The Supreme Court (SC) of India's judgment on March 11, 2026, in Harish Rana vs Union of India brought greater clarity on the complex issue of end-of-life decisions; specifically on withdrawal of care from persons in a "permanent vegetative state" [1]. In an earlier landmark judgment in Aruna Shanbaug vs Union of India in 2011, the Court had allowed petitions in favour of "withholding or withdrawal of life support" to allow "a dignified death", in very rare cases, following specific procedures outlined in that judgment [2]. In 2018, in Common Cause vs Union of India, the SC recognised the "right to die with dignity" as an extension of the fundamental "right to live with dignity" under Article 21 of the Indian Constitution. Patients who were terminally ill could refuse futile or burdensome treatment and could register Advance Directives, against unnecessary suffering caused by such treatment [3]. That judgment detailed the decision-making process to be followed for withdrawal of treatment, in order to protect vulnerable patients and prevent misuse. These procedural steps were later simplified by the SC in 2023 into what is termed "Common Cause Guidelines 2023" [4].
Reconstruction of distal radius defects following oncological resection remains technically challenging. Free fibula flap (FFF) arthrodesis offers a biological and durable reconstructive option; however, reports remain limited. We retrospectively reviewed 8 patients who underwent en bloc resection of Campanacci grade III giant cell tumors (2017-2024) of the distal radius, followed by reconstruction with FFF arthrodesis. Clinical, radiological, and functional outcomes were analyzed, including union, recurrence, complications, donor-site morbidity, and Musculoskeletal Tumor Society, Disabilities of the Arm, Shoulder, and Hand (DASH), and visual analog scale scores. All patients achieved radiographic union (mean 7 mo proximally, 11 mo distally). Median follow-up was 36 months. Seven (87.5%) patients remained disease-free; 1 patient developed multicentric soft-tissue local recurrence with pulmonary metastases, which was managed surgically along with radiotherapy and medical treatment. The patient remained disease-free at last follow-up. Mean Musculoskeletal Tumor Society score was 24.5, DASH score was 20.3, and visual analog scale score was 2.3, indicating satisfactory limb function and minimal pain. Donor-site morbidity was minimal. FFF arthrodesis maintained viability even after postoperative fractures, soft-tissue recurrences, and adjuvant therapy, underscoring its robustness. It represents a valuable microsurgical option when long-term stability and biological incorporation are prioritized.
Shigella is a leading cause of childhood diarrhea in low- and middle-income countries and is increasingly resistant to first-line antibiotics. We conducted a surveillance study to determine the incidence, genomic characteristics, and AMR profiles of Shigella infections in children under five with moderate to severe diarrhea (MSD) in Lusaka, Zambia. Between 15 September 2020 and 30 November 2021, a prospective cohort study of 1,400 children under five was enrolled during a community census in a peri-urban setting and passively followed for 9.5 months for MSD. During enrollment, socio-demographic data were collected using electronic questionnaires, while clinical data were collected through the DHIS platform. The main outcome, Shigella in diarrheal stool in under 5 children, was detected using culture and Loop-mediated Isothermal Amplification (LAMP) targeting the ipaH gene. Cox proportional hazards models were used to assess the incidence and risk factors of Shigella (ipaH) infections. Whole-genome sequencing (WGS) was used to characterize the genomic diversity and antimicrobial resistance genes, complemented by phenotypic antibiotic susceptibility testing. There were 230 first episodes of Shigella over a follow-up time of 9,581.7 child-months, yielding an incidence of 24.0 (95% CI 21.1-27.3) cases per 1,000 child-months, with the highest incidence among 2 to 3-year-olds. The key risk factors identified were the water source (p=0.025) and age group (p=0.014). Genotypic characterization revealed 10 S. flexneri , 9 S. sonnei , and 3 S. boydii . The S. sonnei isolates formed two clusters, differing in virulence factors and plasmid profiles, indicating two possible circulating strains. Shigella isolates exhibited phenotypic and genotypic multidrug resistance, including against trimethoprim, aminoglycosides, and beta-lactams. Plasmid-mediated quinolone resistance (qnrS1) was identified in four S. flexneri isolates, with