Antifungal and antibacterial investigation of quinary Zr Al Fe Co Ni layered double hydroxide and its Al Fe Co Ni quaternary and Fe Co Ni tertiary roots.

Layered double hydroxides (LDH) are promising 2D nanomaterials being investigated for several engineering and biomedical applications. In this work, quinary Zr Al Fe Co Ni LDH and its Al Fe Co Ni LDH quaternary and Fe Co Ni LDH tertiary roots were prepared and characterized. All samples showed an aggregated, layered morphology with zero surface charge and approximately 300 nm of hydrodynamic size. BET surface area of Al Fe Co Ni LDH showed a remarkable value of 143.25 m2 g-1 as opposed to 26.2 m2 g-1 and 45.4 m2 g-1 for Fe Co Ni LDH and Zr Al Fe Co Ni LDH, respectively. The antimicrobial activity of the prepared samples was assessed against the many pathogenic bacteria; Bacillus (B.) subtilis, Escherichia (E.) coli, Haemophilus (H.) influenza, Listeria (L.) monocytogenes, Staphylococcus (S.) aureus, and Streptococcus (St.) pneumonia, and six fungal species. Furthermore, anti-biofilm activity, growth curve assay, and effect of UV illumination were examined against various pathogenic microbes. Zr Al Fe Co Ni displayed remarkable antibacterial activity, as indicated by the lowest values of the minimum inhibitory concentrations (MIC) of 4-166.7 µg mL-1. Results for fungal strains varied in terms of their susceptibilities for the different samples tested. Zn Al Fe Co Ni was able to inhibit the biofilm formation of S. aureus (96.09%), E. coli (98.32%), and Candida (C.) albicans (95.93%). This study shown that certain LDH categories, particularly Zr Al Fe Co Ni, may be promising antibacterial agents against variety of pathogenic microorganisms that cause serious infections.

Microstructure Evolution during High-Pressure Torsion in a 7xxx AlZnMgZr Alloy.

A homogenized, supersaturated AlZnMgZr alloy was processed via severe plastic deformation (SPD) using a high-pressure torsion (HPT) technique for different revolutions at room temperature to obtain an ultrafine-grained (UFG) microstructure. The microstructure and mechanical properties of the UFG samples were then studied using transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and tensile and hardness measurements. The main purpose was to study the effect of shear strain on the evolution of the microstructure of the investigated alloy. We found a very interesting evolution of the decomposed microstructure in a wide range of shear strains imposed by HPT. While the global properties, such as the average grain size (~200 nm) and hardness (~2200 MPa) appeared unchanged, the local microstructure was continuously transformed. After 1 turn of HPT, the decomposed UFG structure contained relatively large precipitates inside grains. In the sample processed by five turns in HPT, the segregation of Zn atoms into grain boundaries (GBs) was also observed. After 10 turns, more Zn atoms were segregated into GBs and only smaller-sized precipitates were observed inside grains. The intensive solute segregations into GBs may significantly affect the ductility of the material, leading to its ultralow-temperature superplasticity. Our findings pave the way for achieving advanced microstructural and mechanical properties in nanostructured metals and alloys by engineering their precipitation and segregation by means of applying different HPT regimes.

Optimization of Water Based Drilling Fluid Properties with the SiO2/g-C3N4 Hybrid.

Drilling fluids are an essential component of drilling operations in the oil and gas industry. Nanotechnology is being used to develop advanced drilling fluid additives. This study looked at the viability of synthesizing SiO2/g-C3N4 hybrid extending the Stober process followed by its addition in different concentrations to water-based drilling fluids and studying impact on the rheological and fluid loss properties of the fluids. The synthesized hybrid was analyzed using XRD, SEM, TGA, and FTIR. Subsequently, it was used to develop the water-based drilling mud formulations and subjected to measurements in accordance with API standard practices. The studies were carried out at various SiO2/g-C3N4 nanoparticle concentrations under before hot rolling (BHR) and after hot rolling (AHR) conditions. The outcomes demonstrated that the rheological and fluid loss properties were enhanced by the addition of SiO2/g-C3N4 nanoparticles, as it worked in synergy with other additives. Additionally, it was discovered that the nanoparticles improved the drilling fluid thermal stability. The experimental findings indicate a significant influence of SiO2/g-C3N4 nanoparticles on base fluid properties including rheology and fluid loss as the most remarkable, especially at higher temperatures. The significant improvements in yield point and 10 s gel strength were 55 and 42.8% under BHR and 216 and 140% under AHR conditions, respectively. Permeability plugging test (PPT) fluid loss was reduced by 69.6 and 87.2% under BHR and AHR conditions, respectively, when 0.5 lb/bbl nanoparticles were used in formulations. As a result, SiO2/g-C3N4 nanomaterial has the potential to be used as drilling fluid additive in water-based drilling fluids.

