bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endocrinology and Pediatric Exercise Science—The Year That Was 2017
Authors: Eliakim Alon 
Published: February 2018

The Pediatric Exercise Science “Year That Was” section aims to highlight the most important (to the author’s opinion) manuscripts that were published in 2017 in the field of endocrinology and pediatric exercise science. This year’s selection includes studies showing that 1) in pubertal swimmers, there is a decrease in insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) during intense training (a catabolic-type hormonal response) with an anabolic “rebound” characterized by a significant increase of these growth factors during training tapering down. Moreover, it was shown that changes of IGF-I and IGFBP-3 paralleled changes in peak and average force but not with endurance properties, showing decreases during intense training and increases during tapering; 2) a meta-analysis showing that growth hormone administration elicits significant changes in body composition and possible limited effect on anaerobic performance but does not increase either muscle strength or aerobic exercise capacity in healthy, young subjects; and 3) short-term exercise intervention can prevent the development of polycystic ovary syndrome in a dose-dependent manner in letrozole-induced polycystic ovary syndrome rat model with high-intensity exercise being most effective. The implication of these studies to the pediatric population, their importance, and the new research avenues that were opened by these studies is emphasized.
Modeling the Emergence of Antibiotic Resistance in the Environment: an Analytical Solution for the Minimum Selection Concentration
Authors: Greenfield Ben K. , Shaked Shanna , Marrs Carl F. , Nelson Patrick , Raxter Ian , Xi Chuanwu , McKone Thomas E. , Jolliet Olivier 
Published: February 2018

ABSTRACT

Environmental antibiotic risk management requires an understanding of how subinhibitory antibiotic concentrations contribute to the spread of resistance. We develop a simple model of competition between sensitive and resistant bacterial strains to predict the minimum selection concentration (MSC), the lowest level of antibiotic at which resistant bacteria are selected. We present an analytical solution for the MSC based on the routinely measured MIC, the selection coefficient (
sc
) that expresses fitness differences between strains, the intrinsic net growth rate, and the shape of the bacterial growth dose-response curve with antibiotic or metal exposure (the Hill coefficient [κ]). We calibrated the model by optimizing the Hill coefficient to fit previously reported experimental growth rate difference data. The model fit varied among nine compound-taxon combinations examined but predicted the experimentally observed MSC/MIC ratio well (
R
2
≥ 0.95). The shape of the antibiotic response curve varied among compounds (0.7 ≤ κ ≤ 10.5), with the steepest curve being found for the aminoglycosides streptomycin and kanamycin. The model was sensitive to this antibiotic response curve shape and to the
sc
, indicating the importance of fitness differences between strains for determining the MSC. The MSC can be >1 order of magnitude lower than the MIC, typically by the factor
sc
κ
. This study provides an initial quantitative depiction and a framework for a research agenda to examine the growing evidence of selection for resistant bacterial communities at low environmental antibiotic concentrations.
Effects of Renal Impairment and Hemodialysis on the Pharmacokinetics and Safety of the Glecaprevir and Pibrentasvir Combination in Hepatitis C Virus-Negative Subjects
Authors: Kosloski Matthew P. , Zhao Weihan , Marbury Thomas C. , Preston Richard A. , Collins Michael G. , Pugatch David , Mensa Federico , Kort Jens , Liu Wei 
Published: February 2018

