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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↗

PubMed2026

Enhancement of secondary organic aerosol formation from isoprene photooxidation by ammonia.

Ammonia (NH3) can participate in atmospheric secondary organic aerosol (SOA) formation by reacting with organic acids and carbonyl compounds in particle phase, but its influence on the gas phase chemistry remains unclear. This study performed a series of smog chamber experiments to investigate the influence of NH3 on the formation of SOA from isoprene photooxidation by OH radicals. Both gas and particle phase products were measured with a series of state-of- art instruments including a nitrate ion chemical ionization mass spectrometer (nitrate-CIMS) and high-resolution time-of-flight aerosol mass spectrometer (HR-TOF-AMS). Our results showed that in the presence of NH3 SOA in the chamber significantly increased, along with an enhanced oxidation of isoprene. CIMS analysis further showed that NH3 in the chamber homogeneously reacts not only with gas-phase organic acids but also with gaseous low volatility oxygenated organic molecules (OOMs) to generate extremely low volatility and ultralow volatility NH3-OOMs clusters. Quantum chemical calculation showed that NH3 can spontaneously interact with OOMs to form NH3-OOMs clusters by forming hydrogen bonds with RCOOH, R-OOH, and R-OH. These clusters can promote new particles formation and particle growth through nucleation and condensation, directly enhancing the isoprene SOA production with a contribution of 78% to the enhanced SOA. Moreover, the formation of NH3-OOMs clusters also results in more isoprene consumed by OH radicals, indirectly increasing the SOA production with a contribution of 22 % to the enhanced SOA. Our work for the first time clarified a synergetic effect of NH3 on isoprene SOA formation, which should be accounted for by models.

Aerosols↗

PubMed2026

Comparison of black carbon measurements using filter-specific reference transmittance to those using lab blanks or an average of unloaded filters.

Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). We analyzed 5,379 15 mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial to assess the influence that different methods of I0 estimations have on eBC measures. We compared eBC measurements using filter-specific I0 values (Method 1) to those using three other methods of I0 estimation: the lab blank scan from a given session (Method 2), the average of all pre-sample filter scans (Method 3), and the average of all lab blank filter scans (Method 4). We assessed the agreement between Method 1 and the alternative methods using Bland-Altman analysis. We also assessed the relationship between Method 1 and the alternative methods across the complete measurement range and after stratifying exposure data into quartiles according to Method 1 eBC exposures. The mean (SD) personal eBC exposure for Method 1 was 7.8 μg/m3 (5.9), and exposures ranged from 1.3 to 46.8 μg/m3. Compared to Method 1, eBC using Methods 2, 3, and 4 were higher by 0.7 μg/m3, 0.1 μg/m3, and 0.7 μg/m3, respectively. The performances of linear regression models between Method 1 and all other methods were moderate to strong (R2 range: 0.42-0.93) in the second, third, and fourth quartiles; however, the models in the first quartile (eBC range: 1.3-2.9 μg/m3) performed poorly (R2 = 0.25-0.26), with error approximately 25% of the mean. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.Implications: Filter-based optical techniques compare light transmission intensities between loaded (I) and unloaded (I0) filters as a measure of light-absorbing mass for subsequent estimations of equivalent black carbon (eBC). To assess the influence that different methods of I0 estimations have on eBC measures, we analyzed 5,379 15 mm Teflon filters from the Household Air Pollution Intervention Network (HAPIN) trial. Our findings suggest that, in most instances, conventional methods for obtaining I0 values can be used to sufficiently characterize eBC; however, analyzing filters before sampling adds appreciably to the accuracy of eBC estimations in lower concentration settings.

Soot↗

PubMed2026

Addition of High-Dose Vitamin D3 to Standard Treatment in Patients With Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703).

