A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans.

Sterol regulatory element-binding proteins (SREBPs) activate genes involved in the synthesis and trafficking of cholesterol and other lipids and are critical for maintaining lipid homeostasis. Aberrant SREBP activity, however, can contribute to obesity, fatty liver disease, and insulin resistance, hallmarks of metabolic syndrome. Our studies identify a conserved regulatory circuit in which SREBP-1 controls genes in the one-carbon cycle, which produces the methyl donor S-adenosylmethionine (SAMe). Methylation is critical for the synthesis of phosphatidylcholine (PC), a major membrane component, and we find that blocking SAMe or PC synthesis in C. elegans, mouse liver, and human cells causes elevated SREBP-1-dependent transcription and lipid droplet accumulation. Distinct from negative regulation of SREBP-2 by cholesterol, our data suggest a feedback mechanism whereby maturation of nuclear, transcriptionally active SREBP-1 is controlled by levels of PC. Thus, nutritional or genetic conditions limiting SAMe or PC production may activate SREBP-1, contributing to human metabolic disorders.

Evaluating Methods for Mapping Historical Redlining to Census Tracts for Health Equity Research.

Neighborhood characteristics including housing status can profoundly influence health. Recently, increasing attention has been paid to present-day impacts of "redlining," or historic area classifications that indicated less desirable (redlined) areas subject to decreased investment. Scholarship of redlining and health is emerging; limited guidance exists regarding optimal approaches to measuring historic redlining in studies of present-day health outcomes. We evaluated how different redlining approaches (map alignment methods) influence associations between redlining and health outcomes. We first identified 11 existing redlining map alignment methods and their 37 logical extensions, then merged these 48 map alignment methods with census tract life expectancy data to construct 9696 linear models of each method and life expectancy for all 202 redlined cities. We evaluated each model's statistical significance and R2 values and compared changes between historical and contemporary geographies and populations using Root Mean Squared Error (RMSE). RMSE peaked with a normal distribution at 0.175, indicating persistent difference between historical and contemporary geographies and populations. Continuous methods with low thresholds provided higher neighborhood coverage. Weighting methods had more significant associations, while high threshold methods had higher R2 values. In light of these findings, we recommend continuous methods that consider contemporary population distributions and mapping overlap for studies of redlining and health. We developed an R application {holcmapr} to enable map alignment method comparison and easier method selection.

Towards conceptual convergence: A systematic review of psychological resilience in family caregivers of persons living with chronic neurological conditions.

BACKGROUND: The demand for family caregiving in persons with chronic neurological conditions (CNCs) is increasing. Psychological resilience may empower and protect caregivers in their role. Thus, a synthesis of resilience evidence within this specific population is warranted. AIM: In this systematic review we aimed to: (1) examine the origins and conceptualizations of resilience; (2) summarize current resilience measurement tools; and (3) synthesize correlates, predictors and outcomes of resilience in family caregivers of persons with CNCs. DESIGN: We sourced English articles published up to July 2020 across five databases using search terms involving CNCs, family caregivers and resilience. RESULTS: A total of 50 studies were retained. Nearly half (44%) of the studies used trait-based resilience definitions, while about one third (36%) used process-based definitions. Twelve different resilience scales were used, revealing mostly moderate to high-resilience levels. Findings confirmed that resilience is related to multiple indicators of healthy functioning (e.g., quality of life, social support, positive coping), as it buffers against negative outcomes of burden and distress. Discordance relating to the interaction between resilience and demographic, sociocultural and environmental factors was apparent. CONCLUSIONS: Incongruity remains with respect to how resilience is defined and assessed, despite consistent definitional concepts of healthy adaptation and equilibrium. The array of implications of resilience for well-being confirms the potential for resilience to be leveraged within caregiver health promotion initiatives via policy and practice. PATIENT OR PUBLIC CONTRIBUTION: The findings may inform future recommendations for researchers and practitioners to develop high-quality resilience-building interventions and programmes to better mobilize and support this vulnerable group.

CoRest1 regulates neurogenesis in a stage-dependent manner.

BACKGROUND: Developmental processes, including neuronal differentiation, require precise regulation of transcription. The RE-1 silencing transcription factor (Rest), is often called a "master neuronal regulator" due to its large number of neural-specific targets. Rest recruits CoRest (Rcor) and Sin3 corepressor complexes to gene regulatory sequences. CoRest not only associates with Rest, but with other transcription regulators. In this study, we generated zebrafish rcor1 mutants using transcription activator-like effector nucleases (TALENS), to study its requisite role in repression of Rest target genes as well as Rest-independent Rcor1 developmental functions. RESULTS: While rcor1 mutants have a slight decrease in fitness, most survived and produced viable offspring. We examined expression levels of RE1-containing genes in maternal zygotic rcor1 (MZrcor1) mutants and found that Rcor1 is generally not required for the repression of Rest target genes at early stages. However, MZrcor1 mutants undergo more rapid neurogenesis compared to controls. We found that at gastrula stages, Rcor1 acts as a repressor of her gene family, but at later stages, her6 decreased in the MZrcor1 mutant. CONCLUSIONS: Based on these findings, the central role of CoRest1 in neurogenesis is likely due to a Rest-independent role rather than as a Rest corepressor.

Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP.

The sterol regulatory element-binding protein (SREBP) transcription factor family is a critical regulator of lipid and sterol homeostasis in eukaryotes. In mammals, SREBPs are highly active in the fed state to promote the expression of lipogenic and cholesterogenic genes and facilitate fat storage. During fasting, SREBP-dependent lipid/cholesterol synthesis is rapidly diminished in the mouse liver; however, the mechanism has remained incompletely understood. Moreover, the evolutionary conservation of fasting regulation of SREBP-dependent programs of gene expression and control of lipid homeostasis has been unclear. We demonstrate here a conserved role for orthologs of the NAD(+)-dependent deacetylase SIRT1 in metazoans in down-regulation of SREBP orthologs during fasting, resulting in inhibition of lipid synthesis and fat storage. Our data reveal that SIRT1 can directly deacetylate SREBP, and modulation of SIRT1 activity results in changes in SREBP ubiquitination, protein stability, and target gene expression. In addition, chemical activators of SIRT1 inhibit SREBP target gene expression in vitro and in vivo, correlating with decreased hepatic lipid and cholesterol levels and attenuated liver steatosis in diet-induced and genetically obese mice. We conclude that SIRT1 orthologs play a critical role in controlling SREBP-dependent gene regulation governing lipid/cholesterol homeostasis in metazoans in response to fasting cues. These findings may have important biomedical implications for the treatment of metabolic disorders associated with aberrant lipid/cholesterol homeostasis, including metabolic syndrome and atherosclerosis.

Axillary ultrasonography for early-stage invasive breast cancer.

BACKGROUND: Among women with early invasive breast cancer and 1-2 positive sentinel nodes, sentinel lymph node biopsy (SLNB) is non-inferior to axillary lymph node dissection (ALND).1-3 However, preoperative axillary ultrasonography (AxUS) may not be sensitive enough to discriminate burden of nodal metastasis in these patients, potentially leading to overtreatment.4-6 This study compares axillary operation rates in patients who did and did not receive preoperative AxUS, assessing its utility and risks for overtreatment. METHODS: This is a retrospective cohort study of patients with clinical T1/T2 breast tumors who were clinically node negative and underwent an axillary operation. RESULTS: Patients who had preoperative AxUS received more ALND compared to patients who did not (5.6% vs. 1.4%, p â€‹< â€‹0.001). There was no significant difference in the number of additional axillary operations following SLNB (2.1% vs. 2.3%, p â€‹= â€‹0.77). CONCLUSION: Eliminating preoperative AxUS is associated with fewer invasive ALND procedures, without increased rate of axillary reoperations.

"If the college adjusted the prices ": comparing food secure and insecure college students during the COVID-19 pandemic.

Objective: We examined how students' food insecurity related to their demographic information, academic experiences, use of food programs, and reflections on food during the COVID-19 pandemic. Participants: 246 NYC undergraduates during the first 9 months of the pandemic. Methods: Students reported on food insecurity (eg, USDA's 10-item AFSSM), household income, impact of food insecurity on academics, GPA, and use of food programs. They wrote two food narratives. Results: 135 (54.88%) participants reported high food security; 51 (20.73%) reported low or very low food security. Compared to high food security students, low and very low-security students were more likely to identify as Black and first-generation immigrants, reported lower household income, more frequently used food programs, had a lower GPA, reported more academic difficulties, and wrote more often about financial and programmatic difficulties related to food. Conclusions: Food-insecure students need greater financial, academic, and programmatic support during public health crises.

Dietary Patterns and Obesity in Chinese Adults: A Systematic Review and Meta-Analysis.

Certain dietary patterns are associated with an increased risk of obesity and its comorbidities. However, these associations vary across populations. The prevalence of obesity has been rising amid a drastic nutrition transition in China during the country's rapid economic growth. This systematic review and meta-analysis were conducted to summarize how dietary patterns are associated with obesity in the Chinese population. We searched for articles from 1 January 2000 to 1 February 2022 in PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus that assessed the relationship between dietary patterns and obesity outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a random effects model. From the 2556 articles identified from the search, 23 articles were included in the analysis. We found that the traditional Chinese dietary pattern was associated with a lower risk of overweight/obesity (OR = 0.69, 95% CI: 0.57, 0.84, p < 0.001), whereas the Western dietary pattern was associated with a higher OR of overweight/obesity, but not reaching statistical significance (OR = 1.34, 95% CI: 0.98, 1.84, p = 0.07). There were inconsistent results for other dietary patterns, such as meat/animal protein and plant/vegetarian patterns. In conclusion, the traditional Chinese diet characterized by vegetables, rice, and meat was associated with a lower risk of obesity. The heterogeneity in characterizing dietary patterns contributes to the inconsistency of how dietary patterns are associated with obesity in the Chinese population.

Changes in Racial and Ethnic Disparities in Access to Care and Health Among US Adults at Age 65 Years.

