Novel detoxifier of spironolactone against triptolide-induced hepatotoxicity through inhibition of RPB1 degradation.

ETHNOPHARMACOLOGICAL RELEVANCE: Triptolide is a major bioactive and toxic ingredient isolated from the traditional Chinese herb Tripterygium wilfordii (T. wilfordii) Hook F. It exhibits potent antitumor, immunosuppressive, and anti-inflammatory biological activities; however, its clinical application is hindered by severe systemic toxicity. Two preparations of T. wilfordii, including T. wilfordii glycoside tablets and T. wilfordii tablets, containing triptolide, are commonly used in clinical practice. However, their adverse side effects, particularly hepatotoxicity, limit their safe use. Therefore, it is crucial to discover potent and specific detoxification medicines for triptolide. AIM OF THE STUDY: This study aimed to investigate the detoxification effects and potential mechanism of action of spironolactone on triptolide-induced hepatotoxicity to provide a potential detoxifying strategy for triptolide, thereby promoting the safe applications of T. wilfordii preparations in clinical settings. MATERIALS AND METHODS: Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and crystal violet staining. Nuclear fragmentation was visualized using 4',6-diamidino-2-phenylindole (DAPI) staining, and protein expression was analyzed by Western blotting. The inhibitory effect of spironolactone on triptolide-induced hepatotoxicity was evaluated by examining the effects of spironolactone on serum alanine aminotransferase and aspartate aminotransferase levels, as well as liver pathology in a mouse model of triptolide-induced acute hepatotoxicity. Furthermore, a survival assay was performed to investigate the effects of spironolactone on the survival rate of mice exposed to a lethal dose of triptolide. The effect of spironolactone on triptolide-induced global transcriptional repression was assessed through 5-ethynyl uridine staining. RESULTS: Triptolide treatment decreased the cell viability, increased the nuclear fragmentation and the cleaved caspase-3 levels in both hepatoma cells and hepatocytes. It also increased the alanine aminotransferase and aspartate aminotransferase levels, induced the hepatocyte swelling and necrosis, and led to seven deaths out of 11 mice. The above effects could be mitigated by pretreatment with spironolactone. Additionally, molecular mechanism exploration unveiled that spironolactone inhibited triptolide-induced DNA-directed RNA polymerase II subunit RPB1 degradation, consequently increased the fluorescence intensity of 5-ethynyl uridine staining for nascent RNA. CONCLUSIONS: This study shows that spironolactone exhibits a potent detoxification role against triptolide hepatotoxicity, through inhibition of RPB1 degradation induced by triptolide and, in turn, retardation of global transcriptional inhibition in affected cells. These findings suggest a potential detoxification strategy for triptolide that may contribute to the safe use of T. wilfordii preparations.

Global Metabolomics Using LC-MS for Clinical Applications.

Metabolomics can be used for a multitude of purposes, including monitoring of treatment effects and for increasing the knowledge of the pathophysiology of a wide range of diseases. Global (commonly referred to as "untargeted") metabolomics is hypothesis-generating and provides the opportunity to discover new biomarkers. Being versatile and having a high degree of selectivity and sensitivity, liquid chromatography-mass spectrometry (LC-MS) is the most common technique applied for metabolomics. We here present our global metabolomics LC-electrospray ionization-MS/MS method. The sample preparation procedures for plasma, serum, dried blood spots, urine, and cerebrospinal fluid are simple and nonspecific to reduce the risk of analyte loss. The method is based on reversed-phase chromatography using a diphenyl column. The high-resolution Q Exactive Orbitrap MS with data-dependent acquisition provides MS/MS spectra of a wide range of analytes. Our method covers a large part of the metabolome regarding hydrophobicity and compound class.