IMPORTANCE: In a phase 2 randomized clinical trial, high-dose vitamin D3 added to standard treatment improved progression-free survival (PFS) compared with standard-dose vitamin D3 in patients with metastatic colorectal cancer (mCRC). OBJECTIVE: To determine if high-dose vitamin D3 added to standard chemotherapy improves outcomes in patients with previously untreated mCRC. DESIGN, SETTING, AND PARTICIPANTS: Double-blind phase 3 randomized clinical trial enrolling 455 patients with previously untreated mCRC, conducted in the US through the National Clinical Trials Network from October 2019 to December 2022 (database freeze: July 15, 2024). INTERVENTIONS: mFOLFOX6 (modified FOLFOX6 [5-fluorouracil, leucovorin, oxaliplatin]) or FOLFIRI (5-fluorouracil, leucovorin, irinotecan) plus bevacizumab every 2 weeks with either high-dose vitamin D3 (8000 IU daily × 14 days as loading dose followed by 4000 IU daily) or standard-dose vitamin D3 (400 IU daily) until disease progression, intolerable toxicity, or withdrawal of consent. MAIN OUTCOMES AND MEASURES: The primary end point was PFS assessed by the unstratified log-rank test. Secondary end points included objective response rate, overall survival, and toxicity. Prespecified subgroup analyses of PFS were performed according to known prognostic factors. RESULTS: Among 455 randomized patients (median age, 59 years; 181 [40%] female) with median follow-up 20 months, the median PFS for high-dose vitamin D3 (n = 228) was 11.8 months (95% CI, 10.3-13.3) vs 10.3 months (95% CI, 9.4-12.2) for standard-dose vitamin D3 (n = 227) (1-sided log-rank P = .25). There were no significant differences in objective response rate between high-dose and standard-dose vitamin D3 (51% [95% CI, 44%-58%] vs 44% [95% CI, 37%-50%], respectively; P = .12), or in overall survival (median, 25.6 vs 27.0 months; 1-sided log-rank P = .66). There were no clinically meaningful differences in the most common grade 3 or greater adverse events between the high- and standard-dose groups, including neutropenia (n = 67 [32%] vs n = 62 [30%]) and hypertension (n = 42 [20%] vs n = 49 [23%]) or in incidence of vitamin D-associated toxicities. CONCLUSIONS AND RELEVANCE: Among patients with previously untreated mCRC, addition of high-dose vitamin D3, vs standard-dose vitamin D3, to standard chemotherapy plus bevacizumab did not improve PFS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04094688.

Aged↗

PubMed2026

Desmodium styracifolium Total Flavone Capsules for Urolithiasis: A Phase 3 Randomized Clinical Trial.

IMPORTANCE: No oral medication is currently approved for the management of urolithiasis. Guang Jing Qian Cao (Desmodium styracifolium total flavone capsules; hereinafter, Guang Jing), a traditional Chinese herbal extract, has shown clinical benefits for urolithiasis, but randomized clinical trials are needed to assess its effectiveness. OBJECTIVE: To evaluate whether Guang Jing improves stone passage rates (SPRs) compared with placebo in adults with urolithiasis. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled, phase 3 randomized clinical trial was conducted at 34 sites in China from December 2017 to April 2020. Participants included adults (aged 18-70 years) with diagnosed ureteral stones. Data analysis was conducted on November 4, 2020. INTERVENTION: Participants were randomized 3:1 to receive oral Guang Jing (0.6 g) or matching placebo 3 times daily for 28 days, in addition to investigator-prescribed background medication. MAIN OUTCOMES AND MEASURES: The primary outcome was SPR by day 28, confirmed by computed tomography. Secondary outcomes included SPR by day 14, stone migration rate, and stone migration distance. Between-group comparisons were performed using the Cochran-Mantel-Haenszel test for categorical outcomes and t tests for continuous outcomes. RESULTS: A total of 606 participants were randomly assigned to receive Guang Jing (n = 458) or placebo (n = 148). Their mean (SD) age was 43.0 (12.0) years, 474 (78.2%) were male, and the mean (SD) stone size was 0.6 (0.1) cm. The SPR by day 28 was significantly higher for the Guang Jing group compared with the placebo group (204 of 457 [44.6%] vs 50 of 148 [33.8%]; relative risk, 1.32 [95% CI, 1.03-1.69]; P = .03), with an absolute risk difference of 10.9 (95% CI, 2.0-19.7) percentage points. No significant between-group differences in SPR by day 14 (Guang Jing vs placebo: 133 [29.1%] vs 33 [22.3%]; P = .14) or stone migration distance (mean [SD], 29.5 [51.8] mm vs 29.7 [43.8] mm; P = .11) were observed. Adverse event rates were similar for the Guang Jing and placebo groups (88 [19.3%] vs 27 [18.2%]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, treatment with Guang Jing significantly increased the expulsion of 5- to 10-mm ureteral stones by day 28, with a favorable safety profile. These findings suggest that Guang Jing may be an additional medical expulsive therapy option for appropriately selected patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR-IIR-17013275.

