Structural Racism as a Contributor to Lung Cancer Incidence and Mortality Rates Among Black Populations in the United States.

BACKGROUND: Although racial disparities in lung cancer incidence and mortality have diminished in recent years, lung cancer remains the second most diagnosed cancer among US Black populations. Many factors contributing to disparities in lung cancer are rooted in structural racism. To quantify this relationship, we examined associations between a multidimensional measure of county-level structural racism and county lung cancer incidence and mortality rates among Black populations, while accounting for county levels of environmental quality. METHODS: We merged 2016-2020 data from the United States Cancer Statistics Data Visualization Tool, a pre-existing county-level structural racism index, the Environmental Protection Agency's 2006-2010 Environmental Quality Index (EQI), 2023 County Health Rankings, and the 2021 United States Census American Community Survey. We conducted multivariable linear regressions to examine associations between county-level structural racism and county-level lung cancer incidence and mortality rates. RESULTS: Among Black males and females, each standard deviation increase in county-level structural racism score was associated with an increase in county-level lung cancer incidence of 6.4 (95% CI: 4.4, 8.5) cases per 100,000 and an increase of 3.3 (95% CI: 2.0, 4.6) lung cancer deaths per 100,000. When examining these associations stratified by sex, larger associations between structural racism and lung cancer rates were observed among Black male populations than among Black females. CONCLUSION: Structural racism contributes to both the number of new lung cancer cases and the number of deaths caused by lung cancer among Black populations. Those aiming to reduce lung cancer cases and deaths should consider addressing racism as a root-cause.

Observation of interlayer plasmon polaron in graphene/WS2 heterostructures.

Harnessing electronic excitations involving coherent coupling to bosonic modes is essential for the design and control of emergent phenomena in quantum materials. In situations where charge carriers induce a lattice distortion due to the electron-phonon interaction, the conducting states get "dressed", which leads to the formation of polaronic quasiparticles. The exploration of polaronic effects on low-energy excitations is in its infancy in two-dimensional materials. Here, we present the discovery of an interlayer plasmon polaron in heterostructures composed of graphene on top of single-layer WS2. By using micro-focused angle-resolved photoemission spectroscopy during in situ doping of the top graphene layer, we observe a strong quasiparticle peak accompanied by several carrier density-dependent shake-off replicas around the single-layer WS2 conduction band minimum. Our results are explained by an effective many-body model in terms of a coupling between single-layer WS2 conduction electrons and an interlayer plasmon mode. It is important to take into account the presence of such interlayer collective modes, as they have profound consequences for the electronic and optical properties of heterostructures that are routinely explored in many device architectures involving 2D transition metal dichalcogenides.

Income Inequality, Gender Disparities, and Ethnic Differences: Investigating Allostatic Load in American Adults.

AIM: To estimate the association between income inequality and allostatic load score (AL) in adults ages 20 years and older, with a particular focus on the differential impacts across racial and gender groups. By examining this association, the study seeks to inform targeted policy interventions to mitigate health disparities exacerbated by economic inequality. METHODS: Utilizing data from the 1999-2016 National Health and Nutrition Examination Survey (NHANES), we assessed AL through eight biomarkers: systolic blood pressure (mm Hg), diastolic blood pressure (mm Hg), pulse rate (beats/min), body mass index (kg/m2), glycohemoglobin (%), direct HDL cholesterol (mg/dL), total cholesterol (mg/dL), and serum albumin (g/dL). Employing negative binomial regression (NBRG), we estimated incidence rate ratios (IRR) for a sample comprising 7367 men and 7814 women, adjusting for age, race/ethnicity, marital status, education, health insurance, comorbidity, and mental health professional utilization. Gini coefficients (GC) were calculated to assess income inequality among men and women. RESULTS: Findings revealed that men exhibited a higher poverty-to-income ratio (PIR) compared to women (3.12 vs. 2.86, p < 0.01). Yet, women experienced higher rates of elevated AL (AL > 4) (31.8% vs. 29.0%) and were more adversely affected by income inequality (GC: 0.280 vs. 0.333). NBRG results indicated that high PIR individuals had a lower IRR (0.96; CI:0.92-0.95) compared to their low PIR counterparts, a trend observed in women but not men. High PIR was notably protective among White non-Hispanic (WNH) men and women. Additionally, vigorous and moderate physical activity engagement was associated with lower AL (IRR: 0.89, CI: 0.85-0.93). CONCLUSION: The study emphasizes the importance of implementing policies that target AL in low-income populations across all racial groups, with a specific focus on Black non-Hispanic (BNH) and Hispanic communities. By prioritizing these groups, policies can more effectively target the nexus of income inequality, health disparities, and allostatic load, contributing to the reduction of health inequities.

