Suicide and self-harm by burns in Pakistan: a scoping review protocol.

INTRODUCTION: Suicide is a global public health problem. Self-inflicted burns are one of the most severe methods of suicide, with high morbidity and mortality. Low-income and middle-income countries contribute 40% of all suicidal burns. Pakistan lacks comprehensive burns surveillance data, which prevents an understanding of the magnitude of the problem. This scoping review aims to understand the scope of the problem of suicide and self-harm burns in Pakistan and to identify knowledge gaps within the existing literature related to this specific phenomenon. METHODS AND ANALYSIS: This scoping review will follow the methodological framework proposed by Arksey and O'Malley. We will search electronic databases (PubMed, Cochrane, Google Scholar and Pakmedinet), grey literature and a reference list of relevant articles to identify studies for inclusion. We will look for studies on self-inflicted burns as a method of suicide and self-harm in Pakistan, published from the beginning until December 2023, in the English language. Two independent reviewers will screen all abstracts and full-text studies for inclusion. The data will be collected on a data extraction form developed through an iterative process by the research team and it will be analysed using descriptive statistics. ETHICS AND DISSEMINATION: Ethical exemption for this study has been obtained from the Institutional Review Board Committee of Aga Khan University Karachi, Pakistan. The findings of the study will be disseminated by conducting workshops for stakeholders, including psychiatrists, psychologists, counsellors, general and public health physicians and policymakers. The findings will be published in national and international peer-reviewed journals.

Gut microbiome as a treatment in colorectal cancer.

BACKGROUND: The gut microbiome plays a role in the development and progression of colorectal cancer (CRC). AIM AND OBJECTIVE: This review focuses on whether the gut microbiome is involved in the development and regulation of the host immune system. METHODS: The gut microbiome can influence the production and activity of immune cells and molecules that help to maintain the integrity of the intestinal barrier and prevent inflammation. Gut microbiota modulates the anti-cancer immune response. The gut microbiota can influence the function of immune cells, like T cells, that recognize and eliminate cancer cells. Gut microbiota can affect various aspects of cancer progression and the efficacy of various anti-cancer treatments. RESULTS: Gut microbiota provide promise as a potential biomarker to identify the effect of immunotherapy and as a target for modulation to improve the efficacy of immunotherapy in CRC treatment. CONCLUSION: The potential synergistic effect between the gut microbiome and anti-cancer treatment modalities provides an interest in developing strategies to modulate the gut microbiome to improve the efficacy of anti-cancer treatment.

This review focuses on the gut microbiome in the development and regulation of the host immune system. Gut microbiota provides potential biomarkers to identify the effect of immunotherapy and as a target for modulation of immunotherapy in the treatment of CRC. This provides potential synergistic effects between the gut microbiome and anti-cancer treatment modalities.

Perceptions of Suicide among Pakistanis: Results of an Online Survey.

OBJECTIVE: In Pakistan, a predominantly Muslim country, information on the patterning of suicidal thoughts and behaviors, as well as associated public perceptions and opinions, is limited. We sought to advance knowledge on suicide and self-harm in Pakistan with a large, online survey. METHOD: Leveraging results from a twelve-item online survey (N = 5,157) circulated by the largest English language newspaper in Pakistan, we assessed personal experiences, opinions, and attitudes toward help-seeking in the context of suicide. We calculated proportions with 95% confidence intervals for endorsed responses and implemented binomial generalized linear models with odds ratios to assess differing response tendencies by age, gender, and urban/rural residence. RESULTS: Personal experiences related to suicide and self-harm as well as encounters in social circles were common. Mental illness tended to be recognized as a high likelihood contributor to suicide death over and above nonviolent interpersonal problems. Most considered suicide a way to escape pain, and few considered suicide to be immoral. Barriers to help-seeking included social deterrents, inaccessibility, and unaffordability. Women and youth emerged as higher risk groups, though the status of rural Pakistanis remained unclear. CONCLUSION: The survey provides a preliminary basis for considering the unique experiences and perspectives of the public in shaping suicide prevention and intervention efforts in Pakistan.

