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PubMed2026

Thoracic paravertebral block with different doses of liposomal bupivacaine versus ropivacaine for postoperative analgesia in single-port thoracoscopic lung surgery: a randomized clinical trial.

OBJECTIVE: To evaluate the analgesic efficacy of thoracic paravertebral block (TPVB) with different doses of liposomal bupivacaine (LB) or ropivacaine in patients undergoing single-port thoracoscopic lung surgery. METHODS: A total of 105 patients scheduled for video-assisted single-port thoracoscopic lung surgery were randomized in a 1:1:1 ratio into three groups: low-dose LB group (group LL), high-dose LB group (group HL), or ropivacaine group (group R). All received ultrasound-guided TPVB at the T5/6 level preoperatively. The primary outcome was the area under the curve (AUC) of NRS of pain at activity (AUC-aNRS) from 1 to 72 h postoperatively. Secondary outcomes included the AUC of NRS of pain at rest (AUC-rNRS) from 1 to 72 h postoperatively, NRS of pain at rest and at activity at 1, 6, 24, 48, and 72 h postoperatively, and the cumulative opioid consumption at 24, 48, and 72 h postoperatively. Additionally, postoperative recovery and adverse events were assessed. RESULTS: AUC-aNRS differed significantly among groups (p = 0.0092), with high-dose LB lower than low-dose LB (p = 0.0071), but not versus ropivacaine. No significant difference was found in AUC-rNRS (p > 0.05). The group-by-time interactions for NRS of pain at rest and at activity were not significant (p > 0.05). Cumulative opioid consumption at 24, 48, and 72 h was lower in group HL versus group LL (all p < 0.017), but not versus ropivacaine. Postoperative recovery and adverse events showed no differences (p > 0.05). CONCLUSION: LB combined with TPVB is not superior to ropivacaine for postoperative analgesia in single-port thoracoscopic lung resection.

Humans↗

PubMed2026

Comparison of ultrasound-guided two-point block of the rhomboid intercostal vs. thoracic paravertebral for postoperative analgesia in patients undergoing three-port thoracoscopic surgery: a prospective, randomized, non-inferiority study.

BACKGROUND: The anesthetic characteristics of ultrasound-guided two-point rhomboid intercostal block (RIB) have not been fully established. This study compared the analgesic efficacy of ultrasound-guided two-point RIB with that of two-point thoracic paravertebral block (TPVB) for postoperative pain control and recovery in patients undergoing three-port thoracoscopic surgery. METHODS: Seventy patients aged 18-80 years scheduled for three-port thoracoscopic pulmonary resection were block-randomized in a 1:1 ratio to receive either TPVB or RIB. Both techniques were performed using 10 mL of 0.5% ropivacaine at each injection site. The primary outcome was the numerical rating scale (NRS) pain score at rest 24 h after surgery, with a predefined non-inferiority margin of Δ = 1. Secondary outcomes included NRS at rest and during coughing at 0.5, 2, 4, 12, 18, 24, and 48 h postoperatively, as well as the 24h postoperative Quality of Recovery-40 (QoR-40) score. RESULTS: The final analysis included 34 patients in the TPVB group and 34 in the RIB group. The mean difference in resting NRS scores at 24 h between the two groups was 0.088 (95% CI, -0.377 to 0.553), confirming the non-inferiority of RIB. However, the need for rescue analgesia was numerically greater in the RIB group than in the TPVB group (p = 0.045). The 24-h postoperative QoR-40 scores and cumulative sufentanil consumption within 48 h after surgery were comparable between the groups (both p > 0.05). CONCLUSION: Ultrasound-guided two-point RIB provided postoperative analgesia that was non-inferior to TPVB in patients undergoing three-port thoracoscopic surgery.

Adolescent↗

PubMed2026

Targeting cortico-striatal-amygdalar networks via theta-band frontoparietal synchronization in opioid use disorder: a randomized tACS-fMRI Trial.

