Adductor jerk during transurethral resection of bladder tumour (TURBT) is a common complication caused by obturator nerve stimulation, particularly in tumours located on the lateral or posterolateral bladder wall. Obturator nerve block (ONB) is widely used to prevent this complication. The pericapsular nerve group (PENG) block is a newer regional technique that may also reduce adductor jerk by blocking branches of the obturator and accessory obturator nerves. This study compared the efficacy of ultrasound-guided PENG block and ONB in preventing adductor jerk during TURBT. This prospective, single-blinded, randomised study included patients undergoing TURBT for posterolateral bladder tumours under spinal anaesthesia. Patients received either ultrasound-guided ONB or PENG block. The primary outcome was the prevention of adductor jerk. Secondary outcomes included conversion to general anaesthesia, bladder perforation, postoperative pain scores, and quadriceps muscle strength. Sixty-two patients were analysed, with 31 patients in each group. The incidence of adductor jerk was similar between groups using Fisher's exact test (P = 1.000). Numerical Rating Scale scores at 6 hours were significantly lower in the PENG block group (median: 3.00 [2.00-3.00]) compared to the ONB group (median: 4.00 [3.00-4.00]), and this difference was statistically significant (Mann-Whitney U = 224, P < 0.001). Quadriceps muscle strength at 6 hours was comparable between groups with a median score of 5.00 in both groups, and the difference was not statistically significant (Mann-Whitney U = 418, P = 0.130). No bladder perforation was observed in either group. Ultrasound-guided PENG block is comparable to ONB in preventing adductor jerk during TURBT and provides better postoperative analgesia.
Fascia iliaca block is recommended as part of multimodal analgesia for patients with hip fracture, but early delivery and timestamped documentation are difficult to confirm in routine practice. This retrospective clinical audit assessed whether early delivery could be demonstrated from routine documentation in an operative hip-fracture pathway. The primary audit measure was fascia iliaca block documented within 2 h of emergency department arrival; exploratory outcomes included 48-h oral morphine equivalent dose, postoperative delirium, 30-day mortality and length of stay. Of 204 analysable episodes, 13 (6.4%; 95% confidence interval 3.8% to 10.6%) had fascia iliaca block documented within 2 h. A further 155 of 359 cleaned operative episodes (43.2%) had no recorded fascia iliaca block timing category. Exploratory outcome comparisons were underpowered because the early-delivery group was small. The findings identify a practical perioperative documentation and pathway gap requiring targeted improvement, mandatory timestamped recording and repeat audit.
Ketamine is being proposed for the prevention of rebound pain. This meta-analysis systematically reviews evidence from randomised controlled trials on the efficacy of ketamine (intravenous or perineural) in preventing rebound pain in adults undergoing surgery under regional nerve block. A systematic search for randomised controlled trials evaluating ketamine/esketamine (perineural or intravenous) for preventing rebound pain was conducted across databases up to March 2025. Adults receiving regional nerve block with or without ketamine/esketamine were included. The primary outcome was the incidence of rebound pain. Secondary outcomes included onset time and severity of rebound pain, patient satisfaction, and adverse effects. Six trials enroling 890 patients were included. Ketamine/esketamine significantly reduced the incidence of rebound pain [odds ratio (OR) 0.43, 95% confidence interval (CI) 0.32 to 0.59; P < 0.00001; I² = 39%]. The intravenous subgroup showed a significant reduction (OR 0.48, 95% CI 0.34 to 0.68; P < 0.00001; I² = 21%). The esketamine-versus-control subgroup also favoured active treatment (OR 0.37, 95% CI 0.22 to 0.64; P = 0.0004; I² = 51%). Hallucinations were significantly more frequent with active treatment (OR 12.73, 95% CI 2.98 to 54.41; P = 0.0006; I² = 0%). Current evidence suggests that intravenous and perineural ketamine/esketamine reduce the incidence of rebound pain after a peripheral regional nerve block.
