Weight Status and BMI-Related Traits in Adolescent Friendship Groups and Role of Sociodemographic Factors: The European IDEFICS/I. Family Cohort

BackgroundDuring adolescence, health behaviors and weight status are increasingly influenced by friendship and peer networks. This paper examines resemblances in weight-related characteristics and how they differ by sociodemographic factors.MethodsOver 3,000 friendships were reported by 1,603 adolescents, aged 11–16 years, who participated in the school-based I. Family study in 6 European countries. Each “source child” named 1–10 friends for whom standardized weight-related traits were available in the same survey. The mean value of the friends'' traits weighted by time spent together was calculated, and related to the source child''s trait. Country, age and sex of the source child, parental education, and immigrant background were considered for confounding and moderation.ResultsSource children''s z-scores of body fat percent and BMI were positively associated with their friends'' characteristics, in particular if they had highly educated parents. Positive associations were also found regarding the frequency of fast-food consumption, impulsivity, screen time, preference for sugar-sweetened foods, and hours spent in sports clubs, in increasing order of effect size. Additionally, correlations were observed between friends'' cognitive and school functioning and being bullied. No associations were seen for a preference for high-fat foods, weight concerns, and health-related quality of life. Finally, parental education and immigrant background were associated between friends in all countries except Sweden, where no associations were observed.ConclusionAdolescent friends shared a number of weight-related characteristics. For weight measures per se, positive associations with friends'' characteristics were only observed in adolescents with high parental education. Associations regarding energy-balance behaviors and indicators of school-related well-being did not differ by parental education. Parental education and immigrant background correlated positively in friends in most countries showing that social aggregation is already occurring in adolescence. The wide spectrum of friendship associations in weight-related traits and behaviors suggests that health promotion initiatives in adolescents should be directed towards peer groups in both school-related and leisure-time environments.ISRCTN RegistryPan-European IDEFICS/I. Family children cohort (ID ISRCTN62310987; https://doi.org/10.1186/ISRCTN62310987).     

Upregulation of GAD65 mRNA in the medulla of the rat model of metabolic syndrome

Metabolic syndrome is characterized by obesity, elevated blood pressure (BP), insulin resistance, and hypercholesterolemia. Recently an animal model of this disorder has been proposed in rats selectively bred based on their performance on a treadmill-running task. Accordingly, low capacity runner (LCR) rats exhibited all of the diagnostic criteria for metabolic syndrome, including elevated BP, as compared to their high capacity runner (HCR) counterparts [U. Wisløff, S.M. Najjar, O. Ellingsen, P.M. Haram, S. Swoap, Q. Al-Share, M. Fernstrom, K. Rezaei, S.J. Lee, L.G. Koch, S.L. Britton, Cardiovascular risk factors emerge after artificial selection for low aerobic capacity, Science 307 (2005) 418–420]. Previous studies have highlighted the importance of GABAergic neurotransmission in the medullary cardiovascular-regulatory areas in the central control of BP. Thus, we hypothesized a dysregulation in GABAergic transmission in the medullary cardiovascular-regulatory nuclei of LCR rats. To begin testing this hypothesis we carried out experiments examining expression of the GABA synthetic enzymes, GAD65 and GAD67, mRNAs in the two rat strains via radioactive in situ hybridization. Our results showed GAD65 and GAD67 mRNAs were widely expressed throughout the brainstem; quantification revealed increased GAD65 mRNA expression in LCR animals in the caudal nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (VLM) as compared to HCR rats. Conversely, no differences in the expression of GAD67 were detected in these regions. These data are consistent with the notion of altered GABAergic neurotransmission in the NTS and VLM in metabolic syndrome, and point to the importance of these regions in cardiovascular regulation.     

Methylation profiling of benign and malignant breast lesions and its application to cytopathology.

