bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between the Changes over Time of Bone and Muscle Health in Children and Adults: A Systematic Review and Meta-Analysis
Authors: Médéa Locquet , Charlotte Beaudart , Nancy Durieux , Jean-Yves Reginster , Olivier Bruyère
Published: February 2019

Various cross-sectional studies provide an abundance of evidence that shows a relationship between bone quantity and muscle health. However, one question remains, less-often studied: is their development - or decline – associated? The aim of the research was to conduct a systematic review and meta-analysis to summarize the studies exploring the association between changes in bone mineral density (BMD) and changes in muscle parameters (registration CRD42018093813). We searched for prospective studies, both in children and adults, by consulting electronic databases (Ovid-MEDLINE, Ovid-AMED, Scopus). Each review steps were performed by two independent reviewers. For outcomes reported by less of 3 studies, we synthetized the results narratively. In other cases, a meta-analysis was performed, giving an overall r coefficient and its 95% confidence interval (CI). Fifteen papers were included. In connection with the change of BMD, 10 studies concerned the parallel change of lean mass, 4 were about grip strength, and 1 was about physical performance. Children were the population of interest for 5 studies, while the aging population was the focus of the other studies. The correlation between hip BMD and lean mass was significant, with an overall coefficient r = 0.37 (95% CI 0.23-0.49). High heterogeneity was observed between studies but the length of follow-up, sex and study quality did not seem to significantly influence results. The systematic review allowed some other highlights: a significant link between changes in BMD and changes in muscle strength was observed (p-value <0.05 in the 4 studies), in addition to changes in performance (1 study, r = 0.21, p-value = 0.004). Despite the heterogeneity between studies, we highlighted a significant association between the change of BMD and the change of various muscle parameters. Future studies should investigate preventive and therapeutic strategies that are based on a single entity: the ‘muscle-bone unit’.
Keystoneness, centrality, and the structural controllability of ecological networks
Authors: Cagua Edgar Fernando , Wootton Kate L. , Stouffer Daniel B.
Published: February 2019

An important dimension of a species' role is its ability to alter the state and maintain the diversity of its community. Centrality metrics have often been used to identify these species, which are sometimes referred as “keystone” species. However, the relationship between centrality and keystoneness is largely phenomenological and based mostly on our intuition regarding what constitutes an important species. While centrality is useful when predicting which species' extinctions could cause the largest change in a community, it says little about how these species could be used to attain or preserve a particular community state.

Here we introduce structural controllability, an approach that allows us to quantify the extent to which network topology can be harnessed to achieve a desired state. It also allows us to quantify a species' control capacity—its relative importance—and identify the set of species that are critical in this context because they have the largest possible control capacity. We illustrate the application of structural controllability with ten pairs of uninvaded and invaded plant‐pollinator communities.

We found that the controllability of a community is not dependent on its invasion status, but on the asymmetric nature of its mutual dependences. While central species were also likely to have a large control capacity, centrality fails to identify species that, despite being less connected, were critical in their communities. Interestingly, this set of critical species was mostly composed of plants and included every invasive species in our dataset. We also found that species with high control capacity, and in particular critical species, contribute the most to the stable coexistence of their community. This result was true, even when controlling for the species' degree, abundance/interaction strength, and the relative dependence of their partners.

Synthesis. Structural controllability is strongly related to the stability of a network and measures the difficulty of managing an ecological community. It also identifies species that are critical to sustain biodiversity and to change or maintain the state of their community and are therefore likely to be very relevant for management and conservation.
Subnational Location Capital: The Role of Subnational Institutional Actors and Socio‐spatial Factors on Firm Location
Authors: Monaghan Sinéad M. , Gunnigle Patrick , Lavelle Jonathan
Published: February 2019

Firms do not simply locate, but rather seek to accrue location‐based advantages such as knowledge, market insidership and resource utilization. Adopting the lens of social capital, this paper explores how subnational institutional actors facilitate location capital for firms. Using qualitative case study analysis of six multinational companies (MNCs), we highlight the important role of subnational institutional actors in fostering three dimensions of subnational location capital – structural, relational and cognitive. We show that subnational location capital, defined as the economic and social assets accessible through relationships within a subnational location, enable firms to derive advantages via subnational engagement. These findings contribute to the growing literature on the dynamic interaction of firms with subnational location, particularly the nuanced role of subnational institutional actors with MNCs.
Educational practitioners’ perceptions of ADHD: a qualitative study of views of the home lives of children with ADHD in the UK
Authors: Russell Abigail Emma , Tay Marianne , Ford Tamsin , Russell Ginny , Moore Darren
Published: February 2019

