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PubMed2026

Proteome-level evidence that tebuconazole, both alone and in interaction with thiacloprid, affects epigenetic events in bumblebee heads.

Tebuconazole, a widely used ergosterol biosynthesis-inhibiting fungicide, can affect nontargets, especially when combined with insecticides. We employed label-free quantitative proteomics to investigate the effects of long-term exposure to sublethal concentrations (100 μg/L) of tebuconazole, either by itself or alongside the neonicotinoid thiacloprid (100 μg/L), on the heads of Bombus terrestris workers. A Bayesian factor power analysis revealed that the experiment produced conclusive proteomic results. Tebuconazole treatment revealed eleven differentially abundant proteins, which increased elevenfold with thiacloprid. The proteins that changed in the same direction in both treatments suggest the occurrence of epigenetic events because they are involved in histone trimethylation (H3K4me3), pre-mRNA processing, and folate (vitamin B9) metabolism. Following co-exposure, the abundance of histone H2A.V and its associated proteins was affected. Two important detoxification-related proteins, CYP6BE1 and CYP6AQ1 (honey bee homologs), were identified, as well as proteins that suggest hormonal and neurotoxic effects. Overall, this study suggests that tebuconazole affects key epigenetic processes in bumblebee heads at the proteome level, though this was not confirmed at the biological level or through orthogonal methods. The tested chemicals were previously found to affect trimethylations, but not H3K4me3. We suggest analyzing the different trimethylations, their interplay, and associated hallmarks, such as folate levels. SIGNIFICANCE: The effects of pesticides and their combinations on organisms can be unexpected until they are examined using modern, complex methods. High-throughput proteomics can provide data on important biochemical processes affected by pesticides, offering a different perspective to that at the expression level. Despite their low acute toxicity, a group of fungicides that inhibit (ergo)sterol biosynthesis (EBI or SBI) are considered dangerous to pollinators, including bumblebees. This is due to the increasing toxicity of insecticides through the inhibition of cytochrome P450 detoxification enzymes. We found that tebuconazole had a similar effect on epigenetic events when used alone or in combination with the insecticide thiacloprid. Key proteins suggest that H3K4 histone trimethylation (H3K4me3) was impacted. To our knowledge, this expands the existing evidence suggesting that tebuconazole/triazole fungicides affect histone trimethylation H3K27me3. Since literature shows that thiacloprid affects H3K9me3, it is possible that thiacloprid and tebuconazole interact in these epigenetic events that affect each other. Overall, our results suggest that tebuconazole affects proteins involved in histone trimethylation, pre-mRNA processing, and folate metabolism. These are all hallmarks of epigenetic processes and were further extended by the co-exposure of tebuconazole and thiacloprid to more differently abundant proteins. Additionally, the results provide data on cytochrome P450s of the CYP6 family, which act as detoxifying proteins, as well as proteins that indicate hormonal and neurotoxic effects in bumblebee heads. Finally, the results of the Bayesian power analysis confirmed the meaningfulness of the proteomic data analyzed in this study. If the new findings obtained at the proteome level are verified by different methods, the full extent of the side effects of tebuconazole can be revealed.

Animals↗

PubMed2026

Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.

BACKGROUND: Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated. METHODS: In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first. RESULTS: Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], -0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P = 0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen. CONCLUSIONS: Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.).

