Embedded Education (BEE) program (Web site: http://www.mhistreet.com/; Twitter: @MHISTREET; Facebook: The MHI Street Initiative) The team continues their work as members collaborate with public health communications trainee to develop additional marketing materials with positive mental health messaging and resources targeted to barbers and their clients.
Between sessions, the authors and their team visited all of the barbershops in Ward 8 (n = 13) and approximately half the barbershops in Ward 7 (n = 6) to share information about the project. All but one barbershop showed interest in the BEE session. The authors then arranged the dates and times for the BEE Squad to perform the intervention.
The Kirkpatrick Training Evaluation Model was used to evaluate the core intervention of this initiative, embedded education with storytelling in the barbershop [61]. The Kirkpatrick Model is a four-level evaluation method for assessing learning processes and considers any style of training, both informal and formal, to determine aptitude based on four criteria: reaction, learning, behavior, and result.
The authors and their partners used reflection and facilitation summary at the end of each barber and community member training session. Presenters elicited feedback from the audience to learn how they were interpreting the information by having ‘check-in’ points and pausing the education sessions periodically to talk through any misunderstandings or emotionally difficult topics. The lead facilitator was a trained psychologist and was able to debrief and provide feedback in a professional and therapeutic manner.
Post-then-Pre evaluations were conducted after the training sessions with the barbers during the pilot (N = 5) and the BEE Squad (N = 40). All of the barbers completed the evaluation and approximately half of the BEE Squad did so. Without exception, all of the trained team members reported an increase in knowledge related to mental health in their community. Additionally, at the beginning of each session with the barbers, the previous session’s content was reviewed, and any comments, confusion or participant feedback were clarified.
After educational sessions were completed, participants practiced their storytelling and presentations with the larger group. The group and facilitators provided feedback. When visiting barbershops, each BEE Squad presenter was accompanied by a BEE Squad ‘buddy’ and a member of the MHISTREET team to ensure the accuracy and proper delivery of the messaging. Presentation styles varied greatly, but the accuracy of the content was reportedly consistent among the BEE Squad.
The MHISTREET team received IRB approval to collect data in the barbershops by distributing surveys after BEE Squad presentations. However, the team quickly determined that conducting surveys with clients in barbershops would not work. Clients were willing to talk and contribute informally but were not comfortable answering surveys. Consequently, barbershop sessions became brief presentations of storytelling with subsequent question and answer periods. This format also provided a forum for clients to share opinions, thoughts, and fears comfortably. The less-structured format removed barriers to delivery. Feedback on the format provided evidence for the feasibility and acceptability of this intervention as barbers and customers were highly engaged in conversation around mental health. Some reported that this was their first opportunity to speak about this topic. Barbers and barbershop owners became comfortable accepting flyers with information about local resources and mental health information. The team was able to leave materials in 85% of barbershops in Ward 8 at the conclusion of the Clinical Scholars’ funding.
The initial success of the MHISTREET initiative demonstrates the positive outcomes achievable when an engaged multidisciplinary and influential community network functions cohesively to improve mental health literacy through embedded education. Access to relevant data, purposed to inform the initiative, has driven the creation and maintenance of alliances in the built environment of Washington DC. Alliances between barbers, healthcare providers, and community stakeholders in the local Southeast DC community has proven to be of great benefit toward achieving the aim of this initiative, which is to provide a non-traditional, non-healthcare platform for black men to share and hear stories of mental health resilience, encourage mental health-related conversations among barbershop clients, and serve as a bridge to mental health services.
The MHISTREET initiative encouraged both barbers and BEE Squad members to recognize improving mental health literacy is a likely precursor to undertaking health-preserving actions necessary for mental health wellness and maintenance. BEE Squad members also recognize embedded education is a viable means of improving mental health literacy. Recognition was likely facilitated by the “autonomy-compatible interactions” among Black men, barbershop clients and barbers, and networks of professionals, community-based leaders, and organizations. When people assume responsibility for their own mental health as a direct result of improved literacy, they are making an autonomous decision. Autonomous decisions are likely to result in acts of health-preservation such as seeking medical care or sharing stories of lived experiences of mental health issues to help address them.
A key challenge faced by all involved in delivering the MHISTREET initiative was navigating the process of helping Black men and barbershop clients undertake health-preserving actions, without overriding or undercutting their autonomy to do so. This is a common challenge faced by consortia delivering initiatives designed to help others help themselves. In the context of this initiative, overcoming this challenge required all involved to recognize and uphold two self-evident truths: 1) Help must start from the present situation of the men who share their stories of resilience in the face of mental health issues, and 2) MHISTREET cannot be delivered as a benevolent gift or “plug-in” program. Rather, the focus should be on devising ways to cost-effectively replicate the initiative in other cities to maximize local support available for improving the mental health literacy of Black American men.
The MHISTREET initiative uses the benefit of non-traditional, proactive, and behaviorally-focused self-management support. Results suggest BEE may be an effective form of structured education by which self-management strategies for mental health issues can be learned and applied by Black men. Embedded education has the potential to both alleviate the pressure on and work in concert with health and social care services. If Black men make early informed decisions that result in early care-seeking, issues with mental health could potentially be less chronic at the point of care and less difficult to manage. Such efficiency could translate into less severe mental health disorders and fewer health and social care dollars spent on treatment and recovery. The MHISTREET team encourages like-minded groups in cities across the US and beyond to replicate this initiative to determine its true health and economic value when widely disseminated.
Perhaps the most critical aspect of this work was building trust within the community. Being a professional and healthcare provider does not automatically grant one trust. The trust required to work with barbers, community stakeholders, and other concerned citizens comes with time and following through on your word. Without trust, none of this work is possible.
One of the project goals was to work across sectors with a variety of healthcare and non-healthcare professionals. Being part of the Ward 8 Health Council was a good entrée, and networking continued by engaging with anyone and everyone who expressed an interest in this work. Through building diverse networks, the authors learned that having more thought diversity and perspectives on the team led to a greater understanding of the problem and more thoughtful and “real-world” solutions.
New grass-root programs do not happen immediately but take time to develop. Progress occurs in “fits and starts” and does not follow a particular curve. You must be flexible with your model and not make assumptions when the work begins. In addition, opportunities may arise unexpectedly and you must be ready to take advantage of them. Plans also backfire or do not work as envisioned, and you must have a plan B, C, and D!
