Maternal obesity has little effect on the immediate offspring but impacts on the next generation

Maternal obesity during pregnancy has been linked to an increased risk of obesity and cardiometabolic disease in the offspring, a phenomenon attributed to developmental programming. Programming effects may be transmissible across generations through both maternal and paternal inheritance, although the mechanisms remain unclear. Using a mouse model, we explored the effects of moderate maternal diet-induced obesity (DIO) on weight gain and glucose-insulin homeostasis in first-generation (F1) and second-generation offspring. DIO was associated with insulin resistance, hyperglycemia and dyslipidemia before pregnancy. Birth weight was reduced in female offspring of DIO mothers (by 6%, P = .039), and DIO offspring were heavier than controls at weaning (males by 47%, females by 27%), however there were no differences in glucose tolerance, plasma lipids, or hepatic gene expression at 6 months. Despite the relative lack of effects in the F1, we found clear fetal growth restriction and persistent metabolic changes in otherwise unmanipulated second-generation offspring with effects on birth weight, insulin levels, and hepatic gene expression that were transmitted through both maternal and paternal lines. This suggests that the consequences of the current dietary obesity epidemic may also have an impact on the descendants of obese individuals, even when the phenotype of the F1 appears largely unaffected

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Contains reports on four research projects.National Aeronautics and Space Administration (Grant NsG-334)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 28-043-AMC-02536(E

Characterisation of Brachycephalic Obstructive Airway Syndrome in French Bulldogs Using Whole-Body Barometric Plethysmography.

Brachycephalic obstructive airway syndrome (BOAS) is an important health and welfare problem in several popular dog breeds. Whole-body barometric plethysmography (WBBP) is a non-invasive method that allows safe and repeated quantitative measurements of respiratory cycles on unsedated dogs. Here respiratory flow traces in French bulldogs from the pet population were characterised using WBBP, and a computational application was developed to recognise affected animals. Eighty-nine French bulldogs and twenty non-brachycephalic controls underwent WBBP testing. A respiratory functional grading system was used on each dog based on respiratory signs (i.e. respiratory noise, effort, etc.) before and after exercise. For development of an objective BOAS classifier, functional Grades 0 and I were considered to have insignificant clinical signs (termed here BOAS-) and Grades II and III to have significant signs (termed here BOAS+). A comparison between owner-perception of BOAS and functional grading revealed that 60 % of owners failed to recognise BOAS in dogs that graded BOAS+ in this study.WBBP flow traces were found to be significantly different between non-brachycephalic controls and Grade 0 French bulldogs; BOAS- and BOAS+ French bulldogs. A classifier was developed using quadratic discriminant analysis of the respiratory parameters to distinguish BOAS- and BOAS + French bulldogs, and a BOAS Index was calculated for each dog. A cut-off value of the BOAS Index was selected based on a receiver operating characteristic (ROC) curve. Sensitivity, specificity, positive predictive value, and negative predictive value of the classifier on the training group (n=69) were 0.97, 0.93, 0.95, and 0.97, respectively. The classifier was validated using a test group of French bulldogs (n=20) with an accuracy of 0.95. WBBP offers objective screening for the diagnosis of BOAS in French Bulldogs. The technique may be applied to other brachycephalic breeds affected by BOAS, and possibly to other respiratory disease in dogs.Funding was provided by (1) The Kennel Club Charitable Trust (KCCT), Grant no.: RG 71960, http://www.thekennelclub.org.uk/our-reso​urces/kennel-club-charitable-trust/, to DRS JFL; and (2) Cambridge Overseas Trust (Taiwan Cambridge Scholarship), https://www.cambridgetrust.org/about/cam​bridge-overseas-trust/, to NCL.This is the final published version. It first appeared at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130741

Complete replication of hepatitis C virus in cell culture.

Many aspects of the hepatitis C virus (HCV) life cycle have not been reproduced in cell culture, which has slowed research progress on this important human pathogen. Here, we describe a full-length HCV genome that replicates and produces virus particles that are infectious in cell culture (HCVcc). Replication of HCVcc was robust, producing nearly 10(5) infectious units per milliliter within 48 hours. Virus particles were filterable and neutralized with a monoclonal antibody against the viral glycoprotein E2. Viral entry was dependent on cellular expression of a putative HCV receptor, CD81. HCVcc replication was inhibited by interferon-alpha and by several HCV-specific antiviral compounds, suggesting that this in vitro system will aid in the search for improved antivirals

Role of endothelial nitric oxide synthase in isoflurane conditioning-induced neurovascular protection in subarachnoid hemorrhage

Background Delayed cerebral ischemia remains a common and profound risk factor for poor outcome after subarachnoid hemorrhage (SAH). The aim of our current study is to define the role of endothelial nitric oxide synthase (eNOS) in isoflurane conditioning-induced neurovascular protection after SAH. Methods and Results Ten- to 14-week-old male wild-type mice (C57BL/6) as controls and eNOS knockout male mice (strain # 002684) were obtained for the study. Animals underwent either sham surgery, SAH surgery, or SAH with isoflurane conditioning. Anesthetic post conditioning was performed with isoflurane 2% for 1 hour, 1 hour after SAH. Normothermia was maintained with the homeothermic blanket. In a separate cohort, nitric oxide synthase was inhibited by a pan nitric oxide synthase inhibitor, L-nitroarginine methyl ester. Vasospasm measurement was assessed 72 hours after SAH and neurological function was assessed daily. Isoflurane-induced changes in the eNOS protein expression were measured. eNOS protein expression was significantly increased by isoflurane conditioning in naïve mice as well as mice subjected to SAH. Vasospasm of the middle cerebral artery and neurological deficits were evident following SAH versus sham surgery, both in wild-type mice and eNOS knockout mice. Isoflurane conditioning attenuated vasospasm and neurological deficits in wild-type mice. This delayed cerebral ischemia protection was lost in L-nitroarginine methyl ester -administered mice and eNOS knockout mice. Conclusions Our data indicate isoflurane conditioning provides robust protection against SAH-induced vasospasm and neurological deficits, and that this delayed cerebral ischemia protection is critically mediated via isoflurane-induced augmentation of eNOS

