Unilateral Quadriceps Fatigue Induces Greater Impairments of Ipsilateral versus Contralateral Elbow Flexors and Plantar Flexors Performance in Physically Active Young Adults.

Non-local muscle fatigue (NLMF) studies have examined crossover impairments of maximal voluntary force output in non-exercised, contralateral muscles as well as comparing upper and lower limb muscles. Since prior studies primarily investigated contralateral muscles, the purpose of this study was to compare NLMF effects on elbow flexors (EF) and plantar flexors (PF) force and activation (electromyography: EMG). Secondly, possible differences when testing ipsilateral or contralateral muscles with a single or repeated isometric maximum voluntary contractions (MVC) were also investigated. Twelve participants (six males: (27.3 ± 2.5 years, 186.0 ± 2.2 cm, 91.0 ± 4.1 kg; six females: 23.0 ± 1.6 years, 168.2 ± 6.7 cm, 60.0 ± 4.3 kg) attended six randomized sessions where ipsilateral or contralateral PF or EF MVC force and EMG activity (root mean square) were tested following a dominant knee extensors (KE) fatigue intervention (2×100s MVC) or equivalent rest (control). Testing involving a single MVC (5s) was completed by the ipsilateral or contralateral PF or EF prior to and immediately post-interventions. One minute after the post-intervention single MVC, a 12×5s MVCs fatigue test was completed. Two-way repeated measures ANOVAs revealed that ipsilateral EF post-fatigue force was lower (-6.6%, p = 0.04, d = 0.18) than pre-fatigue with no significant changes in the contralateral or control conditions. EF demonstrated greater fatigue indexes for the ipsilateral (9.5%, p = 0.04, d = 0.75) and contralateral (20.3%, p < 0.01, d = 1.50) EF over the PF, respectively. There were no significant differences in PF force, EMG or EF EMG post-test or during the MVCs fatigue test. The results suggest that NLMF effects are side and muscle specific where prior KE fatigue could hinder subsequent ipsilateral upper body performance and thus is an important consideration for rehabilitation, recreation and athletic programs.

Non-local Muscle Fatigue Effects on Muscle Strength, Power, and Endurance in Healthy Individuals: A Systematic Review with Meta-analysis.

BACKGROUND: The fatigue of a muscle or muscle group can produce global responses to a variety of systems (i.e., cardiovascular, endocrine, and others). There are also reported strength and endurance impairments of non-exercised muscles following the fatigue of another muscle; however, the literature is inconsistent. OBJECTIVE: To examine whether non-local muscle fatigue (NLMF) occurs following the performance of a fatiguing bout of exercise of a different muscle(s). DESIGN: Systematic review and meta-analysis. SEARCH AND INCLUSION: A systematic literature search using a Boolean search strategy was conducted with PubMed, SPORTDiscus, Web of Science, and Google Scholar in April 2020, and was supplemented with additional 'snowballing' searches up to September 2020. To be included in our analysis, studies had to include at least one intentional performance measure (i.e., strength, endurance, or power), which if reduced could be considered evidence of muscle fatigue, and also had to include the implementation of a fatiguing protocol to a location (i.e., limb or limbs) that differed to those for which performance was measured. We excluded studies that measured only mechanistic variables such as electromyographic activity, or spinal/supraspinal excitability. After search and screening, 52 studies were eligible for inclusion including 57 groups of participants (median sample = 11) and a total of 303 participants. RESULTS: The main multilevel meta-analysis model including all effects sizes (278 across 50 clusters [median = 4, range = 1 to 18 effects per cluster) revealed a trivial point estimate with high precision for the interval estimate [- 0.02 (95% CIs = - 0.14 to 0.09)], yet with substantial heterogeneity (Q(277) = 642.3, p < 0.01), I2 = 67.4%). Subgroup and meta-regression analyses showed that NLMF effects were not moderated by study design (between vs. within-participant), homologous vs. heterologous effects, upper or lower body effects, participant training status, sex, age, the time of post-fatigue protocol measurement, or the severity of the fatigue protocol. However, there did appear to be an effect of type of outcome measure where both strength [0.11 (95% CIs = 0.01-0.21)] and power outcomes had trivial effects [- 0.01 (95% CIs = - 0.24 to 0.22)], whereas endurance outcomes showed moderate albeit imprecise effects [- 0.54 (95% CIs = - 0.95 to - 0.14)]. CONCLUSIONS: Overall, the findings do not support the existence of a general NLMF effect; however, when examining specific types of performance outcomes, there may be an effect specifically upon endurance-based outcomes (i.e., time to task failure). However, there are relatively fewer studies that have examined endurance effects or mechanisms explaining this possible effect, in addition to fewer studies including women or younger and older participants, and considering causal effects of prior training history through the use of longitudinal intervention study designs. Thus, it seems pertinent that future research on NLMF effects should be redirected towards these still relatively unexplored areas.