There is little research exploring educational practitioners’ experiences of working with children with attention deficit/hyperactivity disorder (ADHD). The current study aimed to understand educational practitioners’ beliefs concerning the home lives of children with ADHD, and how they perceive that home lives affect children’s behaviour in school. Forty‐two practitioners from primary, secondary and pupil referral schools participated in focus groups or interviews. Thematic analysis was used to identify themes arising from the data. Three themes emerged as relevant to beliefs about the home lives of children with ADHD: inconsistency, psychosocial adversity and isolation. Educational practitioners relate their experiences of working with children to what they believe occurs at home. On the basis of these findings, we make recommendations for strategies that school practitioners can use when working with children with ADHD.
Do High‐sensitivity Troponin and Natriuretic Peptide Predict Death or Serious Cardiac Outcomes After Syncope?
Authors: Clark Carol L. , Gibson Thomas A. , Weiss Robert E. , Yagapen Annick N. , Malveau Susan E. , Adler David H. , Bastani Aveh , Baugh Christopher W. , Caterino Jeffrey M. , Diercks Deborah B. , Hollander Judd E. , Nicks Bret A. , Nishijima Daniel K. , Shah Manish N. , Stiffler Kirk A. , Storrow Alan B. , Wilber Scott T. , Sun Benjamin C.
Published: February 2019

Objectives

An estimated 1.2 million annual emergency department (ED) visits for syncope/near syncope occur in the United States. Cardiac biomarkers are frequently obtained during the ED evaluation, but the prognostic value of index high‐sensitivity troponin (hscTnT) and natriuretic peptide (NT‐proBNP) are unclear. The objective of this study was to determine if hscTnT and NT‐proBNP drawn in the ED are independently associated with 30‐day death/serious cardiac outcomes in adult patients presenting with syncope.

Methods

A prespecified secondary analysis of a prospective, observational trial enrolling participants ≥ age 60 presenting with syncope, at 11 United States hospitals, was conducted between April 2013 and September 2016. Exclusions included seizure, stroke, transient ischemic attack, trauma, intoxication, hypoglycemia, persistent confusion, mechanical/electrical invention, prior enrollment, or predicted poor follow‐up. Within 3 hours of consent, hscTnT and NT‐proBNP were collected and later analyzed centrally using Roche Elecsys Gen 5 STAT and 2010 Cobas, respectively. Primary outcome was combined 30‐day all‐cause mortality and serious cardiac events. Adjusting for illness severity, using multivariate logistic regression analysis, variations between primary outcome and biomarkers were estimated, adjusting absolute risk associated with ranges of biomarkers using Bayesian Markov Chain Monte Carlo methods.

Results

The cohort included 3,392 patients; 367 (10.8%) experienced the primary outcome. Adjusted absolute risk for the primary outcome increased with hscTnT and NT‐proBNP levels. HscTnT levels ≤ 5 ng/L were associated with a 4% (95% confidence interval [CI] = 3%–5%) outcome risk, and hscTnT > 50 ng/L, a 29% (95% CI = 26%–33%) risk. NT‐proBNP levels ≤ 125 ng/L were associated with a 4% (95% CI = 4%–5%) risk, and NT‐proBNP > 2,000 ng/L a 29% (95% CI = 25%–32%) risk. Likelihood ratios and predictive values demonstrated similar results. Sensitivity analyses excluding ED index serious outcomes demonstrated similar findings.

Conclusions

hscTnT and NT‐proBNP are independent predictors of 30‐day death and serious outcomes in older ED patients presenting with syncope.
Comparison of Subjective Responses to Oral and Intravenous Alcohol Administration Under Similar Systemic Exposures
Authors: Plawecki Martin Henry , Durrani Adnan Mahmood , Boes Julian , Wetherill Leah , Kosobud Ann , O'Connor Sean , Ramchandani Vijay A.
Published: February 2019

Background

Individuals perceive the effects of alcohol differently, and the variation is commonly used in research assessing the risk for developing an alcohol use disorder. Such research is supported by both oral and intravenous (IV) alcohol administration techniques, and any differences attributable to the route employed should be understood. Our objective was to test whether an individual's subjective responses to alcohol are similar when the breath alcohol concentration (BrAC) trajectory resulting from oral administration is matched by IV administration.

Methods

We conducted a 2‐session, within‐subject study in 44 young adult, healthy, nondependent drinkers (22 females and 22 males). In the first session, subjects ingested a dose of alcohol which was individually calculated, on the basis of total body water, to yield a peak BrAC near 80 mg/dl, and the resulting BrAC trajectory was recorded. A few days later, subjects received an IV alcohol infusion rate profile, precomputed to replicate each individual's oral alcohol BrAC trajectory. In both sessions, we assessed 4 subjective responses to alcohol: SEDATION, SIMULATION, INTOXICATION, and HIGH; at baseline and frequently for 4 hours. We compared the individuals’ baseline‐corrected responses at peak BrAC and at half‐peak BrAC on both the ascending and descending limbs. We also computed and compared Pearson‐product moment correlations of responses by route of administration, the Mellanby measure of acute adaptation to alcohol, and the area under the entire response curve for each subjective response.