A voluntary online survey about suicide with over 5,000 responses from a cross-section of Pakistani populationResults illuminate popular opinions on suicide risk and mental health treatmentWomen and youth appear to be especially vulnerable warranting targeted intervention.

Terminology and methods used to differentiate injury intent of hospital burn patients in South Asia: Results from a systematic scoping review.

INTRODUCTION: A key component in the classification of all injury types is to differentiate whether the injury was deliberately inflicted and by whom, commonly known as "intent" in the surveillance literature. These data guide patient care and inform surveillance strategies. South Asia is believed to have the greatest number of intentional burn injuries, but national surveillance data is not disaggregated by injury intent. Scientific literature can be used for injury surveillance where national data collection does not exist. In order to synthesise research findings, it is essential to assess the potential impact of misclassification bias. We therefore conducted a systematic scoping review to understand terminology and methods used to differentiate injury intent of hospital burn patients in South Asia. METHODS: We followed the methods in our registered protocol (https://doi.org/10.17605/OSF.IO/DCYNQ). Studies met defined population, concept, context, and study design criteria. The databases Embase, MEDLINE, CINAHL, PsycInfo, and PakMediNet were searched. Two reviewers independently screened results. Data were extracted in a standardised manner and verified. The rigour of the method used to differentiate injury intent was appraised. RESULTS: 1435 articles were screened. Of these, 89 met our inclusion criteria. Most articles were from India and Pakistan, and used an observational study design. There were 14 stem terms used in the articles. The most common was "cause". There were 40 classifier terms. The most common were "accident", "suicide", and "homicide". Few articles defined these terms. The method used to differentiate injury intent was only described explicitly in 17% of articles and the rigour of the methods used were low. Where methods of differentiation were described, they appear to be based on patient or family report rather than multidisciplinary assessment. CONCLUSION: The heterogeneity in terms, lack of definitions, and limited investigation of injury intent means this variable is likely to be prone to misclassification bias. We strongly recommend that the global burn community unites to develop a common data element, including definitions and methods of assessment, for the concept of burn injury intent to enable more reliable data collection practices and interstudy comparisons.

Explainable AI for Material Property Prediction Based on Energy Cloud: A Shapley-Driven Approach.

The scientific community has raised increasing apprehensions over the transparency and interpretability of machine learning models employed in various domains, particularly in the field of materials science. The intrinsic intricacy of these models frequently results in their characterization as "black boxes", which poses a difficulty in emphasizing the significance of producing lucid and readily understandable model outputs. In addition, the assessment of model performance requires careful deliberation of several essential factors. The objective of this study is to utilize a deep learning framework called TabNet to predict lead zirconate titanate (PZT) ceramics' dielectric constant property by employing their components and processes. By recognizing the crucial importance of predicting PZT properties, this research seeks to enhance the comprehension of the results generated by the model and gain insights into the association between the model and predictor variables using various input parameters. To achieve this, we undertake a thorough analysis with Shapley additive explanations (SHAP). In order to enhance the reliability of the prediction model, a variety of cross-validation procedures are utilized. The study demonstrates that the TabNet model significantly outperforms traditional machine learning models in predicting ceramic characteristics of PZT components, achieving a mean squared error (MSE) of 0.047 and a mean absolute error (MAE) of 0.042. Key contributing factors, such as d33, tangent loss, and chemical formula, are identified using SHAP plots, highlighting their importance in predictive analysis. Interestingly, process time is less effective in predicting the dielectric constant. This research holds considerable potential for advancing materials discovery and predictive systems in PZT ceramics, offering deep insights into the roles of various parameters.

Implementation and expansion of laboratory capacity for molecular diagnostics in response to COVID-19 and preparedness for other emerging infectious diseases in the Islamic Emirate of Afghanistan.

