The role of transcutaneous electrical nerve stimulation for menstrual pain relief: A randomized control trial.

BACKGROUND: Abdominal pain due to menses (primary dysmenorrhea) is an extremely pervasive and debilitating symptom affecting up to 90% of menstruating individuals. OBJECTIVE: The objective of this randomized control trial was to investigate the effect of a commercial transcutaneous electrical nerve stimulation unit, Therabody PowerDot® (Therabody Inc., Los Angeles) on dysmenorrhea compared with non-steroidal anti-inflammatory drug use. DESIGN: This was a randomized cross-over study. METHODS: A total of 47 participants agreed to participate in the study, with 34 completing it. Participants completed treatments across three consecutive menstrual cycles in randomized order: single-unit transcutaneous electrical nerve stimulation (Uno), dual unit transcutaneous electrical nerve stimulation (Duo), and non-steroidal anti-inflammatory drug use (Control). Upon onset of dysmenorrhea, participants applied transcutaneous electrical nerve stimulation to their abdomen for a minimum of 30 min. Control participants were instructed to take non-steroidal anti-inflammatory drugs as needed. Surveys were used to record pain before and after treatment. We hypothesized that the PowerDot would decrease self-reported pain scores, and decrease non-steroidal anti-inflammatory drug consumption during menses. RESULTS: Participants experienced a statistically and clinically significant reduction in pain during the Control (-3.52 ± 1.9), Uno (-2.10 ± 1.6), and Duo (-2.19 ± 1.7) cycles (p < 0.001). The doses of non-steroidal anti-inflammatory drugs consumed during the Control cycle (3.5 ± 2.6), was significantly different as compared with that of Uno (1.5 ± 3.0), or Duo (1.1 ± 2.6) (p = 0.004). CONCLUSIONS: Use of a commercial transcutaneous electrical nerve stimulation unit results in significant decrease in pain. Although not as robust as the relief in pain induced by non-steroidal anti-inflammatory drugs, the adverse events of transcutaneous electrical nerve stimulation are minimal in comparison. Therefore, transcutaneous electrical nerve stimulation appears to be a viable alternative to pain relief from dysmenorrhea. CLINICAL TRIAL REGISTRATION: NCT05178589.

The role of electrical signals for period pain reliefMenstruation, also known as the period, is a cyclicly occurring event in people who are assigned female at birth. Often, the period is associated with abdominal pain that can be debilitating for many. This abdominal pain is typically treated using over-the-counter medications, such as ibuprofen; however, there several noted side effects that can arise from use of such medication. As such, this study aimed to understand if a device (Therabody PowerDot^®; Therabody Inc., Los Angeles) that sends an electrical current to pads placed over the abdomen, much like a heating pad, could be used to decrease pain during the period to a similar level as medication. The research team studied three consecutive periods with differing setups: a single, elongated pad, placed on the lower abdomen (Uno), two circular pads placed on the lower abdomen (Duo), or no use of the device, only medication (Control). The researchers analyzed data from 34 individuals. It was found that all three cycles experienced a significant decrease in pain, with the control cycle having a greater decrease in pain than both the Uno and Duo. This study suggests that the electrical stimulation used here can greatly decrease pain during the period, though not as substantial as medication.

Initial development of skill with a reversed bicycle and a case series of experienced riders.

Riding a bicycle is considered a durable skill that cannot be forgotten. Here, novice participants practiced riding a reversed bicycle, in which a reversing gear inverted the handlebar's rotation. Although learning to ride the reversed bicycle was possible, it was slow, highly variable, implicit, and followed an S-shape pattern. In the initial learning phase, failed attempts to ride the normal bicycle indicated strong interference between the two bicycle skills. While additional practice decreased this interference effect, a subset of learners could not ride either bicycle after eight sessions of practice. Experienced riders who performed extensive practice could switch bicycles without failed attempts and exhibited similar performance (i.e., similar handlebar oscillations) on both bicycles. However, their performance on the normal bicycle was worse than that of the novice bicycle riders at baseline. In conclusion, "unlearning" of the normal bicycle skill precedes the initial learning of the reversed bicycle skill, and a signature of such unlearning is still present following extensive practice.

Low Load With BFR vs. High Load Without BFR Eccentric Hamstring Training Have Similar Outcomes on Muscle Adaptation.