Theta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD) to measure network engagement and behavioral outcomes. Sixty male participants with OUD were randomized to receive 20 min of active or sham 6 Hz tACS (HD electrodes over F4 and P4). Structural, resting-state, task-based fMRI drug cue reactivity, and repeated cue-induced craving assessments were collected immediately before and after stimulation. Pre-registered outcome measures were analyzed using time × group interaction models to examine (1) modulation of drug cue-related brain activity, (2) changes in craving, (3) alterations in functional connectivity, and (4) relationship between electric field, neural responses, and craving behavior. (1) A significant Time × Group interaction revealed decreased post-stimulation opioid cue-related activity in the active group relative to sham, involving key nodes in reward processing (ventral striatum, amygdala and ventral tegmental area) (FWE corrected α = 0.05) (2) subjective craving did not differ significantly between groups (3) Group by time generalized psychophysiological interaction analyses showed increased right frontoparietal network engagement (β = 2.63, p= 0.0308) following stimulation, and increased top-down inhibitory regulation of frontoparietal network on right ventral striatum (β = 1.99, p= 0.037) and left medial amygdala (β = 1.97, p= 0.039) (4) Electric field strength in the right frontal/parietal node predicted frontoparietal network engagement in the active group (r = 0.43, p= 0.02). Together, these findings demonstrate that theta-band frontoparietal tACS can modulate activity and task-dependent coupling within cortical-subcortical circuits in OUD, supporting network-targeted neuromodulation as a potential intervention for addiction.

Humans↗

PubMed2026

Effects of single-injection vs. continuous brachial plexus blocks for shoulder surgeries on patient-reported outcomes: a systematic review and meta-analysis with trial sequential analysis of randomised controlled trials.

INTRODUCTION: Single-injection and continuous brachial plexus block techniques are used widely for postoperative analgesia in patients undergoing shoulder surgery. Although patient-reported outcomes are described in individual studies, their effects have not been synthesised comprehensively using a patient-centred framework. We sought to compare the effects of single-injection vs. continuous brachial plexus block techniques on patient-reported outcomes in adult patients following elective shoulder surgery. METHODS: Databases were searched from inception to October 2025 and randomised controlled trials reporting patient-reported outcomes were included. Co-primary outcomes were postoperative patient-reported pain intensity at rest and during movement at 12 h, 24 h and 48 h post-surgery. Secondary outcomes included nausea and vomiting; sleep quality; patient satisfaction; opioid requests; and functional scores. Random-effects meta-analysis and trial sequential analysis were performed, with risk of bias and quality of patient-reported outcome reporting assessed. RESULTS: Twenty randomised controlled trials that included 1198 patients were analysed. Continuous brachial plexus blocks were associated with lower pain at rest at 12 h, 24 h and 48 h, with mean differences (MD) of -1.96 (95%CI -2.81 to -1.11, p < 0.001), -1.66 (95%CI -2.27 to -1.05, p < 0.001) and - 1.18 (95%CI -1.84 to -0.53, p < 0.001), respectively. Pain on movement could only be pooled at 24 h and 48 h and showed MD -2.04 (95%CI -4.26-0.19, p = 0.07) and - 1.30 (95%CI -3.67-1.07, p = 0.28) respectively. The co-primary outcomes approached or exceeded the predefined minimal clinically important difference for pain scores after shoulder surgery, in favour of continuous techniques. DISCUSSION: Continuous brachial plexus blocks are associated with better pain at rest and other patient-centred outcomes following shoulder surgery, while effects on dynamic pain and long-term functional recovery remain uncertain.

