Metagenomic Next-Generation Sequencing for Identification and Quantitation of Transplant-Related DNA Viruses.

Infections with DNA viruses are frequent causes of morbidity and mortality in transplant recipients. This study describes the analytical and clinical performance characteristics of the Arc Bio Galileo Pathogen Solution, an all-inclusive metagenomic next-generation sequencing (mNGS) reagent and bioinformatics pipeline that allows the simultaneous quantitation of 10 transplant-related double-stranded DNA (dsDNA) viruses (adenovirus [ADV], BK virus [BKV], cytomegalovirus [CMV], Epstein-Barr virus [EBV], human herpesvirus 6A [HHV-6A], HHV-6B, herpes simplex virus 1 [HSV-1], HSV-2, JC virus [JCV], and varicella-zoster virus [VZV]). The mNGS 95% limit of detection ranged from 14 copies/ml (HHV-6) to 191 copies/ml (BKV), and the lower limit of quantitation ranged from 442 international units (IU)/ml (EBV) to 661 copies/ml (VZV). An evaluation of 50 residual plasma samples with at least one DNA virus detected in prior clinical testing showed a total percent agreement of mNGS and quantitative PCR (qPCR) of 89.2% (306/343), with a κ statistic of 0.725. The positive percent agreement was 84.9% (73/86), and the negative percent agreement was 90.7% (233/257). Furthermore, mNGS detected seven subsequently confirmed coinfections that were not initially requested by qPCR. Passing-Bablok regression revealed a regression line of y = 0.953x + 0.075 (95% confidence interval [CI] of the slope, 0.883 to 1.011; intercept, -0.100 to 0.299), and Bland-Altman analysis (mNGS - qPCR) showed a slight positive bias (0.28 log10 concentration; 95% limits of agreement, -0.62 to 1.18). In conclusion, the mNGS-based Galileo pipeline demonstrates analytical and clinical performance comparable to that of qPCR for transplant-related DNA viruses.

Efficacy of Acute Intermittent Hypoxia on Physical Function and Health Status in Humans with Spinal Cord Injury: A Brief Review.

Spinal cord injury (SCI) results in a loss of motor and sensory function and is consequent with reductions in locomotion, leading to a relatively sedentary lifestyle which predisposes individuals to premature morbidity and mortality. Many exercise modalities have been employed to improve physical function and health status in SCI, yet they are typically expensive, require many trained clinicians to implement, and are thus relegated to specialized rehabilitation centers. These characteristics of traditional exercise-based rehabilitation in SCI make their application relatively impractical considering the time-intensive nature of these regimens and patients' poor access to exercise. A promising approach to improve physical function in persons with SCI is exposure to acute intermittent hypoxia (IH) in the form of a small amount of sessions of brief, repeated exposures to low oxygen gas mixtures interspersed with normoxic breathing. This review summarizes the clinical application of IH in humans with SCI, describes recommended dosing and potential side effects of IH, and reviews existing data concerning the efficacy of relatively brief exposures of IH to modify health and physical function. Potential mechanisms explaining the effects of IH are also discussed. Collectively, IH appears to be a safe, time-efficient, and robust approach to enhance physical function in chronic, incomplete SCI.

Chronic activity-based therapy does not improve body composition, insulin-like growth factor-I, adiponectin, or myostatin in persons with spinal cord injury.

UNLABELLED: Spinal cord injury (SCI) induces dramatic changes in body composition including reductions in fat-free mass (FFM) and increases in fat mass (FM). OBJECTIVE: To examine changes in body composition in response to chronic activity-based therapy (ABT) in persons with SCI. DESIGN: Longitudinal exercise intervention. METHODS: Seventeen men and women with SCI (mean age=36.1±11.5 years) completed 6 months of supervised ABT consisting of load bearing, resistance training, locomotor training, and functional electrical stimulation. At baseline and after 3 and 6 months of ABT, body weight, body fat, and FFM were assessed using dual-energy X-ray absorptiometry, and fasting blood samples were obtained to assess changes in insulin-like growth factor-I (IGF-I), adiponectin, and myostatin. RESULTS: Across all subjects, there was no change (P>0.05) in body weight, percent body fat, or FFM of the leg, arm, or trunk, whereas whole-body FFM declined (P=0.02, 50.4±8.4 to 49.2±7.4 kg). No changes (P=0.21-0.41) were demonstrated in IGF-I, adiponectin, or myostatin during the study. CONCLUSIONS: Chronic ABT focusing on the lower extremity does not slow muscle atrophy or alter body fat, body mass, or regional depots of FFM in persons with SCI. Further, it does not induce beneficial changes in adiponectin, myostatin, or IGF-I. Alternative exercise-based therapies are needed in SCI to reverse muscle atrophy and minimize the onset of related health risks.