The strength of this and similar projects is the voice of the community. This work cannot be accomplished by outsiders, (clinicians, academics, etc.) without the collaborative effort of people who live, work, and play in the community. Community voices are invaluable and often lead to new insights and ideas. People who know the community know what will work and what will not. To have sustainability and buy-in, community engagement at all levels of the project is requisite.
A comprehensive toolkit can be found at: https://clinicalscholarsnli.org/community-impact.
Natriuretic peptides are hormones that exert cardiovascular and renal effects. Their congenital absence or genetic ablation leads to serious consequences, especially in the cardiovascular system. Thus, cardiovascular health could be improved through genetic and pharmacological manipulation of these natriuretic peptides [1]. Although natriuretic peptides are key players in the regulation of cardiovascular and renal systems, accumulating evidence shows that they could play pivotal roles in counteracting metabolic diseases and conditions such as obesity, type 2 diabetes, and insulin resistance that adversely affect human population across the world. One of the most attractive therapeutic approaches to combat obesity and type 2 diabetes is the activation of brown adipose tissue that has been rediscovered in adult humans in the late 2000s. Stimuli that activate this tissue have been explored in many animal models and in humans [2]. Since the discovery of their potent lipolytic effects on human adipose tissue in the early 2000s [3, 4], many studies have been focused on the effect of natriuretic peptides on glucose and lipid metabolism pathways that are altered in obesity and type 2 diabetes [5]. In addition, promising results came from the studies on activation of brown adipose tissue. These studies reveal that natriuretic peptides might serve as a pathophysiological link between brown adipose tissue activation and metabolic diseases. In fact, obesity, type 2 diabetes, and insulin resistance may commonly manifest in the same patient, all of which are associated with heart failure and development of multiple organ failure due to impaired oxidative metabolism [6]. Therefore, better understanding of the metabolic effects of natriuretic peptides on lipid metabolism during obesity and type 2 diabetes would pave the way for treatment and prevention of those maladies that are blamed for both deaths and impaired quality of life. This chapter provides a general overview of natriuretic peptide system and adipose tissue and discusses genetic, physiological, and pharmacological evidence of natriuretic peptide system linking adipose tissue to obesity and type 2 diabetes.
Natriuretic peptides (NPs) are peptide hormones responsible for maintaining cardiovascular homeostasis. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) constitute the main mammalian natriuretic peptide (NP) system [7, 8]. Emerging evidence shows that these peptides play critical roles in different systems of the body [9]. ANP, the first member of the NP system, is mostly produced and stored in the atrial myocytes, and it is released in response to various stimuli such as heart wall stretch and atrial distension [10]. The discovery of ANP led to the assumption that the heart was formerly an endocrine organ. ANP is first generated as a 152-amino-acid precursor, which is subsequently cleaved into its biologically active form by corin, a transmembrane serine protease that works as a pro-atrial natriuretic peptide-converting enzyme [11]. Initially identified in porcine brain, BNP is the second member of the NP system and is also known as a ventricular natriuretic peptide. It is produced as a 134-amino-acid precursor before being processed into its biologically active form [12, 13]. ProBNP-108 and BNP-32 are the two most physiologically active variants of BNP. BNP-32 is mostly expressed in the atria, but proBNP-108 is primarily expressed in the ventricular myocardium. ProBNP-108 is cleaved by furin, a proprotein convertase, to produce BNP-32 and NT (N-Terminal)-BNP-76 [14]. ANP levels rise in response to increased atrial pressures, whereas BNP levels rise in response to ventricular overload [15]. During congestive heart failure and cardiac hypertrophy, both ANP and BNP are substantially expressed by the atrium and ventricle, with BNP expression levels being reported to be excessively higher than ANP levels [16, 17]. Patients affected by hypertension and obesity, on the other hand, were found to have low plasma ANP levels [18] due to reduced natriuretic peptide release and increased natriuretic peptide clearance (depending on natriuretic peptide receptor C overexpression) [19, 20] and/or due to the activation of the renin-angiotensin-aldosterone system [21]. CNP, the third member of the NP system, is derived from a 126-amino-acid precursor, which is subsequently cleaved by furin into two endogenous forms, CNP-53 and CNP-22 [22, 23]. CNP has been found in a variety of organs, including the heart, kidney, lung, endothelial cells, bone, and the central nervous system, despite its low circulating concentration [24, 25]. CNP is primarily involved in vascular homeostasis and has anti-hypertrophic and anti-fibrotic actions on cardiac myocytes and fibroblasts, respectively, due to its endothelial origin [26, 27]. Later on, two new members of the NP system have been discovered. Of those, D-type natriuretic peptide (DNP, also known as Dendroaspis natriuretic peptide) is a physiologically active peptide molecule of 38 amino acids that was first discovered in the venom of the green mamba snake (
The NP signals are conveyed by its transmembrane receptors. A transmembrane natriuretic peptide receptor A (NPRA) is encoded by the
Adipose tissue (AT) is a specialized connective tissue that carries out a diverse set of tasks such as energy storage, hormone production, thermal insulation, and thermogenesis [46]. AT, corresponding to roughly 5–50% of human body weight [47], consists of two basic components: cells and extracellular matrix [48]. AT has abundantly adipocytes (also called adipose cells or fat cells), among which other cell types are mesenchymal stem cells, preadipocytes, macrophages, fibroblasts, endothelial cells, and smooth muscle cells [46]. AT is a key player in energy storage and consumption. The excess energy is efficiently stored in the form of neutral triglycerides (TGs) in the AT via lipogenesis, an anabolic pathway encompassing fatty acid synthesis and triglyceride synthesis [49]. On the other hand, when energy consumption is greater than its production, the stored energy is rapidly mobilized to bring into use [50]. This highlights the fact that AT is a dynamically remodelable tissue responsible for storage and reallocation of lipids in response to cellular energy excess or depletion [51]. Furthermore, AT fulfills other physiological tasks and is now regarded as a significant endocrine organ.