Adolescent↗

PubMed2026

A narrative systematic review of definitions and diagnostic criteria for disordered eating and eating disorders in type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes and disordered eating (T1DE) affects 8-37.1% of adults and is associated with high rates of morbidity and mortality. The absence of a standardised case definition of T1DE and its severity hinders effective screening, diagnosis and treatment. This systematic review aimed to (1) synthesise existing case definitions and diagnostic criteria for T1DE in adults and (2) identify key characteristics to inform consensus for future diagnostic criteria. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Eligible studies involved adults (≥18 years) with type 1 diabetes assessing disordered eating; paediatric studies, mixed samples without disaggregated data, non-empirical designs and non-English publications were excluded. PubMed, MEDLINE, EMBASE, CINAHL and PsycINFO were searched up to November 2025 for peer-reviewed studies involving adults with T1DE. Qualitative and quantitative data on definitions, diagnostic criteria and assessment tools were extracted. Study quality was appraised using a modified Graphical Appraisal Tool for Epidemiological studies (GATE) checklist. Due to heterogeneity of data, a narrative synthesis of findings was performed to describe current definitions of T1DE. RESULTS: Sixty-one studies met the inclusion criteria, with a pooled sample of 111,208 participants (76% women) from over 22 countries. T1DE was defined using a heterogeneous array of terms, diagnostic frameworks and assessment tools (29 distinct methods). The Diabetes Eating Problem Survey-Revised (DEPS-R) was the most used questionnaire, but many studies relied on criteria adapted from general eating disorder classifications or generic questionnaires. Approximately three-quarters of the studies assessed insulin omission behaviours, but the operationalisation of the cognitions for insulin omission varied widely. Beyond physiological markers such as HbA1c and BMI, studies explored various diabetes-related and psychological constructs, although often considering diabetes and disordered eating separately rather than as an integrated condition. CONCLUSIONS/INTERPRETATION: This systematic review highlights the lack of a unified, evidence-based definition of T1DE, resulting in inconsistent screening, diagnostic and reporting practices. Establishing clear, consistent, evidence-based diagnostic criteria and screening questionnaires for T1DE is critical to improving early detection and developing targeted interventions. These findings provide a foundation for refining T1DE definitions as a stepping stone to an international consensus definition. STUDY REGISTRATION: PROSPERO registration no. CRD420250223622 FUNDING: King's College London and King's College Hospital through the KMRT KCH Joint Research Committee studentship. This work was also conducted as part of the National Institute for Health Research (NIHR; CS-2017-17-023)-funded STEADY project (Safe management of people with Type 1 diabetes and EAting Disorders studY). NZ's salary was part-funded by the NIHR via the NIHR Clinician Scientist award to MS; JT and KI are part-funded by the NIHR Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. MS was funded through her NIHR Clinician Scientist Fellowship (CS-2017-17-023).

Humans↗

PubMed2026

Prevalence of Slowly Expanding Lesions in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Chronic active lesions (CALs) reflect chronic inflammation in multiple sclerosis (MS). Slowly expanding lesions (SELs) are CALs identified on conventional MRI by linear, concentric expansion over time, while paramagnetic rim lesions (PRLs) are CALs characterized by a paramagnetic rim on susceptibility-sensitive MRI. However, the prevalence of SELs and their overlap with PRLs remain unclear. The aims of this study were to (1) estimate the proportion of SELs among all T2 lesions and the proportion of patients with at least 1 SEL and (2) assess the proportion of SELs overlapping with PRLs. METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase on February 1, 2026, for studies evaluating SELs in MS. At least 2 authors independently assessed study eligibility. Primary outcomes were the pooled proportion of SELs among T2 lesions and the proportion of patients with at least 1 SEL. We estimated mean per-patient volumes of SELs and total T2 lesions and the proportion of SELs overlapping with PRLs. Random-effects generalized linear mixed-effects models and inverse-variance methods were used, with between-study heterogeneity assessed using τ2 and I2 and robustness using sensitivity analyses. Univariable meta-regression explored heterogeneity. PROSPERO: CRD42024603778. RESULTS: Of 5,980 records, 20 studies comprising 4,786 patients with MS were included (mean age: 43.6 ± 6.3 years; 63.7% female). Sample sizes varied by outcome. SELs accounted for 14% (95% CI 10-21) of all T2 lesions, and 78% (67-85) of patients had at least 1 SEL. After sensitivity analysis, per-patient mean volumes were 1.42 mL (0.79-2.06) for SELs and 10.6 mL (8.53-12.67) for total T2 lesions. In total, 11% (6-20) of SELs overlapped with PRLs. In subgroup analyses, proportions of SELs were similar in relapsing-remitting and progressive MS (15%), but the proportion of patients with at least 1 SEL was higher in progressive MS. Between-study heterogeneity was high across analyses with no significant sources identified. DISCUSSION: Although SELs represent a minority of T2 lesions, most patients have at least 1 SEL and a subset overlaps with PRLs, suggesting a partial correspondence between these 2 imaging markers of chronic inflammatory activity. Limitations include possible publication bias, high unexplained heterogeneity, differences in SEL identification methods, and differences in MRI time point number/timing.

Humans↗

PubMed2026

Dexamethasone as an adjuvant to continuous erector spinae plane block for postoperative analgesia after video-assisted thoracoscopic surgery for pulmonary nodule surgery: a randomized controlled trial.

