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Diurnal differences in the effects of heat exposure on renal function: A randomized controlled crossover trial.

High temperature is a major risk factor for kidney injury, and population exposure to nighttime heat is increasing as the climate warms. However, whether renal responses to heat exposure differ between daytime and nighttime remains unclear. Forty-one healthy adults participated in a randomized crossover experiment conducted in a controlled laboratory setting. Participants were exposed to heat (32°C during daytime; 30°C during nighttime) and thermoneutral conditions (26°C) for 8 h. Blood and urine samples were collected before and after each exposure to examine various renal biomarkers reflecting glomerular filtration function, tubular injury, and early kidney stress. Heat exposure affected both blood and urinary biomarkers of kidney function, with notable diurnal differences in renal responses. Daytime heat exposure primarily affected blood markers of glomerular filtration, increasing creatinine by 7.67% (95% CI: 4.73%-10.61%) and cystatin C by 3.05% (95% CI: 0.17%-5.93%), while reducing estimated glomerular filtration rate by 0.05% (95% CI: 0.02%-0.08%). In contrast, nighttime heat exposure predominantly elevated urinary biomarkers of early kidney stress, including insulin-like growth factor-binding protein 7 (58.40%, 95% CI: 27.66%-89.14%), kidney injury molecule-1 (47.25%, 95% CI: 18.91%-75.59%), and tissue inhibitor of metalloproteinases-2 (51.88%, 95% CI: 22.26%-81.51%). Moreover, increases in insulin-like growth factor-binding protein 7 were significantly greater at night than during the day. Sleep-related parameters, including sleep quality, duration, and heart rate variability, partially mediated nighttime heat effects on renal responses. These results indicated that heat exposure induced different diurnal patterns in renal responses.

Humans

The co-existence of Ehlers-Danlos syndrome and postural orthostatic tachycardia syndrome: A systematic review of the literature.

There is a growing body of literature evaluating both postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS). We conducted a systematic review to evaluate what is currently known about the co-existence of both conditions. A search of MEDLINE and EMBASE was performed in December 2025 and data were collected in tables and pooled to determine the prevalence of POTS in EDS and EDS in POTS. A total of 30 studies were included with 8421 patients with EDS and 12,983 patients with POTS. The average age across 16 studies that reported mean age was 33.3 years. POTS in patients with EDS ranges from 17.5% to 92.7% depending on the population. EDS in patients with POTS ranges from 17.9% to 50.0% depending on the population. One study suggested that patients with EDS and POTS had greater medication use, pain medications and greater number of clinic visits compared to POTS alone while another suggests that these patients have greater gastrointestinal symptoms and the odds were greatest for postprandial distress syndrome, chronic nausea and vomiting syndrome, vomiting and post-prandial fullness. We conclude that EDS and POTS frequently co-occur, and proportions of patients with POTS and EDS depends on the population evaluated. Overall, more research is needed to better understand how to effectively manage patients living with both EDS and POTS.

Humans

Efficacy of esketamine in reducing nausea and vomiting after anesthesia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative nausea and vomiting (PONV) are significant perioperative challenges. This study evaluated the efficacy of perioperative esketamine in preventing PONV. MATERIALS AND METHODS: We systematically searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to August 2025 for randomized controlled trials investigating the effect of perioperative esketamine on PONV. The primary outcome was PONV incidence. Secondary outcomes included time to first flatus, postoperative pain degree, anxiety scores, agitation, anesthesia recovery time, and post-anesthesia care unit (PACU) stay duration. Data were analyzed using RevMan 5.4 and STATA 15.0 software. Sensitivity and subgroup analyses were performed to assess result stability and explore potential sources of heterogeneity. RESULTS: Thirty-eight randomized trials (3,425 patients) were included. Esketamine reduced the risk of nausea (RR=0.69, 95% CI: 0.53-0.90) and vomiting (RR=0.75, 95% CI: 0.57-0.98), shortened time to first flatus (SMD=-0.81, 95% CI: -1.48 to -0.15), and decreased rescue analgesic needs within 2 days (SMD=0.32, 95% CI: 0.2-0.5). However, it prolonged anesthesia recovery time (SMD=0.97, 95% CI: 0.28-1.67) and PACU stay (SMD=0.76, 95% CI: 0.27-1.26). CONCLUSIONS: Perioperative esketamine may reduce PONV and aid gastrointestinal recovery, but its potential to delay anesthesia recovery and PACU discharge requires consideration. Further studies are needed to clarify its risk-benefit profile. DATE OF FIRST SUBMISSION TO PROSPERO: 10 March 2024. DATE OF THE START OF STUDY SCREENING AGAINST ELIGIBILITY CRITERIA: 21 March 2024.