Staggered structural dynamic-mediated selective adsorption of H2O/D2O on flexible graphene oxide nanosheets.

Graphene oxide (GO) is the one of the most promising family of materials as atomically thin membranes for water-related molecular separation technologies due to its amphipathic nature and layered structure. Here, we show important aspects of GO on water adsorption from molecular dynamics (MD) simulations, in-situ X-ray diffraction (XRD) measurements, and ex-situ nuclear magnetic resonance (NMR) measurements. Although the MD simulations for GO and the reduced GO models revealed that the flexibility of the interlayer spacing could be attributed to the oxygen-functional groups of GO, the ultra-large GO model cannot well explain the observed swelling of GO from XRD experiments. Our MD simulations propose a realistic GO interlayer structure constructed by staggered stacking of flexible GO sheets, which can explain very well the swelling nature upon water adsorption. The transmission electron microscopic (TEM) observation also supports the non-regular staggered stacking structure of GO. Furthermore, we demonstrate the existence of the two distinct types of adsorbed water molecules in the staggered stacking: water bonded with hydrophilic functional groups and "free" mobile water. Finally, we show that the staggered stacking of GO plays a crucial role in H/D isotopic recognition in water adsorption, as well as the high mobility of water molecules.

Discovery of two non-UDP-mimic inhibitors of O-GlcNAc transferase by screening a DNA-encoded library.

Finding potent inhibitors of O-GlcNAc transferase (OGT) has proven to be a challenge, especially because the diversity of published inhibitors is low. The large majority of available OGT inhibitors are uridine-based or uridine-like compounds that mimic the main interactions of glycosyl donor UDP-GlcNAc with the enzyme. Until recently, screening of DNA-encoded libraries for discovering hits against protein targets was dedicated to a few laboratories around the world, but has become accessible to wider public with the recent launch of the DELopen platform. Here we report the results and follow-up of a DNA-encoded library screening by using the DELopen platform. This led to the discovery of two new hits with structural features not resembling UDP. Small focused libraries bearing those two scaffolds were made, leading to low micromolar inhibition of OGT and elucidation of their structure-activity relationship.

The Association of Oncology Provider Density With Black-White Disparities in Cancer Mortality in US Counties.

BACKGROUND: Black-White racial disparities in cancer mortality are well-documented in the US. Given the estimated shortage of oncologists over the next decade, understanding how access to oncology care might influence cancer disparities is of considerable importance. We aim to examine the association between oncology provider density in a county and Black-White cancer mortality disparities. METHODS: An ecological study of 1048 US counties was performed. Oncology provider density was estimated using the 2013 National Plan and Provider Enumeration System data. Black:White cancer mortality ratio was calculated using 2014-2018 age-standardized cancer mortality rates from State Cancer Profiles. Linear regression with covariate adjustment was constructed to assess the association of provider density with (1) Black:White cancer mortality ratio, and (2) cancer mortality rates overall, and separately among Black and White persons. RESULTS: The mean Black:White cancer mortality ratio was 1.12, indicating that cancer mortality rate among Black persons was on average 12% higher than that among White persons. Oncology provider density was significantly associated with greater cancer mortality disparities: every 5 additional oncology providers per 100 000 in a county was associated with a .02 increase in the Black:White cancer mortality ratio (95% CI: .007 to .03); however, the unexpected finding may be explained by further analysis showing that the relationship between oncology provider density and cancer mortality was different by race group. Every 5 additional oncologists per 100 000 was associated with a 1.6 decrease per 100 000 in cancer mortality rates among White persons (95% CI: -3.0 to -.2), whereas oncology provider density was not associated with cancer mortality among Black persons. CONCLUSION: Greater oncology provider density was associated with significantly lower cancer mortality among White persons, but not among Black persons. Higher oncology provider density alone may not resolve cancer mortality disparities, thus attention to ensuring equitable care is critical.

