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Effects of Vacuum Compression Therapy on Healing of Chronic Lower Limb Ulcers: A Randomised Controlled Study.

Chronic lower limb ulcers remain difficult to manage when unresponsive to conventional treatment. This study evaluated the clinical and physiological effects of vacuum compression therapy on wound healing and quality of life. Fifty patients with chronic lower limb ulcers were randomised to receive 12 sessions of vacuum compression therapy plus standard care or standard care alone over 4 weeks. Wound dimensions, exudate, pain intensity and quality of life were assessed at baseline and post-treatment. Estimated wound volume was calculated as length × width × depth. Tissue oxygenation was measured at the dorsum of the foot in the experimental group. The vacuum compression therapy group showed greater improvements in wound width, depth, volume and quality of life. Estimated wound volume decreased by 61% in the intervention group, whereas no statistically significant volume reduction was observed in controls. Local tissue oxygenation in the experimental group increased by 43%. Baseline wound size was associated with poorer quality of life. Vacuum compression therapy may enhance wound healing and quality of life in patients with chronic lower limb ulcers. Observed increases in local tissue oxygenation represent exploratory physiological findings within the treated cohort that warrant controlled comparative evaluation. Trial Registration: ClinicalTrials.gov identifier: NCT07737184.

Humans

Effect of atenolol versus ivabradine on heart rate variability in patients of schizophrenia with clozapine-induced tachycardia: a randomized controlled trial.

BACKGROUND: A third of schizophrenia cases are resistant to antipsychotics, where clozapine is the only FDA-approved medication. Clozapine use is often limited by intolerable adverse effects. Persistent tachycardia occurs in approximately 25-54% patients receiving clozapine. Heart rate variability (HRV) is a non-invasive, clinically relevant marker of autonomic nervous system functioning. Atenolol and Ivabradine are usually prescribed for clozapine-induced tachycardia (CIT), although evidence guiding their optimal use remains limited. AIM: This study aimed to compare the effects of atenolol versus ivabradine on HRV in patients with treatment-resistant schizophrenia (TRS) receiving clozapine. METHODS: This open-label randomised clinical trial, conducted at a tertiary-care center over 20 months, involved TRS patients on clozapine for more than three months and having persistent tachycardia. Twenty patients received atenolol 25mg once-daily, while twenty received ivabradine 5mg twice-daily for two months. The primary outcome was the change in the frequency domain of HRV, while the secondary outcomes were time-domains, central and peripheral blood pressure, pulse rate and treatment-emergent adverse events (TEAE). RESULTS: While both drugs significantly reduced pulse-rates (atenolol: -20.56&#xb1;13.00, p<0.001; ivabradine: -21.855&#xb1;12.873, p<0.001). Within-group analysis showed that, the atenolol group had significant improvements in high-frequency [HF] power (p=0.048) and LF/HF ratio (p=0.044), along with a non-significant trend towards increased total power (p=0.053); no significant within-group changes were observed in the ivabradine group. CONCLUSION: No significant between-group differences in HRV parameters were established between atenolol and ivabradine. Ivabradine could be a viable option in patients where atenolol is either contraindicated or not tolerated. Future larger multicentric studies are needed for greater generalisability. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06505668.

Humans

Effects of aerosol aging on composition and light-absorbance of nitrogen-containing organic compounds: Evidences from ultra-high-resolution mass spectrometry analysis.

Nitrogen-containing organic compounds (NOCs) are key components of particulate matter (PM), but their compositional evolution and light-absorbing properties during atmospheric aging remain poorly understood. In this study, ultra-high-performance liquid chromatography coupled with Orbitrap mass spectrometry was used to semi-quantitatively analyze 59 PM1 samples collected in Shanghai. NOCs accounted for 31 % and 64 % of the detected species in negative (ESI-) and positive (ESI+) ionization modes, respectively. Atmospheric aging significantly reduced the molecular diversity of polar organics, with both the number and mass concentration percentages of CHON- compounds showing significant negative correlations with aging degree. Van Krevelen analysis demonstrated a decrease in the number of carboxylic-rich alicyclic molecules and their CHON- contributions during the aging process (from 37.7 % in fresh samples to 21.2 % in aged samples). CHN+ compounds, a major NOCs group in ESI+ mode, also decreased with aging. Correlation analyses involving the Bep/(Bep+Bap) ratio, relative humidity, and mass absorption efficiency at 365 nm revealed a decline in light absorption capacity with aging, suggesting aqueous-phase oxidation as a dominant aging mechanism. CHON- and CHN+ compounds were identified as the principal light-absorbing constituents in PM1. This work provides new insights into the aging-induced transformations of NOCs in urban PM1, and their changing role in light absorption, highlighting the need for further investigation of the aging mechanisms of NOCs.

