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High dietary fat causes increased bile acid secretion into the gastrointestinal tract and is associated with colon cancer. Since the bile acid deoxycholic acid (DOC) is suggested to be important in colon cancer etiology, this study investigated whether DOC, at a high physiologic level, could be a colon carcinogen. Addition of 0.2% DOC for 8–10 months to the diet of 18 wild-type mice induced colonic tumors in 17 mice, including 10 with cancers. Addition of the antioxidant chlorogenic acid at 0.007% to the DOC-supplemented diet significantly reduced tumor formation. These results indicate that a high fat diet in humans, associated with increased risk of colon cancer, may have its carcinogenic potential mediated through the action of bile acids, and that some dietary anti-oxidants may ameliorate this carcinogenicity.

Recent evidence indicates that meiosis arose very early in eukaryotic evolution, which suggests that essential features of meiosis were already present in the prokaryotic ancestors of eukaryotes. Furthermore, in extant organisms, proteins with central functions in meiosis are similar in sequence and function to key proteins in bacterial transformation. In particular, RecA recombinase—which performs the central functions of DNA homology search and strand exchange in bacterial transformation—has orthologs in eukaryotes that carry out similar functions in meiotic recombination. Both transformation and meiosis (including meiotic recombination) in eukaryotic microorganisms are induced by stressful conditions, such as overcrowding, resource depletion, and DNA-damaging conditions, suggesting that these processes are adaptations for dealing with stress. If such environmental stresses were a persistent challenge to the survival of early microorganisms, then continuity of selection through the prokaryote to eukaryote transition probably would have followed a course in which bacterial transformation naturally gave rise to the recombination process that is central to eukaryote meiosis.

Purpose: Healthcare organizations strive to increase physician engagement and decrease attrition. However, little is known about which specific worklife areas may be targeted to improve physician engagement or retention, especially after stressful events such as a COVID19 surge. Our objective was to identify demographic characteristics and worklife areas most associated with increased physician engagement and decreased intent to leave in pediatric faculty. Patients and Methods: In September 2020, we conducted a cross-sectional survey of faculty at an academic, tertiary-care children's hospital. A convenience and voluntary sampling approach was used. The survey included demographics, Maslach Burnout Index-Human Services Survey (MBI-HSS) and the Areas of Worklife Survey (AWS). The MBI-HSS was used to measure faculty engagement. The AWS measures satisfaction with six worklife areas (workload, control, reward, fairness, community, values). We used bivariate analyses to examine relationships between worklife areas and engagement and between worklife areas and intent to leave. We included multivariate logistic regression models to examine worklife areas most associated with increased work engagement and decreased intent to leave. Results: Our response rate was 41% (113/274 participants). In bivariate analysis, engaged faculty reported higher satisfaction in all worklife areas. In multivariate analyses, positive perceptions of workload (odds ratio (OR) 2.83; 95% confidence interval (CI), 1.2-6.9), control (OR, 3.24; 95% CI 1.4-7.3), and community (OR, 6.07; 95% CI 1.9-18.7) were associated with engagement. Positive perceptions of values (OR, 0.07; 95% CI 0.02-0.32) and community (OR, 0.19; 95% CI 0.05-0.78) were negatively associated with intent to leave. Conclusion: We found that positive perceptions of workload, control, and community were most associated with engagement. Alignment of values and increased sense of community were associated with decreased intent to leave. Our findings suggest specific worklife areas may be targeted to increase faculty engagement and retention. Plain Language Summary: Physician engagement and retention are growing concerns for healthcare organizations. We conducted a cross-sectional survey of pediatric faculty after a COVID19 surge in 2020 to examine whether there are worklife areas highly associated with physician engagement and decreased intent to leave their current practice. We found that respondents with high positive perceptions of their workload, autonomy and community in their workplace were more likely to be engaged, and that respondents who felt that their values aligned with their organization's values and felt a positive sense of community were less likely to report intent to leave the organization. Prioritizing improvements in physician workload, autonomy, and community, and recruiting physicians with similar values may be an effective strategy for organizations who desire to increase physician engagement and retention. Keywords: physician burnout, workforce, physician well-being

