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PubMed2026

Cine-derived mitral annular relaxation velocity for detection of preclinical left ventricular diastolic dysfunction.

OBJECTIVES: Imaging diastolic dysfunction in pre-clinical heart failure (HF) is challenging. We evaluated a novel cardiac MRI (CMR) biomarker, CMR e-prime (CMR-MARV), in patients at risk of HF. METHODS: In this substudy of the PARABLE trial (NCT04687111), 236 patients (71.6 ± 7.7 years, 61.6% male) fulfilling trial-defined ALVDD citeria underwent CMR with measurement of mitral annular relaxation velocity (CMR-MARV) at four mitral annular anchor points. Diastolic strain rates from FT were also assessed. Twenty-five age- and sex-matched controls were included (73.8 ± 3.1 years, 52% male). Group differences were tested with t-tests, diagnostic accuracy with ROC analysis, and predictors of diastolic dysfunction with adjusted logistic regression. RESULTS: Compared with controls, patients had significantly higher indexed maximal left atrial volume (LAVimax), LV end-diastolic and end-systolic volumes, and LV mass (all p < 0.001). Of FT variables, only peak diastolic longitudinal velocity differed between groups (p < 0.001). In multivariate models, CMR-MARV correlated with radial, circumferential, and longitudinal diastolic strain rates, radial and longitudinal diastolic velocities (all p < 0.001), echocardiographic e' (r = 0.20, p = 0.007), LV mass (r = -0.18, p = 0.008), LAVimax (r = -0.18, p = 0.008), and NT-proBNP (r = -0.30, p < 0.0001). LAVimax and CMR-MARV were strongly independently associated with ALVDD (AUC 0.89 and 0.76, respectively; p < 0.0001). A combined model (LAVimax + CMR-MARV) achieved excellent discrimination (AUC 0.91, 95% CI 0.86-0.97, p < 0.0001). Independent predictors included LAVimax, CMR-MARV, and peak diastolic longitudinal velocity (all p < 0.001). CONCLUSION: CMR-MARV provides a simple cine-derived measure of longitudinal relaxation that correlates with established structural and biochemical markers of diastolic burden. Within an at-risk population, it offers incremental functional information beyond conventional parameters and may support multiparametric CMR phenotyping of preclinical diastolic dysfunction.

Aged↗

PubMed2026

Association of the Charlson Comorbidity Index With 1-Year Outcomes in Patients With Macular Edema Secondary to Retinal Vein Occlusion.

OBJECTIVE: To determine the predictive value of the Charlson Comorbidity Index (CCI) for outcomes in patients with macular edema secondary to retinal vein occlusion (RVO). DESIGN: Retrospective clinical cohort study. SUBJECTS: Patients seen between 2013 and 2023 at the Cole Eye Institute, Cleveland Clinic, were included. All patients were >18, diagnosed with RVO (International Classification of Diseases (ICD)-9 and 10 codes), had a complete CCI score, and had at least 1 year of ophthalmic follow-up data after their first intravitreal injection (baseline). Patients with ocular surgery, trauma, or panretinal photocoagulation were excluded. METHODS: Age-adjusted CCI scores were calculated for each patient from chart review. For patients with bilateral RVO, one eye was selected randomly. Patients were stratified into tertiles by CCI distribution: tertile 1 (CCI 0-5; mean 3.4), tertile 2 (age-CCI 4.1-6; mean 4.9), and tertile 3 (CCI ≥ 8; mean 9.6). Multivariable linear regression was performed to determine the predictive value of CCI and other covariates on visual and anatomical outcomes. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 1-year follow-up. RESULTS: A total of 972 patients met all criteria, with an average age-adjusted CCI score of 6.2. Each one-point increase in CCI predicted 0.38 fewer letters in BCVA at follow-up (P < .001). Baseline BCVA was a significant predictor of follow-up BCVA in all tertiles (P < .001). In the third tertile, each one-point increase in CCI was associated with a 0.72 letter reduction in follow-up BCVA (P < .001). For CST, baseline CST was strongly predictive of final CST (P < .001), while CCI was only significant in the first tertile, where each point increase in CCI predicted a 13.7 µm increase in CST (P = .02). In RVO subtype interaction models, the age-adjusted CCI × CRVO interaction was not statistically significant for either 1-year BCVA (P = .269) or 1-year CST (P = .695). CONCLUSIONS: Higher CCI scores are significantly associated with worse visual outcomes in patients with RVO, particularly in the combined population and most comorbid patients (tertile 3). CCI was significantly associated with higher (thicker) CST only among the least comorbid patients (tertile 1).