Crise global da atenção primária à saúde / Global crisis in primary health care / Crisis global de la atención primaria

Enquanto no Norte Global se discute uma crise na Atenção Primária à Saúde, a maioria dos países nunca chegou a constituir sistemas de saúde baseados propriamente numa atenção primária robusta. Nesse cenário, o Brasil apresenta uma tendência mais favorável, com conquistas importantes para a atenção primária e a medicina de família e comunidade nos últimos dez anos. Restam desafios a serem superados para que o Sistema Único de Saúde alcance níveis satisfatórios de acesso a seus serviços, com profissionais adequadamente formados e valorizados pela população.

While the Global North is discussing a crisis in primary health care, the majority of countries have never managed to establish health systems based on robust primary care. Brazil presents a more favorable trend, with important achievements for primary care and family practice over the last ten years. There are still challenges to be overcome so that the Unified Health System achieves satisfactory levels of access to its services, with professionals who are properly trained and valued by the public.

Mientras que en el Norte Global se habla de una crisis de la atención primaria, la mayoría de los países nunca han creado realmente sistemas sanitarios basados en una atención primaria robusta. Brasil, muestra una tendencia más favorable, con importantes logros para la atención primaria y la medicina familiar y comunitaria en los últimos diez años. Aún quedan retos por superar para que el Sistema Único de Salud alcance niveles satisfactorios de acceso a sus servicios, con profesionales debidamente formados y valorados por la población.

Burden of disease attributable to high body mass index: an analysis of data from the Global Burden of Disease Study 2021.

Background: Obesity represents a major global health challenge with important clinical implications. Despite its recognized importance, the global disease burden attributable to high body mass index (BMI) remains less well understood. Methods: We systematically analyzed global deaths and disability-adjusted life years (DALYs) attributable to high BMI using the methodology and analytical approaches of the Global Burden of Disease Study (GBD) 2021. High BMI was defined as a BMI over 25 kg/m2 for individuals aged ≥20 years. The Socio-Demographic Index (SDI) was used as a composite measure to assess the level of socio-economic development across different regions. Subgroup analyses considered age, sex, year, geographical location, and SDI. Findings: From 1990 to 2021, the global deaths and DALYs attributable to high BMI increased more than 2.5-fold for females and males. However, the age-standardized death rates remained stable for females and increased by 15.0% for males. Similarly, the age-standardized DALY rates increased by 21.7% for females and 31.2% for males. In 2021, the six leading causes of high BMI-attributable DALYs were diabetes mellitus, ischemic heart disease, hypertensive heart disease, chronic kidney disease, low back pain and stroke. From 1990 to 2021, low-middle SDI countries exhibited the highest annual percentage changes in age-standardized DALY rates, whereas high SDI countries showed the lowest. Interpretation: The worldwide health burden attributable to high BMI has grown significantly between 1990 and 2021. The increasing global rates of high BMI and the associated disease burden highlight the urgent need for regular surveillance and monitoring of BMI. Funding: National Natural Science Foundation of China and National Key R&D Program of China.

Plasma adenosine deaminase-1 and -2 activities are lower at birth in Papua New Guinea than in The Gambia but converge over the first weeks of life.

Introduction: Dynamic cellular and molecular adaptations in early life significantly impact health and disease. Upon birth, newborns are immediately challenged by their environment, placing urgent demands on the infant immune system. Adenosine deaminases (ADAs) are enzymatic immune modulators present in two isoforms - ADA-1 and ADA-2. Infants exhibit low ADA activity, resulting in high plasma adenosine concentrations and a consequent anti-inflammatory/anti-Th1 bias. While longitudinal studies of plasma ADA have been conducted in infants in The Gambia (GAM), little is known regarding ADA trajectories in other parts of the world. Methods: Herein, we characterized plasma ADA activity in an infant cohort in Papua New Guinea (PNG; n=83) and compared to ontogeny of ADA activity in a larger cohort in GAM (n=646). Heparinized peripheral blood samples were collected at day of life (DOL) 0, DOL7, DOL30, and DOL128. Plasma ADA-1, ADA-2, and total ADA activities were measured by chromogenic assay. Results: Compared to GAM infants, PNG infants had significantly lower ADA-1 (0.9-fold), ADA-2 (0.42-fold), and total ADA (0.84-fold) activities at birth which converged by DOL30. Discussion: Overall, discovery of a distinct baseline and a consistent pattern of increasing plasma ADA activity in early life in two genetically and geographically distinct populations validates and extends previous findings on the robustness of early life immune ontogeny.