AT has been divided into two major subclasses: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is responsible for the production of some pro-inflammatory cytokines and chemokines, including interleukin 6 (IL-6), IL-18 and tumor necrosis factor-alpha (TNF-α), that modulate inflammation [48, 52]. In addition, adipocytes in WAT (white adipocytes) secrete many adipocyte-derived paracrine and endocrine molecules (collectively called “adipokines”), including leptin and adiponectin that regulate energy metabolism [47, 48]. Leptin is regarded as a master regulator of energy balance. It controls glucose metabolism and energy expenditure and suppresses food intake through binding to the long form of the leptin receptor (LEPR) that is highly expressed in brain areas responsible for the control of feeding and energy expenditure [53]. However, the leptin’s ability to lower food consumption is dependent on the melanocortin-3 receptor (MC3R) in the brain, which regulates energy homeostasis [54]. Adiponectin, a well-known homeostatic factor, yields insulin sensitivity-promoting effects by inhibiting hepatic glucose production and stimulating fatty acid oxidation in skeletal muscles [55]. By turning our focus to WAT and BAT below, we give further information about these different types of adipose tissue.
In healthy individuals, WAT makes up at least 10% of the total body weight. Energy storage, hormone secretion, thermal insulation, regulation of insulin sensitivity, and prevention of traumatic injuries to vital organs are among its basic tasks [49]. Adipocytes in the WAT (white adipocytes) have low mitochondrial abundance and store TGs as large intracellular lipid droplets [56]. WAT is mainly subdivided into subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) [57]. In humans, SAT is mostly found in the gluteal and femoral regions. It may be divided into two types: deep SAT and superficial SAT, which differ morphologically and metabolically [58]. Deep SAT has been linked to the pathophysiology of obesity-related metabolic complications, whereas superficial SAT is more associated with protective roles against metabolic derangements [59, 60, 61]. Located around the internal organs, VAT exists in pericardial, gonadal, omental, mesenteric, and retroperitoneal storages, and protects them from mechanical damage and friction [62]. SAT and VAT show marked differences in adipocyte phenotype, gene expression signature, and lipolytic and endocrine activities [63].
BAT, as a thermogenic tissue, protects the body from cold environments by dissipating chemical energy derived from fuel substrates as heat [64]. Brown adipocytes contain many small-sized lipid droplets and copious amounts of mitochondria. They express uncoupling protein 1 (UCP1), also called thermogenin, that uncouples the electron transfer chain from the ATP synthesis to generate heat [65]. Two types of brown adipocytes have been identified. The traditional brown adipocytes are myogenic factor 5-positive (
It has long been considered that BAT merely exists in some mammalian species, including human newborns, hibernating animals, and rodents [68, 69, 70]. However, recent studies have shown that BAT is metabolically activated in adult humans upon cold exposure [71, 72, 73]. Mounting lines of evidence have uncovered the possible mechanisms of action of BAT in counteracting obesity and its coexisting diseases in humans [74]. Some studies have demonstrated that exposure to different cold regimes (e.g., 15–16°C for 6 hours/day for 10 days or 17°C for 2 hours/day for 6 weeks) may stimulate human BAT, enhance non-shivering thermogenesis and reduce body fat mass [75, 76, 77, 78, 79, 80, 81]. However, whether these effects might continue in the long-term period (months to years) remain obscure. On the other hand, several studies have revealed that subcutaneously placed embryonic BAT could reverse type 1 diabetes-related parameters in streptozotocin-treated mice, thus improving glucose homeostasis and weight gain and reversing type 1 diabetes independently from insulin [82, 83, 84, 85]. The extent to which BAT thermogenesis would influence obesity and diabetes relies on the quantity of actively recruited BAT [62, 86]. Another study reported that some central neural modulators would decrease fat mass and body weight by activating BAT thermogenesis and triggering the switch from white adipocytes to brown adipocytes in order to burn off excess energy [64].
Considering their anatomical localization, cardiac adipose tissue stores can be described as pericardial adipose tissue (PAT) and perivascular adipose tissue (PVAT) [86, 87]. The pericardial adipose tissue consists of paracardial adipose tissue and epicardial adipose tissue (EAT). EAT is a metabolically active tissue, which provides energy supply to myocardium in case of augmented energy demand [88]. Given all the adipose tissue reservoirs, EAT utilizes the lipogenesis and lipolysis pathways at the highest rate. EAT exerts modulatory effects on the vascular tone and coronary artery functions through secretion of molecules such as adipokines and nitric oxide (NO) [86]. EAT has been reported to possess brown/beige adipocyte-specific phenotypes in hibernators and human adults due to its thermogenic capacity [70, 89].
PVAT, which is located around veins, arteries, and small vessels [90], plays an active role in fine-tuning endothelial function, vascular tone, and vascular remodeling, and represents a dual endocrine-paracrine organ that produces various immunomodulatory and vasoactive molecules, in addition to cytokines and adipokines like leptin and adiponectin [91, 92]. PVAT makes up just 0.3% of total adipose tissue mass and can contain various numbers of brown, white, and beige adipocytes based on its location in the body and despite differences in the predominant cell type. Moreover, it has been shown that periaortic adipose tissue at the thoracic region in human adults has beige-like characteristics, whilst coronary PVAT exhibits WAT-like characteristics [90].
Obesity is closely related to impaired insulin sensitivity in the liver, skeletal muscles, and white adipose tissue. Obesity-related insulin resistance is one of the most prevalent causes of type 2 diabetes mellitus and is directly linked to diverse cardiometabolic abnormalities including coronary heart disease, atherosclerosis, and hypertension [46, 49, 93]. In response to chronic excessive calorie intake, expansion of adipose tissue through adipocyte hyperplasia (cell number increase) and/or hypertrophy (cell size increase) is a major determinant of metabolic dysfunction and cardiovascular diseases [49, 94]. Hyperplasia might be regarded as a healthy mechanism of AT expansion. However, hypertrophy could lead to adipocyte dysfunction as adipocytes outreach their expansion limits as a result of development of hypoxic conditions, oxidative stress, and pro-inflammatory cytokine release [95]. Thus, the body region where excessive adiposity occurs is one of the most crucial factors identifying the obesity-related cardiometabolic complications [5].
