Leonardo P. Oliveira

MUSCLE ARCHITECTURE AND STRENGTH: ADAPTATIONS TO SHORT-TERM RESISTANCE TRAINING IN OLDER ADULTS

Introduction: Muscle morphology and architecture changes in response to 6 weeks of progressive resistance training were examined in healthy older adults. Methods: In this randomized, controlled design, muscle strength, quality, and architecture were evaluated with knee extension, DEXA, and ultrasound, respectively, in 25 older adults. Results: Resistance training resulted in significant increases in strength and muscle quality of 32% and 31%, respectively. Cross‐sectional area of the vastus lateralis increased by 7.4% (p ≤ 0.05). Physiological cross‐sectional area (PCSA) of the thigh, a composite measure of muscle architecture, was related significantly to strength (r = 0.57; p ≤ 0.01) and demonstrated a significant interaction after training (p ≤ 0.05). Change in PCSA of the vastus lateralis was associated with change in strength independent of any other measure. Conclusions: Six weeks of resistance training was effective at increasing strength, muscle quality, and muscle morphology in older adult men and women. Muscle Nerve 49:584–592, 2014

Emerging Cardiovascular Risk Factors That Account for a Significant Portion of Attributable Mortality Risk in Chronic Kidney Disease

Chronic kidney disease (CKD) increases cardiovascular risk and mortality. However, traditional cardiovascular risk factors do not adequately account for the substantial increase in mortality observed in CKD. The aim of this study was to examine the relative contributions of novel cardiovascular risk factors to the risk between CKD and mortality. The study population included 4,680 consecutive new patients from a tertiary care preventive cardiology program from 1996 to 2005. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease (MDRD) method. Baseline levels of traditional (low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypertension, triglycerides, total cholesterol, and fasting glucose) and emerging (apolipoproteins A-I and B, lipoprotein[a], fibrinogen, homocysteine, and high-sensitivity C-reactive protein) risk factors were examined. All-cause mortality was obtained from the Social Security Death Index. There were 278 deaths over a median follow-up period of 22 months. CKD (estimated glomerular filtration rate <or=60 ml/min/1.73 m(2)) was strongly associated with mortality after adjusting for traditional cardiovascular risk factors (hazard ratio 2.31, 95% confidence interval 1.77 to 3.11, p<0.001) and with the addition of propensity score (hazard ratio 2.33, 95% confidence interval 1.75 to 3.10, p<0.001). Of all the traditional and emerging risk factors monitored, only the addition of homocysteine and fibrinogen significantly attenuated the association between CKD and mortality (adjusted hazard ratio 1.73, 95% confidence interval 1.23 to 2.34, p<0.001), explaining 38% of the attributable mortality risk from CKD. A significant interaction (p=0.004) between homocysteine and estimated glomerular filtration rate was observed whereby the annual mortality rate in subjects with CKD with homocysteine <10 micromol/L (the bottom tertile) was similar to those with normal renal function (1% per year), whereas homocysteine levels >or=12.5 micromol/L (the top tertile) were associated with a sevenfold greater mortality risk. In conclusion, homocysteine and fibrinogen levels explain nearly 40% of the attributable mortality risk from CKD.

Muscle quality index improves with resistance exercise training in older adults

INTRODUCTION Sarcopenia is currently best described as an age-related decline in skeletal muscle mass and function. However, no consensus exists as to how to best quantify muscle function in older adults. The muscle quality index (MQI) was recently recommended as an ideal evidence-based assessment of functional status in older adults. Nevertheless, the usefulness of MQI to assess physical function is limited by whether it is reflective of muscle qualitative changes to an intervention. Thus, the purpose of this investigation was to determine whether MQI changes in response to resistance exercise training and detraining and how such changes correspond to other recommended measures of physical function proposed by suggested definitions of sarcopenia. METHODS Twenty-five older adults (70.6±6.1y; BMI=28.1±5.4kg·m(-2)) completed a 6-week resistance training program in a wait-list controlled, cross-over design. MQI was determined as power output from timed sit to stand (STS), body mass, and leg length. Gait speed, hand grip strength, get-up-and-go and lean body mass (LBM) were evaluated before and after exercise training and detraining. MQI and functional changes to training and detraining were evaluated with repeated measures ANOVA and clinical interpretations of magnitude based inferences. RESULTS Short term resistance training significantly and clinically improved MQI (203.4±64.31 to 244.3±82.92W), gait time (1.85±0.36 to 1.66±0.27s) and sit to stand performance (13.21±2.51 to 11.05±1.58s). Changes in LBM and hand grip strength were not significant or clinically meaningful. De-training for 6-weeks did not result in significant changes in any measure from post-training performance.