these genes located on the IncFIB(K) plasmid, highlighting the potential for horizontal transmission and spread of quinolone resistance in this region. No phenotypic and genotypic resistance to macrolides, the first-line treatment for Shigella in Zambia, was observed. We report a high burden of Shigella with multidrug resistance, including resistance to fluoroquinolones. These findings highlight the increasing resistance of Shigella to first-line antibiotics and underscore the importance of developing safe and effective vaccines, improving WASH conditions, and ongoing AMR surveillance. The EDCTP2 program, supported by the European Union, the Faculty for the Future Foundation (FFTF), the Netherlands Organization for Health Research and Development (ZonMw), and Health-Holland AMR-Global, Gloria, and Track-AMR. Evidence before this study: Despite Shigella being a leading cause of bacterial diarrheal mortality globally, there is a critical lack of up-to-date data on its burden and associated antimicrobial resistance (AMR) in high-risk settings, such as sub-Saharan Africa (SSA). We searched PubMed for studies published between 2000 and May 2025, using the terms " Shigella ," "antimicrobial resistance," and "sub-Saharan Africa." Only three studies (GEMS, MAL-ED, VIDA) involving extensive surveillance in SSA countries were identified, all conducted before 2018. None integrated disease burden, genomic characterization of circulating strains, and both phenotypic and genotypic AMR profiling. In Zambia, we found no published surveillance data on Shigella or resistance patterns in children. The added value of the study: We present an up-to-date, integrated assessment of the burden, genomic diversity, and AMR profiles among Shigella isolates in children under five in SSA, specifically in a high-risk peri-urban setting in Lusaka, Zambia. By prospectively following a large cohort of 1,400 children and combining culture with WGS, we provide detailed insights into the disease burden and epidemiology of circulating Shigella strains and the relevance of candidate vaccine antigens. We reveal a high prevalence of multidrug resistance (MDR), including plasmid-mediated and phenotypic resistance to ciprofloxacin, the first-line treatment for Shigella . We further complement genotypic AMR with phenotypic AMR testing to predict potential resistance genes while measuring antibiotic susceptibility in real clinical settings. Implications of all the available evidence: We demonstrate that Shigella is genomically diverse and an important etiology of moderate to severe gastroenteritis in Zambian children. Risk factors include increasing age and poor WASH. We observed plasmid-mediated resistance to ciprofloxacin and MDR, which threatens the efficacy of current Shigella treatment and risks population-level AMR spread. These results highlight the need for improved WASH, antibiotic stewardship, and the development of effective vaccines, supported by ongoing genomic surveillance, to facilitate disease monitoring, inform treatment guidelines, guide vaccine antigen selection, and inform evidence-based antibiotic stewardship.
Data deficiency is a substantial challenge for extinction risk assessments because incomplete data means we cannot accurately identify priority protected areas for conservation. Here, we use the International Union for Conservation of Nature (IUCN) distributions of amphibians, sharks and rays, fish, mammals, birds, and reptiles to identify hotspots of data deficient species. We found that areas with high numbers of data deficient species were not randomly distributed and did not necessarily overlap with hotspots of biodiversity, particularly in the Amazon and West Africa. Data deficiency hotspots were concentrated around tropical South America, Africa, and Southeast Asia; however, this distribution varied between taxa. Hotspots of data deficient amphibians were concentrated around the tropical Andean forests of Colombia, Peru, and Ecuador; throughout Brazil; and in the New Guinea Highlands. The tropical forests of the Congo River basin, Papua New Guinea, and the Philippines were hotspots for avian data deficiency. Data deficient chondrichthyans were concentrated in the tropical seas, particularly around the western coast of Africa, East Asia, and the tropical Americas. Indochina was identified as the primary hotspot for data deficient freshwater fish, whereas the Indo-Pacific was the primary hotspot for data deficient marine fish. Data deficient marine mammals were broadly distributed around the southern oceans, South America, Southeast Asia, and Northwest Africa. Data deficient