Search Results (32)

Global environmental and climatic changes have become an ever-increasing trepidation worldwide due to the unprecedented changes in temperatures, precipitation, weather, and ecosystems at the international, regional, and local levels. This study attempts to find out the impacts and vulnerabilities of climate-induced hazards and environmental degradation on the lives of Indigenous people in the Chittagong Hill Tracts (CHT), along with finding out the factors of environmental degradation in Indigenous communities. This study also explores the adaptation strategies of Indigenous people in adverse situations in the Chittagong Hill Tracts. For conducting this study, a critical ethnographic approach is adopted, together with participant observation, in-depth interviews (N = 55), and focus group discussions (FGDs) (N = 5, 48 participants), following purposive sampling over one year (October 2019 to October 2020). The findings of this study indicate that climate-induced hazards and environmental crisis brings unprecedented suffering to the lives and livelihoods of Indigenous people. Climate change and variability together with human causes contribute to creating an environmental crisis that threatens food security, creates water scarcity, and disrupts agricultural activities and household properties in Indigenous communities. The findings also indicate that Indigenous people are bound to change their traditional jhum cultivation and adjust their traditional housing structure apart from searching for alternative livelihoods due to climatic events and environmental crises. However, Indigenous people try to adapt to this adverse situation following their life-long experiences and local knowledge. This study helps policymakers as well as governments to understand the major drivers of environmental crisis and climatic events in Indigenous communities, together with finding out the solutions and recuperating the living conditions of the marginalized groups in Bangladesh and beyond. Full article

Air pollution (AP) is a critical environmental factor influencing public health, with well-documented associations with upper respiratory tract (URT) diseases. This study investigates the relationship between ENT emergency department (ENT-ED) visits at Azienda Ospedale Università di Padova (AOPD) and daily concentrations of environmental pollutants during the first year of the COVID-19 pandemic (March 2020–March 2021), compared to pre-pandemic data from 2017. The study focuses on patients diagnosed with URT inflammatory diseases, excluding those with COVID-19 infection, who sought care at the AOPD ENT-ED. Environmental data, including meteorological variables, air pollutants, and major aeroallergen levels, were collected from regional monitoring stations. A total of 4594 patients were admitted in 2020/2021, marking a 37% reduction from 2017, with URT inflammatory admissions decreasing by 52%. A significant decline in PM10, NO₂ and Alternaria levels was observed, whereas Betullaceae and Corylaceae concentrations significantly increased. Multivariate analyses revealed strong associations between aeroallergen exposure and ENT admissions, particularly for Alternaria, which had a notable impact on total admissions (p < 0.001) and was significantly linked to cases of otitis media and tonsillitis. PM10 concentrations on specific days preceding ED visits were associated with increased incidences of pharyngitis and rhinosinusitis (p < 0.05). These findings reinforce the connection between environmental pollutants and ENT emergency visits, highlighting the adverse effects of AP and climate variables on URT diseases, even during a pandemic when enhanced airway protection measures were in place. This study underscores the necessity of stringent air quality regulations and interdisciplinary strategies to mitigate environmental health risks and inform future public health policies. Full article

The life stage between the ages of 30–45 years for women is critical, given the competing demands of occupational advancement, intimate partner relationships, and childcare responsibilities. Cardiovascular disease (CVD) is the leading cause of death among women in the US, which is experienced inequitably by race/ethnicity/nativity and socioeconomic status and is embedded within geographic contexts. The objective of the current study was to examine social inequities in pre-pregnancy risk factors for cardiovascular disease. We analyzed 16 years of geocoded natality data in Texas (N = 2,089,588 births between 2005 and 2020 to mothers aged 30–45 years) linked with census tract- and county-level data. Dependent variables included pre-pregnancy diabetes, hypertension, obesity, and smoking. Independent variables included individual-level race/ethnicity/nativity and educational attainment, tract-level poverty and racial/ethnic concentrations, and county-level urban/rural status, with controls for other sociodemographic characteristics and time trend. Two-level, random intercept hierarchical generalized logistic models were used to estimate associations and model fit. Significant social inequities at the individual-, tract-, and county-levels in each risk factor were found. For example, tract-level variables had substantial and significant association with the four CVD risk factors, ranging from 13% to 72% higher odds in adjusted models. For all four risk factors, the more rural the county of residence was, the higher the odds of having the risk factor (24% to 256% higher odds). Individual-level social inequalities by race/ethnicity/nativity (ORs ranging from 0.04 to 2.12) and education (ORs ranging from 1.25 to 5.20) were also observed. Enhancing our understanding of this important period of life may enable policy and interventions to better support women through this critical life stage. Full article