Nasal High Flow Versus Conventional Oxygen Therapy for Postoperative Cardiothoracic Surgery Patients.

BACKGROUND: Reintubation and complications in postoperative cardiothoracic patients remain high despite medical advancements. A 2-year retrospective, observational study was conducted in postextubated cardiothoracic patients to assess the effectiveness of the current standard-conventional oxygen therapy (COT) compared with a nasal high flow (NHF) therapy. OBJECTIVES: The objective of this study was to understand whether NHF therapy would reduce the need for reintubation and improve clinical outcomes after surgery. METHOD: All consecutive postoperative patients who had same-day elective cardiothoracic surgery in a tertiary hospital were included. The 2013 data were from patients' charts who received COT, and the 2014 data were from patients' charts after the implementation of NHF therapy post extubation as a standard of care. RESULTS: A total of 400 patient charts were analyzed: 221 and 179 patients in the COT and NHF, respectively. No significant difference was seen in the frequency of reintubation (P = .48). Despite both cohorts having the same length of stay (P = .10), patients treated with NHF required less time on supplemental oxygen (P = .001). Day 1 postoperative chest x-ray results did not show any significant differences between groups, whereas day 2 x-rays showed worsening results in the COT cohort (P < .001). Furthermore, the incidence of ventilator-associated pneumonia (VAP) post extubation was significantly higher in the COT cohort, with zero VAP episodes reported in the NHF cohort (P = .02). DISCUSSION: Although this study was not able to demonstrate the reduction in reintubation between groups, the use of NHF compared with COT seems to reduce the time spent on oxygen therapy and decrease the rate of VAP. Further evidence including randomized controlled trials is required to determine the impact of NHF on reintubation and complications in postoperative cardiothoracic surgery.

Impact of 10-Minute Interval Roller Massage on Performance and Active Range of Motion.

Hodgson, DD, Quigley, PJ, Whitten, JHD, Reid, JC, and Behm, DG. Impact of 10-minute interval roller massage on performance and active range of motion. J Strength Cond Res 33(6): 1512-1523, 2019-Roller massage (RM) has been shown to increase range of motion (ROM) without subsequent performance deficits. However, prolonged static stretching (SS) can induce performance impairments. The objective of this study was to examine the effects of combining SS and RM with and without subsequent RM on ROM and neuromuscular performance. Subjects (n = 12) participated in 5 sessions: (a) SS only (SS_rest), (b) SS + RM (SS + RM_rest), (c) SS with RM at 10 and 20 minutes after stretch (SS_RM), (d) SS + RM with RM at 10 and 20 minutes after stretch (SS + RM_RM), and (e) control. For the SS conditions, the quadriceps and hamstrings received passive SS for 2 × 30 seconds each. For the SS + RM conditions, SS was applied to the quadriceps and hamstrings for 30 seconds each, and RM was performed for 30 seconds per muscle. SS_RM and SS + RM_RM conditions received an additional 30-second RM at 10 and 20 minutes after warm-up, whereas sessions without additional RM rested for the same duration. Testing measures included hip flexion (HF) and knee flexion (KF) active and passive ROM, hurdle jump height and contact time, countermovement jump height, and maximal voluntary isometric contraction force. Initial KF and HF ROM improvements provided by SS_RM and SS + RM_RM were sustained up to 30 minutes after intervention. Furthermore, SS_RM exhibited greater ROM compared with sessions lacking additional RM in active and passive HF as well as active and passive KF. Similarly, SS + RM_RM elicited greater KF and HF ROM improvements than SS_rest. In conclusion, active KF and HF ROM improvements were prolonged by additional RM, whereas neuromuscular performance remained relatively unaffected.

Effectiveness of Traditional Strength vs. Power Training on Muscle Strength, Power and Speed with Youth: A Systematic Review and Meta-Analysis.