Tobacco and nicotine use among active component U.S. military service members: a comparison of 2018 estimates from the Health Related Behaviors Survey and the Periodic Health Assessment.

This study compared estimates of the prevalence of and risk factors for tobacco and nicotine use obtained from the 2018 Health Related Behaviors Survey (HRBS) and Periodic Health Assessment (PHA) survey. The HRBS and the PHA are important Department of Defense sources of data on health behavior collected from U.S. military service members. While their collection methods differ, some survey questions are similar, which provides an opportunity to compare survey estimates. Active duty service members consistently reported a much lower prevalence of all types of tobacco and nicotine use on the PHA compared to the HRBS: cigarettes (11.1% vs. 18.4%), e-cigarettes (7.3% vs. 16.2%), chewing tobacco (9.7% vs. 13.4%), any tobacco or nicotine use (25.3% vs. 37.8%), and use of 2 or more tobacco or nicotine products (5.8% vs. 17.4%). Associations between tobacco and nicotine use as well as demographic and other behavioral variables were fairly similar, including age, sex, education, race and ethnicity, rank, and alcohol use. The associations with service branch, body mass index, and sleep were inconsistent. This results of this study suggest that the PHA can provide timely information on trends in military tobacco and nicotine use over time, but much higher estimates from the confidential, voluntary HRBS reported in this study suggest that the command-directed PHA may substantially underestimate the prevalence of all types of tobacco and nicotine use.

Coverage of HIV pre-exposure prophylaxis (PrEP) within the active duty U.S. military, 2023.

Estimates of HIV pre-exposure prophylaxis (PrEP) coverage in the U.S. military, defined as the proportion of the persons taking HIV PrEP out of the estimated number of persons who had indications for it, have never been published. The objective of this study was to provide an estimate of HIV PrEP coverage comparable to U.S. civilian estimates. The population with indications for HIV PrEP was obtained from the Department of Defense 2018 Health Related Behaviors Survey, a stratified random sample of members of all military service branches. The military PrEP coverage estimate of 31.6% in 2023 was lower than the national U.S. estimate of 36.0% in 2022. Among the military population of men who have sex with men (MSM), an estimated 24.6% of service members had indications for PrEP, similar to the national estimate of 24.7%. MSM comprised 66% of all military service members with HIV PrEP indications, compared to 40% in the U.S. general population. The U.S. military should continue deliberate, sustained, and effective actions to address sexual health inequities among MSM, aligned and coordinated with societal efforts including improved coverage of HIV PrEP to prevent HIV transmission.

Health behavior profiles and association with mental health status among US active-duty service members.