BACKGROUND: While dexamethasone is proven to enhance single-shot erector spinae plane block (ESPB), its role as an adjuvant in continuous ESPB catheters is unclear. This randomised controlled trial evaluated whether adding dexamethasone to ropivacaine improves analgesia after video-assisted thoracoscopic surgery (VATS). METHODS: 85 patients undergoing VATS with continuous ESPB were randomised to receive postoperative infusion of either 0.2% ropivacaine(C-ESPB group) or ropivacaine with 10 mg dexamethasone(D + C-ESPB group). The primary outcome was resting pain visual analog scale (VAS)at 12 h postoperatively, while secondary outcomes included QoR-15 scores, tramadol consumption, time to first analgesic requirement, postoperative adverse events, 3-month incidence of chronic pain, catheter-related complications, pain intensity at other times, and hospital stay. RESULTS: The D + C-ESPB group had significantly lower resting pain at 12 h [2.56 (1.03) vs 3.24 (1.21), mean difference -0.680, p = 0.006]; and lower coughing pain at 12 h [4.60 (1.48) vs 5.69 (1.35), mean difference 1.086, p < 0.001], with analgesic superiority sustained through 72 h. Quality of Recovery-15 scores were higher at 12 h [124.70 (12.48) vs 117.26 (12.24); mean difference -7.436, p = 0.007] and 48 h [141.60 (5.51) vs 138.98 (6.64); mean difference -2.628, p = 0.050]; Total tramadol consumption over 72 h was markedly reduce [0 (0,100) vs 100 (75,100), z = -3.807, p < 0.001], and hospital stay was shorter [Mean (SD) 6.09 (1.34) d vs 6.93 (1.55)d, p < 0.001]. The intervention did not, however, alter the 3-month incidence of chronic postsurgical pain (31% vs 34%, p = 0.756). CONCLUSION: Dexamethasone significantly enhances the analgesic efficacy of continuous ESPB, improving early pain control, recovery quality, and opioid-sparing after VATS, but does not reduce the incidence of chronic persistent surgical pain.

Humans↗

PubMed2026

Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.

Renal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.

Animals↗

PubMed2026

Efficacy of targeted neuromodulation treatments: a clinical report.

BACKGROUND: Peripheral neuropathy is a debilitating condition characterized by chronic pain, numbness, tingling, burning, and tightness/swelling. Conventional therapies often focus on symptom management, and some patients experience chronic and refractory symptoms. RESEARCH DESIGN AND METHODS: This retrospective clinical analysis evaluated the clinical outcomes of neuromodulation neuropathy treatment using the NeuroGen-Series device in patients with diabetic peripheral neuropathy (DPN) or idiopathic peripheral neuropathy (IPN). 9,805 unique patients who underwent 133,741 treatments between 18 August 2017, and 23 July 2024, were analyzed. Patients were divided into treatment completers (≥24 sessions) and noncompleters (<24 sessions). Paired t-tests confirmed statistically significant reductions in pre- and post-treatment symptom scores (p < 0.001). RESULTS: Among completers, symptom severity decreased by an average of 46.2%. Tingling and pain showed the greatest improvement, while tightness/swelling and numbness showed the least reduction. 64% of patients reported improvement after one session, and 84% reported improvement after 24 sessions. Nonresponders accounted for 5.8% of patients overall. Younger patients and those with higher initial symptom severity were more likely to discontinue treatment. CONCLUSIONS: Overall, neuromodulation treatment resulted in statistically significant reductions in symptom severity, though nonresponders and high attrition rate highlight the need for individualized treatment strategies and further investigation.

Humans↗

PubMed2026

Glycaemic burden disrupts innate immunity in TB by modulating CD206 expression and macrophage antimicrobial responses.

Tuberculosis (TB) and diabetes mellitus (DM) represent a growing dual global health burden, with chronic hyperglycaemia recognized as a major modifier of host immunity against Mycobacterium tuberculosis (Mtb). Macrophages, central to pathogen recognition, phagocytosis, antigen presentation, and intracellular killing, may be particularly vulnerable to diabetic metabolic dysregulation. This study evaluated phenotypic and functional macrophage alterations in individuals with pulmonary TB, type 2 DM, TB-DM comorbidity, and healthy controls. Surface receptor expression was analysed by multicolour flow cytometry, while phagocytosis and intracellular bacterial clearance were assessed using FITC-labelled Mtb assays and colony-forming unit enumeration. Hyperglycaemia was associated with reduced CD11b, MARCO, and TLR2 expression alongside upregulation of the mannose receptor CD206, which correlated positively with HbA1c levels, indicating a shift toward a permissive M2-like phenotype. Phagocytic uptake of Mtb was significantly impaired and inversely correlated with HbA1c. Antigen-presenting capacity was selectively compromised, with reduced CD80 and CD86 expression in DM and TB-DM groups, while HLA-DR remained unchanged. Intracellular Mtb killing was markedly diminished in diabetic macrophages. These findings demonstrate that chronic hyperglycaemia profoundly disrupts macrophage innate immunity, contributing to increased TB susceptibility and poor infection control in diabetic populations.

