共找到 20 条结果
暂无摘要（点击查看详情）
Rapid urbanisation in India has intensified stress on urban water systems, where inadequate sewage treatment, intermittent distribution, and fragmented governance compromise drinking-water quality across diverse city typologies. These weaknesses disproportionately affect informal settlements, increasing exposure to microbial contamination and chronic toxicants such as nitrate, fluoride, arsenic, and industrial pollutants. Beyond acute infections, growing evidence suggests that urban aquatic environments function as amplification reservoirs for antimicrobial resistance. This perspective synthesises evidence across water, sanitation, environmental surveillance, and health systems to examine how infrastructure gaps and weak integration with public health monitoring sustain preventable disease burdens. It reframes urban water quality as a public health function rather than solely a municipal service, highlighting the limits of infrastructure-centric metrics. Pragmatic interventions, including continuous pressurised supply, strengthened sewage and effluent control, integrated water-quality and disease surveillance, and explicit linkage to AMR containments, should be prioritised, with success measured through reductions in morbidity and resistance.
Limited data are available on long-term outcomes after percutaneous coronary intervention (PCI) of coronary drug-eluting stent (DES) in-stent restenosis (ISR) depending on clinical presentation with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS). Thus, the aim of this observational, retrospective study was to address this lack of evidence. Between January 2007 and February 2021, a total of 3,511 patients with 5,497 ISR lesions were treated at 2 large-volume centers in Munich, Germany, of which 1,029 (29.3%) were treated for ACS. Endpoints of interest were the rates of cardiac death, myocardial infarction (MI), repeat revascularization, and stent thrombosis (ST). Survival was analyzed using the Kaplan-Meier method. Differences between the groups were tested with the log-rank test. Conventional multivariable analysis with adjustment for relevant variables was performed. After ten years, the rates of cardiac death were 42.5% in patients with ACS and 33.3% in patients with CCS (HR 1.63 [95% CI, 1.41-1.88], p < 0.001). 17.4% of ACS patients and 9.5% of CCS patients experienced MI (HR 2.04 [95% CI, 1.65-2.50], p < 0.001). The rates of ST were 3.6% in patients with ACS and 1.2% in patients with CCS (HR 3.18 [95% CI, 1.92-5.24], p < 0.001). The rates of repeat revascularization of target lesion, target vessel and non-target vessel did not differ significantly between both groups in the long-term. In the long-term, the rates of cardiac death, MI and ST after PCI of DES-ISR are significantly higher in ACS patients than in CCS patients.
Studies support the short-term benefit of continuous positive airway pressure (CPAP) therapy on cardiometabolic risk in adults with obstructive sleep apnoea (OSA). Evidence is limited on the benefits of CPAP for preventing acute major adverse cardiovascular events (MACE). This study aimed to assess the association between CPAP use and incidence of MACE in a longitudinal clinical cohort of adults with OSA at a large U.S. healthcare system. Adults with OSA (apnoea-hypopnoea index [AHI]≥5) were identified from Kaiser Permanente Southern California between 2018 and 2020 (N = 34,782). MACE was defined as first occurrence of myocardial infarction, stroke, unstable angina, heart failure or cardiovascular death, using validated electronic health record algorithms. CPAP use (h/night) was based on daily telemonitoring data. Inverse probability of treatment weighted Cox proportional hazards models stratified by OSA severity (mild [5≤AHI<15]), moderate-severe [AHI ≥15]), were used to assess associations between CPAP use and MACE. Among individuals with moderate-severe OSA, those using CPAP <4 h/night (HR [95 % CI] = 0.53 [0.35-0.82]; p = 0.004) or ≥4 h/night (HR [95 % CI] = 0.46 [0.27-0.77]; p = 0.004) had lower MACE incidence compared to those not using CPAP. Increased CPAP use (in hours) was associated with lower MACE incidence in moderate-severe OSA (HR [95 % CI] = 0.90 [0.82-0.98]; p = 0.021). In individuals with mild OSA, CPAP use was not associated with lower MACE incidence. CPAP use was associated with lower MACE incidence in adults with moderate-severe OSA. Treatment of moderate-severe OSA may have a positive impact on prevention of MACE.