Our study provides timely information to address the growing concern about the need to increase oncology supply and the impact it might have on racial disparities in cancer outcomes. This analysis of counties across the US is the first study to estimate the association of oncology provider density with Black-White racial disparities in cancer mortality. We show that having more oncology providers in a county is associated with significantly lower cancer mortality among the White population, but is not associated with cancer mortality among the Black population, thereby leading to a disparity. Our findings suggest that having more oncology providers alone may be insufficient to overcome existing disadvantages for Black patients to access and use high-quality cancer care. These findings have important implications for addressing racial disparities in cancer outcomes that are persistent and well-documented in the US.

"Hang Ups, Let Downs, Bad Breaks, Setbacks": Impact of Structural Socioeconomic Racism and Resilience on Cognitive Change Over Time for Persons Racialized as Black.

Introduction: Older adults racialized as Black experience higher rates of dementia than those racialized as White. Structural racism produces socioeconomic challenges, described by artist Marvin Gaye as "hang ups, let downs, bad breaks, setbacks" that likely contribute to dementia disparities. Robust dementia literature suggests socioeconomic factors may also be key resiliencies. Methods: We linked state-level data reflecting the racialized landscape of economic opportunity across the 20th Century from the U.S. Census (1930-2010) with individual-level data on cognitive outcomes from the U.S. Health and Retirement Study participants racialized as Black. A purposive sample of participants born after the Brown v. Board ruling (born 1954-59) were selected who completed the modified Telephone Interview for Cognitive Status between 2010 and 2020 (N=1381). We tested associations of exposure to structural racism and resilience before birth, and during childhood, young-adulthood, and midlife with cognitive trajectories in mid-late life using mixed-effects regression models. Results: Older adults born in places with higher state-level structural socioeconomic racism experienced a more rapid cognitive decline in later life compared to those with lower levels of exposure. In addition, participants born in places with higher levels of state-level structural socioeconomic resilience experienced slower cognitive change over time than their counterparts. Discussion: These findings reveal the impact of racist U.S. policies enacted in the past that influence cognitive health over time and dementia risk later in life.

Does Consumer Credit Precede or Follow Health Among Older Adults? An Investigation in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Trial.

Background and Objectives: Consumer credit has shown increasing relevance to the health of older adults; however, studies have not been able to assess the extent to which creditworthiness influences future health or health influences future creditworthiness. We assessed the relationships between 4-year pre and postmorbid consumer credit history and self-rated physical and mental health outcomes among older adults. Research Design and Methods: Generalized estimating equations models assessed pre and postmorbid credit history (credit scores, derogatory accounts, and unpaid accounts in collections) and the onset of poor self-rated health (SF-36 score <50) among 1,740 participants aged 65+ in the Advanced Cognitive Training for Independent and Vital Elderly study from 2001 to 2017, linked to TransUnion consumer credit data. Results: In any given year, up to 1/4 of participants had a major derogatory, unpaid, or collections account, and up to 13% of the sample had poor health. Each 50-point increase in credit score trended toward a 5% lower odds of poor health in the next 1 year, a 6% lower odds in the next 2 years, and a statistically significant finding of 13% lower odds by 3 years. A drop in credit score was associated with a 10% greater odds of poor health in the next year, and having a major derogatory account was associated with an 86% greater odds of poor health in the next 3 years. After poor health onset, credit scores continued to see significant losses up to the 3 years, with larger decrements over time. Discussion and Implications: Having a major derogatory account or a sudden loss in credit may be a time to monitor older adults for changes in health. After a downturn in health, supporting older adults to manage their debt may help stabilize their credit.

