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PubMed2026

Orange juice and hesperidin increase flavanone exposure without detectable short-term vascular benefits: a randomized crossover trial.

Orange juice is a major dietary source of hesperidin, a citrus flavanone with vascular protective effects in experimental models. However, whether nutritionally realistic intake levels induce measurable benefits in humans remains unclear. We investigated the effects of orange juice and hesperidin supplementation, at realistic dietary doses, on vascular function, flavanone bioavailability, and molecular responses. Thirty-seven centrally overweight men completed a randomized, double-blind, controlled, three-period crossover trial with three 6-week interventions separated by washout periods. Participants consumed daily 330 mL of 100% orange juice (OJ), an isoenergetic control beverage (CON), or a hesperidin-enriched control beverage (HESP, 210 mg day-1). Fasting vascular, metabolic and anthropometric parameters were assessed before and after each intervention, with flow-mediated dilation (FMD) as the primary endpoint. Postprandial FMD, circulating flavanone metabolites and oxylipin profiles were evaluated following a standardized high-fat meal challenge, and flavanone bioavailability was assessed by 24 h urinary excretion. Whole-blood transcriptomics were performed in a subset (n = 9). Plasma exposure to phase II hesperetin metabolites (AUC0-6 h) and 24 h urinary excretion were comparable after OJ and HESP, indicating effective hesperidin delivery and limited matrix effects on bioavailability. Neither intervention significantly affected fasting or postprandial FMD, vascular, metabolic or anthropometric parameters, or oxylipin profiles versus CON. Marked interindividual variability was observed in vascular responses and flavanone bioavailability, although treatment effects were unrelated to baseline endothelial function or flavanone exposure. Exploratory transcriptomic analyses suggested modulation of pathways involved in vascular biology following OJ and HESP. Under nutritionally realistic conditions, orange juice and hesperidin induced measurable biological engagement without detectable short-term vascular benefits, highlighting the complexity of linking flavanone exposure to functional vascular outcomes in humans.

Humans↗

PubMed2026

Stable chloroform emissions in southeastern China: insights from recent observations.

Chloroform (CHCl3) is a short-lived ozone-depleting substance not currently regulated under the Montreal Protocol. Due to the unique meteorological conditions in East Asia, CHCl3 emitted in this region has a greater potential to reach the stratosphere and contribute to ozone depletion. As an essential component of national CHCl3 emissions, southeastern China has attracted increasing attention. However, long-term observational data in this region remain relatively scarce, with no updates since 2020. In this study, we continuously measured atmospheric CHCl3 concentrations at a remote monitoring station in southeastern China from 1 June 2023 to 31 May 2025. Frequent concentration enhancements were observed during the monitoring period, with mixing ratios ranging from 9.3 to 134.1 ppt and an average value of 36.8 ± 19.7 ppt. Back-trajectory analysis indicated that air masses associated with elevated CHCl3 levels primarily originated from coastal industrial provinces in eastern China. Using the Potential Source Contribution Function and Concentration Weighted Trajectory methods, we identified the Yangtze River Delta (Jiangsu, Anhui, and Zhejiang Provinces) and Jiangxi Province as dominant source regions. Emissions of CHCl3 in southeastern China were estimated using the Tracer Ratio Method to be approximately 30.1 ± 5.3 Gg/yr from 2023-06-01 to 2025-05-31, indicating overall stability relative to earlier estimates and no apparent upward trend. These findings provide updated insights into the current status of CHCl3 emissions in southeastern China and highlight the need for continued monitoring and emission assessment of CHCl3 in East Asia, given its unregulated status and implications for ozone layer recovery.

Air Pollutants↗

PubMed2026

Comparison of short-term clinical outcomes and patient satisfaction between intraoral scanning and conventional impressions for complete-arch implant prostheses: a pilot RCT.