Non-communicable diseases prevention and control by government ministries in Guyana.

Background: Countries of the Caribbean Community signed the Declaration of Port of Spain in 2007 with the vision to stop the epidemic of non-communicable diseases (NCDs). The adoption of the Declaration by member states represented a regional effort, challenging governments, the private sector, and civil society to act together. Multisectoral actions in Guyana aimed at achieving this goal are the focus of this article, demonstrating the work of different actors in addressing the burden of NCDs in the country. Objective: To analyze multisectoral actions developed among five ministries for the implementation of the Declaration of Port of Spain 2007 in Guyana. Methods: This qualitative study was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist and conducted in five ministries (Agriculture, Education, Finance, Health, and Trade) in Georgetown, Guyana. The thematic analysis was guided by a framework consisting of four elements: context (why the policy is needed), content (what the policy is mainly about), process (how the policy was brought forward and implemented), and actors (who participates in and influences the formulation and implementation of the policy). The framework considers how these elements interconnect to shape policy development and implementation processes. Findings: Data analysis provided the researchers with insights into possible topic areas and codes for consideration during the analysis, hence a deductive approach to data analysis was used. The results highlighted the importance of coordination among government entities, national and international agencies, private actors, industry players, and civil society. Participants did not mention the use of responsibility metrics but cited mechanisms that facilitated collaboration. Conclusion: The results showed limitations in transforming multisectoral initiatives into intersectoral collaboration to achieve real integration among the different actors involved, considering the actual context and content. Actions could be more effectively implemented with significant outcomes for NCD control in Guyana.

How does community health feature in Global Financing Facility planning documents to support reproductive, maternal, newborn, child and adolescent health and nutrition (RMNAH-N)? insights from six francophone West African countries.

BACKGROUND: Community health is key for improving Reproductive, Maternal, Newborn, Child, and Adolescent Health and Nutrition (RMNCAH-N). However, how community health supports integrated RMNCAH-N service delivery in francophone West Africa is under-researched. OBJECTIVE: We examined how six francophone West African countries (Burkina Faso, Côte d'Ivoire, Guinea, Mali, Niger, and Senegal) support community health through the Global Financing Facility for Women, Children and Adolescents (GFF). METHODS: We conducted a content analysis on Investment Cases and Project Appraisal Documents from selected countries, and set out the scope of the analysis and the key search terms. We applied an iterative hybrid inductive-deductive approach to identify themes for data coding and extraction. The extracted data were compared within and across countries and further grouped into meaningful categories. RESULTS: In country documents, there is a commitment to community health, with significant attention paid to various cadres of community health workers (CHWs) who undertake a range of preventive, promotive and curative roles across RMNCAH-N spectrum. While CHWs renumeration is mentioned, it varies considerably. Most community health indicators focus on CHWs' deliverables, with few related to governance and civil registration. Challenges in implementing community health include poor leadership and governance and resource shortages resulting in low CHWs performance and service utilization. While some countries invest significantly in training CHWs, structural reforms and broader community engagement are lacking. CONCLUSIONS: There is an opportunity to better prioritize and streamline community health interventions, including integrating them into health system planning and budgeting, to fully harness their potential to improve RMNCAH-N.