Humans↗

PubMed2026

Influence of Repeated-Sprint Bout Duration in Sprint Interval Training Intervention on Physical Performance Adaptations of Young Volleyball Players.

The objective of this study was to examine the effects of repeated-sprint training (RST) with varying bout durations on the physical fitness adaptations of young male volleyball players. Forty athletes were randomly allocated to one of three intervention groups performing RST with varying bout durations and similar repetition volumes, all executed at maximal effort. The 3-sec group (n = 10) completed two sets of 30 bouts, the 6-sec group (n = 10) performed two sets of 15 bouts, and the 9-sec group (n = 10) carried out two sets of 10 bouts, each adhering to a 1:3 work to rest ratio. An active control group (n = 10) engaged solely in regular volleyball training without the RST intervention. Physical fitness measures-including countermovement vertical jump (CMVJ), 10-m and 20-m linear sprints, T-test change-of-direction speed (T-CODS), reactive strength index (RSI), and the Wingate anaerobic power test-were assessed pre- and post-a 6-week training intervention (i.e., 18 sessions). All RST groups showed significant post-intervention improvements in physical fitness (main effect of time, p = 0.001), with greater adaptations compared with the control group and effect sizes ranging from small to very large. The 3-sec bout group demonstrated greater gains in CMVJ, 10-m and 20-m sprint performance, RSI, and peak power output compared with the 9-sec group (all, p < 0.05). Conversely, the 9-sec group exhibited superior adaptations in T-CODS and mean power output relative to the 3-sec group (all, p < 0.05). In conclusion, the 3-sec group experienced greater enhancements in explosive and sprint performances, while the 9-sec group showed superior gains in change of direction and mean power output. These findings indicate that manipulation of sprint-bout duration in RST can be used to optimize distinct performance adaptations in young volleyball players.

Humans↗

PubMed2026

Modelling peak microbial pollution events caused by combined sewer overflows in a source-to-sea system.

Predicting peak microbial pollution events in downstream coastal bathing waters caused by combined sewer overflows (CSOs) is essential for protecting public health. In urban areas, wastewater effluents, CSOs, and surface runoff can contribute to elevated microorganism loads to downstream waters. These pressures are likely to be intensified by growing population density and more frequent heavy rainfalls due to climate change. This study developed a process-based model to simulate Escherichia coli (E. coli) emissions, transport, and fate from the initial sources to coastal beaches. A three-year retrospective simulation (2017-2019) shows that E. coli concentrations in CSO discharges varied widely across the catchment (4.6 - 7.3 (log10 CFU 100 ml-1)). 99th percentile E. coli concentrations (4.0 (log10 CFU 100 ml-1)) at the inland water outlet were dominated by local CSO emissions, whereas 90th percentile E. coli concentrations (3.6 (log10 CFU 100 ml-1)) reflected cumulative upstream contributions from both CSO and effluent emissions. With the simulation accuracy of 89%, the model reliably reproduced the E. coli dynamics on the downstream beach and showed strong performance in representing peak concentrations based on Complementary Cumulative Distribution Function (CCDF) analysis. The process-based model enables quantitative tracking of source contributions and identification of pollution hotspots, providing support for mitigation measures. The study lays down a source-to-sea modelling framework for representing pollution transport across the aquatic continuum and provides a transferable tool for microbial pollution forecasting and climate adaptation planning.

Climate projection↗

PubMed2026

Blood Metabolomic Signatures of 1-Hour Glucose Predict Cardiometabolic Risk.

