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PubMed2026

Global prevalence of metabolic syndrome in adults with obstructive sleep apnea: a systematic review and meta-analysis.

STUDY OBJECTIVES: Metabolic syndrome (MetS) is considered to exhibit increased prevalence among adults with obstructive sleep apnea (OSA), but the reported prevalence estimates among such patients vary. Thus, this systematic review and meta-analysis aimed to investigate the global prevalence of MetS in adults with confirmed OSA. MATERIALS AND METHODS: Ovid Medline, Embase, CINAHL, and the Cochrane Library databases were searched for all primary studies published in English that used standard polysomnography for OSA diagnosis and reported MetS estimates. At least two reviewers independently screened for eligible studies, extracted data, and graded the risk of bias using the Risk of Bias Assessment Tool for Non-randomised Studies. Three-level random-effects model was applied for the meta-analysis, reporting pooled prevalence estimate with 95% confidence intervals (CIs). Pre-specified subgroup analyses and meta-regression were also performed. Heterogeneity was quantified using I2 and chi-square statistics. RESULTS: A total of 102 studies were eligible for inclusion (34 013 adults with OSA from 28 countries). The combined MetS prevalence was 55.4% (95% CI: 51.0%, 59.8%). Considerable heterogeneity was noted among the included studies (I2 = 97.8%), whilst the risk of bias ranged from low to high. Subgroup analysis examining the effects of geographic region, study design, MetS definition, and apnea-hypopnea index threshold showed a significant variation in prevalence estimates across most subgroups (p < 0.0001). Meta-regression analysis indicated a positive association between mean body mass index (β = 0.0772, t = 4.56, p < 0.0001) and MetS prevalence. CONCLUSIONS: MetS has a high prevalence among adults with polysomnography-confirmed OSA, underscoring the need for prompt MetS screening in these patients. Future longitudinal and genetic/mechanistic studies should investigate the factors accounting for this association. PROSPERO REGISTRATION NUMBER: CRD420251073055.

Humans↗

PubMed2026

A Systematic Review and Meta-Analysis of the Global Prevalence of Dry Mouth in Older Adults.

OBJECTIVE: The objective of this study is to update prevalence estimates for xerostomia and salivary gland hypofunction (SGH) among older adults through a systematic review and meta-analysis. BACKGROUND: Dry mouth is common among older adults but is inconsistently assessed and reported. Xerostomia and SGH represent distinct conditions with different diagnostic approaches, leading to heterogeneity in prevalence estimates. MATERIALS AND METHODS: A systematic literature search of Medline (PubMed) and Web of Science was conducted from January 2018 to March 2025. This was supplemented by manual backward citation tracking of the foundational review to identify all eligible pre-2018 epidemiological studies. Only studies utilizing population-representative samples of adults aged 50 years and older with defined diagnostic criteria were included. Risk of bias was formally assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Tool for Prevalence Studies. Pooled prevalence estimates were calculated using random-effects meta-analyses. (PROSPERO: CRD420251009592). RESULTS: A total of 37 studies-encompassing over 1.6 million participants-met the inclusion criteria. The pooled global prevalence of xerostomia among older adults was 21% (95% CI: 19%-23%). For SGH, the pooled prevalence measured via UWS was 12% (95% CI: 4%-24%), whereas SWS yielded a prevalence of 13% (95% CI: 3%-28%). High heterogeneity was observed across all analyses. Differences in diagnostic thresholds and saliva collection methods contributed to the observed variability. CONCLUSION: This updated meta-analysis confirms that xerostomia affects around one-fifth of older adults, while SGH is less common, depending on the diagnostic criteria used. Future research should focus on improving diagnostic consistency and sample representativeness to enable more consistent and robust estimates, and thereby better guide prevention and care in geriatric oral health.

Humans↗

PubMed2026

Global prevalence and associated factors of turnover intention among intensive care nurses: A systematic review and meta-analysis.