A single event can cause a life-long memory. Memories physically reside in neurons, and changes in neuronal gene expression are considered to be central to memory. Early models proposed that specific DNA methylations of cytosines in neuronal DNA encode memories in a stable biochemical form. This review describes recent research that elucidates the molecular mechanisms used by the mammalian brain to form DNA methylcytosine encoded memories. For example, neuron activation initiates cytosine demethylation by stimulating DNA topoisomerase II beta (TOP2B) protein to make a temporary DNA double-strand break (repaired within about 2 hours) at a promoter of an immediate early gene, EGR1, allowing expression of this gene. The EGR1 proteins then recruit methylcytosine dioxygenase TET1 proteins to initiate demethylation at several hundred genes, facilitating expression of those genes. Initiation of demethylation of cytosine also occurs when OGG1 localizes at oxidized guanine in a methylated CpG site and recruits TET1 for initiation of demethylation at that site. DNMT3A2 is another immediate early gene upregulated by synaptic activity. DNMT3A2 protein catalyzes de novo DNA methylations. These several mechanisms convert external experiences into DNA methylations and initiated demethylations of neuronal DNA cytosines, causing changes in gene expression that are the basis of long-term memories.

Background There is growing recognition that wellness interventions should occur in context and acknowledge complex contributors to wellbeing, including individual needs, institutional and cultural barriers to wellbeing, as well as systems issues which propagate distress. The authors conducted a multiple-methods study exploring contributors to wellbeing for junior residents in diverse medical environments who participated in a brief resilience and stress-reduction curriculum, the Stress Management and Resiliency Training Program for Residents (SMART-R). Methods Using a waitlist-controlled design, the curriculum was implemented for post-graduate year (PGY)-1 or PGY-2 residents in seven residency programs across three sites. Every three months, residents completed surveys, including the Perceived Stress Scale-10, General Self-Efficacy Questionnaire, a mindfulness scale (CAMSR), and a depression screen (PHQ-2). Residents also answered free-text reflection questions about psychological wellbeing and health behaviors. Results The SMART-R intervention was not significantly associated with decreased perceived stress. Linear regression modeling showed that depression was positively correlated with reported stress levels, while male sex and self-efficacy were negatively correlated with stress. Qualitative analysis elucidated differences in these groups: Residents with lower self-efficacy, those with a positive depression screen, and/or female residents were more likely to describe experiencing lack of control over work. Residents with higher self-efficacy described more positive health behaviors. Residents with a positive depression screen were more self-critical, and more likely to describe negative personal life events. Conclusions This curriculum did not significantly modify junior residents’ stress. Certain subpopulations experienced greater stress than others (female residents, those with lower self-efficacy, and those with a positive depression screen). Qualitative findings from this study highlight universal stressful experiences early in residency, as well as important differences in experience of the learning environment among subgroups. Tailored wellness interventions that aim to support diverse resident sub-groups may be higher yield than a “one size fits all” approach. Trial registration NCT02621801 , Registration date: December 4, 2015 – Retrospectively registered.

Tertiary treatment interventions are designed to improve access to mental health services for physicians and trainees who are experiencing more severe distress, burnout, or mental health problems. [...]a robust screening program without an accessible connection to adequate mental health services may be minimally effective. Population-specific screening tools have also been developed, including the Medical Student Well-Being Index [32], the postgraduate hospital educational environment measure (PHEEM) [33], and the Professional Quality of Life Scale (PROQOL) [34]. Physicians (as well as other health care professionals) face significant barriers to mental health treatment, including time, confidentiality

