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In this randomized, controlled trial involving women in South Africa and Uganda, twice-yearly subcutaneous lenacapavir was superior to daily oral emtricitabine–tenofovir disoproxil fumarate in preventing HIV infection.

In this research work, a new incremental slab method analysis has been derived to calculate extrusion force and its die pressure distribution during an extrusion process, while a die of arbitrary shape is used. In addition, a computational algorithm has been presented based on the proposed analysis method and Archard’s wear model to investigate the effect of die profile on its working life. Three different die profiles including optimum curved, optimum constant angle, and cylindrical shaped are numerically evaluated. The results revealed that the predicted extrusion loads and die pressure distributions through the implementation of the applied method are in an acceptable agreement with FEM analysis results. Moreover, it has been demonstrated that the maximum wear depth on all die profiles is located at the die exit area, which indicates the predominant effect of the material velocity profile. It is also found that the die life of the two optimum dies would be the same, but the least working life estimated is the working lifetime of the cylindrical die profile.

Discontinuous dynamic recrystallization is a critical microstructural evolution mechanism during high-temperature deformation, influencing material properties significantly. This study develops a two-dimensional phase-field model to predict steady-state creep rates in the AZ31 magnesium alloy, focusing on DRX during creep. To enhance simulation accuracy, initial microstructures are generated from optical microscopy data, enabling simulations at larger scales with higher representativeness. A novel nucleation methodology is implemented, eliminating the need for nuclei order parameter adaptation, improving computational efficiency. Finite element analysis (FEA) is integrated to capture initial instantaneous deformation. The Kocks–Mecking model is employed to describe the evolution of average dislocation density, accounting for work hardening and dynamic recovery within the initial polycrystalline microstructure. Instead of conventional creep testing, impression creep, a cost-effective alternative, is used for validation. This method provides constant stress and steady penetration velocity, simulating creep conditions effectively. The model accurately predicts recrystallization kinetics and microstructural evolution, exhibiting a strong correlation with experimental results, with an error of approximately 5%. This research provides a robust and efficient approach for predicting creep behavior in high-temperature applications, vital for optimizing material selection and predicting component lifespan in industries. The methodology offers a significant advancement in understanding and predicting DRX-driven creep behavior.

Enzyme therapy can be an appropriate treatment option for celiac disease (CeD). Here, we developed Bromelain-Loaded Nanocomposites (BLNCs) to improve the stability and retention of bromelain enzyme activity. After the characterization of BLNCs, the cytotoxicity of BLNCs was determined on the Caco-2 cell line. The effect of BLNCs on gliadin degradation and the production of pro-inflammatory cytokines and anti-inflammatory molecules in peripheral blood mononuclear cells (PBMCs) obtained from celiac patients were assessed. Furthermore, the expression of CXCR3 and CCR5 genes was measured in CaCo-2 cells treated with gliadin, gliadin-digested with BLNCs, and bromelain. Our study demonstrated that the Bromelain entrapment efficiency in these nanoparticles was acceptable, and BLNCs have no toxic effect on cells. SDS-PAGE confirmed the digestion effect of bromelain released from nanocomposites. When Caco-2 cells were treated with gliadin digested by free bromelain and BLNCs, the expression of CXCR3 and CCR5 genes was significantly decreased. PBMCs of celiac patients treated with Bromelain and BLNCs decreased inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) production compared to untreated PBMCs. This treatment also increased IL-10 and CTLA-4 in PBMCs of CeD patients. According to the promising results of this study, we can hope for the therapeutic potential of BLNCs for CeD.

The burden of COVID-19 has been noted to be disproportionately greater in minority women, a population that is nevertheless still understudied in COVID-19 research. We conducted an observational study to examine COVID-19-associated mortality and cardiovascular disease outcomes after testing (henceforth index) among a racially diverse adult women veteran population. We assembled a retrospective cohort from a Veterans Affairs (VA) national COVID-19 shared data repository, collected between February and August 2020. A case was defined as a woman veteran who tested positive for SARS-COV-2, and a control as a woman veteran who tested negative. We used Kaplan–Meier curves and the Cox proportional hazards model to examine the distribution of time to death and the effects of baseline predictors on mortality risk. We used generalized linear models to examine 60-day cardiovascular disease outcomes. Covariates studied included age, body mass index (BMI), and active smoking status at index, and pre-existing conditions of diabetes, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), and a history of treatment with antiplatelet or anti-thrombotic drug at any time in the 2 years prior to the index date. Women veterans who tested positive for SARS-CoV-2 had 4 times higher mortality risk than women veterans who tested negative (Hazard Ratio 3.8, 95% Confidence Interval CI 2.92 to 4.89) but had lower risk of cardiovascular events (Odds Ratio OR 0.78, 95% CI 0.66 to 0.92) and developing new heart disease conditions within 60 days (OR 0.67, 95% CI 0.58 to 0.77). Older age, obesity (BMI > 30), and prior CVD and COPD conditions were positively associated with increased mortality in 60 days. Despite a higher infection rate among minority women veterans, there was no significant race difference in mortality, cardiovascular events, or onset of heart disease. SARS-CoV-2 infection increased short-term mortality risk among women veterans similarly across race groups. However, there was no evidence of increased cardiovascular disease incidence in 60 days. A longer follow-up of women veterans who tested positive is warranted.