Improving adherence to guidelines for the diagnosis and management of pelvic inflammatory disease: a systematic review

Background Evidence suggests adherence to clinical guidelines for pelvic inflammatory disease (PID) diagnosis and management is suboptimal. We systematically reviewed the literature for studies describing strategies to improve the adherence to PID clinical guidelines. Methods. The databases MEDLINE and EMBASE, and reference lists of review articles were searched from January 2000 to April 2012. Only studies with a control group were included. Results. An interrupted time-series study and two randomised controlled trials (RCTs) were included. The interrupted time-series found that following a multifaceted patient and practitioner intervention (practice protocol, provision of antibiotics on-site, written instructions for patients, and active followup), more patients received the recommended antibiotics and attended for followup. One RCT found a patient video on PID self-care did not improve medication compliance and followup. Another RCT found an abbreviated PID treatment guideline for health-practitioners improved their management of PID in hypothetical case scenarios but not their diagnosis of PID. Conclusion. There is limited research on what strategies can improve practitioner and patient adherence to PID diagnosis and management guidelines. Interventions that make managing PID more convenient, such as summary guidelines and provision of treatment on-site, appear to lead to better adherence but further empirical evidence is necessary

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Contains research objectives and reports on three research projects.National Aeronautics and Space Administration (Grant NsG-334)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 28-043-AMC-02536(E

Adaptation strategies in transnational education: a case study of an Australian Master of Health Administration Course offered to Chinese managers

Background: Management decisions in health influence patient care outcomes; however, health management development courses in China are rare. This study aims to document and evaluate a transnational Master of Health Administration (MHA) course launched in 2000 for the benefit of Chinese health managers. Methods: A case study of the MHA program jointly run by an Australian university and a Chinese Medical University was conducted. We reviewed the development of the MHA course through a document analysis (key events recorded in achieves, minutes, and audits) followed by reflection (by two course coordinators), extracting key themes related to adaptative strategies. We then conducted a questionnaire survey of 139 graduates seeking their views on relevance, satisfaction and challenges associated with each subject within the course, the relevance of key management skills (as determined by the Australasian College of Health Service Management competency framework), and the impact of the course on their personal career trajectories. Chi-square tests identified differences in the responses by age, gender, pre-training position, and current workplace. Results: The curriculum pedagogy followed the principles of practice-based reflective learning. Research findings and student feedback shaped the curriculum design and subject content, to enhance management practices of the students. Survey participants expressed high levels of satisfaction and confirmed the relevance of all study subjects. Two subjects, health economics and data management, were perceived as being the most challenging. Of the ten management skills we assessed, relatively low self-rated confidence was found in “strategic thinking” and “planning”. Younger and less experienced graduates were more likely to report learning challenges (p < 0.05). Frontline managers were least likely to obtain promotion by changing employers (χ2 = 6.02, p < 0.05) or being seconded to another position (χ2 = 9.41, p < 0.01). Conclusions: This case study illustrates the suitability of cross-country partnerships in health management training, which offers opportunities for managers to systematically explore and acquire a comprehensive set of management skills applicable to their career needs. Opportunities for developing training aligned to career development opportunities are critical for attracting and developing a competent and well-prepared health service management workforce in China

Primary care physicians' perceptions of barriers and facilitators to management of chronic kidney disease: A mixed methods study.

BackgroundGiven the high prevalence of chronic kidney disease (CKD), primary care physicians (PCPs) frequently manage early stage CKD. Nonetheless, there are challenges in providing optimal CKD care in the primary care setting. This study sought to understand PCPs' perceptions of barriers and facilitators to the optimal management of CKD.Study designMixed methods study.Settings and participantsCommunity-based PCPs in four US cities: Baltimore, MD; St. Louis, MO; Raleigh, NC and San Francisco, CA.MethodologyWe used a self-administered questionnaire and conducted 4 focus groups of PCPs (n = 8 PCPs/focus group) in each city to identify key barriers and facilitators to management of patients with CKD in primary care.Analytic approachWe conducted descriptive analyses of the survey data. Major themes were identified from audio-recorded interviews that were transcribed and coded by the research team.ResultsOf 32 participating PCPs, 31 (97%) had been in practice for &gt;10 years, and 29 (91%) practiced in a non-academic setting. PCPs identified multiple barriers to managing CKD in primary care including at the level of the patient (e.g., low awareness of CKD, poor adherence to treatment recommendations), the provider (e.g., staying current with CKD guidelines), and the health care system (e.g., inflexible electronic medical record, limited time and resources). PCPs desired electronic prompts and lab decision support, concise guidelines, and healthcare financing reform to improve CKD care.ConclusionsPCPs face substantial but modifiable barriers in providing care to patients with CKD. Interventions that address these barriers and promote facilitative tools may improve PCPs' effectiveness and capacity to care for patients with CKD