BACKGROUND: Elevated 1-hour glucose levels during an oral glucose tolerance test strongly predict type 2 diabetes (T2D) and cardiovascular disease. We investigated whether the fasting blood metabolome predicting 1-hour glucose could be a target for improving β-cell function, long-term glycemic trajectories, and reducing the risks of T2D and coronary heart disease. We also investigated whether plasma microRNAs derived from key metabolic organs regulate changes in a metabolomic risk score (MRS) for predicting 1-hour glucose. METHODS: Untargeted blood metabolomics and a frequently sampled 75-g oral glucose tolerance test were performed in participants from the OmniCarb trial (n=162). In an independent weight-loss dietary intervention trial (POUNDS Lost [Preventing Overweight Using Novel Dietary Strategies]), temporal changes in MRS and plasma microRNAs measured by genome-wide sequencing were analyzed. In addition, associations of MRS at baseline and its 10-year changes with long-term risk of incident T2D and coronary heart disease were prospectively investigated in the NHS (Nurses' Health Study). RESULTS: We created a fasting blood MRS for predicting 1-hour glucose (Pearson r=0.8) and found significant associations with half-day (diurnal) postprandial glucose excursions and insulin secretion after 5-week controlled feeding interventions varying in carbohydrate amount and glycemic index. In the POUNDS Lost trial, diet-induced changes in MRSs were related to 2-year trajectories of glucose metabolism; circulating microRNAs regulating cardiometabolic abnormalities were pivotal factors influencing these changes. In the NHS, women in the top 20% of MRS had a multivariate-adjusted relative risk of 3.80 (95% CI, 2.22-6.51) for T2D and 1.48 (95% CI, 1.04-2.12) for coronary heart disease compared with those in the lowest 20%. In addition, 10-year increases in plasma metabolites related to 1-hour glucose were linearly associated with a higher risk of T2D. CONCLUSIONS: Our findings indicate that fasting blood metabolomic signatures predicting elevated 1-hour glucose reflect disease pathophysiology and could be targets for preventing T2D and coronary heart disease.

blood glucose↗

PubMed2026

Acute pre-exercise oral intake of cacao polyphenols attenuates central fatigue development during sustained low-intensity ankle dorsiflexion exercise in healthy young male adults.

This double-blind, randomized, crossover study investigated whether acute cacao polyphenol (CP) ingestion attenuates neuromuscular fatigue in 19 healthy young male adults. After consuming CP or placebo, participants performed sustained isometric ankle dorsiflexion at 25% of maximal voluntary isometric contraction (MVIC) torque until task failure. Neuromuscular function (MVIC torque, voluntary activation [VA%], doublet torque) and electromyographic activity were assessed before, immediately after, and during recovery (1 and 5 min). Salivary chromogranin A and α-amylase were measured at baseline and 1 min post-task. Only VA% and chromogranin A showed significant condition × time interactions (p = 0.027-0.039). VA% significantly decreased from before to immediately after the task and 1 min post-task in both conditions (p ≤ 0.002), with significantly higher values in the CP condition than in placebo immediately after and 1 min post-task (p ≤ 0.037). Chromogranin A significantly increased from baseline to 1 min post-task in the placebo condition (p < 0.001) but not in the CP condition (p = 0.083). These findings suggest that acute CP ingestion attenuates the decline in central motor drive and autonomic stress responses following strenuous exercise, without altering performance or peripheral recovery, supporting its potential as a nutritional strategy for modulating central fatigue.

Humans↗

PubMed2026

Impact of neoprene wetsuits on lung volumes and work of breathing: implications for military diver safety and performance.