OBJECTIVES: To estimate the global prevalence of two distinct turnover intentions among intensive care unit (ICU) nurses-intention to leave the ICU and intention to leave the nursing profession-identify significant sources of heterogeneity, and synthesise associated psychosocial factors. METHODS: Ten databases were systematically searched from inception to September 28, 2025. Two reviewers independently conducted study selection, data extraction, and quality appraisal using Joanna Briggs Institute checklists. Random-effects meta-analyses were performed to estimate pooled prevalence and associated factors. Subgroup and meta-regression analyses explored potential sources of heterogeneity. Associated factors were pooled as odds ratios (ORs) and interpreted within an integrated Job Demands-Resources and Theory of Planned Behavior framework. RESULTS: Forty-six studies published between 2007 and 2025, involving 39,246 ICU nurses, were included. The pooled prevalence was 30.7% for intention to leave the ICU and 27.5% for intention to leave the nursing profession. Significant sources of heterogeneity included ICU type, geographic region, publication year, study design, measurement tool, and sampling method. Depression, burnout, high workload, and unsafe patient-to-nurse ratios were associated with increased turnover intention, whereas positive work environments, perceived organisational support, and nursing competence were protective factors. No significant publication bias was detected. CONCLUSIONS: Turnover intention affects approximately one-third of ICU nurses globally and varies across clinical and geographical contexts. Excessive workload, inadequate organisational support, and unfavourable work environments appear to be important contributors to turnover intention among ICU nurses. IMPLICATIONS FOR CLINICAL PRACTICE: Strategies to reduce turnover intention among ICU nurses should focus on reducing excessive workload, improving staffing conditions, strengthening organisational support, and fostering positive work environments. Promoting supportive and sustainable ICU work environments may help improve nurse retention and maintain the quality of critical care services.

Humans↗

PubMed2026

The global prevalence of horizontal strabismus: A systematic review and meta-analysis with a focus on ethnic variation.

The prevalence of the 2 types of horizontal strabismus, esotropia and exotropia, varies considerably between studies. This variability has been attributed to factors such as geography/environment, research methodology, age of study subjects, and/or ethnicity. Comprehensive estimates of regional and global prevalences of esotropia and exotropia are lacking, making it difficult to recognize true patterns, trends, and etiologies. We compile prevalences and ratios of esotropia to exotropia from 315 population-based studies and 374 clinic-based studies. We analyze data to assess effects of ethnicity, geography, age, and we identify generational changes of horizontal strabismus. Major ethnicities differ in patterns and ratios of esotropia and exotropia prevalence, not only in Caucasians and East Asians, but also Latinos/Hispanics, South Asians, Africans, and Native Americans. Compared to population-based studies, clinic-based studies underestimate exotropia frequency. By weighing prevalences according to the population size of ethnicities, we estimate the worldwide prevalence of horizontal strabismus in the current generation at 1.81% (138.5 million people), comprising 60.0 million people with esotropia (0.67%) and 87.5 million with exotropia (1.14%). In the previous generation, the worldwide prevalence of horizontal strabismus was 1.64% (86.5 million people), comprising 50.5 million with esotropia (0.96%) and 36.0 million with exotropia (0.68%). Esotropia and exotropia prevalences differ between generations within the same ethnicity, indicating that extrinsic factors can modify the underlying intrinsic (genetic) disposition.

Humans↗

PubMed2026

A systematic review and meta-analysis to estimate the global prevalence of leptospirosis in sheep.

Leptospirosis in sheep is a zoonotic concern considering sheep may act as potential reservoirs for Leptospira spp. infection to humans. This study aimed to estimate the pooled prevalence of leptospirosis in sheep worldwide. A comprehensive literature search was conducted across databases following PRISMA guidelines. Meta-analyses were performed using a random effect model in R software (version 4.3.1) to calculate pooled prevalence with 95% confidence intervals (CI). Subgroup analyses were performed based on prevalence types, diagnostic methods and continental regions to explore sources of heterogeneity. A total of 138 studies comprising 54,174 samples and 10,299 positive detections were included in this study. The global pooled prevalence of leptospirosis in sheep was 15.69% (95% CI: 12.69-19.25) with overall heterogeneity (I2) 98%. The prediction interval ranged from 1.09% to 75.91%, indicating wide inter-study variability. The seroprevalence was 16.16% (95% CI: 12.91-20.04) and infection prevalence was 12.98% (95% CI: 8.07-20.22), showing no significant difference (P = 0.40). In addition, the prevalence of leptospirosis in sheep differed significantly across diagnostic methods and continents (P < 0.01), indicating substantial variation influenced by both methodological and geographical factors. The funnel plot revealed marked asymmetry, suggesting potential publication bias which was confirmed by Egger's regression test (P < 0.01). In conclusion, leptospirosis is widely prevalent in sheep globally, with marked geographical and methodological heterogeneity. These findings highlight the epidemiological importance of sheep in leptospirosis transmission and underscore the need for improved surveillance, standardized diagnostic approaches, and targeted control strategies within a One Health framework.

