Treatment of obesity, an ongoing global epidemic, is challenging, as weight-loss efforts require a multidisciplinary approach addressing both behavioral and biologic needs that are not completely understood. Recent studies of the gut microbiome may provide better insight into the condition, and ultimately serve to advance more effective therapies. Research in this field has shifted from analyzing microbiome compositional differences to investigating functional changes that affect disease pathophysiology and outcome. Bacteria-derived metabolites are a way to bridge compositional changes to functional consequences. Through the production of metabolites, such as short chain fatty acids, tryptophan derivatives and bile acids, and interactions with peripheral and central signaling pathways, the gut microbiome may alter the body's metabolic and behavioral responses to food. Here, we summarize these mechanisms driven by gut-derived metabolites, through which the microbiome is thought to contribute to obesity, as well as review recent investigations of interventions related to these metabolites. Limitations of existing research, primarily due to paucity of causal studies in humans, are also discussed in this review.

The status of mental health for adolescents and young adults has aptly been termed a "crisis" across research, clinical, and policy quarters. Arguably, the status quo provision of mental health services for adolescents and young adults is neither acceptable nor salvageable in its current form. Instead, only a wholesale policy transformation of mental health sciences can address crises of this scope. Pandemic-related impacts on mental health, particularly among young adults, have clearly exposed the need for the mental healthcare field to develop a set of transformative priorities to achieve long overdue, systemic changes: (1) frequent mental health tracking, (2) increased access to mental health care, (3) working with and within communities, (4) collaboration across disciplines and stakeholders, (5) prevention-focused emphasis, (6) use of dimensional descriptions over categorical pronouncements, and (7) addressing systemic inequities. The pandemic required changes in mental healthcare that can and should be the beginning of long-needed reform, calling upon all mental health care disciplines to embrace innovation and relinquish outdated traditions.

Unlabelled

To better elucidate the socioeconomic and racial differences in women who received postmastectomy radiation therapy with or without a chest wall boost, the records from 4747 women included in the California Cancer Registry were reviewed. Poor and Hispanic women were more likely to receive a chest wall boost than were more affluent and non-Hispanic women.

Introduction

Healthcare disparities in breast cancer treatment have been well documented. We investigated the socioeconomic status (SES) and racial factors in women with locally advanced breast cancer from the California Cancer Registry who had received postmastectomy radiation therapy (PMRT) with or without a chest wall boost (CWB).

Patients and methods

The records of 4747 women with invasive breast cancer, diagnosed from 2005 to 2009, who had undergone PMRT, were reviewed and stratified by treatment with (n = 2686 [57%]) or without (n = 2061 [43%]) a CWB. Various patient demographic and biologic factors were analyzed using univariate and multivariate analysis.

Results

Receipt of a CWB was associated with race/ethnicity (P < .001), SES (P < .001), tumor size (P = .038), tumor grade (P = .033), human epidermal growth factor 2 (HER2) status (P = .015), American Joint Committee on Cancer stage (P = .001), number of nodes examined (P = .001), and number of positive nodes (P = .037) on univariate analysis. After controlling for confounding factors, race/ethnicity and SES remained independently predictive of a CWB. Hispanic women were more likely to receive a CWB than Asian (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.60-0.90), black (HR, 0.63; 95% CI, 0.48-0.83), or white (HR, 0.81; 95% CI, 0.69-0.95) women. Also, women of low SES were more likely to receive a CWB than women of high SES (HR, 0.74; 95% CI, 0.64-0.86).

Conclusion

We found that poor and Hispanic women were more commonly treated with a CWB than were more affluent and non-Hispanic women with a similar cancer stage, cancer biology, and treatment paradigm.