Introduction: This study investigated the clustering of health behaviors among US active duty servicemembers (ADSM) into risk profiles and explored the association between these profiles with ADSM sociodemographic characteristics and mental health status. Methods: This study utilized secondary data from the 2018 Health Related Behaviors Survey (HRBS), a Department of Defense (DoD) self-administered online survey. Health behaviors included physical activity, screen use, sleep habits, tobacco/substance use, alcohol drinking, preventive health care seeking and condom use at last sex/having multiple sexual partners. Past-year mental health status was measured using the Kessler Screening Scale for Psychological Distress (K6). Latent class analysis (LCA) on health behaviors was used to cluster ADSMs into risk profiles. Multivariable logistic model was used to examine whether ADSM characteristics and mental health status were associated with ADSMs' risk profiles. Results: The LCA identified a four-class model that clustered ADSMs into the following sub-groups: (1) Risk Inclined (14.4%), (2) High Screen Users (51.1%), (3) Poor Sleepers (23.9%) and (4) Risk Averse (10.6). Over a tenth (16.4%) of ADSMs were categorized as having serious psychological distress. Being male, younger, less educated, in the Army, Marine Corps or Navy were associated with higher odds of being Risk Inclined (AOR ranging from 1.26 to 2.42). Compared to the reference group of Risk Adverse ADSMs, those categorized as Risk Inclined (AOR: 8.30; 95% CI: 5.16-13.36), High Screen Users (AOR: 2.44; 95% CI: 1.56-3.82) and Poor Sleepers (AOR: 5.26; 95% CI: 3.38-8.19) had significantly higher odds of having serious psychological distress. Discussion: Study findings suggest opportunities to tailor behavioral and health promotion interventions for each of the distinct risk profiles. For example, ADSM described as Risk Inclined may benefit from preventive mental health services. Solutions for ADSM described as Poor Sleepers may include education on sleep hygiene; instituting duty schedules; and shifting military cultural norms to promote sleep hygiene as a pathway to optimal performance and thus military readiness. ADSM with low-risk behavior profiles such as those described as Risk Averse may prove beneficial in the roll-out of interventions as they act as peer-educators or mentors.

Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors.

BACKGROUND: The lack of specific predictors for type-2 diabetes mellitus (T2DM) severely impacts early intervention/prevention efforts. Elevated branched-chain amino acids (BCAAs: Isoleucine, leucine, valine) and aromatic amino acids (AAAs: Tyrosine, tryptophan, phenylalanine)) show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies. However, improvement is needed to support its clinical utility. AIM: To evaluate the effects of body mass index (BMI) and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight. METHODS: Ninety-seven new-onset T2DM patients (< 12 mo) differing in BMI [normal weight (NW), n = 33, BMI = 22.23 ± 1.60; overweight, n = 42, BMI = 25.9 ± 1.07; obesity (OB), n = 22, BMI = 31.23 ± 2.31] from the First People's Hospital of Yunnan Province, Kunming, China, were studied. One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs. RESULTS: Fasting serum AAAs, BCAAs, glutamate, and alanine were greater and high-density lipoprotein (HDL) was lower (P < 0.05, each) in OB-T2DM patients than in NW-T2DM patients, especially in male OB-T2DM patients. Arginine, histidine, leucine, methionine, and lysine were greater in male patients than in female patients. Moreover, histidine, alanine, glutamate, lysine, valine, methionine, leucine, isoleucine, tyrosine, phenylalanine, and tryptophan were significantly correlated with abdominal adiposity, body weight and BMI, whereas isoleucine, leucine and phenylalanine were negatively correlated with HDL. CONCLUSION: Heterogeneously elevated amino acids, especially BCAAs/AAAs, across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development. The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals, whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals. This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

Impact of Sleep Profiles on Multimorbidity Among US Active-Duty Service Members in the 2018 Health-Related Behaviors Survey.

Purpose: Sleep is a modifiable factor affecting chronic diseases and conditions in the Active-Duty (AD) United States (US) military population. This study assesses the impact of reported sleep health behaviors and sleep profiles on reported multimorbidity in active-duty service members (ADSMs). Participants and methods: The study used a military representative sample of 17,166 active duty SMs from the 2018 Department of Defense Health Related Behaviors Survey (HRBS) to explore sleep patterns and profiles, and medical conditions. Multimorbidity was defined as the presence of two or more medical conditions which we limited to include obesity, hypertension, and hyperlipidemia. The adjusted odds ratios for six sleep-related health behaviors and their unobservable sleep profiles were calculated using a weighted multinomial logistic model. Results: Sleep-related health behaviors were associated with increased odds of obesity, hypertension, and hyperlipidemia. We found higher odds of reported multimorbidity in SMs who reported lack of energy due to poor sleep (adjusted odds ratio [aOR] = 2.35, 95% CI:1.88-2.93), sleep 6 hours or less per night (aOR = 1.95, 95% CI:1.53-2.50), trouble sleeping (aOR = 2.19, 95% CI:1.76-2.72), and use of sleep medications (aOR = 2.10, 95% CI:1.64-2.68). Latent class analysis (LCA) identified three unobservable sleep profiles in SMs: minimal or low-risk sleep patterns (37.43%), moderate-risk sleep patterns (31.11%), and high-risk sleep patterns (31.46%). SMs with high-risk sleep patterns were significantly associated with reported multimorbidity (adjusted odds ratio [aOR] = 3.54, 95% CI:2.75-4.56). Conclusion: We found a strong association between sleep-related health behaviors and their unobservable sleep profiles with multimorbidity in this AD population. Future studies should investigate whether other chronic diseases may be influenced by sleep impairment in the US military population.

