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Effect of a 6-month low-carbohydrate diet on the circulating fatty acid composition in patients with type 2 diabetes: a secondary analysis of an open-label randomized controlled trial.

BACKGROUND: Circulating fatty acid profiles are linked to cardiovascular disease risk and mortality. Short-term interventions suggest that low-carbohydrate diets (LCDs) promote cardioprotective shifts in circulating fatty acids in obesity. OBJECTIVES: We examined whether a 6-mo, non-calorie-restricted, LCD high in fat similarly improves circulating fatty acid composition in adults with type 2 diabetes. METHODS: In an open-label, randomized, controlled trial, 71 individuals with type 2 diabetes were randomly assigned 2:1 to an LCD [maximum of 20 E% (energy per cent) carbohydrates] or a control diet (50-60 E% carbohydrates) for 6 mo with no restriction in energy intake. The prespecified secondary outcomes were the mean difference in change between groups in serum phospholipid fatty acids in weight percentage (wt%) measured by gas chromatography and reported as 95% confidence intervals (CIs) and significance adjusted for multiple comparisons (q value). RESULTS: LCD reduced total saturated [-0.6 (CI: -0.9, -0.2)] and monounsaturated fatty acids [-0.9 (CI: -1.4, -0.3)] and increased total polyunsaturated fatty acids [1.3 (CI: 0.6, 2.0)] compared with the control diet (all q < 0.05). Importantly, LCD reduced palmitoleic acid (16:1n-7) [-0.13 (CI: -0.21, -0.06)], a marker of de novo lipogenesis, by 23% and dihomo-&#x3b3;-linolenic acid (20:3n-6) [-0.38 (CI: -0.67, -0.09)] by 12%, whereas it increased arachidonic acid (20:4n-6) [1.1 (CI: 0.3, 2.0)] by 9% compared with the control diet (all q < 0.05). Moreover, the LCD improved estimated desaturase activities by lowering stearoyl-coenzyme A desaturase 1 [-0.5 (CI: -0.7, -0.2)] and &#x394;6 desaturase [-0.6 (CI: -0.9, -0.2)] and increasing &#x394;5 desaturase [1.05 (CI: 0.3, 1.79)] activities, respectively (all q < 0.01). These changes occurred despite a 2.6-fold higher intake of saturated fatty acids in the LCD group. CONCLUSIONS: A 6-mo, non-calorie-restricted LCD modified the circulating composition of fatty acids in adults with type 2 diabetes in a manner consistent with a potentially favorable cardioprotective profile. This trial was registered at www. CLINICALTRIALS: gov as NCT03068078.

Humans

Activity shapes large herbivores' ecological influences.

The ecological effects of large herbivores are shaped by their spatial and temporal patterns of activity (i.e. where, when and how intensely they use specific locations). When large herbivores' ecological influences are perceived to be undesirable, the traditional approach has been to reduce their population size. This numbers-first logic assumes that ecological effects scale primarily with abundance. We argue that this framing provides an incomplete understanding of large herbivores' ecological impacts. Using African elephants (Loxodonta africana) as a well-documented case study, we show that ecological effects on plants, animals and ecosystem processes correlate more with spatio-temporal patterns of activity than with population size. In large, open systems characterized by strong gradients of water availability, forage quality, shade and risk, elephants concentrate into predictable hotspots while relaxing activity elsewhere, generating localized impacts and opportunities for recovery. By contrast, in small, fenced or fragmented landscapes, where movements are constrained, and gradients are weak, spatial self-regulation breaks down, producing homogenized use and widespread ecological effects. We contend that understanding where, when and under what constraints herbivores use space provides a more general and mechanistic basis for interpreting ecological influence than abundance alone, with implications that extend beyond elephants to large herbivores globally.

Animals

ESC quality indicators for post-myocardial infarction care: transition and chronic coronary syndrome phases.