Numerous national associations and multiple reviews have documented the safety and efficacy of strength training for children and adolescents. The literature highlights the significant training-induced increases in strength associated with youth strength training. However, the effectiveness of youth strength training programs to improve power measures is not as clear. This discrepancy may be related to training and testing specificity. Most prior youth strength training programs emphasized lower intensity resistance with relatively slow movements. Since power activities typically involve higher intensity, explosive-like contractions with higher angular velocities (e.g., plyometrics), there is a conflict between the training medium and testing measures. This meta-analysis compared strength (e.g., training with resistance or body mass) and power training programs (e.g., plyometric training) on proxies of muscle strength, power, and speed. A systematic literature search using a Boolean Search Strategy was conducted in the electronic databases PubMed, SPORT Discus, Web of Science, and Google Scholar and revealed 652 hits. After perusal of title, abstract, and full text, 107 studies were eligible for inclusion in this systematic review and meta-analysis. The meta-analysis showed small to moderate magnitude changes for training specificity with jump measures. In other words, power training was more effective than strength training for improving youth jump height. For sprint measures, strength training was more effective than power training with youth. Furthermore, strength training exhibited consistently large magnitude changes to lower body strength measures, which contrasted with the generally trivial, small and moderate magnitude training improvements of power training upon lower body strength, sprint and jump measures, respectively. Maturity related inadequacies in eccentric strength and balance might influence the lack of training specificity with the unilateral landings and propulsions associated with sprinting. Based on this meta-analysis, strength training should be incorporated prior to power training in order to establish an adequate foundation of strength for power training activities.

An acute session of roller massage prolongs voluntary torque development and diminishes evoked pain.

INTRODUCTION: Roller massage (RM) has been reported to reduce pain associated with exercise-induced muscle soreness and increase range of motion without force or activation impairments. The objective was to examine RM effects on evoked pain and contractile properties. METHODS: Twelve men received three sets of 30-s RM at a perceived discomfort level of 7/10 on a visual analogue scale on the ipsilateral (IPSI-R) stimulated plantar flexors (PF), contralateral PF (CONTRA-R), Sham (light rolling on stimulated PF), or Control. At pre-test, post-test, and 5-min post-test, they received evoked maximal twitch, tetanus, and 70% maximal tetanic stimulation, and performed a maximal voluntary isometric contraction (MVIC). Data analysis included perceived pain and contractile properties. RESULTS: The 70% tetanus illustrated significant 9-10% increases in pain perception with Sham and Control at post- and 5-min post-test, respectively (p < 0.01). There was no pain augmentation with IPSI-R and CONTRA-R. There were no main effects or interactions for most contractile properties. However, MVIC force developed in the first 200 ms showed 9.5% (p = 0.1) and 19.1% (p = 0.03) decreases with IPSI-R at post-test and 5-min post-test. CONCLUSION: Data suggest that RM-induced neural inhibition decreased MVIC F200 and nullified the testing-induced increase in evoked pain associated with 70% tetanic stimulation.

The Interaction of Fatigue and Potentiation Following an Acute Bout of Unilateral Squats.

A prior conditioning resistance exercise can augment subsequent performance of the affected muscles due to the effects of post-activation potentiation (PAP). The non-local muscle fatigue literature has illustrated the global neural effects of unilateral fatigue. However, no studies have examined the possibility of acute non-local performance enhancements. The objective of the study was to provide a conditioning stimulus in an attempt to potentiate the subsequent jump performance of the affected limb and determine if there were performance changes in the contralateral limb. Using a randomized allocation, 14 subjects (6 females, 8 males) completed three conditions on separate days: 1) unilateral, dominant leg, Bulgarian split squat protocol with testing of the exercised leg, 2) unilateral, dominant leg, Bulgarian split squat protocol with testing of the contralateral, non-exercised leg and 3) control session with testing of the non-dominant leg. Pre- and post-testing consisted of countermovement (CMJ) and drop jumps (DJ). The exercised leg exhibited CMJ height increases of 3.5% (p = 0.008; d = 0.28), 4.0% (p = 0.011; d = 0.33) and 3.2% (p = 0.013; d = 0.26) at 1, 5, and 10 min post-intervention respectively. The contralateral CMJ height had 2.0% (p = 0.034; d = 0.18), 1.2% (p = 0.2; d = 0.12), and 2.1% (p = 0.05; d = 0.17) deficits at 1, 5, and 10 min post-intervention respectively. Similar relative results were found for CMJ power. There were no significant interactions for DJ measures or control CMJ measures. The findings suggest that PAP effects were likely predominant for the exercised leg whereas the conditioning exercise provided trivial magnitude although statistically significant neural impairments for the contralateral limb.

