Introducing lifestyle medicine into family medicine: Theory and applications.

"Lifestyle medicine (LM) is an evidence-based therapeutic intervention delivered by clinicians trained and certified in this specialty to prevent, treat, and often reverse chronic disease". Eighty percent of the conditions primary care physicians routinely encounter in their offices, e.g., diabetes mellitus, hypertension, COPD, cardiovascular disease, have root causes in poor lifestyle choices, e.g., smoking, insufficient sleep, being sedentary, eating highly processed foods. Lifestyle is the foundation of most chronic disease management guidelines aimed at reducing morbidity and mortality. Studies have shown that changes in lifestyle can be achieved and the changes link almost directly to reduction in risk for chronic illness. Primary care physicians are ideally positioned to incorporate LM into their practices. It is important to recognize and find solutions to the many barriers to implementing LM from the patient, physician, and system level. There is an urgent need to increase opportunities for practicing physicians to increase their knowledge and skills related to LM and include this in medical school and residency curricula. Many resources exist that can provide the necessary training to seasoned physicians and students/residents to become competent in practicing LM and address barriers to implementing LM. LM has the potential to revolutionize clinical practice by placing a greater emphasis on disease prevention and the role of healthy lifestyle behaviors in disease management and remission.

A Stress Management Program for Higher Risk Medical Students: Preliminary Findings.

Approximately 10 % of first year medical students have clinically relevant anxiety or depression which may affect academic success and quality of life. This study tested the effects of a stress management intervention on indicators of anxiety, depression and self-efficacy in self-selected first year medical students. Forty two medical students volunteered to participate and provided informed consent. An eight session intervention was offered and focused on building relaxation skills, adaptive coping, and basic nutrition. Anxiety, depression, and self-efficacy were assessed pre and post intervention. This group of students had significantly higher baseline values of depression and anxiety but lower self-efficacy compared to a previous study of medical students at the same institution (p < 0.03). After the intervention, statistically significant improvements were observed in anxiety (p < 0.05), and self-efficacy (p < 0.05), but not in depression. The entering levels of anxiety and depression in this group suggested that these students were at risk for later clinical syndromes. Intervention directed to decreasing the effects of stress was associated with improvement in indicators of distress and may modify the longer term risk.

Phosphodiesterase 11A in brain is enriched in ventral hippocampus and deletion causes psychiatric disease-related phenotypes.

Phosphodiesterase 11A (PDE11A) is the most recently identified family of phosphodiesterases (PDEs), the only known enzymes to break down cyclic nucleotides. The tissue expression profile of this dual specificity PDE is controversial, and little is understood of its biological function, particularly in the brain. We seek here to determine if PDE11A is expressed in the brain and to understand its function, using PDE11A(-/-) knockout (KO) mice. We show that PDE11A mRNA and protein are largely restricted to hippocampus CA1, subiculum, and the amygdalohippocampal area, with a two- to threefold enrichment in the ventral vs. dorsal hippocampus, equal distribution between cytosolic and membrane fractions, and increasing levels of protein expression from postnatal day 7 through adulthood. Interestingly, PDE11A KO mice show subtle psychiatric-disease-related deficits, including hyperactivity in an open field, increased sensitivity to the glutamate N-methyl-D-aspartate receptor antagonist MK-801, as well as deficits in social behaviors (social odor recognition memory and social avoidance). In addition, PDE11A KO mice show enlarged lateral ventricles and increased activity in CA1 (as per increased Arc mRNA), phenotypes associated with psychiatric disease. The increased sensitivity to MK-801 exhibited by PDE11A KO mice may be explained by the biochemical dysregulation observed around the glutamate alpha-amino-3-hydroxy-5-methyl-4-isozazolepropionic (AMPA) receptor, including decreased levels of phosphorylated-GluR1 at Ser845 and the prototypical transmembrane AMPA-receptor-associated proteins stargazin (gamma2) and gamma8. Together, our data provide convincing evidence that PDE11A expression is restricted in the brain but plays a significant role in regulating brain function.