The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines produced their first edition in 1999, with subsequent revisions in 2008, 2010, 2016 and 2019. A new iteration of ARIA-ARIA 2024-2025-in collaboration with EAACI is currently being developed, focusing on the management of allergic rhinitis. ARIA 2024-2025 follows the GRADE framework and is endorsed by the European Academy of Allergy and Clinical Immunology (EAACI). A set of approaches has been used to develop guideline questions, including surveying key opinion leaders and using artificial intelligence (AI)-based tools to analyse web searches on allergic rhinitis and to generate questions. Each prioritised guideline question is assessed through an Evidence-to-Decision (EtD) framework. EtDs support the systematic and transparent formulation of recommendations, comprising 12 criteria for which the best available evidence should be sought. In the context of ARIA-EAACI 2024-2025, such evidence is derived not only from randomised controlled trials but also-among others-from patient-generated data sources that better reflect the affected individuals' perspectives. Moreover, ARIA-EAACI 2024-2025 incorporates evidence on planetary health. Developed guideline recommendations will support the creation of digitalised decision algorithms and care pathways. This paper describes the methodology used to develop the person-centred, digitally enabled and AI-assisted ARIA-EAACI 2024-2025. Among others, it describes (i) the development and prioritisation of guideline questions, (ii) sources of evidence for EtDs and (iii) the development of digitalised decision algorithms and care pathways.
The incidence of oropharyngeal cancer (OPC) is increasing. Thus, there is a need for biomarkers that can identify high-risk patients and support personalised treatment. This study investigated the prognostic significance of circulating microRNAs (miRNAs) for progression-free survival (PFS) and overall survival (OS) in patients with OPC undergoing radiotherapy (RT). The expression of 20 circulating miRNAs was analysed in serum samples collected both before and after RT as a possible prognostic marker in patients treated for OPC. We analysed 80 patients with OPC treated with curative-intent RT. The median PFS was 42.9 months (95%CI: 25.6 - not reached), and the median OS was 63.7 months (95%CI: 33.9 - not reached). In univariate analysis, higher pre-treatment levels of miR-21-5p (HR: 2.12, 95%CI: 1.34-3.36) and miR-148a-3p (HR: 1.38, 95%CI: 1.03-1.85), as well as lower post-treatment levels of miR-345-5p (HR: 0.61, 95%CI: 0.41-0.90), were associated with worse survival. These associations remained significant in multivariable analysis adjusted for clinical factors. A combined risk model based on pre-RT miR-21-5p and post-RT miR-345-5p identified a high-risk group with significantly shorter PFS (HR: 3.01, 95%CI: 1.27-7.14) and OS (HR: 3.19, 95%CI: 1.25-8.15) compared with the low-risk group. High pre-RT hsa-miR-21-5p and low post-RT hsa-miR-345-5p were both independently associated with inferior PFS and OS. These results support the clinical relevance of integrating dynamic miRNA profiling into risk-stratification frameworks and may potentially inform more personalised strategies for post-RT monitoring in OPC patients.
High-intensity 5 km running offers an ideal framework to analyze the organism's multidimensional responses. Since previous research primarily analyzed isolated aspects of fatigue, this study aimed to examine the integrated acute neuromuscular, metabolic, and perceptual responses to a 5 km run. Twenty-one recreational male runners participated. Pre- and post-race assessments included body composition, blood lactate, m. rectus femoris ultrasound thickness, quadriceps maximal voluntary isometric contraction (MVIC), heart rate, perceived exertion (Borg CR10), and 5 km finish time. Statistical analysis was performed in the Jamovi software, utilizing descriptive statistics, the Shapiro-Wilk test of normality, the Wilcoxon signed-rank test with effect size calculation, and Spearman's correlation coefficient, at a significance level of p < 0.05. Post-race measurements revealed a significant decrease in quadriceps MVIC (pre: 305 ± 99 N vs. post: 259 ± 88 N; p = 0.002) and an increase in blood lactate (pre: 0.8 ± 0.4 vs. post: 6.9 ± 1.4 mmol/L; p < 0.001), alongside high average heart rates (165 ± 16 bpm). However, ultrasound-assessed muscle architecture remained unchanged. The 5 km run induced pronounced neuromuscular and metabolic fatigue. Unchanged muscle architecture suggests that acute strength decline is primarily mediated by metabolic and neural mechanisms, rather than immediate structural-morphological factors. These findings highlight the value of an integrated assessment approach for understanding acute fatigue responses following high-intensity 5 km running and may contribute to more precise training-load prescription and recovery monitoring in recreational runners.
