Jacobs Institute of Women's Health
George Washington University: Health Sciences Research Commons (HSRC)Not a member yet
51297 research outputs found
Sort by
Inhibition of LARP4-mediated quiescence exit of naive CD4 T cells ameliorates autoimmune and allergic diseases
No full textNaive T cells are maintained under a quiescent state, and their exit from quiescence is a hallmark of antigen stimulation. Here we identify the RNA binding protein La-related protein 4 (LARP4) as an important checkpoint regulator of quiescence exit in naive CD4 T cells. Conditional knockout of LARP4 in naive CD4 T cells leads to an enhanced quiescence state and/or dampened quiescence exit due to altered stability of several messenger RNAs important for T-cell activation. The differentiation of naive CD4 T cells into helper T-cell subsets is also impaired after conditional knockout, leading to ameliorated autoimmune and allergic responses. Lastly, we design a peptide inhibitor of LARP4 (LIPEP), and treatment with LIPEP could perfectly mimic LARP4 deficiency and alleviate the severity of autoimmune and allergic diseases in the corresponding mouse models. Our study reveals a link between RNA stability and CD4 T-cell homeostasis/adaptive activation, highlighting the potential of LARP4 as a preventative and therapeutic target for autoimmune and allergic diseases although at quite high doses
More work for ASHAs? Exploring the role of whatsapp messaging and community health work in urban slum areas of Varanasi, India
No full textIndia\u27s community health workers (CHWs) have taken on an onerous set of responsibilities for the welfare of their clients across a variety of health domains, including providing modern contraception for family planning, promoting childhood vaccinations, and enhancing pregnant women\u27s nutritional outcomes. Governments have also added technology to this mix under the assumption that new digital tools can relieve the work burdens. Through interviews with 22 CHWs, this study found that, besides offering health services for the community, CHWs report an expanding workload that includes several government initiatives. While beneficial in some ways, digital technologies have also introduced new administrative burdens for CHWs, who must manage recordkeeping across incompatible systems. Our findings highlight the complexities of using mhealth technology, emphasizing the need for solutions that enhance rather than replace the vital role of CHWs in fostering trust and overcoming barriers to vaccination. While CHWs continue to play a pivotal role in improving vaccine uptake and navigating the complexities of healthcare delivery, their expanding responsibilities and the nuanced challenges of vaccine hesitancy-particularly in urban slum areas-underscore the need for ongoing support and adaptation of technology to effectively bridge the gap between healthcare systems and the communities they serve
Point-Of-Care Respiratory Diagnosis and Antibiotic Utilization in the Emergency Department: A Prospective Evaluation of Multiplex PCR
No full textOBJECTIVES: Rapid multiplex point-of-care (POC) PCR tests may reduce unnecessary antibiotic prescribing by quickly identifying viral etiologies in patients with acute respiratory infections (ARI). We evaluated the impact of a rapid (~15 min) multiplex PCR test on antibiotic prescribing, provider confidence, patient satisfaction, and emergency department (ED) length of stay (LOS). METHODS: We conducted a prospective, single-center study (March 2024-January 2025) enrolling adults presenting to an urban academic ED with ARI symptoms. Participants underwent rapid multiplex PCR testing (BIOFIRE SPOTFIRE Respiratory Panel), with results provided to clinicians in real time. Antibiotic prescribing, provider and patient perceptions, and ED LOS were assessed through surveys and electronic health record review. A propensity-matched control cohort was used to compare antibiotic prescribing and LOS. The primary outcome was antibiotic prescribing among patients with a confirmed viral etiology; secondary outcomes included overall antibiotic prescribing, ED LOS, and provider-and patient-reported measures. RESULTS: A total of 200 patients were enrolled (mean age 43 years; 56.5% female). Common presenting symptoms included cough (80%), congestion (65%), and sore throat (55%). Patients with confirmed viral infections were significantly less likely to receive antibiotics than those with no detected pathogen (6.5% vs. 20.2%; OR 0.28; 95% CI 0.10-0.68; p = 0.009). Overall antibiotic prescribing rates were similar between experimental and control cohorts (14.9% vs. 12.0%; p = 0.392), but median ED LOS was significantly shorter in the experimental group (4.3 vs. 6.5 h; OR 0.66; 95% CI 0.59-0.74; p \u3c 0.001). Provider diagnostic confidence was high (76%), and most patients reported high satisfaction with testing (92%). CONCLUSIONS: Rapid multiplex PCR testing was associated with reduced antibiotic prescribing for viral infections, shorter ED LOS, high provider confidence, and high patient satisfaction. These findings support the value of ultra-rapid diagnostics for antimicrobial stewardship and patient-centered care in the ED