Comparing Resident and Program Director Perspectives on Wellness Curricula: A CERA Study.

Introduction: Mitigating the stress of graduate medical education has been the focus of residency leadership in the United States. This study examined family medicine (FM) resident and program director (PD) satisfaction with current wellness curricula, including perceptions of availability of resources and emphasis on well-being. Methods: The Council of Academic Family Medicine Educational Research Alliance administered online surveys to PDs accredited by the Accreditation Council for Graduate Medical Education, US-based FM residencies, and resident American Academy of Family Physicians members from April to May 2021. The present study included an assessment of wellness curriculum implementation using the Wellness Element Count (WEC), a satisfaction rating with wellness programming, and a single question assessing perceived changes in emphasis on wellness during COVID-19. Results: A total of 242 residents (5% response rate) and 263 PDs (42% response rate) completed the survey. Residents reported lower WEC indicators compared to PDs (P<.001). Overall, 67.8% of resident respondents were satisfied with their program's wellness efforts, compared to 89.3% of PDs ( P<.001). Perceived emphasis on wellness curricula in the program was associated with greater resident satisfaction (OR=2.75, P<.05); less emphasis on wellness was associated with less resident satisfaction (OR=0.15, P<.001). Conclusions: Residents reported overall lower perceived availability and satisfaction with program wellness efforts compared to PDs, suggesting a disparity between perspectives. Ongoing efforts should be directed at encouraging use of available wellness resources and supporting a culture of well-being.

Novel triazines as potent and selective phosphodiesterase 10A inhibitors.

The identification of highly potent and orally active triazines for the inhibition of PDE10A is reported. The new analogs exhibit low-nanomolar potency for PDE10A, demonstrate high selectivity against all other members of the PDE family, and show desired drug-like properties. Employing structure-based drug design approaches, we investigated the selectivity of PDE10A inhibitors against other known PDE isoforms, by methodically exploring the various sub-regions of the PDE10A ligand binding pocket. A systematic assessment of the ADME and pharmacokinetic properties of the newly synthesized compounds has led to the design of drug-like candidates with good brain permeability and desirable drug kinetics (t(1/2), bioavailability, clearance). Compound 66 was highly potent for PDE10A (IC(50)=1.4 nM), demonstrated high selectivity (>200×) for the other PDEs, and was efficacious in animal models of psychoses; reversal of MK-801 induced hyperactivity (MED=0.1mg/kg) and conditioned avoidance responding (CAR; ID(50)=0.2 mg/kg).

A wellness program for first year medical students.

Entering medical students experience distress symptoms due to the demands of the intensive curriculum, adjustment to new environments and increased responsibilities. The purpose of this controlled, randomized study was to determine the effects of a structured wellness program on measures of anxiety, depression and frequency of acute illness in 449 first year medical students. The effects of eight sessions of stress management were compared to a wait list control group. High risk students were identified based on scores on psychological inventories and number of recent life events (WLE). Results showed that depression, anxiety scores and frequency of acute illness were higher in women than in men, and were higher in students with multiple life events. Significant decreases were observed in depression in the intervention group students when WLE was the covariate (p = .045). Further, the high risk group showed consistently lower depression scores after the intervention compared to high risk wait list controls (p = .003), and these changes were maintained at the end of school year. There were no significant changes in anxiety or frequency of acute illness. Wellness programs can be implemented in medical school and may be particularly useful for entering students with elevated psychological distress.