herpetofauna were concentrated around tropical Asia, whereas tropical South America, Indonesia, and central Africa were the hotspots for data deficient terrestrial mammals. Although data deficiency reflected drivers of biodiversity more broadly (e.g., latitude), other factors were also influential, including the amount of conservation funding invested by a country and population density. Increasing evidence suggests that data deficient species are disproportionately likely to be threatened with extinction. Scientists urgently need to focus their research efforts on these data deficiency hotspots and ensure protected area networks are suitably representative and include data deficient species. Furthermore, the accuracy of status assessments needs to be ascertained, and data deficient species need to be prioritized for study to ensure they are not lost before they are identified. Identificación de puntos calientes de deficiencia de datos faunísticos para dirigir la investigación y el monitoreo urgentes Resumen La falta de datos es un reto importante para las evaluaciones del riesgo de extinción, ya que la información incompleta nos impide identificar con precisión las áreas protegidas prioritarias para la conservación. En este estudio, utilizamos los datos de distribución de la Unión Internacional para la Conservación de la Naturaleza (UICN) sobre anfibios, tiburones y rayas, peces, mamíferos, aves y reptiles para identificar los puntos críticos de especies con datos insuficientes. Descubrimos que las áreas con un elevado número de especies con datos insuficientes no se distribuían de forma aleatoria y no se solapaban necesariamente con los puntos calientes de biodiversidad, especialmente en la Amazonía y África Occidental. Los puntos calientes de especies con datos insuficientes se concentraban en torno a las zonas tropicales de Sudamérica, África y el sudeste asiático; sin embargo, esta distribución variaba entre los taxones. Los puntos calientes de anfibios con datos insuficientes se concentraban en torno a los bosques tropicales andinos de Colombia, Perú y Ecuador; en todo Brasil; y en las tierras altas de Nueva Guinea. Los bosques tropicales de la cuenca del río Congo, Papúa Nueva Guinea y Filipinas eran puntos calientes para las aves con datos insuficientes. Los condrictios con datos insuficientes se concentraban en los mares tropicales, especialmente en torno a la costa occidental de África, el este de Asia y las zonas tropicales de América. Se identificó Indochina como el principal punto caliente para los peces de agua dulce con datos insuficientes, mientras que el Indo‐Pacífico era el principal punto caliente para los peces marinos con datos insuficientes. Los mamíferos marinos con datos insuficientes se distribuían ampliamente por los océanos del sur, Sudamérica, el sudeste asiático y el noroeste de África. La herpetofauna con datos insuficientes se concentraba en la zona tropical de Asia, mientras que la zona tropical de Sudamérica, Indonesia y África central eran los puntos calientes para los mamíferos terrestres con datos insuficientes. Si bien la falta de datos reflejaba factores que influyen en la biodiversidad de manera más general (por ejemplo, la latitud), también influían otros factores, como la cantidad de fondos destinados a la conservación por parte de un país y la densidad de población. Cada vez hay más indicios de que las especies con datos insuficientes tienen una probabilidad desproporcionadamente mayor de estar en peligro de extinción. Los científicos deben centrar urgentemente sus esfuerzos de investigación en estos puntos calientes de falta de datos y garantizar que las redes de áreas protegidas sean adecuadamente representativas e incluyan a las especies con datos insuficientes. Además, es necesario verificar la precisión de las evaluaciones de estado, y se debe dar prioridad al estudio de las especies con datos insuficientes para garantizar que no se pierdan antes de ser identificadas.
Anti-amyloid immunotherapies in Alzheimer's disease (AD) are newly authorized for use in the European Union (AD). In a national online survey in 2024, we aimed to assess French practitioners' opinion and knowledge regarding indications and risk management plan. Answers were based on clinical trial criteria. On 303 practitioners, most knew general indications except 19.1% who considered prescribing without AD biomarkers. Side effects were correctly identified, but specific knowledge on amyloid-related imaging abnormalities was lacking. Tertiary memory clinic practitioners had better knowledge on indications (p < 0.001) and side effects (p = 0.033).