Humans↗

PubMed2026

Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology. METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n = 38) or sham stimulation (n = 36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0 mA, 20 min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements. RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74 ± 2.76 vs. sham: 2.69 ± 2.69; t = 4.799, p < 0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p < 0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p < 0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting. CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

Humans↗

PubMed2026

The analgesic efficacy of intrathecal morphine compared to peripheral regional analgesia in total hip arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Following elective total hip arthroplasty, pain continues to be a significant problem. Intrathecal morphine or peripheral regional analgesia, that is local infiltration analgesia or peripheral nerve block, are common analgesic modalities, but it is still not known which is superior. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: The following electronic databases were searched from inception to 24 March 2026: CENTRAL; Ovid Embase; Ovid MEDLINE; Scopus; and Web of Science. ELIGIBILITY CRITERIA: Randomised controlled trials that compared intrathecal morphine to peripheral regional analgesia in patients scheduled for elective total hip arthroplasty under general or spinal anaesthesia. RESULTS: Eight trials and 471 patients were included. The peripheral regional analgesia was peripheral nerve block in six trials and local infiltration analgesia in two trials. No difference was demonstrated between intrathecal morphine and peripheral regional analgesia in regard to the first coprimary outcome, the pain score at rest at 24 h. The quality of evidence was moderate. Intrathecal morphine was found to be superior to peripheral regional analgesia with respect to the second coprimary outcome, the cumulative intravenous morphine equivalent consumption at 24 h. Mean difference (95% CI) was 11.38 mg (4.31-18.45; P  = 0.002, I2  = 81%). The quality of evidence was low. Intrathecal morphine was revealed to be superior to peripheral regional analgesia at 8-12 h for the pain score at rest, 1.24 (0.60-1.88); P  = 0.0001, I2  = 68%; pain score on movement, 1.15 (0.12-2.17), P  = 0.03, I2  = 65%; but the rate of in hospital pruritus was reduced with peripheral regional analgesia, 0.31 (0.17-0.58), P  = 0.0002, I2  = 0%. No differences in functional status were shown. CONCLUSIONS: We found no difference between intrathecal morphine and peripheral regional analgesia in regard to pain score at rest at 24 h. Intrathecal morphine may lead to a favourable effect on some but not all analgesic indices compared to peripheral regional analgesia in elective total hip arthroplasty. The quality of evidence for these positive effects was low. Intrathecal morphine reduced the systemic opioid consumption, but is not in itself an opioid free strategy. This notion is supported by the increased incidence of in hospital pruritus with intrathecal morphine. The quality of evidence for this was high. In view of the quality of evidence, high quality randomised controlled trials are required to substantiate these results.

Humans↗

PubMed2026

Clinical efficacy and brain mechanism characteristics of guide chi and regulate spirit tuina therapy in the treatment of post-stroke walking dysfunction: A randomized controlled trial based on fNIRS.

BACKGROUND: This study aims to preliminarily evaluate the role of Guide Chi and Regulate Spirit(GCRS) Tuina in enhancing walking function in post-stroke patients with walking dysfunction; secondly, by using functional near-infrared spectroscopy (fNIRS), it investigates the effect of GCRS Tuina on the restoration of brain function in this patient population. METHODS: Participants in the control group received 4-week rehabilitation treatment, while those in the Combined Tuina Group (CTG) additionally received GCRS Tuina therapy for another 4 weeks on this basis. Functional Ambulation Category (FAC), Fugl - Meyer Assessment Scale for Lower Extremity Motor Function (FMA - LE), and Modified Barthel Index (MBI) were evaluated at the baseline and after 4 treatment weeks. A gait and motion analysis system was used to measure step length, stride, walking speed, and step frequency. FNIRS was used to measure the resting-state functional connectivity(FC) strength, as well as the β - value and HbO2 concentration mean during the walking task. RESULTS: A total of 60 participants completed the randomized, and 53 completed the trial and entered the statistical analysis. Compared with the Single Rehabilitation Group(SRG), the CTG group had higher FAC, FMA-LE, and MBI scores after 4 weeks. After the treatment course, the standardized step length, stride, walking speed, and step frequency of the CTG were higher than SRG. At the Region of Interest(ROI) level, the CTG exhibited 13 inter-ROI FC strengths that were higher than SRG, and the differences could survive the FDR correction (PFDR<0.05). Under the walking task, the CTG group had higher β values in 18 channels and higher Oxyhemoglobin(HbO2) concentrations in 19 channels than the SRG (PFDR <0.05). CONCLUSION: GCRS Tuina therapy can significantly improve patients' walking function, enhance lower limb motor ability and daily living ability. It can improve walking efficiency. Tuina can significantly increase the FC and enhance the activation levels and HbO2 concentrations. The stimulation of Tuina may help reconstruct the brain's motor control network, restore impaired motor function, promote the occurrence of neural plasticity, strengthen the neural circuits in the cognitive-motor-sensory cortex to improve walking function. TRIAL REGISTRATION: This study has been registered with the International Traditional Medicine Clinical Trial Registry (ITMCTR2024000654).