Results

No significant differences in any measure could be attributed to the route of alcohol administration. Eleven of 12 response comparisons were significantly correlated across the routes of alcohol administration, with 9 surviving correction for multiple measures, as did the Mellanby effect and area under the response curve correlations.

Conclusions

The route of alcohol administration has a minimal effect on subjective responses to alcohol when an individual's BrAC exposure profiles are similar.
Advanced interatrial block is a surrogate for left atrial strain reduction which predicts atrial fibrillation and stroke
Authors: Lacalzada‐Almeida Juan , Izquierdo‐Gómez María Manuela , García‐Niebla Javier , Elosua Roberto , Jiménez‐Sosa Alejandro , Baranchuk Adrian , Bayes de Luna Antonio
Published: February 2019

Background

The association between advanced interatrial block (aIAB) and atrial fibrillation (AF) is known as “Bayes’ Syndrome.” There is little information on the prognostic role that new speckle tracking echocardiographic (STE) imaging techniques could play in it. We have examined the relationship between left atrial (LA) STE and the prediction of new‐onset AF and/or stroke in IAB patients.

Methods

This is an observational prospective and unicentric cohort study with 98 outpatients: 55 (56.2%) controls with normal ECG without IAB, 21 (21.4%) with partial IAB (pIAB) and 22 (22.4%) with aIAB. The end point was new‐onset AF, ischemic stroke and the composite of both.

Results

During a mean follow‐up of 1.9 (1.7–2.3) years, 20 patients presented the end point (18 new‐onset AF and two strokes): 8 (14.5%) in the control group, 3 (14.3%) in pIAB and 9 (40.9%) in aIAB, p = 0.03. In multivariable comprehensive Cox regression analyses, a decrease in absolute value of strain rate during the booster pump function phase (SRa) was the only variable independently related to the appearance in the evolution of the end point, in the first model (age, P‐wave duration and SRa): HR 19.9 (95% CI, 3.12–127.5), p = 0.002 and in the second (age, presence of aIAB and SRa): HR 24.2 (95% CI, 3.15–185.4), p = 0.002.

Conclusions

In patients with IAB, a decrease in absolute value of LA SRa with STE predicts new‐onset AF and ischemic stroke. Future studies should confirm our results and assess the prognostic usefulness of LA STE in patients with IAB.
Diagnostic performance of electrocardiographic criteria for left ventricular hypertrophy among various body mass index groups compared to diagnosis by cardiac magnetic resonance imaging
Authors: Nomsawadi Veerawat , Krittayaphong Rungroj
Published: February 2019

Background

Presence of left ventricular hypertrophy (LVH) increases the risk for cardiovascular event. Many electrocardiographic (ECG) criteria can be used to diagnose LVH; however, high body mass index (BMI) may reduce ECG amplitudes.The aim of this study was to investigate the diagnostic performance of ECG criteria for diagnosing LVH among various BMI groups compared to diagnosis by cardiac magnetic resonance (CMR) imaging.

Methods

Patients who were referred for CMR were enrolled. CMR and ECG were performed on the same day. Left ventricular function, volume, and mass were calculated from CMR. Standard ECG criteria were measured, including: Cornell voltage, Cornell product, Romhilt‐Estes point score system, Sokolow‐Lyon index, and Sokolow‐Lyon‐Rappaport index. Diagnostic performance of each ECG criterion was calculated and analyzed in the following four BMI groups: underweight (<18.5 kg/m2), normal (18.5–22.9 kg/m2), overweight (23–24.9 kg/m2), and obese (≥25 kg/m2).

Results

Of the 1,882 patients that were included, 67 were underweight, 459 were normal weight, 434 were overweight, and 922 were obese. LVH was diagnosed in 34 (50.7%) underweight, 144 (31.4%) normal weight, 100 (23.0%) overweight, and 181 (19.6%) obese patients. Overall specificity of ECG was high (0.89–0.95), and overall sensitivity was low (0.25–0.37). The specificity of each ECG criterion was similar among BMI groups; however, the sensitivity of ECG criteria demonstrated a decreasing trend in the higher BMI groups.

