Systematic review of pharmacological treatments that reduce conditioned taste aversions in rodents: A potential animal model of pediatric feeding disorder and avoidant/restrictive food intake disorder (ARFID).

Avoidant/restrictive food intake disorder (ARFID) is diagnosed when food avoidance leads to clinically significant nutritional, weight/growth, or psychosocial impairment. As many as 81.5% of children and adolescents diagnosed with ARFID have a history of a medical condition associated with pain, fatigue, or malaise. ARFID is diagnosed and treatment begins after the medical condition is resolved but food avoidance remains. Effective treatment involves repeated exposure to eating food and related stimuli aimed at creating inhibitory learning to counteract learned fears and aversions. Treatment usually involves positive reinforcement of food approach behavior and escape extinction/response prevention to eliminate food avoidant behavior. To shed light on the neural mechanisms that may maintain ARFID and to identify candidate pharmacological treatments for adjuncts to behavioral interventions, this paper systematically reviews research on drug treatments that successfully reduce conditioned taste aversions (CTA) in animal models by disrupting reconsolidation or promoting extinction. The mechanism of action of these treatments, brain areas involved, and whether these CTA findings have been used to understand human eating behavior are assessed. Collectively, the results provide insight into possible neural mechanisms associated with resuming oral intake following CTA akin to the therapeutic goals of ARFID treatment and suggest that CTA animal models hold promise to facilitate the development of interventions to prevent feeding problems. The findings also reveal the need to investigate CTA reduction in juvenile and female animals and show that CTA is rarely studied to understand disordered human feeding even though CTA has been observed in humans and parallels many of the characteristics of rodent CTA.

Angiotensin II-Mediated Neuroinflammation in the Hippocampus Contributes to Neuronal Deficits and Cognitive Impairment in Heart Failure Rats.

BACKGROUND: Heart failure (HF) is a debilitating disease affecting >64 million people worldwide. In addition to impaired cardiovascular performance and associated systemic complications, most patients with HF suffer from depression and substantial cognitive decline. Although neuroinflammation and brain hypoperfusion occur in humans and rodents with HF, the underlying neuronal substrates, mechanisms, and their relative contribution to cognitive deficits in HF remains unknown. METHODS: To address this critical gap in our knowledge, we used a well-established HF rat model that mimics clinical outcomes observed in the human population, along with a multidisciplinary approach combining behavioral, electrophysiological, neuroanatomical, molecular and systemic physiological approaches. RESULTS: Our studies support neuroinflammation, hypoperfusion/hypoxia, and neuronal deficits in the hippocampus of HF rats, which correlated with the progression and severity of the disease. An increased expression of AT1aRs (Ang II [angiotensin II] receptor type 1a) in hippocampal microglia preceded the onset of neuroinflammation. Importantly, blockade of AT1Rs with a clinically used therapeutic drug (Losartan), and delivered in a clinically relevant manner, efficiently reversed neuroinflammatory end points (but not hypoxia ones), resulting in turn in improved cognitive performance in HF rats. Finally, we show than circulating Ang II can leak and access the hippocampal parenchyma in HF rats, constituting a possible source of Ang II initiating the neuroinflammatory signaling cascade in HF. CONCLUSIONS: In this study, we identified a neuronal substrate (hippocampus), a mechanism (Ang II-driven neuroinflammation) and a potential neuroprotective therapeutic target (AT1aRs) for the treatment of cognitive deficits in HF.

Heart failure impairs mood and memory in male rats and down-regulates the expression of numerous genes important for synaptic plasticity in related brain regions.

Chronic heart failure (HF) is a serious disorder that afflicts more than 26 million patients worldwide. HF is comorbid with depression, anxiety and memory deficits that have serious implications for quality of life and self-care in patients who have HF. Still, there are few studies that have assessed the effects of severely reduced ejection fraction (≤40 %) on cognition in non-human animal models. Moreover, limited information is available regarding the effects of HF on genetic markers of synaptic plasticity in brain areas critical for memory and mood regulation. We induced HF in male rats and tested mood and anxiety (sucrose preference and elevated plus maze) and memory (spontaneous alternation and inhibitory avoidance) and measured the simultaneous expression of 84 synaptic plasticity-associated genes in dorsal (DH) and ventral hippocampus (VH), basolateral (BLA) and central amygdala (CeA) and prefrontal cortex (PFC). We also included the hypothalamic paraventricular nucleus (PVN), which is implicated in neurohumoral activation in HF. Our results show that rats with severely reduced ejection fraction recapitulate behavioral symptoms seen in patients with chronic HF including, increased anxiety and impaired memory in both tasks. HF also downregulated several synaptic-plasticity genes in PFC and PVN, moderate decreases in DH and CeA and minimal effects in BLA and VH. Collectively, these findings identify candidate brain areas and molecular mechanisms underlying HF-induced disturbances in mood and memory.