Humans↗

PubMed2025

The molecular mechanism of cuproptosis and research progress in pancreatic diseases.

PURPOSE: Cuproptosis has been proven to be a novel mode of cell death, distinct from other types of cell death such as necrosis, ferroptosis, pyroptosis, and apoptosis. This study aims to systematically review the molecular mechanisms of cuproptosis in recent years and its research progress in pancreatic diseases. METHODS: By searching PubMed and Web of Science databases, 113 key literatures were included for thematic analysis, covering the molecular mechanism of cuproptosis and its role in the occurrence and development of pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cyst, pancreatic injury and pancreatic neuroendocrine tumor. RESULTS: Cuproptosis refers to the accumulation of copper ions in cells, which leads to instability of ferritin and aggregation of acylated proteins, resulting in oxidative stress-related cell death. Recent studies have shown that cuproptosis plays an important role in the occurrence and development of various pancreatic diseases, such as pancreatic cancer, acute and chronic pancreatitis, diabetes, pancreatic cysts, pancreatic injuries and pancreatic neuroendocrine tumor. The inducers of cuproptosis, such as disulfiram, chloroquinolones, and perilla phenols, alleviate pancreatic cancer by promoting cell cuproptosis. Copper chelators such as tetraethylenepentamine and tetrathiomolybdate promote the recovery of pancreatic injury by inhibiting cell cuproptosis. CONCLUSIONS: Cuproptosis plays a crucial role in the pathogenesis of pancreatic diseases. Further research on the cuproptosis pathway may become a potential target for the treatment of pancreatic diseases.

Animals↗

PubMed2026

Plasticity of hepatic metabolism in Arctic char (Salvelinus alpinus) in response to cyclic hypoxia.

The emergence of cyclic hypoxia puts aquatic organisms' homeostasis under significant strain. Energetic metabolism as well as protein synthesis and folding are particularly altered during hypoxia, while reoxygenation imposes an oxidative challenge. Currently, little is known about how hypoxia-sensitive organisms respond to large oxygen fluctuations. Our previous work on Arctic char revealed that this salmonid, despite being strongly affected by acute hypoxia and reoxygenation (H/R), can successfully reestablish homeostasis, notably through adjustments to hepatic mitochondrial metabolism. However, the mechanisms underlying this acclimation remain poorly understood. We hypothesized that Arctic char remodel their hepatic proteome to optimize energy metabolism, reorganize oxygen-demanding pathways, and maintain cellular homeostasis during repeated H/R cycles. By exposing Arctic char to two or fifteen days of diel cyclic hypoxia, we confirmed this species' limited capacity to respond to acute H/R. Nevertheless, after fifteen cycles, fish adjusted their energetic metabolism through coordinated regulation of carbohydrate and lipid pathways and upregulation of amino acid metabolism. Mitochondrial metabolism was strongly reorganized, particularly at the ubiquinone-Complex III interaction level, alongside adjustments in proline utilization and protein processing. Moreover, protein processing and folding pathways were stimulated in both mitochondria and the endoplasmic reticulum. However, chronic cyclic hypoxia may still promote non-mitochondrial ROS production, DNA replication stress, and impaired immune function. This study highlights how a hypoxia-sensitive fish progressively reorganizes its metabolism and oxygen-demanding pathways to establish a phenotype adapted to chronic cyclic hypoxia, while also revealing the physiological costs associated with this acclimation.

Animals↗

PubMed2026

Design, rationale, and baseline patient characteristics for the Sickle Cell Disease and CardiovAscular Risk-Red cell Exchange (SCD-CARRE) trial.