Aerosols

Validated UPLC-MS/MS quantification and intracellular PK-PD Modeling of periplocin-related cardiac glycosides in H/R-injured H9c2 cells.

Reliable intracellular quantification is essential for characterizing the target-site disposition and exposure-response relationships of bioactive natural products. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of periplocin and four related cardiac glycoside metabolites in H9c2 cell lysates. Acceptable linearity, precision, recovery, and stability were achieved for intracellular quantification. Cells were treated with each compound at 50&#xa0;&#x3bc;M, and intracellular concentrations and cell viability were monitored over 48&#xa0;h. In hypoxia/reoxygenation (H/R) -injured cells, the time to maximum intracellular concentration was shortened for all five compounds, indicating altered cellular disposition under injury conditions. Cell viability was improved by all compounds during the observation period. Pharmacokinetic-pharmacodynamic (PK-PD) integration was performed using a sigmoid Emax model, and acceptable model fits were obtained, with Akaike information criterion (AIC) values ranging from 79.22 to 130.46. Low apparent EC50 values were estimated under this single-dose design, whereas the estimated Ke0 values suggested delayed equilibration with the effect compartment. These findings indicate that sustained cytoprotective responses can be produced by periplocin and related metabolic markers in injured cardiomyocytes. This intracellular bioanalytical strategy provides a quantitative approach for linking cellular exposure to pharmacodynamic response and may support further evaluation of periplocin-related cardiac glycosides.

Tandem Mass Spectrometry

Optimizing focal vibration therapy for balance and gait: A systematic review.

OBJECTIVE: This systematic review evaluated the efficacy of focal (localized) vibration therapy (FVT) applied to muscles/tendons on balance, gait, and mobility, with a specific focus on defining optimal vibration protocols (frequency, amplitude, dosing) and muscle-targeting strategies to maximize sensorimotor recovery. METHODS: A systematic review was conducted across six databases (CINHAL, Embase, Medline, Web of Science, Scopus, CENTRAL) from January 2000 to May 2025. Studies were included if they involved human participants, applied FVT therapeutically, and reported balance, gait, or mobility outcomes. Data extraction included study characteristics, intervention protocols, and outcomes. Methodological quality was assessed using the PEDro scale. RESULTS: Sixty-two studies (n&#x202f;=&#x202f;2090 participants) were included. Methodological quality assessment (PEDro scale) indicated 44% of studies met high-quality standards. Biomechanical analysis identified the quadriceps, gastrocnemius/soleus, and plantar muscles as the most effective vibration sites, given their critical roles in gait propulsion and postural stability. The synthesis of protocol data indicated a promising therapeutic window characterized by a vibration frequency of 80-120&#x202f;Hz (primarily fixed sinusoidal waveforms at a single frequency) and an amplitude of 0.2-0.5&#x202f;mm (reported only in 12 studies; amplitude was not reported in 23 studies), applied bilaterally for a minimum of 3 sessions per week over 4-12 weeks, which could lead to improved balance and gait performance with benefits sustained for up to 5 months. CONCLUSION: FVT shows potential to improve gait and balance, particularly when targeting lower-extremity muscles with optimized vibration parameters. To advance the field, future research must prioritize the development of standardized protocols and investigate neurophysiological mechanisms to refine FVT as a precision bioengineering solution for mobility deficits.

Humans

Improved comprehensive profiling of fecal bile acids through chemical derivatization combined with HPLC-MS/MS analysis.