ABSTRACT: Jones, MJ, Dominguez, JF, Macatugal, C, Coleman, K, Reed, B, and Schroeder, ET. Low load with BFR vs. high load without BFR eccentric hamstring training have similar outcomes on muscle adaptation. J Strength Cond Res 37(1): 55-61, 2023-A key principle of hamstring injury rehabilitation is developing high eccentric force capability through resistance training (RT). However, it can take months before high-load RT is deemed safe and appropriate for rehabilitating serious hamstring injuries. Low-load blood flow restriction (BFR) RT has been identified as an effective alternative when high-load RT is contraindicated but has been scarcely investigated in the hamstring. To address this gap in knowledge, we sought to compare the effect of longitudinal BFR RT with traditional RT on eccentric hamstring power, strength, lean mass, perceived soreness, and acute muscle swell in healthy adults (n = 40; 19 F, 21 M; mean ± SD; age: 24.3 ± 2.6 years). Our crossover design compared the effects of low-load (30% 1RM) eccentric lower extremity training with BFR (BFR-ELET) with traditional high-load (80% 1RM) eccentric lower extremity training (TRAD-ELET) without BFR biweekly for 6 weeks. Outcomes were tested pre/post-intervention with significance at α = 0.05. Both interventions yielded dependent variable outcomes that did not differ significantly except for muscle swell assessed by bioelectrical impedance analysis, which decreased significantly more in the BFR-ELET condition compared with TRAD-ELET (mean ± SD: -0.32 ± 0.02, Φ° 50 kHz), CI: -0.35 to -0.28, Φ° 50 kHz, p < 0.001, Cohen's d = 2.95). Our findings support BFT-ELET as an effective alternative to TRAD-ELET for enhancing strength and identify myocellular swelling as a potential mediator for strength outcomes associated with BFR training.

Effects of a 12-Week Periodized Resistance Training Program on Resting Brain Activity and Cerebrovascular Function: A Nonrandomized Pilot Trial.

Resistance training is a promising strategy to promote healthy cognitive aging; however, the brain mechanisms by which resistance training benefits cognition have yet to be determined. Here, we examined the effects of a 12-week resistance training program on resting brain activity and cerebrovascular function in 20 healthy older adults (14 females, mean age 69.1 years). In this single group clinical trial, multimodal 3 T magnetic resonance imaging was performed at 3 time points: baseline (preceding a 12-week control period), pre-intervention, and post-intervention. Along with significant improvements in fluid cognition (d = 1.27), 4 significant voxelwise clusters were identified for decreases in resting brain activity after the intervention (Cerebellum, Right Middle Temporal Gyrus, Left Inferior Parietal Lobule, and Right Inferior Parietal Lobule), but none were identified for changes in resting cerebral blood flow. Using a separate region of interest approach, we provide estimates for improved cerebral blood flow, compared with declines over the initial control period, in regions associated with cognitive impairment, such as hippocampal blood flow (d = 0.40), and posterior cingulate blood flow (d = 0.61). Finally, resistance training had a small countermeasure effect on the age-related progression of white matter lesion volume (rank-biserial = -0.22), a biomarker of cerebrovascular disease. These proof-of-concept data support larger trials to determine whether resistance training can attenuate or even reverse salient neurodegenerative processes.

Rethinking Parkinson Disease: Exploring Gut-Brain Interactions and the Potential Role of Exercise.