INTRODUCTION: Opioids are commonly prescribed to patients with chronic liver disease, but little is known regarding medication prescribing patterns of hepatologists. Opioid use increased until national guidelines limited opioid prescriptions in early 2016. We aimed to describe rates of opioid and nonopioid analgesics to Medicare beneficiaries by hepatologists from 2013 to 2017 and identify demographic characteristics associated with higher prescribing. METHODS: Prescription data from 2013 to 2017 by 761 hepatologists identified in the Centers for Medicare and Medicaid Services Part D Public Use File were analyzed. Annual prescription volumes were compared for providers with >10 annual prescriptions of a given drug type. Provider characteristics associated with opioid prescriptions were identified through multivariate logistic regression analyses. RESULTS: The proportion of hepatologists prescribing >10 annual opioid prescriptions decreased from 29% to 20.6%. Median annual opioid prescriptions per hepatologist significantly decreased from 24 to 20. Tramadol remained the most prescribed analgesic. Nonopioid analgesic prescription volume did not increase significantly. Provider characteristics associated with increased opioid prescriptions included male sex, practice location in the South and Midwest (vs West), more years in practice, and a greater proportion of beneficiaries who are white or with low-income subsidy claims. Characteristics associated with fewer prescriptions included non-university-based practice, having a greater proportion of female beneficiaries, and later prescription year. DISCUSSION: Hepatologists are prescribing less opioids. However, the prevalence of tramadol use and the lack of increase in nonopioid analgesic use highlights the need for advancing the science and training of pain management in chronic liver disease and targeted implementation of nonopioid treatment programs.

We present novoBreak, a genome-wide local assembly algorithm that discovers somatic and germline structural variation breakpoints in whole-genome sequencing data. novoBreak consistently outperformed existing algorithms on real cancer genome data and on synthetic tumors in the ICGC-TCGA DREAM 8.5 Somatic Mutation Calling Challenge primarily because it more effectively utilized reads spanning breakpoints. novoBreak also demonstrated great sensitivity in identifying short insertions and deletions.

Aim

The Cass Clinic is a student-run free clinic in Detroit, Michigan that treats chronic diseases including hypertension (HTN), diabetes mellitus (DM), and obesity. Our study aims to quantify the effectiveness of our clinic in managing chronic diseases.

Subject and methods

This study assessed selected health outcomes for 137 patients who visited our clinic between September 1, 2017 and August 31, 2018 based on initial and most recent surrogate markers including manual blood pressure, hemoglobin A1c (HbA1c), and body mass index (BMI) recorded in the clinic's medical record system dating back to 2012.

Results

Patients were divided into two groups: occasionally seen patients (OSP) and frequently seen patients (FSP). FSP with HTN had systolic blood pressure (SBP) decreased by an average of 14.1 mmHg and diastolic blood pressure (DBP) decreased by 9.8 mmHg, which were statistically associated with the number of clinic visits. Additionally, all patients treated at Cass Clinic saw a decrease in their HbA1c and BMI. HbA1c in OSP decreased by 0.50%. HbA1c in the FSP decreased by 1.7%. Patients with at least two recorded BMIs (n=73) saw a decrease of 0.13 kg/m².

Conclusion

The data from our analysis support that a student-run free clinic model like Cass Clinic provides long-term value for patients who frequently utilize the clinic. These clinics also act as an important resource for the community by making positive strides toward better health in multiple measurable outcomes, including HTN and DM management.

