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Alzheimer's disease (AD) affects various brain cell types, including astrocytes, which are the most abundant cell types in the central nervous system (CNS). Astrocytes not only provide homeostatic support to neurons but also actively regulate synaptic signaling and functions and become reactive in response to CNS insults through diverse signaling pathways including the JAK/STAT, NF‐κB, and GPCR‐elicited pathways. The advent of new technology for transcriptomic profiling at the single‐cell level has led to increasing recognition of the highly versatile nature of reactive astrocytes and the context‐dependent specificity of astrocyte reactivity. In AD, reactive astrocytes have long been observed in senile plaques and have recently been suggested to play a role in AD pathogenesis and progression. However, the precise contributions of reactive astrocytes to AD remain elusive, and targeting this complex cell population for AD treatment poses significant challenges. In this review, we summarize the current understanding of astrocyte reactivity and its role in AD, with a particular focus on the signaling pathways that promote astrocyte reactivity and the heterogeneity of reactive astrocytes. Furthermore, we explore potential implications for the development of therapeutics for AD. Our objective is to shed light on the complex involvement of astrocytes in AD and offer insights into potential therapeutic targets and strategies for treating and managing this devastating neurodegenerative disorder. [ABSTRACT FROM AUTHOR]

There have been conflicting results regarding the effect of proton pump inhibitors (PPIs) as an adjunctive therapy to oral antidiabetic medication (OAM) in those with type 2 diabetes (T2DM). PPIs increase gastrin levels, causing a rise in insulin. No studies have evaluated the duration of PPI therapy and its effect on glycemic control. Medical records across 8 hospitals between 2007 and 2016 were reviewed for 14,602 patients with T2DM (not on insulin therapy) taking PPIs. Values of HbA1c (baseline, follow-up, and the difference between the two) in those prescribed with PPIs and years of therapy were compared to HbA1c values of those who had no record of PPI use. Baseline and follow-up HbA1c for patients on PPIs were 6.8 and 7.0, respectively, compared to 7.1 and 7.2 in their untreated counterparts (p < 0.001 in both comparisons). For both groups, an increase in baseline HbA1c was seen with time. Those on PPI had an increase in HbA1c of 0.16 compared to 0.08 in those not prescribed PPI. Our results show no relationship between the length of PPI therapy and HbA1c reduction. [ABSTRACT FROM AUTHOR]

Objectives: To perform an evidence-based review evaluating presenting symptoms, imaging, and management for primary paragangliomas of the facial canal (PPFCs).Data Sources: PubMed/MEDLINE, Embase, Cochrane Library, and Web of Science.Review Methods: Studies were assessed for quality of evidence and bias with the Cochrane bias tool, GRADE, and MINORS criteria. Demographic data, imaging modalities, management strategies, and status at last follow-up were obtained.Results: Sixteen studies met inclusion criteria. In total, 21 patients with PPFCs were identified, 19 of which were histologically confirmed. Most common presenting symptoms included unilateral facial nerve dysfunction (n = 14, 73.7%) and pulsatile tinnitus (n = 8, 42.1%). Mean time from reported onset of facial dysfunction was 17.8 months. Computed tomography findings included an expanded descending facial nerve canal (n = 13, 76.5%). All cases with magnetic resonance imaging reported enhancement with contrast. Of the 18 patients who had surgery, 16 (88.9%) underwent full tumor resection while 1 (5.6%) had partial tumor debulking with adjuvant radiotherapy. Overall improvement in facial weakness was documented in 5 of 9 patients (55.6%) with initial facial nerve dysfunction and >6-month follow-up. No evidence of tumor recurrence was reported.Conclusions: PPFCs are extraordinarily rare vascular neoplasms of the temporal bone. Early imaging with both computed tomography and magnetic resonance imaging is essential for narrowing the differential diagnosis, assessing the extent of tumor invasion, and accurate surgical planning. Surgical tumor resection with subsequent facial nerve reconstruction is recommended for patients with facial nerve dysfunction, while tumor biopsy or debulking may be indicated when normal facial movement in present. [ABSTRACT FROM AUTHOR]