Therapeutic efficacy of an Fc-enhanced TCR-like antibody to the intracellular WT1 oncoprotein.

PURPOSE: RMFPNAPYL (RMF), a Wilms' tumor gene 1 (WT1)-derived CD8 T-cell epitope presented by HLA-A*02:01, is a validated target for T-cell-based immunotherapy. We previously reported ESK1, a high avidity (Kd < 0.2 nmol/L), fully-human monoclonal antibody (mAb) specific for the WT1 RMF peptide/HLA-A*02:01 complex, which selectively bound and killed WT1(+) and HLA-A*02:01(+) leukemia and solid tumor cell lines. EXPERIMENTAL DESIGN: We engineered a second-generation mAb, ESKM, to have enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) function due to altered Fc glycosylation. ESKM was compared with native ESK1 in binding assays, in vitro ADCC assays, and mesothelioma and leukemia therapeutic models and pharmacokinetic studies in mice. ESKM toxicity was assessed in HLA-A*02:01(+) transgenic mice. RESULTS: ESK antibodies mediated ADCC against hematopoietic and solid tumor cells at concentrations below 1 µg/mL, but ESKM was about 5- to 10-fold more potent in vitro against multiple cancer cell lines. ESKM was more potent in vivo against JMN mesothelioma, and effective against SET2 AML and fresh ALL xenografts. ESKM had a shortened half-life (4.9 days vs. 6.5 days), but an identical biodistribution pattern in C57BL/6J mice. At therapeutic doses of ESKM, there was no difference in half-life or biodistribution in HLA-A*02:01(+) transgenic mice compared with the parent strain. Importantly, therapeutic doses of ESKM in these mice caused no depletion of total WBCs or hematopoetic stem cells, or pathologic tissue damage. CONCLUSIONS: The data provide proof of concept that an Fc-enhanced mAb can improve efficacy against a low-density, tumor-specific, peptide/MHC target, and support further development of this mAb against an important intracellular oncogenic protein.

Targeting the intracellular WT1 oncogene product with a therapeutic human antibody.

The Wilms tumor 1 (WT1) oncoprotein is an intracellular, oncogenic transcription factor that is overexpressed in a wide range of leukemias and solid cancers. RMFPNAPYL (RMF), a WT1-derived CD8+ T cell human leukocyte antigen (HLA)-A0201 epitope, is a validated target for T cell-based immunotherapy. Using phage display technology, we discovered a fully human "T cell receptor-like" monoclonal antibody (mAb), ESK1, specific for the WT1 RMF peptide/HLA-A0201 complex. ESK1 bound to several leukemia and solid tumor cell lines and primary leukemia cells, in a WT1- and HLA-A0201-restricted manner, with high avidity [dissociation constant (Kd)=0.1 nM]. ESK1 mediated antibody-dependent human effector cell cytotoxicity in vitro. Low doses of naked ESK1 antibody cleared established, disseminated, human acute lymphocytic leukemia and Philadelphia chromosome-positive leukemia in nonobese diabetic/severe combined immunodeficient γc-/- (NSG) mouse models. At therapeutic doses, no toxicity was seen in HLA-A0201 transgenic mice. ESK1 is a potential therapeutic agent for a wide range of cancers overexpressing the WT1 oncoprotein. This finding also provides preclinical validation for the strategy of developing therapeutic mAbs targeting intracellular oncogenic proteins.

Posttransplant lymphoproliferative disorder complicating hematopoietic stem cell transplantation in a patient with dyskeratosis congenita.

Dyskeratosis congenita (DC) is a rare inherited disorder characterized by bone marrow failure and cancer predisposition. We present a case of a 28-year-old woman with DC who was admitted for hematopoietic stem cell transplantation (HSCT) for aplastic anemia and who developed acute myeloid leukemia with complex genetic karyotype abnormalities including the MLL (11q23) gene, 1q25, and chromosome 8. After transplantation, a monomorphic Epstein-Barr virus (EBV) negative posttransplant-associated lymphoproliferative disorder (PTLD) diffuse large B-cell lymphoma was discovered involving the liver, omental tissue, and peritoneal fluid samples showing additional MLL (11q23) gene abnormalities by fluorescence in situ hybridization. Despite treatment, the patient died of complications associated with transplantation and invasive fungal infection. This case represents the first bona fide documented case of EBV-negative monomorphic PTLD host derived, with MLL gene abnormalities in a patient with DC, and shows another possible mechanism for the development of a therapy-related lymphoid neoplasm after transplantation.

