Sabin Vaccine Institute

Background: Low estrogen levels during menopause reduce nitric oxide (NO) production, contributing to decline in skeletal muscle quality and function. Although acute and short-term dietary nitrate supplementation has demonstrated promising effects, long-term benefits, particularly on muscle quality in postmenopausal women, are not well established. Objectives: The objective was to investigate the effects of long-term (12-week) nitrate-rich beetroot extract supplementation on morphological and functional muscle quality, rate of force development (RFD), maximal strength, and circulating nitrate/nitrite concentrations in postmenopausal women. Methods: In a randomized, double-blind, placebo-controlled design, 20 postmenopausal women (21 years ± 7 since menopause) consumed 20 g/day of a nitrate-rich beetroot extract (BET; 548 mg nitrate/day) or a nitrate-depleted beetroot extract (PLA; 43 mg nitrate/day) for 12 weeks. Outcome measures, including muscle quality (functional via muscle strength/thickness ratio; morphological via ultrasound echo intensity), RFD, maximal voluntary isometric contraction (MVIC), and serum nitrate/nitrite levels, were evaluated at baseline, 8 weeks, and 12 weeks. Results: BET significantly increased serum nitrate (0.005) and nitrite (0.022) levels compared to PLA at both week 8 and week 12. Morphological muscle quality also improved significantly in the BET group (interaction effect, p = 0.014). Early-phase rate of force development (RFD) increased between 30 and 100 ms, whereas late-phase RFD increased between 100 and 200 ms. RFDpeak also improved by week 8, and these gains were maintained through week 12 (interaction effect, p < 0.05). Although there was no significant difference between groups for functional muscle quality, MVIC increased at week 12 in the BET group, but no significant Time × Group interaction was observed. Conclusions: Twelve weeks of nitrate-rich beetroot extract supplementation improved morphological muscle quality and RFD, suggesting potential clinical relevance for preventing structural and neuromuscular function decline in postmenopausal women. This study was registered with ReBEC (RBR-87qh649) and approved on 8 October 2024.

Motivation:Seroincidence—the rate of new infections in a population—is a key measure for understanding pathogen transmission dynamics and informing public health action. Estimating seroincidence from cross-sectional data is complicated by antibody waning, cross-reactivity, and individual heterogeneity in antibody responses.Implementation:serocalculator is an open-source R package that uses a likelihood-based framework incorporating antibody decay models, biological variability, and measurement noise to estimate seroincidence rates from cross-sectional serological data.General features:The package supports overall and stratified seroincidence estimation using single or multiple biomarkers. It requires three inputs: (1) a pre-estimated seroresponse model characterizing post-infection antibody waning; (2) noise parameters capturing biological and assay-related variability; and (3) quantitative antibody responses from a cross-sectional survey. It is computationally efficient, well-documented, and includes a point-and-click R Shiny interface. These features promote usability across research and public health.Availability:The package serocalculator is freely available on CRAN, with development versions on GitHub.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly aggressive malignancy with limited treatment options. Targeting metabolic vulnerabilities and disrupting redox stress pathways has gained increasing attention as a potential therapeutic strategy. γ-Glutamyl-selenomethylselenocysteine (GGMSC) is a selenium-containing compound structurally related to seleno-L-methylselenocysteine (MSC), which has shown anticancer potential in preclinical models, although its molecular effects in PDAC are not well defined. In this study, we investigated the transcriptomic response to high-dose GGMSC in two PDAC cell lines, CAPAN-2 and HPAF-II. RNA sequencing and cytotoxicity assays revealed marked sensitivity to GGMSC in CAPAN-2 cells, associated with activation of oxidative stress and ferroptosis-related pathways, alongside downregulation of metabolic and cell cycle genes. Conversely, HPAF-II cells displayed limited transcriptional alterations and maintained proliferative and metabolic programs. These findings offer insights into the molecular mechanisms underlying GGMSC-induced transcriptional responses in PDAC and suggest potential avenues for future investigations of selenium-based therapies in pancreatic cancer.