Humans↗

PubMed2026

Metabolic Stress Testing Reveals Persistent Lipid-Handling Dysfunction in Women With Polycystic Ovary Syndrome Despite Exercise Training.

AIM: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and metabolic dysfunction, yet baseline metabolomic studies show inconsistent findings. We investigated whether metabolic abnormalities in PCOS emerge under physiological stress and how these responses are modified by exercise training. MATERIALS AND METHODS: Twelve women with PCOS and 10 controls completed hyperinsulinaemic-euglycaemic clamps with randomised saline or lipid infusion, before and after 8 weeks of supervised exercise. Plasma metabolomics (163 metabolites) were measured at baseline, post-infusion and post-clamp. Linear mixed-effects models assessed Group × Timepoint × Intervention interactions. RESULTS: No baseline metabolite differences were observed between groups. A significant three-way interaction (p = 0.008) indicated condition-dependent trajectory divergence. Post hoc analysis revealed a specific divergence during post-exercise lipid challenge (p = 0.048). Women with PCOS showed reduced suppression of ether-linked phosphatidylcholines during insulin-stimulated lipid loading (PC ae C44:4, p = 0.031), despite exercise-induced improvements in fitness and normalisation of amino acid profiles. Exploratory metabolite ratios suggested impaired substrate coordination under stress. CONCLUSIONS: Metabolic defects in PCOS are stress-dependent and not detectable at rest. Exercise training improves resting metabolism but reveals persistent impairment in adaptive lipid handling during combined insulin and lipid challenges, suggesting impaired coordination of substrate supply during metabolic stress. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ISRCTN42448814.

Humans↗

PubMed2026

Effect of different liposomal bupivacaine concentrations in ultrasound-guided superior trunk block on postoperative analgesia and mobility: a randomized double-blind controlled trial protocol for shoulder arthroscopy.

BACKGROUND: Shoulder arthroscopy frequently causes severe postoperative pain that may impede recovery. Liposomal bupivacaine provides prolonged analgesia, and ultrasound-guided superior trunk block (STB) offers comparable analgesia to interscalene block with a lower risk of hemidiaphragmatic paralysis. However, the optimal concentration of liposomal bupivacaine for STB remains unknown. METHODS: This randomized, double-blind, controlled trial will enrol 282 adult patients scheduled for elective arthroscopic rotator cuff repair. Patients will be randomly allocated (1:1:1) to receive ultrasound-guided STB with liposomal bupivacaine 66 mg (Group A), 44 mg (Group B) or 33 mg (Group C), each diluted to 10 mL. The co-primary outcomes are (1) rest pain Numeric Rating Scale (NRS) score at 48 h post-surgery and (2) cumulative oral morphine milligram equivalents (MME) consumption within 0-48 h after surgery. Secondary outcomes include rest pain NRS scores at 6, 24 and 72 h; motor function assessed by Muscle Balance Scale, Bromage score and American Shoulder and Elbow Surgeons (ASES) score at 6, 24, 48 and 72 h; and Quality of Recovery-15 (QoR-15) score at 24 and 48 h. DISCUSSION: This study will provide evidence on the optimal concentration of liposomal bupivacaine for STB in arthroscopic shoulder surgery, aiming to achieve effective and prolonged analgesia without compromising shoulder mobility.

