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The optimal surgical excision margins are uncertain for patients with thick (>2 mm) localised cutaneous melanomas. In our previous report of this multicentre, randomised controlled trial, with a median follow-up of 6·7 years, we showed that a narrow excision margin (2 cm vs 4 cm) did not affect melanoma-specific nor overall survival. Here, we present extended follow-up of this cohort. In this open-label, multicentre randomised controlled trial, we recruited patients from 53 hospitals in Sweden, Denmark, Estonia, and Norway. We enrolled clinically staged patients aged 75 years or younger diagnosed with localised cutaneous melanoma thicker than 2 mm, and with primary site on the trunk or upper or lower extremities. Patients were randomly allocated (1:1) to treatment either with a 2-cm or a 4-cm excision margin. A physician enrolled the patients after histological confirmation of a cutaneous melanoma thicker than 2 mm. Some patients were enrolled by a physician acting as responsible for clinical care and as a trial investigator (follow-up, data collection, and manuscript writing). In other cases physicians not involved in running the trial enrolled patients. Randomisation was done by telephone call to a randomisation office, by sealed envelope, or by computer generated lists using permuted blocks. Patients were stratified according to geographical region. No part of the trial was masked. The primary outcome in this extended follow-up study was overall survival and the co-primary outcome was melanoma-specific survival. All analyses were done on an intention-to-treat basis. The study is registered with ClinicalTrials.gov, number NCT03638492. Between Jan 22, 1992, and May 19, 2004, 936 clinically staged patients were recruited and randomly assigned to a 4-cm excision margin (n=465) or a 2-cm excision margin (n=471). At a median overall follow-up of 19·6 years (235 months, IQR 200–260), 621 deaths were reported—304 (49%) in the 2-cm group and 317 (51%) in the 4-cm group (unadjusted HR 0·98, 95% CI 0·83–1·14; p=0·75). 397 deaths were attributed to cutaneous melanoma—192 (48%) in the 2-cm excision margin group and 205 (52%) in the 4-cm excision margin group (unadjusted HR 0·95, 95% CI 0·78–1·16, p=0·61). A 2-cm excision margin was safe for patients with thick (>2 mm) localised cutaneous melanoma at a follow-up of median 19·6 years. These findings support the use of 2-cm excision margins in current clinical practice. The Swedish Cancer Society, Stockholm Cancer Society, the Swedish Society for Medical Research, Radiumhemmet Research funds, Stockholm County Council, Wallström funds.

This study aimed to investigate the effects of mental fatigue on physical and cognitive performance (lower-limb power, isometric and handgrip strength, and psychomotor vigilance). Twenty-two physically active young adults (12 males, 10 females; Mage = 20.82 ± 1.47) were randomly assigned to either a Mental Fatigue (MF) or Control group (CON). The MF group showed a statistically significant (p = 0.019) reduction in non-dominant handgrip strength, declining by approximately 2.3 kg (about 5%), while no such change was observed in the CON group or in dominant handgrip strength across groups. Reaction time (RT) was significantly impaired following the mental fatigue protocol: RT increased by 117.82 ms, representing an approximate 46% longer response time in the MF group (p < 0.001), whereas the CON group showed a smaller, non-significant increase of 32.82 ms (~12% longer). No significant differences were found in squat jump performance, indicating that lower-limb explosive power may be less affected by acute mental fatigue. These findings demonstrate that mental fatigue selectively impairs fine motor strength and cognitive processing speed, particularly reaction time, while gross motor power remains resilient. Understanding these effects is critical for optimizing performance in contexts requiring fine motor control and sustained attention under cognitive load.