AIMS: We aimed to develop the European Society of Cardiology (ESC) quality indicators (QIs) for myocardial infarction (MI), from 1 year after hospital discharge, corresponding to transition to the chronic coronary syndrome phases. METHODS AND RESULTS: We collaborated with the European Association of Preventive Cardiology (EAPC) and developed QIs for the long-term management of patients following MI. We applied the ESC methodology for QI development by (i) determining key domains of post-MI care; (ii) developing candidate QIs by performing a systematic review of the literature, and (iii) selecting the final set of QIs using a modified Delphi approach. In total, 18 QIs were identified across seven domains of care including (i) structural framework, (ii) risk assessment and follow-up, (iii) pharmacological management, (iv) rehabilitation, behavioural, and preventive interventions, (v) coronary revascularization, (vi) clinical outcomes, and (vii) patient-reported outcomes. CONCLUSION: We present the ESC QIs from 1 year after hospitalization for MI, to standardize and address gaps in care for this high-risk group. These QIs are supported by evidence from contemporary literature, endorsed by expert consensus, and aligned with the 2024 ESC guidelines on the management of chronic coronary syndromes. LAY SUMMARY: Measures to evaluate and improve the long-term management of patients following a heart attack are needed. In this paper, we identified key aspects of care that can help clinicians, decision-makers and patients improve the quality of care, from one year after a heart attack onwards, and help address inequalities and variations in clinical practice.

Humans

Distress Intolerance, Social Anxiety, and Depressive Symptoms in Adolescents: Evidence from Random-Intercept Cross-Lagged Panel and Cross-Lagged Panel Network Analyses.

Social anxiety and depressive symptoms frequently co-occur during adolescence, yet the mechanisms underlying their longitudinal associations remain insufficiently understood. Distress intolerance has been proposed as a transdiagnostic risk factor implicated across internalizing symptoms. However, it remains unclear whether distress intolerance is predicted by social anxiety and depressive symptoms, as well as the underlying mechanisms among these three constructs. The specific symptoms most centrally involved in these cross-domain associations remain poorly understood. The present study investigated the longitudinal associations among distress intolerance, social anxiety, and depressive symptoms using a dual-method framework combining random-intercept cross-lagged panel models (RI-CLPM) and cross-lagged panel network (CLPN) analyses. A total of 1,378 Chinese adolescents (Mage = 12.57, SDage = 0.63; 50.4% female) were assessed at three time points with six-month intervals between waves. The RI-CLPM analyses revealed that higher distress intolerance prospectively predicted subsequent increases in both social anxiety and depressive symptoms, whereas elevated social anxiety and depressive symptoms in turn predicted subsequent increases in distress intolerance. Moreover, distress intolerance mediated the longitudinal associations between social anxiety and depressive symptoms. Additionally, distress intolerance was also indirectly associated with its own subsequent levels through social anxiety and depressive symptoms. The CLPN analyses revealed that fear of negative evaluation and fatigue were the strongest predictors of other network nodes from T1 to T2 and from T2 to T3, respectively. In contrast, distress intolerance symptoms were predominantly predicted by other nodes in both cross-lagged networks. These findings extend prior views of distress intolerance as a unidirectional vulnerability by showing that distress intolerance is also predicted by social anxiety and depressive symptoms and accounts for part of their longitudinal associations across adolescence.

Humans

Female genital mutilation knowledge, attitudes and training needs among health professionals in non-practicing countries: A literature review.

BACKGROUND: With increasing globalization and migration, the number of women affected by female genital mutilation who reside in countries where the practice is not traditionally performed is constantly increasing. Healthcare providers in these settings are required to address the complex health needs of this vulnerable population. We aimed to synthesize recent literature on their knowledge, preparedness, and educational background. METHODS: We conducted a systematic review across PubMed, Scopus and Embase, identifying papers published from January 2015 onwards, examining providers' knowledge, education and attitudes toward female genital mutilation in non-practicing countries. Both quantitative and qualitative observational studies were eligible. Given heterogeneity in study populations, outcome definitions, and assessment tools, findings were synthesized narratively. The review protocol was registered with the International Prospective Register of Systematic Reviews (CRD420251044761). FINDINGS: 1046 records were screened by title and abstract, and 140 full-text articles were assessed for eligibility. 31 studies met the inclusion criteria (23 quantitative, 8 qualitative). Many providers reported clinical experience with women affected by female genital mutilation, yet substantial variability was observed in knowledge, training, and attitudes. Gaps were particularly evident regarding legislation, World Health Organization classification, clinical guidelines, referral pathways, workplace protocols. Midwives and younger professionals tended to demonstrate higher knowledge levels. Training exposure ranged from 5% to 91%, and many participants perceived it as insufficient. Qualitative findings echoed these patterns, highlighting challenges in female genital mutilation classification, legal awareness, documentation systems, the impact of providers' cultural beliefs on care delivery. CONCLUSION: Considerable efforts are needed to equip healthcare providers to deliver high-quality, culturally competent care to women affected by female genital mutilation. Research should develop validated tools to assess preparedness, adopt mixed-methods strategies to capture patient and provider perspectives, and guide standardized, up-to-date training programs, strengthening knowledge in managing female genital mutilation.