Background: Afghanistan experienced various outbreaks before and during the Covid-19 pandemic, including dengue, Crimean Congo hemorrhagic fever (CCHF), measles, and acute watery diarrhea (AWD). Diagnostic and surveillance support was limited, with only the Central Public Health Laboratory equipped to handle outbreak responses. This article highlights initiatives taken to improve diagnostic capabilities for COVID-19 and other outbreaks of public health concern encountered during the pandemic. Background: The World Health Organization (WHO) Afghanistan Country Office collaborated with the WHO Eastern Mediterranean Regional Office (EMRO), Central Public Health Laboratory (CPHL), and National Influenza Center (NIC) to enhance COVID-19 diagnostic capacity at national and subnational facilities. To alleviate pressure on CPHL, a state-of-the-art laboratory was established at the National Infectious Disease Hospital (NIDH) in Kabul in 2021-2022, while WHO EMRO facilitated the regionalization of testing to subnational facilities for dengue, CCHF, and AWD in 2022-2023. Results: COVID-19 testing capacity expanded nationwide to 34 Biosafety Level II labs, improving diagnosis time. Daily testing rose from 1000 in 2020 to 9200 in 2023, with 848,799 cumulative tests. NIDH identified 229 CCHF cases and 45 cases nationally. Dengue and CCHF testing, decentralized to Nangarhar and Kandahar labs, identified 338 dengue and 18 CCHF cases. AWD testing shifted to NIDH and five subnational facilities (Kandahar, Paktia, Balkh, Herat, and Nangarhar labs), while measles testing also decentralized to nine subnational facilities. Conclusion: Afghanistan implemented a remarkable, multisectoral response to priority pathogens. The nation now possesses diagnostic expertise at national and subnational levels, supported by genomic surveillance. Future efforts should concentrate on expanding and sustaining this capacity to enhance public health responses.

Situation Analysis of Suicide and Self-Harm in the WHO Eastern Mediterranean Region.

OBJECTIVE: An estimated 41,000 lives are lost to suicide each year in World Health Organization Eastern Mediterranean Region Office (WHO EMRO) countries. The objective of this study was to conduct a situation analysis for suicide and self-harm in the WHO EMRO region. METHODS: Data on suicide were obtained from the WHO Global Health Estimates for the years 2000-2019. Information on risk groups efforts to prevent self-harm and suicide in the EMRO region were retrieved through scientific studies, grey literature, and public websites. RESULTS: During 2000-2019, the age-standardized suicide rate was 6.7 per 100,000 inhabitants, albeit there are concerns regarding data quality. Self-harm and suicide remain criminal acts in more than half of the countries. Few countries have a national plan for prevention of suicide. Toxic agents, such as pesticides and black henna, are easily available and frequently used for suicide in some areas, as are firearms and self-immolation. Successful prevention measures include means restriction and psychosocial interventions after self-harm. CONCLUSION: Many WHO EMRO countries remain underserved in terms of mental health care. Decriminalization of suicide and means restriction might be further promoted. Online-based tools for mental health literacy and psychosocial therapy are other options to explore.

Suicidal behavior remains a criminal act in more than half of the WHO EMRO countries.Easily available toxic agents, such as pesticides and black henna, and firearms are common methods used for suicidal behavior in the WHO EMRO countries.Access to mental health care is limited in many of the WHO EMRO countries.Online-based psychoeducation and psychosocial intervention programs might be further explored as preventive efforts.

Impact of the COVID-19 Pandemic on the Management of Gallbladder, Biliary Tract, and Pancreatic Diseases.

