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Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

Female

Artificial Intelligence in Diagnosing Depression Through Behavioural Cues: A Diagnostic Accuracy Systematic Review and Meta-Analysis.

AIM: To synthesise existing evidence concerning the application of AI methods in detecting depression through behavioural cues among adults in healthcare and community settings. DESIGN: This is a diagnostic accuracy systematic review. METHODS: This review included studies examining different AI methods in detecting depression among adults. Two independent reviewers screened, appraised and extracted data. Data were analysed by meta-analysis, narrative synthesis and subgroup analysis. DATA SOURCES: Published studies and grey literature were sought in 11 electronic databases. Hand search was conducted on reference lists and two journals. RESULTS: In total, 30 studies were included in this review. Twenty of which demonstrated that AI models had the potential to detect depression. Speech and facial expression showed better sensitivity, reflecting the ability to detect people with depression. Text and movement had better specificity, indicating the ability to rule out non-depressed individuals. Heterogeneity was initially high. Less heterogeneity was observed within each modality subgroup. CONCLUSIONS: This is the first systematic review examining AI models in detecting depression using all four behavioural cues: speech, texts, movement and facial expressions. IMPLICATIONS: A collaborative effort among healthcare professionals can be initiated to develop an AI-assisted depression detection system in general healthcare or community settings. IMPACT: It is challenging for general healthcare professionals to detect depressive symptoms among people in non-psychiatric settings. Our findings suggested the need for objective screening tools, such as an AI-assisted system, for screening depression. Therefore, people could receive accurate diagnosis and proper treatments for depression. REPORTING METHOD: This review followed the PRISMA checklist. PATIENTS OR PUBLIC CONTRIBUTION: No patients or public contribution.

Humans

Automated CEAP Classification of Venous Duplex Reports Using Multimodal Artificial Intelligence.

OBJECTIVE: To develop and internally validate a prototype multimodal artificial intelligence system for automated CEAP (Clinical, Etiological, Anatomical and Pathophysiological) classification of venous duplex ultrasound (VDUS) reports, integrating natural language processing of free-text components with computer vision analysis of hand-drawn anatomical diagrams. METHODS: Single centre retrospective observational study using routinely collected clinical data. One thousand consecutive venous duplex ultrasound reports from Cambridge University Hospitals NHS Foundation Trust, UK (July 2024 - May 2025) were labelled according to the CEAP classification, excluding the Etiological component, which could not be reliably determined from duplex reports alone. Transfer learning was applied using ClinicalBERT for text and MobileNetV3 for diagrammatic data. Clinical classes were predicted from request line text. Text- and image-based pathophysiological models were developed for four anatomical territories (Great Saphenous Vein, Small Saphenous Vein, Deep system, Perforators), combined using late fusion with probability averaging. RESULTS: The clinical CEAP model achieved accuracy of 0.91, macro-F1 of 0.82, and macro-AUC of 0.98. Pathophysiological prediction varied, with text models broadly outperforming image models. Fusion yielded heterogeneous benefits, improving SSV performance but reducing Deep system accuracy. The performance of the final pathophysiological CEAP fusion models varied across anatomical territories: accuracy ranged from 0.70-0.92 and macro-AUC from 0.80-0.92. CONCLUSION: This study demonstrates the feasibility of automated CEAP classification from VDUS reports. Despite class imbalance affecting minority class predictions, the strong discriminatory performance validates this multimodal ML model for extracting clinically meaningful information from real-world data. This approach offers potential, pending external validation, to streamline vascular services through automated triage and guideline-compliant decision making.

Artificial intelligence

Infertility treatment in women with epilepsy: A systematic review.