Humans

The effect of dexmedetomidine in mechanically ventilated patients with sepsis and septic shock: a meta-analysis of randomized controlled trials.

PURPOSE: Dexmedetomidine (DEX) is a central sympatholytic with sedative properties widely used in critically ill patients. However, its effects in patients with sepsis and septic shock remain controversial. This meta-analysis evaluated the efficacy and safety of DEX compared to other sedatives in mechanically ventilated patients with sepsis and septic shock. METHODS: A systematic search was conducted across PubMed, Embase, Scopus, and Cochrane Library from inception through May 1, 2025 for randomized controlled trials comparing DEX with other sedatives or placebo in mechanically ventilated patients with sepsis and septic shock. Primary outcomes included overall mortality and Sequential Organ Failure Assessment (SOFA) scores. Secondary outcomes encompassed duration of mechanical ventilation (MV), length of stay in Intensive Care Unit (ICU), incidence of hypotension and bradycardia. RESULTS: Fifteen studies involving 3,882 patients (1,945 in the DEX group, 1,937 in the control group) were included. DEX was demonstrated no significant differences compared to other sedatives or placebo in overall mortality (Risk Ratio [RR] 0.98, 95% Confidence Interval [CI] 0.90 to 1.07, p = 0.71, I2 = 0%), SOFA scores (Mean Difference [MD] - 0.14, 95% CI -0.81 to 0.52, p = 0.67, I2 = 0%), length of stay in ICU (MD -0.32, 95% CI -1.69 to 1.06, p = 0.65, I2 = 77%), or incidence of hypotension (RR 1.15, 95% CI 0.81 to 1.62, p = 0.44, I2 = 14%). However, DEX significantly reduced the duration of MV (MD -0.54, 95% CI -0.98 to -0.10, p = 0.02, I2 = 25%) but was associated with an increased incidence of bradycardia (RR 1.67, 95% CI 1.22 to 2.28, p = 0.001, I2 = 0%). CONCLUSIONS: In mechanically ventilated patients with sepsis and septic shock, DEX shortened duration of MV but was associated increased bradycardia risk. No mortality or organ dysfunction benefits were observed. These findings suggest DEX is a reasonable therapeutic option to facilitate earlier ventilator weaning in selected patients (particularly those without shock), but careful monitoring for cardiovascular adverse effects is warranted.

Humans

Effects of 12 weeks of resistance and concurrent training with graded protein intakes on lipid profile, kidney and liver biomarkers in middle-aged to older women.

PURPOSE: To examine secondary lipid, kidney-related, and liver-enzyme responses to three protein intakes during resistance training (RT) alone or the same RT plus cycling (CT) in middle-aged to older women. METHODS: In this randomized 2×3 factorial trial, 108 women aged 40-77 years were assigned to RT or CT and 0.8, 1.6, or 2.2 g kg-1 d-1 protein for 12 weeks. This complete-case secondary analysis included 83 participants. Linear mixed-effects models tested Time × Training, Time × Protein, and Time × Training × Protein effects, with false-discovery-rate-adjusted omnibus tests and Holm-adjusted contrasts. RESULTS: Triglycerides, total cholesterol, LDL-C, and apolipoprotein B decreased and HDL-C increased in all conditions. Lipid changes differed by protein condition, and several were more favorable with CT; however, CT comprised RT plus additional cycling and greater exercise exposure. Urea, blood urea nitrogen, creatinine, the blood urea nitrogen-to-creatinine ratio, and cystatin C increased, whereas three eGFR estimates decreased. Responses differed mainly between 0.8 and the two higher protein conditions, with little evidence of differences between 1.6 and 2.2 g kg-1 d-1. ALT, AST, and GGT differed by protein condition; AST and GGT also showed training-dependent responses. CONCLUSIONS: The dietary and exercise interventions modified lipid and clinical-chemistry responses. Because energy and food composition were not fully matched and CT added cycling to RT, the findings do not isolate protein dose or exercise modality. Changes in eGFR estimates and liver enzymes do not establish organ injury or long-term safety.

Humans

Sustained cognitive and functional effects of pro-cognitive interventions for bipolar disorder: A systematic review of randomised controlled trials.