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Lung adenocarcinoma is a common malignancy that requires new treatments. Arsenic trioxide (ATO) exerts antitumor activity in various cancers; however, its mechanisms of action in lung adenocarcinoma remain unclear. The 24-h half-maximal inhibitory concentration (IC50) of ATO on human lung adenocarcinoma A549 cells was determined using the Cell Counting Kit-8 assay. Cells were treated with the IC50 concentration in the experimental group, and untreated cells served as the control group. A comparative assessment of cell proliferation, apoptosis, invasion, and migration was performed. Transcriptome sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to identify differentially expressed genes and enriched pathways. Candidate pathway proteins were validated by western blot analysis. The 24-h IC50 of ATO was 99.12 μmol/L. The ATO-treated group exhibited reduced proliferation, increased apoptosis, and decreased invasion and migration ( P < 0.05) compared with that in the control group. Transcriptome analysis revealed 4,522 upregulated and 4,045 downregulated genes, with enrichment in the mammalian target of rapamycin (mTOR) signaling pathway, base excision repair (BER), and apoptosis pathways. At the protein level, total mTOR expression did not significantly change, whereas phosphorylated mTOR (p-mTOR), APE-1, Bcl-2, and Bcl-XL were downregulated, and cleaved caspase-8 and cleaved caspase-9 were upregulated ( P < 0.05). These results indicate that ATO suppresses the malignant phenotype of A549 cells by inhibiting mTOR phosphorylation, downregulating key BER components, and activating the extrinsic and intrinsic apoptotic pathways, providing experimental evidence for further studies of ATO in lung adenocarcinoma therapy.
Immune escape remains a major barrier to durable cancer immunotherapy. Although checkpoint blockade has transformed cancer treatment, resistance commonly reflects broader tumor-intrinsic and microenvironmental programs that sustain immune dysfunction. At this interface, STAT3 emerges as a central organizing node. Beyond its canonical role in inflammatory and oncogenic signaling, STAT3 links tumor cell plasticity, immune suppression, and metabolic adaptation across the tumor ecosystem. In tumor cells, STAT3 promotes stemness, survival, checkpoint ligand expression, impaired antigen presentation, and immunosuppressive secretomes. In immune compartments, it drives regulatory T cell expansion, myeloid-derived suppressor cell accumulation, tumor-associated macrophage polarization, and dendritic cell dysfunction, thereby stabilizing an immune-resistant niche. STAT3 also reinforces immune escape through metabolic rewiring and multicellular feed-forward circuits. These features make STAT3 an attractive but challenging therapeutic target. Here, we discuss how STAT3 functions at the tumor-immune interface to coordinate immune escape and highlight therapeutic opportunities for targeting this axis in cancer.
Endometrial receptivity (ER) serves as a critical determinant for successful embryo implantation, yet its molecular complexity and limited clinical assessment methods pose significant challenges. Despite advancements in assisted reproductive technology (ART), recurrent implantation failure (RIF) linked to ER abnormalities persists, creating a need for precise, non-invasive diagnostics. This review outlines ER research, from the biology of the window of implantation (WOI) to the roles of immune components and the microbiome in shaping the receptive microenvironment. Multi-omics integration reveals regulatory networks across transcriptomic, epigenomic, proteomic, and metabolomic levels, with uterine fluid biomarkers emerging as promising non-invasive candidates. The analysis further covers how chronic endometritis (CE), adenomyosis, and polycystic ovary syndrome (PCOS) impair ER: through mechanisms including inflammatory imbalance, microbial dysbiosis, abnormal extracellular matrix remodeling, and hormonal dysregulation. Commercial ER tests face limitations, including insufficient evidence and inconsistent results, which undermine their clinical reliability. A significant translational gap remains between biomarker discovery and clinical application. Current challenges involve technical standardization and data integration, and poor model generalizability. Future progress requires combining multi-omics with artificial intelligence (AI) to establish standardized clinical pathways, advancing ER assessment into precision medicine, and improving global infertility management.