Introduction Biliary diseases are a major acute general surgical burden. Laparoscopic cholecystectomy is the gold standard surgical procedure, although it was discontinued during an outbreak. Effective management permits decisive therapy, symptom alleviation, and fewer hospitalizations and complications. Throughout the initial COVID-19 situation, surgical procedures for patients were delayed. Invasive services were required to employ conservative or non-operative therapy, which could lead to increased recurring presentations and biliary-pancreatic problems. Aim Examining the impact of COVID-19 on the outcomes and hospitalizations of patients suffering from gallstone, biliary tract, and pancreatic diseases.  Methods The retrospective analysis included patients with the following ICD-10 codes who presented to our unit: cholelithiasis (K80), cholecystitis (K81), and acute pancreatitis (K85). We compared the interval of the first COVID-19 pandemic wave, from March to August 2020, with the period before the pandemic, referred to as Pre-COVID-19. After applying exclusion criteria, a total of 868 patients were enrolled in the trial, having initially recruited around 1,400 individuals using these codes. Patients with inaccurate coding, cancer, or non-stone disease were excluded (e.g., alcoholic pancreatitis). The demographic information, admission details, investigations, surgical therapy, operating specifics, and postoperative complications of the patients were noted. Changes in surgical management, patient representation, and postoperative complications were the key outcomes. Results A statistically significant (p<0.05) rise was seen in repeat presentations in the COVID group, most likely due to the failure of definitive treatment. The other outcome is the distribution of presentations was comparable, patients with acute cholecystitis and gallstone pancreatitis showed statistically significant (p<0.05) lower rates of definitive therapy. Conclusion During the COVID period, all surgeries except those for cancer were halted. Unknown causes led to several consequences related to the gallbladder, biliary tract, and pancreas. Patients with cholecystitis, gallstone pancreatitis, and pancreatic inflammation experienced a lower probability of treatment. The increase in hospitalizations and self-presentations indicated that definitive therapy, designed to restrict COVID-19 exposure, actually increased patient risk. Despite this risk, we had no COVID-19 instances in our cohort. The evaluation of the long-term consequences of the pandemic on acute pancreatitis and its care will require a large-scale, multicenter investigation.

Terminology and methods used to differentiate injury intent of hospital burn patients in South Asia: a systematic scoping review protocol.

BACKGROUND: The greatest proportion of burn injuries globally occur in South Asia, where there are also high numbers of intentional burns. Burn injury prevention efforts are hampered by poor surveillance data on injury intent. There is a plethora of local routinely collected data in the research literature from South Asia that could be used for epidemiological purposes, but it is not known whether the definitions and methods of differentiation of injury intent are sufficiently homogenous to allow valid study comparisons. METHODS: We will conduct a systematic scoping review to understand terminology and methods used to differentiate injury intent of hospital burn patients in South Asia. The objectives of the study are to: determine the breadth of terminology and common terms used for burn injury intent; to determine if definitions are comparable across studies where the same term is used; and to appraise the rigour of methods used to differentiate burn injury intent and suitability for comparison across studies. The databases Embase, MEDLINE, CINAHL, PsycINFO, and PakMediNet will be searched. Screening and data extraction will be completed independently by two reviewers. To be included, the article must be as follows: peer reviewed, primary research, study cutaneous burns, based on hospital patients from a country in South Asia, and use intent terminology or discuss a method of differentiation of injury intent. Results will be restricted to English language studies. No date restrictions will be applied. A plain language summary and terminology section are included for non-specialist readers. DISCUSSION: Results will be used to inform stakeholder work to develop standardised terminology and methods for burn injury intent in South Asia. They will be published open access in peer-reviewed journals wherever possible. SYSTEMATIC REVIEW REGISTRATION: This review has been registered with the Open Science Framework ( https://doi.org/10.17605/OSF.IO/DCYNQ ).

Short-Term Forecasting of Monkeypox Cases Using a Novel Filtering and Combining Technique.

