bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells
Authors: Mladinich Megan C. , Schwedes John , Mackow Erich R. 
Published: July 2017

ABSTRACT

Zika virus (ZIKV) is a mosquito-borne
Flavivirus
that has emerged as the cause of encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in human bodily fluids for up to 6 months, is sexually transmitted, and traverses the placenta and the blood-brain barrier (BBB) to damage neurons. Cells that support persistent ZIKV replication and mechanisms by which ZIKV establishes persistence remain enigmatic but central to ZIKV entry into protected neuronal compartments. The endothelial cell (EC) lining of capillaries normally constrains transplacental transmission and forms the BBB, which selectively restricts access of blood constituents to neurons. We found that ZIKV (strain PRVABC59) persistently infects and continuously replicates in primary human brain microvascular ECs (hBMECs), without cytopathology, for >9 days and following hBMEC passage. ZIKV did not permeabilize hBMECs but was released basolaterally from polarized hBMECs, suggesting a direct mechanism for ZIKV to cross the BBB. ZIKV-infected hBMECs were rapidly resistant to alpha interferon (IFN-α) and transiently induced, but failed to secrete, IFN-β and IFN-λ. Global transcriptome analysis determined that ZIKV constitutively induced IFN regulatory factor 7 (IRF7), IRF9, and IFN-stimulated genes (ISGs) 1 to 9 days postinfection, despite persistently replicating in hBMECs. ZIKV constitutively induced ISG15, HERC5, and USP18, which are linked to hepatitis C virus (HCV) persistence and IFN regulation, chemokine CCL5, which is associated with immunopathogenesis, as well as cell survival factors. Our results reveal that hBMECs act as a reservoir of persistent ZIKV replication, suggest routes for ZIKV to cross hBMECs into neuronal compartments, and define novel mechanisms of ZIKV persistence that can be targeted to restrict ZIKV spread.

IMPORTANCE
ZIKV persists in patients, crossing placental and neuronal barriers, damaging neurons, and causing fetal microencephaly. We found that ZIKV persistently infects brain endothelial cells that normally protect neurons from viral exposure. hBMECs are not damaged by ZIKV infection and, analogous to persistent HCV infection, ZIKV constitutively induces and evades antiviral ISG and IFN responses to continuously replicate in hBMECs. As a result, hBMECs provide a protective niche for systemic ZIKV spread and a viral reservoir localized in the normally protective blood-brain barrier. Consistent with the spread of ZIKV into neuronal compartments, ZIKV was released basolaterally from hBMECs. Our findings define hBMEC responses that contribute to persistent ZIKV infection and potential targets for clearing ZIKV infections from hBMECs. These results further suggest roles for additional ZIKV-infected ECs to facilitate viral spread and persistence in the protected placental, retinal, and testicular compartments.
Longitudinal characterisation of function and structure of Bietti crystalline dystrophy: report on a novel homozygous mutation in CYP4V2
Authors: Lockhart Catherine M , Smith Travis B , Yang Paul , Naidu Malini , Rettie Allan E , Nath Abhinav , Weleber Richard , Kelly Edward J 
Published: July 2017

BackgroundBietti crystalline dystrophy (BCD) is a rare inherited disorder characterised by fine crystalline deposits in the corneal limbus and retinal posterior pole. In 2004, mutations in the CYP4V2 gene were identified as the cause of BCD. Here, we describe the report of a homozygous point mutation in a patient with BCD and provide detailed characterisation of functional and structural changes over 20 years.MethodsAt regular intervals, the patient underwent repeat ophthalmic evaluations. DNA was extracted from buccal swabs, amplified by standard PCR and analysed for homology to the CYP4V2 sequence. Homology modelling was conducted using Iterative Threading ASSEmbly Refinement and molecular dynamics simulations using GROningen MAchine for Chemical Simulations.ResultsThe proband, a 47-year-old woman of German ancestry was diagnosed with crystalline retinopathy at age 25. Over the next 20 years, visual acuity and function gradually declined with progression of retinal pigment epithelium and choroidal atrophy. When first tested at 39 years of age, the multifocal electroretinogram (ERG) was markedly abnormal, more so for the right eye, whereas the full-field ERG was more symmetrical and lagged other measures of visual function. Gene sequencing showed a single C>T point mutation in exon 9 encoding a R400C amino acid change. Computational modelling suggests the mutation impairs function due to loss of a hydrogen bonding interaction with the propionate side chains of the haeme prosthetic group.ConclusionThis is the first report of a homozygous R400C mutation in CYP4V2 with protein modelling showing high likelihood of enzyme dysfunction. The comprehensive long-term clinical follow-up provides insight into disease progression and highlights possible anti-inflammatory modulation of disease severity.
A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults
Authors: Morton Robert W , Murphy Kevin T , McKellar Sean R , Schoenfeld Brad J , Henselmans Menno , Helms Eric , Aragon Alan A , Devries Michaela C , Banfield Laura , Krieger James W , Phillips Stuart M 
Published: July 2017