BackgroundSepsis, an organ dysfunction caused by deregulated host response to infection, is a major health problem worldwide. Sepsis is associated with high rates of mortality, especially in critically ill patients. Curcumin may improve sepsis through its anti-inflammatory and antioxidant effects. This study aimed to investigate the effects of curcumin-piperine administration in critically ill septic patients.MethodThis double-blind randomized controlled trial (RCT) conducted on 66 patients with sepsis hospitalized in the intensive care unit (ICU). Patients were randomized to either the intervention group receiving two tablets of curcumin-piperine (each containing 500 mg curcuminoids and 5 mg piperine) (n = 33), or the placebo group receiving two matched tablets of placebo (n = 33) daily for 7 consecutive days along with enteral feeding. Clinical, laboratory, and biochemical indices were evaluated before and after the intervention. Statistical analyses were performed based on an intention-to-treat method.ResultMortality was observed in 10 patients in the curcumin-piperine group, and 12 patients in the control group. Curcumin-piperine significantly reduced bilirubin-total (P = 0.02), bilirubin-direct (P = 0.02), pH (P < 0.001), C-reactive protein (P = 0.04), erythrocyte sedimentation rate (P < 0.001), and platelet count (P = 0.01) compared with the placebo. A significantly lower reduction was found in red blood cell (P = 0.003), hemoglobin (P = 0.001), and hematocrit (P = 0.002) levels in the intervention vs. placebo group. In addition, mean corpuscular hemoglobin (P < 0.001) and mean corpuscular hemoglobin concentration (P = 0.001) were significantly higher in the intervention vs. placebo group.ConclusionCurcumin–piperine supplementation over a short period had beneficial effects on some inflammatory and laboratory indices in critically ill patients with sepsis.Trial registrationIRCT20150613022681N4; available on:https://en.irct.ir/trial/52661. Registration date: 2021-01-02, 1399/10/13.

There is a shortage of rapid, accurate, and low-cost assays for diagnosing enteric fever. The dual-path platform for typhoid (DPPT) assay had high accuracy in retrospective studies with banked plasma samples. We aimed to evaluate the diagnostic accuracy of the DPPT assay in a prospective study using fingerstick capillary blood. For this prospective diagnostic accuracy study, we enrolled children younger than 18years, who presented at the Bangladesh Shishu Hospital and Institute (Dhaka, Bangladesh) with at least 3days of fever. We collected blood and nasal swabs, and did the following assays to assess the accuracy of DPPT: blood culture, serological assays for typhoid fever (DPPT assay, Widal, and Test-it), and molecular assays to identify alternative aetiologies (eg, respiratory syncytial virus [RSV], influenza, dengue virus, and Rickettsia spp). The primary outcomes of the study were the sensitivity and specificity of the DPPT assay for diagnosis of enteric fever. We evaluated the accuracy of combined anti-haemolysin Eand anti-lipopolysaccharide IgA readings using the DPPT assay in distinguishing culture-confirmed enteric fever from alternative aetiologies using receiver operating characteristic area under the curve (AUC). Given the imperfect reference standard diagnostics for enteric fever, we used Bayesian latent class models, incorporating results from the typhoid and alternative aetiology diagnostics, to estimate the sensitivity and specificity of the DPPT assay. We also did subgroup analyses for the assay across multiple biological variables. Between Aug 17, 2021, and July 16, 2022, we enrolled 501participants who presented with at least 3days of fever. 223 (45%) of 501participants were female and 278 (55%) were male. 77participants had culture-confirmed enteric fever (62 Salmonella entericaserotype Typhi and 15 Salmonella entericaserotype Paratyphi A) and 70were culture-negative with PCR-confirmed alternative aetiology (34 influenza Aor B, 22dengue virus, seven Rickettsia spp, six RSV, and one participant co-infected with RSV and dengue virus). The AUC for DPPT on fingerstick capillary blood in distinguishing typhoid from alternative aetiologies was 0·969 (95% CI 0·943-0·994). In latent class analysis, the sensitivity of DPPT was 93%(95% credible interval [CrI] 87-97) and specificity was 89% (85-93). The balanced accuracy was higher for DPPT (91%, 95% CrI 87-94) than blood culture (81%, 78-85), Test-it (77%,74-79), or Widal (70%, 67-73). Assay performance did not vary by sex, age, duration of fever at presentation, antibiotic use before presentation, Salmonella serotype, or sample type. The point-of-care DPPT assay achieved high diagnostic accuracy for enteric fever in a highly endemic community. This assay has the potential to improve clinical outcomes for enteric fever, allowing rapid diagnosis and treatment, and could facilitate more appropriate antimicrobial use. National Institute of Health, Bill & Melinda Gates Foundation, and Child Health Research Foundation.