Main findings: Although community health is a key component of the Investment Cases and the Project Appraisal Documents of most of the six francophone West African countries studied, the level of investment varies considerably between countries, and mostly skewed to community health workers, with very little left over for broader community engagement and oversight processes.Added knowledge: The study describes community health actors, community health interventions and monitoring within a global health initiative, how they fit into the wider health system, the challenges and weaknesses they face and the measures taken to mitigate them, and how they are budgeted.Global health impact for policy and action: There is a need to adopt a holistic community health systems approach, rather than one focused mainly on CHWs, to fully harness community health's potential to improve reproductive, maternal, newborn, child, and adolescent health and nutrition.

Temporal and spatial convergence: the major depressive disorder burden attributed to intimate partner violence against women.

Background: There is a strong causal relationship between intimate partner violence and major depressive disorder, which partly endangers women's safety across the life course and potentially affects the development of future generations. The international community has placed a high priority on addressing the intimate partner violence and the resulting burden of mental illness. Data collection needs to be captured across the temporal trend and spatial distribution for major depressive disorder attributed to intimate partner violence, to reflect the priorities and expectations of survivors.Method: This research obtained raw disability-adjusted life years (DALYs) information for major depressive disorder attributed to intimate partner violence from the Global Burden of Disease 2019. Using estimated annual percentage change and two-way fixed effects models, a secondary spatio-temporal analysis of the age-standardized DALYs rate from 1990 to 2019 was performed.Results: In 2019, DALYs lost among women experiencing major depressive disorder (3.16 million) accounted for 37.18% of the DALYs lost worldwide due to intimate partner violence. The age-standardized DALYs rate of major depressive disorder attributed to intimate partner violence was 108.57 per 100,000. The highest was concentrated in the menopausal transition (45-55), with 133.61 per 100,000, and particularly distributed in Uganda (429.31 per 100,000). The early reproductive period (15-19) showed the increasing age-standardized DALYs rate from 1990 to 2019, which was mainly driven by Malaysia (3.73% per year). Furthermore, countries with higher initial levels of the age-standardized DALYs rate were growing faster than those with lower levels.Conclusions: The burden of major depressive disorder attributed to intimate partner violence showed biological and spatial inequality, prioritized intervention should be targeted at vulnerable stage women in their early reproductive period and menopausal transition. Combined political, socio-cultural as well as medical measures to prevent violence and treat major depressive disorder should be implemented and developed.

Vulnerability to different biological stages of the burden of experiencing intimate partner violence leading to major depressive disorder in women. Women in their reproductive years and during the menopausal transition were more vulnerable.Intimate partner violence-induced depressive disorder is trending younger, with an increasing burden on girls aged 15­19 over the past 30 years.The burden of major depressive disorder attributed to intimate partner violence varies increasingly across countries.

Vulnerability, social value and the equitable sharing of benefits from research: beyond the placebo and access debates.

The vulnerability of research participants is a critical topic for the 2024 revision of the Declaration of Helsinki, with the proposal to include "social value. " However, this proposal has been withdrawn and the relationship between the two concepts has not been clarified. This paper attempts to clarify: (1) the recent reform for the ethical inclusion of vulnerable study participants to promote diversity; (2) the social value, prerequisite for everyone, especially for those who are vulnerable and the most in need; (3) the requirements for promoting the inclusion of vulnerable participants, in particular the review of the norms for placebo-controlled trials and post-trial access; (4) finally, the direction of research ethics reform to achieve social value and equitable global health.

Projected impact of climate change on human health in low- and middle-income countries: a systematic review.