It has been considered that enlargement of VAT has established a strong link between adverse metabolic alterations and increased cardiovascular risk, while expansion of SAT makes a minor contribution to these adverse outcomes [49]. The “portal hypothesis” may account for one of the possible reasons for this difference. The portal hypothesis propounds that visceral fat tissue in obese patients increasingly releases free fatty acids (FFAs) and cytokines into the portal vein, resulting in their accumulation in the liver. Then, hepatic fat accumulation promotes the development of hepatic insulin resistance and type 2 diabetes [96, 97, 98]. This condition that increases the amount of FFAs transported to the liver via the portal circulation is also linked to atherogenic lipid profile and hepatic steatosis [98]. Another possible reason for this difference is that VAT is more susceptible to the effects of pro-inflammatory molecules than other adipose tissues, since increased adiposity creates a pro-inflammatory milieu. It has been reported that VAT has higher expression and secretion of several pro-inflammatory mediators including TNF-α and IL-6, as compared to SAT [99, 100]. Augmented expression of pro-inflammatory cytokines causes phosphorylation of serine/threonine residues of insulin receptor substrate proteins, leading to dissociation of insulin receptor substrate proteins from effector proteins in the insulin signaling cascade pathway and resulting in the development of insulin resistance [101]. In addition, pro-inflammatory cytokines cause local and systemic inflammation by triggering recruitment of macrophages and T-lymphocytes to the relevant sites [102]. Resident macrophages play a crucial role in the promotion and perpetuation of adipocyte dysregulation and insulin resistance. Furthermore, experimental evidence shows that necrotic cell death in adipose tissue over the course of obesity might induce the recruitment of pro-inflammatory M1 macrophages, which produce multiple pro-inflammatory cytokines that exacerbate chronic inflammation and insulin resistance [103]. Additionally, it has been shown that anti-inflammatory adiponectin is expressed at a lower level in VAT than in SAT and its circulating concentrations are reduced in obese people with augmented visceral fat accumulation [104].
SAT has a restricted potential to expand owing to its poor adipogenesis capability. This limited capacity results in adipocyte hypertrophy, promoting the formation of fat storages in non-adipose tissues such as in the heart, liver, and skeletal muscles [105]. This deleterious mechanism of adipogenesis is also regarded as “lipotoxicity” and is linked to the development of systemic insulin resistance and enhanced risk of type 2 diabetes. It has been put forward that intrahepatic content of TGs represents a more acceptable marker of insulin resistance than VAT [106]. On the other hand, PVAT exhibits hyperplastic and hypertrophic characteristics in obesity [107]. It has been propounded that “obesity triad” encompassing oxidative stress, inflammation, and hypoxia might be the major mechanism responsible for PVAT dysfunction in obesity. Adipocyte dysfunction during obesity arises from the “whitening” of PVAT, which creates a hypoxic and pro-inflammatory milieu affecting the vasculature [86]. Moreover, reduced adiponectin production by PVAT in obesity promotes endothelial dysfunction [108]. In this respect, studies using genetically-modified and diet-induced animal models of obesity revealed that anticontractile properties of PVAT are totally lost [49].
Adequate insulin signaling in AT is a crucial factor in the maintenance of systemic blood glucose homeostasis, as evidenced by a number of mice models, even though skeletal muscle is responsible for the bulk of insulin-stimulated glucose uptake [109]. Adipocyte-specific glucose transporter type 4 (GLUT4) knockout in mice affects skeletal muscle and liver insulin signaling, which results in glucose intolerance, insulin resistance, and hyperinsulinemia [110]. Adipocyte-specific insulin receptor-knockout mice exhibited basal glucose uptake in a similar fashion, but insulin-stimulated glucose uptake by adipocytes was considerably lower than in controls. These mice had improved systemic glucose tolerance [111]. It is worthy to note that this difference might arise from the activation of alternative signaling pathways to compensate for the innate lack of adipocyte insulin signaling pathway. A recent study on adipocyte-specific insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF-1R) knockout (one of these receptors: IRKO, IGF-1RKO or both of them: double KO, DKO) mice found that while all KO groups had equivalent or lower fat mass than controls, IRKO and DKO mice showed systemic insulin resistance and hepatic steatosis in comparison with the controls and IGF-1RKO groups. The combined ablation of these receptors led to serious glucose homeostasis disturbances [112]. Together, these findings indicate that when there are deficiencies in insulin receptor signaling in the innate AT, a compensatory mechanism may be triggered possibly through insulin-independent signaling pathways in other insulin-responsive tissues in order to counteract systemic glucose intolerance. However, this evidence suggests that adequate insulin signaling inside the AT is critical for overall health.
Impacts of AT insulin sensitivity on systemic health may be mediated by the regulation of adipose tissue lipolysis that breaks down triglycerides into FFAs and glycerol. Situations like fasting, exercise, and stress induce lipolysis through adrenergic activation, thus mobilizing energy storage. In case of fed state, insulin inhibits lipolysis in the direction of lipid storage. As a result, defective insulin signaling in AT could lead to an increase in basal lipolysis rate [113]. Since the inflammatory cytokine TNF may stimulate lipolysis independently of insulin signaling, chronic low-grade inflammation caused by obesity may also trigger excessive FFA release by adipocytes and promote lipotoxicity and lipid-induced insulin resistance [114, 115]. Obesity and insulin resistance have extensively been linked to elevated rates of basal lipolysis. The ensuing rise in circulating FFA levels increases metabolic dysfunction by promoting lipid accumulation in the liver and muscle [113]. Disturbances in lipid storage, such as those caused by obesity or lipodystrophy, can impair adipocyte function and lead to insulin resistance. Insulin resistance in the adipose tissue disrupts normal adipocyte signaling and metabolism, leading to an increase in lipolysis. Ectopic lipid accumulation and insulin resistance in other tissues, such as skeletal muscle and liver, can result from chronically increased circulating lipids. Insulin resistance in the liver is deleterious because insulin signaling controls hepatic glucose synthesis. All of these events have the potential to produce a major effect on metabolic health, culminating in a vicious cycle that perpetuates systemic metabolic illness [48, 113]. Type 2 diabetes and hepatic lipid accumulation are common in situations with high basal lipolysis, such as Cushing’s syndrome [116, 117], as well as in cases of lipoatrophy when circulating lipids are excessive [118]. Although the bulk of whole-body glucose uptake could not have been directly taken up by AT, it is obvious that impairment in glucose uptake and lipid accumulation in AT have an impact on other insulin-responsive organs, modulating the overall status of systemic health [48]. Much more remains to be found out how altered adipose tissue metabolism is going to contribute to metabolic conditions such as obesity, insulin resistance, and type 2 diabetes.