OBJECTIVE: To compare framework passive fit, subjective evaluations, and short-term clinical outcomes between conventional impressions (CI) and intraoral scanning (IOS) for complete-arch implant-supported fixed dental prostheses (CIFDPs). METHODS: In this randomized controlled trial, 22 patients were allocated to the CI or IOS groups. All participants received a definitive one-piece CIFDP. The primary outcome was framework passive fit, assessed using the Vision and Tactile Score (V&T score), which included framework lift-off, the single-screw test, the full-screw test, smoothness of screw insertion, and radiographic gap assessment. Secondary outcomes included operator evaluation, patient satisfaction using a visual analog scale (VAS), early implant survival, marginal bone loss (MBL), modified Plaque Index (mPII), and complications at the 6-month follow-up. RESULTS: Twenty-two patients were enrolled (CI: n = 11; IOS: n = 11), and one patient in the CI group was lost to follow-up. No statistically significant difference in the V&T score was observed between the CI and IOS groups (4.66 ± 0.17 vs. 4.65 ± 0.28; P = 0.93). The operator reported greater nervousness during the CI procedure than during IOS (21.82 ± 15.69 vs. 8.64 ± 7.47; P < 0.05). Patients in the CI group reported significantly greater discomfort, including nausea and anxiety, than those in the IOS group (P < 0.05). At the 6-month follow-up, the early implant survival rate was 100% in both groups. No significant differences were found between the groups in MBL (0.09 ± 0.09 vs. 0.06 ± 0.10 mm; P = 0.43) or mPII (0.10 ± 0.12 vs. 0.10 ± 0.28; P = 0.99). CONCLUSION: IOS and CI achieved comparable short-term clinical outcomes in patients who met the predefined inclusion criteria, including controlled implant number, spacing, and angulation. IOS provided a more favorable experience for both operators and patients. CLINICAL SIGNIFICANCE: In complete-arch implant restorations, intraoral scanning may provide clinical outcomes comparable to those of conventional impressions while improving patient comfort.

Humans↗

PubMed2026

Affective reactivity to a remote computer-based Trier Social Stress Test during a planned quit attempt: associations with short-term cigarette smoking lapse risk.

BACKGROUND: The Trier Social Stress Test (TSST) elicits affective responses and has been linked to smoking behavior. However, its remote use during a planned quit attempt-when stress reactivity may influence early lapse-remains understudied. OBJECTIVE: To quantify affective reactivity to a remotely administered TSST on a planned quit date following overnight abstinence and evaluate associations with cigarette use and lapse within 48 h. METHODS: This secondary analysis used data from a randomized controlled trial of adult smokers completing a remotely administered TSST following overnight nicotine abstinence. Urge, anxiety, and stress were assessed using visual analog scales and summarized using area under the curve (AUC) metrics. Smoking outcomes included cigarette count and lapse within 48 h. Associations were estimated using generalized estimating equations. RESULTS: In adjusted models, anxiety reactivity-but not urge or stress-was associated with cigarette count and lapse. Greater anxiety exposure (AUCtot) and change above baseline (AUCab) were associated with higher cigarette count (IRR=1.0004, 95%CI:1.0002-1.001, p=.002; IRR=1.01, 95%CI: 1.002-1.01, p=.002) and increased odds of lapse (OR=1.001, 95%CI: 1.0001-1.002, p=.03; OR=1.02, 95%CI: 1.001-1.03, p=.03). Effect sizes were small. CONCLUSIONS: Anxiety reactivity under nicotine deprivation was associated with increased cigarette use and lapse 48 h post quit attempt, suggesting individual differences in stress-evoked anxiety may serve as a behavioral marker for early lapse. Remote TSST administration appears feasible for eliciting affective responses on a quit date.

Humans↗

PubMed2026

How to assess different types of abstract concepts in brain disorders: A systematic review.

The clinical evaluation of semantic knowledge has predominantly relied on tools targeting concrete concepts, whereas abstract knowledge has historically received limited attention despite its importance in everyday communication. Only a few instruments have explored the internal subdivision of abstract knowledge, likely due to the intrinsic difficulty of defining specific types of concepts or dimensions, resulting in a fragmented and heterogeneous neuropsychological assessment framework that limits our understanding of this domain. This systematic review examined the tools used to assess various types of abstract concepts in clinical populations. A literature search has been performed on the electronic databases of PubMed and Google Scholar (last update: October 2025). A total of 17 tests is reviewed, differing in the test characteristics, i.e. ranging from automatic to controlled processes and varying in ecological validity, the type of stimuli employed, and the abstract dimensions explored. Most studies have focused on neurodegenerative patients, while comparatively few have examined other clinical conditions. The risk of bias of the reviewed studies was assessed using an ad hoc developed instrument. This review highlights the need for future research to extend investigations to additional abstract domains and clinical populations, while also identifying key challenges related to stimulus selection and the determination of the most appropriate assessment framework.