Animals↗

PubMed2026

Global prevalence of hereditary hemorrhagic telangiectasia-associated variants estimated by analysis of large-scale genomic databases.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with an overwhelming hemorrhagic phenotype. It is mainly caused by variants in the ENG and ACVRL1 genes. HHT prevalence is currently estimated to be 1 in 5000 individuals, but the disease is likely underdiagnosed due to variable clinical presentation, misdiagnosis, and delayed recognition. OBJECTIVES: To estimate the global genetic prevalence of HHT-associated variants in ENG and ACVRL1. METHODS: We analyzed 3 large population-scale genomic databases: gnomAD, All of Us, and Regeneron Genetics Center-Million Exome. We considered known pathogenic and likely pathogenic variants of ENG and ACVRL1 and extended the analysis to potentially pathogenic variants passing the pathogenic criteria established by the guidelines for HHT of the American College of Medical Genetics and Genomics/Association for Molecular Pathology. RESULTS: The genetic prevalence of HHT ranged from 1.753 to 2.555 in 5000 individuals, when considering only pathogenic and likely pathogenic variants, and from 2.874 to 4.327 in 5000 individuals, when also potentially pathogenic variants were considered. CONCLUSION: This study assesses the prevalence of HHT-associated variants in the general population. Our unbiased approach demonstrates that the genetic prevalence of the disease is substantially higher than currently estimated.

Humans↗

PubMed2025

Worldwide prevalence of haemorrhoids: a systematic review and meta-analysis.

BACKGROUND: Haemorrhoidal disease (HD) is one of the most common anorectal disorders globally, significantly impacting individuals' quality of life and productivity. Despite its importance, global prevalence remains unclear due to limited population-specific studies. This study aimed to systematically assess the global prevalence of HD through a systematic review and meta-analysis. METHODS: We conducted a systematic review and meta-analysis by searching PubMed, Scopus, Embase, Web of Science, and Google Scholar up to March 31, 2025, without language restrictions. Studies reporting prevalence of haemorrhoids in general, clinical, or high-risk populations were included. Exclusion criteria comprised studies lacking total sample size, focusing on other anorectal conditions, or using duplicate or insufficient data. Four independent reviewers extracted and appraised study quality using the Joanna Briggs Institute tool. The primary outcome was pooled point prevalence of HD, analyzed using a random-effects model with 95% confidence intervals (CIs). The study was registered in PROSPERO (CRD420251045600). RESULTS: From 6,312 records, 150 studies (210 datasets) comprising 8,960,338 individuals were included. The global pooled point prevalence was 25.92% (95% CI: 22.62-29.22). Lifetime prevalence was 27.19% (95% CI: 14.77-39.60), and one-year prevalence was 21.65% (95% CI: 14.33-28.97). Prevalence was higher in women (27.33%, 95% CI: 21.84-32.82) than in men, and highest in the African region 28.07% (95% CI: 15.34-40.79). Invasive diagnostic methods (28.05%, 95% CI: 23.86-32.26) yielded higher prevalence estimates than non-invasive methods. Also, factors showing associations with HD in unadjusted analyses include older age, obesity, pregnancy, diabetes, family history, constipation, and hypertension. CONCLUSION: HD remains a prevalent condition globally, with minor variation across regions. The burden is consistent regardless of socioeconomic context. Diagnostic method and population characteristics influence prevalence estimates. These findings underscore the importance of targeted prevention and early intervention strategies, especially for at-risk groups.

Humans↗

PubMed2026

Putting Globus Into Context: Prevalence, Characteristics, and Overlap With Other Disorders of Gut-Brain Interaction.