Conclusion

All ECG criteria demonstrated relatively high specificity and relatively low sensitivity. Although the specificity across groups remained similar, higher BMI was found to be associated with decreased sensitivity.
Balloon catheter for induction of labor in women with one previous cesarean and an unfavorable cervix
Authors: Huisman Claartje M. A. , ten Eikelder Mieke L. G. , Mast Kelly , Oude Rengerink Katrien , Jozwiak Marta , van Dunné Frédérique , Duvekot Johannes J. , van Eyck Jim , Gaugler‐Senden Ingrid , de Groot Christianne J. M. , Franssen Maureen T. M. , van Gemund Nicolette , Langenveld Josje , de Leeuw Jan Willem , Oude Lohuis Eefje J. , Oudijk Martijn A. , Papatsonis Dimitri , van Pampus Mariëlle , Porath Martina , Rombout‐de Weerd Sabina , van Roosmalen Jos J. , van der Salm Paulien C. M. , Scheepers Hubertina C. J. , Sikkema Marko J. , Sporken Jan , Stigter Rob H. , van Wijngaarden Wim J. , Woiski Mallory , Mol Ben Willem J. , Bloemenkamp Kitty W. M. ,   The PROBAAT‐S project group
Published: February 2019

Introduction

When women with a previous cesarean section and an unfavorable cervix have an indication for delivery, the choice is to induce labor or to perform a cesarean section. This study aims to assess the effectiveness and safety of a balloon catheter as a method of induction of labor in women with one previous cesarean section and an unfavorable cervix compared with an elective repeat cesarean section.

Material and methods

We performed a prospective cohort study in 51 hospitals in the Netherlands on term women with one previous cesarean section, a live singleton fetus in cephalic position, an unfavorable cervix and an indication for delivery. We recorded obstetric, maternal and neonatal characteristics. We compared the outcome of women who were induced with a balloon catheter with the outcome of women who delivered by elective repeat cesarean section. Main outcomes were maternal and neonatal morbidity. Mode of delivery was a secondary outcome for women who were induced. Adjusted odds ratios (aOR) were calculated using logistic regression, adjusted for potential confounders.

Results

Analysis was performed on 993 women who were induced and 321 women who had a repeat cesarean section (August 2011 until September 2012). Among the women who were induced, 560 (56.4%) delivered vaginally and 11 (1.1%) sustained a uterine rupture. Composite adverse maternal outcome (uterine rupture, severe postpartum hemorrhage or postpartum infection) occurred in 73 (7.4%) in the balloon and 14 (4.5%) women in the repeat cesarean section group (aOR 1.58, 95% confidence interval [CI] 0.85‐2.96). Composite adverse neonatal outcome (Apgar score <7 at 5 minutes or umbilical pH <7.10) occurred in 57 (5.7%) and 10 (3.2%) neonates, respectively (aOR 1.40, 95% CI 0.87‐3.48). Women who were induced had a shorter postpartum admission time (2.0 vs 3.0 days (P < 0.0001)).

Conclusions

In women with a previous cesarean section and a need for delivery, induction of labor with a balloon catheter does not result in a significant increase in adverse maternal and neonatal outcomes as compared with planned cesarean section.
An update on prevalence and risk of snus and nicotine replacement therapy during pregnancy and breastfeeding
Authors: Kreyberg I , Nordhagen L S , Bains K E S , Alexander J , Becher R , Carlsen K H , Glavin K , Carlsen K C L
Published: February 2019

Aim

In parallel with falling smoking rates, use of the oral moist tobacco product snus increases among women in reproductive age. We report an update on prevalence and effects of maternal use of snus and nicotine replacement therapy (NRT) during pregnancy and breastfeeding.

Methods

A literature search of human studies in Medline, PubMed and EMBASE was conducted from September 2016 to May 2018, with stepwise screening of abstracts and subsequent relevant full‐text papers for inclusion in Scandinavian and English languages.

Results

Based on three studies, the prevalence of snus use in pregnancy was up to 3.4% in the first trimester and 2.1% in the third trimester. In 12 studies, we found increased risk of several adverse effects, especially preterm delivery, stillbirth and small for gestational age associated with maternal snus use during pregnancy. Knowledge on effects of NRT during pregnancy was conflicting and inconclusive in 10 studies. We did not identify any studies on prevalence or potential health effects of snus or NRT during breastfeeding.

Conclusion

Few studies with updated data on the prevalence and adverse health effects of maternal use of snus and NRT during pregnancy were found. No studies during breastfeeding were identified.
Maternal holding during therapeutic hypothermia for infants with neonatal encephalopathy is feasible
Authors: Craig Alexa , Deerwester Kyle , Fox Leah , Jacobs Julia , Evans Scott
Published: February 2019

Aim

Concerns for infant destabilisation often prohibit parental holding of infants during therapeutic hypothermia (TH). We assessed the feasibility of maternal holding during TH, as the inability to hold can impede bonding.

Methods

Vital signs were assessed in stable infants before, at two‐minute intervals during and 30 minutes after a single 30‐minute holding session. The infant remained on the blanket throughout holding, and both infant and blanket were placed into the mother's arms on top of a thin foam insulating barrier. Mothers and nurses were surveyed about their experience.

