COSMOS: a platform for real-time morphology-based, label-free cell sorting using deep learning.

Cells are the singular building blocks of life, and a comprehensive understanding of morphology, among other properties, is crucial to the assessment of underlying heterogeneity. We developed Computational Sorting and Mapping of Single Cells (COSMOS), a platform based on Artificial Intelligence (AI) and microfluidics to characterize and sort single cells based on real-time deep learning interpretation of high-resolution brightfield images. Supervised deep learning models were applied to characterize and sort cell lines and dissociated primary tissue based on high-dimensional embedding vectors of morphology without the need for biomarker labels and stains/dyes. We demonstrate COSMOS capabilities with multiple human cell lines and tissue samples. These early results suggest that our neural networks embedding space can capture and recapitulate deep visual characteristics and can be used to efficiently purify unlabeled viable cells with desired morphological traits. Our approach resolves a technical gap in the ability to perform real-time deep learning assessment and sorting of cells based on high-resolution brightfield images.

A comparison of three-dimensional kinematics between markerless and marker-based motion capture in overground gait.

Vision-based methods using RGB inputs for human pose estimation have grown in recent years but have undergone limited testing in clinical and biomechanics research areas like gait analysis. The purpose of the present study was to compare lower extremity kinematics during overground gait between a traditional marker-based approach and a commercial multi-view markerless system in a sample of subjects including young adults, older adults, and adults diagnosed with Parkinson's disease. A convenience sample of 35 adults between the age of 18-85 years were included in this study, yielding a total of 114 trials and 228 gait cycles that were compared between systems. A total of 30 time normalized waveforms, including three-dimensional joint centers, segment angles, and joint angles were compared between systems using root mean-squared error (RMSE), range of motion difference (ΔROM), Pearson correlation coefficients (r), and interclass correlation coefficients (ICC). RMSEs for joint center positions were less than 28 mm in all joints with correlations indicating good to excellent agreement. RMSEs for segment and joint angles were in range of previous results, with highest agreement between systems in the sagittal plane. ΔROM differences were within reference values that characterize clinical groups like Parkinson's disease, stroke, or knee osteoarthritis. Further improvements in pelvis tracking, markerless keypoint model definitions, and standardization of comparison study protocols are needed. Nevertheless, markerless solutions seem promising toward unrestricted motion analysis in biomechanics research and clinical settings.

Prediction of gait kinetics using Markerless-driven musculoskeletal modeling.

Video-based motion analysis systems are emerging in the biomechanics research community, yet there is limited exploration of kinetics prediction using RGB-markerless kinematics and musculoskeletal modeling. This project aimed to provide ground reaction force (GRF) and ground reaction moment (GRM) predictions during over-ground gait by introducing RGB-markerless kinematics into a musculoskeletal modeling framework. Full-body markerless kinematic inputs and musculoskeletal modeling were used to obtain GRF and GRM predictions which were compared to measured force plate values. The markerless-driven predictions yielded average root mean-squared error (RMSE) in the stance phase of 0.035 ± 0.009 N∙BW-1, 0.070 ± 0.014 N∙BW-1, and 0.155 ± 0.041 N∙BW-1 in the mediolateral (ML), anteroposterior (AP), and vertical (V) GRFs. This was accompanied by moderate to high correlations and interclass correlation coefficients (ICC) indicating moderate to good agreement between measured and predicted values (95% Confidence Inervals: ML = [0.479, 0.717], AP = [0.714, 0.856], V = [0.803, 0.905]). For ground reaction moments (GRM), average RMSE was 0.029 ± 0.013 Nm∙BWH-1, 0.014 ± 0.005 Nm∙BWH-1, and 0.005 ± 0.002 Nm∙BWH-1 in the sagittal, frontal, and transverse planes. Pearson correlations and ICCs indicated poor agreement between systems for GRMs (95% Confidence Intervals: Sagittal = [0.314, 0.608], Frontal = [0.006, 0.373], Transverse = [0.269, 0.570]). Currently, RMSE is larger than target thresholds set from studies using Kinect, inertial, or marker-based kinematic drivers; but methodological considerations highlighted in this work may help guide follow-up iterations. At this point, further use in research or clinical practice is cautioned until methodological considerations are addressed, although results are promising at this point.

Mercury accumulation, biomagnification, and relationships to δ13C, δ15N and δ34S of fishes and marine mammals in a coastal Arctic marine food web.

