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Mohamed H Aly,1 Sayed S Rahman,2 Waleed A Ahmed,3 Mansour H Alghamedi,4 Abudlrahman A Al Shehri,5 Amna M Alkalkami,2 Mohammed H Hassan6 1Internal Medicine Department, Security Forces Hospital Makkah (SFHM), Makkah al-Mukarrammah, Saudi Arabia; 2Nephrology Department, Internal Medicine Department, Security Forces Hospital Makkah (SFHM), Makkah al-Mukarrammah, Saudi Arabia; 3Infectious Disease Unit, Internal Medicine Department, Security Forces Hospital Makkah (SFHM), Makkah al-Mukarrammah, Saudi Arabia; 4Gastroenterology and Hepatology Department, Internal Medicine Department, Security Forces Hospital Makkah (SFHM), Makkah al-Mukarrammah, Saudi Arabia; 5Rheumatology Department, Internal Medicine Department, Security Forces Hospital Makkah (SFHM), Makkah al-Mukarrammah, Saudi Arabia; 6Medical Biochemistry Department, Faculty of Medicine, South Valley University, Qena, EgyptCorrespondence: Mohammed H HassanMedical Biochemistry Department, Faculty of Medicine, South Valley University, Qena, EgyptTel +201098473605Email mohammedhosnyhassaan@yahoo.comAbstract: COVID-19 is an emerging disease all over the world and spreading at an unpredicted rate, resulting in significant influences on global economies and public health. Clinical, laboratory, and imaging characteristics have been partially described in some observational studies. Not enough systematic reviews on predictors of critical illness and mortality in COVID 19 have been published to date. In this review, we had illustrated the prognostic predictors of COVID-19 by gathering published information on the risk factors related to the outcomes of SARS-CoV-2 infections.Keywords: COVID 2019, SARS-CoV-2, predictors, critical illness, mortality

In a recent study, we used chemical analysis to show that the Caesalpinia mimosoides aqueous extract, which contains a high concentration of simple phenolics, has strong anti-influenza activity. We determined through molecular docking methods that its potential target inhibitor is the neuraminidase. Therefore, our study objectives were to evaluate whether the aqueous-ethanol extract (30% v/v) of this plant species exhibits greater antiviral activity than the aqueous plant extract. The C. mimosoides hydroethanolic extract exhibited potent antioxidant activity in the DPPH assay, with an IC 50 value of 15.01 µg/mL, comparable to authentic quercetin (IC 50  = 12.72 µg/mL) and approximately 4.91 times greater than standard gallic acid (IC 50  = 3.06 µg/mL). Through untargeted metabolomic analyses (UPLC-ESI(±)-QTOF-MS/MS) and subsequent stepwise computational metabolomics analyses, we identified the extract as primarily containing simple phenolics (e.g., gallic acid, ellagic acid, shikimic acid, and chlorogenic acid), flavonoid derivatives (e.g., quercetin, taxifolin, myricitrin, and afzelin), and other bioactive components, including dicarboxylic acids and germacrone. The polyphenol-rich extract showed strong anti-influenza activity, with an IC 50 of 2.33 µg/mL against the influenza A/PR/8/34 virus and no cytotoxic effects, as indicated by a CC 50 greater than 50 µg/mL. This represents an approximately 3.35-fold increase in effectiveness compared to its corresponding aqueous extract (IC 50  = 7.81 µg/mL). Furthermore, the extract demonstrated no hemolytic activity, even at a maximum concentration of 2,000 µg/mL, suggesting its potential as a safe antiviral agent. Molecular docking analyses revealed that the identified phytochemicals can simultaneously interact with the "drug-target binding sites" of neuraminidase (NA) and PB2 subunit of influenza RNA polymerase, indicating their potential polypharmacological effects. The antiviral activity of the ethanolic-aqueous extract against other strains is being explored due to the versatile biological effects of phenolic substances., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Cadmium (Cd) disrupts the immune system and intestinal barrier, increasing infection risk and gut dysbiosis. Its impact on intestinal fungi, particularly the opportunistic pathogen Candida albicans, which can cause systemic infections in immunocompromised patients, is not well understood. Our study revealed that C. albicans exhibited high tolerance and maintained its morphogenetic switching in response to Cd. As C. albicans is not naturally found in the mouse gut, we attempted intestinal colonization of C. albicans-SC5314 strain using standard procedures. However, the intestinal fungal load decreased and was undetectable by 15th day. To assess the effects of sub-chronic Cd exposure, both oral and intravenous methods were used. Oral exposure to C. albicans (10 5  CFU/ml) resulted in a 10-fold increase in intestinal translocation in Cd-exposed mice (0.98 mg/kg) compared to controls. Cd exposure also downregulated intestinal tight junction proteins and increased FITC-dextran permeability, indicating that Cd disrupts the intestinal barrier and facilitates C. albicans translocation. Moreover, Cd-exposed mice showed significant morbidity and higher fungal loads in organs after intravenous non-lethal dose of C. albicans, along with a subdued cytokine response. These findings highlight the significant impact of Cd on fungal pathogenicity and immune response, pointing to the broader health risks of Cd exposure., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Elsevier Inc. All rights reserved.)

