Metabolomics is a scientific discipline focused on the analysis of metabolites in biological samples with the aim of understanding physiological and pathological processes. The development of analytical technologies, such as mass spectrometry and nuclear magnetic resonance, has enabled advances in untargeted and targeted metabolomic analysis. In untargeted analysis, a broad spectrum of metabolites is analysed without prior assumptions, whereas targeted analysis focuses on the quantification of known molecules. Biological samples such as serum, plasma and urine are most commonly used, with the choice depending on the clinical context and the nature of the disease. Despite its potential, metabolomics faces challenges such as technical complexity, biological variability, lack of standardisation, and the need for advanced statistical methods. However, in the last decade, it has been used extensively in the study of sepsis and associated acute kidney injury, a condition with high mortality and limited therapeutic options. In this review, we present metabolomics, the challenges it faces, and the current state of research concerning sepsis-associated acute kidney injury (SA-AKI). Metabolomic studies of SA-AKI have identified potential key biological changes, including enhanced inflammatory signalling, oxidative stress, osmolyte disturbances, and cellular metabolic dysfunction. Although individual metabolites have been recognised as potential diagnostic markers, none can fully capture the complex metabolic changes characteristic of SA-AKI. In the future, the integration of metabolomics with other "omics" and advanced analytical approaches could advance early disease detection, the understanding of pathophysiology, and the development of personalised therapies.

Micro/nanoplastic-induced alterations in cellular fate and full-cycle spermatogenesis: A mechanistic review and perspective on intergenerational risks.

Electrospun PCL/PVA core-sheath nanofibres enabling staged antibiotic and peptide delivery for diabetic foot ulcer dressings.

Chronic pain frequently co-occurs with emotional problems, highlighting the need for integrated treatment approaches. Previously, we evaluated a hybrid emotion-focused treatment with positive results. However, there is a dire need for studies evaluating treatments in 'real world' clinical contexts. Therefore, this study evaluated the effectiveness of this treatment in regular clinical care. Using a sequential single-case experimental AB design with randomized baseline lengths (4, 5 or 6 weeks), pain, emotional problems and cognitive behavioural factors were assessed weekly across a 20-week study period. Additional outcome measurements were collected at pre-, post- and 12-month follow-up. Patients from primary and secondary care (final n = 31) with chronic pain and anxiety/depression were recruited, and their psychologists delivered the treatment. Individual effects were evaluated using non-overlap of all pairs and aggregated effects via multilevel shift models. Acceptability, adherence and fidelity were summarized, and responders and non-responders compared using group-level analyses. Most (87%) demonstrated a treatment response on ≥ 1 outcome, and over half (55%) on ≥ 3 outcomes. One-third were classified as broad responders. Aggregated analysis showed a significant effect on pain interference. The treatment was viewed as credible and acceptable, with greater satisfaction among responders. Non-responders showed more variability in attendance and lower progression through later treatment phases involving exposure. The findings support the feasibility and potential effectiveness of the hybrid emotion-focused treatment for patients in routine clinical care. The treatment benefits most patients to some extent and a smaller subset of patients to a clinically significant extent. This pragmatic trial evaluates effectiveness in a clinically representative patient sample reflecting the complexity of routine care, including pain and psychiatric comorbidity, sociodemographic diversity and health care utilization. The hybrid emotion-focused treatment represents one of several emerging approaches targeting pain-emotion connections. These findings extend results from a prior RCT and highlight the importance of evaluating interventions under real-world clinical conditions.

Background: Sepsis management in elderly populations presents unique challenges due to age-related physiological changes and comorbidities. Current guidelines remain conflicted regarding optimal antibiotic timing. We conducted a retrospective, multicenter study to evaluate the association between antibiotic administration timing and short-term and long-term outcomes in elderly sepsis patients. Methods: This retrospective cohort study analyzed data from the MIMIC-IV (v3.1) database. Patients were categorized into the early group (antibiotics initiated within 1 h) and the late group (antibiotics initiated >1 h after diagnosis). Further analyses were stratified by shock status (septic shock vs non-septic shock) and pathogen type (Gram-positive vs Gram-negative bacteria). Multivariable Cox regression assessed associations between antibiotic administration timing and 28-/180-/365-day hospital mortality. Restricted cubic spline models evaluated dose-response relationships. The primary outcome was 28-day hospital mortality. Secondary outcomes included 180-day and 365-day mortality rates, along with the incidence of continuous renal replacement therapy (CRRT) and mechanical ventilation requirements. Results: A total of 12,425 patients met the inclusion criteria from the MIMIC-IV database. The multivariable-adjusted analysis demonstrated that delayed antibiotics administration was significantly associated with a 35% increased risk of 28-day all-cause hospital mortality (HR = 1.35, 95% CI 1.22-1.52; P < 0.001), a 43% elevated 180-day hospital mortality risk (HR = 1.43, 95% CI 1.30-1.56; P < 0.001), and a 45% higher 365-day mortality risk (HR = 1.45, 95% CI 1.33-1.56; P < 0.001). Stratified analyses revealed mortality benefits persisted in non-shock patients (28-day HR = 1.31, P < 0.001) and Gram-positive infections (28-day HR = 1.63, P < 0.001), whereas no significant associations emerged in septic shock (28-day HR = 0.82, 95%CI 0.65-1.03; P = 0.081) or Gram-negative infections (HR = 1.04, 95%CI 0.87-1.24; P = 0.692). A linear relationship was observed between antibiotic delay and mortality (Nonlinear P = 0.88). Conclusions: Early antibiotic administration improves survival in elderly sepsis patients, particularly non-shock cases and Gram-positive infections. These insights advocate the importance of individualized selection based on patients' clinical context in critical care practice.