BACKGROUND: The impact of assisted reproductive technologies (ART) on seizure control in women with epilepsy remains incompletely understood. METHODS: A systematic review was conducted according to PRISMA guidelines. EMBASE, MEDLINE, CINAHL, Scopus, and the Cochrane Library were searched from inception to March 2025. Eligible studies included observational studies and case-based reports involving women undergoing infertility treatment. RESULTS: A total of 1216 publications were identified, of which four studies met the inclusion criteria, including case reports, a case series, and a cohort study. These studies included 16 women aged 25-46 years undergoing infertility treatment, all but one of whom had epilepsy. Interventions involved in vitro fertilization (IVF), ovulation induction, and hormonal therapies. Patients were treated with a range of antiseizure medications (ASMs), including carbamazepine, clobazam, lamotrigine, levetiracetam, oxcarbazepine, valproate, and zonisamide, either as monotherapy or in combination. Seizure frequency was generally stable, with most patients maintaining baseline seizure control. Seizure exacerbations were uncommon and primarily associated with hormonal therapy and reduced ASM levels, particularly reduced lamotrigine levels. Reported events included breakthrough seizures in the setting of decreased lamotrigine concentrations, seizure clusters associated with follitropin beta, and a new-onset seizure following dehydroepiandrosterone exposure. Across studies, multiple ART attempts resulted in live births with different ASM regimens, as well as in patients not receiving ASMs. CONCLUSION: Available evidence suggests that ART is feasible in women with epilepsy, with most patients maintaining stable seizure control. Hormonal therapy may affect ASM pharmacokinetics and seizure threshold, thereby warranting close monitoring. Larger prospective studies are needed to better define ASM-specific effects and optimize care.

Humans

Toileting dysfunction in SATB2-associated syndrome: results from a caregiver survey.

BACKGROUND: Toilet training and continence are major developmental milestones, but children with neurogenetic conditions often experience extreme difficulties, sometimes never achieving full continence. These challenges impose ongoing burden on caregivers, especially as children age and require toileting assistance outside the home. SATB2-associated syndrome (SAS) is a rare genetic disorder in which such functional issues have not been systematically studied. We sought to assess bladder and bowel function in individuals with SAS and compare symptoms burden to normative data. METHODS: Caregivers completed a survey that included the Vancouver Symptom Score (VSS) for Dysfunctional Elimination Syndrome. VSS scores were analyzed and compared to published norms. Additional data included toilet training milestones, continence status, urinary tract infections, and bowel treatment history. RESULTS: Of the 32 individuals with SAS represented in the caregiver-reported survey, over half (53%) were not toilet trained, and only 22% were fully trained for both day and night (mean age at toilet training 6.9 years). The SAS group (n = 32) had a median total VSS of 16.0 (range: 6-30), indicating clinically significant dysfunction, while control data (n = 49) reported a median of 5.0 (range: 0-12, p < 0.001), with the greatest differences observed in daytime wetting, nighttime wetting, wetting extent, and fecal soiling. CONCLUSIONS: Individuals with SAS experience markedly elevated elimination symptom burden. Findings support the need for early screening and intervention to promote continence and reduce caregiver strain. A clinical pathway is proposed for screening, evaluation, and management of elimination dysfunction in SAS.

Humans

Associations between prescribed amphetamines and spontaneous cervical artery dissection: a matched case-control study.

AIMS: To assess whether prescribed amphetamines are associated with spontaneous cervical artery dissection (sCeAD), an important cause of stroke in young adults. METHODS: We conducted a retrospective matched case-control study within a large academic health system in Chicago, Illinois. Adults aged 18-85&#xa0;years with incident sCeAD were matched 1:4 to controls without dissection on age, sex, and race/ethnicity. The primary exposure was documented amphetamine prescription. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) controlling for relevant vascular and clinical covariates. Sensitivity analyses included strict matched-strata and inverse probability-weighted models. RESULTS: Among 11,463 individuals, including 2,293 cases and 9,170 controls, amphetamine exposure was associated with higher odds of sCeAD (adjusted OR 1.70, 95% CI 1.18-2.46). Results were unchanged in strictly matched strata (OR 1.70, 95% CI 1.18-2.46) and remained directionally consistent after inverse probability weighting (OR 1.40, 95% CI 1.09-1.79). High-dose amphetamine exposure (&#x2265;30&#xa0;mg/day) had the strongest association (OR 1.96, 95% CI 1.18-3.26), whereas low-dose exposure was not statistically significant. CONCLUSION: Prescribed amphetamines were associated with modestly increased odds of sCeAD. While these findings are observational and hypothesis-generating, they may support a possible association in susceptible patients.

Humans

Protective association of the ELMO1 rs741301 variant against diabetes mellitus and diabetic nephropathy: a systematic meta-analysis of case-control studies.