Humans↗

PubMed2026

Effect of transcutaneous auricular vagus nerve stimulation on postoperative pain in patients undergoing thoracoscopic partial lung resection: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Postoperative pain after thoracic surgery remains common and challenging. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation technique with potential analgesic effects. This study aimed to evaluate the efficacy and safety of taVNS for postoperative pain management in patients undergoing thoracoscopic partial lung resection. METHODS: Adults undergoing thoracoscopic partial lung resection were randomized to active or sham taVNS. The primary outcome was cough pain intensity at 48h post-surgery, assessed by Numeric Rating Scale (NRS). Secondary outcomes included cough pain at 24h and 72h, resting pain, moderate-to-severe pain incidence, opioid consumption, quality of recovery, postoperative pulmonary complications , chest tube duration, hospital stay, postoperative nausea/vomiting, and adverse events. RESULTS: Among 119 analyzed patients (active n = 60, sham n = 59), active taVNS reduced cough pain scores at 24h, 48h, and 72h postoperatively, as well as resting pain (p < 0.05). It also lowered the incidence of moderate-to-severe cough pain at 24h and 48h, reduced cumulative postoperative opioid use at 24h and 72h, and decreased rescue analgesia on postoperative day 3 (p < 0.05). Active taVNS was associated with a lower incidence of postoperative pneumothorax (p < 0.05). No serious adverse events occurred. CONCLUSION: Perioperative taVNS was associated with a modest analgesic benefit and reduced postoperative opioid requirements after thoracoscopic partial lung resection. The observed reduction in postoperative pneumothorax requires cautious interpretation, and further multicenter trials are needed to determine its clinical utility.

Humans↗

PubMed2026

Effects of erector spinae plane block on postoperative pain in patients undergoing implant-based breast reconstruction for breast cancer: a randomized controlled trial.

BACKGROUND: Implant-based breast reconstruction after mastectomy causes acute pain. OBJECTIVE: To determine whether a single-shot T5 erector spinae plane block (ESPB) reduces postoperative pain. DESIGN: Single-center, RCT with allocation concealment; blinded assessors and statisticians. SETTING: Tertiary cancer center in China. PATIENTS: 100 adults scheduled for radical mastectomy with implant reconstruction were randomized (1:1); follow-up complete. INTERVENTION: Before induction, ESPB was given under ultrasound guidance at T5 with 30 mL of 0.375% ropivacaine plus dexmedetomidine 1 μg/kg; controls received no block. Standardized general anesthesia and postoperative PCA for both groups. MAIN OUTCOME MEASURES: Resting NRS at 6 h (MCID=1). Secondary outcomes were opioid consumption, quality of recovery, and PONV. RESULTS: ESPB did not significantly reduce resting pain at 6 h at the median (τ =0.50; adjusted difference -0.9; p = 0.08). At the upper tail, pain intensity was lower (τ = 0.75; -1.8; p <0.01). Repeated measures provided additional time-point information, improving estimation precision and test sensitivity. ESPB get lower pain scores at 6, 12, and 24 hours (all p <0.01). But, the 95% CI includes the MCID, the clinical benefit remains uncertain. Opioid use decreased at 24 h (-13.5 mg; p <0.01) and 48 h (-6.6 mg; p <0.01). Quality of recovery improved at 24 h (difference 5 points; p <0.01), but not later. No differences were observed in intraoperative hemodynamics or PONV. CONCLUSIONS: Single-shot T5 ESPB with perineural dexmedetomidine may reduce postoperative pain and opioid requirements and improve early recovery. Further large trials are warranted. Clinical relevance remains to be confirmed. TRIAL REGISTRATION: ClinicalTrials.gov NCT06143020.

