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Introduction The field of medicine is experiencing a crisis as high levels of physician and trainee burnout threaten the pipeline of future physicians. Grit, or passion and perseverance for long-term goals, has been studied in high-performing and elite military units and found to be predictive of successful completion of training in adverse conditions. The Uniformed Services University of the Health Sciences (USU) graduates military medical leaders who make up a significant portion of the Military Health System physician workforce. Taken together, an improved understanding of the relationships between burnout, well-being, grit, and retention among USU graduates is critical to the success of the Military Health System. Materials and Methods The current study was approved by the Institutional Review Board at USU and explored these relations among 519 medical students across three graduating classes. These students participated in two surveys approximately one year apart from October 2018 until November 2019. Participants completed measures on grit, burnout, and likelihood of leaving the military. These data were then merged with demographic and academic data (e.g., Medical College Admission Test scores) from the USU Long Term Career Outcome Study. These variables were then analyzed simultaneously using structural equation modeling to examine the relationships among variables in a single model. Results Results reaffirmed the 2-factor model of grit as both passion and perseverance (or interest consistency). No significant relationships emerged between burnout and other study variables. Sustained and focused interest was predictive of less likelihood of staying in the military. Conclusion This study offers important insights into the relationship among well-being factors, grit, and long-term career planning in the military. The limitations of using a single-item measure of burnout and measuring behavioral intentions in a short time frame during undergraduate medical education highlight the importance of future longitudinal studies that can examine actual behaviors across a career lifespan. However, this study offers some key insights into potential impacts on the retention of military physicians. The findings suggest that military physicians who are most likely to stay in the military tend to embrace a more fluid and flexible medical specialty path. This is critical in expectation setting for the military to train and retain military physicians across a wide range of critical wartime specialties.

Introduction Developing physicians as leaders has gained attention across the United States. Undergraduate medical education (UME) and graduate medical education (GME) leader development programs have increased. During postgraduate years (PGY), graduates bring their leadership education to the bedside; however, associations between leader performance in medical school and GME is largely unknown. It is important to find experiences that can assess leader performance that may be useful to predict future performance. The purpose of this study was to determine if (1) there is a correlation between leader performance during the fourth year of medical school versus leader performance in PGY1 and 3, and (2) leader performance during the fourth year of medical school is associated with military leadership performance in PGY1 and 3s while taking previous academic performance markers into account. Methods This study examined overall leader performance of learners (classes of 2016-2018) during the fourth year of medical school and their graduate leader performance post-medical school. Leader performance was assessed by faculty during a medical field practicum (UME leader performance) and graduate leader performance was assessed by program directors at the end of PGY1 (N = 297; 58.3%) and 3 (N = 142; 28.1%). Pearson correlation analysis examined relationships among UME leader performance and between the PGY leader performance items. In addition, stepwise multiple linear regression analyses were conducted to examine the relationship between leader performance at the end of medical school with military leadership performance in PGY1 and 3, while taking into account the academic performance markers. Results Pearson correlation analyses revealed that the UME leader performance was correlated with 3 of 10 variables at PGY1, and was correlated at PGY3 with 10 out of 10 variables. Results of the stepwise multiple linear regression analysis indicated that leader performance during the fourth year of medical school explained an additional 3.5% of the variance of PGY1 leader performance after controlling for the previous academic performance markers (MCAT total score, USMLE Step 1 score and Step 2 CK score). In contrast, leader performance during the fourth year of medical school alone accounted for an additional 10.9% of the variance of PGY3 leader performance above and beyond the set of academic performance markers. Overall, UME leader performance has more predictive power in PGY leader performance than the MCAT or USMLE Step exams. Conclusions The findings of this study indicate that a positive relationship exists between leader performance at the end of medical school and leader performance in PGY1 and 3 years of residency. These correlations were stronger in PGY3 compared to PGY1. During PGY1, learners may be more focused on being a physician and an effective team member compared to PGY3 where they have a deeper understanding of their roles and responsibilities and can take on more leadership roles. Additionally, this study also found that MCAT and USMLE Step exams performance was not predictive of PGY1 or PGY3 leader performance. These findings provide evidence of the power of continued leader development in UME and beyond.

Introduction Physical and psychological well-being play a critical role in the academic and professional development of medical students and can alter the trajectory of a student’s quality of personal and professional life. Military medical students, given their dual role as officer and student, experience unique stressors and issues that may play a role in their future intentions to continue military service, as well as practice medicine. As such, this study explores well-being across the 4 years of medical school at Uniformed Services University (USU) and how well-being relates to a student’s likelihood to continue serving in the military and practicing medicine. Methods In September 2019, 678 USU medical students were invited to complete a survey consisting of three sections—the Medical Student Well-being Index (MSWBI), a single-item burnout measure, and six questions regarding their likelihood of staying in the military and medical practice. Survey responses were analyzed using descriptive statistics, analysis of variance (ANOVA), and contingency table analysis. Additionally, thematic analysis was conducted on open-ended responses included as part of the likelihood questions. Results Our MSWBI and burnout scores suggest that the overall state of well-being among medical students at USU is comparable to other studies of the medical student population. ANOVA revealed class differences among the four cohorts, highlighted by improved well-being scores as students transitioned from clerkships to their fourth-year curriculum. Fewer clinical students (MS3s and MS4s), compared to pre-clerkship students, indicated a desire to stay in the military. In contrast, a higher percentage of clinical students seemed to “reconsider” their medical career choice compared to their pre-clerkship student counterparts. “Medicine-oriented” likelihood questions were associated with four unique MSWBI items, whereas “military-oriented” likelihood questions were associated with one unique MSWBI item. Conclusion The present study found that the overall state of well-being in USU medical students is satisfactory, but opportunities for improvement exist. Medical student well-being seemed to have a stronger association with medicine-oriented likelihood items than with military-oriented likelihood items. To obtain and refine best practices for strengthening engagement and commitment, future research should examine if and how military and medical contexts converge and diverge throughout training. This may enhance the medical school and training experience and, ultimately, reinforce, or strengthen, the desire and commitment to practice and serve in military medicine.