INTRODUCTION: Neoprene wetsuits may impose mechanical constraints on the chest wall, potentially altering respiratory function. This study investigated the impact of neoprene wetsuits on lung volumes, airway mechanics, and work of breathing (WOB) in healthy male divers. METHODS: A randomised crossover trial was conducted with 31 male divers at the Royal Netherlands Navy Diving Medical Centre. Participants underwent pulmonary function testing, including spirometry, body plethysmography, the forced oscillation technique (FOT), and diffusion capacity measurements, both with and without a hoodless standardised 5 mm neoprene full body wetsuit with a neoprene neck seal. Primary outcomes included changes in forced vital capacity (FVC), functional residual capacity (FRC), airway resistance (Raw), reactance (Xrs), and WOB. RESULTS: Wearing a neoprene wetsuit led to statistically significant reductions in FVC (2.8%, P < 0.05), forced expiration in one second (2.9%, P < 0.05), FRC (4.0%, P < 0.05), and expiratory reserve volume (10.9%, P < 0.05), alongside increases in inspiratory capacity and tidal volume. Raw increased significantly (P < 0.05), while the FOT revealed altered airway mechanics, evidenced by increased Xrs at multiple frequencies (P < 0.05). Diffusion capacity remained unchanged, suggesting preserved alveolar-capillary function. CONCLUSIONS: Neoprene wetsuits induce mechanically restrictive effects on the chest wall, reducing static and dynamic lung volumes and increasing WOB. While these changes may not be clinically relevant at rest, their impact needs to be determined during strenuous or prolonged dives, particularly when combined with other equipment that limits thorax excursions. Future research should explore the effects of the military 5 mm wetsuit under immersed conditions to better understand their operational impact on diver performance and safety.

Male↗

PubMed2026

The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: Preoperative rehabilitation training can optimize functional reserve before radical prostatectomy (RP), thereby improving postoperative outcomes. However, its effects on urinary incontinence, erectile function, and quality of life (QoL) remain controversial. This study systematically evaluated these outcome measures. METHODS: Data from randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, Embase, and CINAHL databases. The risk of bias was assessed using the RoB-2 tool, and meta-analysis was performed using Stata 18.0 software. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were conducted using fixed- or random-effects models according to heterogeneity. Outcomes included urinary incontinence incidence, urinary incontinence severity, erectile function, and QoL at different postoperative follow-up time points. RESULTS: 16 randomized controlled trials involving 1,542 participants were included. Prehabilitation significantly reduced the incidence of urinary incontinence at 1 month (OR = 0.58, 95% CI 0.39-0.84) and 6 months (OR = 0.52, 95% CI 0.28-0.96) after RP, with a non-significant borderline reduction at 3 months, and no significant benefit at 12 months. No significant improvement was observed in urinary incontinence severity or erectile function at any follow-up time point. Prehabilitation significantly improved QoL within 3 months (SMD = -0.70, 95% CI -1.08 to -0.32) and 6 months (SMD = -0.45, 95% CI -0.74 to -0.16) postoperatively. However, within 12 months, the effect size attenuated, showing only a marginal trend that did not reach statistical significance (SMD = -0.33, 95% CI -0.66 to 0.00). Risk of bias was generally moderate. CONCLUSION: Prehabilitation reduces early incontinence and improves QoL post-RP, but its effects on severity and erectile function remain unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [CRD420251183407].

Humans↗

PubMed2026

Determination of 13 per- and polyfluoroalkyl substances in human plasma samples using LC-MS/MS: application to capillary microsamples.

Per- and polyfluoroalkyl substances (PFAS) are chemicals widely applied in industrial processes and highly persistent in the environment, whose extensive use has been linked to adverse health effects. Venous plasma is the conventional matrix for PFAS assessment in blood, and LC-MS/MS is the most used quantification technique. Despite the relevance of this topic, biomonitoring data on human exposure to PFAS in Brazil remain limited. This study validated an LC-MS/MS method for determination of 13 PFAS in human plasma. Blood samples were collected from volunteers by phlebotomy, followed by protein precipitation with acetonitrile containing 1% formic acid (v/v) and solid-phase extraction. Chromatographic separation was achieved on an Acquity UPLC HSS T3 column. The assay was linear over a calibration range of 0.2-20 ng/mL. Intra- and inter-assay precision (CV%) were within the ranges of 2.06-12.0% and 0.25-10.7%, respectively. As for accuracy, results were 89.0-112.9%. Matrix effect ranged from -1.31 to 0.05%. Stability after four freeze/thaw cycles and under autosampler conditions were also confirmed for all analytes. The method was applied to 40 paired venous and capillary plasma samples. Both measures exhibited high correlation (r = 0.926). PFOS was the only compound detected at concentrations ≥0.2 ng/mL (LLOQ) in all samples, with capillary plasma concentrations of 0.85-13.50 ng/mL. In summary, the method showed good validation performance and demonstrated the suitability of capillary plasma samples as an alternative matrix for PFAS quantification.