Humans↗

PubMed2026

Bivalirudin Versus Heparin in Low and Non-Low Bleeding Risk Patients Undergoing Primary PCI for STEMI: The BRIGHT-4 Trial.

BACKGROUND: In the BRIGHT-4 trial, among 6,016 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with a radial artery approach, procedural anticoagulation with bivalirudin plus a post-PCI high-dose infusion for 2 to 4 hours reduced the 30-day primary composite outcome of all-cause death or Bleeding Academic Research Consortium (BARC) types 3 to 5 bleeding, as well as death and bleeding individually, compared with heparin monotherapy. OBJECTIVES: We sought to determine whether the benefits of bivalirudin apply principally to patients who are at low bleeding risk (LBR) as well as non-LBR. METHODS: In a prespecified analysis from BRIGHT-4, outcomes were examined by baseline bleeding risk, with LBR defined as a CRUSADE score <30. RESULTS: At baseline, 4,581 patients (76.1%) were categorized as LBR. Non-LBR patients had higher rates of the 30-day primary endpoint (8.6% vs 2.2%; HR: 4.08 [95% CI: 3.14-5.31]; P < 0.0001), driven by both greater mortality and BARC types 3 to 5 bleeding. In non-LBR patients, the primary outcome occurred in 8.1% of patients randomized to bivalirudin vs 9.2% of those randomized to heparin (difference: -1.1% [95% CI: -4.0% to 1.8%]; HR: 0.88 [95% CI: 0.62-1.26]). In LBR patients, the primary outcome occurred in 1.4% of patients randomized to bivalirudin vs 2.9% of those randomized to heparin (difference: -1.5% [95% CI: -2.3% to -0.6%]; HR: 0.49 [95% CI: 0.32-0.75]) (Pabsolute interaction = 0.81; Prelative interaction = 0.04). The effects of bivalirudin compared with heparin in reducing all-cause death were as robust in LBR patients compared with non-LBR patients (Pabsolute interaction = 0.67; Prelative interaction = 0.06). CONCLUSIONS: Among patients with STEMI undergoing primary PCI with radial artery access, procedural anticoagulation with bivalirudin plus a high-dose post-PCI infusion for 2 to 4 hours reduced the 30-day risk of all-cause death and major bleeding in patients at low bleeding risk as well as in patients at higher-risk of bleeding. (Bivalirudin With Prolonged Full Dose Infusion Versus Heparin Alone During Emergency PCI [BRIGHT-4; NCT03822975]).

Humans↗

PubMed2025

Outcome of conservative management of small renal stones in prepubertal children.

INTRODUCTION: Renal stones are relatively uncommon in the pediatric population. This study aimed to evaluate the utility of conservative management of small renal stones in prepubertal children. PATIENTS AND METHODS: A retrospective chart review was conducted for children (≤12 years old) with small renal stones (3-10 mm) from 2016 to 2023 who underwent conservative management. Management included periodic renal ultrasonography, every 6 months, in addition to good hydration. Stones were confirmed by two consecutive ultrasounds. We recorded the patient's demographics and ultrasound findings (stone side, size, laterality, location, number, and associated hydronephrosis). Surgical intervention was indicated if recurrent loin pain, recurrent UTI, or worsening hydronephrosis (obstructing stone). Nephrolithiasis was considered resolved if stones were not visualized on 2 consecutive ultrasounds. Moreover, we evaluated conservative management outcomes for those presented during infancy (<12 months) versus later. RESULTS: We included 52 patients (65renal units) who presented at a median age of 46.1months (5.3-155.1). Seventy-five percent of patients had incidental renal stones. The median stone size was 4 mm (3-10). Forty-six percent of stones were in the lower calyx. The majority (70.8 %) had no hydronephrosis at presentation. During a median follow-up of 39months, 15patients with 17units (26.2 %) were documented stone-free. Ten patients (19.2 %) had symptomatic stone events, all measured ≥4 mm. Of them, 6 patients (6 units) underwent surgical interventions, and 4 patients (4 units) experienced complications. A ROC curve analysis identified a stone size cutoff of 4 mm (sensitivity 100 % and 29 % specificity) that could be associated with symptomatic stone events. Using a multivariate Cox regression model, stone size was the only significantly associated factor with subsequent surgical intervention (p = 0.007). 19 % (10patients,12units) presented during infancy. Notably, the incidence of stone-free rate was significantly higher during infancy compared to older children (58.3 % vs 18.9 %,respectively). DISCUSSION: During a 39-month follow-up, 4 patients developed complications (2recurrent pain and 2 experienced UTI), supporting the safety of conservative management of small renal stones. This study is limited due to its retrospective design and the reliance on ultrasound as the main imaging method. To minimize that, all ultrasound images were carefully reviewed by two pediatric urologists. Moreover, renal stones were confirmed using strict criteria, which required detection in two consecutive ultrasounds. CONCLUSION: Although 26.2 % of units had spontaneously resolved nephrolithiasis, surgical intervention was only required in 11.5%of patients, all of whom had renal stones≥4 mm. Infants had higher spontaneous resolutions without complications, suggesting that conservative management may be especially effective in this subgroup.