Humans↗

PubMed2026

Comparing the Efficacy of Mechanochemical Ablation Versus Radiofrequency Ablation for Treating Great Saphenous Vein Incompetence: A Meta-Analysis.

BACKGROUND: The objective of this meta-analysis was to compare the efficacy of mechanochemical ablation (MOCA) and radiofrequency ablation (RFA) in the treatment of great saphenous vein (GSV) incompetence. METHODS: Online databases including PubMed, Cochrane Library, Embase, and Web of Science were searched to collect randomized controlled trials (RCTs) and cohort studies comparing MOCA and RFA in the treatment of varicose veins in lower extremities from database inception to October 2025. Primary outcome was anatomic success. Secondary outcomes were visual analog scale (VAS), Aberdeen Varicose Vein Questionnaire score (AVVQ), and complications. Two reviewers independently screened the retrieved literature, extracted data, and assessed the risk of bias in the included studies. Subsequent analysis was performed using RevMan 5.3. RESULTS: A total of four RCTs, one cohort study and retrospective cross-sectional study involving 737 patients (380 MOCA patients and 357 RFA patients) were included. The meta-analysis results showed that the RFA group was significantly better than the MOCA group in short term and long term of anatomical success rate [(odds ratio [OR] = 0.38; 95% confidence interval [CI] (0.20, 0.71), P = 0.003), (OR = 0.17, 95% CI (0.06, 0.45), P = 0.0003)], but patients in the MOCA group had significantly lower perioperative period pain (mean difference [MD] = -4.48, 95% CI (-7.58, -1.37), P = 0.005] and required fewer days to return to normal activities (MD = -0.76, 95% CI, (-0.95, -0.57), P < 0.001). No significant differences were observed between the two groups in minor and major complications [(OR = 0.93, 95% CI (0.66, 1.33), P = 0.70), (OR = 1.30, 95% CI (0.32, 5.28), P = 0.72)] or quality of life scores (MD = -0.45, 95% CI (-2.53 to 1.63), P = 0.67). CONCLUSION: MOCA of GSV incompetence is an effective and safe method. Compared with RFA, it has lower postoperative pain score and faster recovery time. However, the anatomical success rates were significantly lower with MOCA than with RFA. Therefore, long-term follow-up to evaluate the impact on clinical results is required.

Humans↗

PubMed2026

A translational framework for early-phase inner-ear gene therapy: clinical trial design, regulatory strategy, and ethical considerations.

PURPOSE OF REVIEW: Hereditary hearing loss has historically been approached as a diagnostic category rather than a therapeutically modifiable disease. Recent advances in molecular genetics, cochlear gene delivery, and first-in-human clinical trials are changing that. This review summarizes contemporary progress in the genetics of hearing loss, with emphasis on emerging gene-based therapies, clinical trial design, regulatory and ethical considerations, and practical implications for otolaryngologists as biologic treatment enters clinical practice. RECENT FINDINGS: Early clinical trials targeting OTOF -related DFNB9 deafness have demonstrated satisfactory safety profiles and meaningful auditory recovery, establishing the first proof-of-concept for cochlear gene therapy in humans, culminating in the April 2026 FDA approval of Otarmeni. Genetic diagnoses are increasingly informing prognosis, cochlear implant counseling, and therapeutic candidacy. Preclinical research continues to expand toward recessive, dominant, and syndromic hearing loss using gene replacement, antisense, RNA interference, and genome-editing strategies. Substantial challenges remain, including heterogeneous outcome measures, uncertain long-term efficacy, regulatory complexity, and inequitable global access. SUMMARY: The genetics of hearing loss is transitioning from a diagnostic modality to an interventional one. Widespread clinical impact will require advances in vector engineering, equitable implementation, multidisciplinary counseling, and integration with established rehabilitation pathways. For otolaryngologists, genetic literacy is becoming essential to contemporary hearing care.