Myeloid sarcoma (MS), or extramedullary acute myeloid leukaemia tumour (eAML), is a rare hematopoietic neoplasm. Recognised as a distinct entity within acute myeloid leukaemia (AML), MS presents significant diagnostic challenges due to its rarity, clinical heterogeneity, and variable immunophenotypic and genetic characteristics. The mechanisms by which leukaemic stem cells (LSCs) migrate to form solid tumours in extramedullary (EM) sites remain unclear. MS can occur de novo, precede AML, and manifest alongside AML relapse. It can also develop with myelodysplastic syndromes (MDSs) or myeloproliferative neoplasms (MPNs). MS frequently presents in organs such as the skin, lymph nodes, gastrointestinal (GI) tract, and central nervous system (CNS), often resulting in diverse clinical manifestations. Diagnosis relies on a comprehensive approach, including tissue biopsy, bone marrow (BM) evaluation, and advanced imaging modalities. Accurate diagnosis is crucial for risk stratification and treatment selection. Prognosis is influenced by several factors: MS’s anatomical location, timing of MS diagnosis, genetic profile, and possible treatment. This review emphasises the need for comprehensive diagnostic methods to better define individual MS characteristics and prognosis. It explores the role of novel targeted therapies in improving patient outcomes and further highlights the critical need for future multicentre data collection to optimise diagnostic and therapeutic approaches. Full article

Background: Nosocomial lower respiratory tract infections (nLRTIs) are associated with unfavorable clinical outcomes and significant healthcare costs. nLRTIs include hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and other ICU-acquired pneumonia phenotypes. While risk factors for mortality in these infections are critical to guide preventive strategies, it remains unclear whether they vary based on their requirement of invasive mechanical ventilation (IMV) at any point during the hospitalization. Objectives: This study aims to identify risk factors associated with short- and long-term mortality in patients with nLRTIs, considering differences between those requiring IMV and those who do not. Methods: This multinational prospective cohort study included ICU-admitted patients diagnosed with nLRTI from 28 hospitals across 13 countries in Europe and South America between May 2016 and August 2019. Patients were selected based on predefined inclusion and exclusion criteria, and clinical data were collected from medical records. A random forest classifier determined the most optimal clustering strategy when comparing pneumonia site acquisition [ward or intensive care unit (ICU)] versus intensive mechanical ventilation (IMV) necessity at any point during hospitalization to enhance the accuracy and generalizability of the regression models. Results: A total of 1060 patients were included. The random forest classifier identified that the most efficient clustering strategy was based on ventilation necessity. In total, 76.4% of patients [810/1060] received IMV at some point during the hospitalization. Diabetes mellitus was identified to be associated with 28-day mortality in the non-IMV group (OR [IQR]: 2.96 [1.28–6.80], p = 0.01). The 90-day mortality-associated factor was MDRP infection (1.98 [1.13–3.44], p = 0.01). For ventilated patients, chronic liver disease was associated with 28-day mortality (2.38 [1.06–5.31] p = 0.03), with no variable showing statistical and clinical significance at 90 days. Conclusions: The risk factors associated with 28-day mortality differ from those linked to 90-day mortality. Additionally, these factors vary between patients receiving invasive mechanical ventilation and those in the non-invasive ventilation group. This underscores the necessity of tailoring therapeutic objectives and preventive strategies with a personalized approach. Full article

