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Background: Thioacetamide (TAA) is known to cause damage to various organs, including the testes, posing a significant health threat. On the other hand, Curcuma longa (Cl) has been recognized for its antioxidant properties, suggesting a potential protective role against TAA-induced toxicity in the testes. Aim: This study aims to investigate the effect of TAA on testicular function and structure while exploring the therapeutic and protective potential of C. longa versus TAA toxicity. Methods: Thirty-two male albino rats, with an age range of 11–12 weeks and a weight range of 180-200 g, were randomly allocated into four distinct groups. The control group received normal saline, while the Cl group ingested Cl orally at a dose of 500 mg/kg daily. The TAA group, received TAA through intraperitoneal injections at a dose of 200 mg/kg body weight three times per week. Lastly, the Cl with TAA group received Cl orally 2 hours before the TAA injections. After 8 weeks of treatment, we anesthetized the rats and saved blood samples for biochemical analysis. Results: The study revealed significant alterations in various biochemical parameters in the TAA-treated group, as compared with the control. Specifically, there was a significant increase in bilirubin, albumin, cholesterol, triglyceride, very low-density lipoprotein (VLDL-C), white blood cells (WBCs), low-density lipoprotein cholesterol (LDL-C), and platelets (PLT) levels. Conversely, the Cl-treated group exhibited significant reductions in these parameters, along with notable increases in red blood cells (RBCs), high-density lipoprotein cholesterol (HDL-C), and hemoglobin (HB). Conclusion: C. longa demonstrates a protective effect on the testes against TAA-induced toxicity, potentially attributed to its antioxidant properties. This suggests a promising avenue for the use of Cl in mitigating the harmful effects of TAA on testicular function and structure. [Open Vet J 2024; 14(7.000): 1585-1595]

Objective: This study aimed to investigate the impact of thioacetamide (TAA) on the structure and function of the testes and assess the therapeutic effects of Curcuma longa (Cl) against TAA-induced toxicity in rats. Materials and Methods: Thirty-two male albino rats weighing 180–200 gm and aged 11–12 weeks were randomly separated into four groups. The control group was given normal saline, the Cl group was orally administered Cl (500 mg/kg/day), the TAA group received intraperitoneal TAA (200 mg/kg body weight, three times/week), and the Cl with TAA group received Cl orally two hours before TAA administration. After 8 weeks, all rats were anesthetized, and body and testis weights were recorded. Morphological and histological assessments as well as biochemical analyses were conducted. Results: The study revealed a significant decrease in both body and testis weights in the TAA group, accompanied by a substantial increase in luteinizing hormone (LH), follicle-stimulating hor¬mone (FSH), and malondialdehyde (MDA) levels. Testosterone (T) and glutathione (GSH) were significantly decreased in the TAA-treated group compared to the control. Conversely, the Cl-treated group exhibited a substantial decrease in LH, FSH, and MDA levels while showing a significant increase in T and GSH. Conclusion: Cl has been found to have a potential therapeutic role in mitigating TAA-induced testicular damage by acting as an antioxidant. This is supported by a significant decrease in oxi¬dative stress markers and supporting hormonal levels. Further research is needed to understand the underlying mechanisms and explore the clinical applicability of Cl in preventing and treating testicular toxicity. [J Adv Vet Anim Res 2024; 11(3.000): 762-771]

Background: The adverse effects of cytotoxic medications like methotrexate, particularly reproductive damage reported in the numerous experimental studies, limit their effectiveness as anticancer therapies. The current study's objectives were to identify potential histological and immune-histochemical unfavorable changes in the testicles due to methotrexate medication and to assess any possible protective effects of erythropoietin (EPO). Methods and Results: The study included 60 mature male albino rats weighing 200-250g. The animals were divided equally into three groups, each with 20 rats. In Group 1, the control group, the animals received intraperitoneal injections of normal saline twice a week for nine weeks at a dose of 0.5 mg/kg. For nine weeks, animals in Group 2 received intraperitoneal injections of methotrexate hydrate at 0.5 mg/kg twice a week. Animals in Group 3 received subcutaneous injections of 100 IU/kg recombinant human EPO once a week for nine weeks and intraperitoneal injections of methotrexate hydrate at a dosage of 0.5 mg/kg twice a week for nine weeks. Each rat was weighed every week throughout the examinations. An ELISA technique was used to measure the levels of testosterone, malondialdehyde (MDA), total antioxidant capacity (TAC), and ROS in blood serum. Morphological and histopathological changes in testicular tissue were assessed. The body weight in the rats treated with methotrexate was considerably lower than in control group rats. EPO showed clear androgenic and antioxidant activities and reduced the adverse effects of methotrexate on testicular histology. Our results suggest further research into the use of EPO as a drug to protect patients from the adverse effects of methotrexate.