The optimal dose for ultrasound-guided axillary brachial plexus block (ABPB) in children remains poorly defined. This study aimed to find the median effective volume (EV50) of ropivacaine (0.2%) for ABPB in children aged 6-10 years. A prospective, double-blind, dose-finding trial using the Dixon up-and-down method was conducted. Pediatric patients (aged 6-10 years, ASA I-II) undergoing unilateral elbow or below-elbow surgery were enrolled. Ultrasound-guided ABPB was performed using a dual-injection technique with supplemental musculocutaneous nerve blockade. The initial volume of ropivacaine (0.2%) was 0.5 mL/kg, adjusted by 0.05 mL/kg based on the previous patient's response. The study continued until seven inflection points were observed from failure to success. EV50 and EV95 (95% effective volume) were calculated using isotonic regression and bootstrapping, with 95% confidence intervals (CIs). Patient demographics, postoperative pain scores, and adverse events were monitored. Twenty-nine patients were enrolled. The EV50 was 0.350 mL/kg (95% CI: 0.197-0.362 mL/kg), and the EV95 was 0.395 mL/kg (95% CI: 0.385-0.396 mL/kg). No adverse events were observed during the perioperative period. This study provides evidence-based dosing parameters for 0.2% ropivacaine in pediatric ABPB, aiding clinicians in optimizing efficacy and safety. The findings support age-specific precision in pediatric regional anesthesia.
Among all the most prevalent malignant gastrointestinal cancers, colorectal cancer (CRC) occurs frequently in all the populations around the world. Despite remarkable advances in related research, substantial obstacles persist in the prevention and treatment of this malignancy, including safety concerns, adverse side effects, and tumor recurrence. Natural plant-derived compounds have increasingly attracted the attention of researchers in cancer research. Among these compounds, berberine (BBR) is a natural plant substance with multiple functions, which is extracted from Coptis Chinensis that possesses strong antitumor potential. Here we aim to investigate the effects and underlying mechanisms of BBR on CRC using several organoid models developed in our laboratory. We firstly established CRC organoid models derived from KPC transgenic mice and Caco-2 cell line. CRC organoids were treated with different doses of BBR. The morphological characteristics, proliferation, ROS, apoptosis, and cell cycle were carefully evaluated. RNA-Seq assay, epithelial permeability, and lipid probes were also used to examine the underlying molecular mechanisms of BBR on CRC organoids. BBR exhibited no harmful impact on healthy colonic tissues. However, BBR significantly inhibited the growth of both KPC organoids and Caco-2 organoids either at the early formation stage or after the maturity. BBR greatly decreased the ratio of Ki67 and EdU positive cells in CRC organoids and increased the level of ROS in organoids. RNA-Seq data implicated that BBR exerted direct cytotoxic effects on CRC organoids by inducing cell cycle arrest and breaking down the gap junctions. Immunohistochemical (IHC) staining identified the consistent changes of cell cycle arrest and dysfunction of epithelial barrier. FD4 staining showed increased epithelial permeability. Finally, LD540 probes and qPCR identified that BBR significantly blocked the lipid synthesis in CRC organoids. In summary, our study identifies that BBR may suppress the malignant phenotype of CRC organoids via multiple mechanisms, including blocking cell cycle progression and disrupting lipid metabolism.
Water exhibits a wide range of anomalous properties, and various models have been proposed to elucidate its nature. In this study, we reexamine the diversity of water's behavior through the lens of solvating power and fundamental chemical interactions in solution. Electroanalytical and spectroscopic investigations in nonaqueous media reveal that s-block metal ions (Li+, Na+, Mg2+, Ca2+, etc.) possess an intrinsic ability to form both coordination-type (metal-centered species such as [MX n ] m-) and "reverse coordination" complexes (anion-centered species represented by [M n X] m+) with anions when the solvent's solvating power is sufficiently weak. These findings prompted a reconsideration of the role of trace water in nonaqueous systems, leading to a novel interpretation of the dual (or even multiple) nature of water. We propose that the cooperative hydrogen bond interactions within large-scale water assemblies enable bulk water to undergo reversible cleavage and regeneration of O-H bonds. The disruption of this hydrogen bond network-as observed in highly concentrated electrolyte solutions-markedly reduces the hydration power of water, giving rise to unusual chemical phenomena, such as a partial suppression of nitric acid dissociation and enhanced oxidizing ability.