Humans

Cationic porphyrin covalent organic framework reinforced hydroxypropyl methylcellulose films for photodynamic-photothermal sterilization and food preservation.

Microbial contamination in food necessitates effective antimicrobial packaging. While cellulose-based packaging materials suffer from limited antimicrobial efficacy, lack of active functionality, and susceptibility to inducing microbial resistance. To address these challenges, this study synthesized a cationic porphyrin-based covalent organic framework (Por-ICOF) as a multimodal photosensitizer. Por-ICOF was uniformly dispersed via non-covalent interaction within hydroxypropyl methylcellulose (HPMC), creating an HPMC/Por-ICOF composite film. This integration enhanced mechanical strength (increased by 26%), hydrophobicity (WCA 71&#xb0;), and gas barrier properties (OP reduced by 42%, WVP reduced by 36%). Under visible light, the HPMC/Por ICOF film superior absorption generated reactive oxygen species (ROS) and photothermal effects, inactivating 99.2% of Escherichia coli and 99.95% of Staphylococcus aureus within 20&#xa0;min. The composite film exhibited excellent biocompatibility and effectively extended the shelf life of strawberries. This cationic modification strategy for cellulose-based films offers a novel avenue for the design of high-performance antimicrobial food packaging materials.

Food Preservation

Assessing the accuracy and efficiency of an electronic platform for managing childhood illnesses in rural China: A cluster randomized controlled trial.

OBJECTIVES: The Integrated Management of Childhood Illness (IMCI) faces challenges in capacity building and quality control. This trial aims to assess an electronic IMCI (eIMCI) platform in improving the effectiveness and efficiency in disease classification and management by community health workers (CHWs). DESIGN: Cluster randomized controlled trial. SETTING: Rural western China. PARTICIPANTS: 24 CHWs and 72 ill children aged 2 months to 5 years (3 children per CHW). CHWs were randomly assigned to intervention or control groups. INTERVENTIONS: The intervention CHWs received online training and performed disease management using the eIMCI platform featuring integrated training modules and decision-support tools. The control group received traditional face-to-face training and used paper-based IMCI protocols. MAIN OUTCOME MEASURES: Proportion of children correctly diagnosed or classified by CHWs, as determined by a pediatric specialist. Relative risk (RR) between groups was estimated using Poisson Generalized Linear Mixed Models incorporating a random intercept for CHW to account for clustering of children within individual CHWs and adjusting for key covariates at both the CHW and child levels. RESULTS: The intervention group (13 CHWs, 39 children) had a higher rate of correct classification (64.1%) compared to the control group (11 CHWs, 33 children) (39.4%, P&#x2009;=&#x2009;.056). Multivariable regression analysis confirmed this (RR&#x2009;=&#x2009;2.1, 95% CI: 1.5-3.1; P&#x2009;<&#x2009;.001). No significant difference was found in correct treatment rates (38.5% vs. 27.3%, P&#x2009;=&#x2009;.316). Online training reduced time and costs by approximately 80%, though with a slight decrease in post-training evaluation scores. CONCLUSIONS: The eIMCI platform shows potential in enhancing IMCI implementation and significantly reducing the training burden in resource-limited settings. Trial registration: Chinese Clinical Trial Registry: ChiCTR2100042533, https://www.chictr.org.cn/showproj.html?proj=119995.

Humans

Fasting-refeeding regimes induce compensatory growth and muscle transcriptomic remodeling in juvenile Qihe gibel carp (Carassius gibelio var. Qihe).

