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PubMed2026

Glucocorticoid receptor antagonism in major depressive disorder with childhood trauma: a randomized controlled trial.

Childhood trauma (CT) is a key risk factor for major depressive disorder (MDD) onset and persistence. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie this link, and preclinical studies suggest glucocorticoid receptor (GR) antagonism can reverse early life stress effects. This study tested whether the GR antagonist mifepristone reduces depressive symptoms in adults with MDD and CT. The RESET-medication study was a randomized, double-blind, placebo-controlled trial evaluating a 7-day course of mifepristone (1200 mg/day) or placebo in 158 adults with MDD and CT, assessed at baseline, 1 week, 6 weeks (primary endpoint), 3 months, and 6 months. The primary outcome was depressive symptom severity (IDS-SR) at week 6; secondary outcomes included symptom severity at other timepoints, clinical response, remission, anxiety, sleep, stress, disability, and salivary cortisol. At week 6, depressive symptoms declined in both groups, with no significant difference between mifepristone and placebo (b=-0.25, d=-0.03, 95% CI [-0.42, 0.36], pnom=0.887), and no group differences were found for secondary outcomes. Morning and evening cortisol were significantly higher with mifepristone at week 1, consistent with GR antagonism, but not at week 6. Adverse events were more frequent with mifepristone; mild and severe events occurred significantly more often, while the proportion reporting at least one adverse event was numerically higher but not statistically significant (93.6%vs. 82.5%, χ²(1)=3.60, p=0.058). Mifepristone produced the expected endocrine response but did not lead to clinical improvements in individuals with MDD and CT compared to placebo.

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

Adjunctive intermittent theta-burst stimulation for first-episode schizophrenia: A randomized clinical trial.

BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidone and cognitive behavioral therapy (CBT) and explored serum biomarkers indicating treatment response. METHODS: In this randomized, assessor-blind trial, 100 first-episode schizophrenia patients received either iTBS plus risperidone and CBT (iTBS group, n = 50) or risperidone and CBT alone (control, n = 50) for 3 months. The primary outcome was change in PANSS total score at 4 weeks and 3 months. Response was defined as a ≥ 50 % PANSS reduction. Secondary outcomes included cognitive function (MCCB subtests) and serum GDNF, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: The iTBS group showed significantly greater reduction in PANSS total scores than controls at both 4 weeks and 3 months (mean difference at 3 months: -13.3, 95 % CI: -16.8 to -9.8; P < 0.001), with a higher responder rate (76 % vs. 48 %). Significant improvements across all cognitive domains were observed in the iTBS group (all P < 0.001). Post-treatment, the iTBS group exhibited higher GDNF and lower cortisol and DHEA-S levels (all P < 0.001). A combined biomarker panel demonstrated superior discriminative performance for treatment efficacy (AUC=0.865 after cross-validation). Adverse events were comparable between groups. CONCLUSIONS: Adding iTBS to risperidone and CBT significantly improves clinical symptoms and cognitive function in first-episode schizophrenia. The combination of GDNF, cortisol, and DHEA-S shows promise as a composite biomarker for treatment response, though sham-controlled validation is warranted.

Humans↗

PubMed2026

Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas.