Bile acids (BAs) facilitate the digestion and absorption of fats and influence lipid and glucose homeostasis, making them potential therapeutic targets for obesity and related metabolic disorders. The liver and intestinal microbiota modify BAs structurally, generating diverse chemical forms and isomers. Comprehensive profiling of the BA pool is critical for understanding their key biological functions and as a therapeutic approach for related diseases. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) is usually chosen as the preferred method for BA detection due to the complex chemical structures, the wide range of actual concentrations and the complexity of fecal sample matrices. However, free BAs are difficult to ionize, resulting in low detection signals and a lack of characteristic structural fragments to assist in structural identification. In this method, the labeling reagent (2-aminoethyl) trimethylammonium (AETMA) is employed to label the carboxyl group of BAs. Compared with underivatized BAs, the detection sensitivity of unconjugated BAs was enhanced by 25-180 fold, while that of conjugated BAs increased by 6-160 fold. It also generates unique fragment ions and enhances MS response, facilitating the discovery of potential BAs. Methodological parameters were validated using 38 BAs as representatives. Through methodological validation, it was verified that the precision, recovery, matrix effect and stability parameters of the method met acceptable criteria. We also identified 61 confirmed BAs and 55 additional candidate BAs in human pooled fecal samples. It has been successfully applied to fecal BA analysis in obese populations, providing valuable insights into potential therapeutic strategies for obesity.

Tandem Mass Spectrometry

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 &#xb1; 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 &#xb1; 74.97 &#xb5;m vs 331.13 &#xb1; 62.65 &#xb5;m: 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

Respiratory effects of recruitment maneuvers according to lung recruitability assessed by electrical impedance tomography in patients with acute respiratory distress syndrome.

Recruitment maneuvers (RM) can improve oxygenation in patients with acute respiratory distress syndrome (ARDS), but their physiological effects depend on lung recruitability. This secondary analysis of a randomized controlled trial (RCT) evaluated oxygenation, respiratory mechanics, regional ventilation, and cardiorespiratory adverse events responses to a RM followed by electrical impedance tomography (EIT)-guided PEEP titration, using EIT to assess lung recruitability. In this study, fifty patients with moderate-to-severe ARDS underwent a stepwise RM followed by individualized PEEP titration guided by EIT. Lung recruitability was determined using the collapse index at PEEP 6 cmH&#x2082;O (CLPEEP6), defined as the proportion of collapsed lung at this PEEP level. Patients were classified into high- and low-recruitability groups based on median CLPEEP6 values. Oxygenation (PaO&#x2082;/FiO&#x2082;), static compliance (Cstat), driving pressure (Pdriv), regional ventilation distribution, and cardiorespiratory adverse events were compared before and after RM, during subsequent individualized EIT-guided PEEP titration. In patients with high recruitability (CLPEEP6&#x2009;>&#x2009;12.5), the PaO&#x2082;/FiO&#x2082; ratio and Cstat increased significantly after RM (PaO&#x2082;/FiO&#x2082;: 100.8&#x2009;&#xb1;&#x2009;30.3 vs. 125.4&#x2009;&#xb1;&#x2009;38.3&#xa0;mmHg, p&#x2009;<&#x2009;0.05; Cstat: 21.5&#x2009;&#xb1;&#x2009;5.8 vs. 28.0&#x2009;&#xb1;&#x2009;7.0&#xa0;mL/cmH&#x2082;O, p&#x2009;<&#x2009;0.001), Pdriv decreased (19.1&#x2009;&#xb1;&#x2009;3.5 vs. 15.6&#x2009;&#xb1;&#x2009;3.2 cmH&#x2082;O, p&#x2009;<&#x2009;0.001). EIT demonstrated a posterior redistribution of ventilation after RM. In contrast, patients with low recruitability (CLPEEP6&#x2009;&#x2264;&#x2009;12.5) showed no significant mechanical or oxygenation improvement and transient hypotension, arrhythmia, and desaturation appeared numerically more common in this group. No barotrauma or cardiac arrest occurred, and ICU mortality was similar between groups. A strategy combining a RM with subsequent individualized EIT-guided PEEP titration was associated with improved oxygenation and lung mechanics in patients with high lung recruitability, whereas patients with low recruitability showed limited physiological benefit, with cardiorespiratory adverse events appearing numerically more frequent. The EIT-derived CLPEEP6 index represents a feasible and clinically applicable https://clinicaltrials.gov/study/NCT06733168.

Humans

Simultaneous determination of imiquimod and terbinafine in skin permeation studies: Validation of a liquid chromatography method with fluorescence detection.