Humans↗

PubMed2026

Assessing the accuracy and efficiency of an electronic platform for managing childhood illnesses in rural China: A cluster randomized controlled trial.

OBJECTIVES: The Integrated Management of Childhood Illness (IMCI) faces challenges in capacity building and quality control. This trial aims to assess an electronic IMCI (eIMCI) platform in improving the effectiveness and efficiency in disease classification and management by community health workers (CHWs). DESIGN: Cluster randomized controlled trial. SETTING: Rural western China. PARTICIPANTS: 24 CHWs and 72 ill children aged 2 months to 5 years (3 children per CHW). CHWs were randomly assigned to intervention or control groups. INTERVENTIONS: The intervention CHWs received online training and performed disease management using the eIMCI platform featuring integrated training modules and decision-support tools. The control group received traditional face-to-face training and used paper-based IMCI protocols. MAIN OUTCOME MEASURES: Proportion of children correctly diagnosed or classified by CHWs, as determined by a pediatric specialist. Relative risk (RR) between groups was estimated using Poisson Generalized Linear Mixed Models incorporating a random intercept for CHW to account for clustering of children within individual CHWs and adjusting for key covariates at both the CHW and child levels. RESULTS: The intervention group (13 CHWs, 39 children) had a higher rate of correct classification (64.1%) compared to the control group (11 CHWs, 33 children) (39.4%, P = .056). Multivariable regression analysis confirmed this (RR = 2.1, 95% CI: 1.5-3.1; P < .001). No significant difference was found in correct treatment rates (38.5% vs. 27.3%, P = .316). Online training reduced time and costs by approximately 80%, though with a slight decrease in post-training evaluation scores. CONCLUSIONS: The eIMCI platform shows potential in enhancing IMCI implementation and significantly reducing the training burden in resource-limited settings. Trial registration: Chinese Clinical Trial Registry: ChiCTR2100042533, https://www.chictr.org.cn/showproj.html?proj=119995.

Humans↗

PubMed2026

Quantifying the aromatic amino acid metabolome: UPLC-MS/MS analysis of aromatic amino acids and their host and co-metabolites in plasma.

Aromatic amino acids (AAAs), tryptophan, phenylalanine, and tyrosine along with their pathway metabolites have been implicated in the pathogenesis of diseases ranging from cardiovascular, neurological, inflammatory, and cancer diseases, among others. As such, the measurement of the primary AAAs, their host pathway metabolites, and microbiome derived co-metabolites in blood can provide a sensitive reflection of systemic health. The aim of the study was to develop a method for the quantification of 17 metabolites, the three AAAs and various of their metabolites in plasma using a high-throughput ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. The method demonstrated a dynamic range (1 to 16,700 ng/mL), with detection limits (LOD) as low as 0.05 ng/mL. Quantification limits ranged from 3 to 5019 ng/mL (LLOQ) and up to 16,700 ng/mL (ULOQ). Recovery at LQC, MQC, and HQC was satisfactory and consistent across most metabolites, with significant matrix effects observed only for 4-ethylphenol sulfate. Furthermore, intra and inter-day accuracy and precision met all acceptance criteria at all quality control concentrations for most of the metabolites. Measurement of NIST SRM 1950 showcased the method's accuracy for most of the metabolites. Finally, the method was applied on the analysis of plasma samples from 55 individuals (13 males and 42 females) providing information on AAAs and their pathway metabolites relevant concentrations in human plasma.

Amino Acids, Aromatic↗

PubMed2026

Increasing gut short-chain fatty acids protects intestinal barrier function but does not spare muscle glycogen or impact aerobic performance.

Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is needed. This study aimed to determine whether increasing colonic SCFA availability impacts intestinal barrier function, substrate metabolism, muscle glycogen and aerobic performance in healthy adults. Using a randomized, double-blind, crossover design 12 active men (age 18-30 years;40.0 ± 7.1 mL/kg/min) performed prescribed exercise and consumed a provided diet supplemented with acetylated and butyrylated high-amylose maize starch engineered to deliver SCFA to the colon (HAMS-A/B) or low-amylose maize starch (LAMS) for 7 days, separated by a 2 week washout. Indirect calorimetry, stable isotopes and blood, muscle and urine biomarkers were measured on intervention day 8 while participants completed 90 min of steady-state cycle ergometry (ExSS; 60 ± 5%) followed by a 5 km treadmill time trial. HAMS-A/B, relative to LAMS, increased faecal and serum SCFA. Multiple markers of intestinal barrier damage and permeability were lower, and the respiratory exchange ratio during ExSS was higher (0.02 [95% confidence interval (CI): 0.01, 0.03], Ptreatment < 0.001) following HAMS-A/B versus LAMS. However no between-treatment difference in glucose turnover, muscle glycogen depletion (14 µmol/kg/g dry wt. [95% CI: -116, 143], Pinteractio n = 0.613) or TT performance (5 s [95%CI: -44, 54], Ptreatment = 0.816) was observed. Increasing colonic and circulating SCFA modestly altered substrate oxidation and preserved intestinal barrier function during endurance exercise. However effects were not sufficient to spare muscle glycogen or increase aerobic endurance performance, leaving the practical relevance unclear and underscoring challenges inherent in translating promising preclinical findings to humans. KEY POINTS: Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is lacking. A gut microbiota-targeted dietary supplementation strategy was used to deliver SCFA to the colon and successfully increased colonic and systemic SCFA concentrations in healthy, physically active adults before and during an endurance exercise bout and aerobic performance test. Increasing colonic and systemic SCFA availability preserved intestinal barrier function but did not impact glucose turnover, alter protein expression in muscle or spare muscle glycogen during endurance exercise. Increasing colonic and systemic SCFA availability did not impact aerobic endurance performance.

Humans↗

PubMed2026

Ciliochoroidal Effusion and Regional Scleral Thickening in Peripapillary Pachychoroid Syndrome.

PURPOSE: To assess anterior scleral thickness and the presence of ciliochoroidal effusion (CE) in eyes with peripapillary pachychoroid syndrome (PPS), and to compare the results with a cohort of healthy age-matched controls. DESIGN: Retrospective cross-sectional study METHODS: A total of 20 eyes from 12 patients diagnosed with PPS and 30 eyes from 15 healthy control subjects. All participants underwent a comprehensive ophthalmic examination, including spectral-domain optical coherence tomography with enhanced depth imaging (EDI-OCT) and anterior segment OCT (AS-OCT). Choroidal thickness was measured at predefined macular and peripapillary locations, while anterior scleral thickness was assessed 6 mm posterior to the scleral spur in 4 quadrants. Ciliochoroidal effusion was evaluated qualitatively using AS-OCT. Comparisons between groups were performed using linear mixed models with Bonferroni correction (scleral thickness corrected P < .010) RESULTS: The mean age of PPS patients was 75.6 ± 9.8 years, and 16% were females. Anterior scleral thickness was significantly greater in the temporal quadrant in PPS eyes compared to controls (396.85 ± 74.97 µm vs 331.13 ± 62.65 µm: P = .007). Ciliochoroidal effusion was detected in 60% of PPS eyes, predominantly in the superior and temporal sectors, whereas no effusion was observed in healthy controls (P < .001). Eyes with CE exhibited a thicker mean scleral thickness and a thicker subfoveal choroidal thickness compared to eyes without effusion (P < .05). CONCLUSION: Eyes with PPS demonstrated increased temporal scleral thickness and a high prevalence of CE. These findings suggest that scleral characteristics may represent a predisposing anatomical factor in PPS, although the precise pathophysiological mechanisms remain to be elucidated.

Humans↗

PubMed2026

A systematic review of the impact of Mental Health First Aid on medical, nursing and allied healthcare professional students.