Correction: Article Title: Quarantine-related traumatic stress, views, and experiences during the first wave of Coronavirus pandemic: A mixed-methods study among adults in Saudi Arabia.

[This corrects the article DOI: 10.1371/journal.pone.0261967.].

Integrated Endoscopic Craniosynostosis Surgery and Cranial Orthosis Program.

INTRODUCTION: Craniosynostosis results from premature fusion of the cranial sutures. There has been a continuous evolution of surgical correction techniques from an extensive open procedure to the minimally invasive technique. AIMS AND OBJECTIVES: This novel surgical technique has never been previously done in the UAE and this article documents the experience of the first team to endoscopically correct craniosynostosis with planning, surgical techniques, and customized helmet therapy. METHODS: A retrospective case series of 16 nonsyndromic craniosynostosis patients with unicoronal (6), sagittal (5), bicoronal (1), frontosphenoidal (2), and metopic craniosynostoses (2) was corrected endoscopically and followed up with customized cranial helmet. Preoperative and postoperative photography, along with anthropometric measurements were taken. RESULTS: The mean age of all patients at the time of surgery was 101 (90-117) days, mean duration of surgery was 70 minutes (38-129), mean blood loss was 120 mL (100-150), and mean duration of hospital stay 4 days (4-5). No complications and mortality were reported. Mean number of helmets was 2 (1-3). Cranial index improved in all patients with sagittal and bicoronal craniosynostosis. Close cooperation with the orthotist ensured timely helmet therapy and accurate laser scanning documentation in head molding. CONCLUSIONS: This case series has demonstrated that endoscopically craniosynostosis correction is safe, effective, and reliable and is the first reported series from the Middle East. The authors believe that every patient with nonsyndromic single­suture craniosynostosis should be offered endoscopic correction before the age of 6 months. The orthotist forms an important part of the Multi-disciplinary team, enabling successful outcomes.

Perceived Health Status and Medical Conditions Among US Active-Duty Service Members.

Purpose: This paper investigates the association between self-reported perceived health status and doctor-informed medical conditions among US active duty service members (ADSM). Methods: Data are from the 2018 Health-Related Behaviors Survey - a cross-sectional survey weighted to represent the US military (N = 17166). Perceived good health status was defined as having a response choice of "good", "very good", or "excellent" to the question: Would you say your overall physical health is ___? Medical conditions were based on self-reported presence of nine clinical conditions. Analysis included weighted prevalence and log-binomial regression models to explore relationships between ADSM characteristics with perceived good health status as well as concordance between perceived status and medical conditions. Results: ADSM rated their health to be excellent (14.6%), very good (37.7%), good (36.2%), fair (9.7%) and poor (1.7%). About 88.5% perceived a good (to excellent) health status. Perceived good health status was negatively associated with the number of medical conditions present (adjusted odds ratio (aOR): ranging from 0.78 to 0.92) as well as several health behaviors (aOR): ranging from 0.86 to 0.98) and other sociodemographic factors. Among all ADSMs, 51% perceived good health in the absence of medical conditions, while 8% perceived poor health status in the presence of medical conditions. Concordance between perceived health status and medical conditions was significantly lower among ADSM who were older (aOR: 0.61; 95% CI: 0.54-0.69), with dependent children (aOR: 0.89; 95% CI: 0.84-0.95), or had been deployed (aOR: 0.89, 95% CI: 0.84-0.95). Conclusion: The prevalence of perceived good health status among ADSMs was consistent with those documented in the general US population. The interrelationships between ADSM's perceptions, medical conditions and sociodemographic characteristics may have implications for their health literacy and utilization of health services. Study findings suggest that interventions promoting healthy behaviors, health literacy and treatment-seeking may influence perceived health status and mitigate medical conditions among ADSM, thus improving the US Military readiness, resilience and mission success.

Suicidal Behaviors Among Active-Duty US Service Members: Data from the 2018 Health-Related Behaviors Survey.