BACKGROUND: Despite wide utilization of automated red blood cell exchange (RBCX) transfusion in adult patients with sickle cell disease (SCD), no consensus or quality efficacy data exist on its use. The Sickle Cell Disease and CardiovAscular Risk- Red cell Exchange (SCD-CARRE) trial tests the hypothesis that an automated chronic RBCX transfusion strategy reduces acute health care encounters and death while improving quality of life and end-organ function (cardiac, pulmonary and renal) in participants with SCD that are at high risk of death. METHODS: Adult patients with SCD with elevated tricuspid regurgitant jet velocity (TRV) and/or chronic kidney disease were considered to be at high risk of death and were randomly assigned to RBCX plus standard of care vs standard of care alone. Participants assigned to RBCX received 12 months of exchange transfusions to maintain target pretransfusion hemoglobin S% < 30%, post-transfusion hemoglobin S% < 20%, and post-transfusion hemoglobin concentration ≥10 g/dL. All study participants were managed according to NHLBI/ASH/ATS Expert Panel guidelines. The primary endpoint was the number of SCD acute health care encounters or death over 13 months. Secondary endpoints included measures of cardiovascular and renal function, exercise capacity, patient reported outcomes (all collected at baseline, and months 4, 8, and 12), and transfusion-related adverse events (collected monthly). RESULTS: Between 2020 and 2025, the SCD-CARRE trial randomized 173 participants at 23 sites across 3 countries. Enrolled participants had mean (SD) age of 45.8 (11.8) years and 54% were female. At baseline, participants had average TRV of 2.8 (0.5) m/s such that 45.9% had a TRV between 2.5 to 2.9 m/sec and 28.1% had a TRV ≥ 3.0 m/sec. The median (Q1, Q3) eGFR in this cohort was 60 (36, 110) mL/min/1.73 m2. The median (Q1, Q3) 6-minute walk test distance was 375 meters (309, 439), the median daily steps were 3,728 (2,187, 5,821), and participants experienced a median (Q1, Q3) of 2 (1, 5) pain episodes in the year prior to randomization. The trial results are pending. CONCLUSIONS: The SCD-CARRE trial successfully enrolled a cohort of n = 173 adults with SCD. This study highlights a rationale to evaluate the effect of automated chronic RBCX transfusion strategy plus standard of care as compared to standard of care alone in SCD patients at high risk of death with a focus on patient centered outcomes, preservation of cardiovascular function, end-organ complications and death. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT04084080, https://clinicaltrials.gov/study/NCT04084080.

Adult↗

PubMed2026

Effects of automated massage chair therapy on mental health and physical health: A comprehensive study.

BACKGROUND AND OBJECTIVE: Automated massage chair therapy is a non-pharmacological intervention widely believed to enhance wellness, yet evidence regarding its effects remains limited. This 3-part study evaluated the effects of automated massage chair therapy on mental and physical health. METHODS: In Part 1, 20 moderately stressed students were randomized to receive a 20-minute automated massage chair therapy session followed by a 20-minute control session, or vice versa, with a 48-hour washout period. Blood pressure (BP), heart rate (HR), electroencephalogram (EEG), State-Trait Anxiety Inventory (STAI), and Visual Analog Scale (VAS) were measured. In Part 2, 20 hypertensive hospital staff received three 20-minute automated massage chair therapy sessions on alternate days. BP, HR, and skin blood flow (SBF) were measured. In Part 3, 20 hospital staff with chronic low back pain received three 20-minute automated massage chair therapy sessions on alternate days. Electromyogram (EMG) and VAS were measured. RESULTS: Automated massage chair therapy significantly reduced diastolic blood pressure (DBP), HR, stress, and anxiety among moderately stressed students. In hospital staff with hypertension, SBF did not change significantly, whereas BP and HR decreased significantly after automated massage chair therapy. In hospital staff with chronic low back pain, low back function improved, and pain was significantly reduced after automated massage chair therapy. CONCLUSION: These findings indicate that automated massage chair therapy may help reduce stress, lower blood pressure, and alleviate low back pain.

Humans↗

PubMed2026

Determinants of private health insurance uptake and its association with healthcare utilization in Gulf Cooperation Council countries: a systematic review.

All Gulf Cooperation Council (GCC) countries have a multi-payer healthcare system that comprises governmental health coverage (GHC), funded by the government, and private health insurance (PHI), mainly sponsored by employers and purchased by individuals. Both are expected to influence healthcare utilization and contribute to system efficiency and patient well-being. This systematic review explored the determinants of PHI uptake and its association with healthcare service utilization in the presence of GHC in GCC countries. We systematically searched CINAHL, PubMed, Scopus, Web of Science, and Cochrane Library for peer-reviewed studies published between January 2012 and October 2022. Study quality was assessed using the Critical Appraisal Skills Programme (CASP) checklists for both quantitative and qualitative studies, following PRISMA guidelines. Twenty-six studies met the inclusion criteria. Determinants of PHI uptake were mapped to Andersen's Behavioral Model of Health Services Use (BMHSU) and categorized into (1) predisposing factors (sex, age, marital status, and education), (2) enabling factors (employment/income and health system-related factors such as access and perceived service quality), and (3) need factors (health status, including chronic noncommunicable diseases). PHI uptake was positively associated with being male, married, highly educated, employed with a high income, and having chronic diseases. PHI was positively associated with healthcare utilization, particularly routine check-ups, preventive services, and the use of prescribed medicines. In GCC countries, PHI uptake is influenced by sociodemographic and socioeconomic characteristics, health status, and perceived service quality. PHI is also associated with higher healthcare utilization, underlining the need for evidence-informed policies that enhance equity and expand coverage.

