Mitochondrial function following downhill and/or uphill exercise training in rats

Introduction: The goal of this study was to compare the effects of downhill (DH), uphill (UH), and UH‐DH exercise training, at the same metabolic rate, on exercise capacity and skeletal muscle mitochondrial function. Methods: Thirty‐two Wistar rats were separated into a control and 3 trained groups. The trained groups exercised for 4 weeks, 5 times per week at the same metabolic rate, either in UH, DH, or combined UH‐DH. Twenty‐four hours after the last training session, the soleus, gastrocnemius, and vastus intermedius muscles were removed for assessment of mitochondrial respiration. Results: Exercise training, at the same metabolic rate, improved maximal running speed without specificity for exercise modalities. Maximal fiber respiration was enhanced in soleus and vastus intermedius in the UH group only. Conclusions: Exercise training, performed at the same metabolic rate, improved exercise capacity, but only UH‐trained rats enhanced mitochondrial function in both soleus and vastus intermedius skeletal muscle. Muscle Nerve 54 : 925–935, 2016     

Functional connectivity and information flow of the respiratory neural network in chronic obstructive pulmonary disease

Breathing involves a complex interplay between the brainstem automatic network and cortical voluntary command. How these brain regions communicate at rest or during inspiratory loading is unknown. This issue is crucial for several reasons: (i) increased respiratory loading is a major feature of several respiratory diseases, (ii) failure of the voluntary motor and cortical sensory processing drives is among the mechanisms that precede acute respiratory failure, (iii) several cerebral structures involved in responding to inspiratory loading participate in the perception of dyspnea, a distressing symptom in many disease. We studied functional connectivity and Granger causality of the respiratory network in controls and patients with chronic obstructive pulmonary disease (COPD), at rest and during inspiratory loading. Compared with those of controls, the motor cortex area of patients exhibited decreased connectivity with their contralateral counterparts and no connectivity with the brainstem. In the patients, the information flow was reversed at rest with the source of the network shifted from the medulla towards the motor cortex. During inspiratory loading, the system was overwhelmed and the motor cortex became the sink of the network. This major finding may help to understand why some patients with COPD are prone to acute respiratory failure. Network connectivity and causality were related to lung function and illness severity. We validated our connectivity and causality results with a mathematical model of neural network. Our findings suggest a new therapeutic strategy involving the modulation of brain activity to increase motor cortex functional connectivity and improve respiratory muscles performance in patients. Hum Brain Mapp 37:2736–2754, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Photochemical treatment of platelet concentrates with amotosalen and long-wavelength ultraviolet light inactivates a broad spectrum of pathogenic bacteria

BACKGROUND: Bacterial contamination of platelet (PLT) concentrates can result in transfusion-transmitted sepsis. A photochemical treatment (PCT) process with amotosalen HCl and long-wavelength ultraviolet light (UVA), which cross-links nucleic acids, was developed to inactivate bacteria and other pathogens in PLT concentrates. STUDY DESIGN AND METHODS: High titers of pathogenic aerobic and anaerobic Gram-positive bacteria (10 species), aerobic Gram-negative bacteria (7 species), and spirochetes (2 species) were added to single-donor PLT concentrates containing 3.0 x 10(11) to 6.0 x 10(11) PLTs in approximately 300 mL of 35 percent plasma and 65 percent PLT additive solution (InterSol, Baxter Healthcare) or saline. After PCT with 150 micro mol per L amotosalen and 3 J per cm(2) UVA, residual bacterial levels were detected by sensitive microbiologic methods. RESULTS: The level of inactivation of viable bacteria was expressed as log reduction. Log reduction of Gram-positive bacteria for Staphylococcus epidermidis was > 6.6; for Staphylococcus aureus, 6.6; for Streptococcus pyogenes, > 6.8; for Listeria monocytogenes, > 6.3; for Corynebacterium minutissimum, > 6.3; for Bacillus cereus (vegetative), > 5.5; for Lactobacillus sp., > 6.4; for Bifidobacterium adolescentis, > 6.0; for Propionibacterium acnes, > 6.2; and for Clostridium perfringens, > 6.5. Log reduction of Gram-negative bacteria for Escherichia coli was > 6.4; for Serratia marcescens, > 6.7; for Klebsiella pneumoniae, > 5.6; for Pseudomonas aeruginosa, 4.5; for Salmonella choleraesuis, > 6.2; for Yersinia enterocolitica, > 5.9; and for Enterobacter cloacae, 5.9. Log reduction of spirochetes for Treponema pallidum was 6.8 to 7.0, and for Borrelia burgdorferi, > 6.9. CONCLUSION: PCT inactivates high levels of a broad spectrum of pathogenic bacteria. The inactivation of bacteria in PLT concentrates offers the potential to prospectively prevent PLT-transfusion-associated bacteremia.     