Chromoblastomycosis is a chronic, neglected subcutaneous mycosis posing significant therapeutic challenges. A topical strategy combining terbinafine (TBF), an antifungal, with imiquimod (IMQ), a TLR-7/8 agonist immunomodulator, has emerged a promising alternative. However, no validated analytical method is currently available to simultaneously quantify both drugs in skin, which is crucial for novel formulation development. This study reports the development and validation of a simple HPLC method with fluorescence detection (excitation 236&#xa0;nm, emission 340&#xa0;nm) for the simultaneous determination of TBF and IMQ extracted from porcine skin. Separation was achieved on a C8 reversed-phase column (125&#xa0;&#xd7;&#xa0;4.0&#xa0;mm, 5&#xa0;&#x3bc;m) using a mobile phase of methanol and water (60,40, v/v), both containing 0.1% formic acid at a flow rate of 0.8&#xa0;mL/min. The method showed excellent linearity (r&#xa0;>&#xa0;0.999) over 0.01-1.0&#xa0;&#x3bc;g/mL for IMQ and 0.1-2.0&#xa0;&#x3bc;g/mL for TBF. Intra- and inter-day precision demonstrated coefficients of variation below 5%, and recovery rates from skin (79-105%) confirmed accuracy. Limits of detection were 0.001&#xa0;&#x3bc;g/mL for IMQ and 0.004&#xa0;&#x3bc;g/mL for TBF, with quantification limits of 0.02&#xa0;&#x3bc;g/mL and 0.16&#xa0;&#x3bc;g/mL, respectively. This selective, sensitive, and reproducible method represents a valuable analytical tool for supporting the development and quality control of topical formulations for chromoblastomycosis and other fungal skin diseases.

Animals

MRI-Negative Posterior Reversible Encephalopathy Syndrome: Comparison of Hypertensive Encephalopathy With and Without Vasogenic Edema.

OBJECTIVE: To explore whether posterior reversible encephalopathy syndrome (PRES) can present with negative magnetic resonance imaging (MRI) by comparing clinical features between cases of PRES with vasogenic edema and cases of hypertensive encephalopathy without MRI changes. PATIENTS AND METHODS: Patients diagnosed with hypertensive encephalopathy from August 1, 2008, to December 31, 2017, were identified retrospectively and matched by age (&#xb1;5 years) and sex in a 1:2 ratio to patients retrospectively identified as having PRES from January 1, 2002, to November 30, 2017. A review of MRI images and clinical information was performed. RESULTS: We identified 16 cases of hypertensive encephalopathy and 32 age- and sex-matched controls with PRES showing vasogenic edema on MRI. There were no statistically significant differences in the odds of presentation with headache (odds ratio [OR], 1.372; 95% CI, 0.458 to 4.106), encephalopathy (OR, 2.303; 95% CI, 0.433 to 12.236), visual disturbance (OR, 0.826; 95% CI, 0.185 to 3.697), or focal neurologic deficit (OR, 4.000; 95% CI, 0.767 to 20.872). Seizures were more common in patients with vasogenic edema (OR, 0.082; 95% CI, 0.010 to 0.664). There were no significant differences in odds of acute kidney injury (OR, 2.90; 95% CI, 0.679 to 12.449) or odds of having a history of malignancy (OR, 0.295; 95% CI, 0.076 to 1.152), transplantation (OR, 3.347; 95% CI, 0.594 to 18.880), or autoimmune disease (OR, 0.400; 95% CI, 0.104 to 1.532). Systolic blood pressure at presentation was higher in patients with hypertensive encephalopathy and negative MRI as compared with patients with PRES and vasogenic edema (OR, 1.03; 95% CI, 1.01 to 1.05). CONCLUSION: Most presenting symptoms and risk factors were not significantly different between cases of hypertensive encephalopathy with and without vasogenic edema, arguing that the diagnosis of PRES in the setting of acute severe hypertension may not depend on MRI confirmation.

Humans

Aflatoxins and their biosynthetic precursors in lotus seeds: simultaneous UPLC-MS/MS determination, contamination profiling, and matrix-specific accumulation during Aspergillus flavus infection.

