COVID-19 has disproportionately affected socially vulnerable communities characterized by lower income, lower education attainment, and higher proportions of minority populations, among other factors ...(1-4). Disparities in COVID-19 incidence and the impact of vaccination on incidence disparities by community income were assessed among 81 communities in Los Angeles, California. Median community vaccination coverage and COVID-19 incidence were calculated across household income strata using a generalized linear mixed effects model with Poisson distribution during three COVID-19 surge periods: two before vaccine availability (July 2020 and January 2021) and the third after vaccines became widely available in April 2021 (September 2021). Adjusted incidence rate ratios (aIRRs) during the peak month of each surge were compared across communities grouped by median household income percentile. The aIRR between communities in the lowest and highest median income deciles was 6.6 (95% CI = 2.8-15.3) in July 2020 and 4.3 (95% CI = 1.8-9.9) in January 2021. However, during the September 2021 surge that occurred after vaccines became widely availabile, model estimates did not identify an incidence disparity between the highest- and lowest-income communities (aIRR = 0.80; 95% CI = 0.35-1.86). During this surge, vaccination coverage was lowest (59.4%) in lowest-income communities and highest (71.5%) in highest-income communities (p<0.001). However, a significant interaction between income and vaccination on COVID-19 incidence (p<0.001) indicated that the largest effect of vaccination on disease incidence occured in the lowest-income communities. A 20% increase in community vaccination was estimated to have resulted in an additional 8.1% reduction in COVID-19 incidence in the lowest-income communities compared with that in the highest-income communities. These findings highlight the importance of improving access to vaccination and reducing vaccine hesitancy in underserved communities in reducing disparities in COVID-19 incidence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
iDASH (integrating data for analysis, anonymization, and sharing) is the newest National Center for Biomedical Computing funded by the NIH. It focuses on algorithms and tools for sharing data in a ...privacy-preserving manner. Foundational privacy technology research performed within iDASH is coupled with innovative engineering for collaborative tool development and data-sharing capabilities in a private Health Insurance Portability and Accountability Act (HIPAA)-certified cloud. Driving Biological Projects, which span different biological levels (from molecules to individuals to populations) and focus on various health conditions, help guide research and development within this Center. Furthermore, training and dissemination efforts connect the Center with its stakeholders and educate data owners and data consumers on how to share and use clinical and biological data. Through these various mechanisms, iDASH implements its goal of providing biomedical and behavioral researchers with access to data, software, and a high-performance computing environment, thus enabling them to generate and test new hypotheses.
The number of older adults with complex health needs in Ontario is growing. The Ministry of Health and Long-Term Care requested a resource mapping project to assess the current 2018 and projected ...2025 number of specialist physician resources.
Geriatric specialist physicians were defined as geriatricians, geriatric psychiatrists, and Care of the Elderly (COE) physicians. We determined the current number of geriatricians, geriatric psychiatrists, and COEs and clinical full-time-equivalent complement (CFTE) for geriatric medicine and geriatric psychiatry specialists. We projected the number of new trainees expected to enter practice and the number of physicians expected to retire by 2025. We compared these numbers and projections against established specialist/population ratios for geriatricians and geriatric psychiatrists.
There was a deficit of geriatricians and geriatric psychiatrists (geriatricians: CFTE deficit of 150.5; geriatric psychiatrists: CFTE deficit of 116.3). In 2025, the projected CFTE deficit of geriatricians will increase to at least 210.35 and geriatric psychiatrists to 194.6. Only about 30% of COE physicians work in direct support of specialized services for the elderly.
There is significant current and anticipated undersupply in the required number of geriatricians, geriatric psychiatrists, and COE physicians to meet anticipated population demand.