CONTEXT: Diabetes mellitus (DM), an endocrine disorder, is characterised by persistently elevated blood glucose levels due to inadequate insulin production. Diabetic nephropathy (DN), is a critical complication associated with DM, often leading to end-stage renal failure and increased mortality. OBJECTIVE: This meta-analysis aimed to evaluate the association between the ELMO1 rs741301 polymorphism and susceptibility to DN among individuals with diabetes. METHOD: A systematic literature search was conducted for studies published between 2014 and 2024 using Embase, Google Scholar, and PubMed. Eligible case-control studies investigating the association between ELMO1 rs741301 and DN among individuals with DM were selected according to predefined inclusion criteria. Nine case-control studies comprising 880 individuals with DM and 1008 individuals with DN were included in the meta-analysis. RESULTS: The pooled analysis demonstrated a significant protective association between the ELMO1 rs741301 polymorphism and DN under the allelic model (OR = 0.77, 95% CI: 0.67-0.88), recessive model (OR = 0.74, 95% CI: 0.61-0.90), and dominant model (OR = 0.68, 95% CI: 0.53-0.88). In contrast, no statistically significant association was observed under the over-dominant model. CONCLUSION: The findings suggest that the ELMO1 rs741301 polymorphism may be associated with a reduced susceptibility to DN among individuals with DM. These findings provide evidence for a potential genetic contribution of ELMO1 to DN susceptibility and may help improve understanding of the genetic factors underlying diabetic complications. Further well-designed studies in diverse populations are warranted to validate this association.

Humans

Effectiveness of Topical Huzhang Sanhuang with Standard Nursing for Chemotherapy-Induced Phlebitis: Randomized Controlled Study.

Chemotherapy-induced phlebitis (CIP) is a common complication of peripheral intravenous chemotherapy that can cause pain, local inflammation, treatment interruption, and diminished quality of life. This randomized controlled trial evaluated the efficacy and safety of the topical Huzhang Sanhuang (HZSH) formula, combined with standard nursing care, in managing CIP. Ninety-four hospitalized patients with CIP (grade I or higher) were randomly assigned in a 1:1 ratio to receive either topical HZSH formula plus standard nursing care (experimental group, n = 47) or 50% magnesium sulfate wet dressing plus standard nursing care (control group, n = 47) for 14 days. Prespecified outcomes included phlebitis grade, visual analog scale (VAS) pain score, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), symptom resolution time, and safety indicators. By Day 14, patients in the experimental group demonstrated significantly greater improvement in phlebitis severity than those in the control group (risk ratio for grade &#x2265; II, 0.42; 95% confidence interval, 0.20-0.87; P = 0.012). The experimental group also showed significantly larger reductions in VAS pain scores, hs-CRP levels, and IL-6 concentrations (all P < 0.01). Kaplan-Meier analysis further demonstrated faster resolution of multiple local symptoms in the experimental group. Treatment adherence was high in both groups, and no serious adverse events or major safety concerns were observed. These findings indicate that the topical HZSH formula, combined with standard nursing care, is a safe and effective integrative nursing intervention that accelerates clinical recovery, alleviates local symptoms, and reduces the inflammatory burden in patients with chemotherapy-induced phlebitis.

Humans

Effects of extended problem-based learning interventions on undergraduate nursing education: A systematic review.

OBJECTIVE: Exploring the effects of long-term PBL (problem-based learning) intervention on undergraduate nursing students. METHODS: The article retrieved literature from CINAHL Complete, Academic Search Complete, Web of Science, PubMed, EMBASE, OVID, and Cochrane Library up to January 2025. Studies had to meet all of these criteria: (1) They used a randomized controlled trial (RCT) and quasi-experimental design. (2) The PBL pedagogy intervention lasted 4&#xa0;weeks or longer. (3) The participants were undergraduate nursing students. (4) They reported primary outcomes. These included critical thinking, problem-solving skills and self-directed learning. Two researchers screened articles, extracted data, and assessed quality independently using blinding. They used Cochrane ROB2 for RCTs and ROBINS-I for quasi-experimental studies to judge bias risk. Meta-analysis was performed using RevMan 5.4 software. For continuous variables, standardized mean difference (SMD) and 95% confidence interval were calculated. Heterogeneity was assessed by I2 statistic. When I2&#xa0;>&#xa0;50%, sensitivity analysis was conducted. The source of heterogeneity was explored by excluding studies one by one. The primary outcomes included standardized critical thinking, problem-solving, and self-directed learning assessment results. RESULTS: A total of 11 randomized controlled trials and quasi-experimental studies were retrieved and included for meta-analysis. The experimental group significantly outperformed the control group in critical thinking, problem-solving, and self-directed learning, with differences being statistically significant (P&#xa0;&#x2264;&#xa0;0.05). However, high heterogeneity was observed. After sensitivity analysis, the heterogeneity was reduced and the results remained statistically significant, indicating that the findings were not solely dependent on the excluded studies.