N 2 is generally employed as a displacement agent to enhance gas recovery in shale gas-bearing reservoirs. However, the primary displacement mechanism in the subsurface still needs to be clarified due to the characteristics of shale reservoirs with low porosity and abundant nanopores. This study employs the Molecular Dynamics (MD) simulation method to investigate the effects of N 2 on the CH 4 accumulation and displacement processes by adopting practical conditions in the subsurface environment. In equilibrium MD simulation processes, including the N 2 from outside and inner kerogen matrix, keeping the gas ratio of 1:3 for CH 4 and N 2 , the displacement is 52.4% and 65.3%, respectively, which suggests that CH 4 cannot be entirely displaced by surrounding N 2 particles, owing to the strong interaction between CH 4 and the kerogen matrix. For the straightforward displacement process by N 2 , the displacement efficiency is enhanced by 71.7% at the 1:1 gas ratio. Another case of N 2 , in which generation is accompanied by displacement processes, at the ratio 1:2 for N 2 :CH 4 , shows a 47.1% displacement efficiency. This work evidences that the straightforward displacement process is more efficient on CH 4 displacement, which enhances CH 4 production at a pronounced scale and sheds light on the N 2 displacement process in industrial shale gas reservoir production., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Lewis antibodies, such as anti-Le a and anti-Le b , are commonly encountered in routine immunohematology. They are typically IgM in nature and are generally considered clinically insignificant, as they rarely cause hemolytic transfusion reactions (HTRs) or hemolytic disease of the fetus and newborn (HDFN). However, rare cases have been reported where anti-Lewis antibodies caused mild transfusion reactions. In this case report, we describe a 69-year-old male with sepsis secondary to a neck carbuncle who was found to have clinically significant anti-Lewis antibodies. These antibodies presented a challenge during crossmatching, as only two out of seven units of packed red blood cells were compatible. This case underscores the importance of thorough pre-transfusion testing to ensure safe and effective blood transfusion practices., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This project was supported by Universiti Sultan Zainal Abidin (UniSZA) under the Dana Penyelidikan Universiti (UniSZA/2023/GOT/01). Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Mohamad Mustafa et al.)

Hyaluronidases have been a subject of great interest in medical and cosmeceutical applications. Previously, our group demonstrated that the venom glands of Vespa tropica contain hyaluronidase enzymes (VesT2s), and heterologous expression of the corresponding gene ( VesT2a ) in E. coli systems results in inclusion bodies, necessitating functional folding using urea. Here, we report the successful heterologous expression of VesT2a in the Pichia pastoris expression system, with gene construction achieved using Golden PiCS . After confirming gene integration in the yeast genome, methanol-induced cultures yielded an exceptional amount of VesT2a, approximately two-fold higher than that obtained with the constitutive expression vector (P GAP ). Upon culturing in a bioreactor, yeast cells harboring pAOX1-αMF- VesT2a produced secreted proteins with a total yield of 96.45 mg/L. The secreted VesT2a has a molecular weight of 59.35 kDa, significantly higher than the expected molecular weight (~40.05 kDa), presumably due to endogenous glycosylation by the yeast cells. It exhibits optimal activity at 37 °C and pH 3, showing a specific activity of 4238.37 U/mg, and remains active across a broad range of pH and temperature. Notably, it exhibits higher hyaluronidase activity than the crude venom and E. coli -expressed protein, likely due to improved folding via endogenous post-translational modifications, such as disulfide bonds and N-glycosylation; this underscores the potential of heterologous systems for producing venomous hyaluronidases from other species. In silico docking-based analyses further support its catalytic activity and provide insights into seeking natural inhibitors from phenolic-rich plant extracts to alleviate symptoms in patients suffering from insect bites and stings.

Objectives: To determine if ChatGPT can incorporate patient-specific information to provide high-quality answers to parental questions in the PICU. We hypothesized that ChatGPT would generate high-quality, patient-specific responses., Methods: In this cross-sectional study, we generated assessments and plans for 3 PICU patients with respiratory failure, septic shock, and status epilepticus and paired them with 8 typical parental questions. We prompted ChatGPT with instructions, an assessment and plan, and 1 question. Six PICU physicians evaluated the responses for accuracy (1-6), completeness (yes/no), empathy (1-6), and understandability (Patient Education Materials Assessment Tool, PEMAT, 0% to 100%; Flesch-Kincaid grade level). We compared answer quality among scenarios and question types using the Kruskal-Wallis and Fischer's exact tests. We used percent agreement, Cohen's Kappa, and Gwet's agreement coefficient to estimate inter-rater reliability., Results: All answers incorporated patient details, utilizing them for reasoning in 59% of sentences. Responses had high accuracy (median 5.0, [interquartile range (IQR), 4.0-6.0]), empathy (median 5.0, [IQR, 5.0-6.0]), completeness (97% of all questions), and understandability (PEMAT % median 100, [IQR, 87.5-100]; Flesch-Kincaid level 8.7). Only 4/144 reviewer scores were <4/6 in accuracy, and no response was deemed likely to cause harm. There was no difference in accuracy, completeness, empathy, or understandability among scenarios or question types. We found fair, substantial, and almost perfect agreement among reviewers for accuracy, empathy, and understandability, respectively., Conclusions: ChatGPT used patient-specific information to provide high-quality answers to parental questions in PICU clinical scenarios., (Copyright © 2024 by the American Academy of Pediatrics.)

Despite the therapeutic advances in treating malignancies, the efficient radiotherapeutic approaches with deprived adverse reactions still represent a potential clinical inquiry. The current study aims to elucidate the role of gallic acid (GA) in modifying the hazardous renal cytotoxicity induced by acute exposure to radiation. The MTT test was used to evaluate the viability of Vero cells exposed to 2 Gy gamma radiation with or without incubation of GA. In an in vivo model, male Wistar rats were divided into four experimental groups (n = 6): Control, Irradiated (IRR, 5 Gy), GA (100 mg/kg, i.p.) + IRR, and Glycogen synthase kinase inhibitor (GSKI, 3 mg/kg, i.p.) + IRR. Based on the MTT toxicity assay, from 0 and up to 5 μM dosages of GA did not demonstrate any cytotoxicity to Vero cells. The optimal GA dose that could protect the cells from radiation was 5 μM. Furthermore, GA exerted a protective effect from gamma radiation on renal tissue as indicated by corrected renal functions, decreased LDH level in serum, and balanced oxidative status, which is indicated by decreased tissue contents of NOx and TBARS with a significant increase of reduced GSH. These outcomes were inferred by the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression. The overall molecular impact of radiation in damaging the renal tissue may be explained by modifying the upstream AKT activity and its downstream targets GSK-3β/Notch-1. Here, we concluded that the anticipated adverse reaction in the course of radiation exposure could be protected by daily administration of GA., (© 2024 Wiley Periodicals LLC.)