ObjectiveWe performed a systematic review, meta-analysis and meta-regression to determine if dietary protein supplementation augments resistance exercise training (RET)-induced gains in muscle mass and strength.Data sourcesA systematic search of Medline, Embase, CINAHL and SportDiscus.Eligibility criteriaOnly randomised controlled trials with RET ≥6 weeks in duration and dietary protein supplementation.DesignRandom-effects meta-analyses and meta-regressions with four a priori determined covariates. Two-phase break point analysis was used to determine the relationship between total protein intake and changes in fat-free mass (FFM).ResultsData from 49 studies with 1863 participants showed that dietary protein supplementation significantly (all p<0.05) increased changes (means (95% CI)) in: strength—one-repetition-maximum (2.49 kg (0.64, 4.33)), FFM (0.30 kg (0.09, 0.52)) and muscle size—muscle fibre cross-sectional area (CSA; 310 µm2(51, 570)) and mid-femur CSA (7.2 mm2(0.20, 14.30)) during periods of prolonged RET. The impact of protein supplementation on gains in FFM was reduced with increasing age (−0.01 kg (−0.02,–0.00), p=0.002) and was more effective in resistance-trained individuals (0.75 kg (0.09, 1.40), p=0.03). Protein supplementation beyond total protein intakes of 1.62 g/kg/day resulted in no further RET-induced gains in FFM.Summary/conclusionDietary protein supplementation significantly enhanced changes in muscle strength and size during prolonged RET in healthy adults. Increasing age reduces and training experience increases the efficacy of protein supplementation during RET. With protein supplementation, protein intakes at amounts greater than ~1.6 g/kg/day do not further contribute RET-induced gains in FFM.
Levels and trends of childhood undernutrition by wealth and education according to a Composite Index of Anthropometric Failure: evidence from 146 Demographic and Health Surveys from 39 countries
Authors: Vollmer Sebastian , Harttgen Kenneth , Kupka Roland , Subramanian S V 
Published: July 2017

BackgroundGovernments have endorsed global targets to reduce childhood undernutrition as part of the Sustainable Development Goals. Understanding the socioeconomic differences in childhood undernutrition has the potential to be helpful for targeting policy to reach these goals.MethodsWe specify a logistic regression model with the Composite Index of Anthropometric Failure (CIAF) as the outcome and indicator variables for wealth quartiles, maternal education categories and a set of covariates as explanatory variables. Wealth and education variables are interacted with a period indicator for 1990–2000 compared with 2001–2014 to observe differences over time. Based on these regressions we calculate predicted CIAF prevalence by wealth and education categories and over time.ResultsThe sample included 146 surveys from 39 low-income and lower-middle-income countries with an overall sample size of 533 217 children. CIAF prevalence was 47.5% in 1990–2000, and it declined to 42.6% in 2001–2014. In 1990–2000 the CIAF prevalence of children with mothers with less than primary education was 31 percentage points higher than for mothers with secondary or higher education. This difference slightly decreased to 27 percentage points in 2001–2014. The difference in predicted CIAF prevalence of children from the highest and lowest wealth quartiles was 21 percentage points and did not change over time.ConclusionsWe find evidence for persistent and even increasing socioeconomic inequalities in childhood undernutrition, which underlines the importance of previous calls for equity-driven approaches targeting the most vulnerable to reduce childhood malnutrition.
A Self-Management Programme of Activity Coping and Education - SPACE for COPD(C) - in primary care: The protocol for a pragmatic trial
Authors: Bourne Claire LA , Kanabar Pratiksha , Mitchell Katy , Schreder Sally , Houchen-Wolloff Linzy , Bankart M John G , Apps Lindsay , Hewitt Stacey , Harvey-Dunstan Theresa , Singh Sally J 
Published: July 2017