AbstractThe emergence of superbugs and resistant pathogens poses a challenge in scientific and medical research as they threaten public health worldwide. Many herbal natural products currently used in therapies have been suggested to exert antimicrobial, antiviral and even virucidal activities against a vast majority of impervious pathogens. Rhazya stricta, a folk medicinal desert plant from Saudi Arabia was recently revealed to exhibit bactericidal activity against multidrug-resistant (MDR) microorganisms. The pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a threat to public health worldwide. Hence, we examined the antiviral activity of R. stricta against the virus. The R. stricta water extract was prepared at the traditional dose. The antagonistic effects of this extract against pathogens have been proven in previous studies, and those against SARS-CoV-2 were shown in the present study. Therefore, we explored the effects of the plant extracts and fractions against the virus for future drug development. All plant extracts showed antiviral effects against SARS-CoV-2 in the Vero E6 cell lines. Non-alkaloids showed the strongest effect against the virus, followed by weak base alkaloids and finally strong base alkaloids. A cytotoxicity assay was performed to explore the safest dose with the strongest antiviral effects. The non-alkaloid extract derived from R. stricta leaves is a promising antiviral candidate for the development of potential drugs with appropriate activity against COVID-19 and other life-threatening diseases.

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal ‘sentinel’ surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. Funding: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

Summary: Background: The objective of this study is to investigate the trends of exposure and burden attributable to the four main metabolic risk factors, including high systolic blood pressure (SBP), high fasting plasma glucose (FPG), high body-mass index (BMI), and high low-density lipoproteins cholesterol (LDL) in North Africa and the Middle East from 1990 to 2019. Methods: The data were retrieved from Global Burden of Disease Study 2019. Summary exposure value (SEV) was used for risk factor exposure. Burden attributable to each risk factor was incorporated in the population attributable fraction to estimate the total attributable deaths and disability-adjusted life-years (DALYs). Findings: While age-standardized death rate (ASDR) attributable to high-LDL and high-SBP decreased by 26.5% (18.6–35.2) and 23.4% (15.9–31.5) over 1990–2019, respectively, high-BMI with 5.1% (−9.0–25.9) and high-FPG with 21.4% (7.0–37.4) change, grew in ASDR. Moreover, age-standardized DALY rate attributed to high-LDL and high-SBP declined by 30.2% (20.9–39.0) and 25.2% (16.8–33.9), respectively. The attributable age-standardized DALY rate of high-BMI with 8.3% (−6.5–28.8) and high-FPG with 27.0% (14.3–40.8) increase, had a growing trend. Age-standardized SEVs of high-FPG, high-BMI, high-SBP, and high-LDL increased by 92.4% (82.8–103.3), 76.0% (58.9–99.3), 10.4% (3.8–18.0), and 5.5% (4.3–7.1), respectively. Interpretation: The burden attributed to high-SBP and high-LDL decreased during the 1990–2019 period in the region, while the attributable burden of high-FPG and high-BMI increased. Alarmingly, exposure to all four risk factors increased in the past three decades. There has been significant heterogeneity among the countries in the region regarding the trends of exposure and attributable burden. Urgent action is required at the individual, community, and national levels in terms of introducing effective strategies for prevention and treatment that account for local and socioeconomic factors. Funding: Bill & Melinda Gates Foundation.