Compensatory growth, an important adaptive response in fish, holds considerable potential for improving feeding efficiency in aquaculture. To identify an optimal fasting-refeeding strategy for juvenile Qihe gibel carp (Carassius gibelio var. Qihe) and to clarify the mechanisms underlying the compensatory growth, we divided two-month-old fish into four groups, namely S0 group (continuous feeding for 28&#xa0;days), S2 group (4&#xa0;cycles of 2-day fasting followed by 5-day refeeding), S4 group (fasting for 4&#xa0;days followed by refeeding for 24&#xa0;days), and S8 group (fasting for 8&#xa0;days followed by refeeding for 20&#xa0;days), then growth performance, muscle tissue morphology, biochemical responses, and muscle transcriptomic profiles under different feeding regimes were investigated. After a 28-day aquaculture experiment, fish in the S4 group exhibited significantly greater body length and weight than those in the S0, S2, and S8 groups, indicating over-compensatory growth. Histological analysis further showed that muscle growth in the S4 group was mainly associated with myofiber hyperplasia. Different feeding regimes also induced distinct changes in hepatic antioxidant and metabolic enzyme activities, as well as intestinal digestive enzyme activities. Transcriptome analysis revealed that the forkhead box O (FoxO) signaling pathway was significantly enriched during compensatory growth. Key genes, including serum/glucocorticoid regulated kinase 1 (sgk1) and insulin receptor substrate 1 (irs1), were predicted to play important roles in this process. Overall, these results indicate that fasting for 4&#xa0;days followed by refeeding for 24&#xa0;days (the S4 regime) is the optimal strategy for inducing compensatory growth in juvenile Qihe gibel carp. This study provides new insights into the morphological, physiological, and molecular basis of compensatory growth and offers a scientific foundation for developing efficient and sustainable feeding strategies for this species.

Animals

Home-Based Cardiac Rehabilitation Using a Smart Ring and Telephone Counselling: A Randomized Controlled Trial.

BACKGROUND: Home-based cardiac rehabilitation (HB-CR) is a promising alternative to center-based cardiac rehabilitation as it can address several barriers impeding CR implementation because of its enhanced accessibility. However, to date, HB-CR has not garnered adequate attention due to a lack of communication between patients and medical staff. In this study, we aimed to investigate the effectiveness of HB-CR by monitoring the pulse rate (PR) using a smart ring equipped with photoplethysmography. METHODS: Patients with cardiovascular disease were educated on structured HB-CR methods following a symptom-limited cardiopulmonary exercise test (CPET), and were instructed to wear the device during the exercise session. The recorded PR was uploaded to a website via a smartphone and monitored by medical staff. Patients were randomly assigned to one of two groups: intervention or control group. The intervention group received weekly telephone counselling and was encouraged to maintain optimal levels of physical activity. In contrast, the control group only recorded their exercise data without additional interventions. After 3 months of training, the CPET was performed. RESULTS: Among the 64 randomized patients (32 in each group), an intention-to-treat analysis showed that peak oxygen consumption increased over time in both the groups, with a significantly greater improvement in the intervention group. The group-by-time interaction for peak oxygen consumption was statistically significant (estimated mean difference, 2.0 mL/kg/min; 95% confidence interval, 0.7-3.3; P = 0.004). CONCLUSION: HB-CR using a smart device was effective in improving oxygen consumption. However, appropriate monitoring and timely counselling by medical professionals are important for improved outcomes. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0005893.

Humans

Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.

Ionic functionalization of biomaterial coatings has emerged as a powerful strategy to regulate early host responses at the implant interface. However, how combined Ca/Sr incorporation governs the adsorbed proteome and downstream immune signaling remains poorly understood. This study analyses, employing in vitro tests and proteomics, the effect of adding Sr and Ca to Si-based coatings designed to bioactivate Ti implants. Hybrid Si-based coatings were synthesized by the sol-gel route with a fixed Ca content (0.5&#x202f;wt%) and increasing Sr contents (0.5, 1.0, 1.5&#x202f;wt%), and their physicochemical properties, ion release kinetics, and hydrolytic stability were characterized. The coatings remained highly crosslinked despite Ca/Sr incorporation, whereas the highest Sr content increased hydrolytic degradation to around 70% after 56 days. Proteomic analysis identified 183 adsorbed proteins, of which 56 were differentially adsorbed on Ca/Sr-coatings, mainly associated with immune and coagulation pathways. In vitro, RAW 264.7 showed increased gene expression of TNF-&#x3b1; and TGF-&#x3b2;; with an enhanced TNF-&#x3b1; secretion by the addition of Ca and Sr. In parallel, MC3T3-E1 indicated that Ca/Sr-coatings were not cytotoxic and did not impair cell proliferation. However, ALP activity was reduced in the co-doped groups, indicating that the immunomodulatory effects induced by Ca/Sr incorporation were not accompanied by enhanced early osteogenic differentiation. The Ca/Sr combination induced alterations in the adsorption of immune-related proteins, which correlated with the in vitro findings. The deeper insight into how Ca/Sr mixtures modulate protein adsorption on biomaterial surfaces may be key to understanding the immunomodulatory capacity of these bioactive cations.