Evaluating Changes in Family Medicine Applicant Characteristics Following the Onset of Virtual Interviewing.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic obliged the field of graduate medical education to pivot from in-person to virtual residency interviews in 2020. The decreased travel and financial barriers of this format could potentially lead to greater diversity and equity in the primary care workforce. We aimed to evaluate changes in applicant pools from in-person to virtual interviewing cycles. METHODS: We conducted a retrospective review of Electronic Residency Application Services (ERAS) from five US family medicine residencies across five interview cycles (three in-person and two virtual; 2017/2018 through 2021/2022). We compared geographic and demographic data about applicants as well as administrative program data. RESULTS: The study included 25,271 applicants. The average distance between applicants and programs was 768 miles during in-person interview years and 772 miles during virtual interview years (P=.27). Applicants who interviewed with programs were 446 and 459 miles away, respectively (P=.06). During in-person application years, applicants with backgrounds historically underrepresented in medicine (URM) submitted an average of 21% of applications; this increased approximately 1% during virtual interviewing years (OR, 1.08; P=.03). There were no other differences between in-person and virtual application years in rates of URM applicants. Residency programs received more applications from US medical schools (OR, 1.46; P<.0001) and were more likely to interview a US medical school applicant (OR, 2.26; P<.0001) in virtual years. Program fill rates appeared to be lower during virtual years. CONCLUSIONS: The virtual interviewing format did not appear to substantially increase the geographic, racial, or ethnic diversity of applicants, and was associated with increased applications from US medical schools.

Wellness in the Time of COVID: A CERA Follow-up Survey of Program Directors.

BACKGROUND AND OBJECTIVES: Residency program directors (PDs) are tasked with supporting resident well-being, and a 2018-2019 CERA survey found PDs to be generally satisfied with residency wellness curricula. However, less is known about graduate medical education wellness programming following the unprecedented social and public health stressors of 2020. This study aimed to evaluate PDs' satisfaction with wellness programming and perceived changes in wellness program implementation in the context of these factors. METHODS: An online survey was administered by CERA to the program directors of all ACGME-accredited, US-based family medicine residencies. The survey replicated a 2018 CERA survey and assessed PDs' satisfaction with the wellness curriculum and which wellness curricular elements were currently implemented in the residency. RESULTS: The survey was completed by 263 PDs (42% response rate). There was no difference in total number of wellness curricular elements reported in programs in 2021 (M=9.85) vs 2018 (M=9.57; P=.377). Compared to the 2018 survey, PDs reported increased assessment of resident burnout (P=.02), increased scheduled time for personal needs (P=.002), but decreased scheduled time for interpersonal connection (P=.017). Most PDs reported increased emphasis on wellness and the same or increased access to wellness resources compared to 2018 χ2 indicated no significant difference in PD satisfaction with wellness programming between the two years (P=.84). CONCLUSIONS: Despite significant social and public health challenges to curriculum delivery, family medicine PDs did not perceive significant reductions in wellness programming, and in fact reported increases in some specific curricular elements and an overall increased emphasis on well-being. Future studies should explore the factors that facilitate and impede the implementation of wellness programming.

WS-50030 [7-{4-[3-(1H-inden-3-yl)propyl]piperazin-1-yl}-1,3-benzoxazol-2(3H)-one]: a novel dopamine D2 receptor partial agonist/serotonin reuptake inhibitor with preclinical antipsychotic-like and antidepressant-like activity.

The preclinical characterization of WS-50030 [7-{4-[3-(1H-inden-3-yl)propyl]piperazin-1-yl}-1,3-benzoxazol-2(3H)-one] is described. In vitro binding and functional studies revealed highest affinity to the D(2) receptor (D(2L) K(i), 4.0 nM) and serotonin transporter (K(i), 7.1 nM), potent D(2) partial agonist activity (EC(50), 0.38 nM; E(max), 30%), and complete block of the serotonin transporter (IC(50), 56.4 nM). Consistent with this in vitro profile, WS-50030 (10 mg/kg/day, 21 days) significantly increased extracellular 5-HT in the rat medial prefrontal cortex, short-term WS-50030 treatment blocked apomorphine-induced climbing (ID(50), 0.51 mg/kg) in a dose range that produced minimal catalepsy in mice and induced low levels of contralateral rotation in rats with unilateral substantia nigra 6-hydroxydopamine lesions (10 mg/kg i.p.), a behavioral profile similar to that of the D(2) partial agonist aripiprazole. In a rat model predictive of antipsychotic-like activity, WS-50030 and aripiprazole reduced conditioned avoidance responding by 42 and 55% at 10 mg/kg, respectively. Despite aripiprazole's reported lack of effect on serotonin transporters, long-term treatment with aripiprazole or WS-50030 reversed olfactory bulbectomy-induced hyperactivity at doses that did not reduce activity in sham-operated rats, indicating antidepressant-like activity for both compounds. Despite possessing serotonin reuptake inhibitory activity in addition to D(2) receptor partial agonism, WS-50030 displays activity in preclinical models predictive of antipsychotic- and antidepressant efficacy similar to aripiprazole, suggesting potential efficacy of WS-50030 versus positive and negative symptoms of schizophrenia, comorbid mood symptoms, bipolar disorder, major depressive disorder, and treatment-resistant depression. Furthermore, WS-50030 provides a tool to further explore how combining these mechanisms might differentiate from other antipsychotics or antidepressants.