Problem-Based Learning

A chromosomal gtrB homolog and dam differentially contribute to dry-heat and high hydrostatic pressure resistance in Salmonella enterica.

Salmonella enterica can persist in low-moisture foods and shows enhanced dry-heat resistance under low water activity, posing significant food safety challenges. However, the genetic basis of extreme dry-heat resistance and its relationship with other processing stresses remain unclear. In this study, twelve S. enterica strains were screened for dry-heat treatment at 60&#xa0;&#xb0;C and 80&#xa0;&#xb0;C, with S. Infantis CICC21649 identified as the most resistant strain. Comparative genomics and transcriptional analysis identified candidate genes related to envelope integrity and regulation, including gtrB and dam. Deletion of the chromosomal gtrB homolog reduced dry-heat resistance, producing an additional 0.91-log10 reduction relative to the parent strain at 80&#xa0;&#xb0;C. Deletion of dam caused broader stress sensitivity, reducing resistance to both dry heat and high hydrostatic pressure, with the stronger phenotype observed under high hydrostatic pressure. Proteomic analysis of the chromosomal gtrB homolog mutant revealed broad alterations in envelope-associated proteins, transport functions, oxidative stress pathways, and central metabolism under dry-heat stress. These findings indicate that the chromosomal gtrB homolog is an important contributor to extreme dry-heat resistance, whereas dam contributes to resistance against both dry-heat and high hydrostatic pressure, likely through a broader regulatory role in stress adaptation. These results reveal distinct structural and regulatory layers underlying stress adaptation in S. enterica and provide practical guidance for low-moisture food processing by highlighting the need to account for strain-dependent and stress-specific resistance during process validation.

Hydrostatic Pressure

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

Clinical and endocrine correlates of genetic etiologies in severe hypospadias: Study from 34 patients.

OBJECTIVE: Hypospadias is a prevalent congenital anomaly (0.3%-1.0%); however, severe hypospadias (defined as proximal cases with the meatus at the penoscrotal junction, scrotum, or perineum) is a rare and clinically challenging entity with a multifactorial etiology. This study aimed to characterize the interrelationships among the clinical, endocrine, and genetic profiles in children with severe hypospadias. MATERIALS AND METHODS: We conducted a comprehensive analysis of 34 male patients with severe hypospadias. Preoperative hormone levels were measured using two methods: chemiluminescent immunoassay for luteinizing hormone and follicle-stimulating hormone, and liquid chromatography-tandem mass spectrometry for testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), 17&#x3b1;-hydroxyprogesterone (17&#x3b1;-OHP), and other steroids. Genetic analysis was conducted via whole exome sequencing. RESULTS: The diagnostic yield of clinically relevant genetic variants (including pathogenic and likely pathogenic, and variants of uncertain significance) in our cohort was 41.2% (14/34) of patients. Patients carrying these variants exhibited a more complex phenotypic profile compared to non-carriers, including a significantly higher rate of patients with &#x2265;3 associated malformations and a greater prevalence of cryptorchidism. Furthermore, the group with clinically relevant variants showed selective elevations in adrenal-derived precursors, specifically 17&#x3b1;-OHP and DHEA. Correlation analysis revealed significant positive associations of both 17&#x3b1;-OHP levels and the T/DHT ratio with the number of associated malformations. CONCLUSION: This study reveals significant genetic heterogeneity in patients with severe hypospadias. Those carrying genetic variants was associated with more severe clinical phenotypes, while certain endocrine variations, including the elevation of adrenal-derived hormones, were also observed in this cohort.

Humans

The knee-ankle link: impact of knee varus severity on distal joint malalignment and concomitant pathologies.