Casein‐hydrolysates (NaCaH) are desirable functional ingredients, but their bitterness impedes usage in foods. This study sought to validate a paper‐disk approach to help evaluate bitterness in ...NaCaHs and to develop a food‐grade approach to separate a NaCaH into distinct fractions, which could be evaluated by a sensory panel. Membrane filtration generated < 0.2‐µm and <3‐kDa permeates. Further fractionation of the <3‐kDa permeate by flash‐chromatography generated four fractions using ethanol (EtOH) concentrations of 5, 10, 30, and 50%. As some fractions were poorly soluble in water, the fractions were resolubilized in EtOH and impregnated into paper disks for sensory evaluation. Bitterness differences observed in the membrane fractions using this sensory evaluation approach reflected those observed for the same fractions presented as a liquid. The flash‐chromatography fractions increased in bitterness with an increase in hydrophobicity, except for the 50% EtOH fraction which had little bitterness. Amino acid analysis of the fractions showed enrichment of different essential amino acids in both the bitter and less bitter fractions.
Practical applications
The developed food‐grade fractionation system, allowed for a simple and reasonably scaled approach to separating a NaCaH, into physicochemically different fractions that could be evaluated by a sensory panel. The method of sensory evaluation used in this study, in which NaCaH samples are impregnated into paper disks, provided potential solutions for issues such as sample insolubility and limited quantities of sample. As the impregnated paper‐disk samples were dehydrated, their long storage life could also be suitable for sensory evaluations distributed by mail for large consumer studies. The research, in this study, allowed for a greater understanding of the physicochemical basis for bitterness in this NaCaH. As some essential amino acids were enriched in the less bitter fractions, selective removal of bitter fractions could allow for the incorporation of the less bitter NaCaH fractions into food products for added nutritional value, without negatively impacting sensory properties. There is potential for this approach to be applied to other food ingredients with undesirable tastes, such as polyphenols.
Recent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep ...physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible PVS volumes, a putative marker of perivascular dysfunction, are associated with compensatory differences in real-world human sleep behavior.
We analyzed data from 152 cerebrovascular disease patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). PVS volumes were measured using 3T-MRI. Self-reported total sleep time, time in bed, and daytime dysfunction were extracted from the Pittsburgh Sleep Quality Index.
Individuals with greater PVS volumes reported longer time in bed (+0.85 h per log10 proportion of intracranial volume (ICV) occupied by PVS, SE = 0.30, p = 0.006) and longer total sleep times (+0.70 h per log10 proportion of ICV occupied by PVS volume, SE = 0.33, p = 0.04), independent of vascular risk factors, sleep apnea, nocturnal sleep disturbance, depression, and global cognitive status. Further analyses suggested that the positive association between PVS volumes and total sleep time was mediated by greater time in bed. Moreover, despite having on average greater total sleep times, individuals with greater basal ganglia PVS volumes were more likely to report daytime dysfunction (OR 5.63 per log10 proportion of ICV occupied by PVS, 95% CI: 1.38–22.26, p = 0.018).
Individuals with greater PVS volumes spend more time in bed, resulting in greater total sleep time, which may represent a behavioral compensatory response to perivascular space dysfunction.
•Normal perivascular spaces (PVS) play an important role in sleep function.•Perivascular abnormalities may be an important determinant of sleep behavior.•Interventions targeting PVS biology may modify sleep need and daytime dysfunction.
A sizable portion of youth (ages 13-24) living with HIV in the United States have unsuppressed viral load. The AIDS Interventions (ATN) 152 study evaluating the Triggered Escalating Real-Time ...Adherence (TERA) intervention baseline data were examined to identify correlates of high viremia (>5000 copies/mL) and self-reported adherence, which can help in planning of differentiated services for viremic youth. Depression, HIV-stigma, and cannabis use were common in this sample of 87 youth. Almost half (48%) had high viremia, which associated with enacted stigma, moderate- to high-risk alcohol use, mental health diagnosis, and age ≥21. Self-reported adherence was related to viral load and associated with mental and physical health functioning, depression, social support, self-confident decision-making, total and internalized stigma, adherence motivation, and report of a missed a care visit in the past 6 months. Mental health emerged as a common correlate of viral load and adherence. Clinical Trial Registration number: NCT03292432.