Getting It Off the Ground: Key Factors Associated With Implementation of Wellness Programs.

BACKGROUND AND OBJECTIVES: Many residency programs are developing resident wellness curricula to improve resident well-being and to meet Accreditation Council for Graduate Medical Education guidelines. However, there is limited guidance on preferred curricular components and implementation. We sought to identify how specific driving factors (eg, having an identified wellness champion with a budget and protected time to develop wellness programs) impact implementation of essential elements of a resident wellness curriculum. METHODS: We surveyed 608 family medicine residency program directors (PDs) in 2018-2019 on available resources for wellness programs, essential wellness elements being implemented, and satisfaction with wellness programming; 251 PDs provided complete responses (42.5% response rate). Linear and logistic regressions were conducted for main analyses. RESULTS: Having an identified wellness champion, protected time, and dedicated budget for wellness were associated with greater implementation of wellness programs and PD satisfaction with wellness programming; of these, funding had the strongest association. Larger programs were implementing more wellness program components. Program setting had no association with implementation. CONCLUSIONS: PDs in programs allocating money and/or faculty time can expect more wellness programming and greater satisfaction with how resident well-being is addressed.

Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia.

Following several recent reports that suggest that dual cAMP and cGMP phosphodiesterase 10A (PDE10A) inhibitors may present a novel mechanism to treat positive symptoms of schizophrenia, we sought to extend the preclinical characterization of two such compounds, papaverine [1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline] and MP-10 [2-{[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)phenoxy]methyl}quinoline], in a variety of in vivo and in vitro assays. Both of these compounds were active in a range of antipsychotic models, antagonizing apomorphine-induced climbing in mice, inhibiting conditioned avoidance responding in both rats and mice, and blocking N-methyl-D-aspartate antagonist-induced deficits in prepulse inhibition of acoustic startle response in rats, while improving baseline sensory gating in mice, all of which strengthen previously reported observations. These compounds also demonstrated activity in several assays intended to probe negative symptoms and cognitive deficits, two disease domains that are underserved by current treatments, with both compounds showing an ability to increase sociality in BALB/cJ mice in the social approach/social avoidance assay, enhance social odor recognition in mice and, in the case of papaverine, improve novel object recognition in rats. Biochemical characterization of these compounds has shown that PDE10A inhibitors modulate both the dopamine D1-direct and D2-indirect striatal pathways and regulate the phosphorylation status of a panel of glutamate receptor subunits in the striatum. It is striking that PDE10A inhibition increased the phosphorylation of the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor GluR1 subunit at residue serine 845 at the cell surface. Together, our results suggest that PDE10A inhibitors alleviate both dopaminergic and glutamatergic dysfunction thought to underlie schizophrenia, which may contribute to the broad-spectrum efficacy.

Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia.

A 5-fluoro-tetrahydrocarbazole serotonin reuptake inhibitor (SRI) building block was combined with a variety of linkers and dopamine D2 receptor ligands in an attempt to identify potent D2 partial agonist/SRI molecules for treatment of schizophrenia. This approach has the potential to treat a broader range of symptoms compared to existing therapies. Selected compounds in this series demonstrate high affinity for both targets and D2 partial agonism in cell-based and in vivo assays.