Aflatoxin (AF) contamination poses a severe global threat to food and medicinal material safety, yet existing research focuses on terminal AF metabolites while neglecting residual biosynthetic precursors, leading to potential underestimation of contamination risks. In this study, a UPLC-MS/MS method was established for the simultaneous quantification of six AFs and their five precursors in lotus seeds, with optimization of mass spectrum parameters, chromatographic separation conditions, and sample pretreatment. Method validation confirmed linearity (R2&#xa0;>&#xa0;0.99), LODs (0.03-0.36&#xa0;&#x3bc;g/kg), and recoveries (76.53%-120.0%, RSD&#xa0;<&#xa0;15%). Analysis of 41 natural lotus seed samples revealed a 63.4% AF contamination rate, dominated by B-group AFs, while O-methylsterigmatocystin (OMST) and versicolorin hemiacetal (VOH) were identified as the primary co-residual precursors with co-occurrence rates &#x2265; 50%. Notably, AFM1 was predominantly detected in natural samples with AFB1 concentrations exceeding 100&#xa0;&#x3bc;g/kg. Artificial inoculation experiments further demonstrated that sterilization and sealing conditions modulated AF biosynthesis in lotus seeds, with non-sterilized and non-sealed groups showing delayed fungal metabolism and lower toxin accumulation. A significant linear correlation was observed between AFM1 and AFB1 levels (r&#xa0;=&#xa0;0.94) in infected samples, demonstrating their accumulation levels are coupled with fungal overall metabolic flux. Given the high co-occurrence rate of OMST/VOH with AFB1 in natural samples, their individual and combined toxicities require in-depth investigation. This work deciphers matrix-specific AF dynamics in lotus seeds, supporting regulatory standard refinement (e.g., precursor inclusion) and targeted control (e.g., time-sensitive drying after harvest). Further studies will focus on exploring the molecular mechanisms of substrate-dependent AF synthesis.

Aflatoxins

Social support and cognitive function in postmenopausal women.

OBJECTIVE: An active social lifestyle may protect against cognitive decline in older adults, but few studies have examined specific social support dimensions in relation to specific cognitive domains. This study examines associations between social support dimensions and cognitive function in older women. METHODS: The Early versus Late Intervention Trial with Estradiol (ELITE) was a randomized, double-blinded, placebo-controlled trial of oral 17&#x3b2;-estradiol versus placebo in postmenopausal women, designed primarily to evaluate the timing hypothesis on atherosclerosis progression and cognitive decline; the present analysis is a secondary, hypothesis-generating examination of the psychosocial substudy data (2009-2012). A total of 448 women completed psychosocial assessments every 6 months. Cognitive function was assessed at baseline, 2.5, and 5 years using composite scores for executive function, verbal memory, visual memory, and global cognition derived from 14 standardized tests. Perceived social support was assessed using the Medical Outcomes Study-Social Support Survey (MOS-SSS; 0-100 scale). Paired cognitive-psychosocial assessments were analyzed using linear mixed-effects models adjusted for age, marital status, blood pressure medication, BMI, education, income, race, and randomized treatment (hormone therapy or placebo). RESULTS: A total of 298 women (mean age 60.3&#xa0;y) provided 322 paired visits. Positive associations were observed between instrumental social support and visual memory (&#x3b2;(SE)=0.0044(0.0022), 95% CI: -0.00002 to 0.0088, P=0.051) and between positive social interaction and global cognition (&#x3b2;(SE)=0.0092(0.0046), 95% CI: 0.0001-0.0182, P=0.047). In age-stratified analyses, the positive social interaction-global cognition association was significant among women <65 years (P=0.042) but not women &#x2265;65 years (P=0.34). No association survived false discovery rate (FDR) correction for multiple comparisons. CONCLUSIONS: In this sample of healthy middle- to older-aged women, no association between specific dimensions of social support and cognitive domains was statistically significant after correction for multiple comparisons. These hypothesis-generating findings suggest any association is modest at best and warrant confirmation in studies designed specifically for this question.

Cognitive function

Unravelling bioanalytical innovations, degradation processes, and impurity landscapes of VEGFR inhibitors.