Humans↗

PubMed2026

Clinical Performance in Critical Care Simulation under Sleep Deprivation: Effects of Power Napping in the Recovery Napping Protocol for Anesthesiologist Performance (R-NAP) Randomized Controlled Trial.

BACKGROUND: Sleep deprivation is common among anesthesia residents and impairs both technical and nontechnical skills such as leadership. Napping is recommended in fatigue management across healthcare and other safety-sensitive sectors, yet its effectiveness for healthcare providers remains underexplored. This study evaluated whether a 30-min nap opportunity improved simulated crisis performance after a 24-h shift. METHODS: Residents were tested twice: once rested and once using a 24-h shift to induce partial sleep deprivation. Between sessions, they were trained in fatigue management. In the sleep-deprived condition, they were randomized to a nap opportunity or a control condition. Actigraphy objectively assessed sleep and nap duration. The primary endpoint was overall simulated clinical performance (0 to 200; combined technical and nontechnical scores). Secondary endpoints were technical and nontechnical subscales. Group effects were primarily tested using intention-to-treat regression models adjusted for rested performance, previous sleep, and critical care experience. RESULTS: Thirty-five residents were enrolled (nap opportunity, n = 19; control, n = 16). In the primary analysis sample (n = 27), clinical performance was 14.8 points higher after the nap opportunity compared with controls (95% CI, 2.8 to 26.9; P = 0.018), corresponding to a 7.4% improvement. Technical skills did not differ significantly between groups, although more sleep was associated with better technical performance. Nontechnical skills were higher in the nap opportunity condition (+11.0 points; 95% CI, 2.2 to 19.8; P = 0.016), including significant effects of leadership and resource utilization. Exploratory analyses suggested associations between longer nap duration and multiple performance domains, strongest for technical skills ( P = 0.010). CONCLUSIONS: Napping appears to enhance clinical performance, while the nap opportunity, nap duration, and previous sleep deprivation each influenced technical and nontechnical performance in distinct ways. These findings support integrating napping and recovery into medical education and scheduling.

Adult↗

PubMed2026

Contrast Heat-Cold Versus Thermoneutral Showering in Trained Combat Sport Athletes: A Randomized Field Trial of Recovery Outcomes.

Contrast heat-cold showering is popular for recovery, but multisystem evidence and persistence after cessation remain unclear. To evaluate whether a 4-week post-training contrast heat-cold shower intervention produces an integrated recovery profile across four domains (autonomic, endocrine, perceptual, and microvascular) rather than testing a single isolated physiological pathway, across baseline (T0), post-intervention (T1), and 2-week wash-out (T2). Sixty combat-sport athletes were randomized to contrast showers (10 min alternating warm 38-40°C and cold 13-15°C) or an active thermoneutral-shower comparator (10 min, 32-34°C) after training for 4 weeks. Primary analyses were per-protocol (≥ 75% compliance; n = 57), with intention-to-treat sensitivity analyses. Outcomes were Total Quality Recovery (TQR), morning salivary cortisol (two mornings averaged), resting HRV, and post-occlusive reactive hyperemia (PORH). From T0 to T1, favorable between-group changes were observed for resting HR (ΔΔ -2.10 bpm, 95% CI -2.24 to -1.96; g -0.65; p < 0.001), lnRMSSD (ΔΔ 0.123 log units, 95% CI 0.108 to 0.137; g 0.74; p < 0.001), with similar T1 effects for RMSSD and SDNN, and TQR (ΔΔ 0.61 points, 95% CI 0.27 to 0.95; g 0.80; p < 0.001). These T1 autonomic and perceptual changes were not maintained at T2 (all T2-T0 ΔΔ p > 0.05). Cortisol and PORH-derived outcomes showed no statistically clear between-group differences at T1 or T2 (all p > 0.05). Compared with thermoneutral showering, 4 weeks of post-training contrast heat-cold showering produced short-term favorable between-group changes in autonomic regulation and perceived recovery, but not in morning cortisol or PORH-derived microvascular reactivity. These effects were not maintained after wash-out; therefore, causal attribution to the shower intervention alone and claims of persistent physiological adaptation should be made cautiously. Trial registration: ISRCTN15418049.