Objective: The study aimed at designing a pH sensitive Lipid polymeric Hybrid nanoparticle (LPHNP) for targeted release of Paclitaxel (PTX) and Curcumin (CUR) in breast cancer., Significance: Such systems shall result in controlled triggered release in acidic microenvironment of tumor cells with improved pharmacokinetic profile., Methods: Chitosan-coated CUR and PTX coloaded pH-sensitive LPHNPs were synthesized employing nanoprecipitation technique. The synthesized NPs were characterized in terms of particle size, polydispersity index (PDI), zeta potential, and morphology., Results: LPHNPs co-loaded with curcumin (CUR) and paclitaxel (PTX) were successfully formulated, achieving a size of 146 nm, a PDI of 0.18, and an entrapment efficiency exceeding 90%. In vitro release studies demonstrated controlled release of CUR and PTX under tumor pH conditions showing 1.6 fold and 1.7 fold higher release in ABS pH 5 in comparison to PBS 7.4 for PTX and CUR respectively. MTT-assay studies revealed enhanced cytotoxicity of CUR and PTX as LPHNPs showing IC 50 value of free CUR & PTX 480.06 µg/mL decreasing to 282.97 µg/mL for CS-CUR-PTX-LPHNPs. In vivo pharmacokinetic evaluations in rats confirmed significantly improved bioavailability, with a 3.8-fold increase in AUC for CUR and a 6.6-fold increase for PTX. Additionally, the LPHNPs demonstrated controlled release and prolonged retention, evidenced by a 2.2-fold increase in the half-life (t1/2) of CUR and a 1.3-fold increase in the half-life of PTX., The results underscores potential of chitosan-coated LPHNP as a promising delivery platform, offering high drug loading, optimal size for cellular penetration, and prolonged blood circulation for cancer.

Magnesium plays a vast role in the nervous system. In particular, high magnesium in cerebrospinal fluid appears to enhance the neural functions, while low magnesium induces neuronal diseases. The aim of the study was to find out the relation of serum magnesium with idiopathic generalized epilepsy attending in a tertiary care hospital. This cross-sectional comparative study was conducted in the department of Neurology at Mymensingh Medical College and Hospital, Bangladesh from January 2019 to June 2020 following ethical approval. Total 110 purposively selected participants (55 with idiopathic generalized epilepsy and 55 non epileptic apparently healthy individuals) were enrolled in this study. Serum total Mg was measured by EMP-168 Biochemical Analyzer. Average age of epileptic individuals was 33.13±9.5 years and majority was female (60.0%). Mean serum magnesium level was lower in epileptic patients than controls (1.80±0.041 vs. 2.02±0.19 mg/dl; p<0.001). Patients with higher seizure attack (>3 per month) had significantly lower mean serum magnesium level than the patients with seizure attack three or less per month. Serum magnesium levels are reduced in epileptic patients compared to healthy age and gender matched controls. Studies involving larger numbers of patients are needed to confirm these results.

Histone H2B monoubiquitination in budding yeast is a highly conserved post-translational modification. It is involved in normal functions of the cells like DNA Repair, RNA Pol II activation, trans-histone H3K and H79K methylation, meiosis, vesicle budding, etc. Deregulation of H2BK123ub can lead to the activation of proto-oncogenes and is also linked to neurodegenerative and heart diseases. Recent discoveries have enhanced the mechanistic underpinnings of H2BK123ub. For the first time, the Rad6's acidic tail has been implicated in histone recognition and interaction with Bre1's RBD domain. The non-canonical backside of Rad6 showed inhibition in polyubiquitination activity. Bre1 domains RBD and RING play a role in site-specific ubiquitination. The role of single Alaline residue in Rad6 activity. Understanding the mechanism of ubiquitination before moving to therapeutic applications is important. Current advancements in this field indicate the creation of novel therapeutic approaches and a foundation for further study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The increasing prevalence of diabetes and dyslipidemia poses significant health challenges, impacting millions of people globally and leading to high rates of illness and death. This study aimed to explore the potential antidiabetic and hypolipidemic effects of Plu kaow ( Houttuynia cordata Thunb.) ethanolic extract (PK) in streptozotocin (STZ) induced diabetic rats, focusing on its molecular mechanisms. Diabetes was induced in fasting Long Evans rats using streptozotocin (65 mg/kg b. w.), with glibenclamide (5 mg/kg/day) used as the standard experimental drug. The treated groups received oral supplementation of PK (500 mg/kg/day) for 28 days. The study evaluated blood glucose levels, lipid status, body weight, liver, kidney, and heart function biomarkers, antioxidant activity, and histological examination of various organs. Additionally, untargeted metabolomics, cheminformatics, and molecular docking were employed to elucidate the probable mechanisms of action of PK. Based on metabolomic profiling data, the PK was found to contain various putative antidiabetic agents such as kaempferol 7-neohesperidoside, isochlorogenic acid C, rutin, datiscin, and diosmin and they have been proposed to significantly ( p < 0.001) reduce blood glucose levels and modulated hyperlipidemia. PK also improved the tested liver, kidney, and heart function biomarkers and reversed damage to normal pancreatic, liver, kidney, and heart cells in histological analysis. In conclusion, PK shows promise as a potential treatment or management option for diabetes and hyperlipidemia, as well as their associated complications in diabetic rats.

ABO discrepancies in plasma cell myeloma (PCM) present unique challenges in blood typing tests and transfusion management. We present the case of a 51-year-old male with PCM who exhibited discrepancies between forward and reverse blood grouping. Further investigation revealed that the patient's blood type was a variant of blood group B. While type III discrepancies, typically characterized by elevated globulin levels causing false-positive reactions in both forward and reverse blood grouping, are common in multiple myeloma, our case differed due to the loss of B antigens secondary to the malignant condition. This caused a discrepancy in forward blood grouping. The rarity of ABO discrepancies in multiple myeloma underscores the importance of thorough evaluation. Awareness of potential antigen alterations in such patients is crucial to ensure safe transfusion practices., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Adzahar et al.)