From pre-formulation studies to clinical trials, VEGFR-targeted small-molecule tyrosine kinase inhibitors (TKIs) require rigorous analytical standards. Bioanalysis, stability-indicating studies, and impurity profiling are used to examine chromatographic advances for VEGFR-targeted TKIs like sunitinib, pazopanib, axitinib, sorafenib, cabozantinib, vandetanib, apatinib, lenvatinib, nintedanib, and regorafenib. An LC-MS/MS and UPLC-MS/MS routinely show sub ng/mL performance, as shown by LLOQs (0.2&#xa0;ng/mL) for sunitinib and axitinib, 1&#xa0;ng/mL for pazopanib, 5-7&#xa0;ng/mL for sorafenib, 0.5-1.5&#xa0;ng/mL for regorafenib metabolic products, and 0.1-0.5&#xa0;ng/mL for lenvatinib. These approaches are used for pharmacokinetics and therapeutic drug monitoring due to their good correlation coefficient of 0.1-10,000&#xa0;ng/mL, accuracy of 95%-108%, and precision of 15% RSD. UPLC-QTOF-MS/MS distinguishes degradants and metabolites during forced degradation studies, enabling structural elucidation following ICH M7 risk evaluation protocol. HPTLC/MLC offers fast, sensitive screenings, while RP-HPLC/DAD or HPLC-UV offer reliable, cost-effective routine quality-control solutions with LOD/LOQ in the &#x3bc;g/mL range and linearity of 10-240&#xa0;&#x3bc;g/mL. This review lists the structures and CAS numbers of ten VEGFR-2 TKI degradants and metabolites, as well as pharmacopeial impurities in SMILES forms. It will be useful for future method development and regulatory applications. To ensure VEGFR-targeted TKI quality, safety, and therapeutic efficacy, LC-MS/MS for trace quantification and HRMS for structure elucidation provide a robust, future-oriented framework. To improve VEGFR-targeted TKI quality, safety, and regulatory compliance, analytical development should focus on HRMS-based impurity characterization, AI-assisted degradation prediction, green chromatography, and harmonized bioanalytical validation.

Humans

Integrated phytochemical and bioactivity profiling of Xanthium strumarium fruits from Korea and China: Implications for origin-specific quality specification.

BACKGROUND: Geographic origin influences the phytochemical composition and biological activities of medicinal plant resources. Xanthium strumarium L. (XS) fruit is widely used in East Asian traditional medicine. However, current pharmacopeial standards primarily recognize Chinese-derived material, despite the availability and traditional use of XS in Korea. To address this gap and support origin-informed quality specification, we compared fruits from Korea (XS-K) and China (XS-C) using chloroplast genome sequencing, targeted phytochemical profiling (high-performance liquid chromatography (HPLC) for selected phenolics and gas chromatography-flame ionization detection (GC-FID) for fatty acids and phytosterols, and multivariate chemometric analysis. RESULTS: Chloroplast genome analysis revealed high overall similarity but localized divergence around the rpoC2 locus and a greater mutation burden in XS-C, supporting origin-associated genomic differentiation. Phytochemical profiling revealed distinct origin-dependent metabolic signatures. XS-K showed higher levels of phytosterols, chlorogenic acid, 4,5-dicaffeoylquinic acid (4,5-DCQ), and xanthatin was detected only in XS-K, whereas XS-C exhibited greater abundance of total fatty acids, particularly oleic acid. Unsupervised clustering and log2 fold-change ranking confirmed clear compositional separation, and variable importance in projection (VIP) analysis identified chlorogenic acid, &#x3b2;-sitosterol, oleic acid, 4,5-DCQ, and xanthatin as major discriminators between origins. Bioactivity assays demonstrated that XS-K exerted stronger antioxidant effects in ABTS, DPPH and FRAP assays, stronger skin-related enzyme inhibition, and greater antibacterial activity against Staphylococcus aureus, consistent with its enriched phenolic and sterol profile. CONCLUSION: Together, chloroplast sequence variation, targeted metabolite quantification, and screening bioassays consistently distinguished XS-K from XS-C. These findings support the use of candidate markers for the origin-based authentication and quality control of XS fruit-derived ingredients. &#xa9; 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Fruit

A prospective crossover study comparing ICCS-recommended and Palmer-adjusted filling rates in children with spina bifida.

