Who Is at Risk for New Hepatitis B Infections Among People With HIV?

Hepatitis B virus (HBV) increases morbidity and mortality among people with HIV (PWH). We retrospectively analyzed HBV incidence among 5785 PWH. Fourteen had newly positive hepatitis B s antigen (mean 5.2 person-years of follow-up, 46.4/100 000 infections/year). These data show gaps in HBV vaccination and in the preventative efficacy of HBV-specific antiretroviral therapy.

Notch activation during early mesoderm induction modulates emergence of the T/NK cell lineage from human iPSCs.

A robust method of producing mature T cells from iPSCs is needed to realize their therapeutic potential. NOTCH1 is known to be required for the production of hematopoietic progenitor cells with T cell potential in vivo. Here we identify a critical window during mesodermal differentiation when Notch activation robustly improves access to definitive hematopoietic progenitors with T/NK cell lineage potential. Low-density progenitors on either OP9-hDLL4 feeder cells or hDLL4-coated plates favored T cell maturation into TCRab+CD3+CD8+ cells that express expected T cell markers, upregulate activation markers, and proliferate in response to T cell stimulus. Single-cell RNAseq shows Notch activation yields a 6-fold increase in multi-potent hematopoietic progenitors that follow a developmental trajectory toward T cells with clear similarity to post-natal human thymocytes. We conclude that early mesodermal Notch activation during hematopoietic differentiation is a missing stimulus with broad implications for producing hematopoietic progenitors with definitive characteristics.

Disproportionate Burden of COVID-19 Infection Among Hispanic Patients During the First COVID-19 Surge in South Texas.

Introduction: The morbidity and mortality of the COVID-19 pandemic have disproportionately burdened Hispanic populations in the United States. While health equity research is typically conducted in populations where Hispanics are the minority, this project analyzes COVID-19 racioethnic transmission trends over the first 6 months of the pandemic within a large majority-minority city in South Texas. Methods: Patients diagnosed with COVID-19 across inpatient, emergency department, and outpatient settings of a large county health system were included in a clinical registry. For 4644 COVID-19-positive patients between March 16 and August 31, 2020, demographic and clinical data were abstracted from the registry. Race/ethnicity trends over time were compared for patients with and without COVID-19 diagnoses. Logistic regressions identified predictors of inpatient diagnosis by age, race/ethnicity, and testing delay. Results: The proportion of patients with COVID-19 identifying as Hispanic increased rapidly during the pandemic's first months: from 55.6% in March to 85.7% in June. A significantly greater proportion of patients identified as Hispanic within the COVID-19 cohort compared to other diagnoses cohort. Testing delay was 11.6% longer for Hispanic patients, with each day of testing delay associated with 7% increased odds of inpatient COVID-19 diagnosis. Conclusion: These findings highlight the disproportionate impact of COVID-19 on Hispanic populations even within a majority-minority community. In the United States, Hispanic persons are more likely to work frontline jobs, live in multigenerational homes in poverty, and be uninsured. The burden of COVID-19 cases within Bexar County's largest hospital system reflects this systemic inequity. Identifying racioethnic health disparities supports efforts toward mitigating structural factors that predispose minority groups to illness and death.

Genomics analysis of hexanoic acid exposure in Drosophila species.

Drosophila sechellia is a dietary specialist endemic to the Seychelles islands that has evolved to consume the fruit of Morinda citrifolia. When ripe, the fruit of M. citrifolia contains octanoic acid and hexanoic acid, two medium-chain fatty acid volatiles that deter and are toxic to generalist insects. Drosophila sechellia has evolved resistance to these volatiles allowing it to feed almost exclusively on this host plant. The genetic basis of octanoic acid resistance has been the focus of multiple recent studies, but the mechanisms that govern hexanoic acid resistance in D. sechellia remain unknown. To understand how D. sechellia has evolved to specialize on M. citrifolia fruit and avoid the toxic effects of hexanoic acid, we exposed adult D. sechellia, D. melanogaster and D. simulans to hexanoic acid and performed RNA sequencing comparing their transcriptional responses to identify D. sechellia specific responses. Our analysis identified many more genes responding transcriptionally to hexanoic acid in the susceptible generalist species than in the specialist D. sechellia. Interrogation of the sets of differentially expressed genes showed that generalists regulated the expression of many genes involved in metabolism and detoxification whereas the specialist primarily downregulated genes involved in the innate immunity. Using these data, we have identified interesting candidate genes that may be critically important in aspects of adaptation to their food source that contains high concentrations of HA. Understanding how gene expression evolves during dietary specialization is crucial for our understanding of how ecological communities are built and how evolution shapes trophic interactions.