In this paper, we develop high aspect ratio nanofibrils from a polycaprolactone-based thermoplastic polyurethane (TPU) and evaluate their performance as a toughening agent. Poly(methyl methacrylate) (PMMA) was chosen as the matrix material because of its inherent brittleness and low resistance to sudden shocks and impact. We show that the addition of as little as 3 wt % of TPU nanofibrils with an average diameter of ∼98 nm and very high aspect ratio can significantly improve both the tensile toughness (∼212%) and impact strength (∼40%) of the chosen matrix (i.e., PMMA) without compromising its original strength, stiffness, and transparency. We compare the performance of TPU nanofibrils with TPU spherical particles─the form TPU typically manifests into when melt-mixed with an immiscible polymer. Our findings highlight that the structure of TPU plays a crucial role in determining the critical concentration of TPU needed for the brittle-ductile transition of the matrix. We also provide new and valuable insights into the unique interfacial interaction (i.e., formation of fibrillar bridges) observed between the PMMA matrix and TPU. We also show that the inclusion of 3 wt % of TPU nanofibrils can notably enhance resistance to creep deformation, even at temperatures close to the glass transition temperature of the matrix. Finally, we evaluate recyclability and demonstrate that the composite containing 3 wt % of TPU nanofibrils can be mechanically recycled without losing any properties. The proposed TPU nanofibrils can withstand repeated reprocessing at temperatures up to 190 °C due to their very high melting point and thermal stability. This presents the opportunity for them to be utilized not just with amorphous PMMA, but also with a range of other materials that can be processed at or below this temperature to remarkably improve their toughness without sacrificing strength and stiffness.

Carbon dioxide (CO 2 ) injection in unconventional gas-bearing shale reservoirs is a promising method for enhancing methane recovery efficiency and mitigating greenhouse gas emissions. The majority of methane is adsorbed within the micropores and nanopores (≤50 nm) of shale, which possess extensive surface areas and abundant adsorption sites for the sequestration system. To comprehensively discover the underlying mechanism of enhanced gas recovery (EGR) through CO 2 injection, molecular dynamics (MD) provides a promising way for establishing the shale models to address the multiphase, multicomponent fluid flow behaviors in shale nanopores. This study proposes an innovative method for building a more practical shale matrix model that approaches natural underground environments. The grand canonical Monte Carlo (GCMC) method elucidates gas adsorption and sequestration processes in shale gas reservoirs under various subsurface conditions. The findings reveal that previously overlooked pore slits have a significant impact on both gas adsorption and recovery efficiency. Based on the simulation comparisons of absolute and excess uptakes inside the kerogen matrix and the shale slits, it demonstrates that nanopores within the kerogen matrix dominate the gas adsorption while slits dominate the gas storage. Regarding multiphase, multicomponent fluid flow in shale nanopores, moisture negatively influences gas adsorption and carbon storage while promoting methane recovery efficiency by CO 2 injection. Additionally, saline solution and ethane further impede gas adsorption while facilitating displacement. Overall, this work elucidates the substantial effect of CO 2 injection on fluid transport in shale formations and advances the comprehensive understanding of microscopic gas flow and recovery mechanisms with atomic precision for low-carbon energy development.

Neonatal hypoxic-ischemic encephalopathy after perinatal asphyxia causes neurolinguistic disturbances in children without disabilities. Poor academic performance appears as a long-term result. Language intervention is sought to reduce harmful effects on children. The aim of this study is showing the relationship between clinical conditions of hypoxic-ischemic-encephalopathy (HIE) and language disorders in children without disabilities. This cross-sectional study with a neurolinguistic approach was carried out in patients with perinatal asphyxia during childbirth, at the ZH Sikder Women's Medical College Hospital, Bangladesh. Respondents between 4 and 12 years, 76% underwent cranial computed tomography (CT); 82% underwent magnetic resonance imaging (MRI); and 70% underwent electroencephalogram (EEG). Among them were found positive results for neonatal hypoxia ischemic encephalopathy (EHI). These results are related to the following language disorders: reception/perception disorder (64%), sociolinguistic disorders (84%); metalinguistic competence disorder (66%); 86% of children had poor peer relationships and 72% had reading and writing disorders. Concluding, school-age children after perinatal asphyxia who developed Hypoxic-Ischemic Encephalopathy (HIE) had language disorders and poor school performance. There are still challenges to be overcome, as this is the first neurolinguistic approach in Bangladesh. More large-scale studies are needed., (Copyright © 2023 Asociación Colombiana de Psiquiatría. Published by Elsevier España, S.L.U. All rights reserved.)

Stroke is one of the most common neurological disorder and third most common cause of death in the world. Low vitamin D concentrations have been shown to predict risk of cardiovascular disease and all-cause of mortality. The aim of this study was to estimate serum vitamin D level in acute ischemic stroke patients. This comparative cross-sectional type of study was conducted in the Department of Neurology and Department of Medicine at Mymensingh Medical College and Hospital, Bangladesh from November 2017 to June 2019 with a total number of 100 study subjects. Total fifty patients with acute ischemic stroke were enrolled in Group A and another fifty age and sex matched volunteer subjects were enrolled in Group B with no prior history of stroke or transient ischemic attacks. Serum vitamin D levels, fasting plasma glucose and lipid profile were assessed in both groups and compared with each other. P value <0.05 was considered as significant in the study. Mean fasting blood sugar, serum fasting total cholesterol (TC), serum fasting triglycerides, serum fasting Low density lipoprotein (LDL) were significantly higher in Group A than Group B (p<0.05). Serum vitamin D level in Group A was 25.28±8.47ng/ml and in Group B was 30.90±5.80, (p=0.001). Insufficient vitamin D level was found in 52.0% of ischemic stroke patients and in 30% of healthy controls (p=0.0002). Vitamin D deficiency was found in 20.0% ischemic stroke patients and 10.0% in healthy controls. This study demonstrates a positive association between low serum vitamin D level and acute ischemic stroke. Further studies are required to determine whether vitamin D supplementation could improve functional outcome in patients with ischemic stroke.