A substantial proportion of individuals with bipolar disorder (BD) experience considerable cognitive deficits. Existing systematic reviews have evaluated the efficacy of pro-cognitive interventions in BD, but have not established whether any cognitive benefits translate into functional improvements, with evidence for sustained functional effects remaining limited. A systematic search was conducted on MEDLINE, EMBASE, PsycINFO and Cochrane Library from inception until 21 May 2026. Eligible studies were randomised controlled trials (RCTs) in BD reporting cognitive or functional outcomes at three or more months following a pro-cognitive intervention, or examining the translation of cognitive benefits into improvements in functional outcomes at any timepoint. Seven unique RCTs plus three secondary analyses of these trials (n = 615) met the inclusion criteria. Approximately 13% (7/55) of RCTs identified in the search of pro-cognitive interventions in adult BD assessed cognitive or functional outcomes at least 3 months after treatment end. Of the seven unique RCTs, most evaluated cognitive remediation (CR; k = 4). The average follow-up length was 4 months (range: 3-6 months). Three of the four RCTs examining CR reported cognitive benefits at 3 to 6 months, whereas only one CR RCT found consistent functional effects at 3 months. Evidence on the translation of cognitive benefits to functional improvements is scarce and inconsistent. Most trials examining pro-cognitive interventions do not examine whether potential benefits are sustained or whether they translate into improvements in real-world functioning. CR appears to be a promising intervention for achieving durable cognitive gains in BD, although evidence for sustained effects of other interventions is limited.

Humans

Revisiting somatosensory evoked potentials in motor neuron diseases: neurophysiological insights from a large cohort.

OBJECTIVE: To systematically investigate Somatosensory Evoked Potential (SEP) abnormalities in a large cohort of patients with Motor Neuron Disease (MND), and to explore their relationship with Motor Evoked Potentials (MEPs) and clinical phenotypes. METHODS: We retrospectively analyzed 267 patients with confirmed MND who underwent standardized SEPs and transcranial magnetic stimulation. Patients were divided into pure/predominant Upper Motor Neuron (UMN) and pure/predominant Lower Motor Neuron/Amyotrophic Lateral Sclerosis (LMN/ALS) groups. SEP abnormalities were assessed using internal normative data, including prolonged latencies, reduced amplitudes, and increased N20-P25 amplitudes. MEPs were classified semi-quantitatively as normal or abnormal by independent raters. RESULTS: At least one SEP abnormality was detected in 75&#xa0;% of patients, with no significant differences between the UMN and LMN/ALS groups. Increased N20-P25 amplitudes were observed in both phenotypes, suggesting widespread sensory cortical hyperexcitability across the MND spectrum. In contrast, abnormal MEPs were significantly more frequent in UMN patients (p&#xa0;<&#xa0;0.001). No significant association was found between SEP abnormalities and MEP findings. Upper- and lower-limb SEP latencies were strongly correlated (all p&#xa0;<&#xa0;0.001), whereas increased SEP amplitudes did not correlate with latency abnormalities. CONCLUSIONS: SEP abnormalities are highly prevalent in MND and appear largely independent from corticospinal dysfunction. Increased SEP amplitudes likely reflect primary cortical sensory hyperexcitability rather than impaired sensory conduction. SIGNIFICANCE: These findings support the concept of MND as a multisystem network disorder that involves sensory cortical circuits and highlight the role of SEPs in the diagnostic workup.

Humans

Norgestrel drives mitochondrial collapse and plasma membrane impairment in Pacific oyster (Crassostrea gigas) sperm by triggering premature acrosome reaction.