AIMS: Early acute changes in estimated glomerular filtration rate (eGFR) have been well described with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, but less is known about the frequency, prognostic relevance, and implications of these changes after mineralocorticoid receptor antagonist (MRA) initiation in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a post-hoc analysis of 1648 patients enrolled in the TOPCAT trial (Americas regional subgroup), defining an early eGFR dip as a ≥15% decrease in eGFR between baseline and week 4. Landmark analyses assessed the association of eGFR changes, treatment, and the primary composite endpoint (cardiovascular death, HF hospitalization, or aborted cardiac arrest). RESULTS: Within 4 weeks of treatment initiation, 431 (26%) patients experienced acute eGFR decrease with a higher proportion of patients assigned to spironolactone [269 (33%)] compared with placebo [162 (20%)] (odds ratio 1.97; 95% confidence interval 1.58-2.47). An acute eGFR decrease was independently associated with higher risk of subsequent cardiovascular outcomes, irrespective of treatment arm. However, treatment with spironolactone appeared beneficial in reducing the primary cardiovascular outcome irrespective of the presence [hazard ratio 0.75 (0.53-1.08)] or absence [0.80 (0.64-1.00)] of early eGFR decrease (Pinteraction = .81). At any given magnitude of eGFR decline, risk of the primary endpoint was consistently lower with spironolactone compared with placebo (Pinteraction = .64). CONCLUSIONS: Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease. An acute eGFR decrease early after MRA initiation should not automatically prompt treatment discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00094302.

Humans↗

PubMed2026

Application of musculoskeletal ultrasound in postoperative rehabilitation assessment and monitoring after rotator cuff repair: A systematic review.

BACKGROUND: The development of rehabilitation protocols after rotator cuff repair has long lacked objective benchmarks. Traditional time‑based regimens are limited by considerable inter‑individual variability and an increased risk of re‑tear. Musculoskeletal ultrasound allows dynamic assessment of tendon healing and muscle morphology, yet evidence for directly linking its use to rehabilitation decisions remains scarce. OBJECTIVE: To systematically synthesize the evidence on the use of musculoskeletal ultrasound monitoring to inform rehabilitation decision‑making after rotator cuff repair. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) guidelines, we searched PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Data from January 2020 to April 2026. Original studies were included if they involved patients who had undergone rotator cuff repair, used musculoskeletal ultrasound (including gray‑scale ultrasound, elastography, etc.) to evaluate the rotator cuff tendons or shoulder muscles, and reported at least one parameter related to rehabilitation decision-making or functional outcomes. RESULTS: Eleven studies were included. Shear wave velocity (SWV), cross‑sectional area (CSA), and echo intensity (EI) were the most frequently reported ultrasound parameters. Available evidence indicated that SWV increased progressively after surgery, with an overall increase of approximately 22% to 25% from one week to 12 months postoperatively. This dynamic trajectory may serve as a reference baseline for judging rehabilitation progress. An abnormally elevated SWV in the early postoperative period was associated with an increased risk of re‑tear, suggesting that a more conservative rehabilitation strategy should be adopted. Tendon stiffness measured at 12 weeks after surgery independently predicted long‑term return to sport. Regarding muscle parameters, changes in CSA and EI were positively correlated with shoulder function scores, and the combination of these two parameters effectively identified patients with rehabilitation bottlenecks. CONCLUSION: Musculoskeletal ultrasound parameters are associated with the initiation of active movement, adjustment of exercise load, prediction of return‑to‑sport prognosis, and identification of retear risk. Among these, SWV shows particular promise as an objective monitoring parameter for supporting rehabilitation assessment after rotator cuff repair. Future randomized controlled trials are needed to determine whether ultrasound-informed assessment can improve rehabilitation outcomes compared with traditional time-based regimens, and to establish standardized measurement protocols and clinically applicable reference values. Key findings of this review are summarized in S1 File.

Humans↗

PubMed2026

Sex differences in sleep and alcohol consumption outcomes following a digital insomnia intervention.