Seizure duration in functional/dissociative seizures: measurement, variability and diagnostic significance.

Diabetes mellitus (DM) promotes cardiac arrhythmias, whereas melatonin confers antiarrhythmic effects. Cellular targets modified by DM and melatonin largely overlap, which warrants testing melatonin as an antiarrhythmic agent in DM. Herein, we evaluated electrophysiological and antiarrhythmic properties of melatonin in the experimental DM model. Experiments were performed in 41 control and 71 diabetic rats. 34 diabetic animals were treated with melatonin (orally, 10 mg/kg daily) for 1 month, and 37 diabetic animals received a placebo. Electrophysiological studies included electrocardiography, in vivo epicardial mapping with induction of ischemia-reperfusion, and patch-clamp studies in ventricular cardiomyocytes. Collagen deposition was assessed in postmortem histological studies. RT-PCR and Western blotting methods were used to estimate Gja1 gene expression and Cx43 protein level, respectively. Melatonin treatment in diabetic animals did not influence the level of glycaemia, but mitigated the progression of myocardial fibrosis. Melatonin treatment prevented the DM-related decrease in conduction velocity, increase in duration and dispersion of repolarization, as well as corresponding changes in their electrocardiographic correlates (QRS, QT, and Tpeak-Tend intervals, respectively). Melatonin also prevented the development of reperfusion ventricular tachycardia/fibrillation. The patch-clamp studies showed that melatonin treatment significantly reduced calcium current, prevented DM-related action potential duration prolongation, but did not modify DM-related increase in sodium current. RT-PCR studies demonstrated that melatonin treatment prevented the DM-related upregulation of Gja1 gene expression and increase in Cx43 level. Melatonin treatment of diabetic rats conferred antiarrhythmic effects associated with electrophysiological changes reflected in ECG parameters, which warrants further testing of melatonin in a clinical context.

Construct validity, reliability, and sensitivity of proxy-reported pain interference in individuals with cerebral palsy.

An Approach to Globus Sensation: Clinical Pearls for Clinicians.

Mapping strategies and outcomes of evidence-based practice training for clinical nurses: A scoping review.

Changes in breast size, whether enlargement or shrinkage, are a frequent clinical concern. Bilateral size changes are typically associated with benign conditions, while unilateral changes often raise concerns about malignancy, requiring prompt and accurate diagnosis to guide effective management. Through illustrative clinical scenarios, the authors provide a comprehensive review of the evaluation and management of breast size changes and address the spectrum of associated conditions. It is important for radiologists and clinicians to distinguish malignant from benign causes by integrating clinical history, physical examination, and imaging findings, all essential tools in the diagnostic process. Prior imaging, clinical context, and multimodality imaging are explored to provide a structured diagnostic approach. Radiologists are essential in identifying the underlying causes, directing appropriate care, and alleviating patient anxiety. The authors offer a practical framework to guide diagnostic decision making through the synthesis of clinical and imaging data. ©RSNA, 2026 Supplemental material is available for this article.

Assessing nonlinear gait characteristics in multiple sclerosis: Insights from a systematic review.