OBJECTIVE: Globus is characterized by the sensation of a lump in the throat without dysphagia or underlying structural abnormality or major motility disorder. Reported prevalences vary considerably across studies. Globus has been linked to both heartburn and affective disorders. This study aims to determine the global prevalence of globus, its association with heartburn, overlap with disorders of gut-brain interaction (DGBI) and psychosocial disorders, and its impact on health-related quality of life (HRQOL). METHODS: Internet surveys from the Rome Foundation Global Epidemiology study were used (N = 54,127). Rome IV criteria were used to identify globus and concurrent DGBI. Heartburn was defined as symptoms ≥ 2-3 days/week. Psychosocial co-morbidity and somatic symptom severity were assessed with PHQ-4 and PHQ-15, and HRQOL by PROMIS-10. RESULTS: The global prevalence of globus according to Rome IV criteria was 0.75%, representing 12.8% of esophageal DGBI and 1.86% of all DGBI. Prevalence was highest in Western Europe (0.94%) and Asia (0.90%), and lowest in the Middle East (0.31%). Globus was slightly more common in females (55.4%), and most affected individuals were aged between 40 and 64 years (46.6%). Coexisting heartburn was reported in 17.4% of cases, esophageal DGBI in 9.1%, and non-esophageal DGBI in 49.0%. Anxiety and/or depression was present in 60.5%. CONCLUSION: Global prevalence of globus is 0.75%, with a slight female predominance, and is most prevalent below 65 years. Overlap with non-esophageal DGBI was greater than with heartburn symptoms or esophageal DGBI, and most patients had anxiety and/or depressive symptoms.

Humans↗

PubMed2025

Uncovering encrypted antimicrobial peptides in health-associated Lactobacillaceae by large-scale genomics and machine learning.

BACKGROUND: Antimicrobial peptides (AMPs) are well known for their broad-spectrum activity and have shown great promise in addressing the antibiotic-resistant crisis. The Lactobacillaceae family, recognized for its health-promoting effects in humans, represents a valuable source of novel AMPs. However, the global prevalence and distribution of AMPs within Lactobacillaceae remains largely unknown, which limits the efficient discovery and development of novel AMPs. RESULTS: We analyzed all available genomes (10,327 genomes), encompassing 38 genera and 515 species, to investigate the biosynthetic potential (indicated by the number of AMP sequences in the genome) of AMP in the Lactobacillaceae family. We demonstrated Lactobacillaceae species had ubiquitous (69.90%) biosynthetic potential of AMPs. Overall, 9601 AMPs were identified, clustering into 2092 gene cluster families (GCFs), which showed strong interspecies specificity (95.27%), intraspecies heterogeneity (93.31%), and habitat uniqueness (95.83%), that greatly expanded on the AMP sequence landscape. Novelty assessment indicated that 1516 GCFs (72.47%) had no similarity to any known AMPs in existing databases. Machine learning predictions suggested that novel AMPs from Lactobacillaceae possessed strong antimicrobial potential, with 664 GCFs having an additive minimum inhibitory concentration (MIC) below 100 μM. We randomly synthesized 16 AMPs (with predicted MIC < 100 μM) and identified 10 AMPs exhibiting varied-spectrum activity against 11 common pathogens. Finally, we identified one Lactobacillus delbrueckii-originated AMP (delbruin_1) having broad-spectrum (all 11 pathogens) and high antimicrobial activity (average MIC = 38.56 µM), which proved its potential as a clinically viable antimicrobial agent. CONCLUSIONS: We uncovered the global prevalence of AMPs in Lactobacillaceae and proved that Lactobacillaceae is an untapped and invaluable source of novel AMPs to combat the antibiotic-resistance crisis. Meanwhile, we provided a machine learning-guided framework for AMP discovery, offering a scalable roadmap for identifying novel AMPs not only in Lactobacillaceae but also in other organisms. Video Abstract.

Machine Learning↗

PubMed2025

Immunopathogenic mechanisms and immunoregulatory therapies in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the most prevalent chronic liver disease worldwide, with an estimated global prevalence of approximately 30%; however, effective pharmacotherapies are still limited due to its complex pathogenesis and etiology. Therefore, a more thorough understanding of disease pathogenesis is urgently needed. An increasing number of studies suggest that MASLD and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), are driven by chronic overnutrition, multiple genetic susceptibility factors, and pathogenic consequences, including hepatocyte damage and liver inflammation. Hepatic inflammation is the key event fueling the conversion from simple steatosis to steatohepatitis and fibrosis. Current therapies for MASH, including the recently approved thyroid hormone receptor-beta agonist resmetirom or the available incretin mimetics, mainly target metabolic injury to the liver but not inflammation directly. In this review, we provide an in-depth discussion of current data related to the immunological mechanisms of MASLD and summarize the effects of current and experimental therapies on immunoregulation in MASLD.

Humans↗

PubMed2026

Time-resolved proteomic adaptation of multidrug-resistant Acinetobacter baumannii to antimicrobial stress induced by partially purified fraction from Caesalpinia pulcherrima flower using DEqMS.