Humans↗

PubMed2026

Direct background subtraction LC-MS/MS assay for human plasma progesterone: Full validation and comparative application.

OBJECTIVE: To develop and validate a liquid chromatography-tandem mass spectrometry method based on direct background subtraction for the quantification of endogenous progesterone in human plasma. METHODS: Protein precipitation was used for sample preparation with deuterated progesterone as the internal standard. Chromatographic separation was performed on an ACQUITY C18 column using gradient elution with 0.1% formic acid in water and acetonitrile at a flow rate of 0.3 mL/min. Mass spectrometry was operated in positive electrospray ionization mode with multiple reaction monitoring. Instead of using analyte-stripped matrix or surrogate matrix, authentic plasma was directly used for all validation experiments. Quantitation was achieved by subtracting the background signal, and results were compared with those from the classical method using stripped matrix. RESULTS: Excellent linearity was achieved over 0.1-100 ng/mL (R2 ≥ 0.99). Precision, accuracy, recovery, matrix effect, and stability all met FDA and ICH M10 acceptance criteria. Compared with the classical method, the bias in Cmax and AUC0-t was within ±15%, indicating no significant difference between the two methods. CONCLUSION: The direct background subtraction method avoids laborious preparation of blank matrix, eliminates matrix effect discrepancies, and is simple, efficient, and low-cost. It can serve as a general strategy for endogenous substance determination.

Humans↗

PubMed2026

Genome-wide characterization of heat shock protein genes reveals thermal stress-responsive candidates in Litopenaeus vannamei.

Heat shock proteins (HSPs) are conserved molecular chaperones involved in protein folding, refolding, aggregation prevention, and degradation of damaged proteins. However, the genomic organization and thermal responsiveness of HSP genes in the Pacific white shrimp (Litopenaeus vannamei) remain incompletely understood. Here, we performed a genome-wide analysis of the HSP gene family and examined its phylogenetic relationships, structural features, duplication patterns, sequence variation, interaction networks, and transcriptional responses to acute heat stress. A total of 34 HSP genes were identified and classified into the HSP90, HSP70, HSP40/DNAJ, HSP60, and small HSP families. Phylogenetic, motif, gene structure, synteny, and subcellular localization analyses revealed evolutionary conservation and structural diversification among family members. Three duplicated gene pairs were identified, comprising two segmental duplications and one tandem duplication. All pairs exhibited Ka/Ks ratios below 1, consistent with purifying selection of varying strength. Sequence analysis identified 295 nonsynonymous single-nucleotide polymorphisms, of which 12 were consistently predicted to be deleterious by multiple algorithms. Protein-protein interaction analysis indicated enrichment of protein-folding and cellular stress-response functions. RT-qPCR analysis showed significant induction of HSPA4, HSP90AA1, TRAP1, BiP, and DNAJA1 after 6, 12, and 24 h of exposure to 34 °C, whereas DNAJC3 was significantly induced only at 12 h. All six genes reached their highest transcript abundance at 12 h. These findings may provide a genomic framework for HSP genes in L. vannamei and identify candidate genes and variants associated with thermal stress responses.

Animals↗

PubMed2026

Azithromycin-resistant Salmonella enterica Typhi with AcrB R717L/Q mutations in the United States.