The relationship between longevity and diet is genotype dependent and sensitive to desiccation in Drosophila melanogaster.

Dietary restriction (DR) is a key focus in ageing research. Specific conditions and genotypes were recently found to negate lifespan extension by DR, questioning its universal relevance. However, the concept of dietary reaction norms explains why the effects of DR might be obscured in some situations. We tested the importance of dietary reaction norms by measuring longevity and fecundity on five diets in five genotypes, with and without water supplementation in female Drosophila melanogaster (N>25,000). We found substantial genetic variation in the response of lifespan to diet. Flies supplemented with water rescued putative desiccation stress on the richest diets, suggesting that water availability can be an experimental confound. Fecundity declined on these richest diets, but was unaffected by water, and this reduction is thus most likely to be caused by nutritional toxicity. Our results demonstrate empirically that a range of diets need to be considered to conclude an absence of the DR longevity effect.

Implementation of Universal Tumor Screening of Colorectal Cancer for Detection of Lynch Syndrome at a Hispanic-Rich County Hospital.

INTRODUCTION: In 2014, a reflexive screening protocol for Lynch syndrome (LS) via an immunohistochemistry (IHC) assay was shown to be cost-effective; however, the screening rates at a predominant Hispanic-rich institution are unclear. We hypothesized that implementation of a universal tumor screening (UTS) protocol requiring screening for LS via IHC in patients with newly diagnosed colorectal cancer (CRC) at our Hispanic-rich institution would improve detection of LS by increasing screening rates. METHODS AND MATERIALS: This is a retrospective analysis of screening rates of 3 sequential cohorts of newly diagnosed patients with CRC between January 2012 and April 2016 at the University Health System and with follow-up at National Cancer Institute-designated Mays Cancer Center at University of Texas Health San Antonio. Cohort 1 consisted of patients screened using old screening guidelines (PRE). Cohort 2 consisted of patients screened when treating clinicians were receiving education on the new protocol (PERI). Cohort 3 consisted of patients screened after implementation of the UTS protocol (POST). RESULTS: The majority of 312 patients were Hispanic (62.5%), 18.1% were < 50 years, and 81.9% were ≥ 50 years of age (median age, 57 years). Of patients with CRC screened for LS via IHC, the PRE, PERI, and POST cohorts had screening rates of 31%, 64%, and 58%, respectively. We found significant differences when comparing the PRE with POST sequential cohorts (P < .01). CONCLUSION: The quality of Lynch syndrome-related family histories and screening rates were significantly improved after implementation in our Hispanic-rich population. Future studies are warranted to provide insight into clinical effects of increased screening, provider and patient surveillance, and screening-related systemic barriers.

The hidden costs of dietary restriction: Implications for its evolutionary and mechanistic origins.

Dietary restriction (DR) extends life span across taxa. Despite considerable research, universal mechanisms of DR have not been identified, limiting its translational potential. Guided by the conviction that DR evolved as an adaptive, pro-longevity physiological response to food scarcity, biomedical science has interpreted DR as an activator of pro-longevity molecular pathways. Current evolutionary theory predicts that organisms invest in their soma during DR, and thus when resource availability improves, should outcompete rich-fed controls in survival and/or reproduction. Testing this prediction in Drosophila melanogaster (N > 66,000 across 11 genotypes), our experiments revealed substantial, unexpected mortality costs when flies returned to a rich diet following DR. The physiological effects of DR should therefore not be interpreted as intrinsically pro-longevity, acting via somatic maintenance. We suggest DR could alternatively be considered an escape from costs incurred under nutrient-rich conditions, in addition to costs associated with DR.

How to Catch a Smurf? - Ageing and Beyond In vivo Assessment of Intestinal Permeability in Multiple Model Organisms.

The Smurf Assay (SA) was initially developed in the model organism Drosophila melanogaster where a dramatic increase of intestinal permeability has been shown to occur during aging (Rera et al., 2011). We have since validated the protocol in multiple other model organisms (Dambroise et al., 2016) and have utilized the assay to further our understanding of aging (Tricoire and Rera, 2015; Rera et al., 2018). The SA has now also been used by other labs to assess intestinal barrier permeability (Clark et al., 2015; Katzenberger et al., 2015; Barekat et al., 2016; Chakrabarti et al., 2016; Gelino et al., 2016). The SA in itself is simple; however, numerous small details can have a considerable impact on its experimental validity and subsequent interpretation. Here, we provide a detailed update on the SA technique and explain how to catch a Smurf while avoiding the most common experimental fallacies.