Effects of wellness programs in family medicine.

The objective of this research was to determine the effects of wellness programs on quality of life and utilization in an academic family medicine practice in two small controlled studies. One offered stress management and problem solving; the second offered a broader wellness intervention. Outcome measures consisted of scores on the Beck Anxiety Inventory, Hamilton Depression Inventory, CES-D (depression), Health Related Quality of Life, SF-12, and the number of office visits in 6 months. Subjects were randomly assigned to intervention or control groups. Statistical analysis compared pre-test and post-test values of the dependent variables between groups. In study one, where the focus was on relaxation, significant differences between groups were observed in anxiety at post-test (p < .03); the intervention group had lower anxiety levels. In study two which had a more general focus, significant group differences were found in days of poor mental health and number of days of depressed mood; the intervention group had fewer days of poor mental health (p < .05) and depression (p < .05) at post-test. No differences were found in utilization in either study. Based on the results of this research, short term wellness programs can be implemented in family practice and are effective in improving quality of life, but not in deceasing utilization in family practice patients. Matching the design of the program to specific patient needs may increase retention and effectiveness.

Making Sense of Family Medicine Resident Wellness Curricula: A Delphi Study of Content Experts.

BACKGROUND AND OBJECTIVES: The Association of Family Medicine Residency Directors (AFMRD) Physician Wellness Task Force released a comprehensive Well-Being Action Plan as a guide to help programs create a culture of wellness. The plan, however, does not offer a recommendation as to which elements may be most important, least resource intensive, or most feasible. This study sought to identify the most essential components of the AFMRD's Well-Being Action Plan, as rated by expert panelists using a modified Delphi technique. METHODS: Sixty-eight selected experts were asked to participate; after three rounds of surveys, the final sample included 27 participants (7% residents, 38% MD faculty, 54% behavioral science faculty). RESULTS: Fourteen elements were rated as essential by at least 80% of the participants. These components included interventions at both the system and individual level. Of those elements ranked in the top five by a majority of the panel, all but one do not mention specific curricular content, but rather discusses the nature of a wellness curriculum. CONCLUSIONS: The expert consensus was that an essential curriculum should begin early, be longitudinal, identify a champion, and provide support for self-disclosure of struggles.

Antidepressant-like effects of the novel, selective, 5-HT2C receptor agonist WAY-163909 in rodents.

RATIONALE: Activation of one or more of the serotonin (5-HT) receptors may play a role in mediating the antidepressant effects of SSRIs. OBJECTIVE: The present studies were conducted to evaluate the effects of the novel 5-HT2C receptor agonist WAY-163909 in animal models of antidepressant activity (forced swim test (FST), resident-intruder, olfactory bulbectomy (BULB)), in a schedule-induced polydipsia (SIP) model of obsessive-compulsive disorder and in a model for evaluating sexual dysfunction. RESULTS: WAY-163909 (10 mg/kg, i.p. or s.c.) decreased immobility time in Wistar-Kyoto rats in the FST, effects that were reversed by the 5-HT2C/2B receptor antagonist SB 206553. Moreover, in Sprague-Dawley rats, the profile of WAY-163909 (decreased immobility, increased swimming) in the FST was comparable to the effects of SSRIs. Acute treatment with WAY-163909 (0.33 mg/kg, s.c.) decreased rodent aggression at doses lower than those required for decreasing total behavior. Administration of WAY-163909 (3 mg/kg, i.p.) for 5 or 21 days decreased the BULB-induced hyperactivity in rats. Additionally, acute administration of WAY-163909 (3 mg/kg, i.p.) decreased adjunctive drinking in a SIP model. The effects of WAY-163909 were reversed by the 5-HT(2C/2B) receptor antagonist SB 206553 and the selective 5-HT2C receptor antagonist SB 242084. Chronic administration of WAY-163909 produced deficits in sexual function at doses higher (10 mg/kg, i.p.) than those required for antidepressant-like effects in the BULB model. CONCLUSIONS: Taken together, these results demonstrate that the novel 5-HT2C receptor agonist WAY-163909 produces rapid onset antidepressant-like effects in animal models and may be a novel treatment for depression.

