Attenuating Effect of Vigorous Physical Activity on the Risk for Inherited Obesity: A Study of 47,691 Runners

Objective: Physical activity has been shown to attenuate the effect of the FTO polymorphism on body weight, and the heritability of body weight in twin and in family studies. The dose-response relationship between activity and the risk for inherited obesity is not well known, particularly for higher doses of vigorous exercise. Such information is needed to best prescribe an exercise dose for obesity prevention in those at risk due to their family history. Design: We therefore analyzed self-reported usual running distance, body mass index (BMI), waist circumference, and mother’s and father’s adiposity (1 = lean, 2 = normal, 3 = overweight, and 4 = very overweight) from survey data collected on 33,480 male and 14,211 female runners. Age-, education-, and alcohol-adjusted regression analyses were used to estimate the contribution of parental adiposities to the BMI and waist circumferences in runners who ran an average of,3, 3–6, 6–9, $9 km/day. Results: BMI and waist circumferences of runners who ran,3 km/day were significantly related to their parents adiposity (P,10 215 and P,10 211, respectively). These relationships (i.e., kg/m 2 or cm per increment in parental adiposity) diminished significantly with increasing running distance for both BMI (inheritance6exercise interaction, males: P,10 210; females: P,10 25) and waist circumference (inheritance6exercise interaction, males: P,10 29; females: P = 0.004). Compared to,3 km/day, the parental contribution to runners who averaged$9 km/day was diminished by 48 % for male BMI, 58 % for female BMI, 55 % for male waist circumference, and 58 % for female waist circumference. These results could not b

Effects of Volitional Preemptive Abdominal Contraction on Shoulder Proprioception Following Shoulder Muscle Fatigue

The abdominal bracing maneuver, a volitional preemptive abdominal contraction (VPAC) strategy, is potentially beneficial to shoulder exercise performance. It is unclear how VPAC use affects shoulder function, including proprioception and shoulder muscle function following shoulder muscle fatigue caused by upper extremity dominant sports movements. Discovering methods that reduce its effects on shoulder proprioception and shoulder muscle function is important for clinical practice in orthopedic rehabilitation. PURPOSE: To identify VPAC effects on shoulder proprioception abilities and to identify VPAC effects on shoulder muscle electromyographic amplitudes, during seated proprioception trials, both with and without muscle fatigue present. METHODS: Thirty-nine participants (26 women, 13 men) participated in this study. Shoulder proprioception was measured by shoulder flexion reproduction angles. Kinematic data were collected during the shoulder flexion trials to determine the accuracy in the subjects’ ability to reproduce a reference angle. All data were collected before and after a shoulder muscle fatigue protocol. Electromyographic data from the anterior deltoid (AD), posterior deltoid (PD), upper trapezius (UT), lower trapezius (LT), serratus anterior (SA), and infraspinatus (IF) muscles were used to observe muscle contraction amplitudes during the angle reproduction trials. RESULTS: Shoulder reproduction angles were not significantly affected by VPAC or muscle fatigue. Individually, shoulder muscle fatigue significantly increased UT muscle amplitudes (Mdn = 0.059(0.135), p\u3c.008) and LT muscle amplitudes (Mdn = 0.023(0.059), p\u3c.008). VPAC significantly increased shoulder IF muscle amplitudes (Mdn = 0.019(0.038), p\u3c.008). CONCLUSION: The VPAC did not affect shoulder proprioception in this study, showing that the strategy may not be beneficial to improving proprioception in the shoulder joint. The affects of muscle fatigue on the selected shoulder muscles supported the observations in previous literature concerning muscle fatigue effects on selected shoulder muscle. Clinicians can use this information to assist with the creation of therapeutic exercise for the shoulder joint

Quantile-Specific Penetrance of Genes Affecting Lipoproteins, Adiposity and Height