BACKGROUND: Poor sleep is a well-established risk factor for heavy drinking, and evidence suggests that sleep could serve as a potential treatment target for reducing alcohol consumption. The relationship between poor sleep and problematic drinking appears to be stronger among females, but no studies to date have assessed sex differences in alcohol consumption following insomnia treatment. Here, we combine the samples from two clinical trials to investigate sex differences in the effects of a digital cognitive behavioral therapy for insomnia (Sleep Healthy Using the Internet; SHUTi) on sleep and alcohol outcomes. METHODS: 184 heavy drinking individuals with insomnia (weekly binge episodes: 4/5 + drinks in one sitting for females/males; AUDIT score >7; ISI score >14) were randomly assigned to either the SHUTi program (n = 102) or an active control program (n = 82). Participants completed self-report assessments at baseline, immediately following the 9-week intervention period, and at 3 and 6-months post-intervention. RESULTS: Linear mixed effects models showed that SHUTi effects over time were stronger among females than males for improved sleep outcomes and reduced frequency of total and heavy drinking days (ps ≤ 0.038). Follow-up comparisons of within-group effect sizes revealed consistently larger reductions in alcohol consumption among SHUTi females (Cohen's d range = 0.92-2.23) than SHUTi males (Cohen's d range = 0.65-1.95). CONCLUSIONS: Findings suggest that SHUTi may be more efficacious in improving sleep and reducing drinking among females with insomnia compared to males. These results could have important implications for sex-specific prevention and treatment efforts for heavy drinking individuals with insomnia.

Humans↗

PubMed2026

Not just when, but how: An exploratory dual-control approach to video feedback in motor learning.

The present study provides exploratory evidence for a novel dual-control paradigm. It examines whether combining temporal over video feedback timing with learner-controlled interactive playback functions (pause, slow-motion, rewind) would enhance motor skill acquisition beyond temporal autonomy alone. Sixty-four novice adults were randomly assigned to one of four conditions: Full Control (self-controlled timing + interactive replay), Partial Control (self-controlled timing + non-interactive replay), Yoked Full Control (externally controlled timing + interactive replay), or Yoked Partial Control (externally controlled timing + non-interactive replay). Motor accuracy (Radial Error), movement consistency (Bivariate Variable Error), technical execution, and self-efficacy were assessed at pre-test, 24-h retention, and 72-h retention following two acquisition sessions on a dart-throwing task (120 trials total). The Full Control group demonstrated the greatest and most durable learning gains across all outcomes. The Group × Time interaction was significant across all dependent variables (η2ₚ ranging from 0.140 to 0.234), with Full Control demonstrating superior retention at both 24 and 72 h relative to other groups (though differences relative to Partial Control were more pronounced at 72-h retention). Critically, the Yoked Full Control group showed comparatively weaker outcomes despite access to the same interactive playback functions. These findings suggest that interactive video tools may be most useful when learners can regulate both when feedback is accessed and how it is inspected. Theoretical and practical implications for the design of learner-centered video feedback systems are discussed.

Humans↗

PubMed2026

Efficacy of an Adhesive Hydrocolloid Bandage on Wound Healing: Findings of a 28-Day, Single-Centre, Randomised, Controlled Study.

This single-centre, randomised, controlled study assessed the wound healing efficacy of adhesive bandages in eligible healthy adults (N = 36) aged 25-55 with Fitzpatrick skin types II and III using a model of laser-induced wounds. Here, we report data for wounds that were randomised to treatment with either a hydrocolloid bandage for multi-day use (BAND-AID Adhesive Bandage Hydroseal), standard of care (SoC) (BAND-AID Adhesive Bandage Tru-Stay Sheer) or an uncovered control. Primary endpoints included the time to complete healing and a composite wound healing score. Hydrocolloid bandage-treated wounds healed twice as fast as the uncovered control or SoC-treated wounds. Median time (days) to complete healing was significantly faster for the hydrocolloid bandage-treated wounds (6.9) versus SoC (11.9) and uncovered control (11.8). Hydrocolloid bandage-treated wounds had significantly better composite wound healing scores versus SoC and versus uncovered control over 2 weeks. At Day 28, cosmesis was better with hydrocolloid bandage treatment (0.3) versus SoC (0.6) and uncovered control (2.1) (change from baseline in a composite scar score; higher score = worse outcome). Multi-day wound occlusion with a hydrocolloid bandage promoted faster healing and improved cosmesis compared with daily SoC dressings or uncovered control.