Currently, NPs have been well established to be powerful metabolic hormones that are responsible for the fulfillment of key functions in adipose tissue having high expression of NP receptors [119]. Demonstration of ANP mRNA expression by human adipose tissue is a strong indication that ANP exerts autocrine/paracrine effects on this tissue [120]. In 2000, it was evidenced that, in the potency order of ANP > BNP> > CNP, NPs exert potent lipolytic effects on human adipose tissue in both
NPs play additional roles in modulating the release of adipokines and cytokines from adipose tissue. When ANP is added to isolated human adipocytes
The relevant clinical implications of administering NPs as metabolic hormones have been excellently reviewed [22]. Intravenous infusion of ANP in lean and obese human subjects led to a remarkable rise in plasma FFA and glycerol concentrations, indicating lipid mobilization. Microdialysis data in subcutaneous abdominal adipose tissue also revealed that both groups had an increase in the extracellular glycerol concentration during ANP administration [130, 131]. However, this increase was not reversed with the use of propranolol, a ꞵ-adrenergic receptor antagonist used to blunt ꞵ-adrenergic effect of catecholamines on adipose tissue [130]. This finding supports the fact that ANP is a powerful lipolytic hormone that acts independently of the activation of the sympathetic nervous system [130, 131]. It is generally known that, during exercise, the heart releases ANP and BNP into the bloodstream [132]. The increment in ANP and BNP levels in the bloodstream during exercise is a robust indicator of contribution to enhanced energy supply [123]. Similarly, plasma adiponectin concentrations increased in both healthy volunteers [133] and patients with heart failure [126, 134] after intravenous injection of human ANP.
Considering the link between NPs and their receptors, cardiometabolic diseases, insulin resistance, type 2 diabetes, and obesity, substantial progress has been made in the knowledge of metabolic effects of NPs during recent decades (Figure 1). For example, NPs are implicated in many processes including improvement in insulin resistance and induction of lipolysis. Multiple lines of evidence suggest that NPs act as key players in the regulation of metabolic pathways and in the pathophysiology of cardiometabolic diseases, obesity, and type 2 diabetes [22]. The lower availability of NPs could be attributable to their decreased production and release as well as to the increased function of their clearance receptor. Animal experiments revealed that diabetic obese db/db mice and obese Zucker fatty rats have lower cardiac ANP and BNP expression at the mRNA level [135, 136]. However, feeding mice with a high-fat diet had no effect on their plasma BNP levels [137]. NPRC mRNA level rose in the heart of db/db mice [125], but NPRA and NPRC expression decreased and increased, respectively, in white and brown adipose tissue of db/db mice [137]. Moreover, obese mice fed a high-fat diet had increased levels of endopeptidase and neprilysin (which are responsible for NP breakdown) in plasma and in mesenteric fat, indicating a higher NP clearance [138].
Involvement of natriuretic peptides and their receptors in the pathophysiology of obesity, type 2 diabetes, and insulin resistance, with possible implications for cardiometabolic health. Natriuretic peptide signaling evoked through the NPRA and NPRB starts with cGMP signaling, which enhances lipolysis in white adipose tissue, thermogenesis in brown adipose tissue, and oxidative capacity in skeletal muscle under physiological circumstances. These physiological actions protect against obesity, type 2 diabetes, and insulin resistance, thus providing significant cardiometabolic health benefits. In pathological settings, changes in the NPRA/NPRC and NPRB/NPRC ratios in favor of NPRC result in reduced natriuretic peptide production and release, and in increased clearance receptor function. Obesity, type 2 diabetes, and related comorbidities compromise cardiometabolic health and are all partly consequences of the aforementioned alterations in the natriuretic peptide system. ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; cGMP, cyclic guanosine monophosphate; CNP, C-type natriuretic peptide; NPRA, natriuretic peptide receptor A; NPRB, natriuretic peptide receptor B; NPRC, natriuretic peptide receptor C; PGC1α, peroxisome proliferator-activated receptor-gamma coactivator 1-alpha; PPARδ, peroxisome proliferator-activated receptor-delta; UCP1, uncoupling protein 1.
Insulin resistance, type 2 diabetes, and obesity have all been reported to be inversely associated with human plasma NPs [6]. Obese people showed lower plasma BNP levels than non-obese people, indicating a negative relationship between body mass index (BMI) and BNP levels [139]. A cohort study revealed that plasma NT-proANP and NT-proBNP concentrations were inversely related to obesity and to all other components of the metabolic syndrome, with the exception of hypertension [140]. VAT and hepatic fat mass in patients with heart failure were found to be adversely associated with BNP and NT-proBNP plasma levels. In addition, a link between reduced circulating NP levels and altered AT distribution was also found. Elevated levels of NPs, on the other hand, have been reported to be a stronger indicator of obesity profile [141]. The NPRA to NPRC ratio decreased in the adipose tissue of obese patients with type 2 diabetes, indicating increased NP clearance. Treatment with pioglitazone increased the NPRA to NPRC ratio as well as the insulin sensitivity, indicating that a lower NPRA to NPRC ratio is linked to glucose intolerance and insulin resistance [142]. Obese patients also exhibited high neprilysin expression, indicating that NPs break down rapidly and their effects lessen [138]. Overall, these findings suggest that reduced circulating NP levels are closely associated with the progression of numerous metabolic disorders, including type 2 diabetes and obesity. Currently, the capacity of neprilysin inhibitors, such as sacubitril, to raise NP levels is being considered as one of the major strategies for improving the metabolic profile in type 2 diabetes and obesity through remodeling adipose tissue [143]. Nevertheless, further research and clinical trials are required to obtain the optimal metabolic benefits from those drugs and to maximize their effects.