Animals

Oxidative potential of fresh vs. O&#x2083;-aged PM2.5 across urban and rural sources in China.

Fine particulate matter (PM2.5) is a major health risk, yet its impacts are still largely assessed using mass concentration, which does not capture toxicity. Recently, oxidative potential (OP) has emerged as a more relevant metric, reflecting the ability of particles to generate reactive oxygen species. A current challenge, especially in China, is understanding how emission sources and ozone (O3) aging affect PM2.5 toxicity, given that O3 is an increasingly important pollutant there. A work by Ma and co-workers published in J. Environ. Sci. (doi.org/10.1016/j.jes.2024.04.023) addressed this by evaluating the OP of fresh and O3-aged PM2.5 from multiple sources in China using the dithiothreitol (DTT) assay. Biomass burning particles exhibited the highest OP, up to 35 times greater than suburban PM2.5, driven by water-soluble organics and transition metals. While O3 aging generally reduced OP, it also induced complex chemical transformations. These findings highlight that PM2.5 toxicity is dynamic and source-dependent, underscoring the need to move beyond mass-based air quality metrics.

Particulate Matter

Phase 1 Study Evaluating Gefurulimab Pharmacokinetics and Safety Following Delivery Via Autoinjector or Prefilled Syringe With Needle Safety Device in Healthy Adults.

PURPOSE: Gefurulimab, a novel dual-binding nanobody targeting complement component 5 (C5), is in clinical development for anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. Gefurulimab has a low molecular weight, enabling subcutaneous (SC) self-administration by autoinjector (AI) or prefilled syringe with needle safety device (PFS-SD). We compared gefurulimab pharmacokinetic (PK) exposure and safety in healthy adults following a single SC dose administered by AI versus PFS-SD. METHODS: In this phase 1, open-label, randomized, parallel-group study (NCT06208488), healthy participants aged 18 to 65 years were stratified by weight and randomized equally to 1 of 6 combination groups of device and injection site (abdomen/thigh/upper arm). Participants received a single SC dose of gefurulimab on day 1 and were assessed throughout the 92-day evaluation period. Primary endpoints were PK parameters for each device: maximum observed concentration (Cmax) and area under the serum concentration-time curve (AUCinf, AUClast). PK across injection sites, pharmacodynamics, safety, immunogenicity, and device performance were also assessed. FINDINGS: Overall, 175 participants were randomized: AI (n = 87), PFS-SD (n = 88). Geometric least squares mean ratios (90% CI) comparing AI/PFS-SD for Cmax, AUCinf, and AUClast were 97.6% (94.5-100.8), 99.6% (96.1-103.3), and 98.8% (95.2&#x2012;102.6), respectively. Secondary analyses found no meaningful differences in PK parameters across injection sites. Serum-free C5 concentrations over time, treatment-emergent adverse event (TEAE) profiles, and antidrug antibody responses were similar between cohorts. Most TEAEs were mild; none led to study discontinuation. IMPLICATIONS: SC administration of gefurulimab by AI and PFS-SD was well tolerated with comparable exposure, meeting bioequivalence criteria.

Humans

Can't see the forest for the trees: The influence of marker type on inferred phylogenetic relationships in a cosmopolitan bat genus.