Humans↗

PubMed2026

Navigated repetitive transcranial magnetic stimulation for post-stroke recovery: A systematic review and meta-analysis of randomized controlled trials.

Repetitive transcranial magnetic stimulation (rTMS) is a subcategory of non-invasive brain stimulation (NIBS), used to modulate brain plasticity and improve post-stroke recovery. Neuronavigation is used to improve the accuracy of stimulation with the aim of achieving a superior clinical outcome than with conventional targeting. The objective of this review is to evaluate the efficacy of navigated rTMS in subacute and chronic stroke patients in comparison to sham stimulation. We conducted a systematic-review and meta-analysis of randomized controlled trials (RCTs) identified from Pubmed, Scopus and Cochrane CENTRAL. Trials employing neuronavigated rTMS were included of these five types; high and low frequency rTMS, intermittent and continuous theta-burst stimulation (TBS) and Hebbian-type stimulation. 13 RCTs were included after a screening of 1900 studies. 606 patients receiving either active (n = 360) or sham stimulation (n = 246) were assessed. The pooled standardized mean difference (SMD) favored rTMS over sham SMD = 0.4 (95 %CI: 0.11-0.69), with moderate heterogeneity I2 = 55 %. Among stimulation modalities, continuous TBS showed the largest pooled effect. rTMS was also associated with significant improvements in disability-related outcomes, SMD = 0.61 (95 % CI 0.14-1.08). Navigated rTMS is associated with modest but significant improvements in motor and disability outcomes in subacute and chronic stroke. Large comparative trials are required to clarify the potential added value over conventional targeting approaches.

Humans↗

PubMed2026

Soluble CD163 as a Non-Invasive Biomarker in Autoimmune Nephrological and Rheumatological Diseases.

Autoimmune nephrological and rheumatological diseases involve macrophage-driven inflammation, yet disease activity is often assessed using invasive or non-specific measures. Soluble CD163 (sCD163), released from activated monocytes and macrophages, is emerging as a biomarker of macrophage-mediated inflammation in these conditions. This narrative review summarizes current evidence on the diagnostic, prognostic, and disease-monitoring potential of sCD163 measured in blood, urine, and synovial fluid in autoimmune nephrological and rheumatological diseases. This review is based on a narrative analysis of selected publications investigating the clinical utility of sCD163 in autoimmune kidney and rheumatic diseases, with emphasis on correlations with disease activity, histopathological findings, and clinical outcomes. Urinary sCD163 shows excellent diagnostic accuracy for active lupus nephritis (area under the receiver operating characteristic [AUROC] 0.89-0.998), correlates with histological activity index (but not chronicity), and distinguishes ongoing inflammation from chronic damage during treatment. In IgA nephropathy, it predicts remission failure and greater benefit from corticosteroids. In ANCA-associated vasculitis, it identifies active renal involvement (AUROC 0.95 in multicenter cohorts). In rheumatoid arthritis (RA), serum sCD163 correlates with early disease activity, predicts radiographic progression, and detects subclinical macrophage activation in remission. In spondylarthritis, synovial fluid sCD163 reflects a disease-specific M2-polarized macrophage phenotype distinct from RA. Utility is compartmentalized: urinary levels indicate intrarenal macrophage activation, synovial fluid local joint inflammation, and serum systemic activation. sCD163 is a promising macrophage-specific biomarker across autoimmune diseases, but its compartmentalized nature requires context-specific measurement. Before clinical implementation, assay standardization, multicenter validation, and interventional trials showing the benefit of sCD163-guided management are needed.

Humans↗

PubMed2026

APOL1 kidney disease: a critical narrative review of molecular mechanisms, clinical heterogeneity, and the emerging therapeutic landscape.