UNLABELLED: The global prevalence of multidrug-resistant (MDR) bacteria represents an urgent public health challenge, emphasizing the critical need for novel antimicrobial agents. MDR Acinetobacter baumannii, a nosocomial pathogen of critical global concern owing to its capacity to acquire and disseminate antimicrobial resistance, was employed as a bacterial model to investigate the antimicrobial potential of natural products derived from Caesalpinia pulcherrima (L.) Sw. (Fabaceae). This medicinal plant represents a promising reservoir of novel bioactive compounds; however, its molecular effects on the A. baumannii proteome had not previously been characterized. The partially purified ethyl acetate fraction of C. pulcherrima flowers (CPF4) exhibited potent bactericidal activity against susceptible A. baumannii (minimum inhibitory concentration and minimum bactericidal concentration = 31.25 µg/mL), and time-resolved label-free quantitative LC-MS/MS proteomics was subsequently performed on MDR A. baumannii cultures treated with CPF4 at 24 h, 48 h, and 72 h post-treatment alongside untreated controls in biological triplicate, with differential protein expression assessed using differential expression of quantified mass spectrometry data. No significantly differentially expressed proteins were detected at 24 h or 48 h relative to the control, indicating that the proteomic effects of CPF4 manifest predominantly at the late treatment stage. In contrast, a robust late-phase response was identified at 72 h, comprising the coordinated induction of proteins associated with DNA damage repair, transcriptional regulation, and cell surface glycosylation remodeling. The sensor histidine kinase PmrB was significantly upregulated at 72 h vs 48 h (adjusted P = 0.029), implicating the PmrA/PmrB two-component system in late-phase colistin tolerance acquisition under sustained CPF4 exposure. IMPORTANCE: These findings provide mechanistic insight into the adaptive survival strategies employed by multidrug-resistant Acinetobacter baumannii in response to plant-derived antimicrobial challenge and support the further development of Caesalpinia pulcherrima-derived natural products as candidate antimicrobial agents.

Acinetobacter baumannii↗

PubMed2026

Escalation of CTX-M-producing extensively drug-resistant Shigella spp. in Kolkata, India, following the COVID-19 pandemic.

Shigella spp. is recognized by the World Health Organization as a high-priority pathogen due to its global prevalence, unique pathogenic mechanisms, and growing antimicrobial resistance (AMR). Nearly half of all Shigella strains worldwide are now multidrug-resistant (MDR), and the emergence of extensively drug-resistant (XDR) variants-resistant to ciprofloxacin, ceftriaxone, and azithromycin-has severely limited effective treatment options. The present study is based on prospective laboratory surveillance involving 323 Shigella isolates collected during 2021-2023, with pre-COVID-19 pandemic data included from a previously published study solely for historical comparison. The presence of antibiotic resistance genes (ARGs) was investigated, and whole-genome sequencing (WGS) was performed on representative isolates to assess phylogenetic relatedness with global isolates. Approximately 10% of isolates exhibited resistance to third-generation cephalosporins. While only 3% of Shigella isolates carried the blaCTX-M-15 gene from 2013 to 2019, its prevalence increased to 26% by 2022-2023. Among 38 ceftriaxone-resistant S. sonnei isolates, 33 were also resistant to azithromycin, categorizing them as XDR. These isolates showed 48% clonal similarity and high phylogenetic resemblance to the isolates reported from England. Hybrid genome assembly revealed a plasmid harboring both the blaCTX-M-15 and mphA ARGs. Conjugation experiments and plasmid profiling confirmed the plasmid's transferability. We report a rising trend in third-generation cephalosporin resistance among Shigella spp., primarily driven by the spread of extended-spectrum β-lactamase-producing S. flexneri and the emergence of XDR S. sonnei. These findings underscore the urgent need for strengthened national AMR containment strategies and enhanced international surveillance of cephalosporin-resistant Shigella to mitigate this growing public health threat.IMPORTANCEShigella is a leading cause of diarrheal disease globally and has been prioritized by the World Health Organization due to its rapid acquisition of antimicrobial resistance. Our prospective surveillance in Kolkata, India, reveals a worrisome escalation of third-generation cephalosporin resistance over the past decade, primarily associated with the spread of blaCTX-M-15 and the emergence of extensively drug-resistant (XDR) S. sonnei. The detection of plasmids carrying both blaCTX-M-15 and mphA, coupled with evidence of their transferability, highlights the potential for accelerated dissemination of multidrug resistance. When compared with a global data set of international genomes, the Kolkata XDR isolates were found to cluster closely with isolates reported from England. By linking local surveillance with global genomic context, our findings provide critical insights for treatment guidelines, antimicrobial stewardship, and the design of international containment strategies aimed at curbing the rise of cephalosporin- and azithromycin-resistant Shigella.