Humans↗

PubMed2025

Impact of subthreshold troponin levels and temporal trends on short term adverse cardiovascular outcomes in patients discharged from the emergency department: a RACE-IT trial substudy.

BACKGROUND: High-sensitivity cardiac troponin I assays enable early exclusion of myocardial infarction in the emergency department. However, the clinical implications of detectable troponin values below the 99th percentile upper reference limit (4-18 ng/L) remain unclear. OBJECTIVE: To assess the association between subthreshold troponin levels and 30-day outcomes in patients from the RACE-IT trial, using exact troponin values when available. METHODS: This post-hoc analysis of the RACE-IT stepped-wedge randomized controlled trial included patients with troponin ≤ 18 ng/L across nine EDs. Patients were stratified by initial troponin, peak value, absolute change, and percent change. The primary outcome was a 30-day composite of all-cause death, acute MI, percutaneous coronary intervention, and coronary artery bypass grafting. Logistic regression analysis after adjusting for age, sex, race, and coronary artery disease was performed. RESULTS: Among 19,194 patients with troponin ≤ 18 ng/L, 117 (0.6%) experienced the composite outcome. Higher troponin levels were associated with increased event rates in unadjusted analyses. Adjusted analyses showed no independent associations overall, though patients whose highest troponin values fell within the ≥ 11- ≤ 18 ng/L range continued to demonstrate significantly worse outcomes than those with lower peak levels. Elevated troponin values correlated with older age, male sex, and greater comorbidity burden. CONCLUSION: In this post-hoc analysis of patients with troponin values below the 99th percentile URL, absolute levels and temporal changes were not independently associated with 30-day adverse outcomes. These findings support the use of subthreshold troponin values in rapid rule-out protocols, emphasizing the need to consider clinical context and comorbidities in risk assessment.

Humans↗

PubMed2026

Safety Profile of the Non-steroidal Anti-inflammatory Drug Celecoxib in the Short-Term Management of Acute Non-cancer Pain: A Systematic Review with Meta-analysis of Randomised Controlled Trials.

OBJECTIVE: To summarise the literature regarding the safety of short-term use of the non-steroidal anti-inflammatory drug (NSAID) celecoxib. STUDY DESIGN: Systematic review with meta-analysis of randomised trials. Participants comprised individuals of all ages with acute non-cancer pain. Interventions included celecoxib at 200-400 mg/day for up to 10 days. The comparators were placebo, other NSAIDs (including cyclooxygenase-2 [COX-2] inhibitors and non-selective NSAIDS [nsNSAIDS]), or opioids. DATA SOURCES: Five databases were searched from inception to April 2025: Embase, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus. Additionally, a registry was searched: ClinicalTrials.gov. DATA SYNTHESIS: Meta-analyses using Mantel-Haenszel and random-effects model were used to calculate risk ratios (RRs) and 95% confidence intervals (CIs) for severe cardiovascular, respiratory, and gastrointestinal adverse events and secondary outcomes. The Cochrane Risk of Bias Tool for randomised trials (RoB-2) was used to assess bias risk. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) was conducted to assess the certainty of evidence of each reported outcome. RESULTS: Title/abstract and full text screening comprised 3976 and 273 studies, respectively. Fifty studies were included with 10,693 participants. The RRs for adverse events were no different between celecoxib and placebo for severe events (3 studies) (RR 0.44 [95% CI 0.10-2.03]), cardiovascular (3 studies) (RR 0.84 [95% CI 0.24-2.92]), respiratory (4 studies) (RR 1.23 [95% CI 0.29-5.26]), and gastrointestinal events (33 studies) (RR 0.96 [95% CI 0.64-1.43]). There was no difference between celecoxib and NSAIDS for gastrointestinal adverse events, RR 0.89 (95% CI 0.68-1.17). Celecoxib had a lower risk compared to opioids for gastrointestinal events, RR 0.34 (95% CI 0.14-0.86), and showed a lower risk of nausea compared with placebo, RR 0.75 (95% CI 0.60-0.93), and nsNSAIDS, RR 0.80 (95% CI 0.64-0.99). Most studies had some risk of bias concerns, and the overall certainty of evidence for most outcomes was very low. Celecoxib appears to be safe for acute non-cancer pain when compared to placebo, NSAIDS, and opioids. It had a lower risk compared to opioids for gastrointestinal adverse events in general, nausea and vomiting, as well as a lower risk for nausea adverse events when compared to placebo and nsNSAIDS. REGISTRATION: PROSPERO-CRD42025642152.