Low- and middle-income countries (LMICs) contribute relatively little to global carbon emissions but are recognised to be among the most vulnerable parts of the world to health-related consequences of climate change. To help inform resilient health systems and health policy strategies, we sought to systematically analyse published projections of the impact of rising global temperatures and other weather-related events on human health in LMICs. A systematic search involving multiple databases was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify studies with modelled projections of the future impact of climate change on human health. Qualitative studies, reviews and meta-analyses were excluded. The search yielded more than 2500 articles, of which 70 studies involving 37 countries met criteria for inclusion. China, Brazil and India were the most studied countries while the sub-Saharan African region was represented in only 9% of studies. Forty specific health outcomes were grouped into eight categories. Non-disease-specific temperature-related mortality was the most studied health outcome, followed by neglected tropical infections (predominantly dengue), malaria and cardiovascular diseases. Nearly all health outcomes studied were projected to increase in burden and/or experience a geographic shift in prevalence over the next century due to climate change. Progressively severe climate change scenarios were associated with worse health outcomes. Knowledge gaps identified in this analysis included insufficient studies of various high burden diseases, asymmetric distribution of studies across LMICs and limited use of some climate parameters as independent variables. Findings from this review could be the basis for future research to help inform climate mitigation and adaptation programmes aimed at safeguarding population health in LMICs.

Big Data in Epidemiology: Brave New World?

Epidemiology is experiencing a significant shift toward the utilization of big data for health monitoring and decision-making. This article discusses the recent example of the World Health Organization (WHO) global oral health status report and regional summaries, which faced criticisms due to its reliance on big data from the Global Burden of Disease (GBD) study. We address the arguments for and against the use of big data in epidemiology and provide an assessment of the value and limitations of big data epidemiology. Moreover, we provide recommendations as to how the oral health community should reconcile traditional epidemiologic approaches with big data and advanced data analytics. This Perspective article highlights the challenges of the current epidemiologic landscape, the potential of big data, and the need for a balanced approach to data utilization in epidemiology.

Global, regional, and national burden of pancreatitis in children and adolescents.

BACKGROUND: Pancreatitis poses a growing public health concern among children and adolescents, yet comprehensive data on its prevalence, incidence, mortality, and disability-adjusted life years (DALYs) remain scarce. This study aims to analyze global, regional, and national trends in pancreatitis burden over the past 3 decades. METHODS: Using data from the Global Burden of Disease (GBD) 2019 database spanning 1990-2019, we assessed pancreatitis prevalence, incidence, mortality, and DALYs, reporting on numbers, rates, age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized DALYs rate (ASDR), and average annual percentage changes (AAPCs). Trends were analyzed by age, sex, region, and socio-demographic index (SDI) using jointpoint analysis and predictive modeling. RESULTS: Globally, pancreatitis prevalence and incidence rates have increased (AAPC prevalence = 0.13, 95% CI: 0.11-0.16; AAPC incidence = 0.30, 95% CI: 0.28-0.32), while mortality and DALYs rates have decreased (AAPC mortality = -1.30, 95% CI: -1.53, -1.07; AAPC DALYs = -1.21, 95% CI: -1.41, -1.01). Both genders showed similar trends. Children under 5 and adolescents 15-19 had higher mortality and DALYs rates. Low SDI regions experienced the greatest increase in ASIR. Eastern Europe exhibited high and rising ASIR, ASMR, and ASDR. Projections indicate continued rise in prevalence with declining mortality and DALYs. CONCLUSION: Pancreatitis burden in children and adolescents has surged globally, especially in lower SDI regions. These findings underscore the urgent need for targeted interventions and healthcare resources in affected areas.

Epidemiology of Intermediate Uveitis.

Intermediate uveitis is defined as inflammation of the vitreous and pars planitis. Etiology can be infectious, associated with a systemic disease, neoplastic or idiopathic. Pars planitis is the term used for idiopathic intermediate uveitis that presents with snowballs and snowbanks. While relatively rare, intermediate uveitis is present globally and typically affects adult females. Awareness of the presentation and a dilated fundus examination in patients presenting with floaters is essential to the diagnosis. PCR testing has enhanced the ability to diagnose infectious and neoplastic conditions that masquerade as intermediate uveitis. A structured review of systems and focused imaging, and laboratory testing will assist with early diagnosis and initiation of treatment.

Global trends of Pauwels type III femoral neck fractures: bibliometric analysis and visualized study.