BACKGROUND: The G1 and G2 variants of the APOL1 gene represent significant genetic risk factors for APOL1 kidney disease and contribute substantially to the excess burden of renal disease observed in individuals of African ancestry. Importantly, both variants exhibit incomplete penetrance, with only approximately 15-20% of high-risk genotype carriers ultimately developing overt nephropathy. OBJECTIVE: To provide a critically appraised, clinically oriented narrative synthesis of APOL1 kidney disease that (i) assigns an explicit certainty rating to each major mechanistic and clinical claim, (ii) identifies where published estimates diverge, where associations remain contested, and where conclusions have been overstated in the secondary literature, and (iii) aligns terminology, testing guidance and therapeutic expectations with the conclusions of the 2025 KDIGO Controversies Conference and with clinical trial data available to August 2026. METHODS: This literature narrative review was performed using a literature search of PubMed and Scopus focusing on APOL1-related nephropathy. Mainly studies published from 2010 to 2026 were considered; however, some selected historical papers from 2005 to 2010 were used for better understanding of the underlying mechanisms and history. Used search terms were "APOL1," "APOL1 risk variants," "chronic kidney disease," AMPLITUDE trial, MZE829, HORIZON trial, "focal segmental glomerulosclerosis," "HIV-associated nephropathy," "podocyte injury," "inaxaplin," "VX-147," KDIGO 2025, and "antisense oligonucleotides." Trial status and topline results for agents in development were additionally verified against ClinicalTrials.gov registrations and sponsor disclosures. The literature search was last updated on 10 August 2026. The inclusion criteria of the study were peer-reviewed original articles, genome-wide association studies, randomised controlled trials, translational studies, mechanistic investigations, and high-quality review articles published in the English language. Exclusion criteria included conference abstracts without peer review, duplicate papers, non-English publications with unreliable translation, and case reports with no relevance to the underlying mechanisms. More attention was paid to studies focusing on molecular pathogenesis of APOL1 nephropathy, second-hit pathophysiology, genotypes/phenotypes, and new therapies (e.g. inhibitors such as Inaxaplin). The review method and design have been prepared according to SANRA (Scale for the Assessment of Narrative Review Articles) criteria. Among eligible articles, priority was given to studies with larger sample sizes, more recent publication dates, higher-impact peer-reviewed journals, and direct clinical or mechanistic relevance to APOL1-associated nephropathy; where multiple studies addressed the same question, the most methodologically rigorous and most recent source was preferentially cited. To move beyond description, each principal claim carried forward into this review was assigned a qualitative certainty rating (high, moderate, low or very low) on the basis of study design, consistency across independent cohorts, directness of the evidence to human disease, and precision of the estimate. These ratings, together with the study design that would be required to resolve each remaining uncertainty, are presented in Table 5. This grading represents a structured judgement by the authors and is not a formal GRADE assessment. RESULTS: Pathogenic actions of APOL1 risk alleles depend on toxic gain-of-function activities that result from the disruption of ion channels. Mitochondrial dysfunction, endoplasmic reticulum stress, and inflammasome activation play roles as secondary downstream modulators of podocyte damage. The existence of incomplete penetrance and lack of symptoms in people with high-risk alleles highlights the need for secondary triggers, including environmental, infectious, and inflammatory factors, for disease onset and progression. High-risk APOL1 genotypes increase the likelihood of rapidly progressing kidney diseases like FSGS, which amplify susceptibility in HIVAN when accompanied by secondary causes like HIV infection. Management is mainly through renin-angiotensin antagonists, but recent treatments include antisense oligonucleotides, immunomodulators, and small molecule inhibitors like inaxaplin. Although promising, inaxaplin (VX-147) showed a ~47% reduction in urine protein/creatinine ratio (UPCR) in Phase 2a trial; however, these findings are based on a relatively small sample size, an open-label study design, and short-term follow-up, and therefore require confirmation in ongoing Phase 3 studies. As this is a narrative review rather than a primary study, no new patient-level data are reported. Across the studies synthesised, high-risk APOL1 genotypes were consistently associated with podocyte injury and with a faster decline in kidney function than low-risk genotypes; however, the magnitude of this association varied substantially with how cohorts were ascertained. The association is robust and reproducible for focal segmental glomerulosclerosis, HIV-associated nephropathy, and hypertension-attributed kidney failure, and remains inconsistent for diabetic kidney disease. Therapeutic development has accelerated, but the supporting clinical evidence remains early phase. Inaxaplin (VX-147) reduced the urine protein-to-creatinine ratio by approximately 47.6% at week 13 in a 16-participant, single-group, open-label Phase 2a study, and is now being evaluated in the randomised, double-blind, placebo-controlled Phase 2/3 AMPLITUDE trial (NCT05312879), whose pre-specified week 48 interim analysis is anticipated in early 2027. MZE829, an orally administered APOL1 inhibitor, produced a mean 35.6% reduction in the urine albumin-to-creatinine ratio at 12 weeks in the Phase 2 HORIZON study; because HORIZON was a small, open-label, single-arm basket study (15 participants enrolled, 12 evaluable) whose primary endpoints were safety and tolerability, this reduction is neither placebo adjusted nor the result of a formal test of efficacy. To date, no APOL1-targeted agent has demonstrated benefit on a hard kidney endpoint. CONCLUSION: APOL1 is the clearest current example of a genetically defined, mechanism-targetable kidney disease, but its evidence base is uneven. The genetic association is firmly established; whereas much of the mechanistic literature derives from overexpression systems, several downstream pathways remain contested, and every APOL1-targeted therapy is so far supported only by short-term, surrogate-endpoint data. The principal unresolved issues are the determinants of incomplete penetrance, the absence of a validated progression biomarker and of any model reproducing the common slowly progressive phenotype, and the long-term efficacy and safety of APOL1-directed therapy. Genotype-guided risk stratification is therefore best regarded as clinically reasonable but not yet proven, and routine population-level screening is not currently supported.