The relevance of NP receptors and signaling cascade components in metabolic function research has been demonstrated using genetically engineered mouse models. Body weight and fat mass were reduced in NPRC knockout mice (NPRC−/−). Furthermore, adding ANP to adipocyte culture from NPRC knockout mice boosted UCP1 expression, resulting in lipolysis [127]. In comparison to wild-type counterparts, adipocyte-specific NPRC knockout mice (NprcAKO) showed higher thermogenesis, improved insulin sensitivity, and increased glucose uptake into BAT. This recent finding also indicated that NPRC knockout mice were protected from developing insulin resistance and obesity as a result of a high-fat diet. Furthermore, in this diet-induced model of insulin resistance and obesity, adipocyte-specific NPRC deletion inhibited the development of inflammation [144]. The knockout of the NPRA gene, however, has been linked to increased fat mass and cardiac hypertrophy [145]. Guanylyl cyclase-A (GCA) heterozygous knockout [GCA(+/−)] mice fed a high-fat diet gained weight and developed glucose intolerance [144, 146]. However, mice overexpressing PKG (cGK-Tg mice) fed a high-fat diet had lower body weight, less visceral and subcutaneous fat depots, and less ectopic fat deposition, thereby showing a significant enhancement in insulin sensitivity and glucose tolerance [146]. Overall, these data suggest that the NPs/guanylyl cyclase (GC) cascades play a crucial role in conferring resistance to obesity and glucose intolerance. Besides, mice overexpressing BNP (BNP-Tg mice) fed a high-fat diet, had better body weight, and glucose tolerance, indicating that BNP attenuates diet-related obesity and insulin resistance [146]. A recent study conducted on mice overexpressing CNP, specifically in adipocytes (A-CNP-Tg mice), showed better glucose tolerance and insulin sensitivity in another model of high-fat diet-induced obesity, which was linked to increased insulin-stimulated protein kinase B (Akt) phosphorylation. These findings imply that adipocyte-specific CNP overexpression offers protection against adipocyte hypertrophy, increased lipid metabolism, inflammation, and impaired insulin sensitivity during high-fat diet-induced obesity [147].
Insulin resistance, increased lipotoxicity, and reduced-fat oxidative capacity are all linked to faulty NPR signaling in skeletal muscle during obesity. The physiologic activation of NPRA by circulating NP is further inhibited by upregulation of NPRC in skeletal muscle as glucose tolerance impairs with obesity [137]. In humans, a substantial positive relationship was initially discovered between insulin sensitivity and muscle NPRA protein expression, as evaluated by hyperinsulinemic-euglycemic clamp at a dosage that primarily shows insulin sensitivity in skeletal muscle [137]. However, the finding of a negative relationship between body fat and muscle NPRA expression is in line with the negative relationship between total saturated ceramide concentration and muscle NPRA expression, two parameters that adversely influence skeletal muscle and whole-body insulin sensitivity [137, 148, 149]. Coué et al. first documented a functional link between insulin sensitivity and skeletal muscle NPRA signaling, indicating that NPR signaling in skeletal muscle may alter insulin sensitivity in addition to plasma NP levels [137]. Furthermore, muscle NPRA protein was significantly reduced in obese people, but it increased in response to diet-induced weight loss and improved insulin sensitivity. Although the molecular mechanisms that modulate muscle NPRA protein expression remain elusive, the aforementioned findings suggest that muscle NPRA acts as a major determinant of insulin sensitivity [137]. Furthermore, as glucose tolerance deteriorates in obese with impaired glucose tolerance (IGT) and type 2 diabetes, overexpression of muscle NPRC might further suppress the physiologic activation of muscle NPRA, which ultimately results in NP system dysfunction. Given that muscle mass accounts for up to 40% of total body weight, even a small increase in muscle NPRC expression could significantly reduce plasma NP levels by increasing NP clearance rates [137, 150]. As glucose tolerance deteriorates independently of blood glucose concentrations in obese patients, muscle NPRC may be activated by high blood insulin levels, as it has previously been established in adipose tissue [150]. Despite the fact that the obese controls and IGT/type 2 diabetes groups were not age-matched, enhanced NPRC expression in skeletal muscle appeared to be independent of age, since there was no relationship between age and muscle NPRC protein expression [137]. These findings in human muscle were mainly duplicated in obese diabetic mice. Obese diabetic mice had higher levels of NPRC protein in their skeletal muscle, white fat, and brown fat, but only muscle NPRC protein was negatively correlated with plasma BNP levels, suggesting that increased plasma BNP clearance by the muscle could contribute to the NP system dysfunction seen in these mice. Findings by Birkenfeld et al. [133] are consistent with previous studies that have linked higher NPRC mRNA levels in white fat to metabolic impairment in rats and humans [146, 151, 152]. These results have also provided a molecular explanation for the close relationship between NP system dysfunction and insulin resistance in humans, irrespective of adiposity [153]. The concept of NP system dysfunction is corroborated by the results reporting that in NPRC knockout mice blood circulation half-life of NPs and their biological activity in target tissues is dramatically enhanced [154]. More importantly, altered NPRA-to-NPRC protein ratio in skeletal muscle was followed by a significant change in p38 MAPK phosphorylation in db/db versus db/+ animals, indicating a possible signaling impairment, given that p38 MAPK is a typical downstream molecular effector of the NPR signaling pathway [127]. Another study has recently reported that protection against diet-induced obesity and insulin resistance had been attributed to NPRC deletion in adipose tissue (NprcAKO) but not in skeletal muscle (NprcMKO). NprcAKO mice had less inflammation and enhanced energy expenditure, shifting lipid storage from liver to visceral fat. These data led to the conclusion that, when fed a high-fat diet, mouse adipose tissue devoid of NPRC is the primary location of NP-driven metabolic changes [144].
Evidence is accumulating that NPs participate in the physiological and pathophysiological regulation of many metabolic diseases including obesity, insulin resistance, and type 2 diabetes, in addition to their well-known actions in the cardiac, vascular, and renal systems. Although there are some conflicting results of the relationship between NP system deficiency and metabolic diseases, many recent studies have shown that the NP system is defective in those diseases. Reduced NPs synthesis, increased clearance, and/or altered NP receptor expression may impair the positive effects of NPs on target metabolic organs such as heart, skeletal muscle, and adipose tissue during obesity, insulin resistance, and type 2 diabetes. Impaired NPs system signaling causes lipid accumulation in adipose tissue, which leads to visceral adiposity, obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. The strong links between adipose tissue enlargement and dysfunction during obesity, insulin resistance, type 2 diabetes, and cardiovascular disease may have been explained by a number of metabolic pathways that are interrelated in the heart, liver, and skeletal muscles. In this perspective, NP insufficiency might be considered one of the pathways linking adipose tissue dysfunction to obesity, type 2 diabetes, insulin resistance, and cardiovascular disease. There is ample data showing that restoring NPs levels after NP injection leads to positive metabolic outcomes, which supports this idea. The positive association between increased levels of NPs and lower incidence of insulin resistance, obesity, and type 2 diabetes holds promise for future NPs applications. Adipocyte hypertrophy, increased lipid synthesis, and visceral and ectopic fat deposition are all prevented by NPs. Furthermore, promising approaches to converting white adipose tissue into thermogenic brown adipose tissue could offer an effective tool for correcting dysfunctional lipid metabolism during obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. In addition, translation of these promising results into clinical practice would open new avenues to treat obesity, type 2 diabetes, and associated diseases. Therefore, further research is needed to completely comprehend the complex interplay between NP system and adipose tissue, heart, liver and skeletal muscles during obesity, insulin resistance, and type 2 diabetes.