Leadership and followership development are increasingly recognized as important in all fields of the workforce. The Innovative Leadership Model helps leaders increase self-understanding and optimize the performance of organizations by focusing on Leader Type, Developmental Perspective, Resilience, Situational Analysis, and Leadership Behaviors and Mindsets. The Leader-Follower Framework identifies key elements – Character, Competence, Communication, Context – to guide the development of individual leaders and followers across four psychosocial levels – Personal, Interpersonal, Team, Organizational. Each of these approaches has value and has been applied in various settings and contexts. The present chapter offers a new insight relevant to leadership by combining these two perspectives and their component elements. Understanding and developing each of these elements will optimize effective leadership and followership in a wide range of situations and settings.

Introduction Any implicit and explicit biases that exist may alter our interpretation of people and events. Within the context of assessment, it is important to determine if biases exist and to decrease any existing biases, especially when rating student performance to provide meaningful, fair, and useful input. The purpose of this study was to determine if the experience and gender of faculty members contribute to their ratings of students in a military medical field practicum. This information is important for fair ratings of students. Three research questions were addressed: Were there differences between new versus experienced faculty raters? Were there differences in assessments provided by female and male faculty members? Did gender of faculty raters impact ratings of female and male students?. Materials and Methods This study examined trained faculty evaluators’ ratings of three cohorts of medical students during 2015–2017 during a medical field practicum. Female (n = 80) and male (n = 161) faculty and female (n = 158) and male (n = 311) students were included. Within this dataset, there were 469 students and 241 faculty resulting in 5,599 ratings for each of six outcome variables that relate to overall leader performance, leader competence, and leader communication. Descriptive statistics were computed for all variables for the first four observations of each student. Descriptive analyses were performed for evaluator experience status and gender differences by each of the six variables. A multivariate analyses of variance was performed to examine whether there were differences between gender of faculty and gender of students. Results Descriptive analyses of the experience status of faculty revealed no significant differences between means on any of the rating elements. Descriptive analyses of faculty gender revealed no significant differences between female and male faculty ratings of the students. The overall MANOVA analyses found no statistically significant difference between female and male students on the combined dependent variables of leader performance for any of the four observations. Conclusions The study revealed that there were no differences in ratings of student leader performance based on faculty experience. In addition, there were no differences in ratings of student leader performance based on faculty gender.

Exertion-related illness (ERI), despite aggressive efforts with both prevention and emergency action planning, continues to be a considerable threat to both athletes and warfighters. Numerous case reports and series have served to elucidate risk factors, which have in turn become the focus of prevention strategies. While this approach has assisted in mitigating athlete risk, recent institutional guidance has identified the need for greater protection of athletes by accountability of training programs and the recognition of periods of distinct athlete vulnerability. These recommendations, in addition to observations from lessons learned from the aforementioned cluster reports of ERI, have a strong call-out for the role of leadership as both a culprit for injury and a potential mechanism for prevention. This commentary introduces a leader-follower framework and explores this model in the evolution of ERI and offers recommendations as to how we move forward toward making progress in prevention.

Modern healthcare involves teams composed of educators, learners, healthcare providers, patients, patients’ significant others and families, healthcare administrators, and information sources. Principles of social psychology are relevant to interactions among team members when learning and performing professional duties; communicating to build trust, commitment, and teamwork; and collaborating among members of the healthcare team. This paper briefly discusses several classic principles of social psychology and how they apply to healthcare teams and medical education. Understanding and applying these principles will help healthcare providers optimize performance and interactions with colleagues, learners, and patients. It is important to incorporate study and practice of these principles into medical education and professional development.

To bring humor into practice, we conducted a thorough review of humor literature and integrated known therapeutic techniques which have found empirical support over the past decades. There are many common elements to humor theories, despite debates in the field. The theoretical debates are less relevant to the practice of humor, which necessarily should be consistent with all valid theories. We constructed a workshop as a method to explore, integrate, and resolve inconsistencies to bring the theories into practice. Decades of research suggest the way people use humor relates to health. However, few studies target humor to improve health. Existing applications do not incorporate recent humor research or other disciplines, and focus on clinical recovery, rather than general wellbeing. This workshop combined research areas of humor, psychotherapy, health behavior change, and education. We then subjected the workshop to evaluation by a diverse group of humor experts and a diverse group of general participants during a qualitative usability phase. Our ultimate aim was to develop a workshop that was useable and acceptable to people of many ages and backgrounds, as humor and laughter exists in babies through elders and across languages. After revisions made during the usability phase, we broadly disseminated the workshop to assess interest, satisfaction, and partial validity in the final version. Humor experts supported the use of the workshop and integration of humor concepts. General participants provided critical (e.g., time-consuming) and positive feedback (e.g., specific concepts). For the revised workshop, completion rate was comparable to other online platforms (36%; n = 44/122 started). Self-reported satisfaction was statistically positive, and on a pre-post measure, participants’ understanding of humor improved, but motivation and self-efficacy were unchanged. Preliminary data supports the validity and feasibility of the workshop as a working humor training model. Future studies need to assess health outcomes of humor training.