Acute coronary syndrome (ACS) may present with initially nondiagnostic electrocardiographic findings and negative cardiac biomarkers, posing a diagnostic challenge and risk of delayed recognition. This is particularly relevant in cases involving coronary territories that are less well represented on standard ECG or in the setting of multivessel disease. We report the case of a 62-year-old man with hypertension who presented with typical chest pain of 2 hours' duration. Initial evaluation showed sinus rhythm with left axis deviation, consistent with likely left anterior fascicular block, without acute ST-segment elevation. High-sensitivity troponin measurements at 0, 1, and 3 hours were negative. Despite low-risk scores, the patient was admitted for observation due to persistent symptoms. Forty-eight hours later, he developed recurrent chest pain with a marked rise in troponin T and new inferolateral T-wave inversions, confirming evolving myocardial injury. Coronary angiography revealed significant stenosis of the right coronary artery and left circumflex artery, and successful percutaneous coronary intervention was performed. The patient had an uneventful recovery. This case highlights the limitations of early ECG and troponin-based assessment in ACS and underscores the importance of clinical judgment and serial reassessment, particularly in patients with persistent symptoms despite initially reassuring investigations.
Ultrasound-guided ilioinguinal-iliohypogastric nerve block (II-IHNB) provides effective analgesia for inguinal hernia surgery; however, the duration of analgesia with local anaesthetic alone is limited. This study compared dexmedetomidine and magnesium sulphate as adjuvants to ropivacaine for II-IHNB. In this randomised controlled trial, 120 patients were allocated into three groups (n = 40 each). Group A received 0.5% ropivacaine, group B received ropivacaine with magnesium sulphate (5 mg/kg), and group C received ropivacaine with dexmedetomidine (1 µg/kg). The primary outcome was time to first rescue analgesia. Secondary outcomes included visual analogue scale (VAS) scores, 24-hour opioid consumption, sedation, haemodynamic parameters, and adverse events. The time to first rescue analgesia was significantly longer in group C than in group A, with a median difference of 1080 min [95% confidence interval (CI): 923-1125 min; P < 0.001]. The total 24-hour opioid consumption was significantly lower in group C than in group A, with a median difference of - 10 morphine milligram equivalents (95% CI: -15 to - 5; P < 0.001). VAS scores at rest and movement were significantly lower in group C at multiple postoperative time points (P < 0.001). Sedation scores were higher in group C in the immediate postoperative period (P < 0.001), but no clinically significant respiratory depression occurred. Haemodynamic parameters and the incidence of adverse events remained comparable across groups (P > 0.05). Dexmedetomidine is superior to magnesium sulphate as an adjuvant to ropivacaine in II-IHNB, providing prolonged analgesia, reduced opioid consumption, and stable haemodynamics with an acceptable sedation profile.
In this research, biomass-derived carbon quantum dots (CQDs) with solvent-dependent emission colors were synthesized from mangosteen leaves via a solvent-mediated hydrothermal route, in order to elucidate the relationship between structure and emission and to evaluate their potential for multifunctional packaging applications. Systematic morphological and structural analyses demonstrated that the solvent polarity governed the degree of carbonization, particle size, and surface chemistry. Red-emissive CQDs (R-CQDs) were formed in a less polar medium and exhibited larger sp2 domains enriched with hydroxyl groups, whereas blue-emissive CQDs (B-CQDs) synthesized in a polar solvent had smaller sp2 domains with higher values for the content of oxygen- and nitrogen-containing functionalities. These distinctions resulted in excitation-independent red emission for R-CQDs and excitation-tunable blue-green emission for B-CQDs. R-CQDs showed enhanced antioxidant activity (IC50 = 8.84 μg mL-1) relative to B-CQDs (IC50 = 21.03 μg mL-1), while antibacterial activity against Escherichia coli and Staphylococcus aureus was observed exclusively for R-CQDs, indicating a structure-dependent antibacterial response. When the CQDs were incorporated into poly-(vinyl alcohol) (PVA) matrices, the nanocomposite films demonstrated enhanced UV-blocking performance, with R-CQD/PVA film giving stronger attenuation due to enhanced π-π* transitions and more efficient interfacial energy transfer. Storage tests also showed that when tomatoes were packaged with R-CQD/PVA film, ripening was delayed by approximately 7-14 days compared to the control films. These findings establish clear correlations between solvent, structure, and function for biomass-derived CQDs and suggest a sustainable strategy for designing multifunctional nanocomposite films for UV-protective and active food-packaging applications.