This work introduces and discusses the impacts of the water bridge on gas adsorption and diffusion behaviors in a shale gas-bearing formation. The density distribution of the water bridge has been analyzed in micropores and meso-slit by molecular dynamics. Na + and Cl - have been introduced into the system to mimic a practical encroachment environment and compared with pure water to probe the deviation in water bridge distribution. Additionally, practical subsurface scenarios, including pressure and temperature, are examined to reveal the effects on gas adsorption and diffusion properties, determining the shale gas transportation in realistic shale formation. The outcomes suggest carbon dioxide (CO 2 ) usually has higher adsorption than methane (CH 4 ) with a water bridge. Increasing temperature hinders gas adsorption, density distribution decreases in all directions. Increasing pressure facilitates gas adsorption, particularly as a bulk phase in the meso-slit, whereas it restricts gas diffusion by enhancing the interaction strength between gas and shale. Furthermore, ions make the water bridge distributes more unity and shifts to the slit center, impeding gas adsorption onto shale while encouraging gas diffusion. This study provides updated guidelines for gas adsorption and transportation characteristics and supports the fundamental understanding of industrial shale gas exploration and transportation., (© 2024. The Author(s).)

Aims: To explore the relationship between nutritional intake, fermentable oligo-, di, monosaccharides and polyols, and carbohydrate malabsorption, with gastrointestinal symptoms during a 56 km trail ultramarathon event and identify differences in nutritional intake between runners with severe and non-severe gastrointestinal symptoms., Methods: Forty-four ultramarathoners recorded and self-reported dietary intake 3 days before, morning of, and during the ultramarathon with gastrointestinal symptoms obtained retrospectively and nutrient analysis via FoodWorks. Carbohydrate malabsorption was determined via breath hydrogen content pre- and post-race. Spearman's rank-order and Mann-Whitney U-tests were used to identify relationships and differences between groups., Results: Total fermentable oligo-, di, monosaccharides and polyols intake were not associated with gastrointestinal symptoms, but weak associations were observed for lower energy (r s  = -0.302, p = 0.044) and fat intake (r s  = -0.340, p = 0.024) 3 days before with upper gastrointestinal symptoms and higher caffeine intake 3 days before with overall gastrointestinal symptoms (r s  = 0.314, p = 0.038). Total fermentable oligo-, di-, monosaccharides and polyols intake and breath hydrogen were not different between those with severe versus non-severe symptoms (p > 0.05). Although those with severe symptoms had higher caffeine (p = 0.032), and total polyols intake (p = 0.031) 3 days before, and higher % energy from fat (p = 0.043) and sorbitol intake (p = 0.026) during the race, and slower ultramarathon finish times (p = 0.042)., Conclusion: Total fermentable oligo-, di-, and monosaccharides intake and carbohydrate malabsorption were not associated with gastrointestinal symptoms. Additional research on the effect of fat, caffeine, and polyol intake on exercise-associated gastrointestinal symptoms is warranted and presents new nutritional areas for consideration when planning nutritional intake for ultramarathoners., (© 2024 The Authors. Nutrition & Dietetics published by John Wiley & Sons Australia, Ltd on behalf of Dietitians Australia.)

The intricate architecture of the intestinal epithelium, crucial for nutrient absorption, is constantly threatened by environmental factors. The epithelium undergoes rapid turnover, which is essential for maintaining homeostasis, under the control of intestinal stem cells (ISCs). The central regulator, Wnt/β-catenin signaling plays a key role in intestinal integrity and turnover. Despite its significance, the impact of environmental factors on this pathway has been largely overlooked. This study, for the first time, investigates the influence of Cd on the intestinal Wnt signaling pathway using a mouse model. In this study, male BALB/c mice were administered an environmentally relevant Cd dose (0.98 mg/kg) through oral gavage to investigate the intestinal disruption and Wnt signaling pathway. Various studies, including histopathology, immunohistochemistry, RT-PCR, western blotting, ELISA, intestinal permeability assay, and flow cytometry, were conducted to study Cd-induced changes in the intestine. The canonical Wnt signaling pathway experienced significant downregulation as a result of sub-chronic Cd exposure, which caused extensive damage throughout the small intestine. Increased intestinal permeability and a skewed immune response were also observed. To confirm that Wnt signaling downregulation is the key driver of Cd-induced gastrointestinal toxicity, mice were co-exposed to LiCl (a recognized Wnt activator) and Cd. The results clearly showed that the harmful effects of Cd could be reversed, which is strong evidence that Cd mostly damages the intestine through the Wnt/β-catenin signalling axis. In conclusion, this research advances the current understanding of the role of Wnt/β catenin signaling in gastrointestinal toxicity caused by diverse environmental pollutants., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The present study aims to investigate the ability of CaNa2EDTA (ethylenediaminetetraacetic acid) macroparticles and nanoparticles to treat cadmium-induced toxicity in female rats and to compare their efficacies. Forty rats were divided into 4 equal groups: control, cadmium, cadmium + CaNa 2 EDTA macroparticles and Cd + CaNa 2 EDTA nanoparticles. Cadmium was added to the drinking water in a concentration of 30 ppm for 10 weeks. CaNa 2 EDTA macroparticles and nanoparticles (50 mg/kg) were intraperitoneally injected during the last 4 weeks of the exposure period. Every two weeks, blood and urine samples were collected for determination of urea, creatinine, metallothionein and cadmium concentrations. At the end of the experiment, the skeleton of rats was examined by X-ray and tissue samples from the kidney and femur bone were collected and subjected to histopathological examination. Exposure to cadmium increased the concentrations of urea and creatinine in the serum and the concentrations of metallothionein and cadmium in serum and urine of rats. A decrease in bone mineralization by X-ray examination in addition to various histopathological alterations in the kidney and femur bone of Cd-intoxicated rats were also observed. Treatment with both CaNa 2 EDTA macroparticles and nanoparticles ameliorated the toxic effects induced by cadmium on the kidney and bone. However, CaNa 2 EDTA nanoparticles showed a superior efficacy compared to the macroparticles and therefore can be used as an effective chelating antidote for treatment of cadmium toxicity., (© 2023. The Author(s).)