IntroductionNational guidance for chronic obstructive pulmonary disease (COPD) suggests that self-management support be provided for patients. Our institution has developed a standardised, manual-based, supported self-management programme: Self-Management Programme of Activity Coping and Education (SPACE for COPD(C)). SPACE was previously piloted on a 1-2-1 basis, delivered by researchers, to individuals with COPD. Discussions with stakeholders highlighted considerable interest in delivering the SPACE for COPD(C) intervention as a group-based self-management programme facilitated by healthcare professionals (HCPs) in primary care settings. The study aims are to explore the feasibility, acceptability and efficacy for the intervention to be delivered and supported by HCPs and to examine whether group-based delivery of SPACE for COPD(C), with sustained support, improves patient outcomes following the SPACE for COPD(C) intervention.Methods and analysisA prospective, multi-site, single-blinded randomised controlled trial (RCT) will be conducted, with follow-up at 6 and 9 months. Participants will be randomly assigned to either the control group (usual care) or intervention group (a six-session, group-based SPACE for COPD(C)self-management programme delivered over 5 months). The primary outcome is change in COPD assessment test at 6 months.A discussion session will be conducted with HCPs who deliver the intervention to discuss and gain insight into any potential facilitators/barriers to implementing the intervention in practice. Furthermore, we will conduct semi-structured focus groups with intervention participants to understand feasibility and acceptability. All qualitative data will be analysed thematically.Ethics and disseminationThe project has received a favourable opinion from South Hampshire B Research Ethics Committee, REC reference: 14/SC/1169 and full R&D approval from the University Hospitals of Leicester NHS Trust: 152408.Study results will be disseminated through appropriate peer-reviewed journals, national and international respiratory/physiotherapy conferences, via the Collaboration and Leadership in Applied Health Research and Care and through social media.Trial registrationISRCTN17942821; pre-results.
Perceived impacts of the national essential medicines system: a cross-sectional survey of health workers in urban community health services in China
Authors: Zhang Tao , Liu Chaojie , Ren Jianping , Wang Sheng , Huang Xianhong , Guo Qing 
Published: July 2017

ObjectivesThis study aimed to investigate the perceptions of primary care workers about the impacts of the national essential medicines policy (NEMP).SettingA cross-sectional questionnaire survey was undertaken in 42 urban community health centres randomly selected from four provinces in China.Participants791 primary care workers rated the impacts of the NEMP on a 5-point Likert scale.Outcome measuresAn average score for the impacts of the NEMP on four aspects (the practice of health workers, interactions of patients with health workers, operations of health centres and provision of medicines) was calculated, each ranging from 0 to 100. A higher score indicates a more positive rating. Linear regression models were established to determine the sociodemographic characteristics (region, age, gender, profession, training, income) that were associated with the ratings.ResultsThe respondents gave an average rating score of 65.61±11.76, 63.17±13.62, 66.35±13.02 and 67.26±11.60 for the impacts of the NEMP on health workers, patients, health centres and provision of medicines, respectively. Respondents from the central region rated the NEMP higher than those from the eastern and western regions. The pharmacists (β=5.457~7.558, p<0.001) and nurses (β=2.612~3.107, p<0.05) gave a more positive rating on the NEMP than their physician counterparts. A higher income was found to be associated with a decrease in the NEMP ratings. Repetitive training was a predictor of higher ratings.ConclusionsThe NEMP has significant impacts (as perceived by the health workers) on health services delivery in primary care settings. However, the impacts of the NEMP vary by region, professional practice and the income level of health workers. It is important to maintain support from physicians through income subsidies (to compensate for potential loss) and training.
The Women and Their Children’s Health (WaTCH) study: methods and design of a prospective cohort study in Louisiana to examine the health effects from the BP oil spill
Authors: Peters Edward S , Rung Ariane L , Bronson Megan H , Brashear Meghan M , Peres Lauren C , Gaston Symielle , Sullivan Samaah M , Peak Kate , Abramson David M , Fontham Elizabeth T H , Harrington Daniel , Oral Evrim , Trapido Edward J 
Published: July 2017