Visual impairment poses considerable challenges to mobility and everyday tasks, frequently leading to a more sedentary lifestyle and reduced physical fitness levels. Therefore, this study investigated the effects of a tailored aquatic exercise protocol on muscle activation and strength in visually impaired individuals. Thirty women who were blind (mean age = 29.03 ± 2.20 years) were randomly assigned to an experimental (EX) group and a control (CO) group. The EX group participated in three weekly 60-minute aquatic sessions, while the CO group maintained regular activities. Electromyography (EMG) activation and onset time were measured in the tibialis anterior, gastrocnemius medialis, rectus femoris, and biceps femoris. Muscle strength was also assessed in the ankle dorsiflexors and plantarflexors, as well as the knee flexors and extensors. The EX group showed increased EMG activation for the tibialis anterior, gastrocnemius medialis, rectus femoris, and biceps femoris in both anterior-posterior (2.23 MVIC%, 95% CI: 1.13 to 3.34, p < 0.001) and posterior-anterior directions (2.35 MVIC%, 95% CI: 1.80 to 2.91, p < 0.001) compared to CO group. Onset time decreased significantly in the EX group relative to CO group (anterior-posterior: -108.07 ms, 95% CI: -117.23 to -98.89, p < 0.001; posterior-anterior: -98.72 ms, 95% CI: -106.54 to -90.90, p < 0.001). Muscle strength significantly increased in the EX group compared to the CO group, with greater strength in ankle dorsiflexors (4.42 N/kg, 95% CI: 3.42 to 5.42, p < 0.001) and knee extensors (2.72 N/kg, 95% CI: 1.04 to 4.40, p < 0.001). The aquatic exercise program improved neuromuscular function and strength in women with visual impairments, supporting its use in rehabilitation. IRCT2017022132705N1.

Purpose To elucidate the normative values of whole body sagittal alignment and balance of a healthy population in the standing position; and to clarify the relationship among the alignment, balance, health-related quality of life (HRQOL), and age. Methods Healthy Japanese adult volunteers [ n  = 126, mean age 39.4 years (20–69), M/F = 30/96] with no history of spinal disease were enrolled in a cross-sectional cohort study. The Oswestry Disability Index (ODI) questionnaire was administered and subjects were scanned from the center of the acoustic meati (CAM) to the feet while standing on a force plate to determine the gravity line (GL), and the distance between CAM and GL (CAM–GL) was measured in the sagittal plane. Standard X-ray parameters were measured from the head to the lower extremities. ODI was compared among age groups stratified by decade. Correlations were investigated by simple linear regression analysis. Ideal lumbar lordosis was investigated using the least squares method. Results The present study yielded normative values for whole standing sagittal alignment including head and lower extremities in a cohort of 126 healthy adult volunteers, comparable to previous reports and thus a formula for ideal lumbar lordosis was deduced: LL = 32.9 + 0.60 × PI − 0.23 × age. There was a tendency of positive correlation between McGregor slope, thoracic kyphosis, PT, and age. SVA, T1 pelvic angle, sacrofemoral angle, knee flexion angle, and ankle flexion angle, but not CAM–GL, increased with age, suggesting that the spinopelvic alignment changes with age, but standing whole body alignment is compensated for to preserve a horizontal gaze. ODI tended to increase from the 40s in the domain of pain intensity, personal care, traveling, and total score. ODI weakly, but significantly positively correlated with age and PI–LL. Conclusion Whole body standing alignment even in healthy subjects gradually deteriorates with age, but is compensated to preserve a horizontal gaze. HRQOL is also affected by aging and spinopelvic malalignment.

Patients with peripheral artery disease who underwent revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) or placebo. All patients received aspirin. The primary outcome of acute limb ischemia, major amputation for vascular causes, MI, ischemic stroke, or cardiovascular death occurred less frequently with rivaroxaban.

Varicose veins of lower extremities (VVs) are a common multifactorial vascular disease. Genetic factors underlying VVs development remain largely unknown. Here we report the first large-scale study of VVs performed on a freely available genetic data of 408,455 European-ancestry individuals. We identified the 12 reliably associated loci that explain 13% of the SNP-based heritability, and prioritized the most likely causal genes CASZ1, PIEZO1, PPP3R1, EBF1, STIM2, HFE, GATA2, NFATC2, and SOX9. VVs-associated variants within these loci exhibited pleiotropic effects on several phenotypes including blood pressure/hypertension and blood cell traits. Gene set enrichment analysis revealed gene categories related to abnormal vasculogenesis. Genetic correlation analysis confirmed known epidemiological associations between VVs and deep venous thrombosis, weight, rough labor, and standing job, and found a genetic overlap with multiple traits that have not been previously suspected to share common genetic background with VVs. These traits included educational attainment, fluid intelligence and prospective memory scores, walking pace (negative correlation with VVs), smoking, height, number of operations, pain, and gonarthrosis (positive correlation with VVs). Finally, Mendelian randomization analysis provided evidence for causal effects of plasma levels of MICB and CD209 proteins, and anthropometric traits such as waist and hip circumference, height, weight, and both fat and fat-free mass. Our results provide novel insight into both VVs genetics and etiology. The revealed genes and proteins can be considered as good candidates for follow-up functional studies and might be of interest as potential drug targets.