ABSTRACT

Hepatitis C virus (HCV) infection is an independent risk factor for developing chronic renal impairment and end-stage renal disease. Limited treatment options are available for HCV genotype 2, 3, 5, and 6 infections in patients with an estimated glomerular filtration rate (eGFR) of <30 ml/min. Glecaprevir and pibrentasvir are active against all six major HCV genotypes, are primarily excreted in the bile, and have minimal renal elimination. Therefore, combined treatment with these direct-acting antivirals may be useful for patients with HCV infection and chronic kidney disease. A phase 1, multicenter, open-label study evaluated the effects of renal impairment on the pharmacokinetics and safety of glecaprevir-pibrentasvir. In substudy 1, 38 subjects with stage 2 to 5 chronic kidney disease who were not on dialysis or who had normal renal function received single doses of the combination of 300 mg glecaprevir and 120 mg pibrentasvir. In substudy 2, 8 subjects requiring hemodialysis received single doses of the combination of 300 mg glecaprevir and 120 mg pibrentasvir under dialysis and nondialysis conditions. Regression analyses demonstrated increased glecaprevir and pibrentasvir plasma exposures, as determined by the area under the curve, with decreasing renal function, up to 56% and 46%, respectively, in subjects with an eGFR of <15 ml/min/1.73 m
2
. In dialysis-dependent subjects, glecaprevir and pibrentasvir exposures were similar (≤18% difference) when study drugs were administered before hemodialysis or on a nondialysis day. Adverse events were mostly mild, with the most common being self-limited fatigue (3 subjects). The study findings support the clinical evaluation of glecaprevir-pibrentasvir without dose adjustment in HCV-infected subjects with renal impairment. (This study has been registered at ClinicalTrials.gov under registration number NCT02442258.)
Direct Molecular Detection and Genotyping of Borrelia burgdorferi Sensu Lato in Cerebrospinal Fluid of Children with Lyme Neuroborreliosis
Authors: Barstad Bjørn , Quarsten Hanne , Tveitnes Dag , Noraas Sølvi , Ask Ingvild S. , Saeed Maryam , Bosse Franziskus , Vigemyr Grete , Huber Ilka , Øymar Knut 
Published: February 2018

ABSTRACT

The current diagnostic marker of Lyme neuroborreliosis (LNB), the
Borrelia burgdorferi
sensu lato
antibody index (AI) in the cerebrospinal fluid (CSF), has insufficient sensitivity in the early phase of LNB. We aimed to elucidate the diagnostic value of PCR for
B. burgdorferi
sensu lato
in CSF from children with symptoms suggestive of LNB and to explore
B. burgdorferi
sensu lato
genotypes associated with LNB in children. Children were prospectively included in predefined groups with a high or low likelihood of LNB based on diagnostic guidelines (LNB symptoms, CSF pleocytosis, and
B. burgdorferi
sensu lato
antibodies) or the detection of other causative agents. CSF samples were analyzed by two
B. burgdorferi
sensu lato
-specific real-time PCR assays and, if
B. burgdorferi
sensu lato
DNA was detected, were further analyzed by five singleplex real-time PCR assays for genotype determination. For children diagnosed as LNB patients (58 confirmed and 18 probable) (
n
= 76) or non-LNB controls (
n
= 28), the sensitivity and specificity of PCR for
B. burgdorferi
sensu lato
in CSF were 46% and 100%, respectively.
B. burgdorferi
sensu lato
DNA was detected in 26/58 (45%) children with AI-positive LNB and in 7/12 (58%) children with AI-negative LNB and symptoms of short duration. Among 36 children with detectable
B. burgdorferi
sensu lato
DNA, genotyping indicated
Borrelia garinii
(
n
= 27) and non-
B. garinii
(
n
= 1) genotypes, while 8 samples remained untyped. Children with LNB caused by
B. garinii
did not have a distinct clinical picture. The rate of detection of
B. burgdorferi
sensu lato
DNA in the CSF of children with LNB was higher than that reported previously. PCR for
B. burgdorferi
sensu lato
could be a useful supplemental diagnostic tool in unconfirmed LNB cases with symptoms of short duration.
B. garinii
was the predominant genotype in children with LNB.
Escape of Hepatitis C Virus from Epitope I Neutralization Increases Sensitivity of Other Neutralization Epitopes
Authors: Gu Jun , Hardy Joshua , Boo Irene , Vietheer Patricia , McCaffrey Kathleen , Alhammad Yousef , Chopra Abha , Gaudieri Silvana , Poumbourios Pantelis , Coulibaly Fasséli , Drummer Heidi E. 
Published: February 2018