The toxic mechanisms of norgestrel (NGT), an emerging marine pollutant, on the sperm from externally fertilized invertebrates remain elusive. This study employed an integrated physiological and multi-omics framework to elucidate how NGT (10 and 1000&#xa0;ng/L) disrupts acrosome reaction (AR) signaling machinery, thereby impairing the functional integrity of Pacific oyster (Crassostrea gigas, also known as Magallana gigas) sperm. Exposure to NGT triggered a significant, dose-dependent premature AR, characterized by elevated acrosin activity and a loss of acrosomal integrity. Multi-omics integration supports a model in which this premature exocytosis is linked to signaling disturbances, including disruption of calcium signaling and reduced transcript abundance of calmodulin (CaM) and the primary recognition protein zonadhesin (Zan). This signaling interference induced an premature AR, subsequently driving a cascade of bioenergetic and structural failures. At the mitochondrial level, NGT induced abnormal mitochondrial permeability transition pore (mPTP) opening and elevated the transcript levels of antioxidant defense genes (e.g., peroxiredoxin-5, PRDX5). These alterations indicate the occurrence of mitochondrial collapse. Concurrently, scanning electron microscopy verified localized plasma membrane wrinkling and pore formation in sperm. In addition, NGT exposure decreased the transcript abundance of cytoskeleton-related genes, including solute carrier family 26 member 6 (SLC26A6), actin (ACT), and tubulin polymerization promoting protein family member 3 (TPPP3). These molecular changes further disrupted membrane phospholipid homeostasis, as represented by altered glycerophospholipid metabolism. At the same time, cumulative cellular stress was associated with decreased transcript abundance of cytoprotective factors (e.g., baculoviral IAP repeat-containing proteins, birc2) and changes in apoptosis-related genes consistent with activation of a caspase-8-mediated apoptotic programme. In conclusion, NGT, as a representative synthetic progestin, exerts reproductive toxicity by interfering with signaling mediators to induce premature AR, which subsequently exhausts metabolic energy and triggers plasma membrane impairment. These findings provide a critical mechanistic basis for the aquatic ecological risk assessment of synthetic progestins.

Animals

Hydrogen-rich water combined with traditional Chinese medicine compound in the treatment of kidney stones: a randomized controlled prospective clinical trial.

JOURNAL/mgres/04.03/01612956-202701000-00009/figure1/v/2026-09-13T085902Z/r/image-tiff The formation and development of kidney stones are related to abnormal urine metabolism, oxidative stress and inflammation. Hydrogen-rich water has clear efficacy in antioxidant and improving inflammatory status, while Ye-Shi-Shi-Lin-Formula is a clinically effective traditional Chinese medicine compound preparation for treating kidney stones. This randomized controlled prospective clinical trial from July 2025 to March 2026 at the Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine examined the effect of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula on kidney stones. The included 100 patients with kidney stones were randomly divided into blank, hydrogen-rich water, hydrogen-rich water and Chinese medicine, and Chinese medicines groups. The patients received drinking hydrogen-rich water and/or Ye-Shi-Shi-Lin-Formula daily for 12 weeks. All subjects received basic treatment following the guidelines. Imaging examination, urine metabolism testing, renal function, inflammation and oxidative stress index, blood routine and liver function are used to detect the efficacy and safety of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula. Results showed that the total effective rate of kidney stone treatment in blank group, Chinese medicines group, hydrogen-rich water and Chinese medicine group and hydrogen-rich water group was 28%, 76%, 80% and 32%. The Ye-Shi-Shi-Lin-Formula can partially alleviate the oxidative stress, uric acid metabolism and urinary magnesium levels of patients with kidney stone and improve the function of renal tubules. The hydrogen-rich water therapy showed only efficacy in improving glutathione reductase but the combination of hydrogen-rich water and Ye-Shi-Shi-Lin-Formula has shown superior efficacy in improving oxidative stress and related metabolic factors of blood uric acid and urine stones, as well as in renal tubular function. The results indicate that the addition of hydrogen-rich water can improve urinary metabolism and oxidative stress status in the treatment of kidney stones with Ye-Shi-Shi-Lin-Formula. The study was registered at the International Traditional Medicine Clinical Trial Registry (Registration No. ITMCTR2025001446).

Humans

Effectiveness of the DASH diet versus alternative dietary interventions for hypertension management: A systematic review and meta-analysis.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet is widely recommended for blood pressure control; however, its comparative effectiveness relative to other structured dietary interventions remains uncertain. OBJECTIVE: To evaluate the comparative effectiveness of the DASH diet versus alternative dietary interventions on blood pressure and cardiometabolic outcomes in adults. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA guidelines. Multiple databases were searched from inception to February 2026. Eligible studies included adults with elevated blood pressure or hypertension comparing the DASH diet with other dietary interventions or usual care. Continuous outcomes were pooled using random-effects models and expressed as mean differences (MD) or standardized mean differences (SMD). Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 22 randomized controlled trials were included in the qualitative synthesis, of which 10 were included in the meta-analysis. The DASH diet did not demonstrate a statistically significant advantage over comparator diets in reducing systolic blood pressure (MD = 1.30; 95% CI: -1.54 to 4.14) or diastolic blood pressure (MD = 0.21; 95% CI: -3.72 to 4.14), with substantial heterogeneity observed across studies. Significant effects were identified for selected cardiometabolic outcomes, including reductions in urinary sodium excretion (MD = -32.89; 95% CI: -62.76 to -3.01), LDL cholesterol (MD = -8.59; 95% CI: -14.64 to -2.54), and glycated hemoglobin (HbA1c) (MD = -0.49; 95% CI: -0.52 to -0.46), as well as an increase in urinary potassium excretion (MD = 11.76; 95% CI: 4.08 to 19.44). The certainty of evidence ranged from moderate to very low across outcomes. CONCLUSIONS: The DASH diet was not superior to other dietary interventions in reducing blood pressure; however, it demonstrated consistent benefits in selected cardiometabolic parameters. Given the overall low certainty of evidence and substantial heterogeneity, these findings should be interpreted cautiously. Future research should focus on well-designed trials with standardized outcomes and longer follow-up to clarify comparative effectiveness.