In the modern world, new technologies such as artificial intelligence, machine learning, and big data are essential to support healthcare surveillance systems, especially for monitoring confirmed cases of monkeypox. The statistics of infected and uninfected people worldwide contribute to the growing number of publicly available datasets that can be used to predict early-stage confirmed cases of monkeypox through machine-learning models. Thus, this paper proposes a novel filtering and combination technique for accurate short-term forecasts of infected monkeypox cases. To this end, we first filter the original time series of the cumulative confirmed cases into two new subseries: the long-term trend series and residual series, using the two proposed and one benchmark filter. Then, we predict the filtered subseries using five standard machine learning models and all their possible combination models. Hence, we combine individual forecasting models directly to obtain a final forecast for newly infected cases one day ahead. Four mean errors and a statistical test are performed to verify the proposed methodology's performance. The experimental results show the efficiency and accuracy of the proposed forecasting methodology. To prove the superiority of the proposed approach, four different time series and five different machine learning models were included as benchmarks. The results of this comparison confirmed the dominance of the proposed method. Finally, based on the best combination model, we achieved a forecast of fourteen days (two weeks). This can help to understand the spread and lead to an understanding of the risk, which can be utilized to prevent further spread and enable timely and effective treatment.

Gone Too Soon: priorities for action to prevent premature mortality associated with mental illness and mental distress.

Globally, too many people die prematurely from suicide and the physical comorbidities associated with mental illness and mental distress. The purpose of this Review is to mobilise the translation of evidence into prioritised actions that reduce this inequity. The mental health research charity, MQ Mental Health Research, convened an international panel that used roadmapping methods and review evidence to identify key factors, mechanisms, and solutions for premature mortality across the social-ecological system. We identified 12 key overarching risk factors and mechanisms, with more commonalities than differences across the suicide and physical comorbidities domains. We also identified 18 actionable solutions across three organising principles: the integration of mental and physical health care; the prioritisation of prevention while strengthening treatment; and the optimisation of intervention synergies across social-ecological levels and the intervention cycle. These solutions included accessible, integrated high-quality primary care; early life, workplace, and community-based interventions co-designed by the people they should serve; decriminalisation of suicide and restriction of access to lethal means; stigma reduction; reduction of income, gender, and racial inequality; and increased investment. The time to act is now, to rebuild health-care systems, leverage changes in funding landscapes, and address the effects of stigma, discrimination, marginalisation, gender violence, and victimisation.

Novel Synthesis of CuO/GO Nanocomposites and Their Photocatalytic Potential in the Degradation of Hazardous Industrial Effluents.

Photocatalytic degradation of dyes has been the subject of extensive study due to its low cost, eco-friendly operation, and absence of secondary pollutants. Copper oxide/graphene oxide (CuO/GO) nanocomposites are emerging as a new class of fascinating materials due to their low cost, nontoxicity, and distinctive properties such as a narrow band gap and good sunlight absorbency. In this study, copper oxide (CuO), graphene oxide (GO), and CuO/GO were synthesized successfully. X-ray diffractometer (XRD) and Fourier transform infrared (FTIR) spectroscopy confirm the oxidation and production of GO from the graphene of lead pencil. According to the morphological analysis of nanocomposites, CuO nanoparticles of sizes ≤20 nm on the GO sheets were evenly adorned and distributed. Nanocomposites of different CuO:GO ratios (1:1 up to 5:1) were applied for the photocatalytic degradation of methyl red (MR). CuO:GO(1:1) nanocomposites achieved 84% MR dye removal, while CuO:GO(5:1) nanocomposites achieved the highest value (95.48%). The thermodynamic parameters of the reaction for CuO:GO(5:1) were evaluated using the Van't Hoff equation and the activation energy was found to be 44.186 kJ/mol. The reusability test of the nanocomposites showed high stability even after seven cycles. CuO/GO catalysts can be used in the photodegradation of organic pollutants in wastewater at room temperature due to their excellent properties, simple synthesis process, and low cost.

Suicides by pesticide ingestion in Pakistan and the impact of pesticide regulation.