ABSTRACT
The hepatitis C virus (HCV) E2 glycoprotein is a major target of the neutralizing antibody (nAb) response, with multiple type-specific and broadly neutralizing antibody (bnAb) epitopes identified. The 412-to-423 region can generate bnAbs that block interaction with the cell surface receptor CD81, with activity toward multiple HCV genotypes. In this study, we reveal the structure of rodent monoclonal antibody 24 (MAb24) with an extensive contact area toward a peptide spanning the 412-to-423 region. The crystal structure of the MAb24–peptide 412-to-423 complex reveals the paratope bound to a peptide hairpin highly similar to that observed with human MAb HCV1 and rodent MAb AP33, but with a different angle of approach. In viral outgrowth experiments, we demonstrated three distinct genotype 2a viral populations that acquired resistance to MAb24 via N415D, N417S, and N415D/H386R mutations. Importantly, the MAb24-resistant viruses exhibited significant increases in sensitivity to the majority of bnAbs directed to epitopes within the 412-to-423 region and in additional antigenic determinants located within E2 and the E1E2 complex. This study suggests that modification of N415 causes a global change in glycoprotein structure that increases its vulnerability to neutralization by other antibodies. This finding suggests that in the context of an antibody response to viral infection, acquisition of escape mutations in the 412-to-423 region renders the virus more susceptible to neutralization by other specificities of nAbs, effectively reducing the immunological fitness of the virus. A vaccine for HCV that generates polyspecific humoral immunity with specificity for the 412-to-423 region and at least one other region of E2 is desirable.

IMPORTANCE
Understanding how antibodies neutralize hepatitis C virus (HCV) is essential for vaccine development. This study reveals for the first time that when HCV develops resistance to a major class of bnAbs targeting the 412-to-423 region of E2, this results in a concomitant increase in sensitivity to neutralization by a majority of other bnAb specificities. Vaccines for the prevention of HCV infection should therefore generate bnAbs directed toward the 412-to-423 region of E2 and additional bnAb epitopes within the viral glycoproteins.
Paediatric overdiagnosis modelled by coronary abnormality trends in Kawasaki disease
Authors: Coon Eric R , Wilkes Jacob , Bratton Susan L , Srivastava Rajendu 
Published: February 2018

ObjectiveCompare trends in coronary artery (CA) abnormality diagnoses to trends in adverse cardiac outcomes among American children with Kawasaki disease (KD) to assess the fit of detection of CA abnormalities to an established model of overdiagnosis.DesignMulticenter retrospective cohort.Setting48 US children’s hospitals in the Paediatric Health Information System database.ParticipantsChildren <18 years receiving care for KD between 2000 and 2014.Main outcome measuresThe main outcomes were rates of CA abnormality diagnoses and adverse cardiac outcomes, measured during a child’s incident KD visit and longitudinally at all subsequent visits to the same hospital, through December 2016. CA abnormalities were considered severe if long-term anticoagulation other than aspirin was prescribed. Trends were tested using mixed effects logistic regression, adjusting for patient demographics.ResultsAmong 17 809 children treated for KD, a CA abnormality was diagnosed in 1435 children (8%), including 1117 considered non-severe and 318 severe. The rate of non-severe CA abnormality diagnoses increased from 45 per 1000 patients with KD in 2000 to 81 per 1000 patients with KD in 2014, representing an adjusted 2.3-fold increased odds (95% CI 1.8 to 3.0) of diagnosis. There was no significant change in diagnoses of severe CA abnormalities. Adverse cardiac outcomes were stable over the study period at 19 per 1000 patients with KD (P=0.24 for trend).ConclusionsThe rising rate of detection of non-severe CA abnormalities accompanied by an unchanging rate of adverse cardiac outcomes among American children with KD fits an overdiagnosis pattern.
Compliance with guidelines for disease management in diabetes: results from the SwissDiab Registry
Authors: Schimke Katrin E , Renström Frida , Meier Sandro , Stettler Christoph , Brändle Michael 
Published: February 2018

ObjectiveTight glycemic control and aggressive treatment of additional cardiovascular risk factors can substantially reduce risk of diabetes-related complications. In 2013, the Swiss Society of Endocrinology and Diabetology (SSED) established national criteria on good disease management in diabetes, but little is known about compliance in clinical care. Here we assessed to what extent patients from two tertiary care centers in the German-speaking part of Switzerland enrolled in the Swiss Diabetes (SwissDiab) Registry adhere to the SSED criteria.Research design and methodsSwissDiab is a prospective observational cohort study of patients regularly treated at Swiss tertiary diabetes centers. Data were collected through standardized annual health examinations. Baseline participant descriptive statistics, stratified by diabetes mellitus type 1 (DM1) and type 2 (DM2), were compared with SSED targets for glycemic control, blood pressure, blood lipids, weight maintenance, and ophthalmic examination.ResultsBy the end of 2016, 604 participants with DM1 (40%) and DM2 (60%) had data available for analyses, 36% and 29% women, respectively. At baseline, all the SSED targets were met with two exceptions: a glycated hemoglobin A1c value <7% was measured in 32% of participants with DM1 (SSED target: ≥40%) and 47% and 56% of overweight or obese participants with DM1 and DM2, respectively, received nutritional counseling in the previous year (SSED target: ≥80%).ConclusionsThe SSED targets for good disease management in diabetes were achieved in the majority of participants at the time of enrollment, but results also highlight areas where disease management can be improved, particularly the role of nutrition counseling.
Comparison of a newly established emotional stimulus approach to a classical assessment-driven approach in BLS training: a randomised controlled trial
Authors: Kuckuck Karl , Schröder Hanna , Rossaint Rolf , Stieger Lina , Beckers Stefan K , Sopka Sasa 
Published: February 2018