BACKGROUND AND OBJECTIVES: Azithromycin is a critical oral treatment for typhoid fever caused by Salmonella enterica serovar Typhi (Salmonella Typhi), since XDR has rendered other first-line treatment options ineffective. Azithromycin resistance conferred by amino acid changes in AcrB, an AcrAB-TolC efflux pump component, represents an emerging public health concern. Leveraging phenotypic and genotypic data from U.S. Salmonella Typhi surveillance systems, this study describes the prevalence, phenotype and genomic epidemiology of Salmonella Typhi with AcrB mutations in U.S. patients since the first detection in 2015. METHODS: AST and WGS data of >3000 Salmonella Typhi isolates were used to identify all cases with an AcrB mutation in the United States (2015-2025). We calculated annual prevalence and MIC ranges. Phylogenetic analysis was used to contextualize U.S. cases of Salmonella Typhi with an AcrB mutation within all globally reported cases. RESULTS: While the prevalence of AcrB mutations in the United States is low (1.5%), it has risen significantly in recent years, from 0.2% in 2016-2022 to 2.2% in 2023-2025. This increase is predominantly driven by clonal expansion of existing strains circulating in South Asia. AcrB mutations do not reliably confer resistance to azithromycin (MIC ≥ 32 mg/L), complicating clinical interpretation. CONCLUSIONS: The prevalence of AcrB mutations in Salmonella Typhi is increasing in the United States, and likely globally, given that U.S. data function as an informal proxy for regions without routine surveillance infrastructure. Clinical outcomes data are needed to inform Salmonella Typhi treatment guidelines and potentially amend clinical breakpoints for azithromycin.

Journal Article↗

PubMed2026

Genome-wide identification, structural characterization, and evolutionary analysis of growth-related gene families in African catfish (Clarias gariepinus).

The somatotropic axis encompassing growth hormone (GH), insulin-like growth factor (IGF), myostatin (MSTN), and prolactin (PRL) signalling cascades is the master regulator of somatic growth, metabolism, and development in vertebrates. African catfish (Clarias gariepinus), a commercially pivotal aquaculture species, now possesses a chromosome-level reference genome (CGAR_prim_01v2); however, a systematic, genome-wide characterization spanning all five interconnected growth-related gene families has not previously been undertaken in this species. Here, we identified and characterized 15 growth-related genes spanning gh1, ghra, ghrb, Igf1, Igf2a, Igf2b, igf1ra, Igf1rb, Igf2r, Mstna, Mstnb, prl, prlra, prlrb, and smtlb distributed across 13 chromosomes. Complete one-to-one orthology with zebrafish confirmed strong dosage-balance conservation across >120 million years of teleost divergence. Physicochemical analysis resolved a clear biochemical dichotomy between compact, basic secreted ligands (19.88-45.81 kDa; pI up to 10.02) and large, acidic, heavily glycosylated membrane receptors (56.82-270.80 kDa; pI 4.85-5.97). Phylogenetic analysis confirmed 3R whole-genome duplication origins for all paralog pairs, while synteny analysis revealed a disruption of the ancestral gh1-prl chromosomal block in C. gariepinus, a finding that warrants further comparative and functional investigation. This genomic atlas provides the sequence and structural information including exon-intron boundaries, domain architecture, and chromosomal coordinates needed as a prerequisite for future marker-assisted selection and CRISPR-based myostatin-editing efforts in African catfish aquaculture, though translation into applied breeding outcomes will require subsequent functional and expression studies.

Animals↗

PubMed2026

Not just when, but how: An exploratory dual-control approach to video feedback in motor learning.

The present study provides exploratory evidence for a novel dual-control paradigm. It examines whether combining temporal over video feedback timing with learner-controlled interactive playback functions (pause, slow-motion, rewind) would enhance motor skill acquisition beyond temporal autonomy alone. Sixty-four novice adults were randomly assigned to one of four conditions: Full Control (self-controlled timing + interactive replay), Partial Control (self-controlled timing + non-interactive replay), Yoked Full Control (externally controlled timing + interactive replay), or Yoked Partial Control (externally controlled timing + non-interactive replay). Motor accuracy (Radial Error), movement consistency (Bivariate Variable Error), technical execution, and self-efficacy were assessed at pre-test, 24-h retention, and 72-h retention following two acquisition sessions on a dart-throwing task (120 trials total). The Full Control group demonstrated the greatest and most durable learning gains across all outcomes. The Group × Time interaction was significant across all dependent variables (η2ₚ ranging from 0.140 to 0.234), with Full Control demonstrating superior retention at both 24 and 72 h relative to other groups (though differences relative to Partial Control were more pronounced at 72-h retention). Critically, the Yoked Full Control group showed comparatively weaker outcomes despite access to the same interactive playback functions. These findings suggest that interactive video tools may be most useful when learners can regulate both when feedback is accessed and how it is inspected. Theoretical and practical implications for the design of learner-centered video feedback systems are discussed.

Humans↗

PubMed2026

Longitudinal functional trajectory and surgical outcomes after intracranial meningioma resection: implications for surgical decision-making in older patients.