BACKGROUND: Knee varus deformity is traditionally managed as an isolated joint pathology; however, persistent distal symptoms following proximal realignment suggest a more extensive kinetic chain dysfunction. The degree to which knee varus severity dictates distal malalignment and secondary pathologies remains poorly quantified in the current literature. METHODS: This systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines (PROSPERO: CRD420261363327). A comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library was performed from inception to April 2026. Studies examining the relationship between knee varus (HKA angle) and radiographic distal alignment or pathologies were included. Data synthesis utilized random-effects models, with prevalence analyzed via generalized linear mixed models (GLMM). RESULTS: Fourteen studies were included in the final synthesis. While pooling of continuous radiographic parameters was limited by high statistical heterogeneity in Talar Tilt (I2&#xa0;=&#xa0;96.5%), individual large-cohort data (Huang et al.) indicated that severe knee varus (HKA&#xa0;>&#xa0;10&#xb0;) was associated with increased odds of concomitant ankle osteoarthritis (OR 2.29; 95% CI 1.28-4.11) and a specific cohort prevalence of 37.1%. Furthermore, single-arm prevalence data revealed divergent trends across different study populations, with compensatory hindfoot valgus reaching 69.9% in some cohorts and rigid varus up to 63.9% in others. CONCLUSIONS: Severe genu varum is associated with distal kinetic chain alterations and concomitant ankle pathologies. However, due to the extreme heterogeneity and divergent distal adaptations observed across different cohorts, standardized knee-centric protocols may be insufficient. Further longitudinal and interventional studies are required to establish phenotype-specific rehabilitation guidelines.

Humans

Health risk assessment of inorganic arsenic: an umbrella review.

Inorganic arsenic (iAs) is a toxic environmental pollutant linked to serious health risks, prompting global regulatory efforts. This study identifies major health conditions associated with iAs exposure using text network analysis, and assesses health risk assessments through an umbrella review and dose-response analysis. It synthesizes previous systematic reviews to offer a broader perspective on iAs-related health effects. An optimized text network analysis-based search strategy was applied across multiple databases to identify relevant systematic reviews. An umbrella review framework was employed to synthesize and reinterpret findings across systematic reviews. The methodological quality of included systematic reviews was assessed using the A MeaSurement Tool to Assess systematic Reviews 2 tool. Extracted data on study characteristics, exposure levels, and risk estimates were analyzed to evaluate the dose-response relationship between iAs exposure and health outcomes. From 922 systematic reviews, 36 were included and categorized into 10 health condition groups. For example, seven SRs found a significant dose-response relationship between iAs and bladder cancer, with one systematic review reporting relative risks of 2.70, 4.20, and 5.80 at 10, 50, and 150&#x202f;&#xb5;g/L, respectively. Individual study analysis further showed that each 10&#x202f;&#xb5;g/L increase in iAs raised bladder cancer risk by 3.11&#x202f;% (p=0.003). iAs exposure is associated with hypertension, diabetes, cardiovascular disease, and adverse fetal outcomes. Dose-dependent increases in bladder cancer, lung cancer, and hypertension risks were observed. These findings support more precise health risk assessments and regulatory strategies.

Humans

From premature adrenarche to adult metabolic risk and hyperandrogenism: a systematic review and meta-analysis.

CONTEXT: Idiopathic premature adrenarche (IPA) has been associated with a higher risk of metabolic and reproductive dysfunction, but long-term/adult outcomes remain incompletely known. OBJECTIVE: To assess the relationship between IPA and metabolic syndrome, as well as polycystic ovarian syndrome, in premenarcheal adolescent and adult women. METHODS: We conducted a systematic review and meta-analysis of observational studies reporting outcomes in females with IPA after menarche. Databases were searched through February 2025. Primary outcomes included body mass index (BMI), insulin resistance markers, and clinical and biochemical markers of hyperandrogenism. Data were pooled using random-effects models. The GRADE approach was applied to assess the certainty of evidence. RESULTS: A total of 21 studies comprising 635 females with IPA and 307 age-matched controls were included. Compared to controls, IPA individuals showed significantly higher BMI (mean difference: 1.4; CI: 1.0-1.9), fasting insulin, and homeostasis model assessment of insulin resistance, indicating persistent insulin resistance. Markers of hyperandrogenism, including Ferriman-Gallwey score, dehydroepiandrosterone sulfate, and Free androgenic index, were also elevated. Secondary analyses revealed higher triglycerides, lower high-density lipoprotein, increased leptin, and greater carotid intima-media thickness, supporting an early pattern of cardiometabolic risk. GRADE assessment rated most outcomes as low certainty. CONCLUSION: Women with a history of IPA are at increased risk of long-term insulin resistance and hyperandrogenism, with early signs of adverse cardiometabolic profiles. These findings support the need for long-term monitoring in this population.

