Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study

Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (p < 0.001) in the fit group (mean 1.21 ± 3.42) compared to the unfit group (mean -0.74 ± 2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth

The Ecm11-Gmc2 complex promotes synaptonemal complex formation through assembly of transverse filaments in budding yeast

During meiosis, homologous chromosomes pair at close proximity to form the synaptonemal complex (SC). This association is mediated by transverse filament proteins that hold the axes of homologous chromosomes together along their entire length. Transverse filament proteins are highly aggregative and can form an aberrant aggregate called the polycomplex that is unassociated with chromosomes. Here, we show that the Ecm11-Gmc2 complex is a novel SC component, functioning to facilitate assembly of the yeast transverse filament protein, Zip1. Ecm11 and Gmc2 initially localize to the synapsis initiation sites, then throughout the synapsed regions of paired homologous chromosomes. The absence of either Ecm11 or Gmc2 substantially compromises the chromosomal assembly of Zip1 as well as polycomplex formation, indicating that the complex is required for extensive Zip1 polymerization. We also show that Ecm11 is SUMOylated in a Gmc2-dependent manner. Remarkably, in the unSUMOylatable ecm11 mutant, assembly of chromosomal Zip1 remained compromised while polycomplex formation became frequent. We propose that the Ecm11-Gmc2 complex facilitates the assembly of Zip1 and that SUMOylation of Ecm11 is critical for ensuring chromosomal assembly of Zip1, thus suppressing polycomplex formation

A virtual agent to support individuals living with physical and mental comorbidities: Co-design and acceptability testing

Background: Individuals living with long-term physical health conditions frequently experience co-occurring mental health problems. This comorbidity has a significant impact on an individual's levels of emotional distress, health outcomes, and associated health care utilization. As health care services struggle to meet demand and care increasingly moves to the community, digital tools are being promoted to support patients to self-manage their health. One such technology is the autonomous virtual agent. Objective: This study aimed to co-design the content, functionality, and interface modalities of an autonomous virtual agent to support self-management for patients with an exemplar long-term condition (LTC; chronic pulmonary obstructive disease [COPD]) and then to assess the acceptability and system content. Methods: We conducted 2 co-design workshops and a proof-of-concept implementation of an autonomous virtual agent with natural language processing capabilities. This implementation formed the basis for video-based scenario testing of acceptability with adults with a diagnosis of COPD and health professionals involved in their care. Results: Adults (n=6) with a diagnosis of COPD and health professionals (n=5) specified 4 priority self-management scenarios for which they would like to receive support: at the time of diagnosis (information provision), during acute exacerbations (crisis support), during periods of low mood (emotional support), and for general self-management (motivation). From the scenario testing, 12 additional adults with COPD felt the system to be both acceptable and engaging, particularly with regard to internet-of-things capabilities. They felt the system would be particularly useful for individuals living alone. Conclusions: Patients did not explicitly separate mental and physical health needs, although the content they developed for the virtual agent had a clear psychological approach. Supported self-management delivered via an autonomous virtual agent was acceptable to the participants. A co-design process has allowed the research team to identify key design principles, content, and functionality to underpin an autonomous agent for delivering self-management support to older adults living with COPD and potentially other LTCs

Micro-epidemiology of Plasmodium falciparum malaria: Is there any difference in transmission risk between neighbouring villages?

BACKGROUND: Malaria control strategies are designed as a solution for either the whole region or the whole country and are assumed to suit every setting. There is a need to shift from this assumption because transmission may be different from one local setting to another. The aim of this study was to assess the risk of clinical malaria given the village of residence among under-five children in rural north-western Burkina Faso. METHODS: 867 children (6–59 months) were randomly selected from four sites. Interviewers visited the children weekly at home over a one-year period and tested them for fever. Children with fever were tested for malaria parasites. An episode of clinical malaria was defined as fever (axillary temperature ≥ 37.5°C) + parasites density ≥ 5,000 parasites/μl. Logistic regression was used to assess the risk of clinical malaria among children at a given site of residence. RESULTS: Children accumulated 758 person years (PYs). Overall, 597 episodes of clinical malaria were observed, giving an incidence rate of 0.79 per PY. The risk of clinical malaria varied amongst the four sites. Taking one village as reference the odds ratio for the other three sites ranged from 0.66; 95%CI: 0.44–0.98 to 1.49; 95%CI: 1.10–2.01. CONCLUSION: Malaria control strategies should be designed to fit the local context. The heterogeneity of transmission should be assessed at the district level to allow cost-effective resource allocation that gives priority to locations with high risk. Functional routine health information systems could provide the necessary data for context specific risk assessment

Ca2+/Calmodulin-Dependent Protein Kinase Kinase Is Not Involved in Hypothalamic AMP-Activated Protein Kinase Activation by Neuroglucopenia