INTRODUCTION: Suicide is a major public health problem in Pakistan, accounting to approximately 19,331 deaths every year. Many are due to consumption of acutely toxic pesticides; however, there is a lack of national suicide data, limiting knowledge and potential for intervention. In this paper, we aimed to review the literature on pesticide self-poisoning in Pakistan to identify the most problematic pesticides in relation to national pesticide regulations. METHODS: Information on the currently registered and banned pesticides was obtained from Ministry of National Food Security and Research while data on pesticide import and use was extracted from FAOSTAT. We searched the following sources for articles and research papers on poisoning in Pakistan: Cumulative Index to Nursing and Allied Health (CINAHL), Google Scholar, Applied Social Sciences Index and Abstracts (ASSIA), Excerpta Medica (EMBASE), National Library of Medicine's MEDLINE (PUBMED), PS102YCHINFO and Pakmedinet.com using the search terms 'self-poisoning', 'deliberate self-harm', 'suicide', 'methods and means of suicide', 'organophosphate', 'wheat pill', 'aluminium phosphide', 'acute poisoning', OR 'pesticides', AND 'Pakistan'. RESULTS: As of May 2021, 382 pesticide active ingredients (substances) were registered in Pakistan, of which five were WHO hazard class Ia (extremely hazardous) and 17 WHO hazard class Ib (highly hazardous). Twenty-six pesticides, four formulations, and seven non-registered pesticides had been banned, of which two were WHO class Ia and five Ib. We identified 106 hospital-level studies of poisoning conducted in Pakistan, of which 23 did not mention self-poisoning cases and one reported no suicidal poisoning cases. We found no community or forensic medicine studies. Of 52,323 poisoning cases identified in these papers, 24,546 [47%] were due to pesticides. The most commonly identified pesticide classes were organophosphorus (OP) insecticides (13,816 cases, 56%) and the fumigant aluminium phosphide (3 g 56% tablets, often termed 'wheat pills'; 686 cases, 2.7%). Few studies identified the particular pesticides involved or the resulting case fatality. CONCLUSION: We found pesticide poisoning to be a major cause of poisoning in Pakistan, with OP insecticides and the fumigant aluminium phosphide the main pesticides identified. Withdrawal of Class I pesticides (as proposed to occur nationally in 2022) and high concentration aluminium phosphide tablets should rapidly reduce suicidal deaths by reducing the case fatality for low-intention poisoning cases. National cause of death data and forensic toxicology laboratory data identifying the pesticides responsible for deaths will be important to assess impacts of the proposed national ban.

Reproductive Toxicity Evaluation of Graphene-Based Tumor Cell Nucleus-Targeting Fluorescent Nanoprobes on Reproduction and Offspring Health.

A new graphene-based fluorescent nanoprobe for tumor cell nucleus (GTTNs) was synthesized in our laboratory that penetrates the cell membrane and particularly targets cancer cell nucleus and displays tremendous potential for clinical applications. Although acute and subacute toxicity studies have been conducted on GTTNs, a primary result could be drawn that GTTNs appear to have almost no acute and subacute toxicity. However, as an important part of safety evaluation, the influences on reproductive and offspring developmental toxicity are still absent. In this study, male mice were injected intravenously with GTTNs, and the survival status, histopathology of the testes and epididymides, proliferation and apoptosis of testicular tissue, and sperm motility of mice were measured. To evaluate the short- and long-term fertility in male mice, different male mice resided with untreated female mice on days 1 and 30 after the end of the last treatment, and the offspring health parameters were assessed by measuring pup numbers, body weight, and organ indexes of the pups. The results indicated that GTTNs-exposed male mice retained good fertility, healthy structure of testes and epididymides, and production of healthy sperm. Meanwhile, there were no significant differences between the offspring and the control group. In consideration of GTTNs with broad prospects for biomedical applications, our results contribute a basis for further understanding of its biosafety.

Alu antisense RNA ameliorates methylglyoxal-induced human lens epithelial cell apoptosis by enhancing antioxidant defense.