Introduction: PIM kinases are targets for therapeutic intervention since they are associated with a number of malignancies by boosting cell survival and proliferation. Over the past years, the rate of new PIM inhibitors discovery has increased significantly, however, new generation of potent molecules with the right pharmacologic profiles were in demand that can probably lead to the development of Pim kinase inhibitors that are effective against human cancer.Method: In the current study, a machine learning and structure based approaches were used to generate novel and effective chemical therapeutics for PIM-1 kinase. Four different machine learning methods, namely, support vector machine, random forest, k-nearest neighbour and XGBoost have been used for the development of models. Total, 54 Descriptors have been selected using the Boruta method.Results: SVM, Random Forest and XGBoost shows better performance as compared to k-NN. An ensemble approach was implemented and, finally, four potential molecules (CHEMBL303779, CHEMBL690270, MHC07198, and CHEMBL748285) were found to be effective for the modulation of PIM-1 activity. Molecular docking and molecular dynamic simulation corroborated the potentiality of the selected molecules. The molecular dynamics (MD) simulation study indicated the stability between protein and ligands.Discussion: Our findings suggest that the selected models are robust and can be potentially useful for facilitating the discovery against PIM kinase.

Over the past decade, there has been a dramatic increase in the use of various technologies in the Architecture, Engineering, and Construction sector. Artificial intelligence has played a significant role throughout the different phases of the design and construction process. A growing body of literature recognizes the importance of artificial neural network applications in numerous areas of the construction industry and the built environment, presenting a need to explore the main research themes, attributes, benefits, and challenges. A three-step extensive research method was utilized by conducting a bibliometric search of English language articles and conducting quantitative and qualitative analyses. The bibliometric analysis aimed to identify the current research directions and gaps forming future research areas. The scientometric analysis of keywords revealed diverse areas within the construction industry linked to ANNs. The qualitative analysis of the selected literature revealed that energy management in buildings and construction cost predictions were the leading research topics in the study area. These findings recommend directions for further research in the field, for example, broadening the application ranges of ANNs in the current Construction 4.0 technologies, such as robotics, 3D printing, digital twins, and VR applications. [ABSTRACT FROM AUTHOR]

Summary: Background: Given the projected trends in population ageing and population growth, the number of people with dementia is expected to increase. In addition, strong evidence has emerged supporting the importance of potentially modifiable risk factors for dementia. Characterising the distribution and magnitude of anticipated growth is crucial for public health planning and resource prioritisation. This study aimed to improve on previous forecasts of dementia prevalence by producing country-level estimates and incorporating information on selected risk factors. Methods: We forecasted the prevalence of dementia attributable to the three dementia risk factors included in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 (high body-mass index, high fasting plasma glucose, and smoking) from 2019 to 2050, using relative risks and forecasted risk factor prevalence to predict GBD risk-attributable prevalence in 2050 globally and by world region and country. Using linear regression models with education included as an additional predictor, we then forecasted the prevalence of dementia not attributable to GBD risks. To assess the relative contribution of future trends in GBD risk factors, education, population growth, and population ageing, we did a decomposition analysis. Findings: We estimated that the number of people with dementia would increase from 57·4 (95% uncertainty interval 50·4–65·1) million cases globally in 2019 to 152·8 (130·8–175·9) million cases in 2050. Despite large increases in the projected number of people living with dementia, age-standardised both-sex prevalence remained stable between 2019 and 2050 (global percentage change of 0·1% [–7·5 to 10·8]). We estimated that there were more women with dementia than men with dementia globally in 2019 (female-to-male ratio of 1·69 [1·64–1·73]), and we expect this pattern to continue to 2050 (female-to-male ratio of 1·67 [1·52–1·85]). There was geographical heterogeneity in the projected increases across countries and regions, with the smallest percentage changes in the number of projected dementia cases in high-income Asia Pacific (53% [41–67]) and western Europe (74% [58–90]), and the largest in north Africa and the Middle East (367% [329–403]) and eastern sub-Saharan Africa (357% [323–395]). Projected increases in cases could largely be attributed to population growth and population ageing, although their relative importance varied by world region, with population growth contributing most to the increases in sub-Saharan Africa and population ageing contributing most to the increases in east Asia. Interpretation: Growth in the number of individuals living with dementia underscores the need for public health planning efforts and policy to address the needs of this group. Country-level estimates can be used to inform national planning efforts and decisions. Multifaceted approaches, including scaling up interventions to address modifiable risk factors and investing in research on biological mechanisms, will be key in addressing the expected increases in the number of individuals affected by dementia. Funding: Bill & Melinda Gates Foundation and Gates Ventures.