The Gateway Hypothesis is based on epidemiological data and states there is a progression of drug use from use of a softer drug (e.g., nicotine) to use of a harder drug (e.g., morphine). It has been suggested that this sequence is causal and is relevant to drug prevention policies and programs. The present experiment used an animal model to investigate whether the Gateway Hypothesis involves a causal progression. Subjects were 16 female and 16 male Sprague-Dawley rats with ages comparable to late adolescence/emerging adulthood in humans. Subjects received nicotine (6 mg/kg/day) or saline for 21 days SC via osmotic minipump and subsequently were allowed to self-administer IV morphine (0.5 mg/kg/injection, 3 h/day) for 10 days. Results did not confirm the Gateway Hypothesis. In fact, rats pre-exposed to nicotine self-administered significantly less morphine than did rats pre-exposed to saline. These findings may be relevant to future drug use prevention policies and programs.

Healthcare providers must acquire extensive knowledge and skills to help promote physical health, behavioral health, and wellness; prevent and treat illnesses and injuries; encourage and guide rehabilitation; counsel and assist with decisions relevant to health, life, and death. In addition, 21st Century healthcare providers must develop leadership knowledge and skills to optimize their interactions and effectiveness with healthcare teams, patients, and patients’ significant others. Emotional intelligence is recognized as an essential component of leader education and development. It is important to optimally educate and develop healthcare providers with regard to components of emotional intelligence: self-awareness, self-regulation, social-awareness, and social regulation. Self-awareness focuses on understanding one’s own behaviors, cognitions, motivations, and emotions. Self-regulation emphasizes self-control and adaptability to various situations and settings. Social awareness includes understanding others’ behaviors, cognitions, motivations, and emotions. Social regulation draws upon the other components of emotional intelligence in order to optimize collaboration and cooperation and attainment of mutual goals with other people. The present paper presents four principles of Social Psychology that are relevant to developing emotionally intelligent healthcare leaders: Field Theory, Informal Social Communication, Social Comparison, and Cognitive Dissonance. Although these principles are well-established and have received extensive attention, analysis, and discussion in the academic social psychology literature, they are rarely mentioned in the emotional intelligence or leadership literatures. Therefore, each of these principles is briefly described in the present paper followed by an explanation of how each principle relates to the development of emotional intelligence in general and to emotionally intelligent healthcare leaders in particular.

Traumatic brain injury (TBI) is known to increase the susceptibility to various age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Although the role of damaged mitochondrial electron transport chain (ETC) in the progression of AD and PD has been identified, its relationship with altered expression of neurodegenerative proteins has not been examined before. This study aimed to investigate 1) how TBI could affect mitochondrial ETC and neurodegeneration in rat brain regions related to behavioral alteration, and 2) if administration of the key mitochondrial substrate pyruvate can improve the outcome of mild TBI (mTBI). In a rat lateral fluid percussion injury model of mTBI, sodium pyruvate in sterile distilled water (1 g/kg body weight) was administered orally daily for 7 days. The protein expression of mitochondrial ETC enzymes, and neurodegeneration proteins in the hippocampus and cerebral cortex and was assessed on Day 7. The hippocampal and cortical expressions of ETC complex I, III, IV, V were significantly and variably impaired following mTBI. Pyruvate treatment altered ETC complex expression, reduced the nitrosyl stress and the MBP expression in the injured brain area, but increased the expression of the glial fibrillary acidic protein (GFAP) and Tau proteins. Pyruvate after mTBI augmented the Rotarod performance but decreased the horizontal and vertical open field locomotion activities and worsened neurobehavioural severity score, indicating a debilitating therapeutic effect on the acute phase of mTBI. These results suggest bidirectional neuroprotective and neurodegenerative modulating effects of pyruvate on TBI-induced alteration in mitochondrial activity and motor behavior. Pyruvate could potentially stimulate the proliferation of astrogliosis, and lactate acidosis, and caution should be exercised when used as a therapy in the acute phase of mTBI. More effective interventions targeted at multiple mechanisms are needed for the prevention and treatment of TBI-induced long-term neurodegeneration.

Conceptual frameworks for Leader and Leadership Education and Development guide the curriculum and assessment of students, faculty, and programs. This commentary defines leader and leadership and p...

The literature has consistently emphasized a relationship between chronic stress and depression as well as the involvement of brain-derived neurotrophic factor (BDNF). It is also well known that there are gender disparities with regard to depression. However, there has been a lack of biobehavioral experimental investigations of these relationships with regard to the role of BDNF in sex differences in response to stress. It was hypothesized that stress (chronic unpredictable mild stress [CUMS], shock stress [SS]) would result in greater deleterious alterations in behavior (open field activity [OFA]) and biological (serum BDNF, body weight [BW]) indices of depression for female rats as compared to male rats. Subjects consisted of 79 Sprague-Dawley rats with 11-16 rats per each condition. CUMS consisted of 14 d of stress whereby on each stress day, rats were exposed to 20-min periods of predator stress and unpredictable environmental stress. SS consisted of a 2-h per day session of immobilization and tail-shocks repeated for three consecutive days. Serum BDNF was collected