Sporadic colon cancer is caused predominantly by dietary factors. We have selected bile acids as a focus of this review since high levels of hydrophobic bile acids accompany a Western-style diet, and play a key role in colon carcinogenesis. We describe how bile acid-induced stresses cause cell death in susceptible cells, contribute to genomic instability in surviving cells, impose Darwinian selection on survivors and enhance initiation and progression to colon cancer. The most likely major mechanisms by which hydrophobic bile acids induce stresses on cells (DNA damage, endoplasmic reticulum stress, mitochondrial damage) are described. Persistent exposure of colon epithelial cells to hydrophobic bile acids can result in the activation of pro-survival stress-response pathways, and the modulation of numerous genes/proteins associated with chromosome maintenance and mitosis. The multiple mechanisms by which hydrophobic bile acids contribute to genomic instability are discussed, and include oxidative DNA damage, p53 and other mutations, micronuclei formation and aneuploidy. Since bile acids and oxidative stress decrease DNA repair proteins, an increase in DNA damage and increased genomic instability through this mechanism is also described. This review provides a mechanistic explanation for the important link between a Western-style diet and associated increased levels of colon cancer.

The mental health effects of medical training are becoming increasingly well-documented, with high rates of burnout, depression, and suicide among residents, fellows, and physicians in practice [3, 4]. [...]current research studies on interventions aimed at improving trainee well-being are primarily exploratory or in pilot stages [9]. [...]we propose the following framework to address both organizational and individual factors. The Johns Hopkins Bloomberg School of Public Health recently published an evidenced-based review of corporate wellness practices that target specific organizational health promotion factors and describe the business case to support them [15] In Table 1, we have integrated the literature into the following seven broad categories and organized them according to the new ACGME Common Program Requirements. Barriers to care should be anticipated and addressed explicitly, including health insurance coverage, affordability, confidentiality, and state-specific requirements for disclosing mental health treatment on medical licensure applications [27].

Helicobacter pylori infection is an established risk factor for gastritis, gastric ulcer, peptic ulcer and gastric cancer. CagA +ve H. pylori has been associated with oxidative DNA damage of gastric mucosa but their combined role in the development of gastric cancer is still unknown. Here we compare the combined expression of cagA and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in normal, gastritis and gastric cancer tissues. Two hundred gastric biopsies from patients with dyspeptic symptoms, 70 gastric cancer tissue samples and 30 gastric biopsies from non-dyspeptic individuals (controls) were included in this study and 8-OHdG was detected by immunohistochemistry (IHC). Histological features and the presence of H. pylori infection were demonstrated by Hematoxylin and Eosin (HE), Giemsa and alcian blue-periodic acid-Schiff ± diastase (AB-PAS ± D) staining. DNA was extracted from tissues and polymerase chain reaction (PCR) performed to determine the presence of ureaseA and cagA genes of H. pylori . The results showed the presence of H. pylori in 106 (53 %) gastric biopsies out of 200 dyspeptic patients, including 70 (66 %) cases of cagA + ve H. pylori. The presence of cagA gene and high expression of 8-OHdG was highly correlated with severe gastric inflammation and gastric cancer particularly, in cases with infiltration of chronic inflammatory cells (36.8 % cagA + ve, 18 %), neutrophilic activity (47.2 %, 25.5 %), intestinal metaplasia (77.7 %, 35.7 %) and intestinal type gastric cancer (95 %, 95.4 %) ( p  ≤ 0.01). In conclusion, H. Pylori cagA gene expression and the detection of 8-OHdG adducts in gastric epithelium can serve as potential early biomarkers of H. Pylori -associated gastric carcinogenesis.

Objective The authors surveyed Psychiatry Residency Training Directors’ (RTDs’) attitudes about the role and feasibility of international rotations during residency training. Method A 21-question survey was electronically distributed that explored RTDs’ beliefs about the value, use, and availability of international clinical and research experiences during residency. Results Of 171 RTDs, 59 (34.5%) completed the survey; 83% of respondents rated the importance of global mental health education as 3- or- above on a scale of 1 (least important) to 5 (most important), but only 42% indicated that such opportunities were made available. The value of such opportunities was thought to lie primarily in professional development and cultural exposure, less so for enhancing core knowledge competencies. Obstacles to such opportunities included lack of accreditation, financial resources, and faculty/administrative support and supervision. Conclusion RTD respondents endorsed the value of international experiences during residency, but their availability and educational impact are not fully supported.