AIM: To determine whether an antisense RNA corresponding to the human Alu transposable element (Aluas RNA) can protect human lens epithelial cells (HLECs) from methylglyoxal-induced apoptosis. METHODS: Cell counting kit-8 (CCK-8) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were used to assess HLEC viability. HLEC viability/death was detected using a Calcein-AM/PI double staining kit; the annexin V-FITC method was used to detect HLEC apoptosis. The cytosolic reactive oxygen species (ROS) levels in HLECs were determined using a reactive species assay kit. The levels of malondialdehyde (MDA) and the antioxidant activities of total-superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) were assessed in HLECs using their respective kits. RT-qPCR and Western blotting were used to measure mRNA and protein expression levels of the genes. RESULTS: Aluas RNA rescued methylglyoxal-induced apoptosis in HLECs and ameliorated both the methylglyoxal-induced decrease in Bcl-2 mRNA and the methylglyoxal-induced increase in Bax mRNA. In addition, Aluas RNA inhibited the methylglyoxal-induced increase in Alu sense RNA expression. Aluas RNA inhibited the production of ROS induced by methylglyoxal, restored T-SOD and GSH-Px activity, and moderated the increase in MDA content after treatment with methylglyoxal. Aluas RNA significantly restored the methylglyoxal-induced down-regulation of Nrf2 gene and antioxidant defense genes, including glutathione peroxidase, heme oxygenase 1, γ-glutamylcysteine synthetase and quinone oxidoreductase 1. Aluas RNA ameliorated methylglyoxal-induced increases of the mRNA and protein expression of Keap1 that is the negative regulator of Nrf2. CONCLUSION: Aluas RNA reduces apoptosis induced by methylglyoxal by enhancing antioxidant defense.

Citrulline and kynurenine to tryptophan ratio: potential EED (environmental enteric dysfunction) biomarkers in acute watery diarrhea among children in Bangladesh.

Two emerging biomarkers of environmental enteric dysfunction (EED) include plasma citrulline (CIT), and the kynurenine (KYN): tryptophan (TRP)/ (KT) ratio. We sought to investigate the plasma concentration of CIT and KT ratio among the children having dehydrating diarrhea and examine associations between concentrations of CIT and KT ratio with concurrent factors. For this analysis, we used cross-sectional data from a total of 102, 6-36 months old male children who suffered from non-cholera acute watery diarrhea and had some dehydration admitted to an urban diarrheal hospital, in Bangladesh. CIT, TRP, and KYN concentrations were determined at enrollment from plasma samples using ELIZA. At enrollment, the mean plasma CIT concentration was 864.48 ± 388.55 µmol/L. The mean plasma kynurenine, tryptophan concentrations, and the KT ratio (× 1000) were 6.93 ± 3.08 µmol/L, 33.44 ± 16.39 µmol/L, and 12.12 ± 18.10, respectively. With increasing child age, KYN concentration decreased (coefficient: - 0.26; 95%CI: - 0.49, - 0.04; p = 0.021); with increasing lymphocyte count, CIT concentration decreased (coef.: - 0.01; 95% CI: - 0.02,0.001, p = 0.004); the wasted child had decreased KT ratio (coef.: - 0.6; 95% CI: - 1.18, - 0.02; p = 0.042) after adjusting for potential covariates. The CIT concentration was associated with blood neutrophils (coef.: 0.02; 95% CI: 0.01, 0.03; p < 0.001), lymphocytes (coef.: - 0.02; 95% CI: - 0.03, - 0.02; p < 0.001) and monocyte (coef.: 0.06; 95% CI: 0.01, 0.11; p = 0.021); KYN concentration was negatively associated with basophil (coef.: - 0.62; 95% CI: - 1.23, - 0.01; p = 0.048) after adjusting for age. In addition, total stool output (gm) increased (coef.: 793.84; 95% CI: 187.16, 1400.52; p = 0.011) and also increased duration of hospital stay (hour) (coef.: 22.89; 95% CI: 10.24, 35.54; p = 0.001) with increasing CIT concentration. The morphological changes associated with EED may increase the risk of enteric infection and diarrheal disease among children. Further research is critically needed to better understand the complex mechanisms by which EED biomarkers may impact susceptibility to dehydrating diarrhea in children.

Crude extract from Euphorbia prostrata extended curative period of glibenclemide in alloxan-induced diabetic rats.