Humans↗

PubMed2026

Fyn signaling in the medial prefrontal cortex regulates resistance to stress-induced object recognition impairments in male rats.

Genome-wide association studies on patients with depression have identified FYN and FYB, an FYN-binding protein, as being linked to depression. We have reported that experimental manipulations in gene expression in the medial prefrontal cortex (mPFC) alter stress-induced object recognition impairments in animals. Therefore, we examined the impact of alterations in FYN and FYB expression in the mPFC of adult male rats on resistance to stress-induced impairments in object recognition. Animals with virus-mediated knockdown or overexpression of Fyn in the mPFC were subjected to either a brief 20-min restraint with 20 intermittent tail shocks, which does not induce object recognition impairment, or a prolonged 60-min restraint with 60 intermittent tail shocks, which does. In an object recognition task, control rats maintained intact object recognition following a brief stress, whereas rats with Fyn knockdown or overexpression in the mPFC showed impaired object recognition. Prolonged stress impaired object recognition in both control rats and rats with Fyn knockdown or overexpression. Additionally, rats with Fyn knockdown in the mPFC exhibited fewer c-Fos-positive cells in the mPFC in response to brief stress, accompanied by a trend toward increased c-Fos in the amygdala compared with control rats. Fyn knockdown also reduced Fyb expression in the mPFC. Furthermore, Fyb knockdown in the mPFC impaired object recognition following brief stress, suggesting that the observed effects are consistent with involvement of a coupled Fyn-Fyb signaling axis rather than Fyn alone. These findings suggest that altered Fyn-related signaling in the mPFC may underlie the resistance to stress-induced object recognition impairments.

Animals↗

PubMed2026

Manual, digital, and AI tumour-infiltrating lymphocyte scoring: a secondary analysis of the APHINITY randomised trial.

BACKGROUND: Stromal tumour-infiltrating lymphocytes (sTILs) are prognostic in early-stage HER2-positive breast cancer, but their role in the context of dual HER2 blockade remains undefined. We evaluated manual, digital, and artificial intelligence (AI)-based sTIL quantification, together with AI-derived spatial metrics, for prognostic and treatment-benefit stratification using tumour samples from the phase 3 APHINITY trial. METHODS: In the APHINITY trial, 4805 patients were randomly assigned to receive chemotherapy plus trastuzumab with pertuzumab or chemotherapy plus trastuzumab with placebo. Median follow-up was 74·1 months (IQR 68·3-75·4). We analysed 4262 haematoxylin and eosin-stained images using manual assessment, an automated digital approach, AI-based lymphocyte quantification (AI percentage lymphocytes), and two AI-derived spatial features (AI-TIL and immune hotspot). Interobserver reproducibility was assessed in 262 randomly chosen tumour samples scored independently by five pathologists. Multivariable Cox models were used to assess associations between TIL levels and invasive disease-free survival (primary outcome in APHINITY), distant recurrence-free interval, and overall survival. The heterogeneity of pertuzumab benefit was evaluated using subgroup analyses, subpopulation treatment effect pattern plot analyses, and nested Cox models with treatment-by-biomarker interaction terms. FINDINGS: Manual scoring showed high interobserver reproducibility (intraclass correlation coefficient 0·84 [95% CI 0·79-0·88]). Concordance between manual and automated methods was modest. AI-based scoring (AI percentage lymphocytes) reclassified 120 (11·6%) of 1035 node-positive tumours from immune-low (by manual scoring) to immune-high; this subgroup of patients showed greater separation of 5-year invasive disease-free survival curves between pertuzumab and placebo groups compared with patients whose tumours were concordantly classified as immune-low by both manual and AI-based approaches. Higher levels of TILs were associated with improved invasive disease-free survival for all sTIL measurement approaches and spatial measurements (hazard ratios [HRs] 0·41-0·93). Pertuzumab was associated with improved invasive disease-free survival at higher sTIL levels across all measurement approaches (HRs 0·36-0·48), but was not associated with higher values of spatial measures. The largest 6-year absolute improvements with pertuzumab were observed in patients with node-positive disease whose tumours scored in the highest level of immune infiltration of manual sTIL scoring (≥70·0%; mean absolute improvement 12·1 percentage points [SD 2·8]). In nested prognostic and predictive models, AI-based immune hotspot scores provided the most consistent additional information when combined with any sTIL measurement (all p<0·010). INTERPRETATION: Standardised manual sTIL scoring was reproducible, and digital and AI-based methods showed consistent prognostic stratification and potential for treatment-benefit stratification despite only modest correlation between platforms. AI spatial metrics provided complementary information beyond sTIL density and could support more scalable immune assessment. Future studies are needed to validate these approaches in independent cohorts and to clarify their clinical utility for stratifying contemporary HER2-directed therapies. FUNDING: None.