CAR-dependent and CAR-independent pathways of adenovirus vector-mediated gene transfer and expression in human fibroblasts

Primary fibroblasts are not efficiently transduced by subgroup C adenovirus (Ad) vectors because they express low levels of the high-affinity Coxsackie virus and adenovirus receptor (CAR). In the present study, we have used primary human dermal fibroblasts as a model to explore strategies by which Ad vectors can be designed to enter cells deficient in CAR. Using an Ad vector expressing the human CAR cDNA (AdCAR) at high multiplicity of infection, primary fibroblasts were converted from being CAR deficient to CAR sufficient. Efficiency of subsequent gene transfer by standard Ad5-based vectors and Ad5-based vectors with alterations in penton and fiber was evaluated. Marked enhancement of binding and transgene expression by standard Ad5 vectors was achieved in CAR-sufficient fibroblasts. Expression by AdDeltaRGDbetagal, an Ad5-based vector lacking the arginine-glycine-aspartate (RGD) alphaV integrin recognition site from its penton base, was achieved in CAR-sufficient, but not CAR-deficient, cells. Fiber-altered Ad5-based vectors, including (a) AdF(pK7)betagal (bearing seven lysines on the end of fiber) (b) AdF(RGD)betagal (bearing a high-affinity RGD sequence on the end of fiber), and (c) AdF9sK betagal (bearing a short fiber and Ad9 knob), demonstrated enhanced gene transfer in CAR-deficient fibroblasts, with no further enhancement in CAR-sufficient fibroblasts. Together, these observations demonstrate that CAR deficiency on Ad targets can be circumvented either by supplying CAR or by modifying the Ad fiber to bind to other cell-surface receptors.     

The reliability of upper- and lower-extremity strength testing in a community survey of older adults

OBJECTIVE: To examine the stability (test-retest reliability) of strength measures in older adults obtained by nontherapist lay examiners by using a hand-held portable muscle testing device (Nicholas Manual Muscle Tester). DESIGN: A prospective relational design was used to collect test-retest data for 1 male subject by using 27 lay raters who completed intensive training in manual muscle. SETTING: Data were collected from older Mexican-American adults living in the community. PARTICIPANTS: Twenty-seven lay raters who completed intensive training in manual muscle testing for a field-based assessment and interview of older adults and 63 Mexican-American subjects completing wave 4 of the Hispanic Established Populations for the Epidemiologic Study of the Elderly. INTERVENTIONS: Training involved reviewing a manual describing each testing position followed by approximately 6 hours of instruction and practice supervised by an experienced physical therapist. Lay raters then collected test-retest information on older Mexican-American subjects. MAIN OUTCOME MEASURE: Stability (test-retest) for a portable manual muscle testing device. RESULTS: Intraclass correlation coefficients (ICCs) were computed for the 27 lay raters examining 1 male subject (2 trials) and 12 lay raters assessing 63 older Mexican-American adults (1 practice and 2 trials recorded). The ICC values for the first 27 lay raters ranged from .74 to.96. The ICC values for the latter 12 lay raters ranged from .87 to.98. No differences were found in ICC values between male or female subjects. CONCLUSIONS: Stable and consistent information for upper- and lower-extremity strength was collected from the older adults participating in this study. The results suggest reliable information can be obtained by lay raters using a portable manual muscle testing device if the examiners receive intensive training.     

Assessment of nutritional status in organ transplant: is transthyretin a reliable indicator?

Transthyretin has been proposed as a nutritional index to screen for malnutrition and monitor the metabolic response to dietary intervention. In the presence of inflammation, circulating transthyretin levels drop regardless of optimal caloric intake. In this case, due to its rapid turnover, the pattern of transthyretin, monitored by means of repeated measures, could indicate the metabolic status (catabolism vs. anabolism). The aim of this review is to investigate the possible role of transthyretin as a nutritional parameter in organ transplantation. The literature on nutritional assessment in transplantation was reviewed and all the data regarding circulating transthyretin levels were analyzed. It appears that, on the one hand, the transthyretin level reflects closely dietary manipulations; on the other hand, it is affected by the inflammatory status. Consequently, interpretation could be difficult during the acute phase immediately after the transplant. Moreover, the role of transthyretin in monitoring the hepatic synthetic function in liver transplant is discussed. In conclusion, transthyretin is a reliable indicator of nutritional status in transplant candidates and potentially useful in the post-transplant phase if the inflammatory status is taken into account.