BACKGROUND: Hip dysplasia is a common cause of hip-related pain in young adults. Hip dysplasia is frequently overlooked by clinicians, leading to delayed diagnosis and subsequent adverse outcomes, including debilitating pain, functional impairments, and poor quality of life. Diagnosing hip dysplasia is often challenging due to its variable clinical presentation, its overlap with other conditions, and the absence of standard diagnostic criteria. Despite these challenges, an emerging body of research provides valuable insight into the management of hip dysplasia. CLINICAL QUESTION: How can new and existing evidence on hip dysplasia be synthesized to support clinicians in understanding its etiopathogenesis and diagnostic approaches-including both imaging and clinical evaluation-and in improving management strategies to enable timely diagnosis and treatment of this common condition? KEY FINDINGS: Hip dysplasia presents with variable symptoms and commonly coexists with other musculoskeletal conditions. Clinical examinations should include assessment of generalized joint hypermobility, hip range of motion, symptom-reproducing tests, and extra-articular structures. Imaging remains essential but must be interpreted in the clinical context. Evidence for non-surgical management, including exercise and education, is emerging but remains limited. CLINICAL APPLICATION: Clinicians should adopt a comprehensive and structured assessment approach that integrates patient history, physical examination, and imaging findings. Awareness of coexisting conditions and alternative pain sources is critical. Early recognition may facilitate timely referral and appropriate management. In the absence of strong condition-specific evidence, clinicians should combine available research with clinical reasoning and consider outcomes beyond pain, including quality of life, physical function, and participation. J Orthop Sports Phys Ther 2026;56(7):382-398. Epub 9 April 2026. doi:10.2519/jospt.2026.13860.

Measurement error, minimal detectable change, and responsiveness of the Brazilian-Portuguese Reaching Performance Scale for Stroke under usual care conditions.

Investigating pre-operative joint-level biomechanics in partial versus total knee arthroplasty.

To describe veterinary clients' view of the Value Matrix (VM) as a tool to aid veterinarian-client decision-making. A cross-sectional online questionnaire was available between April 15 and May 15, 2025. Recruitment involved snowball sampling via social media pages with pet-owner audiences. Demographic information was collected. Participants were presented with a video demonstrating a communication tool, the VM, being used in a simulated interaction between a veterinarian and client. Participants were asked to evaluate various functions of the VM in aiding veterinarian-client decision-making and to rate its utility in various clinical contexts. In total, 204 respondents were included in the final analyses. Most participants owned more than 1 pet, were financially stable, and did not report issues with accessing or adhering to veterinary care recommendations. Participants rated the VM highly in terms of its overall utility for supporting veterinarian-client decision-making (median score, 9 out of 10). Most participants agreed or strongly agreed that the VM would improve their understanding of available options, help them understand benefits and financial costs associated with care options, and help them make informed decisions. Participants indicated the VM would be most useful for decisions involving quality of life or chronic illness or to consult with other decision-makers after an appointment. The VM was viewed positively by participating veterinary clients, offering it as a potential tool to aid decision-making in veterinary practice. The VM can be considered a communication tool to aid veterinarian-client decision-making during clinical interactions.

A POCUS stewardship framework for optimizing pediatric FAST in trauma: A conceptual model and evidence synthesis.

Oncocytic papillary cystadenoma of the parotid gland: characteristic multiparametric MRI signature.

Adjunctive role of T-Spot.TB in evaluating active tuberculosis: a retrospective cohort study in a tertiary-care hospital in a low-burden country.

Accurate interpretation of antifungal minimum inhibitory concentrations (MICs) requires distinguishing species-level intrinsic phenotypes from isolate-level acquired resistance. Many fungi exhibit intrinsic reduced susceptibility (IRS) reflected by wild-type (WT) MIC distributions that are shifted toward higher values (uniformly or with a high-MIC tail). This may lead to the misclassification of high-end WT isolates as resistant and compromise surveillance and cross-center comparability, particularly for rare fungi lacking established breakpoints. In this review, we propose a pragmatic and standardized framework to distinguish intrinsic phenotypes (normal susceptibility, IRS, intrinsic resistance) from acquired resistance based on species-specific WT MIC distributions and standardized WT/non-wild-type (NWT) reporting. This framework is specifically intended to guide interpretation in data-limited settings where WT distributions and epidemiological cut-off values (ECOFFs) are not yet established. MICs within the unimodal species-specific WT range, even if high, should be interpreted as potentially reflecting IRS and not as acquired resistance. Only MICs clearly right-shifted beyond the WT range should be classified as NWT by epidemiological cut-off values or, if unavailable, as putative NWT, and considered candidates for acquired resistance. When breakpoints are lacking, WT versus NWT reporting with explicit comments on IRS/intrinsic resistance is preferable to forced susceptible/resistant (S/R) categorization. In the absence of established WT distributions or ECOFFs, such classification remains provisional and should rely on descriptive MIC patterns, available data sets, and clinical context. Integrating these biological interpretations with pharmacokinetics/pharmacodynamics and clinical context supports optimized dosing, avoids inappropriate drug exclusion, and enables consistent surveillance and multicenter comparisons.