Background: Idiopathic hypereosinophilic syndrome (iHES) is a rare disorder of persistent hypereosinophilia with secondary organ damage, but the full spectrum of organ involvement and the constitutional-symptom burden under systematic ascertainment remain incompletely characterised. Objectives: To describe the clinical phenotype of iHES in a large single-centre cohort, with attention to symptoms typically under-reported in observational series. Methods: We followed 72 consecutive patients with iHES at a tertiary referral centre between January 2017 and May 2025. Defined HES variants were excluded by FIP1L1-PDGFRA RT-PCR and aberrant T-cell phenotyping on flow cytometry; secondary causes were excluded clinically. Each potential organ manifestation was systematically assessed at every visit using a structured clinician-administered checklist. Wilson 95% confidence intervals (CIs) are reported for all proportions. Results: Median age at diagnosis was 45 years (interquartile range [IQR] 31-58); 83% were female. The median number of involved organ systems was 3 (IQR 2-4, range 1-6). Pulmonary (91.7%, 95% CI 83.0-96.1), sinonasal (75.0%, 95% CI 63.9-83.6), musculoskeletal (72.2%, 95% CI 61.0-81.2) and gastrointestinal (66.7%, 95% CI 55.2-76.5) involvement predominated. Constitutional symptoms-principally fatigue-were recorded in 97% of patients (95% CI 90.4-99.2) and tracked clinically with disease activity. Cardiac involvement was infrequent (8.3%, 95% CI 3.9-17.0) but uniformly severe. Conclusions: Under systematic symptom probing, constitutional features and pulmonary/sinonasal involvement were recorded more frequently in this single-centre idiopathic HES cohort than in earlier series that pooled HES variants. However, selection bias from a pulmonology and severe-asthma referral pattern, together with differences in symptom ascertainment, likely contributes to these estimates and limits their generalisability to the broader iHES population. Routine echocardiographic screening and structured assessment of fatigue and cognitive symptoms should be incorporated into iHES monitoring.
Background/Objectives: Asthma therapy aims to achieve asthma control, defined as reduced or absent symptoms, no exacerbations and a minimized risk of future untoward outcomes imposed by either the disease or drug side effects. The study aimed to assess the effectiveness and general clinical safety of shifting from medium- to high-dose BDP/FF in a fixed-dose pMDI extra-fine combination as maintenance therapy in patients with poor asthma control despite regular use of a medium-dose fixed formulation of BDP/FF in a real-world setting. Methods: BREATH was a multicenter, noninterventional, prospective, real-world based observational study enrolling 93 patients with poor asthma control (ACQ-5 ≥ 1.5) and not meeting Global Initiative for Asthma (GINA) clinical criteria for asthma control despite regular medium-dose BDP/FF use, for whom the treating physician decided to shift to regular high-dose BDP/FF and who were followed for 12 weeks at monthly visits. Adherence/compliance with inhaler therapy, asthma exacerbations and asthma-related emergency visits/hospitalizations were monitored. Results: The overall asthma control in the study group improved significantly and progressively, with the mean ACQ-5 score decreasing from 2.8 (SD 0.7) to 0.7 (SD 0.7) points. Visit-to-visit ACQ-5 reductions were significant up to 8 weeks after study entry. The percentage of patients who demonstrated clinically significant improvement in the ACQ-5 score reached 94.4%, with 61.8% fulfilling the ACQ-5 criteria for controlled asthma (58.4% for the GINA clinical criteria). Conclusions: Shifting from medium to high doses of BDP/FF in a fixed-dose combination of pMDI and extra-fine BDP/FF in patients who remain symptomatic despite regular medium-dose BDP/FF therapy may improve short-term asthma control.
