Introduction Sepsis is a global health priority with nearly 50 million cases annually. Cardiovascular dysfunction is common, frequently manifesting as hypotension that persists despite fluid resuscitation. Most affected patients require the use of intravenous (IV) vasoactive agents, typically necessitating intensive care unit (ICU)-level monitoring, invasive interventions and contributing substantially to healthcare costs. Midodrine, an oral alpha-1 agonist approved for orthostatic hypotension, has increasingly been used off-label as a vasopressor-sparing (reducing IV vasopressor use) strategy in sepsis, despite limited and inconsistent evidence. This pragmatic, randomised, open-label trial evaluates the efficacy and safety of midodrine in patients with sepsis-associated hypotension. We hypothesise that, compared with standard care, midodrine administration will reduce the duration of IV vasopressor use. Methods and analysis A total of 308 adult patients with sepsis-associated hypotension will be enrolled (154 per arm). The intervention group will, in addition to standard of care, receive enteral midodrine 10 mg three times daily. Outcomes will be ascertained pragmatically via electronic health record-based data retrieval and adjudicated by research coordinators blinded to treatment assignment. The primary outcome is time alive and off IV vasopressors in the first 28 days (in hours) after randomisation. Secondary outcomes include cumulative vasopressor exposure; use and duration of central venous access; cumulative fluid balance over the first 48 hours and up to 7 days of ICU stay; ICU and hospital length of stay; and ICU-, hospital-, and organ support-free days through day 28. Safety outcomes include adverse events potentially attributable to midodrine during hospitalisation including acute kidney injury. Primary analyses will follow an intention-to-treat framework, including all randomised participants according to their assigned treatment groups. Primary and secondary outcomes will be compared using a van Elteren test stratified by randomisation factors. A predefined secondary Bayesian analysis of the primary outcome will provide complementary estimates of treatment effect. Safety outcomes will be summarised descriptively without formal between-arm hypothesis testing. Ethics and dissemination The Mayo Clinic Institutional Review Board approved this protocol and required written informed consent from all participants (IRB# 24–0 00 121). Findings will be disseminated through peer-reviewed publications and international conference presentations. Trial registration number NCT06319248.

In this paper, the dynamic analysis of a vibro-impact system with ideal excitation and various friction models is performed. A physical model of an oscillating mechanical system with possible impact occurrence is presented and the corresponding mathematical model is derived by using Lagrange’s equations of motion. To describe interaction between impact element and environment, three different friction models are considered: Coulomb, viscous and Coulomb-Stribeck model. Newton’s impact law with a coefficient of restitution is employed to describe relationship between pre-impact and post-impact velocities. The dynamic behavior of the vibro-impact system under the ideal excitation, where the system does not influence the excitation source, is investigated for each friction model by numerically solving the governing equations. The results of numerical analysis are presented through amplitude-frequency diagrams, displacement-time responses and phase portraits. The main objective is to determine the influence of different friction models on amplitude-frequency diagrams, particularly on the regions exhibiting impact and non-impact behavior. For parameter regions with multiple coexisting solutions, basins of attraction are constructed to illustrate the dependence of the system regime on initial conditions.

ABSTRACT Indoor spaces contain diverse microbial communities that shape human health. These microorganisms are particularly relevant to respiratory diseases, including asthma and allergies. Despite growing recognition of the importance of indoor microbial exposures, research in this field is slowed by differences in methods. These inconsistencies make it difficult to compare results and draw conclusions. This systematic review analyses 106 studies published between 2000 and 2025 that investigated indoor microbiomes in dust, air, and other matrices across homes, schools, and other built environments. We assessed sampling strategies, DNA extraction protocols, sequencing technologies, and bioinformatic pipelines, identifying trends, inconsistencies, and areas requiring harmonisation. Passive sampling, particularly dust collection, was the most common approach, while Illumina‐based 16S rRNA and ITS amplicon sequencing dominated molecular analyses. However, variations in targeted gene regions, extraction kits, and analytical tools limited cross‐study comparability. Ecological findings revealed consistent detection of bacterial taxa such as Staphylococcus, Streptococcus, and Corynebacterium, and fungal taxa including Cladosporium, Aspergillus, and Penicillium, with diversity shaped by building characteristics, ventilation, humidity, occupancy, and presence of pets. This review highlights the need for standardised protocols in indoor microbiome research to facilitate reproducibility, enable meta‐analyses, and inform health‐related guidelines for indoor environments.