Although Parkinson disease (PD) has traditionally been considered a disease of the central nervous system, a bidirectional communication system known as the gut-brain axis can influence PD pathogenesis. The dual-hit hypothesis proposed that PD is due to peripheral dysregulations to the gut microbiota, known as dysbiosis. Since then, further investigation has shown that there are multiple pathological sources associated with PD. However, dysbiosis plays a critical role in the disease process. Substantial evidence has identified that cardinal motor symptoms of PD and disease progression are associated with dysbiosis. In other neurodegenerative disorders, dysbiosis has been linked to cognition. Non-PD research has shown that exercise can effectively restore the gut microbiota. Likewise, exercise has become a well-established strategy to improve cognitive and motor function in PD. However, despite the interaction between the gut and brain, and the exercise benefits on gut health, no research to date has considered the effects of exercise on the gut microbiota in PD. Therefore, the purpose of this Perspective is to explore whether exercise benefits observed in PD could partly be due to restorations to the gut microbiota. First, we will review the gut-brain axis and its influence on motor and cognitive function. Next, we will outline evidence regarding exercise-induced restoration of the gut microbiota in non-PD populations. Finally, we will summarize benefits of exercise on motor-cognitive function in PD, proposing that benefits of exercise seen in PD might actually be due to restorations to the gut microbiota. By positing the gut microbiota as a moderator of exercise improvements to motor and cognitive function, we aim to provide a new perspective for physical therapists to prioritize exercise regimens for individuals with PD that can specifically restore the gut microbiota to better improve PD symptoms and prognosis. IMPACT: This Perspective raises awareness that dysregulations to the gut microbiota have recently been attributed to PD symptoms and pathology and that exercise can be an effective therapeutic strategy to improve gut health in individuals with PD. LAY SUMMARY: People with PD have been found to have reduced microbial diversity in their gut, which can play an important role in the progression of the disease. Physical therapists can design therapeutic exercises that might help improve gut health in people with PD.

12 weeks of strength training improves fluid cognition in older adults: A nonrandomized pilot trial.

OBJECTIVES: Resistance training (RT) is a promising strategy to slow or prevent fluid cognitive decline during aging. However, the effects of strength-specific RT programs have received little attention. The purpose of this single-group proof of concept clinical trial was to determine whether a 12-week strength training (ST) program could improve fluid cognition in healthy older adults 60 to 80 years of age, and to explore concomitant physiological and psychological changes. METHODS: Twenty participants (69.1 ± 5.8 years, 14 women) completed this study with no drop-outs or severe adverse events. Baseline assessments were completed before an initial 12-week control period, then participants were re-tested at pre-intervention and after the 12-week ST intervention. The NIH Toolbox Cognition Battery and standard physical and psychological measures were administered at all three time points. During the 36 sessions of periodized ST (3 sessions per week), participants were supervised by an exercise specialist and challenged via autoregulatory load progression. RESULTS: Test-retest reliability over the control period was good for fluid cognition and excellent for crystallized cognition. Fluid composite scores significantly increased from pre- to post-intervention (8.2 ± 6.1%, p < 0.01, d = 1.27), while crystallized composite scores did not (-0.5 ± 2.8%, p = 0.46, d = -0.34). Performance on individual fluid instruments, including executive function, attention, working memory, and processing speed, also significantly improved. Surprisingly, changes in fluid composite scores had small negative correlations with changes in muscular strength and sleep quality, but a small positive correlation with changes in muscular power. CONCLUSIONS: Thus, improvements in fluid cognition can be safely achieved in older adults using a 12-week high-intensity ST program, but further controlled studies are needed to confirm these findings. Furthermore, the relationship with other widespread physiological and psychological benefits remains unclear.

Conducting a VR Clinical Trial in the Era of COVID-19.

The outbreak of severe acute respiratory syndrome coronavirus 2, also known as Coronavirus Disease 2019 (COVID-19) sparked a global public health pandemic that has impacted every aspect of daily life. Medical research was affected, and many clinical trials were halted to minimize COVID-19 transmission risk and spread while the world navigated this novel virus. Here we describe the relaunch of our virtual reality (VR) pilot clinical trial that uses an in-lab brain and body training program to promote brain health in mid-to-late life older adults, in the era of COVID-19. This case series includes five healthy female participants between 51 and 76 years of age, a subset of a larger VR pilot clinical trial that started pre-pandemic. We developed a revised study protocol based on the Center for Disease Control and World Health Organization guidelines to help manage the spread of COVID-19. Since the limited resumption of clinical trials at our institution in August 2020, we successfully completed over 200 in-lab virtual reality training sessions using our revised protocol. During this time, none of the five participants or three study staff reported any COVID-19 symptoms or reported a positive COVID-19 test. More than 40 voluntary COVID-19 tests were completed by our study staff over the last 6 months. All participants rated our safety protocol as very satisfied or extremely satisfied and that they would be very likely or extremely likely to participate in a VR clinical trial during the pandemic. Based on these findings, we suggest that continued VR clinical trial research during the COVID-19 pandemic is achievable and can be safely resumed if specific safety protocols are in place to mitigate the risk of exposure and spread of COVID-19.