Journal Article↗

PubMed2026

Digital healthcare solutions in preoperative care: A systematic review.

OBJECTIVE: Active participation in preoperative anesthesia preparation is crucial to ensure safe and efficient care. Compliance with preoperative instructions improves clinical outcomes, enhances patient satisfaction and optimizes use of healthcare resources. As digital communication becomes increasingly integrated into healthcare, interactive digital tools such as smartphone applications and Short Message Service (SMS) reminders may offer a valuable means of engaging patients in their own care. In this review, we evaluated the role of digital tools in guiding patients during their preoperative care pathway for anesthesia. METHODS: Following registration (CRD420250655119), we conducted a systematic review of studies evaluating the use of smartphone applications or SMS reminders designed to support preoperative preparation for anesthesia or procedural sedation in adult patients undergoing elective procedures. The primary outcome was compliance with preoperative instructions. Secondary outcomes included rate of late cancellations, patient satisfaction and cost-effectiveness. Studies were eligible if they reported at least one of these outcomes. RESULTS: Ten studies (1 RCT and 9 observational studies), including 11501 participants, were identified. Compliance with preoperative instructions was assessed in 8 studies, most of which reported higher compliance in patients receiving digital interventions across multiple instruction domains, although statistical significance was not consistently observed. Evidence suggested a beneficial effect on reducing late cancellations and improving patient satisfaction. However, results varied across study designs, and data on cost-effectiveness were limited. CONCLUSIONS: Digital tools for preoperative anesthesia guidance were associated with higher compliance and showed potential reduction of late cancellations and increase of patient satisfaction. However, the current evidence is predominantly observational and heterogeneous, limiting the strength of conclusions. PRACTICAL IMPLICATIONS: With healthcare systems under pressure, digital technologies may offer a scalable and patient-centered care solution to support preoperative anesthesia preparation. Nonetheless, further high-quality research is needed to evaluate their long-term clinical, economic and equity implications.

Humans↗

PubMed2026

Short-term safety of dual versus single antiplatelet therapy in flow diversion for distal intracranial aneurysms: results from the DART trial.

BACKGROUND AND PURPOSE: Flow diverters (FDs) have become one of the primary treatments for intracranial aneurysms (IAs). However, their use in distal IA has been associated with higher complication rates compared with other techniques. The development of coated FDs, in combination with novel antiplatelet regimens, offers promising strategies to improve the safety profile of FDs in this context. This trial aimed to compare mono antiplatelet therapy (MAPT) using prasugrel versus dual antiplatelet therapy (DAPT) with aspirin and prasugrel for the treatment of distal IA using the p48 MW HPC FD (WallabyPhenox). METHODS: This was a multicenter, prospective, parallel-group, single-blind, non-inferiority randomized trial. Between February 2021 and February 2025, 140 patients were enrolled. After excluding 11 patients, 129 were included in the final analysis. The primary endpoint was the absence of new neurological deficits, defined as no shift in the modified Rankin Scale (mRS) score. The secondary endpoint was the incidence of any stroke. RESULTS: At the 30-day follow-up, 66 patients (98.5%) in the MAPT group and 59 patients (95.2%) in the DAPT group showed no new neurological deficits. With a predefined non-inferiority margin of 5%, the difference of 3.35% confirmed the non-inferiority of MAPT compared with DAPT (p=0.002). The incidence of any stroke was 4/67 (5.9%) in the MAPT group and 6/62 (9.6%) in the DAPT group (p=0.431). CONCLUSION: Prasugrel monotherapy for the treatment of distal IAs using the p48 MW HPC was non-inferior to DAPT within the first 30 days following treatment. CLINICAL TRIAL REGISTRATION: https://ensaiosclinicos.gov.br/rg/RBR-3q9zb73. UTN code: U1111-1290-2489. Research Ethics Committee of the Hospital das Clínicas de Ribeirão Preto - Universidade de São Paulo. CAAE number: 29848720.0.1001.5440.