Results

Ten infants undergoing TH for neonatal encephalopathy had no equipment malfunctions or dislodgement. The mean temperature was 33.4°C prior to and 33.5°C (p = 0.18) after holding. There was no significant bradycardia (heart rate <80 beats per minute), hypotension (mean arterial pressure <40 mm Hg) or oxygen desaturation (<93%). Nurses either strongly agreed (75%) or agreed (25%) with the statement ‘After assisting with the holding protocol, I feel that holding during cooling is safe’. Mothers (100%) strongly agreed that other parents would benefit from holding.

Conclusion

In a small sample of ten stable infants treated with TH for neonatal encephalopathy, holding resulted in no adverse events and positive feedback from mothers and nurses.
Staying with the trouble of institutions
Authors: Philo Chris , Parr Hester
Published: February 2019

This paper provides a commentary on the theme section entitled “Troubling Institutions at the Nexus of Care and Control.” Using the recent book Matters of Care (2017) by Maria Puig de la Bellacasa as a reference point, the authors of the commentary introduce the project of exploring how care and control admix across a range of institutional geographies, reflecting complex assemblages of places, peoples, practices and problems. Taking seriously the prompt by the section editors to think about the “troubling” of institutions, the authors draw provisional distinctions between those that are “troubled” and those that are “troublesome,” mapping across to the range of more‐or‐less institutional – more‐or‐less carceral – spaces considered in the papers comprising the theme section. The commentary concludes with attention, inspired by Donna Haraway's notion of “staying with the trouble,” to the task of staying both with the troubles bundled up in institutional landscapes and, indeed, with the very idea and practice of institutions themselves.
Efficacy and safety of sapropterin dihydrochloride in patients with phenylketonuria: A meta‐analysis of randomized controlled trials
Authors: Qu Jinghan , Yang Ting , Wang Ente , Li Min , Chen Chaoyang , Ma Lingyun , Zhou Ying , Cui Yimin
Published: February 2019

Aims

The aim of the present meta‐analysis was to evaluate the efficacy and safety of sapropterin dihydrochloride in phenylketonuria (PKU) patients.

Methods

The following databases were searched for randomized controlled trials (RCT) regarding PKU patients treated with sapropterin dihydrochloride: PubMed, Embase, Cochrane Library and clinicaltrials. Two authors independently selected studies, assessed the risk of bias and extracted data. The meta‐analysis was performed in RevMan 5.3 provided by the Cochrane Collaboration.

Results

Four studies met the inclusion criteria. In PKU patients with low blood phenylalanine (Phe) concentration, no significant difference was indicated for the decrease of Phe level (weighted mean difference (WMD) = −7.75 μmol L−1; 95% confidence intervals (CI): −82.63 to 67.13, P = 0.84, I2 = 0%), however, the dietary Phe tolerance was significantly improved in the sapropterin group (WMD = 19.89 mg kg−1 d−1; 95% CI: 10.26 to 29.52, P < 0.0001, I2 = 0%). In PKU patients with high blood Phe level, sapropterin showed a significant lowering in blood Phe concentration (WMD = −225.31 μmol L−1; 95% CI: −312.28 to −138.34, P < 0.00001, I2 = 0%). There was no significant difference for adverse events.

Conclusions

Sapropterin could bring benefit for PKU patients with high or low Phe level, due to Phe reduction in a short time or dietary Phe tolerance improvement respectively. Sapropterin has an acceptable safety profile.
Why some are more equal: Family firm heterogeneity and the effect on management’s attention to CSR
Authors: Fehre Kerstin , Weber Florian
Published: February 2019

Research at the family firm–Corporate Social Responsibility (CSR) nexus lacks agreement about whether family firms are more or less socially responsible than their non‐family counterparts, which leads discussion relating to the bright and dark side of socioemotional wealth (SEW). We add to this ongoing debate in two different ways. First, we build on family firm heterogeneity and argue for a gray side to SEW, located between the bright and dark sides that is dependent upon the kind of family firm ownership. Second, we assume that prior research on a diverse set of CSR behaviors may, to some extent, explain the contradicting results; thus, we propose going back a step and focusing on management’s attention to CSR as an important antecedent of CSR behavior. By analyzing the letters to the shareholders of German HDAX firms from 2003 to 2012, this study finds that family ownership positively affects management’s attention to CSR, mainly driven by founders and family foundations. The research adds to our understanding of the family firm–CSR nexus by scrutinizing the role SEW plays in management’s attention to CSR when it comes to family firm heterogeneity.
Female reproductive factors and risk of lymphoid neoplasm: The Japan Public Health Center‐based Prospective Study
Authors: Tanaka Shiori , Sawada Norie , Yamaji Taiki , Shimazu Taichi , Goto Atsushi , Iwasaki Motoki , Inoue Manami , Tsugane Shoichiro ,   for the JPHC Study Group
Published: February 2019