Combining mercury and stable isotope data sets of consumers facilitates the quantification of whether contaminant variation in predators is due to diet, habitat use and/or environmental factors. We investigated inter-species variation in total Hg (THg) concentrations, trophic magnification slope between δ15N and THg, and relationships of THg with δ13C and δ34S in 15 fish and four marine mammal species (249 individuals in total) in coastal Arctic waters. Median THg concentration in muscle varied between species ranging from 0.08 ± 0.04 µg g-1 dw in capelin to 3.10 ± 0.80 µg g-1 dw in beluga whales. Both δ15N (r2 = 0.26) and δ34S (r2 = 0.19) best explained variation in log-THg across consumers. Higher THg concentrations occurred in higher trophic level species that consumed more pelagic-associated prey than consumers that rely on the benthic microbial-based food web. Our study illustrates the importance of using a multi-isotopic approach that includes δ34S when investigating trophic Hg dynamics in coastal marine systems.

Validity of artificial intelligence-based markerless motion capture system for clinical gait analysis: Spatiotemporal results in healthy adults and adults with Parkinson's disease.

Markerless motion capture methods are continuously in development to target limitations encountered in marker-, sensor-, or depth-based systems. Previous evaluation of the KinaTrax markerless system was limited by differences in model definitions, gait event methods, and a homogenous subject sample. The purpose of this work was to evaluate the accuracy of spatiotemporal parameters in the markerless system with an updated markerless model, coordinate- and velocity-based gait events, and subjects representing young adult, older adult, and Parkinson's disease groups. Fifty-seven subjects and 216 trials were included in this analysis. Interclass correlation coefficients showed excellent agreement between the markerless system and a marker-based reference system for all spatial parameters. Temporal variables were similar, except swing time which showed good agreement. Concordance correlation coefficients were similar with all but swing time showing moderate to almost perfect concordance. Bland-Altman bias and limits of agreement (LOA) were small and improved from previous evaluations. Parameters showed similar agreement across coordinate- and velocity-based gait methods with the latter showing generally smaller LOAs. Improvements in spatiotemporal parameters in the present evaluation was due to inclusion of keypoints at the calcanei in the markerless model. Consistency in the calcanei keypoints relative to heel marker placements may improve results further. Similar to previous work, LOAs are within boundaries to detect differences in clinical groups. Results support the use of the markerless system for estimation of spatiotemporal parameters across age and clinical groups, but caution should be taken when generalizing findings due to remaining error in kinematic gait event methods.

Randomized, Double-Blind, Placebo-Controlled Trial of a Throat Spray with Selected Lactobacilli in COVID-19 Outpatients.

Primary care urgently needs treatments for coronavirus disease 2019 (COVID-19) patients because current options are limited, while these patients who do not require hospitalization encompass more than 90% of the people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we evaluated a throat spray containing three Lactobacillaceae strains with broad antiviral properties in a randomized, double-blind, placebo-controlled trial. Before the availability of vaccines, 78 eligible COVID-19 patients were randomized to verum (n = 41) and placebo (n = 37) within 96 h of a positive PCR-based SARS-CoV-2 diagnosis, and a per-protocol analysis was performed. Symptoms and severity were reported daily via an online diary. Combined nose-throat swabs and dried blood spots were collected at regular time points in the study for microbiome, viral load, and antibody analyses. The daily reported symptoms were highly variable, with no added benefit for symptom resolution in the verum group. However, based on 16S V4 amplicon sequencing, the acute symptom score (fever, diarrhea, chills, and muscle pain) was significantly negatively associated with the relative abundance of amplicon sequence variants (ASVs) that included the applied lactobacilli (P < 0.05). Furthermore, specific monitoring of these applied lactobacilli strains showed that they were detectable via quantitative PCR (qPCR) analysis in 82% of the patients in the verum group. At the end of the trial, a trend toward lower test positivity for SARS-CoV-2 was observed for the verum group (2/30; 6.7% positive) than for the placebo group (7/27; 26% positive) (P = 0.07). These data indicate that the throat spray with selected antiviral lactobacilli could have the potential to reduce nasopharyngeal viral loads and acute symptoms but should be applied earlier in the viral infection process and substantiated in larger trials. IMPORTANCE Viral respiratory tract infections result in significant health and economic burdens, as highlighted by the COVID-19 pandemic. Primary care patients represent 90% of those infected with SARS-CoV-2, yet their treatment options are limited to analgesics and antiphlogistics, and few broadly acting antiviral strategies are available. Microbiome or probiotic therapy is a promising emerging treatment option because it is based on the multifactorial action of beneficial bacteria against respiratory viral disease. In this study, an innovative topical throat spray with select beneficial lactobacilli was administered to primary COVID-19 patients. A remote study setup (reducing the burden on hospitals and general practitioners) was successfully implemented using online questionnaires and longitudinal self-sampling. Our results point toward the potential mechanisms of action associated with spray administration at the levels of viral loads and microbiome modulation in the upper respiratory tract and pave the way for future clinical applications of beneficial bacteria against viral diseases.