Fine-resolution information on species relationships and biological diversity is critically needed to guide conservation efforts amidst rapid environmental changes. Systematics, which forms the foundation of this knowledge, has been revolutionized by phylogenomics, utilizing genome-scale datasets. However, the use of diverse marker types, non-comparable taxon sampling, and outgroup selection can lead to conflicting phylogenetic hypotheses. These inconsistencies complicate study comparisons and hinder our ability to assess marker-specific impacts on phylogenetic resolution. The phylogenetic reconstruction of the bat genus Myotis, encompassing over 140 species and characterized by a rapid radiation in the last 20 million years, has been particularly influenced by these challenges. Achieving phylogenetic resolution in Myotis is particularly complex due to subtle interspecific differences in both morphological and molecular traits. Mitochondrial and nuclear markers often produce discordant trees, influenced by hybridization, introgression, and methodological variations. In this study, we employed a consistent taxonomic sample set of 44 Myotis taxa to evaluate the impact of five different genetic marker types on phylogenetic reconstruction. We observed significant discordance between topologies derived from conserved nuclear and mitochondrial markers and found that transposable elements were inadequate for resolving relationships across the entire genus. Our results also clarify the placement of previously problematic taxa within the genus. These findings emphasize the importance of aligning genetic marker choice with specific phylogenetic questions and highlight the influence of taxonomic and methodological variation on phylogenomic outcomes. This work provides a framework for improving phylogenetic inference in rapidly radiating groups and enhances our understanding of evolutionary history in Myotis.

Animals

The effect of combining visuo-vestibular exercises with manual therapy and exercise on sensorimotor function in chronic neck pain: A randomized controlled trial.

OBJECTIVE: To investigate whether adding visuo-vestibular exercises to standard manual therapy and exercise produces superior improvements in sensorimotor function, pain, balance, and functional disability in adults with chronic neck pain. METHODS: This prospective, randomized controlled trial enrolled 58 adults with chronic neck pain (&#x2265;3 months) allocated to a manual therapy and exercise group (MtE; n&#x202f;=&#x202f;29) or MtE plus visuo-vestibular exercises (MtE-VVE; n&#x202f;=&#x202f;29). Both groups completed 12 supervised sessions over six weeks with a daily home exercise programme. Outcomes were assessed at baseline, 6 weeks, and 12 weeks, and included pain intensity (Visual Analog Scale [VAS]), upper extremity reaction time, computerized posturography, the Neck Disability Index (NDI), and cervical muscle endurance. RESULTS: Fifty-four participants (27 per group) completed the study. Both groups improved significantly across all outcomes (p&#x202f;<&#x202f;0.001). At 12-week follow-up, the MtE-VVE group demonstrated superior outcomes: activity-related pain was reduced by an additional 2.00&#x202f;cm (95% CI: 0.75-3.25; p&#x202f;=&#x202f;0.005), bilateral reaction time improved by 1.70&#x202f;s (p&#x202f;=&#x202f;0.001), eyes-open mediolateral sway decreased by 0.50&#x202f;mm (p&#x202f;<&#x202f;0.001), NDI score was 6.30 points lower (95% CI: 3.42-9.18; p&#x202f;<&#x202f;0.001), and cervical flexion and extension endurance improved by 12.00&#x202f;s and 27.70&#x202f;s, respectively (p&#x202f;&#x2264;&#x202f;0.020). CONCLUSION: Adding visuo-vestibular exercises to standard manual therapy and exercise produces clinically meaningful and sustained improvements in activity-related pain, sensorimotor function, postural control, and functional disability in adults with chronic neck pain, and may be recommended as an effective adjunctive intervention.

Humans

Analgesia for Awake Internal Jugular Vein Cannulation in Trauma Emergency Bay: A Randomized Comparison of Ultrasound-Guided Superficial Cervical Plexus Block With Local Infiltration.

BACKGROUND: Internal jugular vein (IJV) cannulation is a critical component of trauma resuscitation but is often associated with significant pain during vessel dilation and suturing when performed under local anesthetic (LA) infiltration. OBJECTIVES: We hypothesized that an ultrasound (USG)-guided superficial cervical plexus block (SCPB) would provide superior analgesia and improve procedural efficiency in awake trauma patients compared to standard LA infiltration. METHODS: This was a prospective, randomized study of conscious, adult trauma patients requiring IJV cannulation. Participants were randomized to receive either 10 mL of 1% lignocaine via ultrasound-guided SCPB (Group S) or LA infiltration (Group L). The primary outcome was procedural pain measured by Numeric Rating Scale (NRS 0-10) during skin puncture, vessel dilation, catheter insertion, and suturing. Secondary outcomes included total procedure time, Verbal Numeric Rating Discomfort Scale (0-10), and complications. RESULTS: We enrolled 60 patients, with 30 patients assigned to each study group. Median NRS pain scores were significantly lower in Group S compared to Group L at all procedural time points (p < 0.01). The total procedure time was reduced by approximately 50% in Group S (7.5 min [interquartile range (IQR) 6.0-9.3]) compared to Group L (15.5 min [IQR 9.5-16.5]; p < 0.01). Patient discomfort scores were also significantly lower in Group S (p < 0.01). No periprocedural complications were reported in either group. CONCLUSION: Ultrasound-guided SCPB may be a useful alternative to local infiltration for IJV cannulation in selected awake trauma patients, when performed by clinicians experienced in ultrasound-guided regional anesthesia. By providing comprehensive sensory coverage, the technique significantly reduces procedural time and enhances patient cooperation without need for systemic sedation.