OBJECTIVES: Euphorbia prostrata is traditionally used alongside antidiabetic agents to manage diabetes. Bioactive ingredients of medicinal herbs may alter the overall pharmacokinetics of antidiabetic agents. METHODS: We assessed hypoglycemic activities of ethanolic plant extract (EPE) singly and its effects on antidiabetic properties of gliclazide, glibenclemide and metformin in allaxonized rats. Varying concentrations of EPE (250 and 500 mg/kg) with or without metformin (10 mg/kg), glibenclemide (2 mg/kg) and gliclazide (5 mg/kg) were orally administered to evaluate herb-drug interaction. RESULTS: The levels of blood glucose declined significantly after treatment with metformin, glibenclemide and gliclazide singly (p<0.01) or concomitantly with EPE (p<0.001). Concentration dependent mild to moderate reduction (5.2 and 10.0%) was registered in blood glucose for 250 and 500 mg/kg of EPE respectively. The overall reduction in blood glucose due to combined treatment with EPE and standard agents was additive. On the other hand, synergistic herb-drug interaction was registered for insulin levels in rats that received glibenclamide and gliclazide alongside EPE. Extract with metformin had antagonistic insulin outcome. Regarding the duration of hypoglycemic activities, periodical changes were similar in case of glibenclamide and gliclazide separately or in combination with EPE. However, in case of metformin with extract, the blood glucose continued to decline for 14 h and retained at 15.0% below the baseline values even after 24 h of treatment. CONCLUSIONS: In conclusion, the extract itself had weak hypoglycemic effects but prolonged the therapeutic duration of metformin to more than 24 h when administered combinedly.

Sociodemographic Characteristics and Patterns of Suicide in Pakistan: An Analysis of Current Trends.

Suicide is a global phenomenon with about 79% of suicides occurring in low and middle-income countries. This study investigated current trends, demographics, and characteristics of completed suicides based on reports from leading Pakistani Newspapers. This study performed a qualitative analysis of completed suicides in Pakistan's four newspapers from January 1st, 2019, through December 31st, 2020. Data about socio-demographic characteristics, methods of suicide, possible motives, and associated features were analyzed. 2295 suicides were reported in Pakistan during 2019 and 2020. About 61.87% were completed by men, and 38.12% by women. The most suicides occurred in individuals ages < 30 years. The predominant method of suicide in this group was ingestion of poisonous substances. The most commonly reported reasons for suicide were domestic conflicts, financial problems, and failure in love/marriage. By providing insight into characteristics of suicide, this study highlights the need for effective suicide prevention policies and programs to tackle rising rates of suicide in Pakistan.

Pharmacological inhibition of cathepsin C (CatC) as a potential approach for cancer therapeutics.

Studies have established that proteolytic enzyme inhibition holds significant promise in cancer prevention and treatment. Cathepsin C (CatC) is conserved lysosomal cysteine dipeptidyl aminopeptidase, which is the key for pro-inflammatory neutrophil serine protease activation and biological functioning. This makes CatC as a promising therapeutic drug target for the management of different cancer types. Considering this, using a wide range of computer aided drug-designing applications, several inhibitors are shortlisted against CatC active pocket, which interact with the enzyme with high affinity and form strong intermolecular interaction network. Compared to control, three molecules ASN_06916232, ASN_06917112 and ASN_06916892 are filtered as best binders of the CatC active pocket with binding energy value of -10.9 kcal/mol, -10.9 kcal/mol and -10.7 kcal/mol, respectively. These compounds interact with several important active side residues of CatC such as Ser233, Cys234, Gly277, Asn380 and His38. Furthermore, the complexes of these compounds with CatC reveal very stable dynamics with average RMSD value less than 3 Å. The binding energy analysis further indicates the compounds to have very stable van der Waals and electrostatic energies. In conclusion, these molecules are promising and require experimental validation to prove them as anti-CatC molecules.Communicated by Ramaswamy H. Sarma.