Introduction Many medical schools in the United States are introducing leader and leadership curricula. However, there is a large gap regarding how to assess leader performance during undergraduate medical education. With the guidance of a conceptual framework, leadership assessment measures can be developed, learners can make expected improvements in performance over time, and assessment measures can be used in relevant, applied, medical teaching settings. Uniformed Services University (USU) medical students are educated to become healthcare leaders who can perform effectively in various settings. Medical students are assessed on multiple occasions for elements of leader performance during “Operation Bushmaster” – the capstone military medical field practicum event for fourth year medical students – by experienced faculty. A conceptual framework guides the assessment approach for leader performance during Bushmaster. The USU Leader and Leadership Education and Development program developed an assessment tool to measure student leader performance used in a military medical field practicum. The present paper examines whether: (1) leader performance can be measured at Bushmaster; (2) leader performance changed during Bushmaster; (3) leader performance elements are related to each other; and (4) overall leader performance is related to other medical academic performance. Materials and Methods Trained faculty assessed students’ leader performance. Data from three cohorts of USU medical students (N = 509) were collected. All data were collected, compiled, deidentified, and analyzed with approval from the USU Institutional Review Board (Protocol number: KM83XV). Descriptive statistics, repeated measures t-tests, trend analyses, and correlation analyses were performed. Results Data were available from 483/509 [95%] students. Results revealed that: (1) average leader performance was satisfactory; (2) overall leader performance and performance on each of the major elements of leader performance significantly improved over the course of Bushmaster; (3) major elements of leader performance were significantly correlated with each other and with overall leader performance; (4) leader performance was not correlated with students’ performance on the MCAT total score or USMLE Step exam scores. Conclusion With the guidance of a conceptual framework, the assessment tool was used to assess leader performance in a relevant, applied, medical teaching setting. The findings of this study indicate that leader performance can be measured. Additionally, leader performance appears to be a separate skillset from medical academic performance and both types of performance can be taught and developed. This was a retrospective correlation study and was conducted during a military medical field practicum at a single institution. Gathering additional validity evidence of the assessment tool is needed. With additional validity evidence, the assessment tool could be applied to other medical exercises in different settings and help with the assessment of leader performance beyond medical school.

This article was migrated. The article was marked as recommended. Problem: Leadership has been identified as an essential component for success in medicine. Many medical schools have initiated Leader and Leadership Education and Development (LEAD) programs to develop physician leaders. Currently, there is no consensus whether teaching leadership is important, who to teach, what topics to teach, and where leadership fits into the curriculum during medical school. Approach: To address these issues, the Uniformed Services University of the Health Sciences (USU) LEAD team convened an inaugural Medical Student LEAD Summit and Working Group Meeting on April 4, 2017. Participants came from public and private U.S. medical schools engaged in LEAD programs, military service academies, the Veterans Administration, and the Association of American Medical Colleges. The purpose of this meeting was to share opinions, experiences, and current practices regarding medical student LEAD. Outcomes: Participants overwhelmingly agreed that: (1) providing LEAD is an essential component of undergraduate medical education; (2) there currently is no single best LEAD program for all medical schools; (3) a clear purpose, goal, philosophy, and conceptual framework consistent with the mission and vision of each institution is needed; (4) assessment of students, programs, faculty must be incorporated; and (5) research and scholarship are essential for LEAD programs. Next Steps: Based on the positive feedback and interest from participants, the USU LEAD team will host a second Summit in April 2018 to follow up with the inaugural participants and to include representatives from additional institutions who are currently conducting or interested in starting their own medical school LEAD programs.

Human performance optimization (HPO) is defined as "the process of applying knowledge, skills and emerging technologies to improve and preserve the capabilities of military members, and organizations to execute essential tasks." The lack of consensus for operationally relevant and standardized metrics that meet joint military requirements has been identified as the single most important gap for research and application of HPO. In 2013, the Consortium for Health and Military Performance hosted a meeting to develop a toolkit of standardized HPO metrics for use in military and civilian research, and potentially for field applications by commanders, units, and organizations. Performance was considered from a holistic perspective as being influenced by various behaviors and barriers. To accomplish the goal of developing a standardized toolkit, key metrics were identified and evaluated across a spectrum of domains that contribute to HPO: physical performance, nutritional status, psychological status, cognitive performance, environmental challenges, sleep, and pain. These domains were chosen based on relevant data with regard to performance enhancers and degraders. The specific objectives at this meeting were to (a) identify and evaluate current metrics for assessing human performance within selected domains; (b) prioritize metrics within each domain to establish a human performance assessment toolkit; and (c) identify scientific gaps and the needed research to more effectively assess human performance across domains. This article provides of a summary of 150 total HPO metrics across multiple domains that can be used as a starting point-the beginning of an HPO toolkit: physical fitness (29 metrics), nutrition (24 metrics), psychological status (36 metrics), cognitive performance (35 metrics), environment (12 metrics), sleep (9 metrics), and pain (5 metrics). These metrics can be particularly valuable as the military emphasizes a renewed interest in Human Dimension efforts, and leverages science, resources, programs, and policies to optimize the performance capacities of all Service members.

Despite long-standing debates about whether leaders are born or made, current thinking within the leadership field is that leaders can be developed. In the arena of health and healthcare, developing effective, value-driven and outcome-focused leaders is critical to address the many challenges facing systems that promote and maintain health as well as focus on healthcare delivery and practices. Effective health and healthcare leaders are needed to set thoughtful policies; educate the public about primary prevention strategies; identify best practices (administrative and clinical); allocate healthcare resources wisely; address healthcare needs and disparities; focus on optimal clinical outcomes and value in the delivery of care; and encourage individuals to engage in behaviors that enhance well-being. This chapter presents seven steps to establish a Leader and Leadership Education and Development (LEAD) program. These steps were based on the authors’ experience establishing a LEAD program at the Uniformed Services University of the Health Sciences (USU) where physicians, advanced practice nurses, dentists, psychologists, and scientists are trained for the Army, Navy, Air Force, and Public Health Service, and civilians are trained to become scientists, academicians, and clinicians with a focus on national service and health. These same steps also could be used as a guide to establish programs that educate and develop leaders for other professions and careers.