Humans↗

PubMed2026

Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

Humans↗

PubMed2026

Prophylactic Surgical Left Atrial Appendage Closure in Bioprosthetic Aortic Valve Replacement: Short-Term Outcomes of Randomized Controlled LAA-CLOSURE Trial.

BACKGROUND: Surgical closure of the left atrial appendage (LAA) reduces stroke risk in patients with atrial fibrillation (AF) undergoing cardiac surgery. We evaluated the safety and efficacy of prophylactic LAA closure during bioprosthetic surgical aortic valve replacement in patients without prior AF. METHODS: In this investigator-initiated, academic, randomized, open-label, multicenter LAA-CLOSURE (Left Atrial Appendage CLOSURE for the Prevention of Thromboembolisms in Patients Undergoing Aortic Bioprosthesis Surgery) trial, 921 patients without prior AF undergoing bioprosthetic surgical aortic valve replacement with or without concomitant surgery were randomized and 904 patients included in the modified intention-to-treat analysis (prophylactic LAA closure, n=445; or usual care, n=459). Median age was 73 years (interquartile range, 69-76), 34.8% were women, and 49% had concomitant coronary artery disease. The primary end point was a composite of cardiovascular death, stroke, or systemic embolism at 30 days. RESULTS: The primary end point occurred in 10 of 434 (2.2%) patients in the LAA closure group and 14 of 452 (3.1%) patients in the control group; however, the treatment effect changed direction at ≈7 days. In the time-split Cox regression model, hazard ratios were 2.4 (95% CI, 0.62-9.4; P=0.20) between 0 and 7 days and 0.29 (95% CI, 0.080-1.0; P=0.056) between 7 and 30 days. No closure-related serious complications or differences in bleeding were observed. Postoperative AF occurred in 205 of 445 (46.1%) versus 184 of 459 (40.1%) patients (relative risk, 1.1 [95% CI, 0.99-1.3]; P=0.07), and AF at discharge in 40 of 445 (9.2%) versus 34 of 459 (7.7%) patients (relative risk, 1.2 [95% CI, 0.77-1.8]; P=0.44), in the closure and control groups, respectively. CONCLUSIONS: Prophylactic LAA closure during bioprosthetic surgical aortic valve replacement was safe and did not increase bleeding. REGISTRATION: URL: clinicaltrials.gov; Unique Identifier: NCT02321137.

Aged↗

PubMed2026

Using Organoids to Unlock the Potential of Human Torpor for Spaceflight.

PURPOSE OF REVIEW: This paper reviews the current understanding of the potential for humans to enter a state of torpor/hibernation, and discusses the possibility of inducing torpor in astronauts for long-duration space travel, including some of the physiological, technological, and ethical considerations associated with its implementation. By exploring means to induce torpor in various human organoid systems, we hope such research can provides insights to comprehensive solutions to overcome some of the major hurdles that limit the potential for human to enter a state of torpor during long-duration deep-space missions, and contribute to the ongoing efforts to make such missions more feasible and safer for astronauts. RECENT FINDINGS: On future deep space missions such as NASA's planned missions to the Moon, Mars, and near-Earth asteroids, astronauts will be continuously exposed to environments that are radically different from those on Earth, each presenting multiple logistical and physiological challenges. Beyond the well-documented physiological effects of microgravity, space travelers will encounter a complex radiation environment that may contribute to significant short- and long-term adverse effects on human physiology and increase the risk of cancer and other diseases. Besides these physical challenges, life support systems must also be designed to mitigate psychological impacts of long-term isolation and confinement - all of which collectively pose formidable engineering problems. Hibernation/torpor is a state of prolonged inactivity and metabolic depression used by a wide variety of mammals to survive periods of cold temperatures and food scarcity, including some primates and perhaps even an extinct early line of hominins that lived nearly half a million years ago. Since modern humans share common ancestry with these hominins and hibernating primates, it is likely the human genome encodes the necessary genetic information to hibernate, or at least enter the similar, more transient state of torpor. The reduced body activity, lowered metabolism, and decreased energy requirements that characterize torpor suggest that developing means of inducing such a state in astronauts could address these challenges, including providing a degree of radioprotection. SUMMARY: This review explores the potential application of human torpor as a countermeasure to address the many challenges posed by long-duration spaceflight beyond low-Earth orbit (LEO), discusses various natural hibernating model systems for studying means of inducing a torpor-like state in humans, and highlights the vast potential of using human organoids to test and validate mechanisms that govern induction and maintenance of torpor to identify the means to one day safely induce this state in astronauts to provide additional protection from the myriad stressors of spaceflight.