Links of Previous Incarceration with Geriatric Syndromes and Chronic Health Conditions Among Older Adults in the United States.

BACKGROUND: This study investigated the association between previous incarceration and various geriatric and chronic health conditions among adults 50 and older in the United States. METHODS: Data came from the National Longitudinal Study of Adolescent to Adult Health - Parent Study (AHPS) collected in 2015-2017, including 2,007 individuals who participated in the parent study (Parent Sample) and 976 individuals who participated in the spouse/partner study (Spouse/Partner Sample). Multiple logistic regression was used to investigate the relationship between previous incarceration and geriatric syndromes (dementia, difficulty walking, difficulty seeing, difficulty with activities of daily living) and chronic health conditions (self-reported poor/fair health, diagnosis of cancer, hypertension, diabetes, heart disease, stroke, chronic lung disease, depression, and alcohol use [4 or more drinks per week]). RESULTS: In adjusted analyses, respondents with previous incarceration in the AHPS had significantly higher odds of reporting difficulty walking, activities of daily living difficulty, cancer diagnosis, depression diagnosis, and chronic lung disease (aORs= 2.21-2.95). Respondents in the AHPS spouse/partner study reported higher odds of difficulty seeing, cancer, depression, chronic lung disease, and heavy alcohol use (aORs= 1.02-2.15). CONCLUSIONS: Previous incarceration may have an adverse impact on healthy aging. Findings highlight the importance of addressing the enduring health impacts of incarceration, particularly as individuals transition into older adulthood.

Auditory brainstem implantation: surgical experience and audiometric outcomes in the pediatric population.

OBJECTIVE: Pediatric data regarding treatment via an auditory brainstem implant (ABI) remains sparse. The authors aimed to describe their experience at their institution and to delineate associated demographic data, audiometric outcomes, and surgical parameters. METHODS: An IRB-approved, retrospective chart review was conducted among the authors' pediatric patients who had undergone auditory brainstem implantation between 2012 and 2021. Demographic information including sex, age, race, coexisting syndrome(s), history of cochlear implant placement, average duration of implant use, and follow-up outcomes were collected. Surgical parameters collected included approach, intraoperative findings, number of electrodes activated, and complications. RESULTS: A total of 19 pediatric patients had an ABI placed at the authors' institution, with a mean age at surgery of 4.7 years (range 1.5-17.8 years). A total of 17 patients (89.5%) had bilateral cochlear nerve aplasia/dysplasia, 1 (5.3%) had unilateral cochlear nerve aplasia/dysplasia, and 1 (5.3%) had a hypoplastic cochlea with ossification. A total of 11 patients (57.9%) had a history of cochlear implants that were ineffective and required removal. The mean length of implant use was 5.31 years (0.25-10 years). Two patients (10.5%) experienced CSF-related complications requiring further surgical intervention. The most recent audiometric outcomes demonstrated that 15 patients (78.9%) showed improvement in their hearing ability: 5 with sound/speech awareness, 5 able to discriminate among speech and environmental sounds, and 5 able to understand common phrases/conversation without lip reading. Nine patients (47.4%) are in a school for the deaf and 7 (36.8%) are in a mainstream school with support. CONCLUSIONS: The authors' surgical experience with a multidisciplinary team demonstrates that the retrosigmoid approach for ABI placement in children with inner ear pathologies and severe sensorineural hearing loss is a safe and effective treatment modality. Audiometric outcome data showed that nearly 79% of these patients had an improvement in their environmental and speech awareness. Further multicenter collaborations are necessary to improve these outcomes and potentially standardize/enhance electrode placement.

Risk of dementia due to Co-exposure to air pollution and neighborhood disadvantage.