Background: This study aimed to 1) determine the prevalence of past-year suicidal ideation (SI) and attempts (SA) among active-duty SMs; 2) determine whether differences exist by age, sex, and race; and 3) assess whether prevalence estimates vary by risk profiles of mental health conditions and substance use. Methods: Data were from the 2018 Health-Related Behavior Survey (HRBS), a cross-sectional survey of active-duty SMs (n = 17,166). We used the logistic model to identify the factors of SI and SA and latent class analysis (LCA) to identify the risk profiles. Results: Among active duty SMs, 8.26% had SI and 1.25% had SA in the past year. Gender and age have been shown to influence how race might contribute to suicidal behaviors. Mental health conditions were associated with higher odds of SI and SA, as were younger ages; LGB identity; being separated, divorced, or widowed; use of e-cigarettes, dual use of e-cigarettes and cigarettes, or drugs; and history of deployment of less than 12 months. Frequencies of cigarette and e-cigarette use were also associated with SI and SA, indicating the odds were increasing by 0.3% for every additional cigarette or e-cigarette used. Five risk profiles were identified: class 1 (illegal drug use), class 2 (mental health needs with tobacco and alcohol use), class 3 (mental health conditions only), class 4 ("low risk" SMs with low levels of illegal drug use, mental health visits, tobacco use, and alcohol use), and class 5 (alcohol use). Compared to class 4 ("low risk"), all other risk profiles were associated with increased odds of suicidal behaviors. Conclusion: Despite the resources and increased access provided for mental health support, the prevalence of SI among active-duty SMs is greater than in the general population of the same age, likely due to additional military exposures and stressors.

Green UPLC method for estimation of ciprofloxacin, diclofenac sodium, and ibuprofen with application to pharmacokinetic study of human samples.

Investigation of a unique and fast method for the determination and separation of a mixture of three drugs viz., ciprofloxacin (CIP), Ibuprofen (IBU), and diclofenac sodium (DIC) in actual samples of human plasma. Also, the technique was used to look at their pharmacokinetics study. Hydrocortisone was chosen as the internal standard (IS). The drugs were chromatographically separated using an Acquity ultra-performance liquid chromatography UPLC ® BEH C18 1.7 µm (2.1 × 150 mm) column with a mobile phase composed of acetonitrile: water (65:35, v/v) adjusted to pH 3 with diluted acetic acid. Plasma proteins were precipitated with acetonitrile. The separated drugs ranged from 0.3 to 10, 0.2-11, and 1-25 µg/mL for CIP, IBU, and DIC, respectively. Calibration curves were discovered to achieve linearity with acceptable correlation coefficients (0.99%). Examination of quality assurance samples showed exceptional precision and accuracy. Following the successful application of this improved technique to plasma samples, the pharmacokinetic characteristics of each selected drug were evaluated using (UPLC) with UV detection at 210 nm. Two green metrics were applied, the Analytical Eco-scale and the Analytical GREEnness Calculator (AGREE). Separation was achieved in only 4-min analysis time. The method's validation agreed with the requirements of the FDA, and the results were sufficient.

Effect of the Equal Channel Angular Pressing on the Microstructure and Phase Composition of a 7xxx Series Al-Zn-Mg-Zr Alloy.

A supersaturated Al-4.8%Zn-1.2%Mg-0.14%Zr (wt%) alloy was processed by the equal-channel angular pressing (ECAP) technique at room temperature in order to obtain an ultrafine-grained (UFG) microstructure having an average grain size of about 260 nm. The hardness and microstructural characteristics, such as the phase composition and precipitations of this UFG microstructure were studied using depth-sensing indentation (DSI), transmission electron microscopy (TEM), as well as non-isothermal scanning of differential scanning calorimetry (DSC), and compared to the properties of the un-deformed sample. Emphasis was placed on the effect of the UFG microstructure on the subsequent thermal processes in DSC measurements. It has been shown that the ECAP process resulted in not only an ultrafine-grained but also a strongly precipitated microstructure, leading to a hardness (2115 MPa) two and a half times higher than the initial hardness of the freshly quenched sample. Because of the significant changes in microstructure, ECAP has also a strong effect on the dissolution (endothermic) and precipitation (exothermic) processes during DSC measurements, where the dissolution and precipitation processes were quantitatively characterized by using experimentally determined specific enthalpies, ΔH and activation energies, Q.