Astronaut Health↗

PubMed2026

Cognitive-metabolic relationship in temporal lobe epilepsy: A systematic review.

OBJECTIVE: To summarize the current literature on neurometabolic dysfunction identified through brain imaging and its cognitive correlates in temporal lobe epilepsy (TLE). BACKGROUND: Cognitive decline contributes to chronic disability in TLE. The pathophysiology of cognitive decline in TLE is poorly understood, limiting therapeutic advances. Characterizing metabolic changes in patients with TLE and cognitive impairment may identify biomarkers and inform new treatment strategies. DESIGN/METHODS: We conducted a systematic review of five major databases, gathering studies published through December 2024, in accordance with PRISMA guidelines. We included all observational studies describing associations between metabolic imaging findings and cognitive measures in TLE. RESULTS: Of 1449 reports, 38 met the inclusion criteria, encompassing 1161 patients with TLE aged 5-66 years. Twenty-two studies applied fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to assess interictal brain glucose metabolism. Two studies utilized PET with other tracers to assess more specific metabolic aspects. Fourteen studies used proton magnetic resonance spectroscopy (1H-MRS) to quantify local concentrations of brain metabolites. Impairment of verbal memory was consistently associated with left temporal lobe metabolite changes. Non-memory cognitive impairments correlated with changes in glucose metabolism, N-acetylaspartate, and gamma-aminobutyrate in both temporal and extratemporal areas. CONCLUSION: 18F-FDG PET remains the most widely used imaging modality to assess cognitive-metabolic correlates in TLE, while other PET tracers and 1H-MRS are potentially underexplored. Verbal memory impairment correlates robustly with left temporal dysmetabolism. Cognitive impairment in TLE is multifaceted and correlates with measurable changes in metabolism in both temporal and extratemporal regions. While our synthesis was restricted by some methodological limitations, these neurometabolic signatures may hold promise as potential biomarkers for identifying risk of cognitive decline and highlight avenues for future research.

Humans↗

PubMed2026

Handle with care: packaging the oocyte epigenome for the next generation.

During oocyte growth, substantial epigenetic programming occurs to establish a distinctive epigenome including appropriately patterned DNA methylation and histone modifications. Oocyte epigenetic programming must be tightly spatiotemporally regulated to ensure that a wide variety of epigenetic modifiers correctly establish their respective modifications to mediate precise control of gene expression. Furthermore, epigenetic modifications in oocytes include canonical and non-canonical genomic imprints, which are transmitted through meiosis to offspring. Significantly, disruptions in oocyte epigenetic programming can cause aberrant developmental outcomes in the next generation mediated by altered imprinting. Polycomb repressive complex 2 is an important epigenetic modifier that establishes histone 3 lysine 27 trimethylation and non-canonical imprints during mouse oogenesis, which are important for normal offspring development. While it is widely recognised that altered oocyte epigenetic programming can disrupt offspring development, mechanisms controlling maternal epigenetic inheritance remain poorly understood. The possibility remains that non-canonical imprinting exists in humans, although this requires confirmation. This review discusses mouse and human oocyte epigenetic programming including interactions between various epigenetic modifiers and modifications that form the unique oocyte epigenome. Understanding how oocyte epigenetic programming is regulated will be crucial in discerning how changes to the oocyte epigenome can disrupt epigenetic memory and alter developmental outcomes in offspring.

Animals↗

PubMed2026

Isometric Exercises for Tendinopathies: A Systematic Literature Review.