BACKGROUND: Co-exposure to air pollution and neighborhood disadvantage may influence cognition decline. We tested these associations in the context of dementia risk. METHODS: We leveraged a cohort of adults ≥65 years (n = 5397) enrolled from 2011 to 2018 in the National Health and Aging Trends Study (NHATS). Particulate matter (PM) ≤ 10 µm in diameter, PM ≤ 2.5 µm in diameter, carbon monoxide, nitric oxide, and nitrogen dioxide - and neighborhood disadvantage were tested for joint associations with dementia risk. Pollutant concentrations at the 2010 census tract level were assigned using the US Environmental Protection Agency's Community Multiscale Air Quality Modeling System. Neighborhood disadvantage was defined using the tract Social Deprivation Index (SDI). Dementia was determined through self- or proxy-report or scores indicative of "probable dementia" according to NHATS screening tools. Joint effects of air pollutants and SDI were tested using quantile g-computation Cox proportional hazards models. We also stratified joint air pollution effects across SDI tertiles. Analyses adjusted for age at enrollment, sex, education, partner status, urbanicity, income, race and ethnicity, years at residence, census segregation, and census region. RESULTS: SDI score (aHR = 1.08; 95% CI 0.96, 1.22), joint air pollution (aHR = 1.03, 95% CI 0.92, 1.16) and joint SDI with air pollution (aHR = 1.04, 95% CI 0.89, 1.22) were not associated with dementia risk. After accounting for competing risk of death, joint SDI with air pollution was not associated with dementia risk (aHR = 1.06; 95% CI 0.87, 1.29). In stratified models, joint air pollution was associated with greater risk of dementia at high (aHR = 1.19; 95% CI 0.87, 1.63), but not at medium or low SDI. CONCLUSION: Air pollution was associated with greater dementia risk in disadvantaged areas after accounting for competing risks. Air pollution associations with dementia incidence may be attenuated when other risk factors are more prominent in disadvantaged neighborhoods.

Caregiving and Obesity among Black American Adults.

Black American adults often report higher rates of obesity and caregiving compared with other racial or ethnic groups. Consequently, many Black American caregivers and care recipients are obese or have obesity-related chronic conditions (e.g., diabetes, hypertension). This study investigated associations between caregiving and obesity among Black Americans, including the role of health behaviors and chronic conditions. The sample included data from 2015 and 2017 Behavioral Risk Factor Surveillance System for non-Hispanic Black (NHB) or African American adult caregivers (n = 2,562) and noncaregivers (n = 7,027). The association between obesity (dependent variable) and caregiving status, fruit consumption, vegetable consumption, physical activity, and number of chronic conditions (independent variables) were evaluated using hierarchical binomial logistic regressions. Caregiving, being female, and chronic conditions were associated with higher odds of obesity, while physical activity was associated with lower odds of obesity. Physical activity, diet, and chronic conditions did not account for differences in obesity among caregiving and noncaregiving Black Americans. Increasing understanding of health behaviors and chronic disease burden of NHB caregivers has implications for programs aiming to improve obesity-related outcomes for caregivers and recipients. Future research should investigate multilevel factors that contribute to observed differences.

Salvage Microsurgery Following Failed Primary Radiosurgery in Sporadic Vestibular Schwannoma.

Importance: Management of sporadic vestibular schwannoma with radiosurgery is becoming increasingly common globally; however, limited data currently characterize patient outcomes in the setting of microsurgical salvage for radiosurgical failure. Objective: To describe the clinical outcomes of salvage microsurgery following failed primary stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) among patients with sporadic vestibular schwannoma. Design, Setting, and Participants: This was a cohort study of adults (≥18 years old) with sporadic vestibular schwannoma who underwent salvage microsurgery following failed primary SRS/FSRT in 7 vestibular schwannoma treatment centers across the US and Norway. Data collection was performed between July 2022 and January 2023, with data analysis performed between January and July 2023. Exposure: Salvage microsurgical tumor resection. Main Outcomes and Measures: Composite outcome of undergoing less than gross total resection (GTR) or experiencing long-term facial paresis. Results: Among 126 patients, the median (IQR) age at time of salvage microsurgery was 62 (53-70) years, 69 (55%) were female, and 113 of 117 (97%) had tumors that extended into the cerebellopontine angle at time of salvage. Of 125 patients, 96 (76%) underwent primary gamma knife SRS, while 24 (19%) underwent linear accelerator-based SRS; the remaining patients underwent FSRT using other modalities. Postoperative cerebrospinal fluid leak was seen in 15 of 126 patients (12%), hydrocephalus in 8 (6%), symptomatic stroke in 7 (6%), and meningitis in 2 (2%). Each 1-mm increase in cerebellopontine angle tumor size was associated with a 13% increased likelihood of foregoing GTR (64 of 102 patients [63%]) or long-term postoperative House-Brackmann grade higher than I (48 of 102 patients [47%]) (odds ratio, 1.13; 95% CI, 1.04-1.23). Following salvage microsurgery, tumor growth-free survival rates at 1, 3, and 5 years were 97% (95% CI, 94%-100%), 93% (95% CI, 87%-99%), and 91% (95% CI, 84%-98%), respectively. Conclusions: In this cohort study, more than half of patients who received salvage microsurgery following primary SRS/FSRT underwent less than GTR or experienced some degree of facial paresis long term. These data suggest that the cumulative risk of developing facial paresis following primary SRS/FSRT by the end of the patient's journey with treatment approximates 2.5% to 7.5% when using published primary SRS/FSRT long-term tumor control rates.