Long COVID After Acquisition of the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) During Pregnancy Compared With Outside of Pregnancy
No full textOBJECTIVE: To evaluate whether the risk of long COVID among individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy differs from that of individuals who were not pregnant at time of virus acquisition. METHODS: We conducted a multicenter observational cohort study at 79 NIH RECOVER (Researching COVID to Enhance Recovery) sites. Individuals assigned female at birth aged 18-45 years with an index (first) SARS-CoV-2 infection on or after December 1, 2021, were included. The exposure was pregnancy (any gestational age) at the time of index SARS-CoV-2 infection. The primary outcome was long COVID 6 months after index infection, defined as RECOVER-Adult Long COVID Research Index score 11 or higher based on a detailed symptom survey. To account for confounding and differential selection between participants who were pregnant and not pregnant at infection, propensity score-matching methods were used to balance the groups on variables potentially associated with both pregnancy status and long COVID. RESULTS: Overall 2,423 participants were included; 580 (23.9%) were pregnant at index SARS-CoV-2 infection. The median age at infection was 33 years (interquartile range 28-38 years), and 2,131 of participants (90.0%) with known vaccination status were vaccinated. After propensity score matching, the adjusted long COVID prevalence estimates 6 months after index infection were 10.2% (95% CI, 6.2-14.3%) among those pregnant at infection and 10.6% (95% CI, 8.8-12.4%) among those not pregnant at infection. Pregnancy was not associated with a difference in adjusted risk of long COVID (adjusted risk ratio 0.96, 95% CI, 0.63-1.48). CONCLUSION: Acquisition of SARS-CoV-2 during pregnancy was not associated with a differential risk of long COVID at 6 months compared with similar-aged individuals who acquired SARS-CoV-2 outside of pregnancy
Serum Proteomic Profile Based on the TGF-β Pathway Stratifies Risk of Hepatocellular Carcinoma
No full textBACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths, primarily due to late-stage diagnosis. In this multicenter study, our goal is to identify functional biomarkers that stratify the risk of HCC in patients with cirrhosis (CP) for early diagnosis. METHODS: Five thousand and eight serum proteins (Somascan) were analysed in Cohort A (477 CP, including 125 HCC). Clustering analysis of the TGF-β pathway-associated protein signature was performed in a longitudinal, prospective Cohort B (312 CP, in which 18 cases developed HCC over a 5-year follow-up period). Next, a multivariable prediction model was built using logistic regression analysis of cross-sectional data from a matched subgroup (n = 328, Cohort C). Model performance was 10-fold cross-validated across the entire Cohort A (n = 477). RESULTS: Longitudinal follow-up analysis revealed that patients with elevated TGF-β-related protein signature displayed a five-fold increased risk of developing HCC (9.68% vs. 1.91%). Compared to cirrhosis, serum MSTN, TGFBR2, and AFP levels raised in HCC were validated by ELISA (n = 200, odds ratio = 1.4-2.9, p \u3c 0.05). In Cohort C, 88 proteins were significantly altered in HCC compared to cirrhosis (p \u3c 0.05). The six-protein panel (TGFBR2, MSTN, AFP, COL18A1, GLUL, TP63) displayed a strong performance in the matched cohort C (AUC 0.87, sensitivity 0.88, specificity 0.72), alongside four clinical factors (Age, Sex, BMI, Bilirubin). A 10-fold cross-validation demonstrated a mean AUC of 0.86 in cohort A, with strong predictive power in obese/MASLD/ALD-related patients (AUCs: 0.862-0.921). CONCLUSIONS: The mechanism-based panel effectively stratifies HCC risk in cirrhotic patients, underscoring the need for Phase II/III validation
Exploring the Role of Internalized Weight Bias as a Metric of Cumulative Social Disadvantage Among People With Obesity or Overweight: Insights From the OBSERVE Study