Multiple studies have shown that symptom-based subtypes of obstructive sleep apnea (OSA) exist and are generalizable to clinical and population-based samples of different race/ethnic and regional backgrounds. However, there have not been studies evaluating the generalizability within a clinical sample of Chinese ancestry. Thus, the aim of the current study was to investigate the generalizability of symptom-based subtypes within clinical patients from China. This is a cross-sectional, multi-center study of patients with OSA from international sleep centers participating in the Sleep Apnea Global Interdisciplinary Consortium (SAGIC). Two Chinese cohorts were collected: 666 patients from Peking University People's Hospital (PKUPH) and 503 patients from other China sites (Peking University International Hospital, Taiwan, and Shanghai). In addition, 694 White patients were included from 7 sites across 5 countries (Iceland, Germany [Berlin], Australia [Sydney, Perth], Brazil, and the United States [Ohio State University and University of Pennsylvania]). Symptom-based subtypes were determined using a latent class analysis (LCA) of 18 self-reported symptom variables and 3 comorbidities. A total of 1,863 patients were included in the LCA. The previously described 5 symptom subtype (disturbed sleep, minimal symptoms, excessively sleepy, moderately sleepy, and upper airway symptoms dominant) were optimal in the PKUPH site, other China sites, and White patients from SAGIC. Chinese patients had higher prevalence of the minimal symptoms subtype (P < .001) compared to White patients. Among the five subtypes, the excessively sleepy subtype exhibited the highest AHI, and ODI. : Based on the included symptoms and comorbidities, five subtypes provided the optimal groupings across both Chinese and White patients in SAGIC. Chinese patients were more likely to present with fewer symptoms. These data further enhance understanding of the generalizability of OSA symptom subtypes across ethnically diverse backgrounds, and pave the way for precision management of OSA in the future.
Lights and sirens (L&S) during Emergency Medical Services (EMS) transport may shorten transport times and improve outcomes in acute stroke but carry significant roadway risk. This study assesses L&S and in-hospital stroke care, including door-to-CT, door-to-intravenous thrombolysis (IVT), door-to-endovascular thrombectomy (EVT), and discharge disposition. This retrospective cohort study analyzed data from 2020 to 2022, including adult patients identified by EMS as having suspected stroke and who had a final diagnosis of stroke or transient ischemic attack. Data were collected from the IMPACT network (70 EMS agencies, 30 hospitals, 2 states). Multivariable regression modeled the association between L&S and door-to-CT, door-to-IVT, and door-to-EVT times, controlling for confounders. Logistic regression modeled the association between L&S and discharge disposition, adjusting for confounders and in-hospital intervention. Of 3,161 patients, 75.4% (n = 2384) were transported with L&S. Transport time with L&S was shorter than without (geometric mean 8.9 minutes [95% CI 8.7-9.1] vs 11.6 minutes [95% CI 11.0-12.1], p < .001). L&S were associated with shorter door-to-CT (ratio estimate, 0.51; 95% CI, 0.46-0.56), but not with door-to-IVT (ratio estimate, 0.94; 95% CI, 0.82-1.08) nor door-to-EVT (ratio estimate, 1.03; 95% CI, 0.76-1.39). L&S were not associated with improved discharge outcomes. While L&S were associated with faster door-to-CT times, they did not shorten time to IVT or EVT or improve discharge outcomes. These findings suggest that perceived urgency of L&S may prompt quicker imaging, but transport time savings are minimal and may not improve outcomes. Alternative EMS prenotification and hospital activation strategies merit consideration.
[This corrects the article DOI: 10.1016/j.ctro.2024.100801.].