Predicting Maximal Oxygen Uptake Using the 3-Minute All-Out Test in High-Intensity Functional Training Athletes.

Maximal oxygen uptake (VO2max) and critical speed (CS) are key fatigue-related measurements that demonstrate a relationship to one another and are indicative of athletic endurance performance. This is especially true for those that participate in competitive fitness events. However, the accessibility to a metabolic analyzer to accurately measure VO2max is expensive and time intensive, whereas CS may be measured in the field using a 3 min all-out test (3MT). Therefore, the purpose of this study was to examine the relationship between VO2max and CS in high-intensity functional training (HIFT) athletes. Twenty-five male and female (age: 27.6 ± 4.5 years; height: 174.5 ± 18.3 cm; weight: 77.4 ± 14.8 kg; body fat: 15.7 ± 6.5%) HIFT athletes performed a 3MT as well as a graded exercise test with 48 h between measurements. True VO2max was determined using a square-wave supramaximal verification phase and CS was measured as the average speed of the last 30 s of the 3MT. A statistically significant and positive correlation was observed between relative VO2max and CS values (r = 0.819, p < 0.001). Based on the significant correlation, a linear regression analysis was completed, including sex, in order to develop a VO2max prediction equation (VO2max (mL/kg/min) = 8.449(CS) + 4.387(F = 0, M = 1) + 14.683; standard error of the estimate = 3.34 mL/kg/min). Observed (47.71 ± 6.54 mL/kg/min) and predicted (47.71 ± 5.7 mL/kg/min) VO2max values were compared using a dependent t-test and no significant difference was displayed between the observed and predicted values (p = 1.000). The typical error, coefficient of variation, and intraclass correlation coefficient were 2.26 mL/kg/min, 4.90%, and 0.864, respectively. The positive and significant relationship between VO2max and CS suggests that the 3MT may be a practical alternative to predicting maximal oxygen uptake when time and access to a metabolic analyzer is limited.

Validation of an Automated and Adjustable Blood Pressure System for Use with a Public Health Station.

OBJECTIVE: A new automated and adjustable blood pressure (BP) system has been developed to improve the accuracy of BP measurements on public-use health stations. This self-fitting BP system includes a mechanical cuff that wraps down to the user's arm prior to bladder inflation. The purpose of this study was to validate the adaptable BP system (ABPS) using the current standards from the Association for the Advancement of Medical Instrumentation (AAMI). METHODS: The AAMI/ISO 81060:2013 standards for clinical validation of non-invasive automated arterial BP measurement devices were followed precisely using the same arm sequential method. For each participant, BP was measured over multiple trials by trained observers alternating a reference sphygmomanometer with the ABPS. All study requirements were met with 85 qualifying participants, each with 3 valid paired determinations. RESULTS: The mean difference between ABPS BP and reference BP using all 255 paired determinations was -2.4 ± 7.7 mmHg for systolic and 1.7 ± 5.7 mmHg for diastolic. The standard deviation of the averaged paired determinations per participant was 6.3 mmHg for systolic and 5.2 mmHg for diastolic. Arm circumference measurements had a mean error of -2.1 ± 2.4 cm (R2 = 0.87). A new prediction model for arm circumference was validated using a holdout dataset (R2 = 0.94). CONCLUSION: The results of the study confirm that the ABPS met all benchmarks established by the AAMI. The device accurately measures BP across a wide range of arm circumferences (24-44 cm) and is suitable for use by individuals to self-monitor BP.

Potential Indirect Mechanisms of Cognitive Enhancement After Long-Term Resistance Training in Older Adults.

The prevalence of dementia and other age-associated cognitive disorders is steadily increasing worldwide. With no cure after diagnosis, successful treatment likely requires maximum adherence to preventative countermeasures. Many potential risk factors are modifiable through exercise. Specifically, mounting evidence suggests that long-term resistance training (RT) can help maintain cognitive abilities with aging and have additional benefits to overall brain health. Physical therapists are uniquely positioned to administer such clinical interventions designed to slow disease progression. However, a neuroscientific foundation for these benefits must be established to justify the integration of RT for brain health into practice. The mechanisms of cognitive decline are commonly linked to fundamental processes of aging. Even healthy older adults experience decreases in physical capacity, vascular function, brain structure and function, glucose regulation, inflammation, mood, and sleep quality. Yet, clinical trials involving RT in older adults have consistently demonstrated improvements in each of these systems with concomitant enhancement of cognitive performance. Beneficial adaptations may indirectly or directly mediate benefits to brain function, and understanding this relationship can help us develop optimal intervention strategies for the aging population.