Humans

Effects of Exergame Balance Training with Variable Cognitive Motor Challenges on Serum BDNF, p-tau181, and Cognitive Functions in Adults with Mild Cognitive Impairment: A Randomized Trial.

INTRODUCTION: Cognitive-motor exergame balance training may increase attentional demands and neuronal processing, potentially affecting serum levels of brain-derived neurotrophic factor (BDNF), A&#x3b2;1-42, and p-tau181, as well as train cognitive abilities in adults with mild cognitive impairment (MCI). This study aimed to compare the effects of exergame balance training of mild, moderate, high-difficulty, and Wii Fit&#x2122; groups on blood serum levels of BDNF, A&#x3b2;1-42, p-tau181, and cognition function in adults with MCI. METHODS: In this four-arm, parallel group randomized clinical trial, 97 adults with MCI were randomly assigned to exergame balance training groups of mild, moderate, high-difficulty, and Wii Fit exergame as a control group. All participants received 40 min/session, 3 times/week for 8 weeks. Assessment of serum levels of p-tau181, A&#x3b2;1-42, BDNF, and cognitive functions was conducted at baseline, after weeks 4 and 8. A mixed-model analysis of covariance was used, with post-baseline measurements (weeks 4 and 8) specified as the within-subject factor and the corresponding baseline value entered as a covariate to adjust for initial between-group variability. RESULTS: A significant group &#xd7; time interaction was found for BDNF, F(3,92) = 6.413, P = 0.017, &#x3b7;p2 = 0.181; p-tau181, F(3,92) = 4.640, P = 0.040, &#x3b7;p2 = 0.138; attention, F(3,92) = 4.171, P = 0.045, &#x3b7;p2 = 0.057; abstraction, F(3,92) = 4.263, P = 0.043, &#x3b7;p2 = 0.058; and visuospatial skills, F(3,92) = 6.931, P < 0.001, &#x3b7;p2 = 0.234. CONCLUSION: Cognitive-motor challenge-based exergame balance training was associated with an increase in serum BDNF, a reduction in p-tau181. In contrast, the A&#x3b2;1-42 levels remained stable. These changes were accompanied by improvement in selective cognitive functions (attention, abstraction, and visuospatial skills) in individuals with MCI. Greater effects were observed in moderate and high-difficulty groups, suggesting the importance of intervention intensity in promoting cognitive and neurobiological outcomes in MCI.

Humans

Cross-tissue multi-omics integration highlights BPHL and mitochondrial targets in Alzheimer's disease.

BACKGROUND: Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), yet specific molecular targets remain to be fully characterized. METHODS: A summary-data-based Mendelian randomization (SMR) framework integrated AD genome-wide association study (GWAS) statistics (39,918 cases) with blood DNA methylation quantitative trait loci (mQTL), gene expression (eQTL), and protein (pQTL) data for 1136 mitochondria-related genes. Associations were assessed using Bayesian colocalization and HEIDI testing. Tissue relevance was evaluated in four brain regions (hippocampus, amygdala, cortex, frontal cortex) using GTEx and external transcriptomic datasets. RESULTS: Screening identified eight candidates supported across blood mQTL and eQTL layers. Stepwise central nervous system (CNS) evaluation singled out biphenyl hydrolase-like (BPHL) as the consistent candidate. Higher genetically predicted BPHL expression was associated with reduced AD risk across the hippocampus (OR=0.920, 95% CI 0.873-0.970), amygdala (OR=0.925, 95%CI 0.880-0.973), cortex (OR=0.943, 95% CI 0.908-0.978), and frontal cortex (OR=0.938, 95%CI 0.901-0.976). These findings aligned with protein-protein interactions connecting BPHL to respiratory complexes and lower BPHL expression in independent AD brains. Functional enrichment converged on oxidative phosphorylation pathways. CONCLUSIONS: By integrating multi-omics data with tissue-specific validation, this study nominates BPHL as a consistent protective candidate in the brain. These findings provide genetic support for mitochondrial molecular perturbations in AD, offering insights for future validation.

