Efficient Identification of HIV Serodiscordant Couples by Existing HIV Testing Programs in South Brazil.

ObjectiveTo examine the feasibility of identifying HIV negative at risk individuals in HIV serodiscordant couples, during voluntary HIV testing in South Brazil.MethodsWe surveyed HIV testers at 4 public testing sites in Rio Grande do Sul. We obtained information on risk behaviors and sexual partnerships. HIV testing and testing for recent infection were performed; HIV prevalence and risk behaviors were assessed among subjects who reported having a steady partner who was HIV positive (serodiscordant group) and compared with the general testing population.ResultsAmong 3100 patients, 490 (15.8%) reported being in a steady relationship with an HIV positive partner. New HIV infections were diagnosed in 23% of the serodiscordant group (vs. 13% in the general population, p = 0.01); among newly positive subjects, recent HIV infections were more frequent (23/86, 26.7%) among testers with positive partners than among the general testing group (52/334; 15.6%; p = 0.016). Less than half of the serodiscordant testers reported having used a condom during the last sexual intercourse with their HIV-positive partner. Participants with inconsistent condom use with steady partner were four times more likely to test positive for HIV compared to those who reported always using condoms with the steady partner (OR: 4.2; 95% CI: 2.3 to 7.5).ConclusionIt is highly feasible to identify large numbers of HIV susceptible individuals who are in HIV serodiscordant relationships in South Brazil testing sites. Condom use within HIV serodiscordant couples is low in this setting, suggesting urgent need for biomedical prevention strategies to reduce HIV transmission

Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex

It is unknown whether adipokines derived from adipose tissues modulate endoplasmic reticulum (ER) stress induced in obesity. Here, we show that visceral adipose tissue-derived serine protease inhibitor (vaspin) binds to cell-surface 78-kDa glucose-regulated protein (GRP78), which is recruited from ER to plasma membrane under ER stress. Vaspin transgenic mice were protected from diet-induced obesity, glucose intolerance, and hepatic steatosis, while vaspin-deficient mice developed glucose intolerance associated with upregulation of ER stress markers. With tandem affinity tag purification using HepG2 cells, we identified GRP78 as an interacting molecule. The complex formation of vaspin, GRP78, and murine tumor cell DnaJ-like protein 1 (MTJ-1) (DnaJ homolog, subfamily C, member 1) on plasma membrane was confirmed by cell-surface labeling with biotin and immunoprecipitation in liver tissues and H-4-II-E-C3 cells. The addition of recombinant human vaspin in the cultured H-4-II-E-C3 cells also increased the phosphorylation of Akt and AMP-activated protein kinase (AMPK) in a dose-dependent manner, and anti-GRP78 antibodies completely abrogated the vaspin-induced upregulation of pAkt and pAMPK Vaspin is a novel ligand for cell-surface GRP78/MTJ-1 complex, and its subsequent signals exert beneficial effects on ER stress-induced metabolic dysfunctions. Diabetes 61:2823-2832, 201

Agarose Spot as a Comparative Method for in situ Analysis of Simultaneous Chemotactic Responses to Multiple Chemokines

yesWe describe a novel protocol to quantitatively and simultaneously compare the chemotactic responses of cells towards different chemokines. In this protocol, droplets of agarose gel containing different chemokines are applied onto the surface of a Petri dish, and then immersed under culture medium in which cells are suspended. As chemokine molecules diffuse away from the spot, a transient chemoattractant gradient is established across the spots. Cells expressing the corresponding cognate chemokine receptors migrate against this gradient by crawling under the agarose spots towards their centre. We show that this migration is chemokine-specific; meaning that only cells that express the cognate chemokine cell surface receptor, migrate under the spot containing its corresponding chemokine ligand. Furthermore, we show that migration under the agarose spot can be modulated by selective small molecule antagonists present in the cell culture medium

The carbonization of aromatic molecules with three-dimensional structures affords carbon materials with controlled pore sizes at the Ångstrom-level

分子構造により細孔径を制御したカーボンを開発. 京都大学プレスリリース. 2021-05-24.Carbon materials with controlled pore sizes at the nanometer level have been obtained by template methods, chemical vapor desorption, and extraction of metals from carbides. However, to produce porous carbons with controlled pore sizes at the Ångstrom-level, syntheses that are simple, versatile, and reproducible are desired. Here, we report a synthetic method to prepare porous carbon materials with pore sizes that can be precisely controlled at the Ångstrom-level. Heating first induces thermal polymerization of selected three-dimensional aromatic molecules as the carbon sources, further heating results in extremely high carbonization yields (>86%). The porous carbon obtained from a tetrabiphenylmethane structure has a larger pore size (4.40 Å) than those from a spirobifluorene (4.07 Å) or a tetraphenylmethane precursor (4.05 Å). The porous carbon obtained from tetraphenylmethane is applied as an anode material for sodium-ion battery