The most common pulmonary diseases length of stay, and characteristics of patients admitted to pulmonary service.

BACKGROUND: Although chronic respiratory diseases are prevalent in Saudi Arabia, there are limited data on the patient burden and associated factors. The aim of this study is to identify the chronic respiratory diseases frequently admitted to pulmonary services and to determine the patient's characteristics, associated comorbidities readmission rate, and reason for a more extended stay in hospital. METHODS: A prospective study was conducted over a 5-year period at King Abdulaziz Medical City-Riyadh, Saudi Arabia, in the Pulmonary Division, between March 2015 and December 2019. Data on demographics, comorbidities, and chronic respiratory diseases were collected. RESULTS: Total patients admitted were 1315 patients, female 54.2%, the mean age was 62.4 (SD±17.6), and the ages ranged from 14 to 98 years. Overall, chronic obstructive pulmonary disease was the most common respiratory disease requiring admission (17.9%), followed by interstitial lung disease (15.8%), bronchiectasis (11.9%), and obesity hypoventilation syndrome (10.8%). The most common comorbidities were obesity (42.5%), diabetes 49.1%, and hypertension 54.9%. Only 135 (10.3%) were readmitted within 30 days posthospital discharge. Among the patients who were readmitted, 103 (76.3%) were readmitted due to issues related to previous admission diagnosis, noncompliance 75 (55.5%), social reasons, and premature discharges in 51 (37.8%) and 29 (21.5%) of the cases, respectively. The respiratory disease varied significantly by gender, age, obesity status, comorbidities, length of stay (LOS), and admissions. CONCLUSION: Chronic respiratory diseases are prevalent in our population and are mainly influenced by gender, age, obesity status, comorbidities, LOS, and admissions. Policymakers and health professionals need to recognize the burden of chronic respiratory diseases on patients and health systems and implement effective prevention programs.

mAb therapy controls CNS-resident lyssavirus infection via a CD4 T cell-dependent mechanism.

Infections with rabies virus (RABV) and related lyssaviruses are uniformly fatal once virus accesses the central nervous system (CNS) and causes disease signs. Current immunotherapies are thus focused on the early, pre-symptomatic stage of disease, with the goal of peripheral neutralization of virus to prevent CNS infection. Here, we evaluated the therapeutic efficacy of F11, an anti-lyssavirus human monoclonal antibody (mAb), on established lyssavirus infections. We show that a single dose of F11 limits viral load in the brain and reverses disease signs following infection with a lethal dose of lyssavirus, even when administered after initiation of robust virus replication in the CNS. Importantly, we found that F11-dependent neutralization is not sufficient to protect animals from mortality, and a CD4 T cell-dependent adaptive immune response is required for successful control of infection. F11 significantly changes the spectrum of leukocyte populations in the brain, and the FcRγ-binding function of F11 contributes to therapeutic efficacy. Thus, mAb therapy can drive potent neutralization-independent T cell-mediated effects, even against an established CNS infection by a lethal neurotropic virus.

Vinpocetine protects against chloroquine-induced cardiotoxicity by mitigating oxidative stress.

Chloroquine (CQ) and hydroxychloroquine (HCQ) are classical antimalarial drugs, and recently have been used for other applications including coronavirus disease 2019 (COVID-19). Although they are considered safe, cardiomyopathy may associate CQ and HCQ applications particularly at overdoses. The goal of the present study was to evaluate the potential protective effect of the nootropic agent vinpocetine against CQ and HCQ adverse effects with a specific focus on the heart. For this purpose, a mouse model of CQ (0.5 up to 2.5 g/kg)/HCQ (1 up to 2 g/kg) toxicity was used, and the effect of vinpocetine was evaluated by survival, biochemical, as well as histopathological analyses. Survival analysis revealed that CQ and HCQ caused dose-dependent lethality, which was prevented by co-treatment with vinpocetine (100 mg/kg, oral or intraperitoneal). To gain deeper understanding, a dose of 1 g/kg CQ-which did not cause death within the first 24 h after administration-was applied with and without vinpocetine administration (100 mg/kg, intraperitoneal). The CQ vehicle group showed marked cardiotoxicity as evidenced by significant alterations of blood biomarkers including troponione-1, creatine phosphokinase (CPK), creatine kinase-myocardial band (CK-MB), ferritin, and potassium levels. This was confirmed at the tissue level by massive alteration of the heart tissue morphology and coincided with massive oxidative stress. Interestingly, co-administration of vinpocetine strongly ameliorated CQ-induced alterations and restored the antioxidant-defense system of the heart. These data suggest that vinpocetine could be used as an adjuvant therapy together with CQ/HCQ applications.