Alzheimer Disease

A 7-mm Covered TIPS Reduces&#xa0;Hepatic Encephalopathy Without Increasing Rebleeding in Cirrhotic Patients With Small Liver: A Randomized Study.

BACKGROUND/AIMS: International guidelines recommend initiating transjugular intrahepatic portosystemic shunt (TIPS) placement with an 8-mm stent. However, there is an evident lack of randomized controlled trials evaluating TIPS diameters <&#x2009;8&#x2009;mm in cirrhotic patients with a relatively small liver. The aim of this study was to determine whether 7&#x2009;mm-covered TIPS, compared with 8-mm stents, could achieve comparable shunt function with a lower incidence of hepatic encephalopathy (HE). METHODS: In this multicenter randomized controlled trial, patients with cirrhosis and relatively small liver were randomized 1:1 to receive TIPS with a 7-mm (n&#x2009;=&#x2009;92) or 8-mm (n&#x2009;=&#x2009;92) covered stent to prevent variceal rebleeding. The primary endpoint was the incidence of overt HE after randomization. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival and a composite of these outcomes, were designated as secondary endpoints. RESULTS: Among the 184 enrolled patients, the predominant etiologies of liver cirrhosis were hepatitis B virus infection (56.0%) and alcohol-related liver disease (20.7%). Over a median follow-up of 26.5&#x2009;months, overt HE occurred in 19 patients (20.7%) in the 7-mm group and 33 patients (35.9%) in the 8-mm group. The 2-year cumulative incidence of overt HE was significantly lower in the 7-mm group than in the 8-mm group (21.4% vs. 37.2%, p&#x2009;=&#x2009;0.02). Stent diameter, post-TIPS portosystemic pressure gradient, pre-covert HE and MELD-Na score were identified as independent risk factors for overt HE. The rates of shunt dysfunction were statistically similar between groups (8.7% vs. 8.7%, p&#x2009;=&#x2009;1.0), as were 2-year rebleeding rates (10.9% vs. 9.8%, p&#x2009;=&#x2009;0.81) and OLT-free survival rates (91.3% vs. 88.0%, p&#x2009;=&#x2009;0.82). CONCLUSIONS: A 7-mm covered TIPS demonstrated comparable shunt function to an 8-mm covered stents, with a significantly lower risk of overt HE. These findings support consideration of 7-mm TIPS stents for preventing variceal rebleeding in cirrhotic patients with a small liver who are undergoing TIPS. TRAIL REGISTRATION: ClinicalTrials.gov, NCT02541825.

Humans

Changes in hippocampal functional connectivity and volume associated with cognitive improvement and decline in amnestic mild cognitive impairment following computerized cognitive training.

BACKGROUND: The hippocampus influences the outcomes of amnestic mild cognitive impairment (aMCI) and undergoes different changes during the cognitive decline or recovery of aMCI compared to elderly individuals with normal cognition, which may reveal disease-dependent neurodegeneration or plasticity. We first aimed to investigate the hippocampal changes associated with cognitive changes in aMCI using a combined case-control study design. METHODS: In total, 50&#x202f;aMCI individuals and 50 healthy controls (HCs) were recruited in Shenyang, China, and separately randomized into training and control groups: aMCI training group, aMCI no training group, HC training group, and HC no training group. The aMCI and HC training groups received computerized cognitive training (CCT) thrice weekly for 12 weeks. Cognitive assessments and MRI data were collected at baseline and follow-up. RESULTS: The primary outcome was significant CCT&#xd7;diagnosis interaction effect on the change in cognitive performance as measured by clock drawing test (CDT) scores (F&#x202f;=&#x202f;4.322, P&#x202f;=&#x202f;0.041); this interaction was driven by CCT specifically in aMCI (F&#x202f;=&#x202f;4.465, P&#x202f;=&#x202f;0.038). Significant CCT&#xd7;diagnosis interaction effects of right-hippocampal FC changes were observed in the bilateral precuneus/cuneus (Pvoxel<0.05) driven by CCT in aMCI (F&#x202f;=&#x202f;5.429, P&#x202f;=&#x202f;0.023), and in the left superior temporal gyrus/middle temporal gyrus (STG/MTG, Pvoxel<0.05), driven by CCT of only in HCs (F&#x202f;=&#x202f;6.587, P&#x202f;=&#x202f;0.013). A significant interaction effect of left-hippocampal FC changes were observed in the right triangular part of the inferior frontal gyrus (IFGtriang, Pvoxel<0.05), driven by CCT in aMCI and HCs (F&#x202f;=&#x202f;6.550, P&#x202f;=&#x202f;0.013; F&#x202f;=&#x202f;7.097, P&#x202f;=&#x202f;0.010). No significant interaction effect on the change in hippocampal GMV was noted (P&#x202f;>&#x202f;0.05). CONCLUSION: CCT can improve the visuospatial ability of aMCI, which is reflected by the CDT scores. CCT can alter hippocampal FC in the bilateral precuneus/cuneus, the right IFGtriang, and the left STG/MTG. The hippocampal GMV is difficult to change in both HCs and aMCI during the cognitive decline. REGISTRATION NUMBER: ChiCTR1900026849. DATE OF REGISTRATION: 24 October 2019 NAME OF TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR).