EHR Implementation in a New Clinic: A Case Study of Clinician Perceptions

Driven by the Health Information Technology for Economic and Clinical Health (HITECH) Act large numbers of physicians and hospitals are now implementing electronic health records (EHR) with the general expectation that such systems will improve the quality, safety and efficiency of health care services. Studies of conversions from paper to electronic records paint a mixed picture with healthcare providers pleased with some aspects of their EHRs but dissatisfied with others. These prior studies focused on conversions from paper to electronic records. Many provider impressions, therefore, may have been influenced by reactions to the process of being required to change well established patterns. In order to help separate such reactions from true evaluations of the efficacy of the EHR, we decided to survey the providers in a new health center. To insure that the information gathered was not merely anecdotal, we used a well-established format starting with a semi-structured interview which facilitates analysis and recognition of major themes. We included questions around several important areas including workflow, communication, patient satisfaction, productivity, documentation, and quality of care. Ten main themes emerged: impeding patient flow, hindering communication in office, improving communication after the visit, improving tracking of patient care, spending less time with patients, requiring more training, wanting more features, diminishing productivity, appreciating benefits of templates, and enhancing internal communication. The need for better training appeared to be of especially high importance as it impacted several of the other themes. We believe that our study helps validate the similar concerns expressed in studies of transitions from paper to electronic record systems. Our method may be generally useful to other clinics because it facilitates timely recognition of themes, both positive and negative, that clinicians and clinic managers would want to know at an early stage. Prompt knowledge of such developing themes may help to accentuate the positive aspects of the EHR and to prevent negative themes from developing into serious problems that might be considered serious unintended consequences of EHR usage.

Insights from internet-based remote intrathoracic impedance monitoring as part of a heart failure disease management program.

Changes in intrathoracic impedance (Z) leading to crossing of a derived fluid index (FI) threshold has been associated with heart failure (HF) hospitalization. The authors developed a remote monitoring program as part of HF disease management and prospectively examined the feasibility and resource utilization of monitoring individuals with an implanted device capable of measuring Z. An HF nurse analyzed all transmitted data daily, as they were routinely uploaded as part of quarterly remote device monitoring, and called the patient if the FI crossed the threshold (arbitrarily defined at 60 Omega) to identify clinically relevant events (CREs) that occurred during this period (eg, worsening dyspnea or increase in edema or weight). A total of 400 uploads were completed during the 4-month study period. During this period, 34 patients (18%) had an FI threshold crossing, averaging 0.52 FI threshold crossings per patient-year. Thirty-two of 34 patients contacted by telephone (94%) with FI threshold crossing had evidence of CREs during this period. However, only 6 (18%) had HF hospitalizations, 19 (56%) had reported changes in HF therapy, and 13 (38%) reported drug and/or dietary plan nonadherence. The average data analysis time required was 30 min daily when focusing on those with FI threshold crossing, averaging 8 uploads for review per working day and 5 telephone follow-ups per week. Our pilot observations suggested that Internet-based remote monitoring of Z trends from existing device interrogation uploads is feasible as part of a daily routine of HF disease management.