Human parainfluenza virus (HPIV) is a major cause of respiratory illnesses in children under five years, with clinical manifestations ranging from mild upper respiratory tract infections to severe lower respiratory tract diseases. This multi-center, cross-sectional study investigated the burden, clinical features, and predictors of respiratory viral infections in hospitalized children across four sites in Jordan. Nasopharyngeal specimens from 1000 eligible children were analyzed. In this article, we focused on HPIV infections. The overall HPIV positivity rate was 22.6%, with HPIV-3 accounting for 90.3% of cases. Significant geographic variability was observed, with higher positivity rates in the southern region. HPIV-positive cases frequently presented with symptoms like nasal congestion, tachypnea, and poor feeding. Co-infections with respiratory syncytial virus (RSV) or influenza were associated with worse outcomes, including an increased need for invasive ventilation. The logistic regression identified male gender, asthma, and respiratory acidosis as predictors of complications. Geographic differences in HPIV prevalence and severity were notable, emphasizing the influence of environmental and socioeconomic factors. These findings underscore the urgent need for enhanced HPIV surveillance, targeted public health interventions, and vaccine development to mitigate the disease burden. This study provides critical insights that guide healthcare strategies and improve outcomes in young children at risk of severe HPIV infections. Full article

Spermatozoa are highly specialized male cells that are characterized by a unique ability to move, which is a critical factor for successful fertilization. The relative simplicity of motility assessment, especially in livestock, has made it a widely used parameter for evaluating ejaculate quality or cryopreserved semen in the clinical field, and an advanced tool in reproductive physiology and toxicology research. Technological advances in image analysis and computational methods have substantially increased its accuracy through the use of computer-assisted sperm analysis (CASA) to minimize subjective bias in motility assessments. Nevertheless, this more objective method still presents some significant challenges, including variability in the sample preparation, imaging conditions, and analytical parameters. These issues contribute to inconsistency and impair the reproducibility and comparability of data between laboratories. The implementation of standardized protocols, combined with comprehensive training and rigorous evaluation, can serve to mitigate some of the emerging inconsistencies. In addition, the in vitro conditions under which CASA analyses are performed often differ significantly from the natural environment of the female reproductive tract in vivo. This review discusses the methodologies, critical issues, and limitations of sperm motility analyses using CASA, with a particular focus on the boar as an important agricultural and biomedical model species in which this system is widely used. Full article

Background: The complex interaction between the gut and urinary microbiota underscores the importance of understanding microbial dysbiosis in pediatric urinary tract infection (UTI). However, the literature on the gut–urinary axis in pediatric UTIs is limited. This systematic review aims to summarize the current literature on the roles of gut and urinary dysbiosis in pediatric UTIs. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search was performed across four databases, including PubMed, Web of Science, Scopus, and EMBASE. All studies published between January 2003 and December 2023 utilizing 16S rRNA sequencing to profile the gut or urinary microbiome in children with UTIs were included. Heat map visualization was used to compare microbial profiles between UTI and control cohorts. The methodological quality assessment was performed using the Newcastle–Ottawa scale (NOS). Results: Eight studies were included in this review. While five studies compared the microbiota signatures between patients and controls, three studies focused solely on the UTI cohort. Also, the gut and urinary microbiome profiles were investigated by four studies each. The consistent loss of microbiome alpha-diversity with an enrichment of specific putative pathobiont microbes was observed among the included studies. Escherichia coli consistently emerged as the predominant uropathogen in pediatric UTIs. In addition to this, Escherichia fergusonii, Klebsiella pneumoniae, and Shigella flexneri were isolated in the urine of children with UTIs, and enrichment of Escherichia, Enterococcus, Enterobacter, and Bacillus was demonstrated in the gut microbiota of UTI patients. On the contrary, certain genera, such as Achromobacter, Alistipes, Ezakiella, Finegoldia, Haemophilus, Lactobacillus, Massilia, Prevotella, Bacteroides, and Ureaplasma, were isolated from the controls, predominantly in the fecal samples. The methodological quality of the included studies was variable, with total scores (NOS) ranging from 5 to 8. Conclusions: The enrichment of specific pathobionts, such as Escherichia coli, in the fecal or urinary samples of the UTI cohort, along with the presence of core microbiome-associated genera in the non-UTI population, underscores the critical role of the gut–urinary axis in pediatric UTI pathogenesis. These findings highlight the potential for microbiome-based strategies in pediatric UTIs. Further studies with larger cohorts, standardized healthy controls, and longitudinal profiling are essential to validate these observations and translate them into clinical practice. Full article