Humans↗

PubMed2026

Ameliorating Effects and Autonomic Mechanisms of Transcutaneous Auricular Vagus Nerve Stimulation on Abdominal Pain in Patients With Functional Dyspepsia and Irritable Bowel Syndrome.

BACKGROUND: Patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS) often experience abdominal pain and reduced quality of life and need effective treatments. This exploratory study aimed to evaluate whether transcutaneous auricular vagus nerve stimulation (taVNS) could improve abdominal pain and quality of life in patients with FD and IBS, and whether the effects were mediated via the autonomic mechanisms. METHODS: A total of 64 patients with abdominal pain (43 FD and 21 IBS) with a pain score of 3 out of 10 or higher were randomized to receive 2 weeks of taVNS or sham-taVNS treatment. The primary outcome was numeric rating scale (NRS) for abdominal pain. The dyspeptic symptom scales (DSS), IBS symptom severity scale score (IBS-SSS), anxiety and depression scores, and the SF36 quality of life scale were assessed before and after the treatment. The electrocardiogram was also recorded for the assessment of autonomic function at baseline and after the treatment. KEY RESULTS: (1) taVNS reduced the abdominal pain score (p < 0.001 for both FD and IBS), the frequency of abdominal pain (p < 0.001 for both FD and IBS), and overall symptom scores in both FD patients and IBS patients (p < 0.001 for FD and IBS). There was no significant difference in the effect of taVNS on abdominal pain between FD and IBS patients. (2) taVNS improved quality of life compared with baseline in both FD and IBS patients. (3) taVNS decreased anxiety (p < 0.001) and depression (p < 0.001). (4) taVNS increased vagal activity. At the end of the taVNS treatment, the vagal activity was negatively correlated with the pain score (r = -0.491, p = 0.004). CONCLUSIONS: Non-invasive taVNS improves abdominal pain, quality of life, and anxiety and depression in patients with FD and patients with IBS, possibly attributed to the enhancement of vagal activity. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2400085697.

Humans↗

PubMed2026

In situ product monitoring in heterogeneous reaction of gaseous trimethylamine on Fe2O3/Fe(NO3)3: Effect of environmental factor and particle property.