No full textBACKGROUND: Experiencing bias and stigma are social determinants of health (SDoH). Recently, internalized weight bias (IWB) has been included as an SDoH in obesity medicine. This study examined the association of IWB with other pillars of SDoH and how IWB contributes to cumulative social disadvantage for people living with obesity. METHODS: A cross-sectional, web-based survey was conducted in the United States (May-December 2022) with a sample of adults with obesity or overweight. Multiple linear regression was performed to evaluate the relationship between WSSQ (higher score indicating experiencing more IWB) and other pillars of SDoH. RESULTS: Participants who reported race as Black (adjusted mean difference [95% CI] -3.86 [-5.21, -2.52]; p \u3c 0.001) or multiracial (-3.26 [-5.37, -1.16]; p = 0.002) had significantly lower total WSSQ scores than those who self-identified as White race. Participants who experienced negative social interactions due to weight had significantly higher total WSSQ scores (7.04 [5.81, 8.27]; p \u3c 0.001) than those who did not. CONCLUSION: The study showed that IWB is associated with certain other pillars of SDoH. Findings highlight the need for a comprehensive and patient-centric approach to managing individuals with greater IWB, which may contribute to a higher cumulative social disadvantage and, consequently, worse health outcomes
Intravenous Fluid Bolus Resuscitation Increases Mortality Risk in Malawian Children with Cerebral Malaria
No full textThe Fluid Expansion as Supportive Therapy (FEAST) clinical trial determined that African children with impaired perfusion receiving bolus intravenous (IV) fluids had increased mortality compared to children with impaired perfusion not receiving bolus IV fluids. Malaria was common in FEAST enrollees, but no stratified analysis for children with cerebral malaria (CM), a common cause of febrile coma in Africa, was reported. We investigated whether bolus fluid expansion changed mortality risk in children with CM. To evaluate this association, we performed a propensity score matched retrospective cohort study with data collected from 1,674 children with CM admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi from 2000 to 2018. After matching of participants by covariate balancing propensity score weighting, children who received an IV fluid bolus had increased mortality risk (odds ratio [OR]: 1.92; 95% CI: 1.36-2.71) compared with those who did not. When stratified by admission systolic blood pressure (SBP), children with an SBP greater than 100 mm Hg receiving bolus fluids had increased mortality (OR: 3.15; 95% CI: 1.81-5.48) compared with those not receiving bolus fluids. In children with an SBP ≤100 mm Hg at admission, receiving bolus IV fluids did not change mortality (OR: 1.44; 95% CI: 0.91-2.26). Bolus IV fluids are an ineffective therapeutic intervention in children with CM and are harmful in those with normal or elevated admission SBPs. Our results confirm the lack of efficacy and potential harm of IV bolus fluid administration in Malawian children with CM
Membranous Nephropathy after Subcutaneous Mercury Injection
No full textINTRODUCTION: Subcutaneous elemental mercury injection is typically not associated with systemic toxicity. This case report describes a man who developed persistent membranous nephropathy temporally associated with intentional subcutaneous elemental mercury injection. CASE REPORT: A 21-year-old man injected elemental mercury into his left forearm after experiencing worsening depression during the COVID-19 pandemic. Several months later, he sought dermatology evaluation due to nodularity at the injection site. He underwent attempted excision of what was presumed to be a left forearm lipoma, but he did not report the history of mercury injection. He subsequently developed proteinuria and was diagnosed with membranous nephropathy. Treatment with rituximab did not improve his condition, and he eventually divulged the history of mercury injection three years after the initial exposure. He underwent surgical excision of the mercury deposits, left forearm flap reconstruction, and chelation with oral succimer. Despite these interventions, his proteinuria and urine protein to creatinine ratio remained persistently elevated, consistent with ongoing membranous nephropathy. DISCUSSION: Renal pathology is associated with mercury toxicity after dermal or inhalational exposure but is rarely reported to occur after subcutaneous injection of elemental mercury. The pathophysiology of mercury-induced membranous nephropathy may involve formation of autoantibodies and cytokines after direct renal tubular injury. Surgical excision is the primary treatment for subcutaneous mercury exposure. Chelation may be considered for patients with evidence of systemic toxicity or ongoing mercury exposure, although the optimal timing of perioperative chelation has not been defined. CONCLUSION: Significant systemic toxicity, including membranous nephropathy, may occur after subcutaneous mercury injection