Methylation of tumor suppressor genes has been implicated in breast cancer development. However, methylation profiles of different breast lesions, subtypes of carcinoma in particular, have not been examined in detail. In this study, we use methylation-specific PCR (MSP) to generate gene methylation profiles of different breast lesions and to test the clinical utility of such profiles. We examined the methylation status of three genes, RARbeta2, RASSF1A, and cyclin D2, on 102 samples of breast tissue, from benign (n = 36), to in situ carcinoma (n = 21), to invasive carcinoma (n = 45). We found that almost all cases of invasive carcinoma (96%) contained at least one methylated gene from our panel, whereas gene methylation was less common among benign lesions (42%) and in situ carcinoma (76%). Of the three genes, cyclin D2 methylation was most specific for malignancy because only 1 of 35 benign cases was methylated at this gene (1 case was not informative). The major histologic subtypes of invasive carcinoma show similar methylation profiles in the genes examined. We next performed MSP analysis on archival breast fine-needle aspiration (FNA) biopsy samples and corresponding surgical biopsy specimens and found a high concordance between the two types of specimens. We then analyzed 17 breast FNA biopsy samples with an indeterminate diagnosis. In this setting, MSP had a high specificity (100%) and modest sensitivity (67%) for identifying malignancy.     

Viral serpin, Serp-1, inhibits endogenous angiogenesis in the chicken chorioallantoic membrane model.

BACKGROUND: Angiogenesis is a critical factor in the development of malignant tumors, in arthritic joints, and in cardiovascular disease. In cardiovascular disease, angiogenesis is recognised both as a potential therapy and as a complicating factor in atherosclerotic plaque rupture and thrombotic obstruction. Serine proteases regulate thrombosis, inflammation, and cell invasion, events that trigger various stages of angiogenesis and are in turn regulated by inhibitors, termed serpins. Serp-1 is a secreted anti-inflammatory viral serpin that profoundly inhibits early mononuclear cell invasion, and the development of atherosclerosis, transplant vasculopathy, and arthritis in a range of animal models. METHODS: The capacity of Serp-1 to alter angiogenesis was evaluated in the chicken chorioallantoic membrane (CAM) model using morphometric analysis of vascular changes and RT-PCR to explore alterations in gene expression. RESULTS: Serp-1 inhibited endogenous angiogenesis in a dose-dependent manner, with associated altered expression of laminin and vascular endothelial growth factor (VEGF). Serp-1 was ineffective in CAMs no longer in the rapid growth phase. Similar inhibition of angiogenesis was detected after inhibition of VEGF, but not after treatment with the inactivated reactive center loop mutant of Serp-1. CONCLUSIONS: The angiogenic process can be controlled using Serp-1, an anti-inflammatory agent that is effective at low concentrations with rapid reversibility, targets endothelial cells, and reduces the availability of VEGF. These properties may be especially important in cardiovascular disease, reducing plaque destabilization. It is likely that the anti-angiogenic activity of Serp-1 contributes to the observed anti-inflammatory and anti-atherogenic actions with potential importance in this therapeutic setting.     

Coordination of multiple muscles in two degree of freedom elbow movements

The present study quantifies electromyographic (EMG) magnitude, timing, and duration in one and two degree of freedom elbow movements involving combinations of flexion-extension and pronation-supination. The aim is to understand the organization of commands subserving motion in individual and multiple degrees of freedom. The muscles tested in this study fell into two categories with respect to agonist burst magnitude: those whose burst magnitude varied with motion in a second degree of freedom at the elbow, and those whose burst magnitude depended on motion in one degree of freedom only. In multiarticular muscles contributing to motion in two degrees of freedom at the elbow, we found that the magnitude of the agonist burst was greatest for movements in which a muscle acted as agonist in both degrees of freedom. The burst magnitudes for one degree of freedom movements were, in turn, greater than for movements in which the muscle was agonist in one degree of freedom and antagonist in the other. It was also found that, for movements in which a muscle acted as agonist in two degrees of freedom, the burst magnitude was, in the majority of cases, not different from the sum of the burst magnitudes in the component movements. When differences occurred, the burst magnitude for the combined movement was greater than the sum of the components. Other measures of EMG activity such as burst onset time and duration were not found to vary in a systematic manner with motion in these two degrees of freedom. It was also seen that several muscles which produced motion in one degree of freedom at the elbow, including triceps brachii (long head), triceps brachii (lateral head), and pronator quadratus displayed first agonist bursts whose magnitude did not vary with motion in a second degree of freedom. However, for the monoarticular elbow flexors brachialis and brachioradialis, agonist burst magnitude was affected by pronation or supination. Lastly, it was observed that during elbow movements in which muscles acted as agonist in one degree of freedom and antagonist in the other, the muscle activity often displayed both agonist and antagonist components in the same movement. It was found that, for pronator teres and biceps brachii, the timing of the bursts was such that there was activity in these muscles concurrent with activity in both pure agonists and pure antagonists. The empirical summation of EMG burst magnitudes and the presence in a single muscle of both agonist and antagonist bursts within a movement suggest that central commands associated with motion in individual degrees of freedom at the elbow may be superimposed to produce elbow movements in two degrees of freedom.     