AMPLITUDE trial↗

PubMed2026

Neuromodulation for Subjective Tinnitus: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: To evaluate the effectiveness and safety of neuromodulation and bimodal stimulation for chronic subjective tinnitus in randomized controlled trials (RCTs). DATA SOURCES: PubMed/MEDLINE, Web of Science, and EMBASE (January 2015-December 2025) searched per PRISMA 2020. REVIEW METHODS: Adult RCTs (≥ 18 years) with chronic subjective tinnitus (> 3 months) assessing validated outcomes (THI, TFI, TQ) for neuromodulation/bimodal interventions vs. sham/controls. Two-stage screening, Cochrane RoB-2 risk-of-bias assessment. Random-effects meta-analyses (REML) were performed when ≥ 3 comparable trials were available; effects reported as standardized mean differences (SMD) with 95% CIs. Main Outcomes and measures included change in tinnitus severity (THI/TFI/TQ) while secondary outcomes included loudness (VAS/NRS), durability, and adverse events. RESULTS: Twenty-six RCTs (n = 1576) met criteria: tES (11; n = 372), rTMS (8; n = 432), acoustic coordinated reset (1; n = 100), vagus nerve stimulation (2; n = 90), and bimodal stimulation (4; n = 582). Meta-analysis showed a nonsignificant pooled effect for tDCS (SMD -0.36; 95% CI -0.75 to 0.02; I 2 = 51%) and rTMS (SMD -0.15; 95% CI -0.37 to 0.07; I 2 = 0%). Single-trial evidence for coordinated reset showed no advantage over broadband noise. VNS demonstrated modest benefits with safety concerns limited to implanted approaches. Bimodal stimulation yielded consistent, clinically meaningful reductions (often ≥ 10-20 points on THI/TFI), with durability up to 12 months. Adverse events were mild/transient across noninvasive modalities. CONCLUSIONS: Noninvasive neuromodulation appears safe with average benefits; among modalities, bimodal stimulation shows the most consistent and durable clinical improvements. Standardized, adequately powered RCTs with harmonized protocols and long-term follow-up are needed to refine targets and dosing.

Humans↗

PubMed2026

The effects of nitrate and nitrite supplementation on mitochondrial respiration in permeabilized muscle fibres in young healthy adults.

Nitric oxide (NO) is a direct regulator of mitochondrial respiration. Nitrate (NO3-) and nitrite (NO2-) are good sources of NO, but whether their effects on mitochondrial respiration differ between in vivo and in vitro administration remains unclear. In Study 1, 8 participants consumed NO3- -rich beetroot juice (BR) (∼12.8 mmol NO3-) and NO3- -depleted placebo beetroot juice (PL) (∼0.08 mmol NO3-) acutely and chronically for 2 weeks in a randomised, double-blind, crossover design. A substrate-uncoupler-inhibitor titration (SUIT) protocol was used to assess mitochondrial respiration using high-resolution respirometry (oxygen tension: ∼200-450 μM) in permeabilized muscle fibres. In Study 2, skeletal muscle samples were collected from 11 participants. In a randomised, crossover design, different doses (0, 1.5, and 3.0 μM) of sodium nitrite (NaNO2) were administered to permeabilized muscle fibres. Mitochondrial respiration was measured using the same SUIT protocol under lower oxygen tension (∼50-200 μM). Although muscle NO3- concentration significantly increased after both acute and chronic BR supplementation, mitochondrial respiration and exercise performance did not differ between PL and BR in either condition. Similarly, absolute oxygen flux across different respiratory states were not different between different doses of NaNO2. However, the leak control ratio, reflecting the degree of uncoupling of mitochondrial respiration, was significantly higher with 3.0 μM NaNO2 administration (0.12 ± 0.05) compared to 0 μM NaNO2 administration (0.09 ± 0.04, P = 0.03). These findings, involving both in vivo and in vitro administration approaches, albeit in the presence of relatively high oxygen concentrations, suggest that neither NO3- nor NO2- improves mitochondrial respiration, at least in young healthy adults.

Humans↗