OBJECTIVE: This study aimed to investigate whether the maximal cystometric capacity (MCC) in children with spina bifida (SB) is indeed lower, as predicted by the Palmer formula, and to evaluate the impact of different bladder filling rates on urodynamic parameters. MATERIALS AND METHODS: This prospective, randomized, two-sequence crossover-controlled study included 70 children aged 3-18 years with spina bifida under regular follow-up. In Group 1, the first two bladder fillings were performed at the ICCS-recommended rate, and the third at 75% of that rate (Palmer formula). In Group 2, the sequence was reversed. Urodynamic parameters, including maximal cystometric capacity (MCC), bladder compliance, detrusor activity, filling pressures, and detrusor leak point pressure (DLPP), were analyzed across fillings. RESULTS: Cystometric bladder capacity was lower during fillings performed at the Palmer-adjusted rate compared with those at the ICCS-recommended rate. The proportion of reduced compliance significantly decreased in Group 1 (p = 0.046) but remained unchanged in Group 2. A significant positive correlation was observed between expected bladder capacity (EBC) and measured MCC in both groups (&#x3c1; &#x2248; 0.5-0.6). The highest correlation and agreement were found in Group 1 during the third filling at the Palmer rate (ICC = 0.606). No significant intra- or intergroup differences were observed in detrusor pressure, end-filling pressure, DLPP, or overactive bladder prevalence. CONCLUSION: Bladder filling rate was associated with differences in both cystometric capacity and bladder compliance in children with spina bifida. Fillings performed according to the Palmer formula (approximately 75% of the ICCS-recommended rate) were associated with capacities that more closely approximated age-expected values and with modest differences in bladder compliance. Conversely, faster filling rates did not produce similar benefits. These findings suggest that slower filling strategies may improve measurement consistency and agreement with expected bladder capacity estimates. However, the magnitude and direct clinical impact of these differences should be interpreted cautiously, particularly in light of the potential influence of sequence-related effects.

Humans

Optimising Exercise Prescription: A Meta-Analysis Examining the Dose Response of Exercise Duration on Cardiorespiratory Fitness Following HIIT and MICT.

BACKGROUND: High-intensity interval training (HIIT) is often promoted as a time-efficient alternative to moderate-intensity continuous training (MICT) for improving cardiorespiratory fitness, yet the duration of HIIT sessions varies considerably across studies. OBJECTIVE: We aimed to characterise the dose-response relationship between exercise session duration and the improvement in cardiorespiratory fitness for HIIT and MICT. METHODS: A dose-response meta-analysis of randomised controlled trials comparing exercise duration in HIIT and MICT, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and registered in PROSPERO (CRD42022335590). Effect sizes were calculated using a random-effects meta-analysis. The primary outcome was maximal oxygen uptake (VO2max). Secondary outcomes included blood pressure, lipid profiles, glucose metabolism markers and body composition measures. A one-stage random-effects dose-response meta-analysis was performed to examine the relationship between exercise duration and adaptations. We searched PubMed and Google Scholar; eligibility criteria for selecting studies were randomised controlled trials in humans, published in English and exercise interventions lasting at least 4&#xa0;weeks. RESULTS: We identified 69 randomised controlled trials (2387 participants). High-intensity interval training elicited greater improvements in VO2max than MICT (d = 0.38, 95% confidence interval 0.27-0.49, p < 0.001). High-intensity interval training demonstrated a non-linear dose-response relationship between exercise session duration and VO2max, with 80% of maximal effect (changes in VO2max = 3.45&#xa0;mL/kg/min) achieved with only ~11&#xa0;min/session (95% confidence interval 9.5-40.2). Moderate-intensity interval training showed a linear dose-response relationship between exercise session duration and VO2max, requiring ~52&#xa0;min/session to achieve 80% of the&#xa0;maximal observed&#xa0;effect (95% confidence interval 30.4-55.8). The dose-response relationship was consistent across populations. High-intensity interval training and MICT had comparable effects in improving cardiometabolic risk factors. CONCLUSIONS: High-intensity interval training demonstrated a non-linear dose response, with 80% of maximal effect on VO2max in ~11&#xa0;min/session, whilst MICT required four to five times longer to reach similar responses. The different types of training had comparable effects on cardiometabolic risk factors.

Journal Article

Ketamine Plus Midazolam versus Fentanyl Plus Midazolam for Sedation and Analgesia during Image-guided Procedures in Interventional Radiology: Randomized Clinical Trial.