Importance: Medicare provides nearly universal health insurance to individuals at age 65 years. How eligibility for Medicare affects racial and ethnic disparities in access to care and health is poorly understood. Objective: To assess the association of Medicare with racial and ethnic disparities in access to care and health. Design, Setting, and Participants: This cross-sectional study uses regression discontinuity to compare racial and ethnic disparities before and after age 65 years, the age at which US adults are eligible for Medicare. There are a total of 2 434 320 respondents in the Behavioral Risk Factor Surveillance System and 44 587 state-age-year observations in the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research Data (eg, the mortality rate for individuals age 63 years in New York in 2017) from January 2008 to December 2018. The data were analyzed between February and May 2021. Exposures: Eligibility for Medicare at age 65 years. Main Outcomes and Measures: Proportions of respondents with health insurance, as well as self-reported health and mortality. To examine access, whether respondents had a usual source of care, encountered cost-related barriers to care, or received influenza vaccines was assessed. Results: Of 2 434 320 participants, 192 346 were Black individuals, 104 294 were Hispanic individuals, and 892 177 were men. Immediately after age 65 years, insurance coverage increased more for Black respondents (from 86.3% to 95.8% or 9.5 percentage points; 95% CI, 7.6-11.4) and Hispanic respondents (from 77.4% to 91.3% or 13.9 percentage points; 95% CI, 12.0-15.8) than White respondents (from 92.0% to 98.5% or 6.5 percentage points; 95% CI, 6.1-7.0). This was associated with a 53% reduction compared with the size of the disparity between White and Black individuals before age 65 years (5.7% to 2.7% or 3.0 percentage points; 95% CI, 0.9-5.1; P = .003) and a 51% reduction compared with the size of the disparity between White and Hispanic individuals before age 65 years (14.6% to 7.2% or 7.4 percentage points; 95% CI, 5.3-9.5; P < .001). Medicare eligibility was associated with narrowed disparities between White and Hispanic individuals in access to care, lowering disparities in access to a usual source of care from 10.5% to 7.5% (P = .05), cost-related barriers to care from 11.4% to 6.9% (P < .001), and influenza vaccination rates from 8.1% to 3.3% (P = .01). For disparities between White and Black individuals, access to a usual source of care before and after age 65 years was not significantly different: 1.2% to 0.0% (P = .24), cost-related barriers to care from 5.8% to 4.3% (P = .22), and influenza vaccinations from 11.0% to 10.3% (P = .60). The share of people in poor self-reported health decreased by 3.8 percentage points for Hispanic respondents, 2.6 percentage points for Black respondents, and 0.2 percentage points for White respondents. Mortality-related disparities at age 65 years were unchanged. Medicare's association with reduced disparities largely persisted after the US Affordable Care Act took effect in 2014. Conclusions and Relevance: In this cross-sectional study that uses a regression discontinuity design, eligibility for Medicare at age 65 years was associated with marked reductions in racial and ethnic disparities in insurance coverage, access to care, and self-reported health.

Effects of a competency-based counseling training program for correctional officers.

The purposes of this study were (a) to determine whether a competency-based counseling training program can be effective in developing the counseling skills of correctional officers with diverse backgrounds and (b) to examine if participants would demonstrate positive changes in counseling skills regardless of their differences among a variety of demographic variables. One hundred and six correctional officers were selected to participate in this study. Both qualitative and quantitative research methods were applied for collecting and analyzing data. The results indicate that the participants' counseling skills were significantly improved. Because the participants demonstrated positive changes in their overall counseling skills, the present research further supports no significant difference among a variety of variables. The training program also brought out deeper reflection on the significant learning experiences, greater theoretical knowledge, as well as greater understanding of the counseling work for the participants.

The Spiraling Case of a Yellow Chef: Isolated Hyperbilirubinemia.

Leptospirosis is a common bacterial disease in tropical regions of the world due to greater exposure to rodents and domestic animals; however, this condition can also occur in US urban areas, though it often goes unrecognized. Gastrointestinal symptoms are very commonly seen, and icteric leptospirosis is often confused for other conditions resulting in delayed diagnosis and worse outcomes. As mortality increases with more extensive hepatic involvement, gastroenterologists should be aware of the constellation of gastrointestinal symptoms related to leptospirosis, as it can occur in the absence of classic exposure history.

Correctional officers' perceptions of a solution-focused training program: potential implications for working with offenders.

The purpose of this exploratory study was to explore correctional officers' perceptions and experiences during a solution-focused training program and to initiate development of a modified pattern for correctional officers to use in jails. The study uses grounded theory procedures combined with a follow-up survey. The findings identified six emergent themes: obstacles to doing counseling work in prisons, offenders' amenability to change, correctional officers' self-image, advantages of a solution-focused approach (SFA), potential advantages of applying SFA to offenders, and the need for the consolidation of learning and transformation. Participants perceived the use of solution-focused techniques as appropriate, important, functional, and of only moderate difficulty in interacting with offenders. Finally, a modified pattern was developed for officers to use when working with offenders in jails. Suggestions and recommendations are made for correctional interventions and future studies.