Program Administrator Burnout in Graduate Medical Education: a Longitudinal Study.

BACKGROUND: Little is known about the level of burnout among program administrators (PAs) in medical education and its impact on the trainee environment. OBJECTIVE: To investigate variations in burnout levels over a 1-year period among a national cohort of PAs and examine any associations between perceived support and isolation. DESIGN: A 1-year longitudinal study conducted to assess burnout levels among PAs across the USA. The Copenhagen Burnout Inventory (score range, 0-100) was used to measure burnout over one academic year (July 2017-June 2018). The generalized estimating equations model was used to measure changes in burnout levels from the start of the academic year. To explore the differences in burnout scores across question response levels, a one-way ANOVA test was utilized and reported as least squares means ± SD. PARTICIPANTS: Individuals who self-identified as PAs in a graduate medical education training program. Among the 1084 persons nationwide who expressed interest, 904 (83%) completed the baseline survey; 29 of the 42 (69%) local administrators completed the survey. "Clients" defined as interns, residents/fellows, and medical students. MAIN MEASURES: Change in burnout score using the validated tool. Hypothesis formulated prior to data collection. KEY RESULTS: Among the 931 participants, the 3rd quarter (March 2018) marked the lowest average personal burnout score (change from the start of academic year, - 3.67; p < 0.001, 95% CI - 5.77 to - 1.58) and work-related burnout score (change, - 3.03; p < 0.001, 95% CI - 5.01 to - 1.06). Client-related burnout was the lowest in September 2017 (change, - 1.46; p = 0.491; 95% CI - 3.54 to 0.62). June 2018: those who strongly agreed to feeling isolated in their current position had an increased personal (69.1 ± 18.4 SD), work-related (72.5 ± 20.8 SD), and client-related (42.3 ± 23.7 SD) burnout score. CONCLUSIONS: PA burnout levels fluctuate over the academic year and are shown to increase as feelings of isolation grow.

Residency and Fellowship Program Administrator Burnout: Measuring Its Magnitude.

BACKGROUND: Little is known about the level of burnout among program administrators (PAs) working in graduate medical education. OBJECTIVE: We created a national database with baseline burnout data for PAs from residency and fellowship programs, including intention to leave their current positions. METHODS: A cross-sectional study was conducted in July 2017 to assess levels of burnout in a national cohort of PAs, who were largely members of online specialty forums. The Copenhagen Burnout Inventory (CBI) was used to measure burnout. Univariate analysis produced descriptive statistics for CBI. We performed a 2-sample t test to measure differences in average burnout scores for those who had thoughts of resigning from their positions and those who had not. RESULTS: Of the approximately 10 205 national PAs, we sampled 1126 (11%). Of the 1126 individuals who received the study information, 931 (83%) completed the baseline survey. Total mean scores for all subscales were elevated (personal: 53.7, SD 21.4; work-related: 52.0, SD 22; and client-related: 30.6, SD 20.8; each scale ranged from 0, low, to 100, high). Burnout scores differed between those contemplating leaving their jobs and those who were not, across all subscales of CBI, including personal (64.2 versus 42.4, -24.18 to -19.44 confidence interval [CI]), work-related (63.5 versus 39.7, -26.12 to -21.35 CI), and client-related (36.6 versus 24.2, -14.95 to -9.84 CI; P < .0001 for all). CONCLUSIONS: In this national survey of PAs, burnout scores measured by the CBI were higher among those who had considered leaving their positions.

We Matter Too! Addressing the Wellness of Program Coordinators in Graduate Medical Education.

INTRODUCTION: Burnout and stress in medical settings have been associated with despondent staff and decreased productivity. Although Program Coordinators (PCs) play an integral role in residency training programs, there exist few, if any, interventions aimed at addressing their burnout. METHODS: A longitudinal study design was used to evaluate data from residency/fellowship training PCs who participated in a wellness retreat held at a single institution in August 2016. Subjects completed anonymous, pre- and post-retreat questionnaires in addition to a 3-month follow-up questionnaire, which included questions used to assess aspects of job demand, resiliency, and well-being. The seven-item Physician Well-Being Index and a logistic regression model were used to assess well-being. Mean values and SDs were reported to examine changes in mental health scores and participants' job satisfaction over the course of the intervention. RESULTS: Nineteen of the 45 (43%) invited residency/fellowship training PCs completed data collection. Coordinators ranged in age from 25 to 64 years; all were female. Well-being, sleep, resiliency, and employee satisfaction scores improved over the assessment period. Well-being scores initially decreased by 0.37 at the postassessment, but increased at follow-up (mean: 2.0; SD 1.7). Stress scores increased from baseline to post, but decreased from baseline to follow-up: 0.2 and -0.2, respectively. DISCUSSION: Residency PCs experienced improvements in mental quality of life, resiliency, stress, and sleep scores on attending the wellness program. Attention to such findings may have important implications, as we address the burnout crisis in the medical education community.