Seven days of ischemic preconditioning augments hypoxic exercise ventilation and muscle oxygenation in recreationally trained males.

This investigation sought to assess whether single or repeated bouts of ischemic preconditioning (IPC) could improve oxyhemoglobin saturation ([Formula: see text]) and/or attenuate reductions in muscle tissue saturation index (TSI) during submaximal hypoxic exercise. Fifteen healthy young men completed submaximal graded exercise under four experimental conditions: 1) normoxia (NORM), 2) hypoxia (HYP) [oxygen fraction of inspired air ([Formula: see text]) = 0.14, ∼3,200 m], 3) hypoxia preceded by a single session of IPC (IPC1-HYP), and 4) hypoxia preceded by seven sessions of IPC, one a day for 7 consecutive days (IPC7-HYP). IPC7-HYP heightened minute ventilation (V̇e) at 80% HYP peak cycling power output (Wpeak) (+10.47 ± 3.35 L·min-1, P = 0.006), compared with HYP, as a function of increased breathing frequency. Both IPC1-HYP (+0.17 ± 0.04 L·min-1, P < 0.001) and IPC7-HYP (+0.16 ± 0.04 L·min-1, P < 0.001) elicited greater oxygen consumption (V̇o2) across exercise intensities compared with NORM, whereas V̇o2 was unchanged with HYP alone. [Formula: see text] was unchanged by either IPC condition at any exercise intensity, yet the reduction of muscle TSI during resting hypoxic exposure was attenuated by IPC7-HYP (+9.9 ± 3.6%, P = 0.040) compared with HYP, likely as a function of reduced local oxygen extraction. Considering all exercise intensities, IPC7-HYP attenuated reductions of TSI with HYP (+6.4 ± 1.8%, P = 0.001). Seven days of IPC heightens ventilation, posing a threat to ventilatory efficiency, during high-intensity submaximal hypoxic exercise and attenuates reductions in hypoxic resting and exercise muscle oxygenation in healthy young men. A single session of IPC may be capable of modulating hypoxic ventilation; however, our present population was unable to demonstrate this with certainty.

IPC recovery length of 45 minutes improves muscle oxygen saturation during active sprint recovery.

Ischemic preconditioning (IPC) involves brief, repeated bouts of limb occlusion and reperfusion capable of improving exercise performance at least partially by enhancing local skeletal muscle oxygenation. This study sought to investigate the effect of a lower limb IPC protocol, with either a 5-min or 45-min post-application delay, on vastus lateralis tissue saturation index (TSI) and systemic cardiac hemodynamics at rest and during short-duration intense cycling. Twelve young adults randomly completed four interventions: IPC (at 220 mmHg) with 5-min delay (IPC5), IPC with 45-min delay (IPC45), SHAM (at 20 mmHg) with 5-min delay (SHAM5), and SHAM with 45-min delay (SHAM45). Following IPC intervention and recovery delay, participants completed 5, 60-s high-intensity (100% Wpeak) cycle sprints separated by 120-sec of active recovery (30% Wpeak). Compared to baseline, TSI immediately following IPC5, but pre-exercise, remained lower than the equivalent for IPC45 (-5.9 ± 1.5%, p = .002). IPC, imposed at least 45-min before the completion of five 60-s sprint cycling efforts, significantly enhanced TSI during active recovery between sprint intervals compared to a 5-min delay (6.6 ± 2.4%, p = .021), and identical SHAM conditions (SHAM5: 5.8 ± 2.2%, p = .024; SHAM45: 6.2 ± 2.5%, p = .029). A 45-min delay following IPC appears to provide heightened skeletal muscle metabolic rebound prior to intense sprint cycling as compared to a 5-min delay. Furthermore, IPC followed by a 45-min delay enhanced recovery of skeletal muscle oxygenation during low intensity active sprint recovery, despite an unchanged decline in skeletal muscle oxygenation during near-maximal sprinting efforts.