Effects of a stress management program on third year medical students' anxiety depression and somatization.

This article was migrated. The article was marked as recommended. Background: Transition from the medical school classroom to the clinical training years requires students to adapt in many ways. Schedules are more variable, with longer clinic hours and travel to affiliated hospitals. Students are also faced with emotional needs of patients coincident with meeting demands from attending physicians. The prevalence of anxiety, depression and overall distress increases during the four years of medical school and particularly during difficult transitions. Methods: Forty medical students entering their first clinical year enrolled in a two session stress management program focused on mindfulness and coping strategies. Sessions were interactive, conducted by a psychologist, social worker and a counselor and comprised evidenced based components. Results: Twenty nine students completed the program. Baseline comparisons between dropouts and eventual completers showed that dropouts were more likely to screen positive for depression, anxiety and somatic tendencies. Program completers evidenced short term increased knowledge about mindfulness and coping and demonstrated significant decreases in anxiety and somatization at the end of the program. Conclusion: Though scheduling of any additional programs during the clinical years of medical school presents significant challenges, students who complete such a program sustain important benefits and evaluate the program positively.

Aplindore (DAB-452), a high affinity selective dopamine D2 receptor partial agonist.

The pharmacology of aplindore (DAB-452) was characterized in CHO-K1 cells stably transfected with the human dopamine D(2) receptor short isoform (CHO-D(2s)) and in a behavioral model for post-synaptic agonism in rats. In [(3)H]-spiperone competition binding studies, aplindore showed high affinity for dopamine D(2) and D(3) receptors and low affinity for the dopamine D(4), serotonin (5-HT)(1A), 5-HT(2) receptors and the alpha1-adrenoceptor. The high potency partial agonist activity of aplindore was demonstrated in [(35)S]guanosine 5'-O-(3-thiotriphosphate) ([(35)S]GTPgammaS) binding, extracellular signal-regulated kinase (ERK)-phosphorylation and intracellular calcium flux assay using fluorometric plate reader ([Ca(2+)](i)-FLIPR) format. The [Ca(2+)](i)-FLIPR assay was conducted with CHO-D(2S) receptor cells also stably expressing chimeric G(alphaq/o)-proteins. In all assay modalities, the potencies and intrinsic activities of aplindore were lower than dopamine and higher than aripiprazole. In contrast to the [(35)S]GTPgammaS binding and ERK-phosphorylation assays, the [Ca(2+)](i)-FLIPR assay was able to detect the low partial agonist activity of SDZ 208-912. In unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, aplindore induced contralateral turning, which was blocked by the dopamine D(2) receptor antagonist raclopride. The dopamine D(2) receptor selective partial agonist profile of aplindore suggests that it should be effective for the treatment of dopaminergic-based disorders, such as schizophrenia and Parkinson's disease.

Curricular integration of social medicine: a prospective for medical educators.

In the United States, the health of a community falls on a continuum ranging from healthy to unhealthy and fluctuates based on several variables. Research policy and public health practice literature report substantial disparities in life expectancy, morbidity, risk factors, and quality of life, as well as persistence of these disparities among segments of the population. One such way to close this gap is to streamline medical education to better prepare our future physicians for our patients in underserved communities. Medical schools have the potential to close the gap when training future physicians by providing them with the principles of social medicine that can contribute to the reduction of health disparities. Curriculum reform and systematic formative assessment and evaluative measures can be developed to match social medicine and health disparities curricula for individual medical schools, thus assuring that future physicians are being properly prepared for residency and the workforce to decrease health inequities in the United States. We propose that curriculum reform includes an ongoing social medicine component for medical students. Continued exposure, practice, and education related to social medicine across medical school will enhance the awareness and knowledge for our students. This will result in better preparation for the zero mile stone residency set forth by the Accreditation Council of Graduate Medical Education and will eventually lead to the outcome of higher quality physicians in the United States to treat diverse populations.