Humans↗

PubMed2026

Lessons for the remaining U.S. states seeking pharmacist authority to prescribe self-administered hormonal contraceptives.

Explore the source record for details and available documents.

contraception↗

PubMed2026

Surgical treatment of schwannomas around the tarsal tunnel: a case series of 40 patients and systematic review of the literature.

OBJECTIVE: Schwannomas in the tibial, plantar, or medial calcaneal nerves around the ankle can mimic symptoms of tarsal tunnel syndrome. Outcomes after resection of schwannomas from these nerves have mainly been reported in case reports. The objectives of this study were to investigate the presentation and results for resection of schwannomas around the tarsal tunnel in a large case series and systematically review the currently available literature. METHODS: Data from 40 patients (27 sporadic and 13 schwannomatosis cases) treated at 2 centers were retrospectively analyzed for preoperative type and duration of symptoms, schwannoma size at presentation, and outcome after resection. The following different locations around the ankle were compared: proximal to the tarsal tunnel (PTT), at the tarsal tunnel (ATT), and distal to the tarsal tunnel (DTT). The severity of symptoms was categorized in increasing order for pain only on touch, during load-bearing activities, and symptoms also at rest. Surgical outcome was assessed based on pain relief and occurrence of complications. The systematic literature review was performed using a PubMed and Embase search. RESULTS: All but 1 patient presented with pain, local at the ankle, or neuropathic pain during weight-bearing activities (13/40, 32.5%). More than half of the patients also experienced symptoms at rest (52.5%). In 14 cases, the schwannoma was located PTT, in 17 cases ATT, and in 9 cases DTT in the plantar nerves. There were no significant differences in size and symptom duration at presentation for the different locations. Tumor size did not correlate with symptom severity. Outcomes after resection were excellent, with complete pain relief in all but 1 patient (97.0%). Complications included wound infection (5%) and temporary decreased sensation on the heel (7.5%). A review of 44 previously reported cases also frequently showed complete pain relief after resection. CONCLUSIONS: The results of this study show that schwannomas around the tarsal tunnel often present with severe pain symptoms, even if the lesion is still relatively small. Resection frequently results in excellent pain relief. During surgery, it may not be necessary to open the entire length of the tarsal tunnel, thereby limiting the size of the incision, especially in schwannomas located proximally or distally to the tarsal tunnel.

Humans↗

PubMed2026

Changes in hemoglobin levels and cardiometabolic health in adults with metabolic syndrome - a secondary outcome analysis of a six-month randomized controlled trial.

BACKGROUND: Lower hemoglobin (Hb) levels within the normal range have been associated with favorable metabolic traits in cross-sectional studies. This study investigated whether changes in Hb levels correlated with changes in physiological and cardiometabolic parameters during a six-month behavioral intervention in individuals with metabolic syndrome. METHODS: The six-month randomized controlled trial aimed to reduce sedentary behavior in adults with metabolic syndrome (n = 64). Key measurements included fasting blood samples, insulin sensitivity during a hyperinsulinemic-euglycemic clamp, insulin-stimulated liver glucose uptake, liver fat content (LFC), indirect calorimetry, cardiorespiratory fitness, and cardiac function. Correlations between changes in these variables and changes in Hb levels at baseline, three, and six months were examined. RESULTS: Cross-sectionally, higher Hb levels correlated with lower insulin sensitivity (r=-0.35, p = 0.005), higher resting O2 consumption (r = 0.41, p < 0.001), higher resting energy expenditure (r = 0.49, p < 0.001), higher LFC (r = 0.40, p = 0.011), and greater left ventricular wall thickness (r = 0.42, p = 0.001). The intervention did not significantly impact Hb levels, and changes in Hb levels did not correlate with most cardiometabolic changes. However, reduced Hb levels correlated with reduced fasting blood glucose (r = 0.29, p = 0.032), improved insulin sensitivity (r = -0.26, p = 0.045), and increased cardiorespiratory fitness (r = -0.29, p = 0.033). CONCLUSIONS: Changes in Hb levels did not consistently correlate with changes in cardiometabolic markers during the intervention. However, reductions in Hb levels may relate to improved insulin sensitivity and fitness. Along cross-sectional correlations, this may be clinically relevant for individuals with metabolic syndrome. Further studies are merited to clarify the role of Hb levels in this high-risk group.