Regional anaesthesia in the emergency department requires reliable techniques with minimal complications. We describe a subdeltoid ultrasound-guided brachial plexus approach targeting a potential "nerve funnel" at the surgical neck of the humerus, bridging infraclavicular and axillary approaches. Cadaveric dissection explored its anatomical basis and correlated it with clinical sonographic findings. This retrospective case series included six adult patients with traumatic upper-limb injuries. Cadaveric observations suggested terminal nerve clustering and proximity of the musculocutaneous and intercostobrachial nerves at the subdeltoid level. All patients achieved adequate anaesthesia with a single 15 mL injection of 0.5% bupivacaine with 4 mg dexamethasone. The mean pain-free duration was 17.3 hours, with consistent tourniquet tolerance and no procedural complications. The subdeltoid approach appears feasible as a single-injection technique for upper-limb procedures. Using a superficial acoustic window and favourable anatomical clustering, it may provide effective coverage with technical simplicity. These preliminary findings require validation in larger prospective studies.
Rechargeable zinc-air batteries (ZABs) require efficient electrocatalysts to boost the sluggish oxygen reduction reaction (ORR)/ oxygen evolution reaction (OER) kinetics at the air cathode. However, designing high-activity catalysts faces considerable challenges due to spatial and electronic constraints. Herein, a boron-doped hollow spherical porous carbon (HS-FeNi-BNC) anchored with Fe-B-Ni diatomic sites is prepared via a facile B-bridging strategy, realizing the regulated construction of heteroatom doping and diatomic active sites. HS-FeNi-BNC possesses abundant micropores/mesopores, uniformly dispersed FeNi diatomic centers (0.27 nm spacing) with a Fe-B-Ni bridge structure, and topological carbon defects induced by B/N co-doping. HS-FeNi-BNC exhibits exceptional trifunctional electrocatalytic performance in alkaline electrolytes, with an ORR E1/2 of 0.864 V, an OER overpotential of 308 mV and a hydrogen evolution reaction (HER) overpotential of 301 mV at 10 mA cm-2. HS-FeNi-BNC-based ZABs achieve an outstanding wide-temperature operating range of -10 °C to 60 °C, a specific capacity of 761.51 mAh g-1 and a Zn utilization efficiency of 92.9%, outperforming Pt/C + RuO2-based ZABs. Density functional theory (DFT) calculations reveal that the Fe-B-Ni bridge structure triggers p-d orbital hybridization, regulating metal site electronic structures, optimizing reaction intermediate adsorption and accelerating interfacial electron transfer. This work advances the development of high-efficiency heteroatom-modified non-noble metal multifunctional catalysts.
Lumbar spinal anaesthesia (LSA) for endoscopic urological procedures often causes extensive sympathetic blockade, leading to hypotension, bradycardia, and delayed ambulation. Thoracic segmental spinal anaesthesia (TSSA) offers targeted sensory blockades with limited motor involvement and improved haemodynamic stability. The primary objective of the study was to compare motor block onset between TSSA and LSA. Secondary objectives included sensory block characteristics, two-segment regression time, haemodynamics, perioperative complications, and patient and surgeon satisfaction. Forty American Society of Anesthesiologists (ASA) class I-II patients were randomised to group T (TSSA, n = 20; 1 mL 0.5% isobaric ropivacaine + 20 µg fentanyl at T11-T12) or group S (LSA, n = 20; 2 mL 0.5% hyperbaric ropivacaine + 20 µg fentanyl at L3-L4). Sensory and motor block, haemodynamic parameters, rescue analgesia, satisfaction scores, and adverse events were recorded. Group T achieved faster sensory block to T10 (1.7 ± 1.08 vs 4.48 ± 1.97 min, P < 0.001), quicker maximum block height (3.42 ± 1.46 vs 8.95 ± 3.3 min, P < 0.001), and shorter two-segment regression (58 ± 6.5 vs 88.77 ± 7.73 min, P < 0.001). Motor block onset was similar (6.6 ± 2.96 vs 5.8 ± 1.67 in groups T and S, respectively), but group S had higher Bromage scores and prolonged blockade (time to Bromage score 0: 61.85 ± 26.37 vs 184.21 ± 30.06 min, P < 0.001). Group S showed greater heart rate and mean arterial pressure reductions (P < 0.05). Patients in Group T ambulated earlier than group S (152.25 ± 29.76 vs 284 ± 26.04 min; P < 0.001). TSSA provides less motor blockade, targeted sensory block, maintains haemodynamic stability, and enables earlier ambulation, making it a safe and effective alternative in endoscopic urological surgery.