India↗

PubMed2026

From decline to resurgence: current perspectives on Mycoplasma pneumoniae.

SUMMARYMycoplasma pneumoniae pneumonia (MPP) is an acute respiratory infection caused by Mycoplasma pneumoniae (MP) and constitutes the primary cause of community-acquired pneumonia (CAP) among children aged 5 years and older in China. The clinical manifestations of MP-associated respiratory disease in children are diverse, ranging from mild upper respiratory symptoms to life-threatening pneumonia. Notably, during the implementation of nonpharmaceutical interventions (NPIs) aimed at curbing SARS-CoV-2 transmission, there was a significant decline in MP infection rates. However, a pronounced global resurgence of MP infections was documented in 2023-2024. The increasing global prevalence of macrolide resistance, particularly in China, coupled with limited alternative antibiotic options for children, increasing rates of coinfections, and the absence of a preventive vaccine, collectively exacerbate treatment challenges and increase the disease burden. Furthermore, the insufficient availability of MP nucleic acid testing and antimicrobial resistance surveillance in primary healthcare settings, coupled with the absence of a comprehensive epidemiological monitoring network, results in a vicious public health cycle. Recent advances and emerging genomic data have provided new insights into its pathogenesis and clinical management. Therefore, in this narrative review, we aim to (i) synthesize the current understanding of the etiological characteristics of MP and the present status of MPP diagnosis and treatment; (ii) analyze recent advances and drivers behind the global resurgence of MP infections; and (iii) propose integrated prevention and control strategies to increase the recognition of MPP and prevent unanticipated outbreaks.

Humans↗

PubMed2026

Antimicrobial resistance in Staphylococcus spp. isolated from sporotrichosis-affected cats in Brazil: Detection of MRSP and MRSA.

Recently, Brazil has experienced a zoonotic emergence of sporotrichosis. The associated cutaneous lesions are often extensive and slow to heal, thereby providing a gateway for opportunistic bacteria belonging to the normal skin microbiota. Among these, Staphylococcus spp. are of particular concern due to their high prevalence and notable levels of antimicrobial resistance. The objective of this study was to identify and characterize Staphylococcus spp. isolated from the cutaneous wounds of domestic cats undergoing treatment for sporotrichosis and exhibiting clinical signs of secondary bacterial infection. A total of 233 samples from 203 cats were analyzed. Staphylococcus spp. was isolated from 156 samples (67%), with S. aureus (42.3%) and S. felis (25.6%) being the most prevalent. Antimicrobial susceptibility testing revealed high levels of resistance to penicillin (51.9%), erythromycin (28.8%), and clindamycin (19.2%). In contrast, most isolates were susceptible to chloramphenicol (98%), ciprofloxacin (96.7%), and nitrofurantoin (93%). Multidrug-resistant strains were identified in 24% (38/156) of the isolates. Overall, 12 isolates (7.7%) were classified as methicillin-resistant staphylococci, including four methicillin-resistant S. pseudintermedius (MRSP) and one methicillin-resistant S. aureus (MRSA). To investigate the genetic profiles and epidemiological relationships of these isolates, all the MRSP and MRSA strains were subjected to whole-genome sequencing. Among the MRSP isolates, four sequence types (STs) were identified, including ST551, the founder of clonal complex (CC)551, which is commonly associated with infection in dogs. The MRSA isolate belonged to ST1176, a member of CC5, which is a globally prevalent lineage and is frequently associated with nosocomial infections in humans. This study demonstrates that Staphylococcus species, including methicillin-resistant isolates, are frequently present in the wounds of sporotrichosis-infected cats exhibiting clinical signs of secondary bacterial infection. The detection of MRSA and MRSP in a cat highlights an additional public health concern associated with feline sporotrichosis and further reinforces the growing concern regarding antimicrobial resistance in companion animals.

Animals↗

PubMed2025

Selecting candidate Neisseria gonorrhoeae strains for oropharyngeal gonorrhoea human challenge: a genomics-based analysis of clinical isolates.