BACKGROUND Schizophrenia (SCH) is a severe neuropsychiatric disorder associated with complex neurobiological alterations and suboptimal therapeutic outcomes. Increasing evidence indicates that mitochondrial dysfunction may contribute to SCH pathophysiology through impaired energy metabolism, oxidative stress, altered calcium homeostasis, and dysregulation of neuronal function. This review aims to summarize current knowledge regarding mitochondrial abnormalities in schizophrenia and to explore their potential involvement in the mechanisms of action of antipsychotic drugs. SUBJECTS AND METHODS A comprehensive review of the current literature was performed, focusing on human studies, cellular and animal models investigating mitochondrial alterations in schizophrenia, as well as studies evaluating the effects of antipsychotic medications on mitochondrial structure and function. RESULTS Available evidence demonstrates structural, molecular, and functional mitochondrial abnormalities in schizophrenia, including alterations in mitochondrial density, respiratory chain activity, oxidative phosphorylation, ATP production, and redox regulation. Antipsychotic drugs influence mitochondrial pathways in a complex and drug-specific manner. Some antipsychotics may impair mitochondrial respiration and increase oxidative stress, whereas others may exert compensatory or protective effects. Mitochondrial alterations may also contribute to cognitive impairment, negative symptoms, treatment response variability, and metabolic adverse effects associated with antipsychotic therapy. CONCLUSIONS Mitochondrial dysfunction represents an important component of schizophrenia pathophysiology and a potential therapeutic target. The interaction between mitochondrial pathways and antipsychotic drug effects highlights mitochondria as a possible pharmacodynamic interface for personalized treatment strategies. Further in vivo studies and biomarker-based approaches are required to clarify drug-mitochondria interactions and improve therapeutic outcomes in schizophrenia.

Simple Summary This study examined whether two neighboring areas on the inner surface of the skull base differ in three native sheep breeds. These areas are difficult to study using traditional methods, but imaging techniques allowed us to examine them in detail. We found differences between breeds in both size and shape, although the differences in shape were more noticeable. The two regions were partly independent but also changed together in a coordinated way. In contrast, their sizes were not strongly related. Overall, the results show that subtle differences between breeds can be detected even in hidden parts of the skull. They also suggest that nearby areas of the skull base are connected in how they vary, which may be useful for future studies of skull structure and development.

Aim To assess the prevalence of burnout syndrome and its association with occupational stressors among physicians and medical technicians/nurses in the Federation of Bosnia and Herzegovina (FBiH). Methods This cross-sectional study was conducted between February 12 and April 12, 2025, using an anonymous online survey. Structured self-administered questionnaire scales were used to assess burnout (Copenhagen Burnout Inventory) and workplace stressors (Occupational Stress Questionnaire). The association of personal, work-related, and patient-related burnout with occupational stressors was assessed. The survey was sent to the members of the Union of Physicians and Dentists in the FBIH, who were asked to forward the link to their medical technicians and nurses. Results Overall burnout symptoms were reported by more than half of the respondents (53.0%), with 75.7% experiencing at least one form of burnout. Personal burnout was the most prevalent (70.9%), followed by work-related burnout (54.2%) and patient-related burnout (40.1%). In multiple regression analysis, overall burnout was driven by the cumulative impact of multiple stressors rather than by any single factor. All stressors were positively correlated with burnout, but conflicts and communication at work (for personal and work burnout) and public criticism (for patient-related burnout) stood out as the strongest predictors. Conclusion This study observed a high prevalence of burnout among physicians and medical technicians/nurses in the FBiH. All examined domains of professional stressors were correlated with all burnout dimensions. Given the importance of preventing and alleviating burnout among health care professionals, this research provides insight into key factors contributing to burnout.

Abstract The escalation of ecological degradation, marked by climatic instability, precipitous biodiversity loss, and systemic chemical infiltration, necessitates a shift toward integrated biotechnological intervention. This analysis considers how the trajectory of diverse advanced methodologies, including environmental DNA (eDNA) surveillance, CRISPR-based genetic restitution, and synthetic biology-driven bioremediation, might be synthesized into a unified Planetary Health Framework. By exploring the convergence of high-precision genomic engineering, AI-augmented bioinformatic modeling, and the tenets of a circular bio-economy, we examine the capacity of technological intervention to ameliorate ecological stressors and restore critical ecosystems. Moving beyond the constraints of conventional conservation, this discourse explores frontier solutions in climate-resilient agrotechnology, photo-driven biomanufacturing, and technologically integrated urban ecology, highlighting the criticality of microbiome modulation and comprehensive genomic repositories in stabilizing the biosphere. By reconciling molecular-level precision with macro-scale systems ecology, this framework points to a trajectory for sustainable development where technological scalability is constrained by, yet optimized for, planetary boundaries. Ultimately, this review addresses the imperatives of ethical oversight and highlights the multi-sectoral governance architectures required for the responsible global deployment of these “living technologies.”