Change in neuroplasticity-related proteins in response to acute activity-based therapy in persons with spinal cord injury.

BACKGROUND: Activity-based therapy (ABT) focuses on regaining motor and sensory function below the level of the lesion in persons with a spinal cord injury (SCI). This is accomplished through repetitive training of specific motor tasks. Research has shown that ABT may increase neuroplasticity in the rat and human spinal cord. OBJECTIVE: The primary aim of this study was to examine acute alterations in neuroplasticity-related proteins during ABT in persons with SCI. METHODS: Volunteers were current participants in an ABT program and consisted of 12 men and 3 women (age, 31.8 ± 10.9 years) with chronic SCI (injury duration, 63.9 ± 54.4 months). A single 2-hour bout of ABT consisted of standing load bearing, body weight-supported treadmill training, whole body vibration, and functional electrical stimulation. Blood samples were obtained at baseline and immediately after completion of each modality to determine serum levels of brain-derived neurotrophic factor (BDNF), prolactin, and cortisol. RESULTS: One-way analysis of variance (ANOVA) with repeated measures was used to examine differences in proteins over time. Results revealed baseline levels of BDNF (2.37 ± 1.41 ng/mL) that were lower than previous research has demonstrated in persons with SCI. No change in BDNF or cortisol was found, although prolactin was significantly reduced in response to ABT. CONCLUSION: Despite the length of the bout, acute changes in BDNF were not observed. Whether different intensities or modalities of ABT may promote acute increases in serum BDNF in individuals with SCI remains to be determined and further study is merited.

Effect of chronic activity-based therapy on bone mineral density and bone turnover in persons with spinal cord injury.

PURPOSE: Osteoporosis is a severe complication of spinal cord injury (SCI). Many exercise modalities are used to slow bone loss, yet their efficacy is equivocal. This study examined the effect of activity-based therapy (ABT) targeting the lower extremities on bone health in individuals with SCI. METHODS: Thirteen men and women with SCI (age and injury duration = 29.7 ± 7.8 and 1.9 ± 2.7 years) underwent 6 months of ABT. At baseline and after 3 and 6 months of training, blood samples were obtained to assess bone formation (serum procollagen type 1 N propeptide (PINP) and bone resorption (serum C-terminal telopeptide of type I collagen (CTX), and participants underwent dual-energy X-ray absorptiometry scans to obtain total body and regional estimates of bone mineral density (BMD). RESULTS: Results demonstrated significant increases (p < 0.05) in spine BMD (+4.8 %; 1.27 ± 0.22-1.33 ± 0.24 g/cm(2)) and decreases (p < 0.01) in total hip BMD (-6.1 %; 0.98 ± 0.18-0.91 ± 0.16 g/cm(2)) from 0 to 6 months of training. BMD at the bilateral distal femur (-7.5 to -11.0 %) and proximal tibia (- 8.0 to -11.2 %) declined but was not different (p > 0.05) versus baseline. Neither PINP nor CTX was altered (p > 0.05) with training. CONCLUSIONS: Chronic activity-based therapy did not reverse bone loss typically observed soon after injury, yet reductions in BMD were less than the expected magnitude of decline in lower extremity BMD in persons with recent SCI.

Activity-based Therapies in Spinal Cord Injury:: Clinical Focus and Empirical Evidence in Three Independent Programs.

This article summarizes presentations of a symposium examining the potential impact of activity-based therapies (ABT) in promoting neurological and functional recovery after spinal cord injury (SCI). The symposium addressed 3 key questions concerning activity-based therapy in SCI: (1) What clinical approaches are used? (2) Is there empirical evidence supporting efficacy of ABT in promoting neurological recovery and improving overall function, health, and quality of life? (3) What are the issues related to long-term viability of ABT?

Acute energy cost of multi-modal activity-based therapy in persons with spinal cord injury.