Liver fibrosis is a common chronic hepatic disease. This study aimed to investigate the effect of pitavastatin (Pit) against thioacetamide (TAA)-induced liver fibrosis. Rats were divided into four groups: (1) control group; (2) TAA group (100 mg/kg, i.p.) three times weekly for 2 weeks; (3 and 4) TAA/Pit-treated group, in which Pit was administered orally (0.4 and 0.8 mg/kg/day) for 2 weeks following TAA injections. TAA caused liver damage manifested by elevated serum transaminases, reduced albumin and histological alterations. Hepatic malondialdehyde (MDA) was increased, and glutathione (GSH) and superoxide dismutase (SOD) were decreased in TAA-administered rats. TAA upregulated the inflammatory markers NF-κB, NF-κB p65, TNF-α and IL-6. Treatment with Pit ameliorated serum transaminases, elevated serum albumin and prevented histopathological changes in TAA-intoxicated rats. Pit suppressed MDA, NF-κB, NF-κB p65, the inflammatory cytokines and PI3K mRNA in TAA-intoxicated rats. In addition, Pit enhanced hepatic antioxidants and boosted the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) mRNA. Moreover, immunohistological studies supported the ability of Pit to reduce liver fibrosis via suppressing p-AKT expression. In conclusion, Pit effectively prevents TAA-induced liver fibrosis by attenuating oxidative stress and the inflammatory response. The hepatoprotective efficacy of Pit was associated with the upregulation of Nrf2/HO-1 and downregulation of NF-κB and PI3K/Akt signalling pathways., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Our group previously demonstrated that Caesalpinia mimosoides Lamk exhibits many profound biological properties, including anticancer, antibacterial, and antioxidant activities. However, its antiviral activity has not yet been investigated. Here, the aqueous extract of C. mimosoides was prepared from the aerial parts (leaves, stalks, and trunks) to see whether it exerts anti-influenza (H1N1) effects and to reduce the organic solvents consumed during extraction, making it a desirable approach for the large-scale production for medical uses. Our plant extract was quantified to contain 7 g of gallic acid (GA) per 100 g of a dry sample, as determined using HPLC analysis. It also exerts potent antioxidant activities comparable to those of authentic GA. According to untargeted metabolomics (UPLC-ESI(-)-QTOF-MS/MS) with the aid of cheminformatics tools (MetFrag (version 2.1), SIRIUS (version 5.8.3), CSI:FingerID (version 4.8), and CANOPUS), the major metabolite was best annotated as "gallic acid", phenolics (e.g., quinic acid, shikimic acid, and protocatechuic acid), sugar derivatives, and dicarboxylic acids were deduced from this plant species for the first time. The aqueous plant extract efficiently inhibited an influenza A (H1N1) virus infection of MDCK cells with an IC 50 of 5.14 µg/mL. Of equal importance, hemolytic activity was absent for this plant extract, signifying its applicability as a safe antiviral agent. Molecular docking suggested that GA interacts with conserved residues (e.g., Arg152 and Asp151) located in the catalytic inner shell of the viral neuraminidase (NA), sharing the same pocket as those of anti-neuraminidase drugs, such as laninamivir and oseltamivir. Additionally, other metabolites were also found to potentially interact with the active site and the hydrophobic 430-cavity of the viral surface protein, suggesting a possibly synergistic effect of various phytochemicals. Therefore, the C. mimosoides aqueous extract may be a good candidate for coping with increasing influenza virus resistance to existing antivirals.

Lactoferrin (LCF), a potent naturally occurring antioxidant, is a crucial component in preventing potassium dichromate (PDC) toxicity. The goal of the current work was to study the potential efficacy of LCF in preventing PDC(CrVI)-induced testicular toxicity and oxidative injury in rats. Six groups of male rats of Wistar stain were randomly categorized into: group 1, which served as the control; group 2 and 3 received LCF (200 and 300 mg/kg orally, respectively); group 4 received PDC (2 mg/kg i.p.); group 5 and 6 pretreated with LCF, followed by PDC as in group 4 with 90 min apart for 28 days. PDC-intoxicated rats showed a significantly altered spermogram with abnormal sperm morphology. PDC significantly upregulated serum FSH and downregulated testosterone levels. Additionally, PDC decreased the levels of testicular key antioxidant biomarkers (catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH)) with elevated lipid peroxidation marker (TBARS) and testicular chromium content. Moreover, it upregulated testicular proinflammatory cytokines, IL-1, IL-6, IL-10, and TNF-α, induced histopathological changes in testes with significant immunohistochemical expression of FasL and moderate expression of Nrf2. Pretreatment with LCF significantly mitigated PDC-induced testicular toxicity by enhancing spermogram, improving hormonal levels, restoring testicular oxidant/antioxidant balance, and decreasing testicular IL-1, IL6, IL-10, and TNFα levels, and amending both FasL and Nrf2 immunohistochemical-expression. Additionally, LCF improved testicular histopathological picture and spermatogenesis. Our results highlight the importance of LCF as a superior protective modulator of PDC-induced testicular injury., (© 2023. The Author(s).)

