The effect of exenatide on cardiovascular risk markers in women with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is associated with an adverse cardiovascular risk profile including a prothrombotic state. Exenatide has been shown to be effective at improving insulin sensitivity and weight loss in PCOS; therefore this study was undertaken to assess its effects on weight, endothelial function, inflammatory markers, and fibrin structure/function in overweight/obese women with PCOS.Methods: Thirty overweight/obese anovulatory women with all 3 Rotterdam criteria received exenatide 5 mcg bd for 4 weeks then 10 mcg bd for 12 weeks. The primary outcome was change in weight; secondary outcomes were changes in endothelial function [Reactive Hyperemia-Peripheral Arterial Tonometry (RH-PAT)], serum endothelial markers (ICAM-1, VCAM-1, E-selectin, and P-selectin), change in inflammation (hsCRP), and alteration in clot structure and function [maximum absorbance (MA), and time from full clot formation to 50% lysis (LT)].Results: Twenty patients completed the study. Exenatide reduced weight 111.8 ± 4.8 to 108.6 ± 4.6 kg p = 0.003. Serum endothelial markers changed with a reduction in ICAM-1 (247.2 ± 12.9 to 231.3 ± 11.5 ng/ml p = 0.02), p-selectin (101.1 ± 8.2 to 87.4 ± 6.6 ng/ml p = 0.01), and e-selectin (38.5 ± 3.3 to 33.6 ± 2.6 ng/ml p = 0.03), without an overt change in endothelial function. Inflammation improved (CRP; 8.5 ± 1.4 to 5.6 ± 0.8 mmol/L p = 0.001), there was a reduction in clot function (LT; 2,987 ± 494 to 1,926 ± 321 s p = 0.02) but not clot structure.Conclusion: Exenatide caused a 3% reduction in weight, improved serum markers of endothelial function, inflammation, and clot function reflecting an improvement in cardiovascular risk indices in these women with PCOS. This suggests exenatide could be an effective treatment for obese women with PCOS

Identifying correlates and determinants of physical activity in youth: How can we advance the field?

This commentary provides a critical discussion of current research investigating the correlates and determinants of physical activity in young people, with specific focus on conceptual, theoretical and methodological issues. We draw on current child and adolescent literature and our own collective expertise to illustrate our discussion. We conclude with recommendations that will strengthen future research and help to advance the field.The work of Andrew J Atkin was supported by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence (RES-590-28-0002). Funding from the British Heart Foundation, Department of Health, Economic and Social Research Council, Medical Research Council, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. The work of Esther MF van Sluijs was supported by the Medical Research Council (MC_UU_12015/7).This is the final version of the article. It first appeared from Elsevier via https://doi.org10.1016/j.ypmed.2016.02.04

Circulating endothelial microparticles reduce in concentration following an exercise programme in women with polycystic ovary syndrome

Purpose: Endothelial dysfunction is a known comorbidity in women with polycystic ovary syndrome (PCOS). The aim was to assess if supervised, moderate intensity exercise could potentially impact markers of endothelial disruption; endothelial cell derived microparticles (EMP). Methods: The current study investigated the effects of a supervised 8-week moderate intensity exercise programme on EMP in women with PCOS (n=11) and control women free from any known disease (n=10). EMP were enumerated via specific antibody (CD105, CD106) labelling and flow cytometry.Results: CD105+MP significantly reduced in women with PCOS from pre to post exercise programme, with CD105+ MP reducing from 2114 CD105+ MP per µl platelet free plasma (PFP) to 424 CD105+ MP per µl PFP (p = 0.025). Control women showed no significant change in CD105+ MP (p = 0.25) after completing the same exercise programme. CD106+ MP showed no change in either PCOS (p = 0.95) or control groups (p = 0.99). No significant correlations existed with the changes in endothelial microparticles (EMP) compared to body composition changes as a result of exercise. Conclusion: Supervised, moderate intensity exercise independent of substantial weight loss reduced circulating CD105+MP, likely reflecting an improvement in endothelial function in women with PCOS compared to healthy control women. Additionally, EMP may be a useful marker for physical improvement in exercise programmes for clinical populations

Impaired heat shock protein 72 expression in women with polycystic ovary syndrome following a supervised exercise programme

Induction of heat shock protein expression and the heat shock (stress) response are seen in exercise. This exercise-induced response is thought protective against cellular stress through the expression of heat shock proteins. The highly inducible heat shock protein 72 (HSP72) has been shown to be expressed in a number of stress-related conditions, but not investigated in women with polycystic ovary syndrome (PCOS). Twenty-one women (10 controls, 11 with PCOS) concluded an 8-week supervised, moderate-intensity exercise programme. Monocytes and lymphocytes were analysed by flow cytometry for HSP72 expression from blood samples prior to, mid-way and at the completion of the programme. The monocyte HSP72 expression showed an increase from baseline values through mid-way (p = 0.025), and at the completion of the programme (p = 0.011) only in the control group, the PCOS group showed no significant change. This pattern was similar for lymphocyte HSP72 expression where a significant increase was found at the completion of the programme (p = 0.01) only in the control group. The magnitude of increased HSP72 expression following completion of the programme was linked to baseline values only in the control group. In conclusion, increased HSP72 expression to exercise over an 8-week period was seen in control but not in PCOS women, suggesting that there is an impairment of HSP72 expression in response to exercise in these women

CT colonography: optimisation, diagnostic performance and patient acceptability of reduced-laxative regimens using barium-based faecal tagging