Effect of home-based strength training program on IGF-I, IGFBP-1 and IGFBP-3 in obese Latino boys participating in a 16-week randomized controlled trial.

Introduction Growing evidence indicates that circulating concentrations of insulin-like growth factor 1 (IGF-I), along with IGF-I relative to IGF-binding proteins (IGFBP), are associated with an increased risk of cancer. In accord, regular exercise is linked with a lower risk of cancer. Purpose To assess the effects of a 16-week home-based strength training (HBST) program on serum IGF-I, IGFBP-1 and IGFBP-3. Methods A total of 32 obese Latino adolescent males (aged 14-18 years) were randomized into a twice-weekly HBST (n = 16) or a control group (C, n = 16) for 16 weeks. The following were measured at pre- and post-intervention: IGF-I, IGFBP-1 and IGFBP-3, glucose/insulin indices by oral and/or intravenous (IV) glucose tolerance tests, strength by one-repetition maximum (1RM), dietary intake by 3-d records, body composition by DEXA and physical activity using the Actigraph GT1X. The generalized linear model (GLM) was used to assess differences in changes among outcome measures between the HBST and C groups. Results Exercise adherence in the HBST group was 89%. IGF-1 showed a trend for significant within-subject improvements (p = 0.078) but no significant within-subject or between-subject differences for IGFBP-1, IGFBP-3 two-glucose, fasting glucose or 2-h glucose (p > 0.05). There was a significant decrease (p > 0.05) in fasting glucose in the C group (p = 0.02) and also in the intervention group (p = 0.03) between baseline and follow-up testing. A significant difference was also found in the C group for 2-h glucose with an increase at follow-up testing (p = 0.04). Conclusions Though not statistically significant (p < 0.05), the results indicated that a 16-week HBST program decreased IGF-I and increased IGFBP-1, along with IGFBP-3, concentrations among overweight/obese Latino boys. However, further studies should consider increasing either the dose or the duration of the intervention to elicit greater improvements in this at-risk pediatric population.

Physiological Performance Measures as Indicators of CrossFit® Performance.

CrossFit® began as another exercise program to improve physical fitness and has rapidly grown into the "sport of fitness". However, little is understood as to the physiological indicators that determine CrossFit® sport performance. The purpose of this study was to determine which physiological performance measure was the greatest indicator of CrossFit® workout performance. Male (n = 12) and female (n = 5) participants successfully completed a treadmill graded exercise test to measure maximal oxygen uptake (VO2max), a 3-minute all-out running test (3MT) to determine critical speed (CS) and the finite capacity for running speeds above CS (D'), a Wingate anaerobic test (WAnT) to assess anaerobic peak and mean power, the CrossFit® total to measure total body strength, as well as the CrossFit® benchmark workouts: Fran, Grace, and Nancy. It was hypothesized that CS and total body strength would be the greatest indicators of CrossFit® performance. Pearson's r correlations were used to determine the relationship of benchmark performance data and the physiological performance measures. For each benchmark-dependent variable, a stepwise linear regression was created using significant correlative data. For the workout Fran, back squat strength explained 42% of the variance. VO2max explained 68% of the variance for the workout Nancy. Lastly, anaerobic peak power explained 57% of the variance for performance on the CrossFit® total. In conclusion, results demonstrated select physiological performance variables may be used to predict CrossFit® workout performance.

Antigravity treadmill training during the early rehabilitation phase following unicompartmental knee arthroplasty: A case series.