The author declares no conflict of interest.
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\\n\\n7. ONLINE PUBLICATION, PRINT AND DELIVERY OF THE BOOK
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\n\n3. PEER REVIEW RESULTS
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\n\nAfter we receive your proof corrections and a final typeset of the manuscript is approved, your manuscript is sent to our in house DTP department for technical formatting and online publication preparation.
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\n\nThe invoice is generally paid by the author, the author’s institution or funder. The payment can be made by credit card from your Author Panel (one will be assigned to you at the beginning of the project), or via bank transfer as indicated on the invoice. We currently accept the following payment options:
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Only bioactive glass possesses osteogenic property that stimulates proliferation and differentiation of osteoprogenitor cells and in some cases influencing the fibroblastic properties. But, this material has also some disadvantages such as short-term and low mechanical strength along with decreased fracture resistance; but, this was further minimised by ion doping that positively enhanced new bone formation. There are many metal ions such as magnesium (Mg), strontium (Sr), manganese (Mn), iron (Fe), zinc (Zn), silver (Ag) and some rare earths that have been doped successfully into bioactive glass to enhance their mechanical and biological properties. In some of the cases, mesoporous bioactive glass materials with or without such doping have also been employed (with homogeneous distribution of pores in the size ranging between 2 and 50 nm). These biomaterials can be served as scaffold for bone regeneration with adequate mechanical properties to restore bone defects and facilitate healing process by regeneration of soft tissues as well. This chapter encompasses the use of bioactive glass in bulk and mesoporous form with doped therapeutic ions, their role in bone tissue regeneration, use as delivery of growth factors as well as coating material for orthopaedic implants.",book:{id:"5164",slug:"advanced-techniques-in-bone-regeneration",title:"Advanced Techniques in Bone Regeneration",fullTitle:"Advanced Techniques in Bone Regeneration"},signatures:"Samit Kumar Nandi, Arnab Mahato, Biswanath Kundu and Prasenjit\nMukherjee",authors:[{id:"60514",title:"Dr.",name:"Samit",middleName:null,surname:"Nandi",slug:"samit-nandi",fullName:"Samit Nandi"}]},{id:"37120",doi:"10.5772/29607",title:"Trigeminocardiac Reflex in Neurosurgery - Current Knowledge and Prospects",slug:"the-trigeminocardiac-reflex-in-neurosurgery-current-knowledge-and-prospects",totalDownloads:3423,totalCrossrefCites:10,totalDimensionsCites:27,abstract:null,book:{id:"749",slug:"explicative-cases-of-controversial-issues-in-neurosurgery",title:"Explicative Cases of Controversial Issues in Neurosurgery",fullTitle:"Explicative Cases of Controversial Issues in Neurosurgery"},signatures:"Amr Abdulazim, Martin N. Stienen, Pooyan Sadr-Eshkevari, Nora Prochnow, Nora Sandu, Benham Bohluli and Bernhard Schaller",authors:[{id:"78171",title:"Prof.",name:"Bernhard",middleName:null,surname:"Schaller",slug:"bernhard-schaller",fullName:"Bernhard Schaller"},{id:"78525",title:"Mr.",name:"Amr",middleName:null,surname:"Abdulazim",slug:"amr-abdulazim",fullName:"Amr Abdulazim"},{id:"78530",title:"Dr",name:"Pooyan",middleName:null,surname:"Sadr-Eshkevari",slug:"pooyan-sadr-eshkevari",fullName:"Pooyan Sadr-Eshkevari"},{id:"126039",title:"Dr.",name:"Martin",middleName:"Nikolaus",surname:"Stienen",slug:"martin-stienen",fullName:"Martin Stienen"},{id:"126040",title:"Dr.",name:"Nora",middleName:null,surname:"Prochnow",slug:"nora-prochnow",fullName:"Nora Prochnow"},{id:"126041",title:"Dr.",name:"Benham",middleName:null,surname:"Bohluli",slug:"benham-bohluli",fullName:"Benham Bohluli"}]},{id:"26559",doi:"10.5772/28833",title:"Local Antibiotic Therapy in the Treatment of Bone and Soft Tissue Infections",slug:"local-antibiotic-therapy-in-the-treatment-of-bone-and-soft-tissue-infections",totalDownloads:6551,totalCrossrefCites:5,totalDimensionsCites:21,abstract:null,book:{id:"784",slug:"selected-topics-in-plastic-reconstructive-surgery",title:"Selected Topics in Plastic Reconstructive Surgery",fullTitle:"Selected Topics in Plastic Reconstructive Surgery"},signatures:"Stefanos Tsourvakas",authors:[{id:"75532",title:"Dr.",name:"Stefanos",middleName:null,surname:"Tsourvakas",slug:"stefanos-tsourvakas",fullName:"Stefanos Tsourvakas"}]}],mostDownloadedChaptersLast30Days:[{id:"65467",title:"Anesthesia Management for Large-Volume Liposuction",slug:"anesthesia-management-for-large-volume-liposuction",totalDownloads:5965,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The apparent easiness with which liposuction is performed favors that patients, young surgeons, and anesthesiologists without experience in this field ignore the many events that occur during this procedure. Liposuction is a procedure to improve the body contour and not a surgery to reduce weight, although recently people who have failed in their plans to lose weight look at liposuction as a means to contour their body figure. Tumescent liposuction of large volumes requires a meticulous selection of each patient; their preoperative evaluation and perioperative management are essential to obtain the expected results. The various techniques of general anesthesia are the most recommended and should be monitored in the usual way, as well as monitoring the total doses of infiltrated local anesthetics to avoid systemic toxicity. The management of intravenous fluids is controversial, but the current trend is the restricted use of hydrosaline solutions. The most feared complications are deep vein thrombosis, pulmonary thromboembolism, fat embolism, lung edema, hypothermia, infections and even death. The adherence to the management guidelines and prophylaxis of venous thrombosis/thromboembolism is