Background: Pauwels type III femoral neck fractures, as a serious type of femoral neck fractures, have brought about a heavy economic burden on families and society for the high disability rate. Through bibliometric research and visualized analysis, this study aimed at elucidating the global research status of Pauwels type III femoral neck fractures to date, and predicting the future research trends in this field. Methods: Publications and associated information on Pauwels type III femoral neck fractures to date were retrieved from Web of Science Core Collection, and by VoSviewer and R package "bibliometrix", bibliometric analysis and visual presentation was conducted. Results: By retrieval, a total of 98 studies were refinedly extracted, and the volume of publications in this field increased year-over-year. China ranked first in terms of total publication volume and H-Index, with its total citation records second only to the United States. The country with the highest average citation frequency was Switzerland. SHANGHAI JIAO TONG UNIVERSITY was the most productive research institution. Among the authors in this field, Li, Jiantao had published the most researches. INJURY INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED and JOURNAL OF ORTHOPAEDIC TRAUMA were the two magazines with the highest publication volume, total citation records, and H-index. According to keywords co-occurrence analysis, the research content in the past 24 years is mainly divided into four different dimensions. Finite element analysis, femoral neck system, medial buttress plate, cannulated screws, hip screw, open reduction, complications are hot topics for future research. Conclusions: According to the global trends analysis of publications production, Pauwels type III femoral neck fractures are receiving increasing attention and input from scholars. China has made the greatest scientific research contribution among countries, but its academic quality should be improved further. The modified therapeutic methods designed for addressing the complications of traditional internal fixation for Pauwels III femoral neck fractures will be the future research hotspot.

Cardiac troponin T associates with left ventricular function and synchrony assessed by CMR in the general population: results from the Akershus Cardiac Examination 1950 Study.

Background and aim: Cardiac troponin T (cTnT) is a blood biomarker of myocardial injury that is associated with future adverse cardiovascular events in the general population. Left ventricular (LV) global longitudinal strain (GLS) and mechanical dispersion (MD) are metrics of systolic function and synchrony that can be obtained from cardiac imaging. Studies suggest an association between cTnT and echocardiographically assessed GLS and MD, but it is unknown whether cTnT relates to these metrics when assessed by cardiac magnetic resonance (CMR). We hypothesized that cTnT associates with GLS and with MD assessed by CMR feature tracking (CMR-FT) in the general population. Methods and results: cTnT and CMR-FT measurements were performed in 186 community dwellers from the Akershus Cardiac Examination 1950 Study. The participants' age ranged from 68 to 70 years. Median cTnT concentration was 7.0 ng/L (interquartile interval 5.0-12.6 ng/L), median absolute value of GLS was 17.3% (interquartile interval 15.7-18.8%), and median MD was 80.7 milliseconds (interquartile interval 61.8-105.0 milliseconds). In multivariable linear regression models adjusted for common clinical risk factors of cardiovascular disease, with GLS and MD as outcome and cTnT as the predictor variable of interest, log10 transformed cTnT was significantly associated with both absolute GLS [ß-coefficient -1.65, confidence interval (-2.84, -0.46)] and MD [ß-coefficient 28.56, confidence interval (12.14, 44.92)]. Conclusion: In older adults from the general population, higher cTnT concentrations are associated with worse systolic function and synchrony assessed by CMR-FT LV GLS and MD, adding information about myocardial function to traditional risk factors.

Events preceding death after high-risk surgery analyzed by Global Trigger Tool and reflective-thematic approach.