Many leader types have been described and are useful. Because so many leader types have been identified, they may be interpreted as competing with each other rather than as complementary or alternative types that depend on individual leaders, the groups that are being led, or the situations in which leadership occurs. This chapter suggests that it is valuable to identify a leader type that can serve as an umbrella term and concept to capture principles relevant to all types of effective leadership. The identification of an overarching, effective leader type is based on a psychobiosocial perspective that draws from field theory in the social sciences and from the stress literature. Based on these literatures, the term “allostatic leader” is offered to describe an ideal leader who responds, adapts, learns, and changes with experience to become even more effective in subsequent situations. Consequently, a clear operational and holistic definition can best focus leader education and development programs to optimally grow effective leaders.

Impulsivity, a tendency toward immediate action without consideration of future consequences, is associated with a wide array of problematic behaviors. Response impulsivity, a type of behaviorally-assessed impulsivity characterized by behavioral disinhibition, is also associated with health risk behaviors. Response impulsivity is distinct from choice impulsivity, which is characterized by intolerance for delay. Lewis rats have higher levels of choice impulsivity than Fischer rats (Anderson & Woolverton, 2005; Madden et al., 2008; Stein et al., 2012). However, no studies have examined whether Lewis and Fischer rats have different levels of response impulsivity. The present research examined response impulsivity in the two rat strains. Subjects were 16 male Lewis and Fischer rats. Rats’ response impulsivity was measured using the Five Choice Serial Reaction Time Task (5-CSRTT). In addition, their locomotor activity was measured in locomotor activity chambers. Lewis rats had more premature responses than Fischer rats during the 5-CSRTT assessment [F(1, 14) = 5.34, p < 0.05], indicating higher levels of response impulsivity. Locomotor activity did not differ between rat strain groups [F(1, 14) = 3.05, p = .10], suggesting that overall movement did not account for group differences in response impulsivity on the 5-CSRTT. It can be concluded from this research that Lewis rats have higher levels of response impulsivity than Fischer rats, and therefore provide a valid rat model of individual differences in impulsivity.

Environmental enrichment decreases nicotine reactivity in male rats, but these effects have not been examined in females. This research was conducted to examine the effects of enrichment on nicotine behavioral sensitization (i.e., nicotine reactivity) in male and female rats. One hundred forty-four Sprague-Dawley rats (72 male, 72 female) were raised in isolation, social enrichment (groups of three rats [SE]), or combined physical enrichment and social enrichment (groups of three rats with novel toys [PESE]) housing conditions. As adults, they received daily subcutaneous injections of saline or nicotine (0.1, 0.5, or 1.0 mg/kg) for 12 days; locomotor activity was measured on drug days 1, 5, 9, and 12. Before drug administration, PESE and SE decreased activity in males; only PESE decreased activity in females, F(2, 120) = 6.51, p < .01. In the drug phase, nicotine behavioral sensitization occurred, F(8.46, 341.04) = 20.71, p < .001, and was greater in females than males, F(8.340, 319.715) = 2.072, p < .05. Enrichment decreased nicotine behavioral sensitization in both sexes, F(16.91, 341.04) = 2.48, p < .01. In conclusion, nicotine behavioral sensitization occurred in male and female rats and was attenuated by environmental enrichment. This research has implications for treatment and prevention strategies in humans. Programs that incorporate aspects of social and environmental stimulation may have enhanced effectiveness in preventing and reducing cigarette smoking and may have implications for relapse prevention.