Global and local evolutionary dynamics of Dengue virus serotypes 1, 3, and 4.

Evolutionary studies on Dengue virus (DENV) in endemic regions are necessary since naturally occurring mutations may lead to genotypic variations or shifts in serotypes, which may lead to future outbreaks. Our study comprehends the evolutionary dynamics of DENV, using phylogenetic, molecular clock, skyline plots, network, selection pressure, and entropy analyses based on partial CprM gene sequences. We have collected 250 samples, 161 in 2017 and 89 in 2018. Details for the 2017 samples were published in our previous article and that of 2018 are presented in this study. Further evolutionary analysis was carried out using 800 sequences, which incorporate the study and global sequences from GenBank: DENV-1 (n = 240), DENV-3 (n = 374), and DENV-4 (n = 186), identified during 1944-2020, 1956-2020, and 1956-2021, respectively. Genotypes V, III, and I were identified as the predominant genotypes of the DENV-1, DENV-3, and DENV-4 serotypes, respectively. The rate of nucleotide substitution was found highest in DENV-3 (7.90 × 10-4 s/s/y), followed by DENV-4 (6.23 × 10-4 s/s/y) and DENV-1 (5.99 × 10-4 s/s/y). The Bayesian skyline plots of the Indian strains revealed dissimilar patterns amongst the population size of the three serotypes. Network analyses showed the presence of different clusters within the prevalent genotypes. The data presented in this study will assist in supplementing the measures for vaccine development against DENV.

Intrinsic disorder in the open reading frame 2 of hepatitis E virus: a protein with multiple functions beyond viral capsid.

BACKGROUND: Hepatitis E virus (HEV) is the cause of a liver disease hepatitis E. The translation product of HEV ORF2 has recently been demonstrated as a protein involved in multiple functions besides performing its major role of a viral capsid. As intrinsically disordered regions (IDRs) are linked to various essential roles in the virus's life cycle, we analyzed the disorder pattern distribution of the retrieved ORF2 protein sequences by employing different online predictors. Our findings might provide some clues on the disorder-based functions of ORF2 protein that possibly help us in understanding its behavior other than as a HEV capsid protein. RESULTS: The modeled three dimensional (3D) structures of ORF2 showed the predominance of random coils or unstructured regions in addition to major secondary structure components (alpha helix and beta strand). After initial scrutinization, the predictors VLXT and VSL2 predicted ORF2 as a highly disordered protein while the predictors VL3 and DISOPRED3 predicted ORF2 as a moderately disordered protein, thus categorizing HEV-ORF2 into IDP (intrinsically disordered protein) or IDPR (intrinsically disordered protein region) respectively. Thus, our initial predicted disorderness in ORF2 protein 3D structures was in excellent agreement with their predicted disorder distribution patterns (evaluated through different predictors). The abundance of MoRFs (disorder-based protein binding sites) in ORF2 was observed that signified their interaction with binding partners which might further assist in viral infection. As IDPs/IDPRs are targets of regulation, we carried out the phosphorylation analysis to reveal the presence of post-translationally modified sites. Prevalence of several disordered-based phosphorylation sites further signified the involvement of ORF2 in diverse and significant biological processes. Furthermore, ORF2 structure-associated functions revealed its involvement in several crucial functions and biological processes like binding and catalytic activities. CONCLUSIONS: The results predicted ORF2 as a protein with multiple functions besides its role as a capsid protein. Moreover, the occurrence of IDPR/IDP in ORF2 protein suggests that its disordered region might serve as novel drug targets via functioning as potential interacting domains. Our data collectively might provide significant implication in HEV vaccine search as disorderness in viral proteins is related to mechanisms involved in immune evasion.