Abstract: The introduction of biological therapies has revolutionized inflammatory bowel disease (IBD) management. A critical consideration in developing these therapies is ensuring adequate drug concentrations at the site of action. While blood-based biomarkers have shown limited utility in optimizing treatment (except for TNF-alpha inhibitors and thiopurines), tissue drug concentrations may offer valuable insights. In antimicrobial therapies, tissue concentration monitoring is standard practice and could provide a new avenue for understanding the pharmacokinetics of biological and small-molecule therapies in IBD. Various methods exist for measuring tissue concentrations, including whole tissue sampling, MALDI-MSI, microdialysis, and fluorescent labeling. These techniques offer unique advantages, such as spatial drug-distribution mapping, continuous sampling, or cellular-level analysis. However, challenges remain, including sampling invasiveness, heterogeneity in tissue compartments, and a lack of standardized bioanalytical guidelines. Drug pharmacokinetics are influenced by multiple factors, including molecular properties, disease-induced changes in the gastrointestinal tract, and the timing of sample collection. For example, drug permeability, solubility, and interaction with transporters may vary between Crohn’s disease and ulcerative colitis. Research into the tissue concentrations of drugs like anti-TNF agents, ustekinumab, vedolizumab, and tofacitinib has shown variable correlations with clinical outcomes, suggesting potential roles for tissue concentration monitoring in therapeutic drug management. Although routine clinical application is not yet established, exploring tissue drug concentrations may enhance understanding of IBD pharmacotherapy. Full article

Background/Objectives: Human brain aging is a complex process that affects various aspects of brain function and structure, increasing susceptibility to neurological and psychiatric disorders. A number of nongenetic (e.g., environmental and lifestyle) and genetic risk factors are found to contribute to the varying rates at which the brain ages among individuals. Methods: In this paper, we conducted both an exposome-wide association study (XWAS) and a genome-wide association study (GWAS) on white matter brain aging in the UK Biobank, revealing the multifactorial nature of brain aging. We applied a machine learning algorithm and leveraged fractional anisotropy tract measurements from diffusion tensor imaging data to predict the white matter brain age gap (BAG) and treated it as the marker of brain aging. For XWAS, we included 107 variables encompassing five major categories of modifiable exposures that potentially impact brain aging and performed both univariate and multivariate analysis to select the final set of nongenetic risk factors. Results: We found current tobacco smoking, dietary habits including oily fish, beef, lamb, cereal, and coffee intake, length of mobile phone use, use of UV protection, and frequency of solarium/sunlamp use were associated with the BAG. In genetic analysis, we identified several SNPs on chromosome 3 mapped to genes IP6K1, GMNC, OSTN, and SLC25A20 significantly associated with the BAG, showing the high heritability and polygenic architecture of human brain aging. Conclusions: The critical nongenetic and genetic risk factors identified in our study provide insights into the causal relationship between white matter brain aging and neurodegenerative diseases. Full article