BACKGROUND: Neisseria gonorrhoeae is a human pathogen of major public health importance due to its increasing global prevalence and antimicrobial resistance (AMR). Evidence suggests that oropharyngeal infection plays a key role in N gonorrhoeae transmission and AMR; however, our understanding of oropharyngeal gonorrhoea pathogenesis is poor. A controlled human infection model (CHIM) for oropharyngeal gonorrhoea will improve understanding of infection and accelerate urgently needed novel gonorrhoea prevention and therapeutic strategies. As the first step in the development of this CHIM, we describe a systematic approach to CHIM strain selection that leverages genomics and clinical data. METHODS: In this genomics-based analysis, we applied a systematic N gonorrhoeae challenge strain selection strategy incorporating genomic and clinical data to a primary dataset of clinical isolates of N gonorrhoeae collected from adult patients in Victoria, Australia, between Jan 1 and Dec 31, 2017, and July 1, 2019, and June 30, 2021. This selection strategy used clinical, phenotypic, and genomic characteristics to define a set of eight criteria that aimed to ensure the contemporary global clinical relevance of the candidate strains; select strains that would be applicable for the assessment of current and future gonorrhoea vaccines; and maximise participant safety by reducing the risk of disseminated gonococcal infection and clinically significant AMR. We applied these criteria to our primary dataset to generate a panel of potential challenge strains. From this final dataset of potential challenge strains, we predetermined that we would select up to ten isolates to proceed to the next stage of detailed phenotypic characterisation for final N gonorrhoeae CHIM strain selection. FINDINGS: 5881 isolates comprised the primary dataset. After application of the selection criteria, most of the isolates (5795 [98·6%] of 5881) were excluded, mostly due to having clinically significant AMR and poor contemporary global clinical relevance. The remaining 86 N gonorrhoeae challenge strain candidates comprised five multilocus sequence types and six N gonorrhoeae multiantigen sequence types, many of which were represented by a single isolate. Of these 86 strains, five isolates were selected to maximise coverage of the phylogenetically distinct groups within the 86 candidate challenge strains and ensure representation of strains collected from various anatomical sites. INTERPRETATION: We transparently describe a novel, systematic, and rational genomics-based strategy for oropharyngeal gonorrhoea CHIM strain selection that improves the efficiency and transparency of CHIM strain selection and enables identification of contemporary and clinically relevant potential challenge strains. A final N gonorrhoeae challenge strain will be selected from the subset of five shortlisted candidates after detailed phenotypic assessment. FUNDING: Medical Research Future Fund, Australian National Health and Medical Research Council and Australian Government Research Training Program.

Humans↗

PubMed2026

Evaluation of carbapenem inactivation method-based phenotypic assays for the detection of GES-type carbapenemases in Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii.

UNLABELLED: Detection of GES-type carbapenemases remains challenging because of their low prevalence and frequently weak hydrolytic activity against carbapenems. Carbapenem inactivation method (CIM)-based assays are widely used as phenotypic screening tools for carbapenemase detection; however, their performance in large collections of GES producers has not been systematically evaluated. We assessed the performance of CIM, modified CIM (mCIM), and CIM-Tris in a diverse collection of GES-producing clinical isolates, including 110 Enterobacterales and 108 Pseudomonas aeruginosa, recovered from Spanish hospitals (2010-2024), and 10 Acinetobacter baumannii isolates, mostly obtained from a hospital in Egypt. Whole-genome sequencing was carried out for species confirmation and resistome analysis. Meropenem MICs were determined by broth microdilution. Overall, 92.1% of isolates were GES-carbapenemase producers (CP), whereas 7.9% expressed GES-type extended-spectrum β-lactamases (ESBLs). In Enterobacterales (predominantly carrying blaGES-6), mCIM improved sensitivity compared with CIM (63.6% vs 40.0%), although many isolates remained undetected due to low meropenem MICs (MIC50, 0.5 µg/mL). In CP-P. aeruginosa (mainly blaGES-5), CIM, mCIM, and CIM-Tris showed sensitivities of 89.1%, 94.6%, and 100%, respectively; however, CIM-Tris yielded false-positive results in 50% of non-CP isolates (mostly blaGES-1 producers). Meropenem MICs in P. aeruginosa were higher (MIC50, >32 µg/mL). In A. baumannii, CIM-Tris improved sensitivity compared with CIM (100% vs 25.0%). These findings indicate that CIM-based methods can detect GES-type carbapenemases, but performance varies according to bacterial species and GES variant, and reduced specificity may occur in isolates producing GES-type ESBLs. Complementary molecular testing may therefore be necessary to ensure accurate detection of GES-type carbapenemases in routine clinical laboratories. IMPORTANCE: GES-type carbapenemases represent an important but underrecognized diagnostic challenge due to their low global prevalence, heterogeneous hydrolytic activity, and the limited performance data available for routine phenotypic detection methods. Although CIM-based assays are widely implemented in clinical microbiology laboratories for carbapenemase screening, their performance against GES-producing organisms has not been comprehensively evaluated across different bacterial genera and GES variants. In this study, we evaluated the performance of CIM, modified CIM (mCIM), and CIM-Tris in a large multicenter collection of well-characterized GES-producing clinical isolates, including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Our findings demonstrate substantial variability in assay performance according to bacterial species and GES variant. Notably, mCIM improved sensitivity among Enterobacterales with low meropenem MICs, whereas CIM-Tris achieved excellent sensitivity in P. aeruginosa and A. baumannii but at the expense of reduced specificity in isolates producing GES-type ESBLs. To the best of our knowledge, this is the first study directly comparing multiple CIM-based approaches in such a large and taxonomically diverse collection of GES-producing isolates.