Background Opioid-benzodiazepine regimens remain common for radiologist-administered procedural sedation despite respiratory and analgesic effectiveness concerns. Purpose To compare intraprocedural pain and patient-reported experience between ketamine/midazolam and fentanyl/midazolam during image-guided procedural sedation. Materials and Methods This randomized clinical trial was conducted at a single academic center between June 2025 and February 2026. Adults undergoing image-guided lung or bone biopsy or abscess drainage were randomized to fentanyl/midazolam or ketamine/midazolam administered by interventional radiologists. Procedures were performed using US, CT, CT fluoroscopy, or combined CT and US guidance. The primary outcome was maximum intraprocedural pain (0-10 on the Numeric Rating Scale). Secondary outcomes included sedation depth, physiologic parameters, oxygen desaturation, patient-reported experience assessed using a modified Heidelberg questionnaire, and complications. Results Among 264 randomized procedures (132 procedures per group) in 260 participants (median age, 68 years [IQR, 61-75 years]; 135 [52%] female), ketamine/midazolam resulted in lower maximum intraprocedural pain than fentanyl/midazolam (mean difference, -1.4 points [95% CI: -2.0, -0.8]; P < .001). Pain scores greater than 4 occurred less frequently with ketamine/midazolam (2.3% vs 17%; absolute difference, 14 percentage points [95% CI: 8, 21]; P < .001). Ketamine/midazolam was associated with higher nadir oxygen saturation (mean difference, +1.4% [95% CI: 0.6, 2.2]; P = .001) and fewer oxygen desaturation events below 90% (three [2.3%] vs 13 [9.8%]; absolute difference, 7.6 percentage points [95% CI: 1.9, 13.3]; P = .02). Ketamine/midazolam produced deeper sedation and higher intraprocedural systolic blood pressure. Hallucinations occurred more frequently with ketamine/midazolam (15 [11.4%] vs five [3.8%]; absolute difference, 7.6 percentage points [95% CI: 1.3, 13.9]; P = .03), though overall procedural comfort, reduced recall, and perceived adequacy of sedation were improved. Procedure-related and sedation-related complications did not differ between groups. Conclusion Radiologist-administered ketamine/midazolam during image-guided procedural sedation improved analgesia and patient-reported experience with fewer hypoxemic events and no increase in complications compared with fentanyl/midazolam. Clinical trial registration no. NCT07040163

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Assessment of the safety and efficacy of sodium pentaborate pentahydrate in individuals with overweight and obesity: a randomized, double-blind, placebo-controlled, phase 1/2 dose-finding trial.

The present study aimed to examine the short-term safety and tolerability of sodium pentaborate pentahydrate (NaB) and to explore preliminary efficacy and dose selection as secondary objectives in individuals with overweight or obesity. In this randomized, double-blind, placebo-controlled, phase 1/2 trial, conducted from July 2024 to January 2025, 177 adults with overweight or obesity were randomized, of whom 116 completed the 12-week trial. Participants received placebo or NaB at doses of 200, 400, 600, 800, or 1,000&#x2009;mg for 12&#x2009;weeks, alongside a standardized diet and exercise programme. The primary safety objective was to investigate short-term safety and tolerability through adverse events, hypoglycaemic episodes, gastrointestinal adverse events, and changes in haematological and biochemical parameters. The primary exploratory efficacy outcome was percentage change in body weight from baseline to week 12. Secondary and exploratory efficacy outcomes included body weight, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, glycaemic markers, lipid parameters, and blood pressure. Baseline characteristics were broadly similar across groups (all p&#x2009;&#x2265;&#x2009;0.05), and no major short-term safety signal was observed. Mean body weight decreased in the 400&#x2009;mg (-2.6&#x2009;kg), 600&#x2009;mg (-1.2&#x2009;kg), and 1,000&#x2009;mg groups (-3.1&#x2009;kg). Compared with placebo, the 1,000&#x2009;mg dose resulted in the largest reductions in body weight (mean difference, -2.30&#x2009;kg; p&#x2009;=&#x2009;0.01) and BMI (mean difference, -0.85&#x2009;kg/m2; p&#x2009;=&#x2009;0.02). The 1,000&#x2009;mg dose showed preliminary efficacy for reducing body weight and BMI over 12&#x2009;weeks compared with placebo, with no major short-term safety signal and no clinically meaningful changes in renal, hepatic, or haematological markers. All reported adverse events were mild. These short-term findings are exploratory and require confirmation in future phase 3 trials with extended follow-up to investigate long-term safety and efficacy.

Humans