Humans

Effect of a PROtein-enriched MEDiterranean diet and EXercise (PROMED-EX) on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline: the PROMED-EX randomized controlled trial.

BACKGROUND: Undernutrition in older adults is associated with adverse health outcomes including cognitive decline, yet evidence for effective preventive strategies is limited. OBJECTIVES: The objective of this study was to investigate effects of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in "at risk" community-dwelling older adults. METHODS: A total of 105 participants (69% female; aged 67.7 &#xb1; 6.1 y) at risk of undernutrition and cognitive decline were randomized to 1 of 3 groups: 1) PROMED-EX (personalized dietary counseling plus home-based exercise); 2) PROMED (personalized dietary counseling only); or 3) CON (healthy eating leaflet). The primary outcome was change in nutritional status at 6 mo, measured by the Mini Nutritional Assessment (MNA; 0-30 points). Secondary outcomes included neurocognitive test battery (NTB) z-score, PROMED diet quality score (0-14), physical performance, and health-related quality of life. Analyses followed an intention-to-treat approach using linear regression to assess between-group differences in 6-mo outcomes. RESULTS: At baseline, the mean MNA score was 22.5 &#xb1; 2.3. After 6 mo, nutritional status improved significantly in both intervention groups compared with CON: mean differences in MNA were 2.7 [95% confidence interval (CI): 1.3, 4.2] for PROMED and 2.9 (95% CI: 1.5, 4.3) for PROMED-EX (both P < 0.001). Cognitive function also improved, with NTB z-score differences of 0.3 (95% CI: 0.1, 0.5; P = 0.01) in PROMED and 0.2 (95% CI: 0.0, 0.4; P = 0.02) in PROMED-EX compared with CON. Diet quality scores significantly increased with mean differences of 4.0 (95% CI: 2.9, 5.0) for PROMED and 3.9 (95% CI: 2.8, 4.9) for PROMED-EX compared with CON (both P < 0.001). Despite low adherence to exercise, additional benefits were observed for physical performance and quality of life. CONCLUSIONS: Dietary intervention improved nutritional status in community-dwelling older adults at risk of undernutrition. Correcting undernutrition could help to slow cognitive decline and promote physical health and quality of life during aging. This study was registered at clinicaltrials.gov as NCT05166564.

Humans

A systematic review of macaque brain stimulation: Trends and future directions.

Neurostimulation techniques can powerfully modulate neural circuit activity and provide causal insights into the relationship between brain function and behavior. Macaque monkeys have long been a key animal model for brain stimulation studies. While stimulating the macaque brain with one or a few electrodes has already taught us much about brain function and dysfunction, recent technological advances promise a future with more precise stimulation using many more electrodes. However, such possibilities also increase the number of choices an experimenter has when designing their study. We can learn from a rich past, but a comprehensive overview of which brain regions have been studied and with what stimulation parameters is lacking. Here, we present a PRISMA-compliant systematic review of 734 macaque brain stimulation studies using electrical and/or optogenetic stimulation. We find a striking bias in which brain areas have traditionally been stimulated: a mere 10 brain regions account for half of all studies, with the remainder of studies investigating approximately 150 other areas. Across studies, stimulation frequency robustly predicted direct behavioral effects independent of brain region, while amplitude did not. Future studies could more systematically explore less studied regions through lower stimulation frequencies (e.g., 20-50&#x202f;Hz) alongside established ranges (&#x223c;200&#x202f;Hz). Tools such as fMRI or optical imaging can capture neural circuit engagement evoked by these frequencies, even when behavioral effects are absent or remain subtle. Our synthesis offers a guide towards the next steps in high-channel-count, high-precision stimulation approaches.