Humans

Serotypic and Genomic Diversity of Vibrio anguillarum in Rainbow Trout Farms in Turkey: Implications for Vibriosis Control and Vaccine Candidate Selection.

Outbreaks of vibriosis caused by Vibrio anguillarum are a persistent constraint on rainbow trout (Oncorhynchus mykiss) aquaculture. However, information on the population structure of field strains in Turkey has been lacking. Here, we report the first systematic serotypic, proteomic, and genomic characterization of 23 V. anguillarum isolates collected over 10&#x2009;years from rainbow trout farms located in six major aquaculture regions of Turkey. Serological analyses based on microagglutination, supported by ELISA characterization of hyperimmune sera, identified a clear predominance of serotype O1, whereas isolate V12 exhibited a non-agglutinating, atypical O-antigen profile. Protein profiling (SDS-PAGE) and immunoblotting showed largely conserved whole-cell protein patterns among the isolates, but distinct immunogenic bands at 14, 18, and 40&#x2009;kDa were detected in isolates V18 and V21. Long-read whole-genome sequencing revealed that most Turkish isolates grouped within the global O1 clade, while V12, V25, and V28 isolates occupied more distant branches. Comparative genomics demonstrated a conserved core virulence gene set (RTX toxins, siderophore and iron-uptake systems, motility and adhesion factors, Type VI secretion system), with strain-dependent variation in accessory loci such as anguibactin and T6SS-I. Experimental infections of rainbow trout demonstrated significant differences in virulence among isolates (p&#x2009;<&#x2009;0.05), with the V18 isolate showing high, the V15 intermediate, and the V12 low-mortality rates. By elucidating the relationship among the serotype, immunogenic protein profiles, virulence gene repertoires, and in&#xa0;vivo pathogenicity, this study provides a comprehensive overview of the antigenic and genomic diversity of Vibrio anguillarum isolates from Turkey. Notably, the identification of V18 and V21 as promising candidate strains for further vaccine evaluation, characterized by high virulence and unique immunogenic features, provides a scientific foundation for the development of serotype-specific vaccination strategies to mitigate vibriosis-associated losses in aquaculture.

Animals

Direct and spillover hospitalisation patterns during climate hazards across regions of different health-system resilience levels in China: a nationwide retrospective analysis.