OBJECTIVES To estimate the proportion of children who meet the restrained sitting guidelines (i.e. <1 h in continuous restrained sedentary). The secondary aim was to determine which factors contribute to the probability a child will meet the restrained sitting guidelines. DESIGN Secondary data analysis of 32 countries participating in the SUNRISE International Study. METHODS Parent surveys were used to collect child demographic information and total restrained sitting. Physical activity was assessed with an accelerometer (ActiGraph wGT3X-BT). A generalized linear mixed model was used to determine the probability of a child meeting the restrained sitting guidelines based on sex, age, geographic region, time spent in a vehicle, and hours of total physical activity. Separate models were run by country income level. RESULTS Final analysis included 2647 children (4.3 ± 0.5 years, 50.6% girls, 49.0% rural). Overall, 81.9% of participants met the restrained sitting guidelines. Odds of meeting the guidelines were 35% lower for children in urban areas and 71% lower for spending 60 min or more in a vehicle. Every additional hour of physical activity increased the odds of meeting the guidelines by a factor of 1.25. These relationships differed when stratified by country income level. CONCLUSIONS While most children meet the guidelines, a focus on children living in urban areas, spending more time in vehicles, and those who engage in less physical activity is warranted.

Introduction: Acute abdominal pain (AAP) constitutes a frequent presenting complaint in the emergency department (ED). Distinguishing between mild and potentially life-threatening cases requires a structured approach and effective triage. This study aimed to describe the main nontraumatic causes of AAP, assess urgency, and analyze case distribution by age and gender, as well as admission and discharge patterns. Patients and Methods: All records of adult patients presenting with abdominal pain between August and December 2023 were retrospectively analyzed. The entire patient sample (n = 257) was classified into 15 different diagnostic groups. Results: From the total count of patients, n = 257, there were 154 females (59.92%) and 103 males (40.08%). According to our study, the leading cause of AAP was renal colic (n = 67; 26.07%), followed by nonspecific abdominal pain (NSAP) (n = 48, 18.68%), urinary tract infections (UTIs) (n = 38, 14.79%), and biliary colic and cholecystitis (n = 32, 12.45%). In terms of hospitalization, 195 patients (75.88%) were discharged, and 62 patients (24.12%) were admitted. Logistic regression analysis revealed that the likelihood of hospitalization was approximately twofold higher in males (odds ratio [OR] = 2.03), whereas females exhibited a reduced probability (OR = 0.49). Conclusion: A higher proportion of AAP cases was observed among females in our ED sample, with renal colic, NSAP, UTI, and biliary disorders being the most common diagnoses. A high discharge rate (75.9%) reflects that most AAP cases were non-emergent; however, careful triage remains essential, particularly in male patients due to their higher admission risk.

Background/Objectives: Shoulder disorders are among the most prevalent musculoskeletal conditions, with lifetime prevalence reaching 67% and substantial associated disability and economic burden. Geographic barriers and workforce shortages impede access to optimal rehabilitation. This narrative review aims to synthesize current evidence on tele-diagnostics and tele-rehabilitation in shoulder disorders, evaluate clinical outcomes and implementation factors, and explore models for integrating these complementary approaches. Methods: A structured but non-systematic literature search was conducted across PubMed, Scopus, and Web of Science covering publications from January 2010 through December 2025, using terms related to telehealth, tele-rehabilitation, tele-diagnostics, and shoulder disorders. Priority was given to randomized controlled trials, systematic reviews, feasibility studies, and clinical practice guidelines in adult populations. A total of 97 articles were included in the final narrative synthesis. Results: Tele-diagnostic approaches demonstrate acceptable reliability for range-of-motion assessment and general diagnostic classification, though glenohumeral instability evaluation remains challenging remotely. Multiple randomized controlled trials suggest non-inferior outcomes for tele-rehabilitation compared to conventional physiotherapy across rotator cuff repair, shoulder arthroplasty, and conservative management, with generally high patient satisfaction. Certainty of evidence is currently low to moderate due to short follow-up durations, modest sample sizes, and heterogeneous protocols. Key implementation barriers include the digital divide, inability to deliver manual therapy, and insufficient long-term outcome data. Conclusions: Current evidence supports telehealth as a viable complement to conventional shoulder care, with the strongest evidence base for postoperative tele-rehabilitation. Hybrid care models appear clinically feasible, though widespread adoption requires standardized outcomes, longer-term trials, and strategies addressing health equity barriers.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by debilitating pain and progressive joint destruction. Tumor necrosis factor-alpha (TNF-α), a key pro-inflammatory cytokine, has been implicated in modulating both peripheral and central pain pathways. TNF-α inhibitors, initially developed to halt structural damage in RA, have demonstrated substantial efficacy in pain relief, independent of their anti-inflammatory properties. This narrative review explores the mechanistic pathways through which TNF-α contributes to pain sensitization and highlights the role of TNF-α inhibitors in disrupting these pathways. Evidence suggests that these biologics not only reduce synovial inflammation but also modulate neuroinflammatory circuits, altering pain perception at the spinal and supraspinal levels. Despite their clinical success, variability in patient response and concerns regarding long-term safety necessitate further research into personalized therapeutic strategies. Identifying biomarkers predictive of pain relief could enhance treatment precision. Ultimately, the integration of TNF-α inhibitors into multidisciplinary pain management approaches holds promise for improving clinical outcomes and quality of life in RA.