BACKGROUND: Postoperative mortality might be influenced by postoperative care, vigilance, and competence to rescue. This study aims to describe the course of events preceding death in a high-risk surgical cohort. METHODS: We analyzed hospital records of patients who died within 30 days after surgery in 4 high volume hospitals using (1) reflective narrative thematic approach to identify recurring themes reflecting issues with conduct of care and (2) Global Trigger Tool to describe incidence, timing, and types of adverse events (AEs) leading to harm. RESULTS: Preoperative predicted median risk of death in the studied group was 9%/13% according to SORT/P-POSSUM, respectively. Nine recurring themes were identified. Prominent themes were "consensus concerning aim and/or risk with planned surgery," "level of (intraoperative) competence and monitoring," and in the postoperative period "level of care and vigilance" on signs of deterioration. We found a total of 303 AEs, with only three patients (5%) having no adverse events. Most common severity category was "I," that is "contributed to patient's death" (n = 110, 36% of all AEs). Of these, 60% were classified as preventable or probably preventable. The peak incidence of AEs was seen on the day of index surgery. Most common types of AEs were "failure of vital functions" (n = 79, 26%), followed by infections (n = 45, 15%). CONCLUSIONS: A high predicted risk of death and a peak of adverse events on the day of index surgery were detected. Identified themes reflect lack of documented multi-professional consensus on how to handle prevalent perioperative risk, vigilance, and postoperative level of care.

Noncaloric monosaccharides induce excessive sprouting angiogenesis in zebrafish via foxo1a-marcksl1a signal.

Artificially sweetened beverages containing noncaloric monosaccharides were suggested as healthier alternatives to sugar-sweetened beverages. Nevertheless, the potential detrimental effects of these noncaloric monosaccharides on blood vessel function remain inadequately understood. We have established a zebrafish model that exhibits significant excessive angiogenesis induced by high glucose, resembling the hyperangiogenic characteristics observed in proliferative diabetic retinopathy (PDR). Utilizing this model, we observed that glucose and noncaloric monosaccharides could induce excessive formation of blood vessels, especially intersegmental vessels (ISVs). The excessively branched vessels were observed to be formed by ectopic activation of quiescent endothelial cells (ECs) into tip cells. Single-cell transcriptomic sequencing analysis of the ECs in the embryos exposed to high glucose revealed an augmented ratio of capillary ECs, proliferating ECs, and a series of upregulated proangiogenic genes. Further analysis and experiments validated that reduced foxo1a mediated the excessive angiogenesis induced by monosaccharides via upregulating the expression of marcksl1a. This study has provided new evidence showing the negative effects of noncaloric monosaccharides on the vascular system and the underlying mechanisms.

Consuming too much sugar can damage blood vessels and contribute to diseases like diabetes and heart disease. Artificial sweeteners have been suggested as a healthier alternative, and are now included in many products like sodas and baked goods. However, some studies have suggested that people who consume large amounts of artificial sweeteners also have an increased risk of cardiovascular disease. Others suggest individuals may also experience spikes in blood sugar levels similar to those observed in people with diabetes. Yet few studies have examined how artificial sweeteners affect the network of vessels that transport blood and other substances around the body. To investigate this question, Wang, Zhao, Xu, et al. studied zebrafish embryos which had been exposed to sugar and a type of artificial sweetener known as non-caloric monosaccharides. Various imaging tools revealed that high levels of sugar caused the embryos to produce more new blood vessels via a process called angiogenesis. This excessive growth of blood vessels has previously been linked to diabetic complications, including cardiovascular disease. Wang, Zhao, Xu, et al. found that zebrafish embryos exposed to several different non-caloric monosaccharides developed similar blood vessel problems. All the sweeteners tested caused immature cells lining the blood vessels to develop into active tip cells that promote angiogenesis. This led to more new blood vessels forming that branch off already existing veins and arteries. These findings suggest that artificial sweeteners may cause the same kind of damage to blood vessels as sugar. This may explain why people who consume a lot of artificial sweeteners are at risk of developing heart disease and high blood sugar levels. Future studies could help scientists learn more about how genetics or other factors affect the health impact of sugars and artificial sweeteners. This may lead to a greater understanding of the long-term health effects of artificially sweetened foods.