PURPOSE: Musculoskeletal disorders are among the most common reasons for medical consultation, with tendinopathies accounting for up to 30% of such presentations. Although exercise remains the cornerstone of management, the most effective modality continues to be debated. Eccentric exercise has long been the mainstay, but the role of isometric exercise in pain modulation and functional recovery remains unclear. This systematic review aims to evaluate the current evidence on the efficacy of isometric exercises in the management of tendinopathies across various anatomic sites. METHODS: A systematic search was conducted in PubMed, MEDLINE, Embase, and the Cochrane Library from inception to August 1, 2025. Eligible studies included randomized controlled trials and prospective or retrospective cohort studies assessing isometric exercise interventions for tendinopathy, with or without comparator groups. Case series and case reports were excluded. Data extracted included participant demographic characteristics, site of tendinopathy, symptom duration, treatment duration, adherence, and outcome measures such as Victorian Institute of Sports Assessment (A, P, or G), visual analog scale, Patient-Specific Functional Scale, 36 item short form health survey (SF-36), and EuroQol 5-Dimension questionnaires. Imaging outcomes (ultrasound or magnetic resonance imaging) were recorded where available. Methodological quality and risk of bias were assessed using the Cochrane Risk of Bias tool in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. FINDINGS: The search identified 304 articles, of which 13 randomized controlled trials met the inclusion criteria, encompassing 336 participants (40% female). Tendinopathy sites included the patellar (n = 4), Achilles (n = 3), lateral elbow (n = 2), rotator cuff (n = 2), wrist extensor (n = 1), and gluteal (n = 1) tendons. Median symptom duration was 23 months (interquartile range, 3-51 months). Intervention periods ranged from a single 45-minute session to 4-month exercise programs. Treatment adherence was high initially (nearly 100%) but declined over time, with 70% of participants in the isometric and 58% in the control (isotonic) groups completing ≥80% of sessions. Pain reduction and functional improvement were statistically significant in only 3 studies. Imaging-based outcomes were inconsistently reported, and study heterogeneity precluded meta-analysis. Overall methodological quality was rated as good in 3 studies and poor in 10. IMPLICATIONS: Current evidence provides limited support for the superiority of isometric exercise in tendinopathy management. Although isometric regimens appear tolerable and may confer short-term analgesic benefits, their long-term efficacy relative to eccentric or isotonic protocols remains uncertain. Future research should prioritize standardized outcome measures, longer follow-up, and uniform diagnostic criteria to strengthen the evidence base for exercise prescription in tendinopathies.

Humans↗

PubMed2026

Effect of photobiomodulation on pain relief and functional improvement in fractures: a systematic review and meta-analysis.

INTRODUCTION: Fractures, the most common type of trauma, can cause considerable distress to patients. Pain can not only affect the comfort of fracture patients but also delay their participation in rehabilitation training. Photobiomodulation (PBM) has been associated with pain reduction and the promotion of tissue healing. This systematic review and meta-analysis aimed to evaluate the efficacy of PBM in reducing pain and promoting rehabilitation in patients with fractures. METHODS: This study was registered on PROSPERO (CRD42024591373). We systematically searched PubMed, EMBASE, the Cochrane Library and Web of Science for RCTs that investigated PBM in fractures as of August 2025. The primary outcome was the pain score. The secondary outcomes included functional and healing. RESULT: Finally, 12 and 9 studies were ultimately included in the systematic review and meta-analysis, respectively. The pooled analysis showed that the one-week pain score was lower in the PBM group than in the placebo group (MD -0.74, 95% CI -1.00, -0.47, p < 0.0001, I2 = 0%). Subgroup analysis showed that the difference between the two groups was statistically significant regardless of fracture site or acupoint irradiation. Changes in pain scores were statistically significant in both groups at different wavelength combinations. The improvement in grip strength at 4 weeks was significantly greater in PBM than in placebo (MD 5.03, 95% CI 4.29, 5.78; p < 0.0001; I2 = 0%). There were no significant differences in pain and functional scores at 4-26 weeks. Bone healing did not show differences between the two groups. No side effects reported. CONCLUSION: PBM appears to relieve short-term pain in fractures and improve grip strength in patients with upper limb fractures, but does not show significant long-term benefits. Evidence for mandibular functional recovery and bone healing remains inconsistent. Future studies should determine therapeutic parameters and their impact on bone healing and long-term functional outcomes across fracture types.

Humans↗