In this paper, the effect of two stages of cyclic expansion–extrusion (CEE) process on fiber crystallographic textures of pure copper is investigated using crystal plasticity finite element method. In the first approach, the expansion and extrusion stages are idealized by equi-biaxial tension and equi-biaxial compression, respectively. Through the second approach, the real strain history of the extrusion stage is captured by embedding a polycrystalline aggregate in the billet. The simulated results illustrate the effect of the expansion stage and redundant shear strain during the extrusion stage on the inverse pole figure maps after a pass of CEE process. Also, the published results confirm the reliability of the predicted fiber textures which acknowledge the accuracy of the second approach for a complete pass of the CEE technique to understand the role of shear strain on the fiber texture.

Abstract Context Although iodine-induced hyperthyroidism is a potential consequence of iodinated radiologic contrast administration, its association with long-term cardiovascular outcomes has not been previously studied. Objective To investigate the relationships between hyperthyroidism observed after iodine contrast administration and incident atrial fibrillation/flutter. Methods Retrospective cohort study of the U.S. Veterans Health Administration (1998-2021) of patients age ≥18 years with a normal baseline serum thyrotropin (TSH) concentration, subsequent TSH <1 year, and receipt of iodine contrast <60 days before the subsequent TSH. Cox proportional hazards regression was employed to ascertain the adjusted hazard ratio (HR) with 95% CI of incident atrial fibrillation/flutter following iodine-induced hyperthyroidism, compared with iodine-induced euthyroidism. Results Iodine-induced hyperthyroidism was observed in 2500 (5.6%) of 44 607 Veterans (mean ± SD age, 60.9 ± 14.1 years; 88% men) and atrial fibrillation/flutter in 10.4% over a median follow-up of 3.7 years (interquartile range 1.9-7.4). Adjusted for sociodemographic and cardiovascular risk factors, iodine-induced hyperthyroidism was associated with an increased risk of atrial fibrillation/flutter compared with those who remained euthyroid after iodine exposure (adjusted HR 1.19, 95% CI 1.06-1.33). Females were at greater risk for incident atrial fibrillation/flutter than males (females, HR 1.81, 95% CI 1.12-2.92; males, HR 1.15, 95% CI 1.03-1.30; P for interaction = .04). Conclusion Hyperthyroidism following a high iodine load was associated with an increased risk of incident atrial fibrillation/flutter, particularly among females. The observed sex-based differences should be confirmed in a more sex-diverse study sample, and the cost–benefit analysis of long-term monitoring for cardiac arrhythmias following iodine-induced hyperthyroidism should be evaluated.

Background.Treatment of invasive mold infection in immunocompromised patients remains challenging. Voriconazole has been shown to have efficacy and survival benefits over amphotericin B deoxycholate, but its utility is limited by drug interactions. Liposomal amphotericin B achieves maximum plasma levels at a dosage of 10 mg/kg per day, but clinical efficacy data for higher doses are lacking. Methods.In a double-blind trial, patients with proven or probable invasive mold infection were randomized to receive liposomal amphotericin B at either 3 or 10 mg/kg per day for 14 days, followed by 3 mg/kg per day. The primary end point was favorable (i.e., complete or partial) response at the end of study drug treatment. Survival and safety outcomes were also evaluated. Results.Of 201 patients with confirmed invasive mold infection, 107 received the 3-mg/kg daily dose, and 94 received the 10-mg/kg daily dose. Invasive aspergillosis accounted for 97% of cases. Hematological malignancies were present in 93% of patients, and 73% of patients were neutropenic at baseline. A favorable response was achieved in 50% and 46% of patients in the 3- and 10-mg/kg groups, respectively (difference, 4%; 95% confidence interval, -10% to 18%; P > .05); the respective survival rates at 12 weeks were 72% and 59% (difference, 13%; 95% confidence interval, -0.2% to 26%; P > .05). Significantly higher rates of nephrotoxicity and hypokalemia were seen in the high-dose group. Conclusions.In highly immunocompromised patients, the effectiveness of 3 mg/kg of liposomal amphotericin B per day as first-line therapy for invasive aspergillosis is demonstrated, with a response rate of 50% and a 12-week survival rate of 72%. The regimen of 10 mg/kg per day demonstrated no additional benefit and higher rates of nephrotoxicity.