Cancer therapy remains challenged by limited treatment efficacy, cancer-related malnutrition and substantial toxicity, underscoring the need for novel strategies to improve therapeutic responses. Omega-3 fatty acids, particularly docosahexaenoic acid (DHA), exhibit both nutritional and bioactive properties, including anti-inflammatory effects and the ability to enhance tumor cell susceptibility to oxidative stress and ferroptosis. To improve stability and delivery, omega-3 fatty acids can be formulated into nanoemulsions that facilitate cellular uptake and may potentiate anticancer therapies. Therefore, we developed a panel of nanoemulsions with defined omega-3 and 9 fatty acid profiles derived from algae, fish and olive oils. All formulations exhibited high physicochemical stability, nanoscale droplet sizes and compendial quality. While pure oil showed minimal biological activity, nanoemulsification markedly increased cytotoxicity, and the novel DHA-rich algae oil emulsion displayed strong and selective antitumor effects without affecting normal fibroblasts. Combination studies indicated tumor type-dependent enhancement of chemotherapeutic efficacy. RNA sequencing indicated activation of ferroptosis-associated pathways and suppression of DNA replication and cell-cycle progression by the novel DHA-rich algae oil emulsion. To expand translational relevance for tumor specific target therapies, a HER2⁺/ER⁻ patient-derived breast cancer cell line and matched cancer-associated fibroblasts were established and characterized. In conclusion, these findings identify the new formulation prototype as a selective and biologically active nanocarrier for DHA which is capable of enhancing tumor type specific therapies, selective chemotherapeutic efficacy and potentially inducing ferroptosis-driven antiproliferative programs. These results highlight the promising potential of DHA as lipid component in a nanoscale droplet size formulation for future combination cancer therapies.

ABSTRACT Introduction: Repaired TOF (rTOF) is a common condition in adult congenital heart disease care. The aim of this article is to investigate how inflammatory markers and volume overload affect rTOF, and how these factors correlate with echocardiographic findings in the right heart cavities. Methods: This study included 32 adult patients (mean age, 27.44 ± 6.22 years) who had undergone surgical correction of TOF during infancy. All participants underwent transthoracic echocardiography, and laboratory assessments included measurements of N-terminal pro-B-type natriuretic peptide (NT-proBNP; reference range ≤125 pg/mL) and high-sensitivity C-reactive protein (hs-CRP; reference range ≤2.0 mg/L). Results: Significant correlations were found between NT-proBNP levels and right ventricular (RV) fractional area change (FAC) (r = −0.55, P = 0.001), tricuspid annular plane systolic excursion (TAPSE) (r = −0.35, P = 0.04), RV basal diameter (r = 0.47, P = 0.006), and right atrium (RA) area (r = 0.50, P = 0.003). Similarly, hs-CRP levels showed strong associations with RV FAC (r = −0.58, P < 0.001), TAPSE (r = −0.45, P = 0.009), RV basal diameter (r = 0.43, P = 0.01), and RA area (r = 0.43, P = 0.01). NT-proBNP had a significant impact (P = 0.017; EXP B = 0.982) on RV FAC. A decrease of 10 units in NT-proBNP was associated with a 17% reduction likelihood of having RV FAC <35%. Conclusion: The proinflammatory response (hs-CRP) and volume load (NT-proBNP) are directly correlated with echocardiographic parameters of the right heart cavities in patients with rTOF, suggesting that patients may benefit from treatment with anti-inflammatory drugs, as well as medications targeting diastolic dysfunction.