Spinal anaesthesia is an effective alternative technique for short-duration endoscopic urological procedures. Conventional 0.5% hyperbaric bupivacaine may be associated with prolonged motor blockade and haemodynamic instability, potentially delaying ambulation and discharge. This study aimed to compare the efficacy and safety of 0.25% and 0.5% hyperbaric bupivacaine for spinal anaesthesia in ambulatory endoscopic urological procedures. In this prospective, randomised, double-blind controlled study, 60 patients with American Society of Anesthesiologists physical status I and II undergoing elective lower urological endoscopic procedures were allocated into two groups (n = 30 each). Group A received 5 mg of 0.25% hyperbaric bupivacaine (2 mL), and Group B received 10 mg of 0.5% hyperbaric bupivacaine (2 mL) intrathecally. The primary outcomes were onset and duration of sensory and motor block. Secondary outcomes included haemodynamic changes, postoperative pain assessed using the visual analogue scale (VAS), time to ambulation, and duration of stay in the post-anaesthesia care unit. The onset of sensory block was faster and the duration of sensory and motor block was significantly longer in Group B (P < 0.001). The ambulation time and post-anaesthesia care unit stay were significantly prolonged in Group B (P < 0.001). Haemodynamic fluctuations were more frequent with 0.5% bupivacaine. Post-operative pain scores at 2 h were lower in Group B (P < 0.001). Low-dose 0.25% hyperbaric bupivacaine provides effective spinal anaesthesia with improved haemodynamic stability, earlier ambulation, and faster recovery compared to 0.5% hyperbaric bupivacaine, making it suitable for ambulatory endoscopic urological procedures.
Radiofrequency ablation (RFA) is generally considered a safe treatment for hepatocellular carcinoma. Although cardiovascular complications have been occasionally reported, they are primarily attributed to sedatives and analgesics or the vasovagal reflex. However, a unique case is presented where RFA itself was suspected of inducing a progressive atrioventricular disorder. An 80-year-old male underwent RFA for hepatocellular carcinoma. His electrocardiogram showed a first-degree atrioventricular block on admission. Prior to ablation, fentanyl and propofol were administered. Severe bradycardia developed immediately after initiation of ablation. RFA and propofol infusion were terminated, leading to prompt heart rate recovery. After approximately five minutes, ablation was resumed without propofol, but severe bradycardia recurred. The electrocardiogram during RFA revealed a complete atrioventricular block. Therefore, the procedure was terminated. A 12-lead electrocardiogram performed after the aborted procedure revealed progression to a second-degree AV block (Mobitz type II) requiring pacemaker implantation. The exact mechanism of this effect remains unclear, though progression of the atrioventricular conduction disorder was considered to be induced by RFA. Careful intraoperative patient management is crucial during RFA.
