Neurotization Improves Contractile Forces of Tissue-Engineered Skeletal Muscle

Engineered functional skeletal muscle would be beneficial in reconstructive surgery. Our previous work successfully generated 3-dimensional vascularized skeletal muscle in vivo. Because neural signals direct muscle maturation, we hypothesized that neurotization of these constructs would increase their contractile force. Additionally, should neuromuscular junctions (NMJs) develop, indirect stimulation (via the nerve) would be possible, allowing for directed control. Rat myoblasts were cultured, suspended in fibrin gel, and implanted within silicone chambers around the femoral vessels and transected femoral nerve of syngeneic rats for 4 weeks. Neurotized constructs generated contractile forces 5 times as high as the non-neurotized controls. Indirect stimulation via the nerve elicited contractions of neurotized constructs. Curare administration ceased contraction in these constructs, providing physiologic evidence of NMJ formation. Histology demonstrated intact muscle fibers, and immunostaining positively identified NMJs. These results indicate that neurotization of engineered skeletal muscle significantly increases force generation and causes NMJs to develop, allowing indirect muscle stimulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63133/1/ten.2007.0003.pd

Cross-validation of a Prediction Equation for Energy Expenditure of an Acute Resistance Exercise Bout

Previously, our laboratory introduced a regression equation for predicting net kcal consumption of a resistance exercise (RE) bout: Total net kcal = 0.874(height, cm) - 0.596(age, years) - 1.016(fat mass, kg) + 1.638(lean mass, kg) + 2.461(total volume x 10-3) - 110.742 (R2 = 0.773, SEE=28.5 kcal). PURPOSE: The purpose of this study was to validate this regression equation using the same variables as predictors. METHODS: Forty-seven healthy, active subjects (23 men, 24 women, 20-58 yrs, 173.5 ± 10.5 cm, 85.5 ± 19.0 kg, VO2max 36.0 ± 8.4 ml/kg/min) were randomly divided into validation and cross-validation groups (nv = 24, ncv = 23). The validation group’s data was used to develop an equation to predict net kcal consumption, which was applied to the cross-validation group’s data to estimate net kcal consumption. Similarly, a prediction equation was derived from the cross-validation group’s raw data and applied to that of the validation group. The strength of the relationship between each group’s measured and estimated net kcal consumption was assessed via correlational analysis. RESULTS: Multiple linear regression yielded the following estimates of net kcal consumption: validation net kcal = 1.125(height, cm) – 0.662(age, years) – 0.800(fat mass, kg) + 1.344(lean mass, kg) + 2.278(total volume x 10-3) – 144.846 (R2 = 0.751, p \u3c 0.0001, SEE=29.7 kcal); cross-validation net kcal = 0.515(height, cm) - 0.520(age, years) - 1.220(fat mass, kg) + 1.995(lean mass, kg) + 2.620(total volume x 10-3) – 59.988 (R2 = 0.823, p \u3c 0.0001, SEE=29.2 kcal). These equations had a cross-validation coefficient of 0.902 and a double cross-validation coefficient of 0.863. CONCLUSION: The strong relationship between the measured and estimated net kcal consumption of both the cross-validation and validation group lead us to conclude that the regression equation derived by this laboratory is valid for estimating net energy expenditure for a total RE bout

Significant Predictors of Nonalcoholic Fatty Liver Disease in Texas Firefighters

Risk factors for Nonalcoholic Fatty Liver Disease (NAFLD) include obesity, hypertension, dyslipidemia, and diabetes mellitus. Not only are these prevalent in the general US population, but they are also present at high rates in a specific subset responsible for public safety – firefighters. PURPOSE: The aim of the present study is to use logistic regression to predict the likelihood of occurrence of NAFLD in firefighters using a subset of health-related factors associated with common cardiometabolic risk factors. METHODS: Data were collected on 136 firefighters (128 males, 8 females; 36.3 ± 9.0 yrs; 95.7 ± 17.0 kg; 178.9 ± 7.4 cm; 29.8 ± 4.2 kg/m2) participating in FITLIFE, a university-based fitness program at Texas A&M University. Nominal logistic regression with stepwise removal was used to estimate the best model to predict fatty liver disease. Stepwise removal identified resting systolic blood pressure (RSBP, mm HG), Body Mass Index (BMI, kg/m2), visceral adipose tissue (VAT, cm2), whether or not has hypertension or is on medication (HTNMED; 0=No,1=Yes), and plasma triglyceride concentrations (TG, mg/dL) as independent predictors (p\u3c0.05). Odds ratios (OR) were calculated to determine the change in the odds of NAFLD per unit increase in each predictor. RESULTS: Logistic regression yielded the following equation to predict the probability of developing NAFLD: Logit = -22.5176 + 0.0918(RSBP) + 0.2154(BMI) + 0.0065(TG) + 0.0161(VAT) + 1.830(HTNMED) (R2 = 0.4655, p \u3c 0.001). Of the predictors, the ORs from largest to smallest were 6.235, 1.240, 1.096, 1.016, and 1.002 for HTNMED, BMI, RSBP, VAT, and TG, respectively. CONCLUSION: Using RSBP, BMI, VAT, TG, and HTNMED as predictors, this study demonstrates that the probability of developing NAFLD in Texas firefighters can be reasonably predicted. This regression model and individual predictors may be used by health practitioners as a cost-effective screening tool to identify those at higher risk for NAFLD