Association between myosin heavy chain protein isoforms and intramuscular anabolic signaling following resistance exercise in trained men

Resistance exercise stimulates an increase in muscle protein synthesis regulated by intracellular anabolic signaling molecules in a mammalian/mechanistic target of rapamycin (mTOR)‐dependent pathway. The purpose of this study was to investigate acute anabolic signaling responses in experienced, resistance‐trained men, and to examine the association between myosin heavy chain (MHC) isoform composition and the magnitude of anabolic signaling. Eight resistance‐trained men (24.9 ± 4.3 years; 91.2 ± 12.4 kg; 176.7 ± 8.0 cm; 13.3 ± 3.9 body fat %) performed a whole body, high‐volume resistance exercise protocol (REX) and a control protocol (CTL) in a balanced, randomized order. Participants were provided a standardized breakfast, recovery drink, and meal during each protocol. Fine needle muscle biopsies were completed at baseline (BL), 2 h (2H) and 6 h post‐exercise (6H). BL biopsies were analyzed for MHC isoform composition. Phosphorylation of proteins specific to the Akt/mTOR signaling pathway and MHC mRNA expression was quantified. Phosphorylation of p70S6k was significantly greater in REX compared to CTL at 2H (P = 0.04). MHC mRNA expression and other targets in the Akt/mTOR pathway were not significantly influenced by REX. The percentage of type IIX isoform was inversely correlated (P < 0.05) with type I and type IIA MHC mRNA expression (r = −0.69 to −0.93). Maximal strength was also observed to be inversely correlated (P < 0.05) with Type I and Type IIA MHC mRNA expression (r = −0.75 to −0.77) and p70S6k phosphorylation (r = −0.75). Results indicate that activation of p70S6k occurs within 2‐h following REX in experienced, resistance‐trained men. Further, results also suggest that highly trained, stronger individuals have an attenuated acute anabolic response.

Intramuscular anabolic signaling and endocrine response following high volume and high intensity resistance exercise protocols in trained men

Resistance exercise paradigms are often divided into high volume (HV) or high intensity (HI) protocols, however, it is unknown whether these protocols differentially stimulate mTORC1 signaling. The purpose of this study was to examine mTORC1 signaling in conjunction with circulating hormone concentrations following a typical HV and HI lower‐body resistance exercise protocol. Ten resistance‐trained men (24.7 ± 3.4 years; 90.1 ± 11.3 kg; 176.0 ± 4.9 cm) performed each resistance exercise protocol in a random, counterbalanced order. Blood samples were obtained at baseline (BL), immediately (IP), 30 min (30P), 1 h (1H), 2 h (2H), and 5 h (5H) postexercise. Fine needle muscle biopsies were completed at BL, 1H, and 5H. Electromyography of the vastus lateralis was also recorded during each protocol. HV and HI produced a similar magnitude of muscle activation across sets. Myoglobin and lactate dehydrogenase concentrations were significantly greater following HI compared to HV (P = 0.01–0.02), whereas the lactate response was significantly higher following HV compared to HI (P = 0.003). The growth hormone, cortisol, and insulin responses were significantly greater following HV compared to HI (P = 0.0001–0.04). No significant differences between protocols were observed for the IGF‐1 or testosterone response. Intramuscular anabolic signaling analysis revealed a significantly greater (P = 0.03) phosphorylation of IGF‐1 receptor at 1H following HV compared to HI. Phosphorylation status of all other signaling proteins including mTOR, p70S6k, and RPS6 were not significantly different between trials. Despite significant differences in markers of muscle damage and the endocrine response following HV and HI, both protocols appeared to elicit similar mTORC1 activation in resistance‐trained men.

C‐terminal agrin fragment is inversely related to neuromuscular fatigue in older men

Introduction: The aim of this study was to examine the relationship between serum C‐terminal agrin fragment (CAF) concentrations and neuromuscular fatigue in older adults. Methods: Twenty‐two healthy older men and women volunteered for this study. Resting fasted blood samples were collected and prepared for measurement of serum CAF concentration by a commercially available ELISA kit. The onset of neuromuscular fatigue was measured by monitoring electromyographic fatigue curves from the vastus lateralis muscle using the physical working capacity at fatigue threshold (PWCFT) test. Results: A significant inverse correlation for men was observed between CAF and PWCFT (r = −0.602; P = 0.05), but not for women (r = 0.208; P = 0.54). After controlling for age and body mass index, significant correlations (r = −0.69; P = 0.042) remained for men, but not for women (r = 0.12; P = 0.76). Conclusions: These data suggest that serum CAF concentrations were significantly related to the onset of neuromuscular fatigue independent of age and BMI in men only. Muscle Nerve 51: 132–133, 2015

Monocyte Recruitment after High-Intensity and High-Volume Resistance Exercise.