Diagnostic performance of the Idylla™ respiratory panel for molecular detection of influenza A/B in patients presenting to primary care with influenza-like illness during 3 consecutive influenza seasons.

BACKGROUND: Influenza virus (IFV) is often encountered in primary care. Implementation of a rapid diagnostic test for its detection at the point-of-care would enable discrimination from other viral causes of influenza-like-illness (ILI) and might be helpful in individual patient management. In this study, the diagnostic performance of such a point-of-care platform was evaluated. METHODS: Respiratory samples (n = 1490) from ILI-patients in primary care in 15 European countries were collected as part of a prospective clinical trial. Both children (n = 252) and adults (n = 1238) were sampled during 3 consecutive periods of high IFV endemicity. Samples were analysed in a central laboratory, after storage at -70 °C, with the Idylla™ Respiratory Panel, detecting both IFV and RSV, on the Idylla™ platform. The Fast Track Diagnostics (FTD) Respiratory Pathogens 21 plus assay was used as reference. A subset of samples (n = 192) was analysed both fresh and after being frozen. RESULTS: The reference method detected IFV-A in 42% and IFV-B in 13% of the samples. Sensitivity of the Idylla for detection of IFV-A and IFV-B was 98.2% and 92.3% and specificity 97.7% and 98.4% respectively. False negative samples contained significantly lower viral loads than true positive samples (FTD mean Ct-value 30.7 versus 26.1 for IFV-A and 30.4 versus 25.1 for IFV-B, p < 0.001). Comparable results were obtained for Idylla analysis using fresh and frozen samples. CONCLUSIONS: The Idylla Respiratory Panel is a promising point-of-care test for detection of IFV in ILI patients due to its excellent diagnostic performance, minimal training requirements and limited hands-on time.

Neither Postabsorptive Resting Nor Postprandial Fat Oxidation Are Related to Peak Fat Oxidation in Men With Chronic Paraplegia.

The peak rate of fat oxidation (PFO) achieved during a graded exercise test is an important indicator of metabolic health. In healthy individuals, there is a significant positive association between PFO and total daily fat oxidation (FO). However, conditions resulting in metabolic dysfunction may cause a disconnect between PFO and non-exercise FO. Ten adult men with chronic thoracic spinal cord injury (SCI) completed a graded arm exercise test. On a separate day following an overnight fast (≥ 10 h), they rested for 60 min before ingesting a liquid mixed meal (600 kcal; 35% fat, 50% carbohydrate, 15% protein). Expired gases were collected and indirect calorimetry data used to determine FO at rest, before and after feeding, and during the graded exercise test. Participants had "good" cardiorespiratory fitness (VO2peak: 19.2 ± 5.2 ml/kg/min) based on normative reference values for SCI. There was a strong positive correlation between PFO (0.30 ± 0.08 g/min) and VO2peak (r = 0.86, p = 0.002). Additionally, postabsorptive FO at rest was significantly and positively correlated with postprandial peak FO (r = 0.77, p = 0.01). However, PFO was not significantly associated with postabsorptive FO at rest (0.08 ± 0.02 g/min; p = 0.97), postprandial peak FO (0.10 ± 0.03 g/min; p = 0.43), or incremental area under the curve postprandial FO (p = 0.22). It may be advantageous to assess both postabsorptive FO at rest and PFO in those with SCI to gain a more complete picture of their metabolic flexibility and long-term metabolic health.

Exercise Interventions Targeting Obesity in Persons With Spinal Cord Injury.

Spinal cord injury (SCI) results in an array of cardiometabolic complications, with obesity being the most common component risk of cardiometabolic disease (CMD) in this population. Recent Consortium for Spinal Cord Medicine Clinical Practice Guidelines for CMD in SCI recommend physical exercise as a primary treatment strategy for the management of CMD in SCI. However, the high prevalence of obesity in SCI and the pleiotropic nature of this body habitus warrant strategies for tailoring exercise to specifically target obesity. In general, exercise for obesity management should aim primarily to induce a negative energy balance and secondarily to increase the use of fat as a fuel source. In persons with SCI, reductions in the muscle mass that can be recruited during activity limit the capacity for exercise to induce a calorie deficit. Furthermore, the available musculature exhibits a decreased oxidative capacity, limiting the utilization of fat during exercise. These constraints must be considered when designing exercise interventions for obesity management in SCI. Certain forms of exercise have a greater therapeutic potential in this population partly due to impacts on metabolism during recovery from exercise and at rest. In this article, we propose that exercise for obesity in SCI should target large muscle groups and aim to induce hypertrophy to increase total energy expenditure response to training. Furthermore, although carbohydrate reliance will be high during activity, certain forms of exercise might induce meaningful postexercise shifts in the use of fat as a fuel. General activity in this population is important for many components of health, but low energy cost of daily activities and limitations in upper body volitional exercise mean that exercise interventions targeting utilization and hypertrophy of large muscle groups will likely be required for obesity management.