R3833 --> 842.14 --> Glioblastoma (GBM) is a malignant brain cancer that results in patient death within two years following diagnosis. The GBM tumor microenvironment has an important impact on the formation, progression, and drug resistance of this lethal disease. The GBM tumor microenvironment is composed of a variety of cell types that can support tumor growth like microglia. Microglia are immune cells that can switch from a classical, tumoricidal M1 phenotype to an alternative, tumor promoting M2 phenotype which encourages tumor growth. However, there are limited studies about the specific effect(s) that microglia have on GBM thus requiring further research into how these cells affect GBM tumors. Given the importance of the tumor microenvironment to GBM tumor progression, targeting key signaling pathways in tumor‐associated cells that are involved in sustaining GBM tumors could be an effective way to reduce tumor progression. One signaling pathway involved in causing different cancers is the nuclear factor‐kappa B (NF‐κB) pathway, which has been implicated in M1 to M2 phenotype polarization. Therefore, this study focuses on characterization of the p65fl/fl/CX3CR1creER/+ mouse model, which is an inducible p65 knockout mouse model for studying how inhibition of canonical NF‐κB signaling in microglia affects GBM tumors. After tamoxifen is administered to the mouse, p65, a transcription factor of the canonical NF‐κB pathway, should be deleted in microglia due to the C‐X3‐C chemokine receptor 1 (CX3CR1) promoter. Tamoxifen binds to the estrogen receptor on the cre recombinase (creER) so that the cre recombinase can recombine the floxed p65 (p65fl/fl) gene in microglia. Characterization of this particular mouse model is necessary to determine if the floxed p65 gene is effectively deleted in microglia from these mice. Liquid chromatography‐mass spectrometry analysis has shown that the orally administered tamoxifen was present and quantifiable in the brains of tamoxifen‐treated mice to induce recombination. Based on data from PCR and western blots, tamoxifen given to the p65 knockout mice induced partial deletion of the floxed p65 gene in isolated microglia compared to p65 knockout mice given the vehicle control. Preliminary flow cytometry data suggested that p65 deletion in microglia occurred in p65fl/fl/CX3CR1creER/+ mice that received GBM implantations and tamoxifen treatment compared to a vehicle control group. Overall, the data from this study suggested that the floxed p65 gene is partially deleted in microglia of the tamoxifen‐treated p65 knockout mice compared to the vehicle control mice. [ABSTRACT FROM AUTHOR]

The introduction of ultrasound guidance for regional anesthesia has resulted in an explosion of interest in its use for postoperative analgesia, particularly for orthopedic surgery. Regional anesthesia demonstrates unequivocal superiority compared with systemic opioids with respect to analgesia, reduced opioid consumption, increased patient satisfaction, and earlier achievement of discharge criteria. Improved acute postoperative analgesia can facilitate effective rehabilitation. Investigators are in the early stages of reporting the effects of regional anesthesia on functional outcome. Recent studies reporting functional outcomes have been plagued with sample sizes of inadequate power to generate meaningful results. Furthermore, the functional outcome measures are used inappropriately in terms of clinically meaningful difference, assessment intervals, and/or duration of follow-up. This report aims to address these issues by discussing functional outcomes used in the physiotherapy or orthopedic literature and their appropriate utilization, so that future research into the effects of regional anesthesia can be methodologically sound. Outcomes discussed include those that are physical-performance-based (ie, range of motion, quadriceps strength, Timed Up and Go test, 6-Minute Walk Test, Stair Time, and Self-paced Walk Test) and those that are self-reported (ie,Western Ontario and McMaster Universities Osteoarthritis Index, Knee Osteoarthritis Severity Score, Lower Extremity Function Scale). [ABSTRACT FROM AUTHOR]

• A significant unmet need for hepatitis B vaccination in adults remained in Viet Nam. • More people in the young age groups should be recommended for hepatitis B vaccination. • The social disparity in hepatitis B vaccination existed in various socioeconomic statuses. • Hepatitis B vaccination should be recommended for the broader population to achieve elimination. Gaps in adult hepatitis B vaccination were undefined in Vietnam, a lower-middle-income country. To address these gaps, this study defined hepatitis B vaccine coverage in adults and its associated factors in Ho Chi Minh City (HCMC), Viet Nam. We also proposed interventional strategies, prioritizing gap identification to facilitate hepatitis B elimination by 2030 and beyond. During 2019–2020, a multi-stage cluster serosurvey with probability proportional to size was conducted to representatively invite 20,000 adults (18 years or older) throughout HCMC for hepatitis B screening (HBsAg, anti-HBs, and anti-HBc). Serologic results defined two dependent variables: vaccine-induced immunity (i.e., isolated anti-HBs) and susceptibility (i.e., HBV naive). Associations of dependent variables with surveyed demographics, socioeconomic statuses, behaviors, and medical history at risk for hepatitis B were evaluated using weighted Poisson regression. The prevalence was 18.5% (95%CI, 17.3-20.0%) for vaccine-induced immunity and 37.7% (35.6-39.8%) for susceptibility. Even though analyses in the general population revealed a falling trend in vaccine-induced immunity prevalence from younger to older age groups, sensitivity analyses in the non-infected population (i.e., those who were both negative for HBsAg and anti-HBc) showed that younger age groups, especially those aged 30 to 50 years, had the lowest prevalence. Social inequalities existed in different ethnicities, residence areas, education levels, house ownership, and health insurance statuses. There was no significant association between vaccine-induced immunity or susceptibility and risky behaviors and medical histories. This study depicts a significant unmet need for hepatitis B vaccination in the general adult population in HCMC, Viet Nam. Indeed, the lack of vaccination was unevenly distributed regarding age groups, geographical areas, and socioeconomic statuses, which reveals profound social disparities. Therefore, to achieve hepatitis B elimination goals, besides the current recommendations for infants and risk-based strategies, hepatitis B vaccination should be recommended for the broader population. [ABSTRACT FROM AUTHOR]