Abstract Background and Purpose Oligodendrocyte (OL) death is important in focal cerebral ischemia. TIMP-3 promotes apoptosis in ischemic neurons by inhibiting proteolysis of TNF-α superfamily of death receptors. Since OLs undergo apoptosis during ischemia, we hypothesized that TIMP-3 contributes to OL death. Methods Middle cerebral artery occlusion (MCAO) was induced in Timp-3 knockout (KO) and wild type (WT) mice with 24 or 72 h of reperfusion. Cell death in white matter was investigated by stereology and TUNEL. Mature or immature OLs were identified using antibodies against glutathione S-transferase-π (GST-π) and galactocerebroside (GalC), respectively. Expression and level of proteins were examined using immunohistochemistry and immunoblotting. Protein activities were determined using a FRET peptide. Results Loss of OL-like cells was detected at 72 h only in WT ischemic white matter where TUNEL showed greater cell death. TIMP-3 expression was increased in WT reactive astrocytes. GST-π was reduced in ischemic white matter of WT mice compared with WT shams with no difference between KO and WT at 72 h. GalC level was significantly increased in both KO and WT ischemic white matter at 72 h. However, the increase in GalC in KO mice was significantly higher than WT; most TUNEL-positive cells in ischemic white matter expressed GalC, suggesting TIMP-3 deficiency protects the immature OLs from apoptosis. There were significantly higher levels of cleaved caspase-3 at 72 h in WT white matter than in KO. Greater expression of MMP-3 and -9 was seen in reactive astrocytes and/or microglia/macrophages in WT at 72 h. We found more microglia/macrophages in WT than in KO, which were the predominant source of increased TNF-α detected in the ischemic white matter. TACE activity was significantly increased in ischemic WT white matter, which was expressed in active microglia/macrophages and OLs. Conclusions Our results suggested that focal ischemia leads to proliferation of immature OLs in white matter and that TIMP-3 contributes to a caspase-3-dependent immature OL death via TNF-α-mediated neuroinflammation. Future studies will be needed to delineate the role of MMP-3 and MMP-9 that were increased in the Timp-3 wild type.

The growth of clinical science as a field depends on the work of engaged mentors nurturing future generations of scientists. Effective research mentoring has been shown to predict positive outcomes, including greater scholarly productivity, reduced attrition, and increased satisfaction with training and/or employment, which ultimately may enhance the quality of the clinical-science research enterprise. Barriers to effective research mentoring, however, pose significant challenges for both mentees and mentors, as well as for labs, training programs, and/or departments. We discuss some key issues as they apply to clinical-science mentoring and note how they are affected across different developmental levels (undergraduate, postbaccalaureate, doctoral, internship, postdoctoral associates, and early career faculty). Although we do not proclaim expertise on these issues-and have struggled with them in our own careers-we believe an open discussion around best mentoring practices will enhance our collective effectiveness and help mentees and our field to flourish. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background and aims

Nonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions. Early detection can identify at-risk patients who can be linked to hepatology care. The vibration-controlled transient elastography (VCTE) controlled attenuation parameter (CAP) is biopsy validated to diagnose hepatic steatosis (HS). We aimed to develop a novel clinical predictive algorithm for HS using the CAP score at a Veterans' Affairs hospital.

Methods

We identified 403 patients in the Greater Los Angeles VA Healthcare System with valid VCTEs during 1/2018-6/2020. Patients with alcohol-associated liver disease, genotype 3 hepatitis C, any malignancies, or liver transplantation were excluded. Linear regression was used to identify predictors of NAFLD. To identify a CAP threshold for HS detection, receiver operating characteristic analysis was applied using liver biopsy, MRI, and ultrasound as the gold standards.

Results

The cohort was racially/ethnically diverse (26% Black/African American; 20% Hispanic). Significant positive predictors of elevated CAP score included diabetes, cholesterol, triglycerides, BMI, and self-identifying as Hispanic. Our predictions of CAP scores using this model strongly correlated (r = 0.61, p < 0.001) with actual CAP scores. The NAFLD model was validated in an independent Veteran cohort and yielded a sensitivity of 82% and specificity 83% (p < 0.001, 95% CI 0.46-0.81%). The estimated optimal CAP for our population cut-off was 273.5 dB/m, resulting in AUC = 75.5% (95% CI 70.7-80.3%).

Conclusion

Our HS predictive algorithm can identify at-risk Veterans for NAFLD to further risk stratify them by non-invasive tests and link them to sub-specialty care. Given the biased referral pattern for VCTEs, future work will need to address its applicability in non-specialty clinics. Proposed clinical algorithm to identify patients at-risk for NAFLD prior to fibrosis staging in Veteran.