This study investigates the spatial disparities in flood risk and social vulnerability across 66,543 census tracts in the Conterminous United States (CONUS), emphasizing urban–rural differences. Utilizing the American Community Survey (ACS) 2016–2020 data, we focused on 16 social factors representing socioeconomic status, household composition, racial and ethnic minority status, and housing and transportation access. Principal Component Analysis (PCA) reduced these variables into five principal components: Socioeconomic Disadvantage, Elderly and Disability, Housing Density and Vehicle Access, Youth and Mobile Housing, and Group Quarters and Unemployment. An additive model created a comprehensive Social Vulnerability Index (SVI). Statistical analysis, including the Mann–Whitney U test, indicated significant differences in flood risk and social vulnerability between urban and rural areas. Spatial cluster analysis using Local Indicators of Spatial Association (LISA) revealed significant high flood risk and social vulnerability clusters, particularly in urban regions along the Gulf Coast, Atlantic Seaboard, and Mississippi River. Global and local regression models, including Ordinary Least Squares (OLS) and Geographically Weighted Regression (GWR), highlighted social vulnerability’s spatial variability and localized impacts on flood risk. The results showed substantial regional disparities, with urban areas exhibiting higher flood risks and social vulnerability, especially in southeastern urban centers. The analysis also revealed that Socioeconomic Disadvantage, Group Quarters and Unemployment, and Housing Density and Vehicle Access are closely related to flood risk in urban areas, while in rural areas, the relationship between flood risk and factors such as Elderly and Disability and Youth and Mobile Housing is more pronounced. This study underscores the necessity for targeted, region-specific strategies to mitigate flood risks and enhance resilience, particularly in areas where high flood risk and social vulnerability converge. These findings provide critical insights for policymakers and planners aiming to address environmental justice and promote equitable flood risk management across diverse geographic settings. Full article

(1) Background: Urinary tract infection (UTI) is a leading cause of emergency department visits and hospital admissions. Despite many studies identifying UTI-related risk factors for bacteremia or sepsis, a significant gap remains in developing predictive models for in-hospital mortality or the necessity for emergent intensive care unit admission in the emergency department. This study aimed to construct interpretable machine learning models capable of identifying patients at high risk for critical outcomes. (2) Methods: This was a retrospective study of adult patients with urinary tract infection (UTI), extracted from the Medical Information Mart for Intensive Care IV Emergency Department (MIMIC-IV-ED) database. The critical outcome is defined as either in-hospital mortality or transfer to an intensive care unit within 12 h. ED visits were randomly partitioned into a 70%/30% split for training and validation. The extreme gradient boosting (XGBoost), random forest (RF), and support vector machine (SVM) algorithms were constructed using variables selected from the stepwise logistic regression model. The XGBoost model was then compared to the traditional model and clinical decision rules (CDRs) on the validation data using the area under the curve (AUC). (3) Results: There were 3622 visits among 3235 unique patients diagnosed with UTI. Of the 2535 patients in the training group, 836 (33%) experienced critical outcomes, and of the 1087 patients in the validation group, 358 (32.9%) did. The AUCs for different machine learning models were as follows: XGBoost, 0.833; RF, 0.814; and SVM, 0.799. The XGBoost model performed better than others. (4) Conclusions: Machine learning models outperformed existing traditional CDRs for predicting critical outcomes of ED patients with UTI. Future research should prospectively evaluate the effectiveness of this approach and integrate it into clinical practice. Full article