Neighborhood Segregation and Access to Live Donor Kidney Transplantation.

Importance: Identifying the mechanisms of structural racism, such as racial and ethnic segregation, is a crucial first step in addressing the persistent disparities in access to live donor kidney transplantation (LDKT). Objective: To assess whether segregation at the candidate's residential neighborhood and transplant center neighborhood is associated with access to LDKT. Design, Setting, and Participants: In this cohort study spanning January 1995 to December 2021, participants included non-Hispanic Black or White adult candidates for first-time LDKT reported in the US national transplant registry. The median (IQR) follow-up time for each participant was 1.9 (0.6-3.0) years. Main Outcome and Measures: Segregation, measured using the Theil H method to calculate segregation tertiles in zip code tabulation areas based on the American Community Survey 5-year estimates, reflects the heterogeneity in neighborhood racial and ethnic composition. To quantify the likelihood of LDKT by neighborhood segregation, cause-specific hazard models were adjusted for individual-level and neighborhood-level factors and included an interaction between segregation tertiles and race. Results: Among 162 587 candidates for kidney transplant, the mean (SD) age was 51.6 (13.2) years, 65 141 (40.1%) were female, 80 023 (49.2%) were Black, and 82 564 (50.8%) were White. Among Black candidates, living in a high-segregation neighborhood was associated with 10% (adjusted hazard ratio [AHR], 0.90 [95% CI, 0.84-0.97]) lower access to LDKT relative to residence in low-segregation neighborhoods; no such association was observed among White candidates (P for interaction = .01). Both Black candidates (AHR, 0.94 [95% CI, 0.89-1.00]) and White candidates (AHR, 0.92 [95% CI, 0.88-0.97]) listed at transplant centers in high-segregation neighborhoods had lower access to LDKT relative to their counterparts listed at centers in low-segregation neighborhoods (P for interaction = .64). Within high-segregation transplant center neighborhoods, candidates listed at predominantly minority neighborhoods had 17% lower access to LDKT relative to candidates listed at predominantly White neighborhoods (AHR, 0.83 [95% CI, 0.75-0.92]). Black candidates residing in or listed at transplant centers in predominantly minority neighborhoods had significantly lower likelihood of LDKT relative to White candidates residing in or listed at transplant centers located in predominantly White neighborhoods (65% and 64%, respectively). Conclusions: Segregated residential and transplant center neighborhoods likely serve as a mechanism of structural racism, contributing to persistent racial disparities in access to LDKT. To promote equitable access, studies should assess targeted interventions (eg, community outreach clinics) to improve support for potential candidates and donors and ultimately mitigate the effects of segregation.

Adherence to the healthy eating index-2010 and alternative healthy eating index-2010 in relation to metabolic syndrome among African Americans in the Jackson heart study.