Blood flow restriction training (BFRT) has attracted attention due to its advantages in muscle strength enhancement. This paper investigates the effects of different training programs on teenage female wrestlers' lower limb strength. Twenty-four teenage female wrestlers were recruited and randomly divided into three groups, namely the blood flow restriction training group (BFRT group), the regular group (HST group), and the combined group (BFRT-HST group). The BFRT group performed low-intensity blood flow restriction half-squat training (LI-BFR-HST), the HST group performed high-intensity half-squat training (HI-HST), while the BFRT-HST group performed LI-BFR-HST twice per week and HI-HST once per week (LI-BFR-HST & HI-HST). The intervention training was implemented three times a week for six weeks. The changes of knee joint peak torque, vertical jump height, and peak rate of force development (PRFD) were compared. The results showed significant improvements (p < 0.05) within each group: (1) BFRT-HST group: The peak torque (ω = 180°/s) of right knee extension and left knee flexion significantly increased; both squat jump (SJ) and countermovement jump (CMJ) heights, and PRFD during SJ and CMJ significantly increased.(2) BFRT group: The SJ height and PRFD during SJ significantly increased.(3) HST group: The CMJ height and PRFD during CMJ significantly increased.The results suggest that the LI-BFR-HST & HI-HST combined training strategy effectively improves the rate of force development in teenage female wrestlers' lower limbs.

The discovery of a relatively complete Australopithecus sediba adult female skeleton permits a detailed locomotor analysis in which joint systems can be integrated to form a comprehensive picture of gait kinematics in this late australopith. Here we describe the lower limb anatomy of Au. sediba and hypothesize that this species walked with a fully extended leg and with an inverted foot during the swing phase of bipedal walking. Initial contact of the lateral foot with the ground resulted in a large pronatory torque around the joints of the foot that caused extreme medial weight transfer (hyperpronation) into the toe-off phase of the gait cycle (late pronation). These bipedal mechanics are different from those often reconstructed for other australopiths and suggest that there may have been several forms of bipedalism during the Plio-Pleistocene.

Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle–brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57–0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35–0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69–1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45–1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12–2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17–2·40; p=0·0043). Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding. Bayer AG.

BackgroundInconsistent nomenclature and anatomical descriptions of regional anesthetic techniques hinder scientific communication and engender confusion; this in turn has implications for research, education and clinical implementation of regional anesthesia. Having produced standardized nomenclature for abdominal wall, paraspinal and chest wall regional anesthetic techniques, we aimed to similarly do so for upper and lower limb peripheral nerve blocks.MethodsWe performed a three-round Delphi international consensus study to generate standardized names and anatomical descriptions of upper and lower limb regional anesthetic techniques. A long list of names and anatomical description of blocks of upper and lower extremities was produced by the members of the steering committee. Subsequently, two rounds of anonymized voting and commenting were followed by a third virtual round table to secure consensus for items that remained outstanding after the first and second rounds. As with previous methodology, strong consensus was defined as ≥75% agreement and weak consensus as 50%–74% agreement.ResultsA total of 94, 91 and 65 collaborators participated in the first, second and third rounds, respectively. We achieved strong consensus for 38 names and 33 anatomical descriptions, and weak consensus for five anatomical descriptions. We agreed on a template for naming peripheral nerve blocks based on the name of the nerve and the anatomical location of the blockade and identified several areas for future research.ConclusionsWe achieved consensus on nomenclature and anatomical descriptions of regional anesthetic techniques for upper and lower limb nerve blocks, and recommend using this framework in clinical and academic practice. This should improve research, teaching and learning of regional anesthesia to eventually improve patient care.