Dengue is endemic in over 100 countries worldwide, predominantly in the subtropical and tropical regions and the incidence has been increasing globally. Patients with severe dengue may develop massive bleeding, disseminated intravascular coagulopathy and multi-organ failure. Bleeding may occur in various body cavities and muscles; however, bleeding in the retroperitoneal space is uncommon. We report a case of a 37-year-old gentleman who presented with a 4-day history of fever associated with chills and rigours. On Day 6 of illness, he complained of left lumbar and left iliac fossa pain which was aggravated by movement. A computed tomography angiography scan of the abdomen showed the presence of a retroperitoneal haematoma, left iliopsoas and quadratus lumbarum intramuscular haematoma with active bleeding and left abdominal wall muscles haematoma. His condition gradually improved after multiple blood transfusions and he gained full recovery. Spontaneous retroperitoneal haematoma is an uncommon complication of severe dengue infection. Early diagnosis based on high index of clinical suspicion using appropriate imaging will aid in prompt management of these cases and may prevent deaths., (© 2023 John Wiley & Sons Ltd.)

Exclusive breastfeeding (EBF) provides significant health benefits to children. However, mothers may find it difficult to continue EBF for 6 months. The present analysis aimed to examine the influence of the Suchana intervention-a large-scale programme implemented with the aim of improving the health and nutritional status of mothers and children from poor households in the Sylhet region of Bangladesh-on EBF and stunting among children under 6 months. Baseline and endline data were obtained from the Suchana evaluation. EBF was defined as an infant (<6 months) only receiving breast milk in the previous 24 h. Childhood stunting was defined as a length-for-age z-score of less than -2 among children of the same age. Multiple logistic regression analysis was used to assess the associations of the Suchana intervention with EBF and stunting. EBF prevalence improved from 64% at baseline to 85% at the endline in the intervention area, with the intervention group having 2.25 times higher odds of EBF compared to the control group. Stunting prevalence reduced from 28% at baseline to 24% at the endline in the intervention group, but after controlling for covariates, the association between stunting and the intervention was not significant. However, the interaction analysis showed significantly lower stunting prevalence among EBF children in both intervention and control areas. The Suchana intervention had a positive impact on the EBF practice of rural children in a vulnerable region of Bangladesh, and EBF was identified as a significant factor associated with stunting. The findings suggest that the continuation of the EBF intervention has the potential to have an impact on reducing stunting in the region, highlighting the importance of promoting EBF to improve child health and development., (© 2023 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Lead (Pb)-induced reprotoxicity is a detrimental consequence of Pb exposure, which results in abnormal spermatogenesis, testicular degeneration, and pathogenic sperm changes. The association between impaired male reproductive function and Pb-induced oxidative stress (OS) has been demonstrated, with consequent testicular antioxidant deficiency. The current study investigated the protective role of the natural antioxidant hesperidin (HSD) against lead-acetate (PbAc)-induced testicular toxicity. Male Wistar rats (n = 40) were randomly divided into four experimental groups: Group I (negative control) received 2.0 mL/kg BW 0.9% saline; Group II received 100 mg/kg BW PbAc; Group III received 100 mg/kg BW HSD; and Group IV received HSD two hours before PbAc using the abovementioned doses. The treatments were administered daily for 30 consecutive days. The results showed that HSD treatment significantly restored PbAc-induced decrease in body, epididymal, and testicular weights as well as in semen parameters, reproductive hormones, and testicular markers of OS. Reduced MDA levels and improved testicular histopathological findings were also observed. Collectively, this study sheds light on the preventive role of HSD against PbAc-induced testicular injury, which is mediated via the suppression of OS and the modulation of reproductive hormones as well as the plausibility of HSD being used as a supplementary therapeutic option for recovery.

Improvement in hand hygiene has been strongly associated with positive outcomes in maternal and child health. Although Bangladesh has a high level of awareness of key hygiene messages, the practice of handwashing, the most effective hygiene behavior, is low. Suchana, a multisectoral nutrition program, aims to increase knowledge and practices around various water, sanitation, and hygiene settings in Sylhet region, the northeast of rural Bangladesh. This study aimed to investigate the changes in indicators related to handwashing knowledge and practices among Suchana beneficiaries in final compared with baseline evaluations. Data were derived from the baseline and final cross-sectional evaluation survey. The following handwashing knowledge and practices were considered: handwashing before preparing food, before eating food and feeding children, before serving food, after defecation, and after touching animals. The descriptive findings indicate that Suchana intervention improved handwashing knowledge and practices in the intervention area compared with the control. The odds of having knowledge of hand washing before preparing food (adjusted odds ratio [aOR]: 1.60; 95% CI: 1.30-1.98), before eating food and feeding children (aOR: 1.68; 95% CI: 1.25-2.25), before serving food (aOR: 1.35; 95% CI: 1.04-1.76), after defecation (aOR: 1.74; 95% CI: 1.25-2.41), and after touching animals (aOR: 1.67; 95% CI: 1.29-2.16) were higher in intervention area than the control area. Similarly, the impact on maternal handwashing practices at final evaluation indicated successful effects of the intervention. These results suggest scaling-up of similar interventions for larger populations living in vulnerable areas of rural Bangladesh.