Premed survival: understanding the culling process in premedical undergraduate education.

PURPOSE: Why undergraduate students pursue or drop a premedical curriculum has received only scant attention. In this study the authors attempted to uncover reasons why students either persevere in their premedical studies or seek alternative careers. METHOD: Using convenience sampling, the authors surveyed 97 undergraduates at a small liberal arts college from November 2000 to March 2001. Of those surveyed, 44 were former premed students who completed a three-page questionnaire about why they had decided not to become physicians; 53 premed students completed a two-page questionnaire about their career aspirations. RESULTS: The response rate was 100%. Premed students were attracted to the field by the intellectual stimulation and the power to help others, yet most were also very concerned about being in debt, dealing with patients who might die, and the compatibility of medicine with having a family. Women students were more concerned than the men about having only limited time to become acquainted with patients on a social level (71% of women versus 45% of men: p =.05). The decision of students to forgo a career as a physician was shaped by apprehensions regarding the years of work required in residency, the need to be on call, unacceptably low grades, and the realization that other attractive career options are available. Of those who said low grades were a deciding factor, most (78%) named organic chemistry as the single course that had affected their plans. Students who acknowledged the role of their poor performance in organic chemistry were more likely to be dissatisfied with their change in plans than were those who did not identify this course as influential (44% versus 29%). CONCLUSIONS: Although the sampling technique and sample size severely limit the authors' ability to generalize their findings, the data offer a starting point for those interested in the reasons for the drop in medical school applicants. The authors state the fact that most former premed students admitted organic chemistry had played a significant role in the change in their career plans deserves attention, and it may be time to consider whether a single course should contribute to eliminating persons who might otherwise excel as physicians.     

Inhibition of C5 or absence of C6 protects from sepsis mortality

Inhibiting complement anaphlytoxin C5a during sepsis may prevent sepsis mortality. Although human anti-C5 antibodies exist, their therapeutic use in microbial sepsis has been avoided because of the hypothesis that inhibiting C5b will prevent formation of the bactericidal membrane attack complex (MAC) and worsen clinical outcome. We wished to test the hypothesis that inhibition of C5 would improve outcomes in sepsis. Sepsis was induced in rats by laparotomy and cecal ligation and puncture (CLP) by an IACUC-approved protocol. Sham animals underwent laparotomy without CLP. Following CLP rats were randomized to receive a single IV dose of purified IgG ant-C5 antibody (Ab) or control IgG Ab. Anti-C5 Ab treated rats (n = 20) had significantly lower mortality vs. controls (n = 21), 20% vs. 52% (P = 0.019, log-rank). Analysis of bacterial load by culture of spleen and liver homogenates showed a reduction in colony forming units in anti-C5 Ab treated rats vs. control IgG (P = 0.003 and 0.009, respectively). Anti-C5 treatment reduced lung injury as measured by total MPO content of lung tissue (P = 0.024). Finally, rats genetically deficient in C6 production, unable to form MAC but capable of producing C5a and C5b, were protected from CLP-induced sepsis mortality. Our results show that in anti-C5 antibody therapy prevents CLP sepsis-induced mortality and improves lung injury. Inhibition of the complement MAC does not increase bacterial load or mortality, therefore, the use of anti-C5 therapy may be beneficial rather than detrimental in sepsis.     

NKG2D blockade prevents autoimmune diabetes in NOD mice

NKG2D is an activating receptor on CD8(+) T cells and NK cells that has been implicated in immunity against tumors and microbial pathogens. Here we show that RAE-1 is present in prediabetic pancreas islets of NOD mice and that autoreactive CD8(+) T cells infiltrating the pancreas express NKG2D. Treatment with a nondepleting anti-NKG2D monoclonal antibody (mAb) during the prediabetic stage completely prevented disease by impairing the expansion and function of autoreactive CD8(+) T cells. These findings demonstrate that NKG2D is essential for disease progression and suggest a new therapeutic target for autoimmune type I diabetes.