Fish scale waste was valorized to develop a biodegradable active film with enhanced preservation performance. Gelatin and hydroxyapatite were extracted and combined with chitosan, while syringaldehyde was incorporated as a natural crosslinker and antibacterial agent to construct a dual-network structure. The combination of HAP reinforcement and SA-induced crosslinking promoted the formation of a denser organic-inorganic network structure, thereby improving the physical performance and functional properties of the films. Compared with the blank GC film, the incorporation of HAP and SA led to the formation of GCHS films with overall enhanced physical performance and functionality. Especially, the optimized GCHS3 film exhibited improved elongation at break (51.7%), UV-blocking ability (blocking >99% of UV passage), DPPH radical scavenging activity (82.3%), and antibacterial effects against Escherichia coli and Staphylococcus aureus (with inhibition zone diameters of 14.09 mm and 24.00 mm, respectively). During cold storage of beef samples, the GCHS3 film efficiently inhibited microbial growth, delayed the accumulation of total volatile basic nitrogen, and retarded pH increase, while maintaining the original color characteristics of beef. Consequently, the shelf life was extended to 9 days, which is superior to PE packaging. This study provides a novel strategy to incorporate fish scale-derived inorganic fillers and natural crosslinkers into protein-polysaccharide systems. The GCHS3 film exhibits great potential as a sustainable alternative for active food packaging, especially for fresh meat preservation.
Lead (Pb) and chromium (Cr) are priority soil hazards: Pb is a potent neurotoxicant and Cr (VI) is a recognized carcinogen, both persisting for decades and threatening groundwater and human health through ingestion and leaching. At large industrial sites, the delineated three-dimensional extent of these metals directly governs remediation volume, cost, and residual exposure risk. To resolve hazard distributions at decision-relevant resolution, we developed D-MSN, a deep-learning-enhanced extension of the Mean Surface with Stratified Nonhomogeneity (MSN) model. D-MSN integrates masked spatial attention, gated residual networks, and meta-polynomial trend learning to jointly capture in-stratum correlation, between-stratum heterogeneity, and cross-stratum dependency. Applied to Pb and Cr at an abandoned integrated iron-and-steel complex in China (2.81 km², 12,900 samples spanning coking, sintering, ironmaking, steelmaking, rolling, and captive power generation) under stratified spatial-block cross-validation, D-MSN outperformed inverse distance weighting, 3D ordinary kriging, 3D-MSN, and DKNN, reducing MAE and RMSE by ∼35% and ∼38% relative to ordinary kriging. The model-derived hotspots spatially coincide with known process units, revealing diffuse Cr signatures near slag-handling and material-storage areas and compact Pb plumes near sintering, blast-furnace, and captive-power-plant operations. Unlike conventional smoothing-based interpolation methods, D-MSN preserves localized hotspot structures and supports source-oriented interpretation. Coupling D-MSN with Monte Carlo dropout further yields probabilistic exceedance maps under GB 36600-2018, identifying decision-uncertain volumes that deterministic interpolators systematically conceal. The practical implications of stratified-heterogeneity-aware modeling for risk-based contaminated site management are highlighted by the fact that the interpolation method alone changes the delineated remediation volume by about 36% in comparison to standard kriging, with cost implications on the order of 108 CNY.
Arsenic pollution of water and soil is a global environmental and public health issue that requires sustainable remediation. Metal-tolerant plant species are used in phytoremediation to significantly remove metals from contaminated locations. This study tested Hydrocotyle umbellata L. against five Arsenic concentrations (500,750,1000,1250,1500 µg L-1 from T1 to T5 respectively,) in Hoagland solution for 10 days to assess its phytoextraction potential. This was done using triplicate randomized block design. Pearson Correlation analysis, ANOVA, Multivariate Regression, and CART models are used for statistical analyses. These statistical characteristics were used to examine H. umbellata's Arsenic uptake and its effects on factors like fresh and dry weight, translocation factor (TF), bio-concentration factor (BCF), chlorophyll content (Chl.), and electrolyte leakage. All treatments had BCF greater than 1 and a maximum BCF value was shown by T5 as 32.65. The strong metal uptake, greatest BCF reduced dry weight indicates physiological stress in H. umbellata, which can collect and translocate Arsenic from roots to stolon. Highest BCF and TF values accompanying As translocation to shoots indicate H. umbellata's phytoextraction capacity and adaptation to Arsenic stress. Hydrocotyle umbellata is a good option for environmental remediation in places with mild As contamination, according to the study’s findings. The plant showed a significant As uptake in all of plant parts. Additionally, the transfer of As metal to aboveground portions (leaves and stolon), which may subsequently be harvested and metal removed, confirmed H. umbellata’s suitability as a phytoremediation agent for As.