The thymus provides a specialized microenvironment for T cell development and selection, yet the cellular heterogeneity and molecular dynamics that govern human prenatal thymopoiesis remain incompletely characterized. We constructed an integrative single-cell atlas of human prenatal thymocytes from 7 to 23 post-conception weeks by combining five published datasets. Selection intermediates were classified based on coreceptor expression patterns. Pseudotime analysis, regulon profiling, metabolic analysis, and cell-cell communication modeling were applied to characterize developmental dynamics. We identified three transitional populations, Sel. int. DP, Sel. int. CD4, and Sel. int. CD8, positioned between DP and single-positive stages. Critically, our findings reveal that CD4/CD8 lineage commitment in the developing human thymus is not a single event, but an asymmetric, multi-stage dynamic process. This asymmetry manifests in three distinct dimensions. First, at the signaling level, Sel. int. CD4 cells exhibit enriched TCR and cytokine signaling activities compared to their Sel. int. CD8 counterparts. Second, at the temporal level, CD4 lineage traits emerge coincident with cellular activation, whereas CD8 lineage characteristics appear only after activation subsides. Third, at the microenvironmental level, Sel. int. CD8 and CD8+ T cells display the most extensive interaction networks with thymic stromal cells. Pseudotime analysis delineated two developmental paths branching at the Sel. int. DP stage toward the CD4+ and CD8+ lineages, revealing four distinct gene expression patterns encompassing activation, viral response, differentiation, and apoptotic programs. Collectively, this atlas provides a comprehensive resource for understanding the asymmetric, multi-stage dynamics of human prenatal T cell development and the cellular crosstalk that orchestrates CD4/CD8 lineage commitment.
Insulin resistance (IR) is considered a key pathogenic mechanism of peripheral artery disease (PAD). The estimated glucose disposal rate (eGDR) serves as a practical surrogate marker of IR. The study aimed to investigate the association between eGDR and incident PAD risk in the general population. A total of 456,743 participants free of PAD at baseline were included from the prospective UK Biobank cohort. In addition, we examined the cross-sectional association between eGDR and prevalent PAD among 7,208 participants from the National Health and Nutrition Examination Survey (NHANES) as a supplementary analysis. Multivariable Cox regression analysis showed that participants in the highest eGDR quartile (Q4) experienced the greatest reduction in the risk of developing PAD compared with the reference group [Q4 vs. Q1; fully adjusted hazard ratio (HR) = 0.67, 95% confidence interval (CI): 0.63-0.72, P < 0.001]. Restricted cubic spline (RCS) curve and threshold effect analysis also suggested a significant nonlinear inverse relationship between eGDR and PAD risk, with an inflection point at 7.829 (P for overall < 0.001; P for nonlinearity < 0.001). Two-piecewise Cox regression further indicated that below the threshold, an increase in eGDR was associated with a greater reduction in PAD risk (HR = 0.85, 95% CI: 0.84-0.87, P < 0.001). A similar inverse association between eGDR and prevalent PAD was observed in the NHANES analysis. eGDR was inversely associated with PAD. Further studies are needed to explore the clinical utility of this association.
Tooth morphogenesis in mice provides valuable insights into the cellular and molecular mechanisms governing organ shape. During the critical transition from the dental placode to the early cap stage (E12.5-E14.5), epithelial invagination and shape changes are accompanied by complex cellular rearrangements, including suprabasal intercalation and collective cell behaviors. This study examined how Syndecan-4 (Sdc4), focal adhesion kinase (FAK), and basement membrane-related interactions are deployed during early mandibular first molar development. We performed a stage-matched reanalysis of publicly available single-cell RNA-seq datasets, together with morphometric and spatial validation, to characterize epithelial state changes across E12.5-E14.5. At E12.5, DE-like epithelial cells displayed a proliferative odontogenic program enriched for cell-cycle regulators and key signaling pathways, including Wnt and Hippo. By E13.5, extracellular matrix components, including collagen, laminin, and agrin, together with focal adhesion-related pathways, became prominent in association with epithelial remodeling. At E14.5, upregulation of adhesion and structural scaffold components was consistent with tissue stabilization during morphogenesis. Across these stages, the data suggest a temporal shift from proliferative odontogenic activity to ECM-adhesion remodeling and then to tissue stabilization during early molar morphogenesis. Integrating the transcriptomic, morphometric, and spatial findings, we propose that an ECM-Sdc4-FAK-related signaling axis may contribute to epithelial invagination and the emergence of buccolingual asymmetry. More broadly, these findings highlight cell-matrix interactions as an important component of the early tooth morphogenetic environment, while functional perturbation studies will be needed to establish direct causality.