OBJECTIVE: As the population ages, meningiomas are increasingly encountered in older patients, yet longitudinal functional outcomes following surgery across age groups remain incompletely characterized. This study evaluated age-related differences in clinical and tumor characteristics, functional trajectory, and surgical outcomes. METHODS: This was a retrospective cohort study of 396 consecutive patients who underwent surgery for intracranial meningiomas at a single academic center between January 2023 and September 2025. Patients were stratified into 5 age groups (< 65, 65-69, 70-74, 75-79, and ≥ 80 years). Neurological deficits and Karnofsky Performance Status (KPS) were assessed preoperatively, at discharge, and at last follow-up. Logistic regression analyses identified predictors of prolonged length of stay (LOS) (> 5 days) and poor functional outcome at discharge (KPS < 80). RESULTS: Older patients presented with greater comorbidity burden, larger tumors, and lower preoperative KPS (all p < 0.05), while gross-total resection was achieved at comparable rates across all age groups (p = 0.504). A clinically meaningful inflection point was observed around age 75 years, with KPS < 80 at discharge rising from 7.4% and 9.7% in the < 65-year and 70- to 74-year subgroups and to 36.2% and 57.1% in the 75- to 79-year and ≥ 80-year subgroups (p < 0.001), and median LOS increased from 4 days in the younger groups to 9 and 7 days in the 75- to 79-year and ≥ 80-year groups (p < 0.001). However, recovery rates among patients who experienced functional decline at discharge were comparable across age strata. On multivariable analysis, independent predictors of prolonged LOS were age ≥ 75 years (OR 2.31, p = 0.019), diabetes mellitus (OR 2.85, p = 0.004), posterior fossa location (OR 2.1, p = 0.008), tumor diameter (OR 1.33, p < 0.001), postoperative edema (OR 2.58, p = 0.015), and neurosurgical complications (OR 3.18, p = 0.002). Independent predictors of poor functional outcome at discharge were age ≥ 75 years (OR 5.84, p < 0.001), lower preoperative KPS (OR 2.8, p < 0.001), posterior fossa location (OR 3.72, p = 0.003), neurosurgical complications (OR 3.56, p = 0.008), and recurrent meningioma (OR 2.89, p = 0.025). Among 70 endoscopic endonasal approach patients, higher preoperative deficit burden and subtotal resection rates were observed compared to open craniotomy, though overall functional outcomes were comparable. CONCLUSIONS: Surgical risk in meningioma resection increases from age 75 years onwards, yet recovery capacity following initial functional decline remains similar across all age groups. Preoperative functional status, tumor location, comorbidity burden, and recurrence history should guide surgical decision-making rather than age alone.

Humans↗

PubMed2026

Longitudinal whole-genome analysis of bluetongue virus identifies conserved serotype-specific genomes and distinct genomic constellations within a Colorado sheep flock (2021-2023).

Bluetongue virus (BTV) is a segmented double-stranded RNA virus of ruminants transmitted by Culicoides spp. biting midges. Although the genome consists of ten segments, classification into serotypes is primarily based on genome segment 2. However, reassortment among genomic segments is a major driver of BTV evolution and diversity. This study used longitudinal whole-genome sequencing to characterize BTV genomes collected from 2021 to 2023 within a single sheep flock in Colorado, where multiple serotypes co-circulate. Whole-genome sequences were generated from fourteen blood samples representing four serotypes: BTV-6, -11, -13, and -17. Longitudinal sampling identified multiple BTV serotypes within individual sheep across consecutive years. Tanglegram analysis comparing segment phylogenies to the segment 2 tree demonstrated incongruent topologies across all genomic segments, suggestive of reassortment or the circulation of distinct genomic constellations. Nucleotide-level comparisons revealed high sequence homology among same-serotype samples from the same year, while the greatest genetic divergence was observed among BTV-17 genomes collected in different years. Additionally, all BTV-13 genomes contained a previously undescribed nonsynonymous substitution in segment 10 predicted to extend the encoded protein by three amino acids. Together, these findings demonstrate that highly conserved BTV genomes and distinct genomic constellations can be detected at the flock level across multiple years. This longitudinal whole-genome approach reveals the genetic complexity of endemic BTV populations, including novel variants and genomic patterns consistent with reassortment that are lost with conventional serotyped-based approaches, highlighting the need to integrate whole-genome characterization into endemic BTV monitoring programs.

Animals↗

PubMed2026

Validated UPLC-MS/MS quantification and intracellular PK-PD Modeling of periplocin-related cardiac glycosides in H/R-injured H9c2 cells.