BACKGROUND: Health-system resilience serves as a key contributor in mitigating adverse health impacts during climate hazards. However, quantitative insights into resilience-associated health-care utilisation patterns and targeted adaptation policies remain scarce. We aimed to capture the spatiotemporal health impacts in disaster-exposed counties and their neighbouring counties in China during storms, floods, tropical cyclones, and blizzards or winter storms; understand the association between health-system resilience metrics and hazard-attributable hospitalisations; and develop evidence-based adaptation policies towards climate extremes. METHODS: In this retrospective, observational analysis of county-level aggregated hospitalisation data, we used a propensity score matching-difference-in-differences framework to assess the spatiotemporal changes of nine types of disease-specific hospitalisations in both disaster-exposed and neighbouring regions during storms, floods, tropical cyclones, and blizzards in China. We quantified the relative importance and health gains of health-system metrics during such hazards through random forest approach with interpretable partial dependence plots to derive evidence-based adaptation recommendations. FINDINGS: We included hospitalisation data from Jan 1, 2016 to Dec 31, 2023. In this period, 3241 county-hazard event combinations and 41&#x2009;747&#x2009;482 hospitalisations were recorded across 955 Chinese counties. The disaster-exposed regions experienced an initial decline in hospitalisation rates, followed by admission surges after disasters. For example, infectious disease admissions decreased by 11&#xb7;92% (95% CI -10&#xb7;53 to -13&#xb7;31) during the flood-active period but increased by 7&#xb7;68% (6&#xb7;46-8&#xb7;91) after 1-2 weeks of floods. Neighbouring zones were also affected through spillover effects, with infectious disease admissions increasing by 3&#xb7;18% (1&#xb7;76-4&#xb7;61) after 1-2 weeks of the floods. Cardiovascular disease, injuries, infectious, respiratory, and mental disorders were more sensitive across all regions. Particularly for disaster-exposed counties, cardiovascular hospitalisations increased by 14&#xb7;31% (7&#xb7;34-21&#xb7;29) during the tropical cyclone-active period. Notably, compared with low-resilience counties, high-resilience counties were associated with 19&#xb7;48-30&#xb7;03% smaller hazard-related relative changes in hospitalisation rates during the hazard-active period and 27&#xb7;07-31&#xb7;08% smaller hazard-related relative changes in hospitalisation rates in post-hazard periods. For instance, during the storm-active period, the increase in respiratory hospitalisations was 7&#xb7;21% (0&#xb7;67-13&#xb7;75) in high-resilience counties versus 12&#xb7;13% (5&#xb7;20-19&#xb7;05) in low-resilience counties. Health workforce (relative importance 14&#xb7;58% during the hazard-active period and 13&#xb7;80% during the post-hazard period) and service delivery (14&#xb7;10% during the hazard-active period and 14&#xb7;17% during the post-hazard period) were identified as key contributors of health-system resilience. Empirical synergistic effects were observed when combining interventions during the post-hazard period, with the combined effect of service delivery (individual contribution 8%) and workforce (individual contribution 4%) exceeding the sum of their individual contributions (16% reduction in cumulative excess admissions) by 33%. INTERPRETATION: Climate hazards are associated with substantial changes in hospitalisation rates in both disaster-exposed and neighbouring regions. Health-system resilience is essential in addressing disaster-health challenges. Targeted adaptation interventions should be context-appropriate and threshold-aware, thereby maximising the public health benefits relative to resilience-oriented investments in health systems. FUNDING: Gates Foundation and the National Natural Science Foundation of China.

Journal Article

The effect of metformin on the pharmacokinetics of rifampicin, isoniazid, and pyrazinamide in adults with tuberculosis.

Metformin is under investigation as adjunctive host-directed therapy for tuberculosis (TB), which might interact with first-line TB treatment. We used population pharmacokinetic modeling to assess whether metformin alters first-line TB-drug pharmacokinetics in HIV/TB-coinfected adults without diabetes. Rifampicin, isoniazid, and pyrazinamide pharmacokinetics were investigated in participants from a randomized clinical trial of adjunctive metformin (500 mg twice daily to week 12) in adults starting HIV-associated TB treatment. Antiretroviral therapy (ART)-na&#xef;ve participants initiated dolutegravir-based ART within 8 weeks. Intensive and semi-intensive sampling was conducted at week 5; concentration-time data were analyzed using non-linear mixed-effects modeling. Data from 78 individuals (43 receiving metformin, median weight 60.8 kg, 62.8% male, 79.5% on ART) were analyzed. Rifampicin and pyrazinamide were described by one-compartment models with linear elimination; typical clearances were 15.8 L/h (95% CI: 13.5-18.7) and 3.88 L/h (95% CI: 3.54-4.08), respectively. Isoniazid followed a two-compartment model with a mixture model for acetylator status; clearance was 10.5 L/h (95% CI: 9.44-11.9) in slow acetylators and 28.8 L/h (95% CI: 25.6-31.0) in fast/intermediate acetylators. Metformin reduced isoniazid bioavailability by 15.6% (95% CI: 4.45-26.4%, P < 0.009) and rifampicin bioavailability by 24.0% (95% CI: 7.83-36.3%, P < 0.007), decreasing the area under the curve from 0 to 24 h from 18.2 to 15.6 mg&#xb7;h/L and from 35.9 to 27.1 mg&#xb7;h/L, respectively. No significant effect on pyrazinamide was detected. We found that non-diabetic patients on metformin had lower isoniazid and rifampicin bioavailability. Lowered rifampicin exposure might be clinically relevant; simulations suggest that this could be offset by a single 150 mg rifampicin dose.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04930744.

Humans