Background Systemic sclerosis (SSc) patients are at high risk for respiratory failure due to the progression of their disease. Investigating factors predictive of impending respiratory failure in this patient population can be used to improve hospital outcomes. Here, we investigate risk factors associated with developing respiratory failure in patients hospitalized with a diagnosis of SSc in the United States using a large, multi-year, population-based dataset. Methodology This retrospective study was conducted on SSc hospitalizations from 2016 to 2019 with and without a principal diagnosis of respiratory failure from the United States National Inpatient Sample database. A multivariate logistic regression analysis was performed to calculate adjusted odds ratios (OR adj ) for respiratory failure. Results There were 3,930 SSc hospitalizations with a principal diagnosis of respiratory failure and 94,910 SSc hospitalizations without a diagnosis of respiratory failure. Among SSc hospitalizations, multivariable analysis showed that the following were associated with a principal diagnosis of respiratory failure: Charlson comorbidity index (OR adj = 1.05), heart failure (OR adj = 1.81), interstitial lung disease (ILD) (OR adj = 3.62), pneumonia (OR adj = 3.40), pulmonary hypertension (OR adj = 3.59), and smoking (OR adj = 1.42). Conclusions This analysis represents the largest sample to date in assessing risk factors for respiratory failure among SSc inpatients. Charlson comorbidity index, heart failure, ILD, pulmonary hypertension, smoking, and pneumonia were associated with higher odds of inpatient respiratory failure. Patients with respiratory failure had higher in-hospital mortality compared to those without it. Outpatient optimization and inpatient recognition of these risk factors can lead to improved hospitalization outcomes for SSc patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Trang et al.)