Objective: The aim of this study was to construct a predictive model in order to develop an intervention study to reduce the prevalence of stunting among children aged 12-23 months., Design: The study followed a cluster randomised pre-post design and measured the impacts on various indicators of livelihood, health and nutrition. The study was based on a large dataset collected from two cross-sectional studies (baseline and endline)., Setting: The study was conducted in the north-eastern region of Bangladesh under the Sylhet division, which is vulnerable to both natural disasters and poverty. The study specifically targeted children between the ages of 12 and 23 months., Main Outcome Measures: Childhood stunting, defined as a length-for-age z-score <-2, was the outcome variable in this study. Logistic and probit regression models and a decision tree were constructed to predict the factors associated with childhood stunting. The predictive performance of the models was evaluated by computing the area under the receiver operating characteristic (ROC) curve analysis., Results: The baseline survey showed a prevalence of 52.7% stunting, while 50.0% were stunted at endline. Several factors were found to be associated with childhood stunting. The model's sensitivity was 61% and specificity was 56%, with a correctly classified rate of 59% and an area under the ROC curve of 0.615., Conclusion: The study found that childhood stunting in the study area was correlated with several factors, including maternal nutrition and education, food insecurity and hygiene practices. Despite efforts to address these factors, they remain largely unchanged. The study suggests that a more effective approach may be developed in future to target adolescent mothers, as maternal nutrition and education are age-dependent variables. Policy makers and programme planners need to consider incorporating both nutrition-sensitive and nutrition-specific activities and enhancing collaboration in their efforts to improve the health of vulnerable rural populations., Trial Registration Number: RIDIE-STUDY-ID-5d5678361809b., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Diabetic peripheral neuropathy (DPN) is a common diabetic complication. Chrysin (CHY) has many biological properties but poor oral bioavailability. This study investigates the effect of CHY and CHY-loaded nanovesicles (CHY-NVs) on streptozotocin (STZ)-induced DPN in rats. CHY-NVs were prepared by using film hydration method. The formula with the best entrapment efficiency%, lowest particle size, highest zeta potential, and highest in vitro CHY released profile was selected, characterized by Differential scanning calorimetry, Fourier transformation infrared spectroscopy analysis, and examined by Transmission electron microscope. Acute toxicity test, pharmacokinetic study and experimental model of diabetes mellitus were performed on the selected formulation. Wistar rats were considered diabetic by administration of a single intraperitoneal dose of STZ (50 mg/kg). 48 h after STZ administration, hyperglycemic rats were randomly assigned into four groups, one group of untreated hyperglycemic rats and the other three groups received daily oral doses of unloaded NVs, CHY-NVs (25 mg/kg), and CHY-NVs (50 mg/kg), respectively for 21 days. Moreover, five additional groups of healthy rats received: distilled water (control), free CHY, unloaded NVs, and CHY-NVs respectively for 21 days. CHY and CHY-NVs maintained body weight and reduced STZ-induced behavioral changes in rotarod, hind paw cold allodynia, tail cold allodynia, tail flick, and hot plate tests. CHY and CHY-NVs lowered blood glucose, glycated hemoglobin, elevated serum reduced glutathione (GSH), and reduced plasma malondialdehyde (MDA) levels. CHY-NVs elevated phosphatidylinositol 3-kinase (Pi3k), phosphorylated protein kinase B (p-AKT), and reduced nuclear factor kappa B (NF-κB), interleukin-6 (IL-6) in sciatic nerve homogenate. CHY and CHY-NVs increased nerve growth factor (NGF) and decreased glycogen synthase kinase-3β (GSK-3β) gene expressions in the sciatic nerve. In conclusion, CHY and CHY-NVs ameliorated STZ-induced DPN behavioral and histopathological changes via attenuating hyperglycemia, exerting anti-oxidant, anti-inflammatory effects, activating NGF/p-AKT/GSK-3β pathway, and its anti-apoptotic effect. The best pharmacokinetic profile and therapeutic effect was observed in rats treated with CHY-loaded NVs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is second most common neurodegenerative disorder after Alzheimer's disease that may present with both motor and non-motor symptoms (NMSs). Many of the ignored NMSs may potentiate further deterioration of the patient's quality of life (QoL). But there is scarcity of data regarding NMSs of PD patients and their relationship with the disease severity in Bangladesh. This study was aimed to investigate the frequency of NMSs and assess their debatable impact on the severity of PD patients in Bangladesh. This cross-sectional type of observational study was conducted in neurology department of Dhaka Medical College Hospital, Bangladesh from January 2012 to June 2013 which recruited 60 eligible PD patients. The PD patients and disease severity was demonstrated by UK Parkinson's Disease Society Brain Bank criteria for idiopathic PD and the Hoehn and Yahr scale respectively. Whereas, NMSs were demonstrated by the self-structured questionnaire which had encountered 30 common symptoms of PD. The mean age of our study cohort was found 57.88±10.56 years with male female ration 2:1. According to the Hoehn and Yahr (H & Y) severity scale 38.3%, 38.3%, 20.1% and 3.3% patients had been suffering from stage ?, stage II, stage III and stage ?V Parkinson's disease respectively. Irrespective of the severity of the PD the frequency of NMSs was nocturia (66.7%), sadness or blues (65.0%), memory disturbance (61.7%), anxiety (58.3%), insomnia (56.7%), orthostatic hypotension (55.0%), erectile dysfunction (50.0%), urinary urgency (46.7%), anhedonia (45.0%), olfactory disturbance (38.3%), constipation (38.3%), hyper or hypo sexuality (31.7%) and restless leg syndrome (31.7%). However, after head-to-head NMSs analysis, daytime dribbling of saliva (p=0.024), urinary urgency (p=0.036), nocturia (p=0.001), weight loss (p=0.001), anhedonia (p=0.027), excessive daytime sleepiness (p=0.024), insomnia (p=0.007), vivid dream (p=0.024), REM behavior disorder (p=0.010), restless leg syndrome/ periodic leg movements (p=0.043) had significantly been reported higher among the stage II PD patients than that of stage I patients. Whereas fall (p=0.001), dysphagia or choking (p=0.002), constipation (p=0.003), fecal incontinence (p=0.033), excessive daytime sleepiness (p=0.033), anxiety (p=0.036) and anhedonia (p=0.044) were significantly more prevalent among the advanced stage (III) than stage (II) PD patients. Mean total NMS increased significantly with PD severity based on H and Y staging with a mean NMSQ-T (Non-Motor Symptoms Questionnaire Test) of 5.43 in stage 1, 9.22 in stage 2, 13.75 in stage 3 and 17.0 in stage 4 (p=0.0001). This study revealed that there was high frequency of NMSs among the PD patients and most common symptoms were nocturia, sadness, memory impairment, anxiety, insomnia, orthostatic hypotension, erectile dysfunction, anhedonia, urinary urgency and constipation. Finally, the more advanced disease as indicated by a higher H&Y stage was associated with significantly higher number of reported NMSs.