Understanding the implementation and sustainability needs of evidence-based programs for racial and ethnic minoritized older adults in under-resourced communities with limited aging services.

BACKGROUND: Evidence-based programs (EBPs) for older adults effectively improve health outcomes. However, there is a limited understanding of the unique needs of service providers as they consider adopting, implementing, and maintaining programs for older minority adults in low-income communities with limited aging services. METHODS: We conducted semi-structured interviews with key informants of community-based organizations (CBOs) to understand implementation and sustainability needs of CBOs within four racial and ethnically diverse Los Angeles County geographic areas. We performed thematic analysis of interview transcripts. RESULTS: Interviews were conducted with representatives from 25 senior-serving agencies providing aging-related EBPs. CBO representatives reported implementing EBPs in 8 domains: Falls Prevention (68%), Mental Health (64%), Caregiver Health (48%), Chronic Disease Management (48%), Diabetes Management (36%), Arthritis Management (28%), Physical Activity (24%), and Multiple Conditions Management (8%). Themes are presented using the six domains of the Bass and Judge framework for factors impacting successful and sustained EBP implementation. CBOs in low-income and diverse communities described unique challenges with tailoring interventions based on local community context (literacy, language), cultural context, and locally available resources (technology, safe community spaces, transportation) and faced resource-intensive administrative burdens through staff turnover, data collection, sustainable funding, and networking. CONCLUSIONS: Serving racial and ethnic communities has unique challenges that require tailored approaches and additional resources to ensure equitable access to EBPs for all communities. We describe suggestions for enhancing the effective adoption of EBPs among service agencies in under-resourced and diverse aging communities serving populations with aging-related health disparities.

Robust SARS-CoV-2 T cell responses with common TCRαß motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells.

Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%-75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response.

The SWI/SNF ATPase BRG1 stimulates DNA end resection and homologous recombination by reducing nucleosome density at DNA double strand breaks and by promoting the recruitment of the CtIP nuclease.

DNA double strand breaks (DSBs) are among the most toxic DNA lesions and can be repaired accurately through homologous recombination (HR). HR requires processing of the DNA ends by nucleases (DNA end resection) in order to generate the required single-stranded DNA (ssDNA) regions. The SWI/SNF chromatin remodelers are 10-15 subunit complexes that contain one ATPase (BRG1 or BRM). Multiple subunits of these complexes have recently been identified as a novel family of tumor suppressors. These complexes are capable of remodeling chromatin by pushing nucleosomes along the DNA. More recent studies have identified these chromatin remodelers as important factors in DNA repair. Using the DR-U2OS reporter system, we show that the down regulation of BRG1 significantly reduces HR efficiency, while BRM has a minor effect. Inactivation of BRG1 impairs DSB repair and results in a defect in DNA end resection, as measured by the amount of BrdU-containing ssDNA generated after DNA damage. Inactivation of BRG1 also impairs the activation of the ATR kinase, reduces the levels of chromatin-bound RPA, and reduces the number of RPA and RAD51 foci after DNA damage. This defect in DNA end resection is explained by the defective recruitment of GFP-CtIP to laser-induced DSBs in the absence of BRG1. Importantly, we show that BRG1 reduces nucleosome density at DSBs. Finally, inactivation of BRG1 renders cells sensitive to anti-cancer drugs that induce DSBs. This study identifies BRG1 as an important factor for HR, which suggests that BRG1-mutated cancers have a DNA repair vulnerability that can be exploited therapeutically.

Multilevel interventions to prevent and reduce obesity.

The complex, multilevel causes of the ongoing obesity epidemic necessitate multilevel approaches to address the problem. Accordingly, interest in multilevel obesity interventions has expanded rapidly in recent years. We conducted an updated literature review of multilevel interventions for obesity prevention and reduction. We identified six protocols and six articles on completed studies that were published between January 2016 and September 2018. Of the completed studies, four found significant intervention effects on body mass index and/or waist circumference. Two showed significant improvements in diet and two showed significant improvements in physical activity. These studies highlight the promise multilevel interventions offer for addressing obesity at the population level.

Detection of Gluten in Gluten-Free Labeled Restaurant Food: Analysis of Crowd-Sourced Data.