mandatory.",book:{id:"6221",slug:"anesthesia-topics-for-plastic-and-reconstructive-surgery",title:"Anesthesia Topics for Plastic and Reconstructive Surgery",fullTitle:"Anesthesia Topics for Plastic and Reconstructive Surgery"},signatures:"Sergio Granados-Tinajero, Carlos Buenrostro-Vásquez, Cecilia\nCárdenas-Maytorena and Marcela Contreras-López",authors:[{id:"273532",title:"Dr.",name:"Sergio Octavio",middleName:null,surname:"Granados Tinajero",slug:"sergio-octavio-granados-tinajero",fullName:"Sergio Octavio Granados Tinajero"}]},{id:"42855",title:"Critical Care Issues After Major Hepatic Surgery",slug:"critical-care-issues-after-major-hepatic-surgery",totalDownloads:8909,totalCrossrefCites:2,totalDimensionsCites:2,abstract:null,book:{id:"3164",slug:"hepatic-surgery",title:"Hepatic Surgery",fullTitle:"Hepatic Surgery"},signatures:"Ashok Thorat and Wei-Chen Lee",authors:[{id:"52360",title:"Prof.",name:"Wei-Chen",middleName:null,surname:"Lee",slug:"wei-chen-lee",fullName:"Wei-Chen Lee"},{id:"157213",title:"Dr.",name:"Ashok",middleName:null,surname:"Thorat",slug:"ashok-thorat",fullName:"Ashok Thorat"}]},{id:"72175",title:"Fontan Operation: A Comprehensive Review",slug:"fontan-operation-a-comprehensive-review",totalDownloads:1252,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Since the first description of the Fontan operation in the early 1970s, a number of modifications have been introduced and currently staged, total cavopulmonary connection with fenestration has become the most commonly used multistage surgery in diverting the vena caval blood flow into the lungs. The existing ventricle, whether it is left or right, is utilized to supply systemic circuit. During Stage I, palliative surgery is performed, usually at presentation in the neonatal period/early infancy, on the basis of pathophysiology of the cardiac defect. During Stage II, a bidirectional Glenn procedure is undertaken in which the superior vena caval flow is diverted into the lungs at an approximate age of 6 months. During Stage IIIA, the blood flow from the inferior vena cava (IVC) is rerouted into the pulmonary arteries, typically by an extra-cardiac conduit along with a fenestration, generally around 2 years of age. During Stage IIIB, the fenestration is closed by transcatheter methodology 6–12 months after Stage IIIA. The evolution of Fontan concepts, the indications for Fontan surgery, and the results of old and current types of Fontan operation form the focus of this review.",book:{id:"9585",slug:"advances-in-complex-valvular-disease",title:"Advances in Complex Valvular Disease",fullTitle:"Advances in Complex Valvular Disease"},signatures:"P. Syamasundar Rao",authors:[{id:"68531",title:"Dr.",name:"P. Syamasundar",middleName:null,surname:"Rao",slug:"p.-syamasundar-rao",fullName:"P. Syamasundar Rao"}]},{id:"45712",title:"Serdev Sutures® in Middle Face",slug:"serdev-sutures-in-middle-face",totalDownloads:4919,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"2989",slug:"miniinvasive-face-and-body-lifts-closed-suture-lifts-or-barbed-thread-lifts",title:"Miniinvasive Face and Body Lifts",fullTitle:"Miniinvasive Face and Body Lifts - Closed Suture Lifts or Barbed Thread Lifts"},signatures:"Nikolay Serdev",authors:[{id:"32585",title:"Dr.",name:"Nikolay",middleName:null,surname:"Serdev",slug:"nikolay-serdev",fullName:"Nikolay Serdev"}]},{id:"55812",title:"Postural Restoration: A Tri-Planar Asymmetrical Framework for Understanding, Assessing, and Treating Scoliosis and Other Spinal Dysfunctions",slug:"postural-restoration-a-tri-planar-asymmetrical-framework-for-understanding-assessing-and-treating-sc",totalDownloads:7646,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Current medical practice does not recognize the influence of innate, physiological, human asymmetry on scoliosis and other postural disorders. Interventions meant to correct these conditions are commonly based on symmetrical models of appearance and do not take into account asymmetric organ weight distribution, asymmetries of respiratory mechanics, and dominant movement patterns that are reinforced in daily functional activities. A model of innate, human asymmetry derived from the theoretical framework of the Postural Restoration Institute® (PRI) explicitly describes the physiological, biomechanical, and respiratory components of human asymmetry. This model is important because it gives an accurate baseline for understanding predisposing factors for the development of postural disorders, which, without intervention, will likely progress to structural dysfunction. Clinical tests to evaluate tri-planar musculoskeletal relationships and function, developed by PRI, are based on this asymmetric model. These tests are valuable for assessing patient’s status in the context of human asymmetry and in guiding appropriate exercise prescription and progression. Balancing musculoskeletal asymmetry is the aim of PRI treatment. Restoration of relative balance decreases pain, restores improved alignment, and strengthens appropriate muscle function. It can also halt the progression of dysfunction and improve respiration, quality of life, and appearance. PRI’s extensive body of targeted exercise progressions are highly effective due to their basis in the tri-planar asymmetric human model.",book:{id:"5816",slug:"innovations-in-spinal-deformities-and-postural-disorders",title:"Innovations in Spinal Deformities and Postural Disorders",fullTitle:"Innovations in Spinal Deformities and Postural Disorders"},signatures:"Susan Henning, Lisa C. Mangino and Jean Massé",authors:[{id:"204825",title:"Dr.",name:"Susan",middleName:null,surname:"Henning",slug:"susan-henning",fullName:"Susan Henning"},{id:"206242",title:"Dr.",name:"Lisa C",middleName:null,surname:"Mangino",slug:"lisa-c-mangino",fullName:"Lisa C Mangino"},{id:"206245",title:"Dr.",name:"Jean",middleName:null,surname:"Massé",slug:"jean-masse",fullName:"Jean Massé"}]}],onlineFirstChaptersFilter:{topicId:"202",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:18,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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