Loot boxes constitute a monetization mechanism integrated into many video games, which are considered as akin to gambling. Existing research indicates consistent associations among loot box engagement, addictive behaviors (such as symptoms of gaming and gambling disorders), financial problems, and psychiatric symptoms. The presence of loot boxes in video games is now widely considered as a public health concern. In Switzerland, Parliamentary Postulate 23.3004, titled "Protection against additional features in video games (microtransactions)", was submitted to the National council in 2023 and referred to the Federal council. While some jurisdictions have implemented regulatory measures, others partially delegate this responsibility to the industry, thus raising concerns about its credibility and effectiveness. Les coffres à butin, ou loot boxes, constituent un mécanisme de monétisation intégré à la plupart des jeux vidéo et possèdent des caractéristiques similaires à celles des jeux de hasard et d’argent. Les données existantes attestent de liens consistants entre l’utilisation des loot boxes, les comportements addictifs (liés aux jeux vidéo et aux jeux de hasard et d’argent), les problèmes financiers et les symptômes psychiatriques. La présence de loot boxes dans les jeux vidéo est désormais considérée comme un enjeu de santé publique. En Suisse, le postulat 23.3004 intitulé « Protection face aux fonctionnalités supplémentaires des jeux vidéo (microtransactions) » a été déposé en 2023 par le Conseil national et transmis au Conseil fédéral. Si certains États régulent, d’autres confient en partie cette tâche à l’industrie, ce qui peut entraîner une autorégulation peu efficace.
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In recent years, videogames have gathered interest in cognitive neuroscience for their potential to study cognition in dynamical and naturalistic contexts. Yet, the complexity of game environments often challenges traditional modeling approaches, and current annotation methods-typically manual or based on modified games-remain labor-intensive and limited in scope. Here, we introduce a flexible and scalable framework using the gym-retro Python library to emulate a classic action-platformer, Shinobi III: Return of the Ninja Master, and automatically annotate gameplay events directly from the game's memory states. This setup enables the identification of both player actions (e.g., jumping, hitting) and feedback events (e.g., killing an enemy, being hit), without modifying the game. Four individuals played the videogame for a combined total of 32 h (>7 h each) while undergoing functional magnetic resonance imaging (fMRI). Resulting activation maps revealed distributed engagement of visual, motor, executive, and limbic systems, consistent with the cognitive demands of gameplay. Within-participant reproducibility of brain responses across sessions was robust across event types (r ≈ .25-.55), with some consistency observed even for rarer events like HealthLoss. Between-participant correlations were notably lower, reflecting participant-specific neural signatures. Multivoxel pattern analysis showed that brain responses to different in-game events were highly discriminable, with classification accuracy typically around or above 90%, though occasionally dropping to ~40% for less frequent events. These findings demonstrate that automated emulator-based annotations enable robust, interpretable, and scalable mapping of naturalistic cognitive processes using commercial videogames.
Multiple sclerosis (MS) is a chronic neuroinflammatory disorder, and approximately 50% of MS patients develop depression, making it one of the most common comorbidities of the disease. MS-related depression significantly reduces quality of life, worsens neurological disability, and increases suicide risk. Despite its high prevalence, the underlying mechanisms remain unclear. While neuroinflammation and neurotransmitter dysregulation have been implicated, recent evidence suggests that ferroptosis, an iron-dependent form of cell death, may contribute to both neuronal death and mood disturbances in MS patients. Ferroptosis is driven by iron accumulation, lipid peroxidation (LPO), and oxidative stress, all of which are elevated in MS lesions. The inflammatory environment in MS may exacerbate ferroptosis-related processes, potentially contributing to demyelination, neuronal dysfunction, and altered neurotransmitter metabolism-factors strongly linked to depressive symptoms. This review examines the potential role of ferroptosis in MS progression and MS-related depressive symptoms, with a particular focus on oxidative damage and inflammatory signaling related to iron metabolism in the central nervous system (CNS). Understanding these mechanisms may inform future therapeutic hypotheses for MS patients suffering from depression.