Stroke is a significant cause of morbidity and mortality. There are racial, ethnic, and sex-based disparities in treatment and outcomes for patients with stroke. This study determined the association between race, ethnicity, and sex and prehospital stroke identification and discharge disposition. This was a multi-center, retrospective analysis of adult acute stroke patients presenting via Emergency Medical Services (EMS) between 01/01/2020 and 12/31/2022 who met criteria for inclusion into the local Get with the Guidelines - Stroke registry. Multivariable logistic regression modeled the association between sex, race, and ethnicity and EMS impression, adjusting for age, demographics, stroke severity, presentation with classic stroke symptoms, and EMS agency type (urban, suburban, or rural). Multivariable regression modeled discharge disposition, controlling for receiving hospital stroke certification, cardiovascular risk factors, acute intervention, and the above covariates. A total of 3,749 (83.5%) patients were identified with suspected stroke by EMS. After adjusting for covariates, males had greater odds of identification as a stroke compared to females (adjusted odds ration [aOR] 1.26, 95% CI 1.08-1.47); non-White patients had similar odds of identification as a stroke patient compared to White patients (aOR 1.00, 95% CI 0.55-1.82). Males also had higher odds of dying in hospital or being discharged to hospice compared to females (aOR 1.43, 95% CI 1.08-1.88). Male patients were more likely recognized as stroke by prehospital clinicians but had greater odds of a poor discharge disposition. Additional research into causes of these disparities in prehospital stroke identification may improve prehospital patient care and change ultimate outcomes.
Oral and ocular medications are frequently used in the treatment of allergic rhinitis (AR). As part of the update of the Allergic Rhinitis and its Impact on Asthma (ARIA)-EAACI guidelines, this manuscript presents the ARIA-EAACI 2024-2025 recommendations for oral and ocular treatments. The ARIA-EAACI 2024-2025 guideline panel issued recommendations following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence-to-decision framework. Several sources of evidence were used to inform panel judgements and recommendations, including systematic reviews, mHealth and pharmacovigilance data as well as a survey on costs. Eight guideline questions concerning oral treatments for AR and three questions concerning ocular treatments were addressed. These questions led to the recommendations. Overall, these questions concern the choice between different classes of medication. They also discuss the role of oral antihistamines (OAH), leukotriene receptor antagonists (LTRA), ocular antihistamines (OcAH) and ocular mast cell stabilisers. Four questions had not been previously evaluated in ARIA guidelines, while, for the other four, there was a change in the strength or directionality of the recommendations. Overall, these guidelines recommend using intranasal corticosteroids over OAH and using OAH over LTRA. Moreover, they suggest using OAH over OcAH and suggest being against adding LTRA to OAH. Finally, considerations for choosing between different individual OAHs are presented. This ARIA-EAACI 2024-2025 article supports patients, their caregivers and healthcare professionals in choosing oral and ocular treatments for AR. Decisions on treatment should consider the clinical variability of the disease, patients' values and the affordability of medications.
Placenta enriched 1 (PLAC1) is a conserved X chromosome-linked gene expressed in the mammalian placenta. We investigated the biology of PLAC1 in the rat and human placenta. Plac1 transcripts were expressed in the junctional zone of the rat placenta and in intrauterine invasive trophoblast cells. Genome-edited Plac1 mutant animals exhibited placentomegaly. Enlarged placentas were characterized by an expanded junctional zone, an irregular junctional zone-labyrinth zone boundary, a deficiency of intrauterine invasive trophoblast cells, and a late-gestation-stage uterine-placental interface infiltrated with natural killer cells. PLAC1 facilitated rat trophoblast cell differentiation. In contrast, PLAC1 showed minimal contributions to the regulation of the human invasive/extravillous trophoblast cell lineage, but instead PLAC1 expression and actions were linked to syncytiotrophoblast differentiation. Furthermore, the impact of PLAC1 on cellular function is linked to furin (paired basic amino acid cleaving enzyme) in rat and human trophoblast cells. Thus, PLAC1 plays an important role in hemochorial placentation; however, the responsive trophoblast cell lineages and its contributions to placentation are fundamentally distinct in the rat versus human.