beta-Lactamases↗

PubMed2026

ADAM10's combined influence on the diagnostic usefulness of IL 22, IL 10, IL-17 A, and IL-17D in autism spectrum disorders: Predicted role on gut leakiness as co-morbidity.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with increasing global prevalence but a lack of reliable diagnostic biomarkers. Emerging evidence suggests that immune dysregulation, gut-brain axis dysfunction, and increased intestinal permeability play key roles in ASD pathophysiology. This study investigated the combined diagnostic value of ADAM10 and cytokines (IL-10, IL-22, IL-17 A, and IL-17D). Multivariable logistic regression produces an improved ROC curve that improves diagnostic accuracy over individual markers by combining numerous predictors into a single risk score (linear predictor). The technique, which frequently raises individual marker AUCs, entails modelling a binary result, calculating the probability, and visualizing ROC based on the projected probabilities. In this case-control study, plasma levels of ADAM10, IL-10, IL-22, IL-17 A, and IL-17D were measured in 37 male children with ASD and 37 age-matched controls. Group comparisons, correlation analyses, and receiver operating characteristic (ROC) curve analyses, including combined ROC models, were performed. ADAM10, IL-22, and IL-17 A levels were significantly reduced in children with ASD compared to controls, whereas IL-10 and IL-17D showed no significant differences. ADAM10, IL-17 A, and IL-22 demonstrated good diagnostic performance, with AUC values of 0.886, 0.855, and 0.812, respectively. In contrast, IL-10 and IL-17D showed poor discriminatory ability, with AUC values of 0.524 and 0.599, respectively. Combined ROC analysis markedly improved diagnostic accuracy, with all panels including ADAM10 achieving AUC values above 0.90, and some reaching as high as 0.988, with high sensitivity and specificity. The combination of ADAM10 with selected cytokines significantly enhances diagnostic performance compared to individual markers, supporting a link between immune dysregulation, barrier dysfunction, and gut permeability in ASD.

Humans↗

PubMed2026

Protein arginine methyltransferases as metabolic regulators: many roles beyond cancer.

Metabolic syndrome (MetS) comprises a cluster of interconnected metabolic abnormalities that collectively elevate the risk of cardiovascular disease and mortality. With its global prevalence escalating, understanding the molecular underpinnings of MetS has become increasingly imperative. Protein arginine methyltransferases (PRMTs), classically studied for their epigenetic functions and oncogenic properties, are now recognized as pivotal regulators of metabolic homeostasis. Emerging research reveals that these enzymes coordinate crucial aspects of cellular metabolism through multiple mechanisms, including methylation of metabolic transcription factors, modulation of nutrient-sensing pathways, and direct regulation of enzymatic activities in glucose and lipid metabolism. This review summarizes current knowledge on the metabolic roles of PRMTs, specifying their roles in the development and function of major metabolic tissues and their associations with various metabolic disorders. We further review how PRMTs influence metabolic processes by modifying key transcriptional networks and signaling cascades through methylation of different substrates. By integrating these insights, we establish PRMTs as central players in metabolic regulation and assess their potential as therapeutic targets for metabolic diseases beyond their established roles in cancer biology, thereby providing a framework for future research and clinical development.

glucose metabolism↗