Leadership is a growing topic of interest in medicine and medical school education. The Association of American Medical Colleges now identifies leadership as “the most critical component for success”.1 Some medical schools in the United States are introducing leadership curricula, but there is a large gap that still needs to be filled.2 The Uniformed Services University of the Health Sciences educates and trains health professional leaders for the United States Army, Navy, Air Force, and Public Health Service. Leadership education has long been a part of this university’s mission. Recently, the university has expanded its Leader and Leadership Education and Development program that is provided to all Uniformed Services University medical students at the F. Edward Hebert School of Medicine.3 The purpose of this paper is to describe the comprehensive program and its conceptual framework that may be useful for other academic medical leader and leadership education and development programs around the globe. Leader and leadership education and development program It is essential for leader and leadership education programs to define leadership; identify which students should become leaders; base the program on a conceptual framework; develop a curriculum consistent with the goals and conceptual framework; ensure that the program has a sound scholarly basis and include appropriate assessments. Medical students are introduced to leadership and its relevance to medical education on their first day of medical school. Leadership is defined as influence on individuals and groups by enhancing behaviors (actions), cognitions (perceptions, thoughts, and beliefs), and motivations (why people act and think as they do) to achieve goals that benefit the individuals and groups.4-6 Leaders set the vision and inspire followers. The Uniformed Services University uses these definitions and delivers a four-year, comprehensive program as a requisite part of the undergraduate medical education of all medical students. This program uses a variety of pedagogical techniques with emphasis on experiential learning. The program strives to develop adaptive leaders who are prepared to perform in volatile, uncertain, complex, and ambiguous environments.7-9 The program content and assessments are based on the FourCe-PITO Leadership Conceptual Framework. The four major elements of leadership (Four C elements or FourCe) are Character (who the person is), Competence (what the person does), Context (when and where actions occur), and Communication (how information is sent and received). These elements interact with each other and operate across four levels of psychological and social interactions – Personal (the individual), Interpersonal (between individuals), Team (small groups), and Organizational (large groups and systems).4,10 The curriculum is carefully woven throughout all four years of undergraduate medical education focusing on the formation of professional identity, acquisition of relevant knowledge and skills, and learning through experience. The topics of study pertain to leadership, such as crisis communication, effective communication, followership, the performance of individuals and teams under stress, personality and emotional intelligence, self-assessment and peer support, and team building. Each session is based on at least one element of the FourCe-PITO framework. A variety of pedagogical styles and venues are used to deliver the curriculum, including interactive plenary sessions, flipped classrooms, small group exercises, group discussions, applied clinical and field settings. “Near peers” (more senior medical students) and core faculty facilitate small group discussions about leadership in healthcare settings drawing from recent and relevant experiences. Leadership scholarship and research are foundational to this program. All concepts of leadership, management, and followership taught to the students are based on principles, theories, approaches, and techniques that have been developed by scholars and practitioners of leadership.6,11,12 The faculty conduct research and scholarship including evaluation of program effectiveness. Medical and graduate students have the option to participate in research projects. Current projects include gender and leadership; intergenerational leadership; development of leadership assessment tools; innovative teaching strategies.13-16 The program includes assessment of students’ knowledge and performance, faculty knowledge and performance, and program effectiveness. Assessments of leadership are based on quizzes; self-reflection; formative and summative feedback in applied settings; and faculty, peer, self-assessments using the FourCe-PITO framework. Quizzes and self-reflection questions are given after each session, and students provide programmatic feedback. Results from the quizzes, self-reflection responses and feedback are used to improve sessions. The program has developed a self-assessment and peer support tool that is available as a smartphone app to help teach and promote self-awareness. Students are provided with their own formative ratings in each of the leadership elements as well as ratings based on input from several peers. This information enables students to see how they rate themselves compared to how their peers rate them on elements within the leadership framework. Additionally, all students participate in several medical field exercises over the four years where faculty evaluates them in applied settings. All medical students in the program become physicians in the U.S. military or Public Health Service for at least eight years after graduation (and typically remain in these uniformed services for 10 - 25 years). Therefore, the program can assess performance as medical leaders for many years after completion of the medical school’s leadership program. This information is gathered and evaluated as part of the university’s Long-Term Career Outcome Study.15,16 Leadership elements in the database include student demographic information as well as performance during pre-clerkship, clerkship phases of education, and beyond. The merging of these data sets allows for evaluation of leadership performance in relationship to individual differences and medical professional performance.

This article was migrated. The article was not marked as recommended. Problem: Leader and Leadership Education and Development (LEAD) is of growing interest in medical education and is a critical element for success. Several programs world-wide in undergraduate medical education (UME) and graduate medical education (GME) include their own versions of LEAD, but these programs remain relatively unique to university and institution missions. Creating and using a common language across the life-cycle (spanning pre-UME, UME, GME, and beyond) and delivering appropriate curricula and assessments for each stage of the professional life-cycle is essential. Approach: The purpose of the 2019 LEAD Summit and Working Group meeting was to share opinions, experiences, and current practices across the medical professional life-cycle. Attendees offered diverse perspectives relevant to leadership programs before, during, and after medical school. Outcomes: Three themes emerged from the meeting: the importance of common language; relevant and effective curriculum; and meaningful assessment across the life-cycle. Additionally, integration should occur within each step of the life-cycle and across the life-cycle to enhance the learning experience. To achieve these goals requires the development of learners and faculty. Next Steps: Leadership is valuable in medicine. If medical education programs do not value LEAD, then these programs will fail to equip graduates to be effective 21st Century medical professionals. The development of a common language, clear expectations within and among training programs, and accreditation from appropriate organizations would provide some quality control and encourage institutions to provide resources and buy-in from learners and faculty.

N-acetylaspartate (NAA) is recognized as a noninvasive diagnostic neuronal marker for a host of neuropsychiatric disorders using magnetic resonance spectroscopy (MRS). Numerous correlative clinical studies have found significant decreases in NAA levels in specific neuronal systems in an array of neuropsychiatric and substanceabuse disorders. We have recently identified the methamphetamine-induced neuronal protein known as “shati” as the NAA biosynthetic enzyme (aspartate Nacetyltransferase [Asp-NAT]; gene Nat8l). We have generated an Nat8l transgenic knockout mouse line to study the functions of NAA in the nervous system. We were unable to breed homozygous Nat8l knockout mice successfully for study and so used the heterozygous mice (Nat8l 1/2 ) for initial characterization. MRS analysis of the Nat8l 1/2 mice indicated significant reductions in NAA in cortex (238%) and hypothalamus (229%) compared with wild-type controls, which was confirmed using HPLC (229% in forebrain). The level of the neuromodulator N-acetylaspartylglutamate (NAAG), which is synthesized from NAA, was decreased by 12% in forebrain as shown by HPLC. Behavioral analyses of the heterozygous animals indicated normal behavior in most respects but reduced vertical activity in open-field tests compared with age- and sex-matched wild-type mice of the same strain. Nat8l 1/2 mice also showed atypical locomotor responses to methamphetamine administration, suggesting that NAA is involved in modulating the hyperactivity effect of methamphetamine. These observations add to accumulating evidence suggesting that NAA has specific regulatory functional roles in mesolimbic and prefrontal neuronal pathways either directly or indirectly through impact on NAAG synthesis. V C 2013

Motor and sensory deficits are common following traumatic brain injury (TBI). Although rodent models provide valuable insight into the biological and functional outcomes of TBI, the success of translational research is critically dependent upon proper selection of sensitive, reliable, and reproducible assessments. Published literature includes various observational scales designed to evaluate post-injury functionality; however, the heterogeneity in TBI location, severity, and symptomology can complicate behavioral assessments. The importance of choosing behavioral outcomes that can be reliably and objectively quantified in an efficient manner is becoming increasingly important. The Revised Neurobehavioral Severity Scale (NSS-R) is a continuous series of specific, sensitive, and standardized observational tests that evaluate balance, motor coordination, and sensorimotor reflexes in rodents. The tasks follow a specific order designed to minimize interference: balance, landing, tail raise, dragging, righting reflex, ear reflex, eye reflex, sound reflex, tail pinch, and hindpaw pinch. The NSS-R has proven to be a reliable method differentiating brain-injured rodents from non-brain-injured rodents across many brain injury models.