Breaking Barriers: Ensuring Gender Neutral Care on Short Term Surgical Missions.

INTRODUCTION: Gender discrimination is prevalent worldwide in medical and surgical care. In the setting of short-term surgical missions (STSMs) conducted to address the global burden of surgical disease, patient selection raises ethical considerations regarding equitable distribution of limited clinical resources. The goal of this study was to examine if equitable distribution of operative care between male and female patients occurs in STSMs. METHODS: The International Surgical Health Initiative (ISHI) is a US based nonprofit, nongovernmental organization. Records from surgical missions to Ghana (2014-2023) and Sierra Leone (2013-2023) were analyzed to evaluate for gender equity in inguinal hernia repairs, the most common procedure performed. A control group was created from a literature review inclusive of all studies of inguinal hernia repairs that included over 500 patients and patient gender. RESULTS: The review of 26 studies, representing 3,239,043 patients, demonstrated a gender distribution of 13% female. In Sierra Leone 246 inguinal hernia repairs were performed between 2013 and 2023. 28 (11.4%) of the hernia repairs were in females, which was not significantly different from the control group (P = 0.45). In Ghana 150 inguinal hernia repairs were performed between 2014 and 2023. 12 (8%) of the hernia repairs were in females. This was not significantly different from the control group (P = 0.07). CONCLUSIONS: This is the first study investigating the gender equity conducted within the context of humanitarian surgical outreach. Equitable patient selection is a paramount consideration in STSMs, particularly to address gender-related disparities in surgical care.

Mapping new psychoactive substances: Leveraging GIS technology for advanced global surveillance and policy support.

The escalating challenge of New Psychoactive Substances (NPS) necessitates enhanced global monitoring and analysis capabilities. This study introduces an advanced interactive visualization tool that employs Geographic Information System (GIS) technologies to improve the functionality of the UNODC's Early Warning Advisory. The tool enables dynamic observation and analysis of NPS's geographical and temporal distribution, thereby facilitating a comprehensive understanding of their public health impacts. By incorporating detailed choropleth maps and annual and cumulative bar charts, the tool allows policymakers and researchers to visually track and analyze trends in NPS usage and control efforts across different regions. The results demonstrate the tool's effectiveness in providing actionable insights, which support the strategic development of public health policies and interventions to curb the global rise in NPS usage. This initiative illustrates the essential role of digital tools in enhancing public health strategies and responses to emerging drug trends. This rising challenge underscores the urgent need for innovative solutions in monitoring drug trends, a theme explored in this paper. The web tool is available at https://nps-vis.cmdm.tw, and the code is available at https://github.com/CMDM-Lab/nps-vis.

Burden of biliary tract carcinoma in China (1990-2021): Findings from the 2021 Global Burden of Disease Study.

Biliary tract carcinoma (BTC) is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China. Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels, and little is known about the demographic, temporal, and geographic patterns of epidemiological characteristics and disease burden of BTC in China. The incidence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs) due to premature death and years lived with disability (YLDs) of BTC were comprehensively examined by age, sex, and calendar year in the Chinese population, using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study. All-age incidence increased from 17,077 to 51,720 between 1990 and 2021, and the age-standardized incidence rate rose by 13.62%; all-age deaths increased from 17,251 to 37,833, but the age-standardized mortality rate fell by nearly one-fifth. The DALYs rose by 89.57% while the age-standardized DALY rate fell by 23.24%. Variations of the tendencies in BTC burden were found between sexes and age groups. Data for each provincial region indicate that coastal eastern provincial regions have higher incidence and YLD levels, whereas northern provincial regions have higher mortality, DALY, and YLL levels. The proportions of DALYs attributable to high body mass index (BMI) illustrate the growing attribution obesity has made, and high BMI usually puts more burden on northern provincial regions. These results provide evidence to support precise, targeted, and customed public health strategies aimed at enhancing biliary tract health among the Chinese population.