Urbanization-driven, large-scale rural-to-urban migration in China has substantially modernized household energy use and reshaped air pollution exposure pathways. However, the magnitude, underlying drivers, and temporal evolution of the resulting health outcomes from combined indoor and outdoor air pollution remain insufficiently resolved. Here, by coupling a reconstruction of seven decades of migration (1949-2021) with nationwide household energy surveys, we quantify migration-attributable changes in integrated (indoor + outdoor) PM2.5 exposure and mortality. Relative to a no-migration counterfactual from 1949 onward, migration reduced integrated PM2.5 exposure by 27.6 μg·m-3 (15.7-39.4 as the 95% confidence interval) in 2019 and cumulatively avoided 2.3 (1.9-2.6) million deaths since 1949, with reductions in indoor exposure providing the dominant contribution. Arising from rural-urban disparities in household energy use, these health gains were pronounced even during intermediate stages of societal development and are likely to occur in other transitioning economies worldwide. Our study thus challenges the conventional view that rapid urbanization in developing economies is strictly detrimental to environmental health.
It has been confirmed that cholesterol-lowering therapy, particularly the reduction of low-density lipoprotein cholesterol (LDL-C) levels, represents the most effective measure for decreasing the incidence of atherosclerotic cardiovascular disease and related cardiovascular events. Previous studies have shown that active reduction of cholesterol levels significantly increases the goal attainment rate of LDL-C and improves clinical outcomes. Although many cholesterol-lowering medications are currently available in clinical practice and the cholesterol lowering treatment status has improved, the real-world cholesterol management in China, especially the goal attainment rate of LDL-C, is not satisfactory. This issue is closely related to the selection of initial cholesterol-lowering treatment strategies. Furthermore, clinical research has demonstrated that the safety and adherence of cholesterol-lowering therapy are also critical factors influencing treatment effectiveness. In response, the National Cardiovascular Disease Expert Committee Cardiovascular Metabolic Medicine Professional Committee has organized domestic experts to systematically and comprehensively review methods and scientific choices for initiating cholesterol-lowering therapy in the Chinese population and developed a Chinese expert consensus on the selection of initial cholesterol-lowering strategies based on current evidence. It aims to propose optimized initial treatment regimens tailored to individual characteristics, thereby further improving the prevention and management of dyslipidemia in Chinese population.
Pain and fever in pregnancy require treatment, but fetal safety concerns complicate analgesic choice. A recent PLOS Medicine study presents new evidence on the safety of first-trimester NSAID use and congenital malformation risk, but interpreting findings across studies is challenging.
The clinical impact of changes in the bifurcation angle throughout the cardiac cycle (BAC) after percutaneous coronary intervention (PCI) for left main coronary bifurcation lesions (LMCBLs) remains controversial, and the associated long-term evolution post-stenting remains unknown. Therefore, this study aimed to evaluate temporal changes in the BAC and the related impact on lesion progression in patients undergoing single- or dual-stenting. Proximal (PBAC) and distal (DBAC) bifurcation angles were quantified throughout the cardiac cycle using two-dimensional quantitative coronary angiography at optimal views before the procedure, immediately after, and at long-term follow-up. These measurements represented the absolute difference between the end-diastolic and end-systolic angles for the left main (LM) to the left circumflex (LCX) and for the left anterior descending (LAD) to the LCX. Lesion progression was assessed from increases in diameter stenosis percentage (iDS%) from post-procedure to follow-up. A total of 284 patients underwent single-stenting (LM-LAD), and 84 underwent dual stenting (LM-LAD-LCX). Changes in the PBAC were unaffected by interventional strategies or time. The DBAC was narrowed post-stenting in all patients, but rebounded to pre-procedural levels during follow-up in the single-stenting group. In contrast, the DBAC remained at post-procedural levels in the dual-stenting group. Lesion progression was more pronounced in patients with dual stenting, particularly in the LCX. The pre-procedural PBAC correlated linearly with the iDS%-LCX metric in the dual stenting. The PBAC remained stable over time and across strategies, whereas the DBAC decreased post-stenting. During follow-up, the DBAC rebounded in the single-stenting group but remained low in the dual-stenting group. The pre-procedural PBAC represents an independent anatomical risk marker for future LCX progression in patients with dual-stented LMCBLs.