ObjectiveThe study objective was to implement two strategies (short emotional stimulus vs announced practical assessment) in the teaching of resuscitation skills in order to evaluate whether one led to superior outcomes.SettingThis study is an educational intervention provided in one German academic university hospital.ParticipantsFirst-yearmedical students (n=271) during the first3 weeks of their studies.InterventionsParticipants were randomly assigned to one of two groups following a sequence of random numbers: the emotional stimulus group (EG) and the assessment group (AG). In the EG, the intervention included watching an emotionally stimulating video prior to the Basic Life Support (BLS) course. In the AG, a practical assessment of the BLS algorithm was announced and tested within a 2 min simulated cardiac arrest scenario. After the baseline testing, a standardised BLS course was provided. Evaluation points were defined 1 week and 6 months after.Primary outcome measuresCompression depth (CD) and compression rate (CR) were recorded as the primary endpoints for BLS quality.ResultsWithin the study, 137 participants were allocated to the EG and 134 to the AG. 104 participants from EG and 120 from AG were analysed1 week after the intervention, where they reached comparable chest-compression performance without significant differences (CR P=0.49; CD P=0.28). The chest-compression performance improved significantly for the EG (P<0.01) and the AG (P<0.01) while adhering to the current resuscitation guidelines criteria for CD and CR.ConclusionsThere was no statistical difference between both groups’ practical chest-compression-performance. Nevertheless, the 2 min video sequence used in the EG with its low production effort and costs, compared with the expensive assessment approach, provides broad opportunities for applicability in BLS training.
Cost-effectiveness of mechanical thrombectomy within 6 hours of acute ischaemic stroke in China
Authors: Pan Yuesong , Cai Xueli , Huo Xiaochuan , Zhao Xingquan , Liu Liping , Wang Yongjun , Miao Zhongrong , Wang Yilong 
Published: February 2018

ObjectivesEndovascular mechanical thrombectomy is an effective but expensive therapy for acute ischaemic stroke with proximal anterior circulation occlusion. This study aimed to determine the cost-effectiveness of mechanical thrombectomy in China, which is the largest developing country.DesignA combination of decision tree and Markov model was developed. Outcome and cost data were derived from the published literature and claims database. The efficacy data were derived from the meta-analyses of nine trials. One-way and probabilistic sensitivity analyses were performed in order to assess the uncertainty of the results.SettingHospitals in China.ParticipantsThe patients with acute ischaemic stroke caused by proximal anterior circulation occlusion within 6 hours.InterventionsMechanical thrombectomy within 6 hours with intravenous tissue plasminogen activator (tPA) treatment within 4.5 hours versus intravenous tPA treatment alone.Outcome measuresThe benefit conferred by the treatment was assessed by estimating the cost per quality-adjusted life-year (QALY) gained in the long term (30 years).ResultsThe addition of mechanical thrombectomy to intravenous tPA treatment compared with standard treatment alone yielded a lifetime gain of 0.794 QALYs at an additional cost of CNY 50 000 (US$7700), resulting in a cost of CNY 63 010 (US$9690) per QALY gained. The probabilistic sensitivity analysis indicated that mechanical thrombectomy was cost-effective in 99.9% of the simulation runs at a willingness-to-pay threshold of CNY 125 700 (US$19 300) per QALY.ConclusionsMechanical thrombectomy for acute ischaemic stroke caused by proximal anterior circulation occlusion within 6 hours was cost-effective in China. The data may be used as a reference with regard to medical resources allocation for stroke treatment in low-income and middle-income countries as well as in the remote areas in the developed countries.
Does early vitamin B12supplementation improve neurodevelopment and cognitive function in childhood and into school age: a study protocol for extended follow-ups from randomised controlled trials in India and Tanzania
Authors: Winje Brita Askeland , Kvestad Ingrid , Krishnamachari Srinivasan , Manji Karim , Taneja Sunita , Bellinger David C , Bhandari Nita , Bisht Shruti , Darling Anne Marie , Duggan Christopher P , Fawzi Wafaie , Hysing Mari , Kumar Tivendra , Kurpad Anura V , Sudfeld Christopher R , Svensen Erling , Thomas Susan , Strand Tor A 
Published: February 2018