To establish the optimum barium-based reduced-laxative tagging regimen prior to CT colonography (CTC). Ninety-five subjects underwent reduced-laxative (13 g senna/18 g magnesium citrate) CTC prior to same-day colonoscopy and were randomised to one of four tagging regimens using 20 ml 40%w/v barium sulphate: regimen A: four doses, B: three doses, C: three doses plus 220 ml 2.1% barium sulphate, or D: three doses plus 15 ml diatriazoate megluamine. Patient experience was assessed immediately after CTC and 1 week later. Two radiologists graded residual stool (1: none/scattered to 4: >50% circumference) and tagging efficacy for stool (1: untagged to 5: 100% tagged) and fluid (1: untagged, 2: layered, 3: tagged), noting the HU of tagged fluid. Preparation was good (76–94% segments graded 1), although best for regimen D (P = 0.02). Across all regimens, stool tagging quality was high (mean 3.7–4.5) and not significantly different among regimens. The HU of layered tagged fluid was higher for regimens C/D than A/B (P = 0.002). Detection of cancer (n = 2), polyps ≥6 mm (n = 21), and ≤5 mm (n = 72) was 100, 81 and 32% respectively, with only four false positives ≥6 mm. Reduced preparation was tolerated better than full endoscopic preparation by 61%. Reduced-laxative CTC with three doses of 20 ml 40% barium sulphate is as effective as more complex regimens, retaining adequate diagnostic accuracy

Prevalence and Risk Factors of Lassa Seropositivity in Inhabitants of the Forest Region of Guinea: A Cross-Sectional Study

Lassa fever is a viral haemorrhagic fever endemic in West Africa, mainly transmitted to humans by multimammate rats. Several modes of virus transmission are suspected: aerosolisation of the virus, contact with infected rodent excreta, and consumption of rodent meat. Person-to-person transmission also occurs via contact with body fluids of infected persons (blood, urine) and is responsible for numerous outbreaks, mostly in healthcare facilities. Our objective was to precisely describe risk factors for Lassa fever in both rural and urban communities of forest Guinea. For each participant, a standardized questionnaire was completed and a blood sample tested for Lassa virus antibodies. A total of 1424 subjects were interviewed and 977 blood samples tested. The prevalence of Lassa virus antibodies was estimated at 12.9% and 10.0% in rural and urban areas, respectively. The two risk factors were: to have, in the past twelve months, undergone an injection, or lived with someone displaying a haemorrhage. Contrary to our expectation, no factors related to contact with rodents were identified. It is still probable that transmission occurs via indirect contact between rodents and humans in households, but our results highlight the importance of person-to-person transmission via close contact and nosocomial exposure

Sedentary Behavior Research Network (SBRN) - Terminology Consensus Project process and outcome

Background: The prominence of sedentary behavior research in health science has grown rapidly. With this growth there is increasing urgency for clear, common and accepted terminology and definitions. Such standardization is difficult to achieve, especially across multi-disciplinary researchers, practitioners, and industries. The Sedentary Behavior Research Network (SBRN) undertook a Terminology Consensus Project to address this need. Method: First, a literature review was completed to identify key terms in sedentary behavior research. These key terms were then reviewed and modified by a Steering Committee formed by SBRN. Next, SBRN members were invited to contribute to this project and interested participants reviewed and provided feedback on the proposed list of terms and draft definitions through an online survey. Finally, a conceptual model and consensus definitions (including caveats and examples for all age groups and functional abilities) were finalized based on the feedback received from the 87 SBRN member participants who responded to the original invitation and survey. Results: Consensus definitions for the terms physical inactivity, stationary behavior, sedentary behavior, standing, screen time, non-screen-based sedentary time, sitting, reclining, lying, sedentary behavior pattern, as well as how the terms bouts, breaks, and interruptions should be used in this context are provided. Conclusion: It is hoped that the definitions resulting from this comprehensive, transparent, and broad-based participatory process will result in standardized terminology that is widely supported and adopted, thereby advancing future research, interventions, policies, and practices related to sedentary behaviors

Specific antenatal interventions for Black, Asian and Minority Ethnic (BAME) pregnant women at high risk of poor birth outcomes in the United Kingdom: a scoping review

Background: Disparity exists in maternal and infant birth outcomes of Black and Minority Ethnic (BAME) women giving birth in the United Kingdom (UK) compared to the majority. There is therefore a need to reconsider existing maternity service provision to ensure culturally competent services. The purpose of this scoping review was to ascertain what specific maternity interventions have been implemented in the UK for BAME women (2004–2014) so that increased awareness of the need and scope of specific maternity interventions for BAME women can be identified. Methods: A scoping review was conducted in order to determine the evidence base. It was determined that no prior systematic reviews had been conducted and it was apparent that literature in this field was sparse. Scoping review is an ideal method when literature is likely to be heterogeneous and the research field relatively unexplored. A keyword strategy was used implementing population (P), intervention (I), comparison (C) and outcomes (O). Results: An initial 2188 papers were identified. Following screening and review, only 5 heterogeneous papers remained suitable and were included. The included interventions employed sample sizes of N = 160-1441, examined a range of different outcome measures and were delivered across different parts of the UK with high numbers of BAME residents. Conclusions: There is a lack of rigorous research interventions and practice interventions which are currently documented, of specific maternity interventions which are aimed to address culturally competent maternity services and the sharing of best practice addressing the increased risks of BAME women delivering in the UK

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points