OBJECTIVE: The primary objective of this study was to determine whether Healthy Eating Index (HEI) and Alternative Healthy Eating Index (AHEI) scores were associated with incident metabolic syndrome. DESIGN: This study is a secondary analysis of data from the Jackson Heart Study. HEI and AHEI scores were divided into quintiles and Cox proportional hazards regression models were analysed for 1864 African American adults free from metabolic syndrome at Exam 1 to examine the incidence of metabolic syndrome by quintile of dietary quality score. SETTING: Hinds, Madison and Rankin counties, Mississippi, USA. PARTICIPANTS: African American adults, ages 21-94 years, 60·9 % female. RESULTS: Over a mean follow-up time of 6·7 years, we observed 932 incident cases of metabolic syndrome. After adjusting for multiple covariates, a higher HEI score at Exam 1 was not associated with the risk of incident metabolic syndrome, except when looking at the trend analysis for the subgroup of adults with two metabolic syndrome components at Exam 1 (P-trend = 0·03). A higher AHEI score at Exam 1 was associated with the risk of incident metabolic syndrome (hazard ratio for those in the highest quintile compared to the lowest: 0·80 (95 % CI: 0·65, 0·99), P-trend = 0·03). CONCLUSION: These findings suggest that a dietary pattern that scores higher on the AHEI may help reduce the risk of metabolic syndrome, even for adults who already have two of the minimum of three components required for a diagnosis of metabolic syndrome.

Specific labeling of newly synthesized lipopolysaccharide via metabolic incorporation of azido-galactose.

Gram-negative bacteria possess an asymmetric outer membrane (OM) primarily composed of lipopolysaccharides (LPS) on the outer leaflet and phospholipids on the inner leaflet. The outer membrane functions as an effective permeability barrier to compounds such as antibiotics. Studying LPS biosynthesis is therefore helpful to explore novel strategies for new antibiotic development. Metabolic glycan labeling of the bacterial surface has emerged as a powerful method to investigate LPS biosynthesis. However, the previously reported methods of labeling LPS are based on radioactivity or difficult-to-produce analogs of bacterial sugars. In this study, we report on the incorporation of azido galactose into the LPS of the Gram-negative bacteria Escherichia coli and Salmonella typhi via metabolic labeling. As a common sugar analog, azido galactose successfully labeled both O-antigen and core of Salmonella LPS, but not E. coli LPS. This labeling of Salmonella LPS, as shown by SDS-PAGE analysis and fluorescence microscopy, differs from the previously reported labeling of either O-antigen or core of LPS. Our findings are useful for studying LPS biogenesis pathways in Gram-negative bacteria like Salmonella. In addition, our approach is helpful for screening for agents that target LPS biosynthesis as it allows for the detection of newly synthesized LPS that appears in the OM. Furthermore, this approach may also aid in isolating chemically modified LPS for vaccine development or immunotherapy.

Whole-exome sequencing of Nigerian benign prostatic hyperplasia reveals increased alterations in apoptotic pathways.