Serial MRI facilitates the in vivo analysis of the intra- and intersubject evolution of traumatic brain injury lesions. Despite the availability of MRI, the natural history of experimental focal contusion lesions in the controlled cortical impact (CCI) rat model has not been well described. We performed CCI on rats and MRI during the acute to chronic stages of cerebral injury to investigate the time course of changes in the brain. Female Wistar rats underwent CCI of their left motor cortex with a flat impact tip driven by an electromagnetic piston. In vivo MRI was performed at 7 T serially over 6 weeks post-CCI. The appearances of CCI-induced lesions and lesion-associated cortical volumes were variable on MRI, with the percentage change in cortical volume of the CCI ipsilateral side relative to the contralateral side ranging from 18% within 2 h of injury on day 0 to a peak of 35% on day 1, and a trough of -28% by week 5/6, with an average standard deviation of ± 14% at any given time point. In contrast, the percentage change in cortical volume of the ipsilateral side relative to the contralateral side in control rats was not significant (1 ± 2%). Hemorrhagic conversion within and surrounding the CCI lesion occurred between days 2 and 9 in 45% of rats, with no hemorrhage noted on the initial scan. Furthermore, hemorrhage and hemosiderin within the lesion were positive for Prussian blue and highly autofluorescent on histological examination. Although some variation in injuries may be technique related, the divergence of similar lesions between initial and final scans demonstrates the inherent biological variability of the CCI rat model.

Mild traumatic brain injury, caused by the exposure to single or repeated blast overpressure, is a principal concern due to its pathological complexity and neurobehavioral similarities with posttraumatic stress disorder. In this study, we exposed rats to a single or multiple (five total; administered on consecutive days) mild blasts, assessed their behavior at 1 and 16 days postinjury) and performed histological and protein analyses of brains and plasma at an early (2 h) and a late (22 days) termination time point. One day postinjury, multiple-injured (MI) rats showed the least general locomotion and the most depression- and anxiety-related behaviors among the experimental groups; there were no such differences at 16 days. However, at the later time point, both injured groups displayed elevated levels of select protein biomarkers. Histology showed significantly increased numbers of TUNEL+ (terminal-deoxy-transferase-mediated dUTP nick-end labeling)-positive cells in the dorsal and ventral hippocampus (DHC and VHC) of both injured groups as early as 2 h after injury. At 22 days, the increase was limited to the VHC of MI animals. Our findings suggest that the exposure to mild blast overpressure triggers early hippocampal cell death as well as neuronal, glial, and vascular damage that likely contribute to significant, albeit transient increases in depression- and anxiety-related behaviors. However, the severity of the observed pathological changes in MI rats failed to support the hypothesized cumulative effect of repeated injury. We infer that at this blast frequency, a potential conditioning phenomenon counteracts with and reduces the extent of subsequent damage in MI rats.

The overlapping pathologies and functional outcomes of blast-induced TBI (bTBI) and stress-related neurobehavioral disorders like post-traumatic stress disorder (PTSD) are significant military health issues. Soldiers are exposed to multiple stressors with or without suffering bTBI, making diagnosis and treatment as well as experimental modeling of bTBI a challenge. In this study we compared anxiety levels of Naïve rats to ones that were exposed to each of the following conditions daily for 4 consecutive days: C I: transportation alone; C II: transportation and anesthesia; C III: transportation, anesthesia, and blast sounds; Injured: all three variables plus mild blast overpressure. Following behavioral testing we analyzed sera and select brain regions for protein markers and cellular changes. C I, C II, and C III animals exhibited increased anxiety, but serum corticosterone levels were only significantly elevated in C III and Injured rats. C III and Injured animals also had elevated interferon-γ (IFN-γ) and interleukin-6 (IL-6) levels in the amygdala (AD) and ventral hippocampus (VHC). Glial fibrillary acidic protein (GFAP) levels were only significantly elevated in the VHC, prefrontal cortex (PFC), and AD of Injured animals; they showed an apparent increase in ionized calcium-binding adapter molecule (Iba1) and GFAP immunoreactivity, as well as increased numbers of TUNEL-positive cells in the VHC. Our findings demonstrate that experimental conditions, particularly the exposure to blast acoustics, can increase anxiety and trigger specific behavioral and molecular changes without injury. These findings should be taken into consideration when designing bTBI studies, to better understand the role of stressors in the development of post-traumatic symptoms, and to establish a differential diagnosis for PTSD and bTBI.