Quantile-dependent penetrance is proposed to occur when the phenotypic expression of a SNP depends upon the population percentile of the phenotype. To illustrate the phenomenon, quantiles of height, body mass index (BMI), and plasma lipids and lipoproteins were compared to genetic risk scores (GRS) derived from single nucleotide polymorphisms (SNP)s having established genome-wide significance: 180 SNPs for height, 32 for BMI, 37 for low-density lipoprotein (LDL)-cholesterol, 47 for high-density lipoprotein (HDL)-cholesterol, 52 for total cholesterol, and 31 for triglycerides in 1930 subjects. Both phenotypes and GRSs were adjusted for sex, age, study, and smoking status. Quantile regression showed that the slope of the genotype-phenotype relationships increased with the percentile of BMI (P = 0.002), LDL-cholesterol (P = 3×10−8), HDL-cholesterol (P = 5×10−6), total cholesterol (P = 2.5×10−6), and triglyceride distribution (P = 7.5×10−6), but not height (P = 0.09). Compared to a GRS's phenotypic effect at the 10th population percentile, its effect at the 90th percentile was 4.2-fold greater for BMI, 4.9-fold greater for LDL-cholesterol, 1.9-fold greater for HDL-cholesterol, 3.1-fold greater for total cholesterol, and 3.3-fold greater for triglycerides. Moreover, the effect of the rs1558902 (FTO) risk allele was 6.7-fold greater at the 90th than the 10th percentile of the BMI distribution, and that of the rs3764261 (CETP) risk allele was 2.4-fold greater at the 90th than the 10th percentile of the HDL-cholesterol distribution. Conceptually, it maybe useful to distinguish environmental effects on the phenotype that in turn alters a gene's phenotypic expression (quantile-dependent penetrance) from environmental effects affecting the gene's phenotypic expression directly (gene-environment interaction)

Female Burying Beetles Benefit from Male Desertion: Sexual Conflict and Counter-Adaptation over Parental Investment

Sexual conflict drives the coevolution of sexually antagonistic traits, such that an adaptation in one sex selects an opposing coevolutionary response from the other. Although many adaptations and counteradaptations have been identified in sexual conflict over mating interactions, few are known for sexual conflict over parental investment. Here we investigate a possible coevolutionary sequence triggered by mate desertion in the burying beetle Nicrophorus vespilloides, where males commonly leave before their offspring reach independence. Rather than suffer fitness costs as a consequence, our data suggest that females rely on the male's absence to recoup some of the costs of larval care, presumably because they are then free to feed themselves on the carcass employed for breeding. Consequently, forcing males to stay until the larvae disperse reduces components of female fitness to a greater extent than caring for young singlehandedly. Therefore we suggest that females may have co-evolved to anticipate desertion by their partners so that they now benefit from the male's absence

Human behaviour and economic growth: a psychocultural perspective on local and regional development

A renewed emphasis on behavioural traits has emerged as a means of explaining regional and local differences in economic performance and development. Given this, the aim of this study is to identify distinct local psychocultural behavioural profiles and to examine the extent to which these are associated with economic growth. Combining theories of community culture and personality psychology into a holistic spatially-oriented perspective, the paper argues that the types of human behaviour found across local places emerges from the co-evolution of cultural and personality factors. An empirical analysis of localities in Great Britain identifies and explores three underlying psychocultural profiles: Diverse Extraversion; Inclusive Amenability and Individual Commitment. It is found that inclusive amenable and individually committed psychocultural behaviour generally appear to hold back local economic growth, with the exception of recessionary periods. The reverse relationship is somewhat the case for diverse extravert behaviour. It is concluded that a better understanding of the holistic relationship and co-evolution of the cultural and psychological behavioural make-up of localities and regions has the potential to provide new insights into expected development outcomes as well as the forms of policy intervention that are required within regions and localities, each of which has its own individual psychocultural character

P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

Dangerous drug interactions leading to hemolytic uremic syndrome following lung transplantation

<p>Abstract</p> <p>Background</p> <p>To report our experience of a rather uncommon drug interaction, resulting in hemolytic uremic syndrome (HUS).</p> <p>Methods</p> <p>Two consecutive cases of hemolytic uremic syndrome were diagnosed in our service. In both patients the use of macrolides in patients taking Tacrolimus, resulted in high levels of Tacrolimus.</p> <p>Results</p> <p>The first patient was a 48 years old female with Bilateral emphysema. She underwent Single Sequential Lung Transplantation. She developed reperfusion injury requiring prolonged stay. Tacrolimus introduced (Day 51). The patient remained well up till 5 months later; Erythromycin commenced for chest infection. High Tacrolimus levels and a clinical diagnosis of HUS were made. She was treated with plasmapheresis successfully.</p> <p>The second case was a 57 years old female with Emphysema & A1 Antithrypsin deficiency. She underwent Right Single Lung Transplantation. A2 rejection with mild Obliterative Bronchiolitis diagnosed 1 year later and she switched to Tacrolimus. She was admitted to her local Hospital two and a half years later with right middle lobe consolidation. The patient commenced on amoxicillin and clarithromycin. Worsening renal indices, high Tacrolimus levels, hemolytic anemia & low Platelets were detected. HUS diagnosed & treated with plasmapheresis.</p> <p>Conclusions</p> <p>There are 21 cases of HUS following lung transplantation in the literature that may have been induced by high tacrolimus levels. Macrolides in patients taking Cyclosporin or Tacrolimus lead to high levels. Mechanism of action could be glomeruloconstrictor effect with reduced GFR increased production of Endothelin-1 and increased Platelet aggregation.</p