Gas-particle reactions represent an important atmospheric heterogeneous transformation process for organic amines (OAs). Environmental factors and particle properties may impact the gas-particle reaction products. Although the products from gas-particle reactions can be monitored by various in situ techniques, related data remain scarce. Here, the interfacial and gaseous products from the reaction of trimethylamine on Fe2O3/Fe(NO3)3 particles under light irradiation with mixed NO2, O2, SO2 and H2O were monitored using in-situ diffuse reflectance Fourier transform infrared spectroscopy and proton transfer reaction time-of-flight mass spectrometry. Dark reaction of gaseous trimethylamine on Fe2O3/Fe(NO3)3 generated two interfacial products types: N-containing ones (CH3NCH2, CH3NO2, (CH3)2NCHO, and CH3N(OH)CHO) and N-free ones (alcohols, aldehydes and acids), both accumulating with reaction progression. Light irradiation and O2 oxidation enhanced formation of these products, while NO2 promoted the production of CH3NO2 and (CH3)2NCHO. H2O and SO2 occupied the active sites of particles to inhibit the formation of all products. Compared to Fe(NO3)3, Fe2O3 showed absolute dominance in contribution to the formation of products. Considering the smaller particle size of Fe2O3 and excess Fe(NO3)3, the physical mixing of them reduced the generation of interfacial products. Furthermore, gaseous products of CH3OH, HCHO, CH3CHO, HCOOH and CH3COOH detection clarified the N-free interfacial products. The presence of Fe(NO3)3 inhibited the formation of HCOOH and favored the formation of CH3CHO in the gas phase. By combining product information with thermodynamic calculations, the heterogeneous reaction pathways of trimethylamine were tentatively proposed. These findings provide a guiding significance for the migration of OAs in real atmospheric environment.

Methylamines↗

PubMed2026

Transcriptomic responses of Porphyrophora sophorae larvae during licorice root colonization reveal coordinated remodeling of translation, mitochondrial energy metabolism and defense-related genes.

BACKGROUND: Porphyrophora sophorae is a subterranean piercing-sucking scale insect that damages licorice (Glycyrrhiza uralensis) roots, but the molecular responses associated with larval root colonization remain insufficiently defined. METHODS: We compared non-parasitic larvae (NP) and root-colonizing larvae (RC) using six RNA-seq libraries, de novo transcriptome assembly, DESeq2-based differential expression analysis, GO/KEGG enrichment, annotation-based candidate gene screening, and RT-qPCR validation of selected genes. RESULTS: Sequencing yielded 260.91 million clean reads, and de novo assembly produced 60,794 non-redundant transcripts. DESeq2 identified 703 FDR-significant DEGs, including 49 upregulated and 654 downregulated genes in RC larvae. Upregulated genes were mainly associated with translation- and ribosome-related processes, whereas downregulated genes were enriched in mitochondrial, oxidation-reduction, energy metabolism, and oxidative phosphorylation-related functions. Annotation-based screening identified 75 FDR-significant candidate genes associated with chemosensation, defense-related responses, and energy metabolism, with mitochondrial energy metabolism-related genes forming the largest module. RT-qPCR validation based on the raw Ct data showed concordant expression directions for ten selected transcript targets. CONCLUSIONS: Root colonization in P. sophorae larvae was associated with coordinated transcriptional remodeling involving selective activation of translation-related processes, adjustment of mitochondrial energy metabolism, and changes in defense-related gene expression. These results provide candidate molecular targets for future functional studies of host contact, feeding establishment, and physiological adjustment in this subterranean scale insect.

Animals↗

PubMed2026

Patient expectations assessed before randomisation and after the first treatment session, and their associations with pain outcome at 3 months in patients with tennis elbow: a secondary analysis of a randomised controlled feasibility trial in Norwegian secondary care.