UNLABELLED The innate immune response is generally considered to have an important role in tissue remodeling after resistance exercise. PURPOSE The purpose of this study was to compare changes in markers of monocyte recruitment after an acute bout of high-intensity (HVY) versus high-volume (VOL) lower-body resistance exercise. METHODS Ten resistance-trained men (24.7 ± 3.4 yr, 90.1 ± 11.3 kg, 176.0 ± 4.9 cm) performed each protocol in a randomized, counterbalanced order. Blood samples were collected at baseline, immediately (IP), 30 min (30P), 1 h (1H), 2 h (2H), and 5 h (5H) postexercise. Plasma concentrations of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α), myoglobin, and cortisol were measured via assay. Tumor necrosis factor receptor 1 (TNFr1), macrophage-1 antigen (cluster of differentiation 11b [CD11b]), and C-C chemokine receptor 2 (CCR2) expression levels were measured using flow cytometry. TNFr1 and CD11b were assessed on CD14CD16 monocytes, whereas CCR2 was assessed on CD14 monocytes. RESULTS Plasma myoglobin concentrations were significantly greater after HVY compared with VOL (P < 0.001). Changes in plasma TNF-α, MCP-1, and expression levels of CCR2 and CD11b were similar between HVY and VOL. When collapsed across groups, TNF-α was significantly increased at IP, 30P, 1H, and 2H (P values < 0.05), whereas MCP-1 was significantly elevated at all postexercise time points (P values < 0.05). CCR2 expression on CD14 monocytes was significantly lower at IP, 1H, 2H, and 5H (P values < 0.05). CD11b expression on CD14 CD16 was significantly greater at IP (P < 0.014) and 1H (P = 0.009). TNFr1 expression did not differ from baseline at any time point. Plasma cortisol concentrations did not seem to be related to receptor expression. CONCLUSIONS Results indicate that both HVY and VOL protocols stimulate a robust proinflammatory response. However, no differences were noted between resistance exercise training paradigms.

Comparison of Two β-Alanine Dosing Protocols on Muscle Carnosine Elevations

ABSTRACT Objective: β-alanine (BA) is a nonproteogenic amino acid that combines with histidine to form carnosine. The amount taken orally in individual doses, however, is limited due to symptoms of paresthesia that are associated with higher doses. The use of a sustained-release formulation has been reported to reduce the symptoms of paresthesia, suggesting that a greater daily dose may be possible. The purpose of the present study was to determine whether increasing the daily dose of BA can result in a similar increase in muscle carnosine in a reduced time. Methods: Eighteen men and twelve women were randomized into either a placebo (PLC), 6-g BA (6G), or 12-g BA (12G) groups. PLC and 6G were supplemented for 4 weeks, while 12G was supplemented for 2 weeks. A resting blood draw and muscle biopsy were obtained prior to (PRE) and following (POST) supplementation. Plasma and muscle metabolites were measured by high-performance liquid chromatography. The loss in peak torque (ΔPT) was calculated from maximal isometric contractions before and after 250 isokinetic kicks at 180°·sec−1 PRE and POST. Results: Both 12G (p = 0.026) and 6G (p = 0.004) increased muscle carnosine compared to PLC. Plasma histidine was decreased from PRE to POST in 12G compared to PLC (p = 0.002) and 6G (p = 0.001), but no group x time interaction (p = 0.662) was observed for muscle histidine. No differences were observed for any hematological measure (e.g., complete blood counts) or in symptoms of paresthesia among the groups. Although no interaction was noted in ΔPT, a trend (p = 0.073) was observed. Conclusion: Results of this investigation indicate that a BA supplementation protocol of 12 g/d−1, using a sustained-release formulation, can accelerate the increase in carnosine content in skeletal muscle while attenuating paresthesia.