Turmerones are major bioactive compounds of Curcuma species with several beneficial pharmacological activities. In addition, various in vivo and in vitro studies noted that turmerones could affect different cytokines, metabolic pathways, and targets. Turmerones will have the potential to be a candidate agent to lessen many pathological and immunological conditions as a result of these pharmacological activities. In this review, we provided information about the pharmacological actions of turmerones using search engines such as PubMed, Google Scholar, Scopus, and Web of Science.

The expansion of artisanal and small-scale gold mining (ASGM) in the Madre de Dios region of the Peruvian Amazon has transformed primary forests into a novel wetland complex of thousands of abandoned mining ponds. Despite their ecological relevance, post-mining recovery of these systems remains understudied, particularly regarding fish biodiversity and recolonization. In this study, we evaluate fish community richness and composition in mining ponds of different dimensions, years post abandonment, and degree of pulse flood connectivity using traditional collection-based methods and environmental DNA (eDNA) with the 12S and COI markers. We compared these two methods of biodiversity inventory and contrasted results from ASGM waterbodies with those obtained from nearby pristine oxbow lakes. Overall, we registered more fish richness at all sites using eDNA vs traditional methods, especially with the 12S marker. We identified 14 and 13 unique genera using traditional methods and eDNA, respectively, with 40 genera detected by both approaches, evidencing their complementarity. Notably, we found that the degree of pulse flooding connectivity was the main predictor of species richness among the abandoned mining ponds (p-value &lt; 0.05). We registered 11 to 22, 23 to 71, and 56 morphospecies in non-flooded mining ponds, pulse flooded mining ponds and nearby oxbow lakes, respectively. Furthermore, the fish community composition of mining ponds most influenced by pulse flooding were similar to that of pristine lakes. Our findings highlight the role of hydrological connectivity in ecological recovery within mining-impacted wetlands. Future restoration efforts should enhance aquatic connectivity to accelerate recovery in post-mining environments.

Quality improvements (QIs) in dynamic and complex health care contexts require resilience and take variability into account in quality improvement. The Functional Resonance Analysis Method (FRAM) helps us understand resilience and gain insight into (un)desirable variability in the complex system of daily practice. We explored how using FRAM in the Deming cycle of a QI project can help professionals and researchers learn from, reflect upon, and improve complex processes. We used FRAM in a Dutch hospital to study a QI: Critical Care Outreach Service (CCOS). The aim was to use FRAM before and after implementation to create a FRAM model and reflect to health care professionals the mismatch between Work As Imagined (WAI) and Work As Done (WAD). The WAI FRAM model was co-created with professionals before the implementation of CCOS. We used descriptions of tasks and processes for ICU nurses and verified them in 30-minute semistructured interviews (N = 2). WAD was created by input of semistructured interviews with key professionals in CCOS (N = 21) and 3 nonparticipant observations of trained CCOS nurses. We validated WAD in 2 dialogue sessions with key professionals (N = 11). Data collection continued until saturation. Juxtaposing the WAI and WAD models showed that WAD contained additional functions and highlighted unexpectedly complex functions. Reflecting on the application of FRAM with health care professionals revealed opportunities and challenges, especially time investment. FRAM helps professionals outline processes and tasks (WAI), learn from, and reflect upon their daily practice (WAD). FRAM models help professionals identify variability proactively to improve practices that enhance resilient performance.