The recombinant Canarypox ALVAC-HIV/gp120/alum vaccine regimen was the first to significantly decrease the risk of HIV acquisition in humans, with equal effectiveness in both males and females. ...Similarly, an equivalent SIV-based ALVAC vaccine regimen decreased the risk of virus acquisition in Indian rhesus macaques of both sexes following intrarectal exposure to low doses of SIV.sub.mac251 . Here, we demonstrate that the ALVAC-SIV/gp120/alum vaccine is also efficacious in female Chinese rhesus macaques following intravaginal exposure to low doses of SIV.sub.mac251 and we confirm that CD14.sup.+ classical monocytes are a strong correlate of decreased risk of virus acquisition. Furthermore, we demonstrate that the frequency of CD14.sup.+ cells and/or their gene expression correlates with blood Type 1 CD4.sup.+ T helper cells, alpha.sub.4 beta.sub.7 .sup.+ plasmablasts, and vaginal cytocidal NKG2A.sup.+ cells. To better understand the correlate of protection, we contrasted the ALVAC-SIV vaccine with a NYVAC-based SIV/gp120 regimen that used the identical immunogen. We found that NYVAC-SIV induced higher immune activation via CD4.sup.+ Ki67.sup.+ CD38.sup.+ and CD4.sup.+ Ki67.sup.+ alpha.sub.4 beta.sub.7 .sup.+ T cells, higher SIV envelope-specific IFN-gamma producing cells, equivalent ADCC, and did not decrease the risk of SIV.sub.mac251 acquisition. Using the systems biology approach, we demonstrate that specific expression profiles of plasmablasts, NKG2A.sup.+ cells, and monocytes elicited by the ALVAC-based regimen correlated with decreased risk of virus acquisition.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The chemokine receptor CXCR4 is required, together with CD4, for entry by some isolates of HIV-1, particularly those that emerge late in infection. The use of CXCR4 by these viruses likely has ...profound effects on viral host range and correlates with the evolution of immunodeficiency. Stromal cell-derived factor-1 (SDF-1), the ligand for CXCR4, can inhibit infection by CXCR4-dependent viruses. To understand the mechanism of this inhibition, we used a monoclonal antibody that is specific for CXCR4 to analyze the effects of phorbol esters and SDF-1 on surface expression of CXCR4. On human T cell lines SupT1 and BC7, CXCR4 undergoes slow constitutive internalization (1.0% of the cell surface pool/min). Addition of phorbol esters increased this endocytosis rate >6-fold and reduced cell surface CXCR4 expression by 60 to 90% over 120 min. CXCR4 was internalized through coated pits and coated vesicles and subsequently localized in endosomal compartments from where it could recycle to the cell surface after removal of the phorbol ester. SDF-1 also induced the rapid down modulation (half time ∼5 min) of CXCR4. Using mink lung epithelial cells expressing CXCR4 and a COOH-terminal deletion mutant of CXCR4, we found that an intact cytoplasmic COOH-terminal domain was required for both PMA and ligand-induced CXCR4 endocytosis. However, experiments using inhibitors of protein kinase C indicated that SDF-1 and phorbol esters trigger down modulation through different cellular mechanisms. SDF-1 inhibited HIV-1 infection of mink cells expressing CD4 and CXCR4. The inhibition of infection was less efficient for CXCR4 lacking the COOH-terminal domain, suggesting at least in part that SDF-1 inhibition of virus infection was mediated through ligand-induced internalization of CXCR4. Significantly, ligand induced internalization of CXCR4 but not CD4, suggesting that CXCR4 and CD4 do not normally physically interact on the cell surface. Together these studies indicate that endocytosis can regulate the cell-surface expression of CXCR4 and that SDF-1-mediated down regulation of cell-surface coreceptor expression contributes to chemokine-mediated inhibition of HIV infection.
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