Substrate metabolism during recovery from circuit resistance exercise in persons with spinal cord injury.

INTRODUCTION: Whole body energy expenditure and lipid oxidation (Lox) are upregulated during and after exercise. Persons with spinal cord injury (SCI) generally have a blunted ability to utilize fat during exercise, but it is unknown if their substrate partitioning is affected during recovery from exercise. PURPOSE: To determine the effect of a single session of upper body circuit resistance exercise (CRE) on energy expenditure and Lox during exercise recovery in persons with and without SCI. METHODS: Twenty four persons (3 groups; 7 male and 1 female per group) without paralysis (neurologically intact; N) or with chronic (≥ 1 yr) paraplegia (P) or tetraplegia (T) participated. Energy expenditure and substrate partitioning were assessed via indirect calorimetry before, during, and three times after (up to 120 min after) a single session of CRE, or time-matched seated control (CON). RESULTS: During CRE, all groups experienced a similar relative increase in oxygen consumption (49 ± 13, 55 ± 11, and 48 ± 15% VO2peak for N, P, and T, respectively). The Post0-120 energy expenditure was greater following CRE vs. CON (P < 0.01) and independent of injury characteristics (10.6, 22.6, and 14.3% higher than CON for N, P, and T; P = 0.21). The absolute increase in Lox above CON during recovery was similar for N, P, and T (5.74 ± 2.81, 6.62 ± 3.10, and 4.50 ± 3.91 g, respectively; P = 0.45). CONCLUSIONS: Energy expenditure and lipid utilization was increased similarly following circuit exercise in persons without and with spinal cord injury in a manner independent of level of injury.

Effect of Paraplegia on the Time Course of Exogenous Fatty Acid Incorporation Into the Plasma Triacylglycerol Pool in the Postprandial State.

Spinal cord injury (SCI) results in disordered fat metabolism. Autonomic decentralization might contribute to dyslipidemia in SCI, in part by influencing the uptake of dietary fats through the gut-lymph complex. However, the neurogenic contributions to dietary fat metabolism are unknown in this population. We present a subset of results from an ongoing registered clinical trial (NCT03691532) related to dietary fat absorption. We fed a standardized (20 kcal⋅kgFFM-1) liquid meal tolerance test (50% carb, 35% fat, and 15% protein) that contained stable isotope lipid tracer (5 mg⋅kgFFM-1 [U-13C]palmitate) to persons with and without motor complete thoracic SCI. Blood samples were collected at six postprandial time points over 400 min. Changes in dietary fatty acid incorporated into the triacylglycerol (TAG) pool ("exogenous TAG") were used as a marker of dietary fat absorption. This biomarker showed that those with paraplegia had a lower amplitude than non-injured participants at Post240 (52.4 ± 11.0 vs. 77.5 ± 16.0 µM), although this failed to reach statistical significance (p = 0.328). However, group differences in the time course of absorption were notable. The injury level was also strongly correlated with time-to-peak exogenous TAG concentration (r = -0.806, p = 0.012), with higher injuries resulting in a slower rise in exogenous TAG. This time course documenting exogenous TAG change is the first to show a potential neurogenic alteration in SCI dietary fat absorption.

Effects of Exercise Mode on Postprandial Metabolism in Humans with Chronic Paraplegia.