Patients who have undergone unicompartmental knee arthroplasty (UKA) have been reported to exhibit altered gait 19-25 months post-surgery. The most common gait impairment in this population is inadequate knee flexion and a corresponding decrease in the knee extensor moment during loading response (i.e., quadriceps avoidance). The purpose of this case series was to determine whether incorporation of antigravity treadmill training into a standard physical therapy program can eliminate quadriceps avoidance gait during the early rehabilitation phase following UKA. Four females who underwent UKA were recruited for this study. Participants completed antigravity treadmill training three times per week for 12 weeks in addition to their standard physical therapy program. Instrumented gait analysis was performed at baseline (pre-intervention), week 6 (mid-intervention), and week 12 (post-intervention). We found that peak knee flexion and the peak knee extensor moment during the weight acceptance phase of gait increased to normal values following the 12-week intervention period (14.1 ± 6.5° to 20.6 ± 1.5° and 0.4 ± 0.3 to 0.7 ± 0.2 Nm/kg respectively). The findings of this case series suggest that a standard physical therapy program that incorporates early gait training using an antigravity treadmill may be beneficial in eliminating "quadriceps avoidance" during the early rehabilitation phase following UKA.

Metaphyeal and Diaphyseal Dysplasia of the Third Cervical Vertebra Secondary to Physeal Necrosis in a Quarter Horse Foal.

Ischaemia-induced physeal injury has not been described previously in the horse. A 1-month-old Quarter horse foal was submitted for necropsy examination due to an acute onset of ataxia followed by a 4-week history of progressive decline. Focal narrowing of the spinal canal due to ventral compression by the rotation of the cranial aspect of the third cervical vertebra (C3) was observed. The metaphysis and diaphysis of C3 were markedly shortened and white-tan in colour. Microscopically, there was complete loss of the dorsal compact bone of C3 and replacement of 80% of the physis that runs parallel to the vertebral canal with fibrous tissue and thickened viable trabecular bone. Both cranial and caudal physes of C3 showed widespread bands of coagulative necrosis of the hypertrophic and calcifying zones. Marked bone marrow hypoplasia with slight fibrosis was observed in the metaphyses and diaphysis. There was no evidence of fracture or inflammation. The epiphyses were microscopically unremarkable. It was hypothesized that a regional transient incomplete and possibly multiphasic ischaemia involving the nutrient artery caused necrosis of the physes, resulting in dysplasia of the bone. Ischaemic injury to the physis should be considered in the pathogenesis of focal bone dysplasia in horses.

Impact of resistance training on body composition and metabolic syndrome variables during androgen deprivation therapy for prostate cancer: a pilot randomized controlled trial.

BACKGROUND: Prostate cancer patients on androgen deprivation therapy (ADT) experience adverse effects such as lean mass loss, known as sarcopenia, fat gain, and changes in cardiometabolic factors that increase risk of metabolic syndrome (MetS). Resistance training can increase lean mass, reduce body fat, and improve physical function and quality of life, but no exercise interventions in prostate cancer patients on ADT have concomitantly improved body composition and MetS. This pilot trial investigated 12 weeks of resistance training on body composition and MetS changes in prostate cancer patients on ADT. An exploratory aim examined if a combined approach of training and protein supplementation would elicit greater changes in body composition. METHODS: Prostate cancer patients on ADT were randomized to resistance training and protein supplementation (TRAINPRO), resistance training (TRAIN), protein supplementation (PRO), or control stretching (STRETCH). Exercise groups (EXE = TRAINPRO, TRAIN) performed supervised exercise 3 days per week for 12 weeks, while non-exercise groups (NoEXE = PRO, STRETCH) performed a home-based stretching program. TRAINPRO and PRO received 50 g⋅day- 1 of whey protein. The primary outcome was change in lean mass assessed through dual energy x-ray absorptiometry. Secondary outcomes examined changes in sarcopenia, assessed through appendicular skeletal mass (ASM) index (kg/m2), body fat %, strength, physical function, quality of life, MetS score and the MetS components of waist circumference, blood pressure, glucose, high-density lipoprotein-cholesterol, and triglyceride levels. RESULTS: A total of 37 participants were randomized; 32 participated in the intervention (EXE n = 13; NoEXE n = 19). At baseline, 43.8% of participants were sarcopenic and 40.6% met the criteria for MetS. Post-intervention, EXE significantly improved lean mass (d = 0.9), sarcopenia prevalence (d = 0.8), body fat % (d = 1.1), strength (d = 0.8-3.0), and prostate cancer-specific quality of life (d = 0.9) compared to NoEXE (p < 0.05). No significant differences were observed between groups for physical function or MetS-related variables except waist circumference (d = 0.8). CONCLUSIONS: A 12-week resistance training intervention effectively improved sarcopenia, body fat %, strength and quality of life in hypogonadal prostate cancer patients, but did not change MetS or physical function. PRO did not offer additional benefit in improving body composition. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01909440 . Registered 24 July 2013.