Background: Innovative training strategies aimed at improving physiological efficiency are of growing interest in kinesiology and sports performance. Elevation training masks (ETMs) offer a practical means of inducing hypoxia-like stress. However, evidence of their effectiveness in recreationally active populations remains limited. This pilot study examined the efficiency of a five-week progressive ETM protocol combined with high-intensity interval training (HIIT) in eliciting physiological, hematological, and body-composition adaptations relevant to endurance performance. Methods: Nine recreationally active men completed a five-week intervention consisting of three treadmill-based sessions per week: one weekly incremental Conconi test and two structured aerobic-anaerobic HIIT sessions performed with an ETM. Mask resistance was progressively increased to simulate altitudes of approximately 900-3600 m. Hematological variables (erythrocytes, hemoglobin, hematocrit, erythrocyte indices, leukocytes, and platelets), body composition, maximal heart rate (HRmax), and peripheral oxygen saturation (SpO2) were assessed pre- and post intervention. Data were analyzed using paired-sample t-tests and repeated-measures ANOVA, with effect sizes reported (Cohen's d, ω2). Results: A significant main effect of time on SpO2 was observed (F(1, 8) = 130.61, p < 0.001, ω2 = 0.69), along with a significant effect of training week (F(4, 32) = 17.41, p < 0.001, ω2 = 0.43), and a significant Time × Week interaction (F(4, 32) = 15.20, p < 0.001, ω2 = 0.42), indicating progressively greater post-exercise oxygen desaturation with increasing simulated altitude. Significant post-intervention increases were found in erythrocyte count, hemoglobin concentration, and hematocrit (p ≤ 0.009, d = 1.15-1.55), alongside increases in mean corpuscular volume and mean corpuscular hemoglobin. Platelet count increased significantly (p = 0.001, d = 1.68), while leukocyte values remained unchanged (p > 0.05). Body mass index (p = 0.049, d = 0.77) and body fat percentage (p = 0.012, d = 1.08) decreased following the intervention. HRmax tended to be lower at higher simulated altitudes. Conclusions: A five-week progressive ETM-HIIT protocol efficiently induced hematological and body-composition adaptations associated with improved oxygen transport and metabolic efficiency in recreationally active men. These findings support ETM-based training as an accessible strategy for enhancing physiological efficiency in endurance-oriented kinesiology practice, warranting confirmation in larger randomized controlled studies.
Precision nutrition aims to tailor dietary guidance to individual biology, yet current methods struggle to integrate complex molecular and multiomic data into clinical care. Emerging quantum-driven technologies encompassing quantum computing, quantum chemistry, and quantum-enhanced sensors link detailed molecular modeling with real-time metabolic forecasting. Quantum chemical simulations and machine learning model nutrient-protein interactions at the atomic level, whereas quantum algorithms and echo-state networks have been applied to create digital metabolic avatars that predict weight and metabolic trajectories from daily diet and activity data. Quantum computing enables rapid integration of genomic, metabolomic, and microbiome datasets and supports optimization of personalized diet plans. Advances in computational molecular modeling now allow prediction of molecular structures and properties relevant to food components, and prototype quantum metabolic twins have demonstrated the capacity to forecast weight trends from incomplete real-world data. The clinical implications include proactive dietary interventions, noninvasive nutrient deficiency screening, and improved prediction of disease risk from metabolic profiles, all of which can enhance patient outcomes and clinical decision-making. This perspective synthesizes recent advances and delineates research directions at the intersection of quantum science, medical diagnostics, metabolism, and clinical nutrition, with implications for clinicians, physicians, dietitians, and clinical decision support in patient care.
暂无摘要（点击查看详情）
Adrenomedullin (ADM) is a peptide hormone with a broad spectrum of actions on vascular smooth muscle, endothelial cells, and immune cells. These ADM cellular targets are prominent constituents of the uterine-placental interface that undergo structural and functional transformation during pregnancy. To explore the biology of ADM at the uterine-placental interface, we examined ADM expression using in situ hybridization and generated and characterized an ADM mutant rat model using CRISPR-Cas9-mediated genome editing. At midgestation, Adm was prominently expressed in trophoblast giant cells. Adm expression shifted to the mesometrial uterus as gestation progressed. A germline Adm mutant model was generated. Adm heterozygous males and females were fertile; however, Adm heterozygous intercrosses did not generate live Adm null rats. Adm null fetal-placental sites were viable until gestation day (gd) 15.5. Viable null fetuses were not identified after gd 15.5. Fetal and placental growth restriction were evident on gd 13.5. On gd 15.5 some Adm null placentas exhibited prominent hemorrhagic regions, whereas both hemorrhage and edema were evident in gd 15.5 Adm null fetuses. Our results indicate that ADM serves as a regulator of placental and fetal development.
暂无摘要（点击查看详情）