Background The impact of sodium–glucose cotransporter-2 (SGLT2) inhibitors on mortality following myocardial infarction (MI) remains uncertain. Additionally, the role of type 2 diabetes mellitus (T2DM) and heart failure (HF) in modulating the effectiveness of these drugs post-MI are not fully understood. This meta-analysis aimed to assess the association of SGLT2 inhibitors with all-cause mortality in post-MI patients and to explore key moderators influencing this benefit. Methods PubMed, Embase, and Scopus were searched for randomized controlled trials (RTCs) and propensity score-matched (PSM) observational studies assessing SGLT2 inhibitors' impact on post-MI mortality. The primary outcome was all-cause mortality. We pooled hazard ratios (HRs) to estimate the intervention's effect on the overall population and stratified studies into early (SGLT2 inhibitors administered within eight weeks post-MI) and delayed treatment trials. Meta-regression assessed the moderating effects of T2DM and HF. Results  A total of five RCTs and four PSM observational studies involving 26,753 patients (mean [SD] age, 62.9 [10.5] years; 6,406 female [24.0%]; 16,369 T2DM [61.2%]; 13,933 HF [52.1%]) were included. Early and delayed treatment trials comprised 16,165 (60.4%) and 10,588 (39.6%) patients, respectively. SGLT2 inhibitors reduced all-cause mortality following MI (HR 0.79, 95% CI [0.68, 0.91]; p = 0.001; I 2  = 59%). Stratified analysis demonstrated consistent effects in both early (HR 0.76, 95% CI [0.59, 0.98]; p = 0.03; I 2  = 65%) and delayed (HR 0.81, 95% CI [0.67, 0.98]; p = 0.03; I 2  = 60%) treatment. Meta-regression identified T2DM as a significant moderator of the mortality benefit (β = − 0.0049; p = 0.0006). Conclusion In this meta-analysis, early and delayed treatment with SGLT2 inhibitors following MI was associated with a significant reduction in all-cause mortality . Furthermore, the presence of T2DM was associated with a greater mortality reduction, while HF was not significantly associated with the outcome. Graphical Abstract Association of SGLT2 Inhibitors with Mortality Across the Spectrum of Myocardial Infarction. Data from 26,753 post-MI patients are summarized, including baseline characteristics. The plots represent the pooled hazard ratios (HRs) with 95% confidence intervals (CIs), comparing SGLT2 inhibitors to control (placebo/no treatment), with HRs below 1 favoring SGLT2 inhibitors. The diagram shows early and delayed treatment trial subgroups, presenting the number of participants, the percentage receiving SGLT2 inhibitors, and the respective HRs for mortality. The meta-regression panel highlights T2DM and HF as moderators, reporting β-coefficients (β), p-values, and residual heterogeneity (I 2 ). Negative β (−) indicates that as the percentage of the moderator increases, the HR for mortality decreases. Abbreviations: HF, heart failure; MI, myocardial infarction; SGLT2i, sodium–glucose cotransporter-2 inhibitors; T2DM, type 2 diabetes mellitus.

Lipopolysaccharide (LPS) is a toxic and immunogenic agent for human. Additionally, LPS is a good target for some antimicrobial compounds, including antimicrobial peptides (AMPs). LPS-binding peptides (LBPs) can recognize and neutralize LPS. Rabbit and human cathelicidins are AMPs with LPS-binding activity. In this study, we designed and synthesized two new truncated LBPs from rabbit and human CAP18 peptides by in silico methods. After synthesis of peptides, the antimicrobial properties and LPS-binding activity of these peptides were evaluated. The parental rabbit and human CAP18 peptides were selected as positive controls. Next, the changes in the secondary structure of these peptides before and after treatment with LPS were measured by circular dichroism (CD). Human cytotoxicity of the peptides was evaluated by MTT and red blood cells (RBCs) hemolysis assays. Finally, field emission scanning electron microscopy (FE-SEM), confocal microscopy, and flow cytometry were performed to study the action mechanism of these peptides. Results indicated that the hCap18 and rCap18 had antibacterial activity (at a MIC of 4–128 μg/mL). The results of the quantitative LAL test demonstrated that LPS-binding activity of hCap18 peptide was better than rCap18, while rCap18 peptide had better antimicrobial properties. Furthermore, rCap18 had less cytotoxicity than hCap18. However, both peptides were nontoxic for normal human skin fibroblast cell in MIC range. In conclusion, rCap18 has good antibacterial properties, while hCap18 can be tested as a diagnostic molecule in our future studies.