Solution pH jump during antibody and Fc-fusion protein thaw leads to increased aggregation / 药物分析学报

Freeze-thaw cycles impact the amount of aggregation observed in antibodies and Fc-fusion proteins. Various formulation strategies are used to mitigate the amount of aggregation that occurs upon putting a protein solution through a freeze-thaw cycle. Additionally, low pH solutions cause native antibodies to unfold, which are prone to aggregate upon pH neutralization. There is great interest in the mechanism that causes therapeutic proteins to aggregate since aggregate species can cause unwanted im-munogenicity in patients. Herein, an increase in aggregation is reported when the pH is adjusted from pH 3 up to a pH ranging from pH 4 to pH 7 during the thaw process of a frozen antibody solution. Raising the pH during the thaw process caused a significant increase in the percent aggregation observed. Two antibodies and one Fc-fusion protein were evaluated during the pH jump thaw process and similar ef-fects were observed. The results provide a new tool to study the kinetics of therapeutic protein ag-gregation upon pH increase.

Perioperative Testosterone Supplementation Increases Lean Mass in Healthy Men Undergoing Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial.

BACKGROUND: Rehabilitation after repair of the anterior cruciate ligament (ACL) is complicated by the loss of leg muscle mass and strength. Prior studies have shown that preoperative rehabilitation may improve muscle strength and postoperative outcomes. Testosterone supplementation may likewise counteract this muscle loss and potentially improve clinical outcomes. PURPOSE: The purpose was to investigate the effect of perioperative testosterone administration on lean mass after ACL reconstruction in men and to examine the effects of testosterone on leg strength and clinical outcome scores. It was hypothesized that testosterone would increase lean mass and leg strength and improve clinical outcome scores relative to placebo. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Male patients (N = 13) scheduled for ACL reconstruction were randomized into 2 groups: testosterone and placebo. Participants in the testosterone group received 200 mg of intramuscular testosterone weekly for 8 weeks beginning 2 weeks before surgery. Participants in the placebo group received saline following the same schedule. Both groups participated in a standard rehabilitation protocol. The primary outcome was the change in total lean body mass at 6 and 12 weeks. Secondary outcomes were extensor muscle strength, Tegner activity score, and Knee injury and Osteoarthritis Outcome Score. RESULTS: There was an increase in lean mass of a mean 2.7 ± 1.7 kg at 6 weeks postoperatively in the testosterone group compared with a decrease of a mean 0.1 ± 1.5 kg in the placebo group (P = .01). Extensor muscle strength of the uninjured leg also increased more from baseline in the testosterone group (+20.8 ± 25.6 Nm) compared with the placebo group (-21.4 ± 36.7 Nm) at 12 weeks (P = .04). There were no significant between-group differences in injured leg strength or clinical outcome scores. There were no negative side effects of testosterone noted. CONCLUSION: Perioperative testosterone supplementation increased lean mass 6 weeks after ACL reconstruction, suggesting that this treatment may help minimize the effects of muscle atrophy associated with ACL injuries and repair. This study was not powered to detect differences in strength or clinical outcome scores to assess the incidence of testosterone-related adverse events. CLINICAL RELEVANCE: Supraphysiological testosterone supplementation may be a useful adjunct therapy for counteracting muscle atrophy after ACL reconstruction. Further investigation is necessary to determine the safety profile and effects of perioperative testosterone administration on leg strength and clinical outcomes after surgery. REGISTRATION: NCT01595581 (ClinicalTrials.gov).

A pilot randomised controlled trial of a periodised resistance training and protein supplementation intervention in prostate cancer survivors on androgen deprivation therapy.