PurposeThe Deepwater Horizon Oil Spill is the largest marine oil spill in US history. Few studies have evaluated the potential health effects of this spill on the Gulf Coast community. The Women and Their Children’s Health (WaTCH) study is a prospective cohort designed to investigate the midterm to long-term physical, mental and behavioural health effects of exposure to the oil spill.ParticipantsWomen were recruited by telephone from pre-existing lists of individuals and households using an address-based sampling frame between 2012 and 2014. Baseline interviews obtained information on oil spill exposure, demographics, physical and mental health, and health behaviours. Women were also asked to provide a household roster, from which a child between 10 and 17 years was randomly selected and recruited into a child substudy. Telephone respondents were invited to participate in a home visit in which blood samples, anthropometrics and neighbourhood characteristics were measured. A follow-up interview was completed between 2014 and 2016.Findings to date2852 women completed the baseline interview, 1231 of whom participated in the home visit, and 628 children participated in the child’s health substudy. The follow-up interview successfully reinterviewed 2030 women and 454 children.Future plansWaTCH continues to conduct follow-up surveys, with a third wave of interviews planned in 2017. Also, we are looking to enhance the collection of spatially related environmental data to facilitate assessment of health risks in the study population. In addition, opportunities to participate in behavioural interventions for subsets of the cohort have been initiated. There are ongoing studies that examine the relationship between genetic and immunological markers with mental health.
MiYoga: a randomised controlled trial of a mindfulness movement programme based on hatha yoga principles for children with cerebral palsy: a study protocol
Authors: Mak Catherine , Whittingham Koa , Cunnington Ross , Boyd Roslyn N 
Published: July 2017

IntroductionCerebral palsy (CP) is the most common childhood physical disability, with life-long impacts for 1.77 in 1000 children. Although CP is primarily a physical disability, children with CP have an increased risk of experiencing cognitive difficulties, particularly attention and executive function deficits. Impairment in cognitive abilities can lead to subsequent impairment in independent functioning, education, employment and interpersonal relationships. This paper reports the protocol of a randomised controlled trial of a novel family-centred lifestyle intervention based on mindfulness and hatha yoga principles (MiYoga). MiYoga aims to enhance child and parent outcomes for children with CP.Methods and analysisThe aim is to recruit 36 child-parent dyads (children aged 6–16 years; bilateral or unilateral CP; Gross Motor Function Classification System I–III), who will be randomly assigned to two groups: MiYoga and wait list control. The MiYoga programme will be facilitated in a group format for 8 weeks. Assessments will be administered at baseline, prior to MiYoga, following completion of MiYoga, and at 6-month follow-up (retention). The primary outcome will be the child’s sustained attentional ability as measured by the Conner’s Continuous Performance Test II. Other outcomes of interest for children with CP consists of attentional control, physical functioning, behavioural and well-being. For parents, the outcomes of interest are mindfulness, psychological flexibility and well-being. Data will be analysed using general linear models, specifically analysis of covariance and analysis of variance.Ethics and disseminationFull ethical approval for this study has been obtained by the Children’s Health Queensland Hospital and Health Service Research Ethics Committee (HREC/12/QRCH/120) and The University of Queensland (2012000993). If MiYoga is proven effective, its dissemination would assist children with CP and complement their ongoing therapy by improving the ability of the child to pay attention at school and in therapy, and alleviating environmental stressors for both the child and his/her parents.Trial registration numberACTRN12613000729729; Pre-results.http://www.ANZCTR.org.au/ACTRN12613000729729.aspxDate of trial registrationProspectively registered on 2 July 2013–present (ongoing).Findings to dateRecruitment is complete. Data are still being collected at present. We aim to complete data collection by February 2017.
Bubble continuous positive airway pressure in the treatment of severe paediatric pneumonia in Malawi: a cost-effectiveness analysis
Authors: Kortz Teresa Bleakly , Herzel Benjamin , Marseille Elliot , Kahn James G 
Published: July 2017