Humans↗

PubMed2026

Modulation of heart rate and heart rate variability during animal-assisted treatment of patients in a minimally conscious state: A randomized controlled crossover study.

BACKGROUND: Animal-assisted treatment (AATx) is a promising and increasingly used approach in neurorehabilitation, yet its psychophysiological effects remain largely unexplored. Patients in a minimally conscious state (MCS) show severely altered consciousness with minimal but definite behavioral signs of awareness. Because behavioral assessment in this population is limited, psychophysiological measures such as heart rate (HR) and heart rate variability (HRV) may offer valuable insights into autonomic regulation during therapy. AIM: The present study investigated whether AATx influences HR and HRV compared to treatment as usual (TAU). METHODS: A randomized controlled crossover design with repeated measures was conducted. HR and HRV data were recorded using an Empatica E4 wristband, and linear mixed-effects models were fitted for each outcome variable. The analytic sample included twenty-one patients with MCS who completed at least one of the four sessions. RESULTS: We found a significant decrease in mean HR (estimate = -12.75, p = .041) and a significant increase in the standard deviation of normal-to-normal intervals (SDNN) (estimate = 15.76, p = .020) during AATx compared to TAU from the pretreatment to the posttreatment phase, indicating enhanced parasympathetic activation and greater autonomic flexibility. Other HRV parameters revealed no significant effects of AATx, though trends were consistent with the hypotheses. CONCLUSIONS: These findings provide preliminary physiological evidence that AATx can modulate autonomic activity in MCS patients. Despite limitations related to sample size and recording quality, the results highlight the potential of AATx as an emotionally engaging intervention in early neurorehabilitation.

Humans↗

PubMed2026

Epigenetic Gene Networks Governing Immune State Transitions Across the Lifespan.

Immune function across development, tissue repair, aging, and disease depends not only on signaling pathways but also on epigenetic architectures that determine whether coordinated transcriptional programs can be accessed and resolved. Increasing evidence indicates that epigenetic gene networks regulate the accessibility and reversibility of semi-stable immune states, shaping plastic, homeostatic, reparative, and degenerative configurations. We propose the concept of epigenetic transition windows, defined as temporally and contextually restricted intervals during which epigenetic constraints are relaxed, permitting coordinated and reversible transitions between immune states. During development, these windows are broad and support immune tolerance and adaptive plasticity. In adulthood they become spatially and temporally restricted, preserving stability while enabling conditional adaptation. With aging, they progressively narrow, contributing to chronic inflammation, impaired repair, and increased vulnerability to neurodegeneration. Conversely, pathological persistence of regulatory permissiveness may underlie immune evasion and sustained plasticity in cancer. We outline operational genomic readouts for quantifying transition windows, including chromatin accessibility variance, enhancer switching dynamics, reversibility metrics, and cross-cell coordination indices, and derive experimentally testable predictions that distinguish this model from pathway-centric or damage-centric explanations. By reframing immune dysfunction as a failure of regulated state transition rather than excessive signaling alone, this framework integrates inflammaging, trained immunity, immune resolution failure, and tumor immune escape within a unified regulatory architecture and provides a systems-level perspective on immune adaptability across the lifespan.

Epigenesis, Genetic↗