INTRODUCTION: Prostate cancer survivors (PCS) receiving androgen deprivation therapy (ADT) experience deleterious side effects such as unfavourable changes in cardiometabolic factors that lead to sarcopenic obesity and metabolic syndrome (MetS). While loss of lean body mass (LBM) compromises muscular strength and quality of life, MetS increases the risk of cardiovascular disease and may influence cancer recurrence. Exercise can improve LBM and strength, and may serve as an alternative to the pharmacological management of MetS in PCS on ADT. Prior exercise interventions in PCS on ADT have been effective at enhancing strength, but only marginally effective at enhancing body composition and ameliorating cardiometabolic risk factors. This pilot trial aims to improve on existing interventions by employing periodised resistance training (RT) to counter sarcopenic obesity in PCS on ADT. Secondary aims compare intervention effects on cardiometabolic, physical function, quality of life and molecular skeletal muscle changes. An exploratory aim examines if protein supplementation (PS) in combination with RT elicits greater changes in these outcomes. METHODS AND ANALYSIS: A 2×2 experimental design is used in 32 PCS on ADT across a 12-week intervention period. Participants are randomised to resistance training and protein supplementation (RTPS), RT, PS or control. RT and RTPS groups perform supervised RT three times per week for 12 weeks, while PS and RTPS groups receive 50 g whey protein per day. This pilot intervention applies a multilayered approach to ameliorate detrimental cardiometabolic effects of ADT while investigating molecular mechanisms underlying skeletal muscle changes in PCS. ETHICS AND DISSEMINATION: This trial was approved by the University of Southern California Institutional Review Board (HS-13-00315). Results from this trial will be communicated in peer-reviewed publications and scientific presentations. TRIAL REGISTRATION NUMBER: NCT01909440; Pre-results.

Blunted Myoglobin and Quadriceps Soreness After Electrical Stimulation During the Luteal Phase or Oral Contraception.

PURPOSE: Acute muscle damage after exercise triggers subsequent regeneration, leading to hypertrophy and increased strength after repeated exercise. It has been debated whether acute exercise-induced muscle damage is altered under various premenopausal estrogen conditions. Acute contraction-induced muscle damage was compared during exogenous (oral contraceptive, OC), endogenous (luteal phase, HI), or low (menses, LO) estrogen in healthy young women aged 21 to 30 years old. METHODS: Women (OC, n = 9; HI, n = 9; LO, n = 8; total N = 26) performed 1 neuromuscular electrical stimulation (NMES) bout. Soreness, measured via visual analog scale and the Likert Scale of Muscle Soreness for Lower Limb (LSMSLL), quadriceps strength, and plasma myoglobin (Mb), interleukin (IL)-6, IL-8, and granulocyte-colony stimulating factor were measured before and after NMES. RESULTS: NMES performance was similar across groups. Meaningful within-group increases in Mb (effect size [ES] = 1.12) and IL-8 (ES = 0.38) occurred in LO; ES for HI and OC were trivial. ES of the between-group difference in change was moderate for Mb (LO vs. HI = 1.15) and IL-8 (LO vs. HI = 0.86; LO vs. OC = 0.73). 17-ß estradiol correlated moderately and negatively with Mb relative change (r = -.52, p < .05). LO had ~5% greater strength loss than OC and HI. The mean change score for the LSMSLL 2 days post-NMES was clinically greater in LO than OC or HI. CONCLUSIONS: Acute NMES-induced indicators of muscle fiber damage and qualitative muscle soreness may be attenuated during the luteal phase or active OC pill consumption compared with the menstrual phase.

A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients.

Androgen deprivation therapy (ADT), a primary treatment for locally advanced or metastatic prostate cancer, is associated with the adverse effects on numerous physiologic parameters, including alterations in cardiometabolic variables that overlap with components of the metabolic syndrome (MetS). As MetS is an established risk factor for cardiovascular mortality and treatment for prostate cancer has been associated with the development of MetS, interventions targeting cardiometabolic factors have been investigated in prostate cancer patients to attenuate the detrimental effects of ADT. Much support exists for exercise interventions in improving MetS variables in insulin-resistant adults, but less evidence is available in men with prostate cancer. Regular exercise, when performed at appropriate intensities and volumes, can elicit improvements in ADT-related adverse effects, including MetS, and contributes to the growing body of literature supporting the role of exercise in cancer survivorship. This review (1) discusses the biologic inter-relationship between prostate cancer, ADT and MetS, (2) evaluates the current literature in support of exercise in targeting MetS and (3) describes the physiological mechanisms by which exercise may favorably alter MetS risk factors in prostate cancer patients on ADT.