Ureterosigmoidostomy associated signet ring colon cancer presenting as hip pain.

PURPOSE: We present a case of a young male with a history of ureterosigmoidostomy who presented with hip pain, the subsequent workup of which revealed metastatic bone lesions from a primary sigmoid signet ring cell adenocarcinoma. METHODS: Review of literature was conducted using databases PubMed Medline (1966-current), PubMed Central (1970-current), and EMBASE (1988-2009) to explore previous studies on the topic; used the Surveillance, Epidemiology and End Results Program for epidemiological data; and used the National Comprehensive Cancer Network guidelines for management recommendations. RESULTS: Ureterosigmoidostomy is well-documented risk factor for colonic neoplasms, the reported incidence being 2-41% with a latent period of 10 to 30 years and a risk of occurrence 80-7,000 times higher than in the general population. The most common histological type of colon cancer seen after ureterosigmoidostomy is adenocarcinoma, but cases of signet-ring cell carcinoma have also been described. Signet-ring cell adenocarcinoma occurs predominantly in stomach but may infrequently arise from other organs such as breast, urinary bladder, and small and large bowel. CONCLUSIONS: This case underscores the importance of prolonged screening in patients with ureterosigmoidostomies and also calls for heightened awareness among primary care physicians regarding long-term risks associated with this unique entity.

The HoVert technique: a novel method for the sectioning of alopecia biopsies.

BACKGROUND: Cicatricial forms of alopecia, including lichen planopilaris (LPP) and discoid lupus erythematosus (DLE), may present with overlapping clinical features. In such cases, histopathological examination may provide key information for resolving the differential diagnosis. Optimally, microscopical analysis for alopecia requires both vertical and horizontal sections, and this may necessitate multiple samples. Here, we present what we term the "HoVert" technique, which produces horizontal and vertical sections from a single biopsy. We hypothesize that the HoVert technique should be useful for differentiating DLE from LPP. METHODS: A formalin-fixed 4 mm punch scalp biopsy is transected approximately 1 mm below the skin surface to create an epidermal disc and a lower portion. The epidermal disc is bisected and embedded in conventional fashion to obtain vertical sections. The lower portion is serially sectioned and embedded to obtain horizontal sections. RESULTS: The HoVert technique yields vertical sections permitting visualization of the epidermis, the dermal-epidermal junction and perijunctional inflammation. The technique also provides horizontal sections that permit analysis of follicle number, follicle type, perifollicular inflammation and scarring. Evaluation of both vertical and horizontal sections from a single scalp biopsy maximizes the histopathological information obtained and enhances the diagnosis of LPP or DLE in specific cases. CONCLUSIONS: We believe that the HoVert technique represents a simple and diagnostically effective tool in differentiating LPP from DLE. It may also be applicable to the assessment of other forms of alopecia.

Left atrial fibroelastoma.

We describe a 67-year-old man with a history of stroke who was found to have a mass at the left atrial ridge, at the free wall of the left atrium between the left atrial appendage and the pulmonary vein. The mass was removed surgically and pathological analysis showed fibroelastoma. A literature search showed that fibroelastoma in the left atrial ridge frequently causes embolic stroke.

The use of somatosensory evoked potentials to determine the relationship between patient positioning and impending upper extremity nerve injury during spine surgery: a retrospective analysis.

Somatosensory evoked potential (SSEP) monitoring is used to prevent nerve damage in spine surgery and to detect changes in upper extremity nerve function. Upper extremity SSEP conduction changes may indicate impending nerve injury. We investigated the effect of operative positioning on upper extremity nerve function retrospectively in 1000 consecutive spine surgeries that used SSEP monitoring. The vast majority (92%) of upper extremity SSEP changes were reversed by modifying the arm position and were therefore classified as position-related. The incidence of position-related upper extremity SSEP changes was calculated and compared for five different surgical positions: supine arms out, supine arms tucked, lateral decubitus position, prone arms tucked, and the prone "superman" position. The overall incidence of position-related upper extremity SSEP changes was 6.1%. The lateral decubitus position (7.5%) and prone superman position (7.0%) had a significantly more frequent incidence of position-related upper extremity SSEP changes (P < 0.0001, Z-test for Poisson counts) compared with other positions (1.8%-3.2%). No patient with a reversible SSEP change developed a new postoperative deficit in the affected extremity. SSEP monitoring is of value in identifying and reversing impending upper extremity peripheral nerve injury.