Reliable intracellular quantification is essential for characterizing the target-site disposition and exposure-response relationships of bioactive natural products. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of periplocin and four related cardiac glycoside metabolites in H9c2 cell lysates. Acceptable linearity, precision, recovery, and stability were achieved for intracellular quantification. Cells were treated with each compound at 50 μM, and intracellular concentrations and cell viability were monitored over 48 h. In hypoxia/reoxygenation (H/R) -injured cells, the time to maximum intracellular concentration was shortened for all five compounds, indicating altered cellular disposition under injury conditions. Cell viability was improved by all compounds during the observation period. Pharmacokinetic-pharmacodynamic (PK-PD) integration was performed using a sigmoid Emax model, and acceptable model fits were obtained, with Akaike information criterion (AIC) values ranging from 79.22 to 130.46. Low apparent EC50 values were estimated under this single-dose design, whereas the estimated Ke0 values suggested delayed equilibration with the effect compartment. These findings indicate that sustained cytoprotective responses can be produced by periplocin and related metabolic markers in injured cardiomyocytes. This intracellular bioanalytical strategy provides a quantitative approach for linking cellular exposure to pharmacodynamic response and may support further evaluation of periplocin-related cardiac glycosides.

Tandem Mass Spectrometry↗

PubMed2026

Psychometric Evaluation of the Breast Inflammatory Symptom Severity Index Versions 2 and 3 Among Lactating Women.

OBJECTIVE: To evaluate the psychometric properties of Versions 2 and 3 of the Breast Inflammatory Symptom Severity Index (BISSI). DESIGN: Secondary data analysis of clinical trial data. SETTING: Private physiotherapy practices, a public tertiary hospital, and a community in Melbourne, Australia. PARTICIPANTS: Women more than 7 days after birth with inflammatory conditions of the lactating breast (N = 43). METHODS: We performed confirmatory factor analysis of the BISSI Version 2 to examine item loading, which informed development of the BISSI Version 3 (V3). We assessed convergent validity by comparing total BISSI V3 scores with human milk sodium to potassium ratio (Na+:K+) at Trial Days 1, 3, and 10 using Bland-Altman plots. We compared item-level scores for size of affected area with objective receiver operating characteristic curve analysis to assess discriminant validity for symptom severity and Cronbach's alpha for internal reliability. RESULTS: After confirmatory factor analysis, we removed two items, resulting in a six-item BISSI V3. All retained items demonstrated comparable loading on the overall scale. Limits of agreement for total BISSI V3 scores and item-level scores for size of affected area were acceptable at all time points, with more than 90% of observations falling within 2 standard deviations of the mean difference, supporting convergent validity. Discriminant validity of the BISSI V3 was supported. We found high internal reliability at both time points CONCLUSION: Our findings provide evidence for the validity and reliability of the BISSI V3 and support its continued development and for clinical use of the BISSI V3 and human milk Na+:K+ analysis to enhance management of inflammatory conditions of the lactating breast.

breastfeeding↗

PubMed2026

Quantifying the aromatic amino acid metabolome: UPLC-MS/MS analysis of aromatic amino acids and their host and co-metabolites in plasma.

Aromatic amino acids (AAAs), tryptophan, phenylalanine, and tyrosine along with their pathway metabolites have been implicated in the pathogenesis of diseases ranging from cardiovascular, neurological, inflammatory, and cancer diseases, among others. As such, the measurement of the primary AAAs, their host pathway metabolites, and microbiome derived co-metabolites in blood can provide a sensitive reflection of systemic health. The aim of the study was to develop a method for the quantification of 17 metabolites, the three AAAs and various of their metabolites in plasma using a high-throughput ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The method demonstrated a dynamic range (1 to 16,700 ng/mL), with detection limits (LOD) as low as 0.05 ng/mL. Quantification limits ranged from 3 to 5019 ng/mL (LLOQ) and up to 16,700 ng/mL (ULOQ). Recovery at LQC, MQC, and HQC was satisfactory and consistent across most metabolites, with significant matrix effects observed only for 4-ethylphenol sulfate. Furthermore, intra and inter-day accuracy and precision met all acceptance criteria at all quality control concentrations for most of the metabolites. Measurement of NIST SRM 1950 showcased the method's accuracy for most of the metabolites. Finally, the method was applied on the analysis of plasma samples from 55 individuals (13 males and 42 females) providing information on AAAs and their pathway metabolites relevant concentrations in human plasma.