PURPOSE: The purpose of this study was to assess the acute effects of exercise mode and intensity on postprandial macronutrient metabolism. METHODS: Ten healthy men age 39 ± 10 yr with chronic paraplegia (13.2 ± 8.8 yr, ASIA A-C) completed three isocaloric bouts of upper-body exercise and a resting control. After an overnight fast, participants completed circuit resistance exercise (CRE) first and the following conditions in a randomized order, separated by >48 h: i) control (CON), ~45-min seated rest; ii) moderate-intensity continuous exercise (MICE), ~40-min arm cranking at a resistance equivalent to ~30% peak power output (PPO); and iii) high-intensity interval exercise (HIIE), ~30 min arm cranking with resistance alternating every 2 min between 10% PPO and 70% PPO. After each condition, participants completed a mixed-meal tolerance test consisting of a 2510-kJ liquid meal (35% fat, 50% carbohydrate, 15% protein). Blood and expired gas samples were collected at baseline and regular intervals for 150 min after a meal. RESULTS: An interaction (P < 0.001) was observed, with rates of lipid oxidation elevated above CON in HIIE until 60 min after a meal and in CRE at all postprandial time points up to 150 min after a meal. Postprandial blood glycerol was greater in MICE (P = 0.020) and CRE (P = 0.001) compared with CON. Furthermore, nonesterified fatty acid area under the curve had a moderate-to-strong effect in CRE versus MICE and HIIE (Cohen's d = -0.76 and -0.50, respectively). CONCLUSIONS: In persons with paraplegia, high-intensity exercise increased postprandial energy expenditure independent of the energy cost of exercise. Furthermore, exercise combining resistance and endurance modes (CRE) showed the greater effect on postprandial lipid oxidation.

Physiological responses to moderate intensity continuous and high-intensity interval exercise in persons with paraplegia.

STUDY DESIGN: Randomized crossover. OBJECTIVES: To test differences in the duration and magnitude of physiological response to isocaloric moderate intensity continuous (MICE) and high-intensity interval exercise (HIIE) sessions in persons with spinal cord injury (SCI). SETTING: Academic medical center in Miami, FL, USA. METHODS: Ten adult men (mean ± s.d.; 39 ± 10 year old) with chronic (13.2 ± 8.8 year) paraplegia (T2-T10) completed a graded exercise test. Then, in a randomized order, participants completed MICE and HIIE for a cost of 120 kcal. MICE was performed at 24.6% POpeak. During HIIE, exercise was completed in 2 min work and recovery phases at 70%:10% POpeak. RESULTS: MICE and HIIE were isocaloric (115.9 ± 21.8 and 116.6 ± 35.0 kcal, respectively; p = 0.903), but differed in duration (39.8 ± 4.6 vs 32.2 ± 6.2 min; p < 0.001) and average respiratory exchange ratio (RER; 0.90 ± 0.08 vs 1.01 ± 0.07; p = 0.002). During MICE, a workrate of 24.6 ± 6.7% POpeak elicited a V̇O2 of 53.1 ± 6.5% V̇O2peak (10.1 ± 2.2 ml kg-1 min-1). During HIIE, a workrate at 70% POpeak elicited 88.3 ± 6.7% V̇O2peak (16.9 ± 4.2 ml kg-1 min-1), and 29.4 ± 7.7% of the session was spent at or above 80% V̇O2peak. During HIIE working phase, RER declined from the first to last interval (1.08 ± 0.07 vs 0.98 ± 0.09; p < 0.001), reflecting an initially high but declining glycolytic rate. CONCLUSIONS: Compared with MICE, HIIE imposed a greater physiological stimulus while requiring less time to achieve a target caloric expenditure. Thus, exercise intensity might be an important consideration in the tailoring of exercise prescription to address the cardiometabolic comorbidities of SCI.

Multidirectional Walking in Hematopoietic Stem Cell Transplant Patients.

BACKGROUND: The effect of a peritransplant multidirectional walking intervention to target losses in physical function and quality of life (QOL) has not been investigated. PURPOSE: This study examined the effects of a novel multidirectional walking program on physical function and QOL in adults receiving a hematopoietic stem cell transplant (HSCT). METHODS: Thirty-five adults receiving an autologous or allogeneic HSCT were randomized to a multidirectional walking (WALK) or usual care (CONT) group. The WALK group received supervised training during hospitalization; the CONT group received usual care. Patients were assessed at admission (t0), 3 to 5 d post-HSCT (t1), and 30 d post-HSCT (t2). Physical function measures included the 6-min walk test (6MWT), the Physical Performance Test, and the Timed Up and Go test. Health-related QOL was collected using the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) questionnaire. RESULTS: There were no significant between-group changes for physical function or QOL. However, after the intervention (t1 to t2), the WALK group showed significant improvement in aerobic capacity (6MWT, P = 0.01), physical (P < 0.01) and functional well-being (P = 0.04), and overall QOL scores (P < 0.01). The CONT group saw no significant changes in physical function or QOL. Effect sizes showed the WALK group had a larger positive effect on physical function and QOL. Minimal clinically important differences in the 6MWT and FACT-BMT were exceeded in the WALK group. CONCLUSION: A multidirectional walking program during the transplant period may be effective at increasing aerobic capacity and QOL for patients receiving HSCT compared with no structured exercise.