Animals

Specialized pro-resolving mediators in obesity and overweight conditions: A systematic review of human and animal evidence on comparative differences and associations.

Obesity and overweight are characterized by persistent low-grade inflammation. Specialized pro-resolving mediators (SPMs), polyunsaturated fatty acid-derived metabolites, actively promote inflammatory resolution, and their dysregulation has been linked to unresolved inflammation and metabolic disturbances in obesity. This systematic review synthesized human and animal evidence on adiposity-related differences and associations in SPMs and SPM precursors. The protocol was prospectively registered in PROSPERO (CRD420251067464). PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched up to 22 May 2026. Eligible studies included human and animal research comparing SPMs and/or SPM precursors between overweight/obese and normal-weight/lean groups or assessing their associations with adiposity indices. Due to heterogeneity across matrices and analytical platforms, findings were synthesized narratively. Twenty-seven unique studies were included, providing 28 experimental datasets (14 animal and 14 human). The most consistent alterations were observed in adipose tissue and circulation, where overweight/obesity was frequently associated with lower concentrations of SPMs and/or SPM precursors. In humans, circulating Resolvin E1 showed reproducible reductions and was inversely associated with adiposity measures in several cohorts. In contrast, selected metabolites, including SPM Lipoxin A4 and the SPM precursors 15-HETE and 18-HEPE, exhibited mixed directionality across studies. Evidence for hepatic and central nervous system compartments was limited and heterogeneous. Overall, available evidence suggests that excess adiposity is associated with altered SPM and precursor profiles, most consistently in adipose tissue and circulation, whereas hepatic and central nervous system findings remain inconsistent. Future studies using standardized quantification and tissue-specific designs are needed to clarify whether targeting pro-resolving pathways has translational potential in obesity-related metabolic dysfunction.

Animals

Perioperative analgesic efficacy of ultrasound-guided erector spinae plane block and posterior transversus abdominis plane block in paediatric patients undergoing open pyeloplasty: A prospective randomised trial.

PURPOSE: Open pyeloplasty in the paediatric population involves extensive tissue dissection and manipulation, resulting in significant postoperative pain. Ultrasound-guided fascial plane blocks have emerged as an important component of multimodal analgesia in abdominal surgeries. This study compared the analgesic efficacy of ultrasound-guided Erector spinae plane block (ESP) and posterior transversus abdominis plane (pTAP) block in children undergoing open pyeloplasty. METHODS: It is a prospective, randomised, double-blind study conducted at a single paediatric centre in a tertiary care hospital in Asia from January 2022 to June 2023. 40 ASA I-II children were randomised to receive either the ESP block (Group E) or the pTAP block (Group T). Both groups received 0.4 ml/kg, 0.2% ropivacaine with 1 mcg/kg dexmedetomidine. Children with an allergy to local anaesthetics, cardiac, renal or hepatic dysfunction and local site infection were excluded. The primary outcome was cumulative 24 h postoperative acetaminophen consumption. Secondary outcomes included the effects on intraoperative hemodynamics, perioperative opioid consumption, FLACC and Watcha scores, time to first rescue analgesia, and any block-related complications. RESULTS: Weight-normalised 24 h postoperative acetaminophen consumption was significantly lower in the ESP group (13.5 &#xb1; 4.7 mg/kg) compared to the pTAP group (25.4 &#xb1; 8.3 mg/kg), with a mean difference of -12 mg/kg (p < 0.001, 95%CI -16 to -7.6). The median time to first rescue analgesia was significantly longer in the ESP group (18 h [95% CI, 18-24]) than in the TAP group (9 h [95% CI, 6-12]), p < 0.001. Although FLACC scores were significantly lower in the ESP group at 30 min and 12 h postoperatively, the overall longitudinal analysis using a linear mixed-effects model showed no significant difference in the trend of FLACC scores over time between the two groups. There were no block-related complications. CONCLUSION: Ultrasound-guided ESPB provides better, longer-lasting analgesia than posterior TAP block in children undergoing open pyeloplasty. Hence, it may serve as an effective component of multimodal pain management in paediatric open pyeloplasty. CTRI REGISTRATION (CTRI/2022/04/041876) DATED 13/04/2022): https://ctri.nic.in/Clinicaltrials/rmaindet.php?trialid=67747&EncHid=42257.14515&modid=1&compid=19.

Humans