Amino Acids, Aromatic↗

PubMed2026

Frequency of Human Brucellosis Complications in West Asia: A Systematic Review and Meta-Analysis.

BACKGROUND: Brucellosis is a multi-systemic zoonotic infection. The West Asia/Middle East region is an important global hotspot for brucellosis. This systematic review and meta-analysis aimed to aggregate and synthesize all the available evidence regarding the complications of brucellosis in West Asia/Middle East region. METHODS: PubMed, Embase, Scopus, Web of Science, Google Scholar, and Proquest were searched. Selection of studies, data extraction, and the risk of bias assessment were performed in duplicate. Data extraction was performed for 254 complications. Meta-analysis was performed using a random-effects model with Freeman-Tukey double arcsine transformation. Where applicable small-study effects was assessed using funnel plots and Egger's test. Separate by-country, by-age, and by-publication-decade subgroup analyses were performed if feasible. RESULTS: Out of 9518 results, 240 studies (260 references) were included. The majority of the included studies were conducted in Turkey (n = 177). The reported complications varied and different complication categorization systems were detected. The highest pooled estimate was observed for musculoskeletal involvement (50%, 95%CI: 39%-61%, I2 = 96.63%). The evidences is up-to-date until March 4, 2024. CONCLUSIONS: Some complications such as the complications of the eye were not reported in all the countries. Therefore, it's recommended to determine the relative frequency of those complications in regions without such reports. The pooled estimates of different complications of brucellosis were different. There's a need for the standardization of the reporting of the complications of brucellosis to achieve comparability between studies and across different regions.

Brucellosis↗

PubMed2026

Adolescent health across Asia Pacific, 2000-23: a systematic analysis for the Global Burden of Disease Study 2023.

BACKGROUND: The Asia Pacific region is home to more than half of the world's 1·93 billion adolescents (aged 10-24 years). Addressing adolescent health in this region is of global importance, but to date a systematic analysis of key contributors to disease in adolescents has not been done, which is a barrier to responsive action. This systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 aims to provide a comprehensive assessment of adolescent health across the Asia Pacific region, at both the subregional and national levels, encompassing burden of disease, mortality, and prevalence of adolescent risk factors. METHODS: As part of GBD 2023, we obtained estimates for cause-specific mortality, disability-adjusted life-years (DALYs), and risk factor prevalence by sex for adolescents aged 10-24 years and 5-year age groups (10-14 years, 15-19 years, and 20-24 years) across 44 countries and territories (hereafter referred to collectively as Asia Pacific), grouped by seven UN subregions, from 2000 to 2023. We extracted GBD 2023 population counts and estimates of number and rate (per 100 000 population) for mortality and disease burden (DALYs). Risk prevalence estimates were obtained directly from the Institute for Health Metrics and Evaluation, and binge drinking estimates were sourced from WHO. Estimates are reported with 95% uncertainty intervals (UIs) where possible. UIs were estimated by running 250 draws of the posterior distribution, ordering the draws, and selecting the 2·5th and 97·5th percentiles for each metric. FINDINGS: In 2023, in adolescents across Asia Pacific, there were 637 496 deaths and a total disease burden of 115·8 million DALYs, representing 34·1% of global adolescent deaths and 40·6% of the global adolescent burden of disease. Non-communicable diseases (NCDs; particularly mental disorders) were the leading causes of disease burden and mortality (64·8% of DALYs and 43·9% of deaths). Unintentional and transport injuries were also leading causes of death (14·7% of deaths due to transport injury and 13·3% of deaths due to unintentional injury) and leading causes of disease burden particularly among males in south-eastern Asia. In Melanesia, Micronesia, and some parts of south-eastern Asia (Cambodia, Indonesia, Laos, the Philippines, and Timor-Leste), respiratory infections and tuberculosis remained important contributors. Southern Asia had the largest reduction (1·5% per year) in all-cause DALYs over the study period, and Australia and New Zealand (0·2% per year) had the smallest, with females in Australia and New Zealand showing a slight increase contrary to regional trends. Eastern Asia had the largest reduction (2·8% per year) in all-cause mortality rate and Melanesia (0·8% per year) the smallest. Risk factors generally had between-subregion and within-subregion variation; however, some regional trends stood out, with overweight and obesity increasing in all countries across the region, and binge drinking increasing in more countries than not. In 2023, prevalence of smoking in males exceeded that in females in every country, from 40% difference in Timor-Leste to less than 1% difference in Australia. Anaemia prevalence is decreasing in all countries, but female prevalence was higher and reducing at a slower rate than in males. Bullying prevalence was slightly higher in Polynesia, Micronesia, and Melanesia combined, Australia and New Zealand, and eastern Asia compared with southern and south-eastern Asian subregions. INTERPRETATION: Several patterns were consistent across the region: the dominance of mental disorders and NCDs, the universal rise in overweight and obesity (particularly high in Oceanic countries but increasing rapidly in south and south-eastern Asia), and persistent sex-specific challenges across subregions: unintentional injuries and smoking in males, and anaemia in females. Actions to tackle shared risk factors (while accounting for context-specific local health profiles, workforce deficits, cultural factors, and health system capacity) should not be forgone due to local variation. Future research could focus on subnational variation, intersecting inequalities, and multi-sectoral interventions targeting shared risk factors. Priority actions should include regional investment in adolescent mental health services and obesity prevention, targeted injury reduction strategies for high-risk populations, and sex-specific approaches to smoking cessation and anaemia reduction, delivered through local health systems with the capacity and cultural responsiveness to meet local needs. FUNDING: Gates Foundation and Australian Government.