BACKGROUND: Healthcare professional (HCP) students are at high risk of mental health problems, but stigma and fear of career repercussions often deter them from seeking help. Mental Health First Aid (MHFA) is a globally disseminated course teaching the public to identify and respond to people experiencing mental health problems. MHFA training may address some of the challenges faced by HCP students, by improving mental health knowledge and by enhancing well-being and peer support. AIMS: To systematically review the available literature regarding the impact of MHFA training on HCP students' mental health literacy, confidence and intentions to provide help, stigma, peer support and self-care. METHOD: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (International Prospective Register of Systematic Reviews ID: CRD42024589509), five databases were searched. Primary studies evaluating the above outcome measures in HCP students were included. Two authors independently screened references and extracted data. Quality was assessed using the Modified Medical Education Research Study Quality Instrument and Cochrane Risk of Bias tools. A narrative synthesis was performed. RESULTS: Of 2367 records screened, 26 met inclusion criteria. Confidence in supporting others and mental health literacy showed the most consistent improvements following MHFA training, whereas evidence for changes in stigma was mixed. Peer support, self-care and student well-being were infrequently examined, although qualitative data suggested that MHFA had improved openness to help-seeking. CONCLUSIONS: MHFA shows promise in enhancing mental health literacy, confidence and intentions, and in reducing stigma, particularly when supplemented with experiential learning. HCP students may benefit from tailoring of such courses to their specific needs, fostering a culture of peer support, enhancing well-being and introducing basic concepts in mental health.

MHFA↗

PubMed2026

A Novel Multiple Sensory Nerve Block Combination Using Ultrasound Guidance in Knee Arthroplasty: A Randomized Clinical Trial.

INTRODUCTION: Combining adductor canal block (ACB), infiltration between the popliteal artery and posterior capsule of the knee (IPACK), and genicular nerve blocks provides motor-sparing analgesia in total knee arthroplasty (TKA). Adding nerve blocks targeting the nerve to vastus medialis, vastus intermedius, and anterior femoral cutaneous nerve may improve postoperative pain management without affecting mobility. This study evaluated the effect of an eight-nerve block combination for pain relief after TKA versus local infiltration analgesia (LIA). METHODS: Participants were randomized into intervention or standard treatment groups. The intervention group received an eight-nerve block combination using 40 mL ropivacaine, 5 mg/mL, with 75 µg of clonidine. The control group received LIA comprising 150 mL ropivacaine, 2 mg/mL, supplemented with 0.5 mg adrenaline. The primary outcome was postoperative pain intensity, measured by the numeric rating scale (NRS) at postanesthesia care unit (PACU) arrival, 1 hour, 2 hours after PACU arrival, at ward arrival, evening of surgery, morning of postoperative day 1 (POD1), and at 14:00 POD1. Statistical analysis was performed using the Mann-Whitney U test. Secondary outcomes included 48-hour oral morphine equivalent (OME) consumption and length of hospital stay (LOS). RESULTS: A total of 217 patients scheduled for TKA were randomized. No significant differences were observed in the primary outcome. NRS at rest, presented as median (IQR), did not differ between groups at any time point. At PACU arrival 0 (0-3) vs 0 (0-4), at 1 hour 2 (0-4) vs 2 (0-5), at 2 hours 2 (0-6) vs 2.5 (0-4), at ward arrival 3 (2-5) vs 3 (2-5), on the evening of POD0 4 (3-5) vs 3.5 (2-6), on the morning of POD1 4 (3-6) vs 4 (2-5), and at 14:00 POD1 3 (2-5) vs 3 (2-5) for nerve block and LIA groups, respectively (all P > .05). Exploratory secondary outcomes indicated reduced 48-hour OME consumption presented as median (IQR), 70 mg (52.5-96.3), vs 96 mg (61.3-148.8); P = .008) and shortened hospital stay, median (IQR), 1 day (1-2), vs 2 days, (1-3); P < .001) in the nerve block group compared to the LIA group. CONCLUSIONS: No differences were observed in pain scores between the eight-nerve block combination and LIA. Secondary outcomes revealed a reduction in 48-hour opioid consumption and a modestly shorter hospital stay with nerve block compared to LIA.

Humans↗