Cognitive fatigability is a decline in performance over the course of a sustained cognitive task. Objective, time-efficient, and reliable measures of cognitive fatigability remain limited. The Psychomotor Vigilance Task (PVT) has been utilized to quantify sustained attention deficits, but its psychometric properties for MS populations are not well established. To evaluate the reliability and validity of a 10-minute PVT of cognitive fatigability in MS patients. Twenty-two MS patients completed the 10-minute PVT on three occasions, 7-10 days apart. Cognitive fatigability was quantified as performance decline across five consecutive 2-minute blocks using reaction time (RT) and cognitive lapses. Cognitive lapses were analyzed using a ≥ 500-ms and ≥300-ms thresholds. Test-retest reliability was assessed using intraclass correlation coefficients (ICC). Convergent validity was assessed by associations between PVT indices (RT and cognitive lapses) and general cognitive fatigue, and current fatigue. Divergent validity was assessed by associations between PVT indices and global cognition and cardiorespiratory fitness. Across all sessions, participants demonstrated slowing of RT, indicating cognitive fatigability. Cognitive lapses increased over time when the ≥300-ms was applied. Test-retest reliability was excellent for mean RT (ICC=0.934), median RT (ICC=0.928), and cognitive lapses (≥500-ms [ICC=0.925] and ≥300-ms [ICC=0.829]). RT (r = 0.621) and cognitive lapses using the 500-ms (r = 0.477) and 300-ms (r = 0.560) were associated with cognitive fatigue. Neither RT nor cognitive lapse was associated with current fatigue, global cognition, or cardiorespiratory fitness. The 10-minute PVT, using RT and cognitive lapses, is a brief measure of cognitive fatigability in MS for clinical evaluation in MS fatigue.
Soft hand exoskeletons have emerged as promising assistive devices for individuals with impaired hand function. However, most existing systems provide limited dexterity and primarily target users with moderate hand ability, leaving individuals with severe hand paralysis without effective solutions for reliable grasping of diverse objects. Here we report the translational development of a lightweight, textile-based soft robotic exoskeleton glove with wrist dorsiflexion and an active opposable and abductable thumb, designed to restore hand function in a patient with severe right-hand impairment due to amyotrophic lateral sclerosis. We followed a co-creation approach, enhancing dexterity by increasing hand articulations based on patient needs. Furthermore, to enhance the patient's sense of control, a non-invasive surface electromyography-based grasp predictor (97% sensitivity) was combined with motion data and machine learning-based error correction to compensate for weak, noisy muscle signals, compared with healthy controls (n = 15). The exoskeleton enabled the patient to grasp objects, achieve a Box-and-Blocks Test score of 5 and perform meaningful tasks, including feeding himself. We further validated the exoskeleton in patients with stroke (n = 6). While exoskeleton assistance on average reduced Action Research Arm Test scores of moderately impaired patients by 9, severely impaired patients scored 17 points higher when using the exoskeleton. These results indicate that the dexterous soft hand exoskeleton is particularly effective for individuals with severe to near-complete hand paralysis, while its utility for patients with moderate residual function is limited and task dependent.
Nociceptors, primary afferent nerve fibers that signal noxious stimuli, are broadly divided into slowly conducting unmyelinated C fibers and fast-conducting myelinated A fibers. Whereas C-nociceptors have been extensively studied, considerably less is known about the function of A-nociceptors. Here we demonstrate, combining genetic targeting of these fibers in mice with observations in human participants, a key involvement of A-nociceptors in mechanical nociceptive withdrawal reflexes and affective pain. In mice, optogenetic stimulation induced rapid and precise withdrawal reflexes as well as place aversion and facial expression changes consistent with pain affect, while inhibition strongly impaired mechanical nociceptive withdrawal reflexes. Prolonged A-nociceptor activation induced mechanical pain hypersensitivity and central sensitization. In a rare individual lacking thickly myelinated Aβ fibers, and in healthy participants during preferential Aβ-fiber nerve block, mechanical withdrawal reflexes were absent and mechanical pain perception reduced. Together, these findings identify fast-conducting mechano-nociceptors as essential drivers of nocifensive behaviors in mice and humans.