This paper provides insights into the conventional understanding of biliary tract malignancies, with a specific focus on cholangiocarcinoma (CCA). We then delve into the groundbreaking ideas presented by Dr. James Cleary. CCA, originating from biliary tree cells, manifests diverse subtypes contingent upon anatomical localization and differentiation status. These variants exhibit discrete genetic aberrations, yielding disparate clinical phenotypes and therapeutic modalities. Intrahepatic, perihilar, and distal CCAs intricately involve distinct segments of the biliary tree, further categorized as well-differentiated, moderately differentiated, or poorly differentiated adenocarcinomas based on their histological differentiation. Understanding the etiological factors contributing to CCA development assumes paramount importance. Stratifying these factors into two groups, those unrelated to fluke infestations (e.g., viral hepatitis and fatty liver conditions) and those associated with fluke infestations (e.g., chronic liver inflammation), facilitates predictive modeling. The epidemiology of CCA exhibits global variability, with Southeast Asia notably displaying higher incidences attributed primarily to liver fluke infestations. Jaundice resulting from bile duct obstruction constitutes a prevalent clinical manifestation of CCA, alongside symptoms like malaise, weight loss, and abdominal pain. Diagnostic challenges arise due to the symptomatic overlap with other biliary disorders. Employing comprehensive liver function tests and imaging modalities such as computed tomography assumes a pivotal role in ensuring accurate diagnosis and staging. However, the definitive confirmation of CCA necessitates a biopsy. Treatment modalities, predominantly encompassing surgical resection and radiation therapy, hold curative potential, although a considerable subset of patients is deemed unresectable upon exploration. Challenges intensify, particularly in cases classified as cancer of unknown origin, underscoring the imperative for early intervention. Advancements in genomic sequencing have revolutionized precision medicine in CCA. Distinct genomic markers, including fibroblast growth factor receptor 2 (FGFR2) alterations and isocitrate dehydrogenase 1 (IDH1) mutations, have emerged as promising therapeutic targets. FGFR2 alterations, encompassing mutations and rearrangements, play pivotal roles in oncogenesis, with FGFR inhibitors demonstrating promise despite identified resistance mechanisms. Similarly, IDH1 inhibitors face challenges with resistance, despite encouraging early clinical trial results, prompting exploration of novel irreversible inhibitors. Dr. James Cleary’s illuminating discourse underscores the significance of diverse FGFR2 alterations and the potential of IDH1 inhibition in reshaping the treatment landscape for CCA. These findings unveil critical avenues for targeted therapeutic interventions, emphasizing the critical need for ongoing research to optimize outcomes in this challenging cancer subtype, incorporating innovative insights from Dr. Cleary. Full article

Clinical and basic research suggests that bladder ischemia may be an independent variable in the development of lower urinary tract symptoms (LUTS). We have reported that ischemic changes in the bladder involve differential expression and post-translational modifications (PTMs) of the protein’s functional domains. In the present study, we performed in-depth analysis of a previously reported proteomic dataset to further characterize proteins PTMs in bladder ischemia. Our proteomic analysis of proteins in bladder ischemia detected differential formation of non-coded amino acids (ncAAs) that might have resulted from PTMs. In-depth analysis revealed that three groups of proteins in the bladder proteome, including contractile proteins and their associated proteins, stress response proteins, and cell signaling-related proteins, are conspicuously impacted by ischemia. Differential PTMs of proteins by ischemia seemed to affect important signaling pathways in the bladder and provoke critical changes in the post-translational structural integrity of the stress response, contractile, and cell signaling-related proteins. Our data suggest that differential PTMs of proteins may play a role in the development of cellular stress, sensitization of smooth muscle cells to contractile stimuli, and deferential cell signaling in bladder ischemia. These observations may provide the foundation for future research to validate and define clinical translation of the modified biomarkers for precise diagnosis of bladder dysfunction and the development of new therapeutic targets against LUTS. Full article

To date, the scientific literature on health variables for Escherichia coli antimicrobial resistance (AMR) has been investigated throughout several systematic reviews, often with a focus on only one aspect of the One Health variables: human, animal, or environment. The aim of this umbrella review is to conduct a systematic synthesis of existing evidence on Escherichia coli AMR in humans in the community from a One Health perspective. PubMed, EMBASE, and CINAHL were searched on “antibiotic resistance” and “systematic review” from inception until 25 March 2022 (PROSPERO: CRD42022316431). The methodological quality was assessed, and the importance of identified variables was tabulated across all included reviews. Twenty-three reviews were included in this study, covering 860 primary studies. All reviews were of (critically) low quality. Most reviews focused on humans (20), 3 on animals, and 1 on both human and environmental variables. Antibiotic use, urinary tract infections, diabetes, and international travel were identified as the most important human variables. Poultry farms and swimming in freshwater were identified as potential sources for AMR transmission from the animal and environmental perspectives. This umbrella review highlights a gap in high-quality literature investigating the time between variable exposure, AMR testing, and animal and environmental AMR variables. Full article