Although a possible role of reproductive factors in lymphomagenesis has been hypothesized, results of epidemiological studies have been inconsistent. Here, we investigated the association between reproductive factors and the risk of lymphoid neoplasm and its subgroups. We used data from a large‐scale, population‐based prospective study in a Japanese cohort with 42 691 eligible women aged 40‐69 years from 1990 to 1994. During a mean follow up of 18.7 years, we identified 176 cases of lymphoid neoplasm and 90 of non‐Hodgkin lymphoma (NHL). A multivariable‐adjusted Cox proportional hazards regression model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the risk of lymphoid neoplasms and its subgroups according to self‐reported reproductive factors. Parous women had an increased risk of lymphoid neoplasm compared with nulliparous women (HR = 2.51, 95% CI, 1.03‐6.13). An increased risk of lymphoid neoplasms was found in women with later onset of menarche (≤13 years old; reference: 14‐15; HR = 1.75, 95% CI = 1.10‐2.79: ≥16; HR = 1.93, 95% CI = 1.17‐3.19: P‐trend: 0.01) and a shorter menstrual cycle (28‐29 days; reference: ≤27; HR = 1.60, 95% CI = 1.05‐2.43, P‐trend = 0.81). No association was observed between lymphoid neoplasms and other reproductive factors, including age at first birth, breastfeeding, type of menopause, or exogenous hormone use. Our study suggests that ever parity, late age at menarche and a short menstrual cycle length may be associated with the development of lymphoid neoplasms. The inconsistency seen in epidemiological research to date warrants further investigation.
Levels of horse allergen Equ c 4 in dander and saliva from ten horse breeds
Authors: Victor Susanne , Binnmyr Jonas , Lampa Erik , Rask‐Andersen Anna , Elfman Lena
Published: February 2019

Background

Horses are an important source of allergens, but the distribution of horse allergens is poorly understood. Five horse allergens have been identified, Equ c 1‐4 and 6. Equ c 4 seems to be an important allergen, with an IgE‐binding frequency of 77% in horse‐sensitized individuals.

Objectives

The aim of this study was to investigate levels of horse allergen Equ c 4 in dander, saliva and urine from ten horse breeds.

Method

The study population included 170 horses (87 mares, 27 stallions, 56 geldings) from ten breeds. Horse dander, saliva and urine samples were collected. Levels of horse allergen Equ c 4 were quantified using a two‐site sandwich ELISA (mAb 103 and 14G4) and were expressed as Equ c 4 U/μg protein.

Results

The horse allergen Equ c 4 was present in all dander and saliva samples from ten horse breeds, with high within‐breed and inter‐breed variations; GM values were 639 Equ c 4 U/μg protein (range 5‐15 264) for dander and 39.5 (4‐263) for saliva. Equ c 4 was found in 19/21 urine samples. Adjusted for age, sex and changes over time, no differences between breeds could be seen in dander, while in saliva the North Swedish horse showed lower levels of Equ c 4 than any other breed. The levels of Equ c 4 protein in dander and saliva were significantly higher in samples from stallions compared to mares and geldings, independent of breed.

Conclusions and Clinical Relevance

The results show a high variability in allergen levels of Equ c 4 in dander and saliva both within and between breeds. Significantly higher levels were found in stallions compared to mares and geldings, independent of breed. Results suggest that none of the horse breeds studied can be recommended for individuals allergic to Equ c 4.
11C‐Metomidate PET/CT is a useful adjunct for lateralization of primary aldosteronism in routine clinical practice
Authors: O’Shea Paula M. , O’Donoghue Darragh , Bashari Waiel , Senanayake Russell , Joyce Mary B. , Powlson Andrew S. , Browne Darragh , O’Sullivan Gerard J. , Cheow Heok , Mendichovszky Iosif , Quill Denis , Lowery Aoife , Lappin David , Gurnell Mark , Dennedy Michael C.
Published: February 2019

Objective

To describe clinical practice experience of 11C‐Metomidate PET/CT as an adjunct to adrenal vein sampling (AVS) in the lateralization of aldosterone‐producing adenomas (APA) in primary aldosteronism (PA).

Context

Accurate lateralization of APA in the setting of PA offers the potential for surgical cure and improved long‐term cardiovascular outcomes. Challenges associated with AVS, the current gold standard lateralization modality, mean that only a small proportion of potentially eligible patients currently make it through to surgery. This has prompted consideration of alternative strategies for lateralization, including the application of novel molecular PET tracers such as 11C‐Metomidate.

Design

Clinical Service Evaluation/Retrospective audit.