Design and Reporting Considerations for Genetic Screening Tests.

Testing asymptomatic individuals for unsuspected conditions is not new to the medical and public health communities. Protocols to develop screening tests are well established. However, the application of screening principles to inherited diseases presents unique challenges. Unlike most screening tests, the natural history and disease prevalence of most rare inherited diseases in an unselected population are unknown. It is difficult or impossible to obtain a truth set cohort for clinical validation studies. As a result, it is not possible to accurately calculate clinical positive and negative predictive values for likely pathogenic variants, which are commonly returned in genetic screening assays. In addition, many of the genetic conditions included in screening panels do not have clinical confirmatory tests. All these elements are typically required to justify the development of a screening test, according to the World Health Organization screening principles. Nevertheless, as the cost of DNA sequencing continues to fall, more individuals are opting to undergo genomic testing in the absence of a clinical indication. Despite the challenges, reasonable estimates can be deduced and used to inform test design strategies. Herein, we review basic test design principles and apply them to genetic screening.

Evaluation of a novel screening method for fetal aneuploidy using cell-free DNA in maternal plasma.

Objective: To evaluate the test performance of a novel sequencing technology using molecular inversion probes applied to cell-free DNA screening for fetal aneuploidy. Methods: Two cohorts were included in the evaluation; a risk-based cohort of women receiving diagnostic testing in the first and second trimesters was combined with stored samples from pregnancies with fetuses known to be aneuploid or euploid. All samples were blinded to testing personnel before being analyzed, and validation occurred after the study closed and results were merged. Results: Using the new sequencing technology, 1414 samples were analyzed. The findings showed sensitivities and specificities for the common trisomies and the sex chromosome aneuploidies at >99% (Trisomy 21 sensitivity 99.2 CI 95.6­99.2; specificity 99.9 CI 99.6­99.9). Positive predictive values among the trisomies varied from 85.2% (Trisomy 18) to 99.0% (Trisomy 21), reflecting their prevalence rates in the study. Comparisons with a meta-analysis of recent cell-free DNA screening publications demonstrated equivalent test performance. Conclusion: This new technology demonstrates equivalent test performance compared with alternative sequencing approaches, and demonstrates that each chromosome can be successfully interrogated using a single probe.

Acute Soy Supplementation Improves 20-km Time Trial Performance, Power, and Speed.

INTRODUCTION: Isoflavones, a chemical class of phytoestrogens found in soybeans and soy products, may have biological functions similar to estradiol. After binding with ERß or perhaps independently of estrogen receptors, isoflavones may augment vascular endothelial relaxation, contributing to improved limb blood flow. PURPOSE: To determine if acute fermented soy extract supplementation influences 20-km time trial cycling performance and cardiac hemodynamics compared with a placebo. METHODS: Subjects included 25 cyclists and triathletes (31 ± 8 yr, V˙O2peak: 55.1 ± 8.4 mL·kg·min). Each subject completed a V˙O2peak assessment, familiarization, and two 20-km time trials in randomized order after ingestion of a fermented soy extract supplement or placebo. The fermented soy extract consisted of 30 g powdered supplement in 16 fl. ounces of water. The placebo contained the same quantities of organic cocoa powder and water. Each trial consisted of 60 min of rest, 30 min at 55% Wpeak, and a self-paced 20-km time trial. RESULTS: Soy supplementation elicited a faster time to 20-km completion (-0.22 ± 0.51 min; -13 s), lower average HR (-5 ± 7 bpm), and significantly greater power (7 ± 3 W) and speed (0.42 ± 0.16 km·h) during the last 5 km of the time trial compared with placebo. Analysis of the results by relative fitness level (<57 vs ≥ 57 mL⋅kg⋅min) indicated that those with a higher level of fitness reaped the largest performance improvement alongside a reduced HR (-5 ± 7 bpm). CONCLUSIONS: Ingestion of a fermented soy extract supplement improved sprint-distance performance through improvements in both power and speed. For those with great aerobic fitness, soy supplementation may help to decrease cardiac demand alongside performance improvement.