OBJECTIVE: To evaluate patients' expectations of pain improvement before randomisation (T1) and after the first treatment (T2), and to examine how expectations at these two time points were associated with pain outcome measured at 3 months (T3). DESIGN: Exploratory secondary analyses of a three-arm, randomised controlled feasibility trial in patients with tennis elbow comparing heavy slow resistance training, shock wave therapy and advice (1:1:1). SETTING: Outpatient clinic at Oslo University Hospital. PARTICIPANTS: Adults with lateral epicondylalgia, commonly known as tennis elbow. MAIN OUTCOME MEASURES: Expected pain was rated on a Numeric Rating Scale (NRS, 0-10) at T1 and T2. Present pain (NRS, 0-10) was reported at 3 months (T3). Changes in expectations from T1 to T2 were summarised descriptively. Univariable linear regressions assessed associations between T3 pain and expectations at T1 and T2, treatment group and baseline factors. Explained variance was quantified by R2. Multivariable models including demographics and baseline pain were evaluated via adjusted R2. RESULTS: Fifty-four participants were included. In the shock wave group, nine (47%) came to expect greater improvement from T1 to T2; by contrast, in the advice group, seven (41%) expected less improvement. Expectations at T1 were not associated with T3 pain, whereas expectations at T2 were positively associated with T3 pain (b=0.61, 95% CI 0.33 to 0.89, p<0.01, R2=0.27), suggesting that higher expected pain at T2 was associated with higher reported pain at T3. Adding education and baseline pain increased explained variance modestly (R2 from 0.27 to 0.32). CONCLUSION: In this study, expectations measured after randomisation and one treatment session were associated with pain at 3 months for patients with tennis elbow. Larger, prospectively designed studies should investigate how postrandomisation expectations relate to clinical outcomes in non-blinded musculoskeletal trials. TRIAL REGISTRATION NUMBER: NCT04803825.

Humans↗

PubMed2026

Whole-exome characterization of host genetic variation in HIV-associated genes across the high-prevalence Mizo population, Northeast India.

BACKGROUND: The Mizoram state of Northeast India has one of the highest HIV prevalence rates in Asia, yet the host genetic factors influencing HIV susceptibility in this Tibeto-Burman population remain uncharacterised. METHODS: We performed whole-exome sequencing using Illumina NovaSeq 6000, mean coverage 100X on 76 HIV-negative Mizo individuals. Variants were called using GATK HaplotypeCaller v4.3 against GRCh38p14, annotated with ANNOVAR, and filtered using hard-quality thresholds (QD ≥ 2, SOR ≤ 3, MQ ≥ 40, DP ≥ 10, GQ ≥ 20). The allele frequencies were compared against gnomAD v2.1.1 population databases. Hardy-Weinberg equilibrium was assessed using the Wigginton exact test with Bonferroni correction. RESULTS: Post-quality filtering resulted in 12,011 sample-variants across 2,821 unique positions from 36 HIV-associated loci (33 protein-coding genes, 2 chemokine ligands, and 3 lncRNA targets). Of these, 784 observations (51 unique positions) were high-impact nonsynonymous or loss-of-function variants. ADAR rs2229857 (p.K384R, NM_015840) was the most frequently observed variant (Mizo carrier frequency = 0.895; 95% CI: 0.806-0.946). CXCR1 rs16858808 (p.R335C) showed the greatest population enrichment (Mizo carrier frequency = 0.197; 95% CI: 0.123-0.300; 7.65-fold carrier-frequency enrichment versus gnomAD South Asian; CADD = 15.60). Sixteen of 20 tested variants deviated from Hardy-Weinberg equilibrium after Bonferroni correction (p < 0.0025), predominantly showing excess homozygosity consistent with the endogamous Mizo population. The protective variant CCR5-Δ32 was absent in all the 76 individuals tested. CONCLUSION: This first whole-exome characterization of HIV host genes in the Mizo population identifies CXCR1 rs16858808 as the most population-enriched functional variant and reveals a pervasive endogamy signature. These findings provide a population-specific genetic framework for future HIV susceptibility studies and ART pharmacogenomics research.

Humans↗

PubMed2026

The Effect of Pain Catastrophizing on Acupuncture Treatment for Chronic Pain in Cancer Survivors.