Patients

Fifteen individuals with a confirmed diagnosis of PA, undergoing lateralization with 11C‐Metomidate PET/CT prior to final clinical decision on surgical vs medical management.

Measurements

All patients underwent screening aldosterone renin ratio (ARR), followed by confirmatory testing with the seated saline infusion test, according to Endocrine Society Clinical Practice Guidelines. Adrenal glands were imaged using dedicated adrenal CT. 11C‐Metomidate PET/CT was undertaken due to equivocal or failed AVS. Management outcomes were assessed by longitudinal measurement of blood pressure, ARR, number of hypertensive medications following adrenalectomy or institution of medical therapy.

Results

We describe the individual lateralization and clinical outcomes for 15 patients with PA.

Conclusion

11C‐Metomidate PET/CT in conjunction with adrenal CT and AVS provided useful information which aided clinical decision‐making for PA within a multidisciplinary hypertension clinic.
Traders versus the State: Negotiating Urban Renewal in Lào Cai City, Vietnam
Authors: Endres Kirsten W.
Published: February 2019

In recent years, Vietnam has intensified programs aimed at building “civilized, rich, and beautiful” cities. The modernization of urban markets forms part of these efforts. This essay focuses on the contestations and negotiations surrounding the upgrade of a state‐run market in the northern border city of Lào Cai. In order to retain their stall use rights in the new market building, the traders were required to invest a sum that many felt was beyond their immediate means. Frustrated with the top‐down implementation of policy decisions that would potentially displace less affluent vendors from the market, the traders organized in protest and submitted petitions and complaints to various levels of government. In this paper, I critically examine the argumentation strategies employed by both traders and government officials during several formal hearings held in 2014. I argue that rather than arriving at a solution that satisfied the traders’ concerns, the dispute between market traders and state officials ultimately reinforced some of the hegemonic terms in which the marketization and urbanization of Vietnam’s borderlands take place. [Vietnam; Lào Cai City; Market Redevelopment; Urbanization; Protests].
Cost‐effectiveness of trans‐nasal endoscopic sphenopalatine artery ligation vs arterial embolisation for intractable epistaxis: Long‐term analyses
Authors: Costa Nadège , Mounié Michael , Bernard Geraldine , Bieler Laurent , Molinier Laurent , Serrano Elie , de Bonnecaze Guillaume
Published: February 2019

Objectives

Trans‐nasal endoscopic sphenopalatine artery ligation (TESPAL) and endovascular arterial embolisation both provide excellent success rates for intractable epistaxis. Recent economic models suggest that TESPAL could be a cost‐saving strategy. Our main aim was to perform cost‐effectiveness analyses on TESPAL compared with embolisation to treat patients with epistaxis.

Design

We performed retrospective, monocentric, comparative analyses on patients referred to our centre and treated with embolisation or TESPAL.

Setting

This economic evaluation was carried out from a payer's perspective (ie French National Health Insurance) within a time horizon of 12 months.

Participants

Thirty‐seven TESPAL procedures and thirty‐nine embolisation procedures to treat intractable epistaxis were used in the analyses.

Main outcome measures

The primary outcome is presented as the cost per 1% of non‐recurrence. Effectiveness was defined as avoiding recurrence of epistaxis during the 1‐year follow‐up. Cost estimates were performed from the payer's perspective.

Results

Hospitalisation costs were higher for embolisation compared with TESPAL (5972 vs 3769 euros). On average, hospitalisation costs decreased by 41% when a patient was treated by TESPAL compared with an embolisation strategy (P = 0.06). The presence of comorbidities increased hospitalisation costs by 79% (P = 0.04). TESPAL enabled 1867€ to be gained in intractable epistaxis.

Conclusions

The outcomes from our decision model confirm that TESPAL is more cost‐effective for patients with intractable epistaxis.
δ‐Tocotrienol induces apoptosis, involving endoplasmic reticulum stress and autophagy, and paraptosis in prostate cancer cells
Authors: Fontana Fabrizio , Moretti Roberta Manuela , Raimondi Michela , Marzagalli Monica , Beretta Giangiacomo , Procacci Patrizia , Sartori Patrizia , Montagnani Marelli Marina , Limonta Patrizia
Published: February 2019

Objectives

Prostate cancer, after the phase of androgen dependence, may progress to the castration‐resistant prostate cancer (CRPC) stage, with resistance to standard therapies. Vitamin E‐derived tocotrienols (TTs) possess a significant antitumour activity. Here, we evaluated the anti‐cancer properties of δ‐TT in CRPC cells (PC3 and DU145) and the related mechanisms of action.

Materials and methods

MTT, Trypan blue and colony formation assays were used to assess cell viability/cell death/cytotoxicity. Western blot, immunofluorescence and MTT analyses were utilized to investigate apoptosis, ER stress and autophagy. Morphological changes were investigated by light and transmission electron microscopy.