IntroductionAs many as 250 million children under the age of 5 may not be reaching their full developmental potential partly due to poor nutrition during pregnancy and the first 2 years of life. Micronutrients, including vitamin B12, are important for the development of brain structure and function; however, the timing, duration and severity of deficiencies may alter the impact on functional development outcomes. Consequently, to fully explore the effect of vitamin B12on cognitive function, it is crucial to measure neurodevelopment at different ages, in different populations and with vitamin B12supplementation at different times during the critical periods of neurodevelopment.Methods and analysisIn this project, we follow up children from four recently completed randomised placebo-controlled trials of oral vitamin B12supplementation, two in India and two in Tanzania, to explore the long-term effects on neurodevelopmental outcomes and growth. All the included trials provided at least two recommended dietary allowances of oral vitamin B12daily for at least 6 months. Vitamin B12was supplemented either during pregnancy, early infancy or early childhood. Primary outcomes are neurodevelopmental status, cognitive function and growth later in childhood. We apply validated and culturally appropriate instruments to identify relevant developmental outcomes. All statistical analyses will be done according to intention-to-treat principles. The project provides an excellent opportunity to examine the effect of vitamin B12supplementation in different periods during early life and measure the outcomes later in childhood.Ethics and disseminationThe study has received ethical approvals from all relevant authorities in Norway, USA, Tanzania and India and complies fully with ethical principles for medical research. Results will be presented at national and international research and policy meetings and published in peer-reviewed scientific journals, preferably open access.Trial registration numberNCT00641862 (Bangalore);NCT00717730, updated CTRI/2016/11/007494 (Delhi);NCT00197548andNCT00421668(Dar es Salaam).
Neuroimaging of headaches in patients with normal neurological examination: protocol for a systematic review
Authors: Kenteu Bernold , Fogang Yannick F , Nyaga Ulrich Flore , Zafack Joseline G , Noubiap Jean Jacques , Kamtchum-Tatuene Joseph 
Published: February 2018

IntroductionHeadache disorders (HD) are among the most frequent neurological disorders seen in neurology practice. Because secondary HD are rare, patients’ examination is most often unremarkable. However, the will to relieve patients’ anxiety and the fear of prosecutions lead to overuse of neuroimaging thus resulting in the discovery of incidental findings (IF) or normal variants that can lead to futile or harmful procedures. Knowing the probability of identifying a potentially clinically significant lesion in patients with isolated headache could facilitate decision-making and reduce health costs. This review aims to determine the prevalence of incidental findings and normal anatomic variants (NAV) on neuroimaging studies performed in patients presenting with headache and normal neurological examination.Method and analysisStudies reporting neuroimaging findings in patients with headache and normal neurological examination and published before the 30 September 2017 will be identified by searching PubMed, Medline and EMBASE (Excerpta Medica Database). Relevant unpublished papers and conference proceedings will also be checked. Full texts of eligible studies will then be accessed and data extracted using a standard data extraction sheet. Studies will be assessed for quality and risk of bias. Heterogeneity of studies will be evaluated by the χ2test on Cochrane’s Q statistic. The prevalence of NAV and IF across studies and in relevant subgroups will be estimated by pooling the study-specific estimates using a random-effects meta-analysis. Visual analysis of funnel plot and Egger’s test will be used to detect publication bias. The report of this systematic review will be compliant with the Meta-analysis of Observational Studies in Epidemiology guidelines.Ethics and disseminationThe current study is based on published data; ethical approval is, therefore, not required. The final report of this systematic review will be published in a peer-reviewed journal. Furthermore, findings will be presented at conferences and submitted to relevant health authorities.Trial registration numberCRD42017079714.