A comprehensive review of the PARTNER trial

ObjectivePercutaneous transcatheter aortic valve replacement was introduced in 2002, but its effectiveness remained to be assessed.MethodsA prospective, randomized trial (the Placement of Aortic Transcatheter Valves, or PARTNER) was designed with 2 arms: PARTNER A (n = 699) for high-risk surgical patients (Society of Thoracic Surgeons score >10%, surgeon assessed risk of mortality >15%) and PARTNER B (n = 358, patients inoperable by assessment of 2 surgeons). PARTNER A patients were divided into femoral artery access transcatheter aortic valve replacement or none (n = 207), and then randomized to open aortic valve replacement (n = 351) or device (n = 348). Inclusion criteria included valve area <0.8 cm2, gradient >40 mm Hg or peak >64 mm Hg, and survival >1 year. The end point of the study was 1-year mortality.ResultsThirty-day mortality for PARTNER A was 3.4% for transcatheter aortic valve replacement and 6.5% for aortic valve replacement; 1-year mortality was 24.2% and 26.8%, respectively (P = .001 for noninferiority). The respective prevalence of stroke was 3.8% and 2.1% (P = .2), although for all neurologic events, the difference between transcatheter aortic valve replacement and aortic valve replacement was significant (P = .04), including 4.6% for femoral artery access transcatheter aortic valve replacement versus 1.4% for open aortic valve replacement (P = .05). For PARTNER B—transcatheter aortic valve replacement versus medical treatment—30-day mortality was 5.0% versus 2.8% (P = .41), and at 1 year, mortality was 30.7% versus 50.7% (P < .001), respectively. Hospitalization cost of transcatheter aortic valve replacement for PARTNER B was $78,542, or$50,200 per year of life gained. Analysis of PARTNER A strokes showed that hazard with transcatheter aortic valve replacement peaked early, but thereafter remained constant in relation to aortic valve replacement. Two-year PARTNER A data showed paravalvular regurgitation was associated with increased mortality, even when mild (P < .001). Continued access to transapical transcatheter aortic valve replacement (n = 853) showed a mortality of 8.2% and decline in strokes to 2.0%. Of the 1801 Cleveland Clinic patients reviewed to December 2010, 214 (12%) underwent transcatheter aortic valve replacement with a mortality of 1%; in 2011, 105 underwent transcatheter aortic valve replacement: 34 transapical aortic valve replacement, with no deaths, and 71 femoral artery access aortic valve replacement with 1 death.ConclusionsThe PARTNER A and B trials showed that survival has been remarkably good, but stroke and perivalvular leakage require further device development

High Fat Relative to Low Fat Ground Beef Consumption Lowers Blood Pressure and Does Not Negatively Alter Arterial Stiffness