Maternal and Child Health and Nutrition Improvement Project (MCHNP) is an intervention that, adopts financial strategies to provide incentives as a means of motivating community health workers and ensuring accountability. This study highlights on the service delivery component of the intervention; thus, utilization of essential community nutrition and health action. This paper aims to determine the differential impact of MCHNP on maternal health service utilization in Ghana. A retrospective longitudinal pre-test post-test study design was employed. Six administrative regions were used for analyzing the impact of the intervention in uptake of maternal health services. Administrative data were extracted from the DHIMS2 database for the periods of January 2014 to December 2018. Analysis was conducted using interrupted time series analysis (ITSA) due to the absence of a control group. The difference in the pre-intervention and post-intervention means were statistically significant in the Central, Western, Eastern and Upper West region for the proportion of ANC 4 visits. With the exception of Northern region that recorded negative impact (-0.005; p-value >0.05), all the remaining regions recorded positive impacts on the percentage of women that had 4 ANC visits. All six regions had positive impacts in the proportion of women that received supervised delivery. However, none of these impacts were statistically significant; thus, the MCHNP intervention had no significant impact on maternal health outcomes which are, ANC four visits and skilled deliveries.

Asthma is a life-threatening and chronic inflammatory lung disease that is posing a true global health challenge. The genetic basis of the disease is fairly well examined. However, the molecular crosstalk between microRNAs (miRNAs), target genes, and transcription factors (TFs) networks and their contribution to disease pathogenesis and progression is not well explored. Therefore, this study was aimed at dissecting the molecular network between mRNAs, miRNAs, and TFs using robust computational biology approaches. The transcriptomic data of bronchial epithelial cells of severe asthma patients and healthy controls was studied by different systems biology approaches like differentially expressed gene detection, functional enrichment, miRNA-target gene pairing, and mRNA-miRNA-TF molecular networking. We detected the differential expression of 1703 (673 up-and 1030 down-regulated) genes and 71 (41 up-and 30 down-regulated) miRNAs in the bronchial epithelial cells of asthma patients. The DEGs were found to be enriched in key pathways like IL-17 signaling (KEGG: 04657), Th1 and Th2 cell differentiation (KEGG: 04658), and the Th17 cell differentiation (KEGG: 04659) (p-values = 0.001). The results from miRNAs-target gene pairs-transcription factors (TFs) have detected the key roles of 3 miRs (miR-181a-2-3p; miR-203a-3p; miR-335-5p), 6 TFs (TFAM, FOXO1, GFI1, IRF2, SOX9, and HLF) and 32 miRNA target genes in eliciting autoimmune reactions in bronchial epithelial cells of the respiratory tract. Through systemic implementation of comprehensive system biology tools, this study has identified key miRNAs, TFs, and miRNA target gene pairs as potential tissue-based asthma biomarkers.

The approach of Enterprise Architecture (EA) in Technical and Vocational Education and Training (TVET) institutions holds significant potential for the institution's digital transformation. This study explores key factors to sustain digital transformation in TVET Institutions using a Systematic Literature Review (SLR) and semistructured interviews. The SLR provides a comprehensive overview of existing literature on EA in educational contexts, focusing on its role in aligning institutional goals with industry requirements. Common themes and research gaps identified through this review set the stage for empirical investigation. Interviews with IT administrators, academia, and experts offer practical insights into the challenges and opportunities associated with EA implementation in TVET institutions, validating findings from the literature and uncovering unique contextual factors relevant to TVET institutions in Malaysia. The thematic analysis highlights several key factors, namely, management support and their involvement, a clear business vision and goal strategy, and the adoption of emerging technologies such as Artificial Intelligence and the Internet of Things towards sustainable digital transformation in TVET institutions. The findings indicate that a wellimplemented EA framework can significantly drive the digital transformation of TVET institutions, leading to better-prepared graduates and a more adaptable workforce. This study provides a detailed analysis of the key factors to sustain digital transformation in TVET Institutions and offers practical recommendations for policymakers and educational leaders. The insights gained can guide future initiatives aimed at the digital transformation of TVET institutions, contributing to a more competitive and responsive educational sector in Malaysia. [ABSTRACT FROM AUTHOR]