Autoimmune blistering diseases treated with glucocorticoids: An international study of steroid‐induced myopathy

BACKGROUND: Patients with autoimmune blistering diseases (AIBDs) are often exposed to chronic glucocorticoid (GC) treatment with many side effects. Glucocorticoid-induced myopathy (GIM) is a well-established side effect, which particularly affects the proximal muscles. The Glucocorticoid Toxicity Index (GTI) is a validated global assessment tool which quantifies GC toxicity over time. OBJECTIVES: This study marks the first study which analyses GIM in patients with AIBDs. The objectives of this study were to utilize the GTI to investigate the nature and prevalence of GIM in AIBD patients and explore potential risk factors. METHODS: This international cohort study was conducted in blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States of America between February 2019 and July 2023. The GTI tool was completed by a medical practitioner at each patient visit. Data related to glucocorticoid toxicity were entered into the Steritas GTI 2.0 to generate an aggregate improvement and cumulative worsening score at each visit. RESULTS: The study included 139 patients. There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period. Cumulative GC dose correlated positively with myopathy risk, while average dose and treatment duration were not significant. Older age, male gender and obesity more than doubled the likelihood of developing GIM. CONCLUSIONS: GIM is a common side effect experienced by AIBD patients on GC treatment. Muscle weakness is less likely to occur if cumulative GC dose is less than 0.75 mg/kg/day. Studies of exercise programs to mitigate myopathy and newer alternative treatments to reduce cumulative GC dose should be considered

Preliminary examination of the efficacy and safety of a standardized chamomile extract for chronic primary insomnia: A randomized placebo-controlled pilot study

<p>Abstract</p> <p>Background</p> <p>Despite being the most commonly used herbal for sleep disorders, chamomile's (<it>Matricaria recutita</it>) efficacy and safety for treating chronic primary insomnia is unknown. We examined the preliminary efficacy and safety of chamomile for improving subjective sleep and daytime symptoms in patients with chronic insomnia.</p> <p>Methods</p> <p>We performed a randomized, double-blind, placebo-controlled pilot trial in 34 patients aged 18-65 years with DSM-IV primary insomnia for ≥ 6-months. Patients were randomized to 270 mg of chamomile twice daily or placebo for 28-days. The primary outcomes were sleep diary measures. Secondary outcomes included daytime symptoms, safety assessments, and effect size of these measures.</p> <p>Results</p> <p>There were no significant differences between groups in changes in sleep diary measures, including total sleep time (TST), sleep efficiency, sleep latency, wake after sleep onset (WASO), sleep quality, and number of awakenings. Chamomile did show modest advantage on daytime functioning, although these did not reach statistical significance. Effect sizes were generally small to moderate (Cohen's <it>d </it>≤ 0.20 to < 0.60) with sleep latency, night time awakenings, and Fatigue Severity Scale (FSS), having moderate effect sizes in favor of chamomile. However, TST demonstrated a moderate effect size in favor of placebo. There were no differences in adverse events reported by the chamomile group compared to placebo.</p> <p>Conclusion</p> <p>Chamomile could provide modest benefits of daytime functioning and mixed benefits on sleep diary measures relative to placebo in adults with chronic primary insomnia. However, further studies in select insomnia patients would be needed to investigate these conclusions.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT01286324">NCT01286324</a></p

Garlic Extract Diallyl Sulfide (DAS) Activates Nuclear Receptor CAR to Induce the Sult1e1 Gene in Mouse Liver

Constituent chemicals in garlic extract are known to induce phase I and phase II enzymes in rodent livers. Here we have utilized Car+/+ and Car−/− mice to demonstrate that the nuclear xenobiotic receptor CAR regulated the induction of the estrogen sulfotransferase Sult1e1 gene by diallyl sulfide (DAS) treatment in mouse liver. DAS treatment caused CAR accumulation in the nucleus, resulting in a remarkable increase of SULT1E1 mRNA (3,200 fold) and protein in the livers of Car+/+ females but not of Car−/− female mice. DAS also induced other CAR-regulated genes such as Cyp2b10, Cyp3a11 and Gadd45β. Compared with the rapid increase of these mRNA levels, which began as early as 6 hourrs after DAS treatment, the levels of SULT1E1 mRNA began increasing after 24 hours. This slow response to DAS suggested that CAR required an additional factor to activate the Sult1e1 gene or that this activation was indirect. Despite the remarkable induction of SULT1E1, there was no decrease in the serum levels of endogenous E2 or increase of estrone sulfate while the clearance of exogenously administrated E2 was accelerated in DAS treated mice