OBJECTIVE: To examine acute energy costs of multi-modal activity-based therapy (ABT) in men and women with spinal cord injury (SCI). STUDY DESIGN: Descriptive case series. SETTING: An outpatient center in California. PARTICIPANTS: Seven men and women (age = 28.3 ± 11.6 years; duration of injury = 4.3 ± 2.5 years) with injury levels ranging from C5 to T8. INTERVENTION: Activity-based therapy. OUTCOME MEASURES: Oxygen uptake (VO(2)), energy expenditure (kcal/minute), SCI Metabolic Equivalent of Task (MET) (1 MET = 2.7 ml/kg/minute). RESULTS: Oxygen uptake (VO(2)) during ABT ranged from 5.10 to 8.62 ml/kg/minute, with VO(2) consistently higher during modalities involving load bearing versus non-load bearing (P = 0.08). SCI MET values ranged from 1.89 to 3.24 and were significantly higher in subjects with mid-thoracic injury versus low-cervical injury (P = 0.01). CONCLUSION: Data reveal that multi-modal ABT increases VO(2) in persons with SCI, but energy expenditure is relatively low. Strategies must be identified to optimize energy expenditure in the SCI to reduce health risks. Modalities involving load bearing seem to be superior to non-load-bearing activities. VO(2) was greater in response to load-bearing modalities than non-load-bearing modalities. It remains to be determined whether chronic ABT enhances cardiovascular fitness and reduces disease risks in this population.

A tele-assessment system for monitoring treatment effects in subjects with spinal cord injury.

We developed a method for remote measurement of balance and leg force in patients with spinal cord injury (SCI). In a group of 21 patients, both telemedicine and conventional clinical assessments were conducted at baseline and six months later. Telemedicine assessments were successfully acquired and transmitted at first attempt. The time required to set up the telemedicine equipment, position the subject, perform the measurements, and then send the data to the university laboratory was approximately 30 minutes. After six months, several motor and sensory functions showed significant changes. There were significant correlations between changes in remotely-measured leg force and changes in several of the American Spinal Injury Association (ASIA) sensory and motor scores. Changes in balance did not show any significant correlations with changes in the ASIA scores. Intra-rater reliability was better than inter-rater reliability. Use of telemedicine to remotely monitor changes in patients with SCI appears promising.

Substrate metabolism during exercise in the spinal cord injured.

The primary aim of the study was to examine substrate metabolism during combined passive and active exercise in individuals with spinal cord injury (SCI). Nine men and women with SCI (mean age 40.6 +/- 3.4 years) completed two trials of submaximal exercise 1 week apart. Two maintained a complete injury and seven had an incomplete injury. Level of injury ranged from thoracic (T4-T6 and T10) to cervical (four C5-C6 and three C6-C7 injuries). During two bouts separated by 1 week, subjects completed two 30 min sessions of active lower-body and passive upper-body exercise, during which heart rate (HR) and gas exchange data were continuously assessed. One-way analysis of variance with repeated measures was used to examine differences in all variables over time. Results demonstrated significant increases (P < 0.05) in HR and oxygen uptake (VO(2)) from rest to exercise. Respiratory exchange ratio (RER) significantly increased (P < 0.05) during exercise from 0.85 +/- 0.02 at rest to 0.95 +/- 0.01 at the highest cadence, reflecting increasing reliance on carbohydrate from 50.0 to 83.0% of energy metabolism. Data demonstrate a large reliance on carbohydrate utilization during 30 min of exercise in persons with SCI, with reduced contribution of lipid as exercise intensity was increased. Strategies to reduce carbohydrate utilization and increase lipid oxidation in this population should be addressed.

Efficacy of a new rehabilitative device for individuals with spinal cord injury.

BACKGROUND/OBJECTIVE: Regular exercise is required in persons with spinal cord injury (SCI) to reduce the deleterious effects of chronic paralysis. The primary aims of the study were to examine responses to passive and active exercise on a new rehabilitative device for persons with SCI and to examine reliability of these responses over 2 days of testing. METHODS: Nine men and women with chronic SCI completed the study, 2 with a complete injury and 7 with an incomplete injury. The level of injury ranged from thoracic (T4-T6 and T10) to cervical (4 with C5-C6 and 3 with C6-C7 injuries). They completed 2 30-minute sessions of active lower-body and passive upper-body exercise, during which heart rate (HR), blood pressure (BP), gas exchange data, rating of perceived exertion (RPE), and oxygen-hemoglobin saturation were continuously assessed. DATA ANALYSIS: One-way ANOVA with repeated measures was used to examine differences in all variables over time. RESULTS: Results demonstrated significant increases (P < 0.05) in HR, systolic BP, RPE, and oxygen uptake (V(O2)) from rest to exercise. No change (P > 0.05) in diastolic BP or oxygen-hemoglobin saturation was evident. Cronbach's alpha values for HR, systolic BP, and V(O2) recorded over both days of testing ranged from 0.79 to 0.97, indicating adequate consistency. CONCLUSIONS: Data demonstrated that exercise on this device significantly increases HR, V(O2), and systolic BP compared to rest. However, its efficacy for long-term rehabilitation, especially in regular exercisers with SCI, is unknown.