Beef consumption has been stigmatized as an unhealthy dietary choice. However, randomized control trials to support this claim are lacking. PURPOSE: To examine the effect of low-fat (5%) and high-fat (25%) ground beef consumption on blood pressure (BP) and carotid-femoral pulse wave velocity (PWV).METHODS: Twenty-three male subjects (age 40±11 yrs, height 177.4±6.7 cm, weight 97.3±25.0 kg, lean mass 64.5±9.5 kg, fat mass 30.6±19.1 kg) volunteered to participate in this cross-over design study. Each participant completed two, 5-week ground beef interventions in a randomized order with a 4-week washout period in-between. All participants visited the lab four times after an overnight fast. Each visit to the lab consisted of supine BP, dual energy x-ray absorptiometry (DXA) scan to assess body composition, and PWV analysis. The PWV recording was assessed on the right carotid and femoral arteries. The distance used for the PWV calculation was 80% of the actual distance between carotid and femoral sites. All PWV measures were completed according to previously published procedures (Van Bortel, 2011). BP and PWV results were analyzed separately via 2x2 repeated measures ANOVA. RESULTS: Our results indicate there was a significant decrease in systolic BP (p=0.01) following the high-fat ground beef intervention compared to the low-fat. The BP values for low-fat beef and high-fat beef are 120/74 and 116/73 mmHg, respectively. Further, there were no significant differences between the PWV measures. CONCLUSION: Based on our results, high fat ground beef favorably alters systolic BP and does not negatively affect PWV measures

Deconstructing interventions: approaches to studying behavior change techniques across obesity interventions

Deconstructing interventions into the specific techniques that are used to change behavior represents a new frontier in behavioral intervention research. This paper considers opportunities and challenges in employing the Behavior Change Techniques Taxonomy (BCTTv1) developed by Michie and colleagues, to code the behavior change techniques (BCTs) across multiple interventions addressing obesity and capture dose received at the technique level. Numerous advantages were recognized for using a shared framework for intervention description. Coding interventions at levels of the social ecological framework beyond the individual level, separate coding for behavior change initiation vs. maintenance, fidelity of BCT delivery, accounting for BCTs mode of delivery, and tailoring BCTs, present both challenges and opportunities. Deconstructing interventions and identifying the dose required to positively impact health-related outcomes could enable important gains in intervention science

HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

Prioritization of fish communities with a view to conservation and restoration on a large scale European basin, the Loire (France)

The hierarchical organization of important sites for the conservation or the restoration of fish communities is a great challenge for managers, especially because of financial or time constraints. In this perspective, we developed a methodology, which is easy to implement in different locations. Based on the fish assemblage characteristics of the Loire basin (France), we created a synthetic conservation value index including the rarity, the conservation status and the species origin. The relationship between this new synthetic index and the Fish-Based Index allowed us to establish a classification protocol of the sites along the Loire including fish assemblages to be restored or conserved. Sites presenting disturbed fish assemblages, a low rarity index, few threatened species, and a high proportion of non-native species were considered as important for the restoration of fish biodiversity. These sites were found mainly in areas where the assemblages are typical of the bream zone, e.g. with a higher number of eurytopic and limnophilic species. On the contrary, important sites for conservation were defined as having an important conservation potential (high RI, a lot of threatened species, and few nonnatives fish species) and an undisturbed fish assemblage similar to the expected community if habitats are undisturbed. Important sites for conservation were found in the Loire basin’s medium reaches which host assemblages typical for the grayling and the barbell zones, e.g. with a higher number of rheophilic species. The synthetic conservation value index could be adapted and completed with other criteria according to management priorities and capacities

The Rachel Carson Letters and the Making of Silent Spring

Environment, conservation, green, and kindred movements look back to Rachel Carson’s 1962 book Silent Spring as a milestone. The impact of the book, including on government, industry, and civil society, was immediate and substantial, and has been extensively described; however, the provenance of the book has been less thoroughly examined. Using Carson’s personal correspondence, this paper reveals that the primary source for Carson’s book was the extensive evidence and contacts compiled by two biodynamic farmers, Marjorie Spock and Mary T. Richards, of Long Island, New York. Their evidence was compiled for a suite of legal actions (1957-1960) against the U.S. Government and that contested the aerial spraying of dichlorodiphenyltrichloroethane (DDT). During Rudolf Steiner’s lifetime, Spock and Richards both studied at Steiner’s Goetheanum, the headquarters of Anthroposophy, located in Dornach, Switzerland. Spock and Richards were prominent U.S. anthroposophists, and established a biodynamic farm under the tutelage of the leading biodynamics exponent of the time, Dr. Ehrenfried Pfeiffer. When their property was under threat from a government program of DDT spraying, they brought their case, eventually lost it, in the process spent US$100,000, and compiled the evidence that they then shared with Carson, who used it, and their extensive contacts and the trial transcripts, as the primary input for Silent Spring. Carson attributed to Spock, Richards, and Pfeiffer, no credit whatsoever in her book. As a consequence, the organics movement has not received the recognition, that is its due, as the primary impulse for Silent Spring, and it is, itself, unaware of this provenance