Neurological dysfunction after traumatic brain injury (TBI) is caused by both the primary injury and a secondary cascade of biochemical and metabolic events. Since TBI can be caused by a variety of mechanisms, numerous models have been developed to facilitate its study. The most prevalent models are controlled cortical impact and fluid percussion injury. Both typically use "sham" (craniotomy alone) animals as controls. However, the sham operation is objectively damaging, and we hypothesized that the craniotomy itself may cause a unique brain injury distinct from the impact injury. To test this hypothesis, 38 adult female rats were assigned to one of three groups: control (anesthesia only); craniotomy performed by manual trephine; or craniotomy performed by electric dental drill. The rats were then subjected to behavioral testing, imaging analysis, and quantification of cortical concentrations of cytokines. Both craniotomy methods generate visible MRI lesions that persist for 14 days. The initial lesion generated by the drill technique is significantly larger than that generated by the trephine. Behavioral data mirrored lesion volume. For example, drill rats have significantly impaired sensory and motor responses compared to trephine or naïve rats. Finally, of the seven tested cytokines, KC-GRO and IFN-γ showed significant increases in both craniotomy models compared to naïve rats. We conclude that the traditional sham operation as a control confers profound proinflammatory, morphological, and behavioral damage, which confounds interpretation of conventional experimental brain injury models. Any experimental design incorporating "sham" procedures should distinguish among sham, experimentally injured, and healthy/naïve animals, to help reduce confounding factors.

This article was migrated. The article was marked as recommended. Problem: There is a growing call to add leader and leadership education to undergraduate medical education (UME). Yet, there currently are no established standards, competencies, curricula, or requirements for UME leader and leadership education and development (LEAD) programs. The Uniformed Services University of the Health Sciences (USU) F. Edward Hébert School of Medicine LEAD program hosts annual Summit and Working Group meetings to address issues and to share experiences about LEAD programs. Approach: Based on survey results following the 2017 USU LEAD Summit, working group participants reported that the meeting was valuable, should be repeated, and should address the specific topics of curriculum and assessment. Therefore, the 2018 Summit's goal was for participants to share experiences, ideas, and ways forward regarding leader and leadership curricula and assessment measures for UME. Themes from working groups were compiled and reported. Outcomes: Themes within LEAD curriculum include: (1) what to teach: relevant knowledge, skills, and abilities/attitudes (KSA) for specific topics; (2) when to teach: a life-cycle program woven through UME into graduate medical education and beyond; and (3) how to teach: near peers, development of mentors, and near-term, practical applications of skills. Themes within LEAD assessment include: (1) what to assess: alignment with program goals and curriculum within a positive culture of assessment and trust; (2) when to assess: occur at times that are consistent with the learning objectives and curriculum to provide information on incremental "growth" of students and the program; (3) how to assess: use formative and summative, qualitative and quantitative measures that are reliable and valid. Next steps: Based on feedback from working group participants at the 2018 Summit, the USU LEAD team will host a third Summit in April 2019 focusing on leader and leadership education and development across the healthcare work force life cycle.

Canavan disease (CD) is a fatal dysmyelinating genetic disorder associated with aspartoacylase deficiency, resulting in decreased brain acetate levels and reduced myelin lipid synthesis in the developing brain. Here we tested tolerability of a potent acetate precursor, glyceryl triacetate (GTA), at low doses in two infants diagnosed with CD, aged 8 and 13 months. Much higher doses of GTA were evaluated for toxicity in the tremor rat model of CD. GTA was given orally to the infants for up to 4.5 and 6 months, starting at 25 mg/kg twice daily, doubling the dose weekly until a maximum of 250 mg/kg reached. Wild-type and tremor rat pups were given GTA orally twice daily, initially at a dose of 4.2 g/kg from postnatal days 7 through 14, and at 5.8 g/kg from day 15 through 23, and thereafter in food (7.5%) and water (5%). At the end of the trial (approximately 90 to 120 days) sera and tissues from rats were analysed for changes in blood chemistry and histopathology. GTA treatment caused no detectable toxicity and the patients showed no deterioration in clinical status. In the high-dose animal studies, no significant differences in the mean blood chemistry values occurred between treated and untreated groups, and no lesions indicating toxicity were detectable in any of the tissues examined. Lack of GTA toxicity in two CD patients in low-dose trials, as well as in high-dose animal studies, suggests that higher, effective dose studies in human CD patients are warranted.

Exposure to nerve agents results in severe seizures or status epilepticus caused by the inhibition of acetylcholinesterase, a critical enzyme that breaks down acetylcholine to terminate neurotransmission. Prolonged seizures cause brain damage and can lead to long-term consequences. Current countermeasures are only modestly effective against the brain damage supporting interest in the evaluation of new and efficacious therapies. The nutraceutical alpha-linolenic acid (LIN) is an essential omega-3 polyunsaturated fatty acid that has a wide safety margin. Previous work showed that a single intravenous injection of alpha-linolenic acid (500 nmol/kg) administered before or after soman significantly protected against soman-induced brain damage when analyzed 24h after exposure. Here, we show that administration of three intravenous injections of alpha-linolenic acid over a 7 day period after soman significantly improved motor performance on the rotarod, enhanced memory retention, exerted an anti-depressant-like activity and increased animal survival. This dosing schedule significantly reduced soman-induced neuronal degeneration in four major vulnerable brain regions up to 21 days. Taken together, alpha-linolenic acid reduces the profound behavioral deficits induced by soman possibly by decreasing neuronal cell death, and increases animal survival.

Mesenchymal stromal cells secrete a variety of anti-inflammatory factors and may provide a regenerative medicine option for the treatment of traumatic brain injury. The present study investigates the efficacy of multiple intravenous or intracardiac administrations of rat mesenchymal stromal cells or human mesenchymal stromal cells in female rats after controlled cortical impact by in vivo MRI, neurobehavior, and histopathology evaluation. Neither intravenous nor intracardiac administration of mesenchymal stromal cells derived from either rats or humans improved MRI measures of lesion volume or neurobehavioral outcome compared to saline treatment. Few mesenchymal stromal cells (