ObjectivesPneumonia is the largest infectious cause of death in children under 5 years globally, and limited resource settings bear an overwhelming proportion of this disease burden. Bubble continuous positive airway pressure (bCPAP), an accepted supportive therapy, is often thought of as cost-prohibitive in these settings. We hypothesise that bCPAP is a cost-effective intervention in a limited resource setting and this study aims to determine the cost-effectiveness of bCPAP, using Malawi as an example.DesignCost-effectiveness analysis.SettingDistrict and central hospitals in Malawi.ParticipantsChildren aged 1 month–5 years with severe pneumonia, as defined by WHO criteria.InterventionsUsing a decision tree analysis, we compared standard of care (including low-flow oxygen and antibiotics) to standard of care plus bCPAP.Primary and secondary outcome measuresFor each treatment arm, we determined the costs, clinical outcomes and averted disability-adjusted life years (DALYs). We assigned input values from a review of the literature, including applicable clinical trials, and calculated an incremental cost-effectiveness ratio (ICER).ResultsIn the base case analysis, the cost of bCPAP per patient was $15 per day and $41 per hospitalisation, with an incremental net cost of $64 per pneumonia episode. bCPAP averts 5.0 DALYs per child treated, with an ICER of $12.88 per DALY averted compared with standard of care. In one-way sensitivity analyses, the most influential uncertainties were case fatality rates (ICER range $9–32 per DALY averted). In a multi-way sensitivity analysis, the median ICER was $12.97 per DALY averted (90% CI, $12.77 to $12.99).ConclusionbCPAP is a cost-effective intervention for severe paediatric pneumonia in Malawi. These results may be used to inform policy decisions, including support for widespread use of bCPAP in similar settings.
Clinical characteristics of importance to outcome in patients with axial spondyloarthritis: protocol for a prospective descriptive and exploratory cohort study
Authors: Andreasen Rikke Asmussen , Kristensen Lars Erik , Ellingsen Torkell , Christensen Robin , Baraliakos Xenofon , Wied Jimmi , Aalykke Claus , Ulstrup Thomas , Schiøttz-Christensen Berit , Horn Hans Christian , Emamifar Amir , Duerlund Bent , Fischer Lars , Hansen Inger Marie Jensen 
Published: July 2017

IntroductionSpondyloarthritis (SpA) is a heterogeneous spectrum of rheumatic diseases with either predominantly axial inflammatory symptoms of the spine and sacroiliac joints or predominantly peripheral arthritis. The two main entities of axial SpA (axSpA) are ankylosing spondylitis or non-radiographic axSpA (nr-axSpA). Tumour necrosis factor-α inhibitors have revolutionised the treatment of patients with axSpA who failed to respond to non-steroidal anti-inflammatory drugs and physical therapy. Chronic pain is common in patients with SpA and may still persist despite the lack of signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may play a role in the generation of chronic pain in SpA. The painDETECT Questionnaire (PDQ) is a screening tool developed to detect neuropathic pain components. The primary objective is to explore the prognostic value of the PDQ regarding treatment response in patients with axSpA 3 months after initiating a biological agent. Secondary aim is to evaluate the impact of extra-articular manifestations, comorbidities and patient-reported outcomes and elucidate if these factors influence treatment response.Method and analysisWe will include 60 participants (≥18 years of age) diagnosed with axSpA independent of main entity, who initiate or switch treatment of a biologic. Data will be collected at baseline and at endpoint following Danish clinical practice (≥3 months) of treatment with biologics. We will explore whether the PDQ and other phenotypical patient characteristics are prognostically important for response to biological therapy according to established response criteria like 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (50%) and Ankylosing Spondylitis Disease Activity Score.Ethics and disseminationThe study is approved by the Region of Southern Denmark’s Ethics committee (S-20160094) and has been designed in cooperation with patient representatives. The study is registered at clinicaltrials.gov (NCT02948608, pre-results). Dissemination will occur through publication(s) in international peer-reviewed journal(s).