Humans↗

PubMed2026

Efficacy and safety of JAK inhibitors in Behçet syndrome: systematic literature review.

OBJECTIVES: Given the active role of the JAK signaling pathway and the multifactorial immune mediators observed in Behçet syndrome (BS), JAK inhibitors (JAKi) may be promising agents. In this systematic literature review (SLR), we aim to evaluate the efficacy and safety of JAKi in BS. METHODS: A systematic literature search was conducted in Embase, PubMed, and the Cochrane Library to identify all reports on the efficacy and safety of JAKi in patients with BS. The SLR protocol was registered with the International Prospective Registry of Systematic Reviews (CRD420251000172). We additionally presented our patient with gastrointestinal involvement treated with upadacitinib. RESULTS: Among the 92 patients (48 men, mean (SD) age 38.5 (13.5) years), 46 used tofacitinib, 31 used baricitinib, and 15 used upadacitinib. All but 1 patient had used at least one previous conventional immunosuppressive, and 57.6% were refractory to at least one prior tumor necrosis factor inhibitor. JAKi were used in combination with conventional immunosuppressive and/or glucocorticoids in 90.6% of the patients. The primary indication for JAKi initiation was gastrointestinal involvement in 46 (50%) patients including our patient, vascular involvement in 22 (23.9%), uveitis in 19 (20.6%), and mucocutaneous and/or articular involvement in 5 (5.6%) patients. The remission rates for overall, gastrointestinal, vascular, and eye involvement were 85.9%, 82.6%, 90.9%, and 84.2%. Serious adverse events were observed in 5.4% of the patients. No thrombotic events were reported. CONCLUSION: This SLR showed that JAKi may be effective in refractory BS patients with a favorable safety profile.

Humans↗

PubMed2026

Gloeotrichia echinulata genomes from the United States are nontoxigenic and likely geosmin producers.

Six Gloeotrichia echinulata genomes derived from planktonic harmful algal blooms (HABs) with similar colonial morphology have been sequenced from lakes in the west and northeast regions of USA, four of them to completion. The c. 7 Mbp genomes exhibit a high level of conservation, with 98-99% pairwise genome-wide average nucleotide identity and high levels of synteny, representing a single species cluster. We observed strong conservation of gene clusters responsible for the synthesis of the secondary metabolites and bioactive peptides that are characteristic of HAB-forming cyanobacteria. All six G. echinulata genomes lack genes for the synthesis of classic cyanotoxins, including microcystin, but possess genes responsible for the synthesis of the taste and odor compound geosmin. Interestingly, the geoA geosmin synthase gene in three genomes is homologous to other cyanobacterial geoA genes, while the other three geoA genes are related to actinomyces geoA. Phylogenomic analysis places the G. echinulata genomes within a clade of benthic Nostocales, reflecting an ecological niche featuring extensive growth on the sediment surface before colonies disperse into the epilimnion for planktonic growth. We identify genes conserved in all six genomes that could represent physiological adaptations supporting active growth on sediments and pelagic recruitment independent of wind-driven mixing: phycoerythrin light harvesting complexes for optimal photosynthesis at depth; gliding motility to access patchy nutrient distributions; and gas vesicles with relatively small GvpC proteins that predict resistance to higher hydrostatic pressure. The strong genomic similarity across geographically distant populations suggests that G. echinulata in the United States is a tightly related non-toxigenic species group with predictable properties relevant to public health and drinking water management.

Cyanobacteria↗