Humans

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&#xa0;ng/mL), with detection limits (LOD) as low as 0.05&#xa0;ng/mL. Quantification limits ranged from 3 to 5019&#xa0;ng/mL (LLOQ) and up to 16,700&#xa0;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

Randomised, Multicentre Clinical Trial Found That Hypertonic Saline Did Not Reduce the Length of Stay of Hospitalised Patients With Acute Bronchiolitis.

AIM: Bronchiolitis is a major cause of hospitalisation in young children, but the effectiveness of inhaled hypertonic saline remains unclear. We compared treating hospitalised infants with nebulised hypertonic saline or normal saline. METHOD: This multisite, double-blind RCT was conducted from 1 October 2023 to 1 April 2025 in four Polish paediatric units. Children from 5&#x2009;weeks to 24&#x2009;months, who had been hospitalised with mild-to-moderate bronchiolitis, were randomly assigned to receive nebulised 3% hypertonic saline or 0.9% normal saline until discharge. They were followed for 7&#x2009;days. RESULTS: The study comprised 181 children (55% male) with a mean age of 8.3&#x2009;&#xb1;&#x2009;6.3&#x2009;months: 90 were randomised to hypertonic saline and 91 to normal saline. The median hospital stay was 2.68 (1.92-4.03) days in the hypertonic saline group and 2.79 (1.8-3.96) days in the normal saline group. The mean difference was -0.11&#x2009;days (95% confidence interval -0.73 to 0.12, p&#x2009;=&#x2009;0.3). No differences were observed in clinical severity scores between the groups. Readmissions only occurred in the normal saline group (5.9%). CONCLUSION: Hypertonic saline inhalation did not reduce the length of hospital stay or improve clinical severity scores in hospitalised children with bronchiolitis, but it was associated with a lower risk of rehospitalisation.

Humans

Efficacy of high-intensity laser therapy versus ultrasound therapy in patients with knee osteoarthritis: a randomized controlled trial.

PURPOSE: High-intensity laser therapy (HILT) and ultrasound (US) are widely used for knee osteoarthritis (KOA), but comparative efficacy data remain scarce. This study compared HILT and US as exercise adjuncts in patients with KOA. METHODS: In this single-center, assessor-blinded RCT, 66 adults with KOA were randomized 1:1 to HILT or US twice weekly for 6&#xa0;weeks as exercise adjuncts. The primary outcome was WOMAC total score change from baseline to 12&#xa0;weeks post-treatment (minimum important change [MIC]&#x2009;=&#x2009;10 points, applied as an approximation). Secondary outcomes included VAS, OKS, KOOS, and EQ-5D-5L. RESULTS: In ITT analysis (N&#x2009;=&#x2009;66), the HILT group achieved a mean WOMAC reduction of 40.0 vs 8.2 points (adjusted between-group difference: -27.7 points, 95% CI:&#x2009;-&#x2009;39.0 to&#x2009;-&#x2009;16.5; p&#x2009;<&#x2009;0.001, partial &#x3b7;2&#x2009;=&#x2009;0.277). At 12&#xa0;weeks post-treatment, greater improvements across all secondary outcomes were observed in exploratory analyses (p&#x2009;&#x2264;&#x2009;0.012). Furthermore, HILT maintained therapeutic effects up to 12&#xa0;weeks post-treatment, whereas the US group experienced a gradual loss of post-treatment gains. CONCLUSION: HILT combined with exercise produced greater short-term improvements in WOMAC total score than US in patients with KOA, with exploratory findings suggesting consistent benefits in pain, function, and quality of life, and with benefits maintained up to 12&#xa0;weeks after the last treatment session.

Humans