Hypoglycemia and neuroglucopenia stimulate AMP-activated protein kinase (AMPK) activity in the hypothalamus and this plays an important role in the counterregulatory responses, i.e. increased food intake and secretion of glucagon, corticosterone and catecholamines. Several upstream kinases that activate AMPK have been identified including Ca2+/Calmodulin-dependent protein kinase kinase (CaMKK), which is highly expressed in neurons. However, the involvement of CaMKK in neuroglucopenia-induced activation of AMPK in the hypothalamus has not been tested. To determine whether neuroglucopenia-induced AMPK activation is mediated by CaMKK, we tested whether STO-609 (STO), a CaMKK inhibitor, would block the effects of 2-deoxy-D-glucose (2DG)-induced neuroglucopenia both ex vivo on brain sections and in vivo. Preincubation of rat brain sections with STO blocked KCl-induced α1 and α2-AMPK activation but did not affect AMPK activation by 2DG in the medio-basal hypothalamus. To confirm these findings in vivo, STO was pre-administrated intracerebroventricularly (ICV) in rats 30 min before 2DG ICV injection (40 µmol) to induce neuroglucopenia. 2DG-induced neuroglucopenia lead to a significant increase in glycemia and food intake compared to saline-injected control rats. ICV pre-administration of STO (5, 20 or 50 nmol) did not affect 2DG-induced hyperglycemia and food intake. Importantly, activation of hypothalamic α1 and α2-AMPK by 2DG was not affected by ICV pre-administration of STO. In conclusion, activation of hypothalamic AMPK by 2DG-induced neuroglucopenia is not mediated by CaMKK

Differential impact of chronic stress along the hippocampal dorsal–ventral axis

First published online 06 February 2014Stress impacts differently in distinct brain regions. However, so far few studies have focused on the differential responses triggered by stressful stimuli on the intrinsic functional heterogeneity of the hippocampal axis. In this study, we assessed the functional and structural alterations caused by exposure to a chronic unpredictable stress (CUS) paradigm on the dorsal-ventral axis of the hippocampus. The morphological analysis demonstrated that CUS had opposite outcomes in the structure of the dorsal (DH) and ventral hippocampus (VH): whereas in the DH, stress triggered a volumetric reduction as a result of atrophy of CA3 and CA1 apical dendrites, in the VH there was an increase in hippocampal volume concurrent with the increase of CA3 apical dendrites. In parallel, electrophysiological data revealed that stress led to a decrease in VH LTD. In summary, the present work showed that stress impacts differently on the structure and function of the DH and VH which contributes to better understand the overall spectrum of the central effects of stress.Pinto V and Mota C were supported by Fundacao para a Ciencia e Tecnologia (FCT) grants (SFRH/BPD/69132/2010; SFRH/BD/81881/2011, respectively). This work was supported by an FCT grant (PTDC/SAU-NSC/120590/2010). The authors declare no competing financial interests

Systematic Evaluation of Candidate Blood Markers for Detecting Ovarian Cancer

Epithelial ovarian cancer is a significant cause of mortality both in the United States and worldwide, due largely to the high proportion of cases that present at a late stage, when survival is extremely poor. Early detection of epithelial ovarian cancer, and of the serous subtype in particular, is a promising strategy for saving lives. The low prevalence of ovarian cancer makes the development of an adequately sensitive and specific test based on blood markers very challenging. We evaluated the performance of a set of candidate blood markers and combinations of these markers in detecting serous ovarian cancer.We selected 14 candidate blood markers of serous ovarian cancer for which assays were available to measure their levels in serum or plasma, based on our analysis of global gene expression data and on literature searches. We evaluated the performance of these candidate markers individually and in combination by measuring them in overlapping sets of serum (or plasma) samples from women with clinically detectable ovarian cancer and women without ovarian cancer. Based on sensitivity at high specificity, we determined that 4 of the 14 candidate markers--MUC16, WFDC2, MSLN and MMP7--warrant further evaluation in precious serum specimens collected months to years prior to clinical diagnosis to assess their utility in early detection. We also reported differences in the performance of these candidate blood markers across histological types of epithelial ovarian cancer.By systematically analyzing the performance of candidate blood markers of ovarian cancer in distinguishing women with clinically apparent ovarian cancer from women without ovarian cancer, we identified a set of serum markers with adequate performance to warrant testing for their ability to identify ovarian cancer months to years prior to clinical diagnosis. We argued for the importance of sensitivity at high specificity and of magnitude of difference in marker levels between cases and controls as performance metrics and demonstrated the importance of stratifying analyses by histological type of ovarian cancer. Also, we discussed the limitations of studies (like this one) that use samples obtained from symptomatic women to assess potential utility in detection of disease months to years prior to clinical detection