INTRODUCTION: Adherence to a gluten-free (GF) diet is the mainstay of therapy for celiac disease. Until now, those wishing to avoid gluten in restaurants had to rely on menu labels, word of mouth, intuition, and restaurant workers' advice, with a relative dearth of supporting data. We used crowd-sourced data from users of a portable gluten detection device to estimate rates of, and identify risk factors for, gluten contamination of supposed GF restaurant foods. METHODS: We analyzed data from a portable gluten detection device (Nima), collected across the United States during an 18-month period by users who opted to share the results of their point-of-care tests. Data were sorted by region, time of day, median household income in the restaurant's vicinity, restaurant genre, and food items. We used the χ test for bivariate analysis and multiple logistic regression for multivariate analysis to identify predictors of gluten detection in restaurant food. RESULTS: There were 5,624 tests, performed by 804 users, in the examined period. Gluten was detected in 32% of GF labeled foods. Rates of gluten detection differed by meal, with 27.2% at breakfast and 34.0% at dinner (P = 0.0008). GF labeled pizza and pasta were most likely to test positive for gluten, with gluten detected in 53.2% of pizza and 50.8% of pasta samples. On multivariate analysis, GF labeled food was less likely to test positive for gluten in the West than in the Northeast United States (odds ratio 0.80; 95% confidence interval 0.67-0.95). CONCLUSIONS: This study of crowd-sourced data suggests that a substantial fraction of GF labeled restaurant foods contain detectable gluten. Although the highly sensitive Nima device may detect gluten at levels <20 parts per million (ppm), leading to gluten exposure of unknown clinical significance, our findings raise a potential concern. In addition, our findings of higher rates of gluten detection in pizza and pasta provide practical data when providing dining strategies for patients with celiac disease.

Neighborhood Disorder and Obesity-Related Outcomes among Women in Chicago.

Neighborhood psychosocial stressors like crime and physical disorder may influence obesity-related outcomes through chronic stress or through adverse effects on health behaviors. Google Street View imagery provides a low-cost, reliable method for auditing neighborhood physical disorder, but few studies have examined associations of Street View-derived physical disorder scores with health outcomes. We used Google Street View to audit measures of physical disorder for residential census blocks from 225 women aged 18⁻44 enrolled from 4 Chicago neighborhoods. Latent neighborhood physical disorder scores were estimated using an item response theory model and aggregated to the block group level. Block-group level physical disorder scores and rates of police-recorded crime and 311 calls for service requests were linked to participants based on home addresses. Associations were estimated for 6 obesity-related outcomes: body mass index, obesity, total moderate-to-vigorous physical activity, and weekly consumption of sugar-sweetened beverages, fast food, and snacks. Hierarchical regression models estimated cross-sectional associations adjusting for individual sociodemographics and neighborhood poverty. Higher neighborhood physical disorder was associated with greater odds of obesity (OR: 1.43, 95% CI: 1.01, 2.02). Living in a neighborhood with a higher crime rate was associated with an increase in weekly snack consumption of 3.06 (95% CI: 1.59, 4.54).

Bitter peptides activate hTAS2Rs, the human bitter receptors.

Fermented food contains numerous peptides derived from material proteins. Bitter peptides formed during the fermentation process are responsible for the bitter taste of fermented food. We investigated whether human bitter receptors (hTAS2Rs) recognize bitterness of peptides with a heterologous expression system. HEK293 cells expressing hTAS2R1, hTAS2R4, hTAS2R14, and hTAS2R16 responded to bitter casein digests. Among those cells, the hTAS2R1-expressing cell was most strongly activated by the synthesized bitter peptides Gly-Phe and Gly-Leu, and none of the cells was activated by the non-bitter dipeptide Gly-Gly. The results showed that these bitter peptides, as well as many other bitter compounds, activate hTAS2Rs, suggesting that humans utilize these hTAS2Rs to recognize and perceive the structure and bitterness of peptides.

Identification and functional characterization of a voltage-gated chloride channel and its novel splice variant in taste bud cells.

Taste bud cells are epithelial cells with neuronal properties. Voltage-dependent ion channels have been physiologically described in these cells. Here, we report the molecular identification and functional characterization of a voltage-gated chloride channel (ClC-4) and its novel splice variant (ClC-4A) from taste bud cells. ClC-4A skipped an exon near its 5'-end, incurring the loss of 60 amino acids at the N terminus. In situ hybridization and immunohistochemistry localized these two channels' transcripts and proteins to a subset of taste bud cells. Electrophysiological recordings of the heterologously expressed channels in Xenopus oocytes showed that ClC-4 and ClC-4A have opposite sensitivity to pH and unique ion selectivity. The chloride channel blockers niflumic acid and 5-nitro-2-(3-phenylpropylamino)benzoic acid had a slight or no inhibitory effect on the conductance of ClC-4, but both blockers inhibited ClC-4A, suggesting that ClC-4A is a candidate channel for an acid-induced 5-nitro-2-(3-phenylpropylamino)benzoic acid-sensitive current. Furthermore, these two channels may play a role in bitter-, sweet-, and umami-mediated taste transmission by regulating transmitter uptake into synaptic vesicles.