Background: We conducted a community-based seroprevalence study using three HBV seromarkers (HBsAg, anti-HBs, anti-HBc) in Ho Chi Minh City (HCMC), Vietnam, to (1) determine the prevalence of HBV serologic profiles; (2) document factors associated with HBV infection or susceptibility; and (3) propose strategies toward HBV elimination by 2030., Methods: During 2019-2020, we deployed a multistage cluster design with probability proportionate to size, to recruit 20,000 adults for an HBV screening and linkage to care program citywide. Screening results with interpretation, recommendations, and health education materials were returned to participants. Post-study surveys were conducted within three months to identify gaps in linkage to care., Findings: Of the 17,600 adults invited, 15,275 (86.7%) participated in the study, 14,674 (96.1%) completing all data for final analyses. The prevalence of HBsAg (+) and HBV-naïve were 7.5% and 37.7%, respectively. HBV vaccination rates were 18.7% and about 50% of HCMC population had been exposed to HBV. Of the persons with HBsAg (+), 27.1% linked to care (76% used health insurance). There were wide variations in HBsAg (+) and HBV vaccination rates between districts, risk factors, and socio-economic statuses., Interpretation: The significant disease burden of and gaps in the continuum of care highlight the need and urgency to address the HBV public health problem in Vietnam. Using three screening seromarkers that tailor interventions to the needs of HBV micro-populations could be an effective strategy to pursue HBV elimination goals., Funding: Gilead Sciences Inc; Roche Diagnostic International Ltd; Roche Diagnostics-Vietnam; Abbott Diagnostics-Vietnam; Hepatitis B Foundation; Medic MedicalCenter, Vietnam; Center of Excellence for Liver Disease in Vietnam, Johns Hopkins University School of Medicine., Competing Interests: MC.Jr received consulting fees from the Vietnam Viral Hepatitis Alliance. RGG has received grants or research support in last two years from Gilead. RGG has also performed as a consultant or advisor in the past two years to Abbott, AbbVie, Altimunne, Antios, Arrow head, Dynavax, Eiger, Eisai, Enyo, Genentech, Genlantis, Gerson Lehrman Group, Gilead Sciences, Helios, HepaTX, HepQuant, Intercept, Janssen, Merck, Pfizer, Topography Health, and Venatorx. RGG is on scientific or clinical advisory boards for AbbVie, Antios, Dynavax, Enyo, Genentech, Genlantis, Gilead, Helios, HepaTX, HepQuant, Intercept, Janssen, Merck, Pfizer, and Prodigy. RGG is a member of Topography Health clinical trials alliance. RGG is chair of the clinical advisory board for Prodigy. RGG is an advisory consultant for Fibronostics, Fujifilm/Wako, Perspectum, Quest, and Sonic Incytes. RGG is on data safety monitoring boards for Altimmune, Arrowhead, CymaBay Therapeutics, and Durect. RGG currently has consulting confidentiality agreements with Abbvie, Abbott, Access Biologicals, Active Genome Expressed Diagnostics, ADMA Biologics, AEC Partners, Aligos Therapeutics, Arena Pharma ceuticals Inc, Ark Biopharmaceutical Co Ltd, Arrowhead, Arterys Inc, Alexion, Altimmune, Antios Therapeutics, AprosTx, Audentes Therapeutics, Bayer, Bausch/Salix, Cirina, Consumer Health Products Assoc, CymaBay Therapeutics Inc, DiaSorin Inc, Dova Pharmaceuticals, DRG Abacus, DURECT Corporation, Dynavax, Echosens, Eiger, Eisai, Enyo, Exelixis, Fibronostics Inc, Forty-Seven Inc, Fujifilm Wako Diagnostics, Gilead, HepQuant, HepaTx, IDLogiq, Intellia, Intercept, Inotek, Iqvia, Janssen/J&J, KannaLife, Kezar Life Sciences Inc, LabCorp, Laboratory for Advanced Medicine, Labyrinth Holdings, Life Line Screening, Lilly, MedImmune, Merck, New Enterprise Associates, Ogilvy CommonHealth, Organovo, Patient Connect, Perspectum, Pfizer, Pharmaceutical Research Associates, ProdigY Biotech, Prometheus Laboratories, Refuah Solutions, Regulus Therapeutics, Sagimet Inc, Salix, Saol Bermuda Ltd, Shenzhen HEC Industrial Develop ment, Shionogi Inc, Spring Bank, Tonghua Anrate Biopharmaceutical, Topography Health, Trimaran, Venatorx, and Viravaxx AG. RGG reports activities for Speakers Bureau, focusing on HBV, HCV, HDV and liver cancer; specifically, epidemiology, diagnosis, and treatment. In addition, program presentations on vaccination for HBV and management of complications of cirrhosis. RGG has speaker's contracts to do promotional talks for AbbVie, BMS, Eisai, Genentech, Gilead Sciences Inc., and Intercept. RGG is a minor stock shareholder (liver space noted only) for RiboSciences and CoCrystal. RGG holds stock options in Eiger, Gen lantis, HepQuant, AngioCrine, and HepaTx, outside the submitted work. The rest of the authors declare no competing interests., (© 2022 The Author(s).)

Objectives: Vietnam is an endemic area for hepatitis B virus and hepatitis C virus infection (HBV-HCV), yet its largest city, Ho Chi Minh City (HCMC), has no comprehensive policy to educate, screen, treat and protect healthcare workers (HCWs) from viral hepatitis. We conducted a mixed-methods study to document HBV-HCV infection rates, risk factors, local barriers and opportunities for providing education, screening and medical care for HCWs., Design: This mixed-methods study involved an HBV and HCV serological evaluation, knowledge, attitude and practice survey about viral hepatitis and many in-depth interviews. Descriptive statistics and thematic content analysis using inductive and deductive approaches were used., Setting: HCMC, Vietnam., Participants: HCWs at risk of viral hepatitis exposure at three hospitals in HCMC., Results: Of the 210 invited HCWs, 203 were enrolled. Of the 203 HCWs enrolled, 20 were hepatitis B surface antigen-positive, 1 was anti-hepatitis C antibody (anti-HCV Ab)-positive, 57 were anti-hepatitis B core Ab-positive and 152 had adequate anti-hepatitis B surface Ab (anti-HBs Ab) titre (≥10IU/mL). Only 50% of the infected HCWs reported always using gloves during a clinical activity involving handling of blood or bodily fluid. Approximately 50% of HCWs were still not vaccinated against HBV following 1 year of employment. In-depth interviews revealed two major concerns for most interviewees: the need for financial support for HBV-HCV screening and treatment in HCWs and the need for specific HBV-HCV guidelines to be independently developed., Conclusions: The high HBV infection rate in HCWs coupled with inadequate preventive occupational practices among the population in HCMC highlight the urgent needs to establish formal policy and rigorous education, screening, vaccination and treatment programmes to protect HCWs from HBV acquisition or to manage those living with chronic HBV in Vietnam., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)