BACKGROUND: Through whole-exome sequencing of 60 formalin-fixed paraffin-embedded Nigerian (NGRn) benign prostatic hyperplasia (BPH) samples, we identified germline and somatic alterations in apoptotic pathways impacting BPH development and progression. Prostate enlargement is a common occurrence in male aging; however, this enlargement can lead to lower urinary tract symptoms that negatively impact quality of life. This impact is disproportionately present in men of African ancestry. BPH pathophysiology is poorly understood and studies examining non-European populations are lacking. METHODS: In this study, NGRn BPH, normal prostate, and prostate cancer (PCa) tumor samples were sequenced and compared to characterize genetic alterations in NGRn BPH. RESULTS: Two hundred and two nonbenign, ClinVar-annotated germline variants were present in NGRn BPH samples. Six genes [BRCA1 (92%), HSD3B1 (85%), TP53 (37%), PMS2 (23%), BARD1 (20%), and BRCA2 (17%)] were altered in at least 10% of samples; however, compared to NGRn normal and tumor, the frequency of alterations in BPH samples showed no significant differences at the gene or variant level. BRCA2_rs11571831 and TP53_rs1042522 germline alterations had a statistically significant co-occurrence interaction in BPH samples. In at least two BPH samples, 173 genes harbored somatic variants known to be clinically actionable. Three genes (COL18A1, KIF16B, and LRP1) showed a statistically significant (p < 0.05) higher frequency in BPH. NGRn BPH also had five gene pairs (PKD1/KIAA0100, PKHD1/PKD1, DNAH9/LRP1B, NWD1/DCHS2, and TCERG1/LMTK2) with statistically significant co-occurring interactions. Two hundred and seventy-nine genes contained novel somatic variants in NGRn BPH. Three genes (CABP1, FKBP1C, and RP11-595B24.2) had a statistically significant (p < 0.05) higher alteration frequency in NGRn BPH and three were significantly higher in NGRn tumor (CACNA1A, DMKN, and CACNA2D2). Pairwise Fisher's exact tests showed 14 gene pairs with statistically significant (p < 0.05) interactions and four interactions approaching significance (p < 0.10). Mutational patterns in NGRn BPH were similar to COSMIC (Catalog of Somatic Mutations in Cancer) signatures associated with aging and dysfunctional DNA damage repair. CONCLUSIONS: NGRn BPH contained significant germline alteration interactions (BRCA2_rs11571831 and TP53_rs1042522) and increased somatic alteration frequencies (LMTK2, LRP1, COL18A1, CABP1, and FKBP1C) that impact apoptosis. Normal prostate development is maintained by balancing apoptotic and proliferative activity. Dysfunction in either mechanism can lead to abnormal prostate growth. This work is the first to examine genomic sequencing in NGRn BPH and provides data that fill known gaps in the understanding BPH and how it impacts men of African ancestry.

The Association of eHealth Literacy Skills and mHealth Application Use Among US Adults With Obesity: Analysis of Health Information National Trends Survey Data.

BACKGROUND: Physical inactivity and a poor diet are modifiable behaviors that contribute to obesity. Obesity is a well-recognized risk factor for chronic diseases, including diabetes. Mobile health (mHealth) apps can play an important adjuvant role in preventing and treating chronic diseases and promoting positive health behavior change among people with obesity, and eHealth literacy skills have the potential to impact mHealth app use. OBJECTIVE: The purpose of this study was to explore the associations between the 2 dimensions, access and application, of eHealth literacy skills and mHealth app use among US adults (≥18 years of age) with obesity (BMI ≥30 kg/m2). METHODS: Data were obtained from February to June 2020 using the Health Information National Trends Survey 5. A total of 1079 respondents met the inclusion criteria of adults with obesity and owners of smartphones. Individual associations between mHealth app use and sociodemographic variables were explored using weighted chi-square and 2-tailed t tests. A multivariable weighted logistic regression model was fitted, and adjusted odds ratios (ORs) of using mHealth apps with corresponding 95% CIs were reported across multiple sociodemographic variables. An Ising model-weighted network visualization was produced. A receiver operating characteristic curve was calculated, and the area under the curve was reported with the corresponding Delong 95% CI. RESULTS: A majority of respondents were female (550/923, 59.6%) or non-Hispanic White (543/923, 58.8%). Individuals in households earning less than US $50,000 comprised 41.4% (382/923) of the sample. All sociodemographic variables were found to be univariately significant at the 5% level, except employment and region. Results from the multivariable weighted logistic regression model showed that the adjusted odds of using an mHealth app are 3.13 (95% CI 1.69-5.80) and 2.99 (95% CI 1.67-5.37) times higher among those with an access eHealth literacy skill of using an electronic device to look for health or medical information for themselves and an application eHealth literacy skill of using electronic communications with a doctor or doctor's office, respectively. Several sociodemographic variables were found to be significant, such as education, where adjusted ORs comparing subgroups to the lowest educational attainment were substantial (ORs ≥7.77). The network visualization demonstrated that all eHealth literacy skills and the mHealth app use variable were positively associated to varying degrees. CONCLUSIONS: This work provides an initial understanding of mHealth app use and eHealth literacy skills among people with obesity, identifying people with obesity subpopulations who are at risk of a digital health divide. Future studies should identify equitable solutions for people with obesity (as well as other groups) and their use of mHealth apps.