CONTEXT: Pain catastrophizing (PC) predicts worse pain outcomes in cancer survivors. However, little is known whether PC influences pain outcomes of nonpharmacological treatments such as acupuncture. OBJECTIVES: This study aimed to assess the impact of PC on acupuncture efficacy for chronic pain in cancer survivors. METHODS: This secondary analysis of PEACE trial used two-sample t-test and Pearson's chi-squared test to analyze the pain outcomes of cancer survivors who received electroacupuncture (EA) or battlefield acupuncture (BFA). PC was measured using Pain Catastrophizing Scale (PCS). The Brief Pain Inventory (BPI) was used to measure pain severity and interference at the primary endpoint (week 12). RESULTS: Among 266 participants, 41 (15.41%) had a high baseline PC. Among those receiving EA, high PC patients had greater reductions in pain severity (-3.9 vs. -2.1, P = 0.006) and pain interference (-3.8 vs. -2.6, P = 0.04) than low PC. PC was not associated with pain outcomes in BFA group (P > 0.05 for both severity and interference). Among patients with high PC, a greater proportion were responders in the EA group than those in BFA group (83.3% vs. 43.5%, P = 0.009). Among low PC patients, there was no significant difference in the proportion of responders between the EA and BFA groups (66.1% vs. 64.5%, P = 0.8). CONCLUSION: We found that cancer survivors with high baseline PC had greater pain reductions with EA than BFA and compared to low PC patients. These findings suggest that EA may serve as a targeted treatment option for vulnerable patients with high PC and further support precision pain management.

Humans↗

PubMed2026

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 mg for 12 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 ≥ 0.05), and no major short-term safety signal was observed. Mean body weight decreased in the 400 mg (-2.6 kg), 600 mg (-1.2 kg), and 1,000 mg groups (-3.1 kg). Compared with placebo, the 1,000 mg dose resulted in the largest reductions in body weight (mean difference, -2.30 kg; p = 0.01) and BMI (mean difference, -0.85 kg/m2; p = 0.02). The 1,000 mg dose showed preliminary efficacy for reducing body weight and BMI over 12 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↗

PubMed2026

Superficial Cervical Plexus Block and Quality of Recovery after Thyroidectomy: A Randomized Clinical Trial.

BACKGROUND: Whether adding a bilateral superficial cervical plexus block to a thyroidectomy enhanced recovery pathway improves postoperative quality of recovery remains uncertain. METHODS: In a single-center prospective, randomized, double-blind, placebo-controlled trial in adults undergoing thyroidectomy with general anesthesia, participants were randomized to bilateral superficial cervical plexus blocks with 0.25% bupivacaine or saline. All participants received multimodal analgesia with dexamethasone, acetaminophen, nonsteroidal anti-inflammatory drugs, and incisional local anesthetic. The primary outcome was quality of recovery, measured by the QoR-40 survey, on postoperative day 1. Secondary outcomes included the need for rescue opioid, total opioid consumption, nausea, vomiting, antiemetic administration, length of stay in the postanesthesia care unit (PACU), and opioid use on postoperative day 1. RESULTS: A total of 160 participants were randomized to receive a superficial cervical plexus block with bupivacaine 0.25% (n = 78) or saline (n = 82). On postoperative day 1, mean QoR-40 scores were 174 (95% CI, 170 to 178) for bupivacaine and 173 (95% CI, 169 to 177) for saline. The adjusted mean difference between bupivacaine versus saline was 0.91 (95% CI, -3.57 to 5.40; P = 0.688). There were no significant between-group differences in the need for opioids in the PACU or on postoperative day 1, nausea, vomiting, or PACU length of stay. However, the total amount of opioid administered in the PACU was lower in the bupivacaine group (median [interquartile range], 0 [0 to 8]) compared with the saline group (2 [0 to 20]; Hodges-Lehmann location shift, 0 morphine milligram equivalents; 95% CI, -4 to 0; P = 0.017), and fewer participants in the bupivacaine group received rescue antiemetics (3 [3.8%] vs . 13 [16%]; difference, -12%; 95% CI, -22% to -1.8%; P = 0.011). CONCLUSIONS: Bilateral superficial cervical plexus blocks did not improve quality of recovery after thyroidectomy when added to a multimodal analgesic regimen including dexamethasone, acetaminophen, nonsteroidal anti-inflammatory drugs, and incisional local anesthetic but were associated with lower total PACU opioid consumption.

Humans↗