Results

We demonstrated that δ‐TT exerts a cytotoxic/proapoptotic activity in CRPC cells. We found that in PC3 cells: (a) δ‐TT triggers both the endoplasmic reticulum (ER) stress and autophagy pathways; (b) autophagy induction is related to the ER stress, and this ER stress/autophagy axis is involved in the antitumour activity of δ‐TT; in autophagy‐defective DU145 cells, only the ER stress pathway is involved in the proapoptotic effects of δ‐TT; (c) in both CRPC cell lines, δ‐TT also induces an intense vacuolation prevented by the ER stress inhibitor salubrinal and the protein synthesis inhibitor cycloheximide, together with increased levels of phosphorylated JNK and p38, supporting the induction of paraptosis by δ‐TT.

Conclusions

These data demonstrate that apoptosis, involving ER stress and autophagy (in autophagy positive PC3 cells), and paraptosis are involved in the anti‐cancer activity of δ‐TT in CRPC cells.
Differential distribution of the epigenetic marker 5‐hydroxymethylcytosine occurs in hair follicle stem cells during bulge activation
Authors: Leavitt Danielle , Wells Michael , Abarzua Phammela , Murphy George F. , Lian Christine G.
Published: February 2019

Background

Hair follicle (HF) cycling is dependent upon activation and differentiation of an epithelial subpopulation of cells with stem‐like characteristics. These cells express cytokeratin 15 (CK15) and are sequestered within a specialized niche termed the follicular bulge. The pathways that mediate bulge activation are poorly understood, although growing evidence suggests a role for epigenetic events.

Methods

Here we investigated murine and human HFs to determine whether a recently described epigenetic hydroxymethylation marker, 5‐hmC, known to mediate cell growth and differentiation, may play a role in bulge activation.

Results

We found the bulge region of murine HFs to show variable 5‐hmC distribution within the nuclei of CK15‐positive stem cells during early anagen, a pattern that was not associated with resting stem cells of telogen follicles, which did not express 5‐hmC. Moreover, during phases of early anagen that were induced in an organ culture model, spatial alterations in bulge stem cell 5‐hmC reactivity, as assessed by dual labeling, were noted.

Conclusions

These preliminary findings suggest that 5‐hmC may play a dynamic role in bulge activation during anagen growth, and provide a foundation for further experimental inquiry into epigenomic regulation of HF stem cells.
Oral amoxicillin‐clavulanate for treating diabetic foot infections
Authors: Gariani Karim , Lebowitz Dan , Kressmann Benjamin , von Dach Elodie , Sendi Parham , Waibel Felix , Berli Martin , Huber Tanja , Lipsky Benjamin A. , Uçkay Ilker
Published: February 2019

Aim

To assess amoxicillin‐clavulanate (AMC) for the oral therapy of diabetic foot infections (DFIs), especially for diabetic foot osteomyelitis (DFO).

Methods

We performed a retrospective cohort analysis among 794 DFI episodes, including 339 DFO cases.

Results

The median duration of antibiotic therapy after surgical debridement (including partial amputation) was 30 days (DFO, 30 days). Oral AMC was prescribed for a median of 20 days (interquartile range, 12‐30 days). The median ratio of oral AMC among the entire antibiotic treatment was 0.9 (interquartile range, 0.7‐1.0). After a median follow‐up of 3.3 years, 178 DFIs (22%) overall recurred (DFO, 75; 22%). Overall, oral AMC led to 74% remission compared with 79% with other regimens (χ2‐test; P = 0.15). In multivariate analyses and stratified subgroup analyses, oral AMC resulted in similar clinical outcomes to other antimicrobial regimens, when used orally from the start, after an initial parenteral therapy, or when prescribed for DFO.

Conclusions

Oral AMC is a reasonable option when treating patients with DFIs and DFOs.
Ocular drift reflects volitional action preparation
Authors: Watanabe Masayuki , Okada Ken‐ichi , Hamasaki Yuta , Funamoto Mari , Kobayashi Yasushi , MacAskill Michael , Anderson Tim
Published: February 2019

Human cognitive behavior is predictive rather than reflexive because of volitional action preparation. Recent studies have shown that the covert process of volitional action preparation can be decoded from overt fixational eye movements of fixational/microsaccades and pupil dilation. Ocular drift, the slowest fixational eye movements, is also under the active neural control, but its relationship with cognitive behavior is unknown. Here, we examined whether ocular drift also reflects volitional action preparation. We analyzed ocular drift while adult humans maintained fixation on a central visual stimulus as they prepared to generate a volitional saccade. We adopted the antisaccade paradigm in which subjects generate a targeting saccade toward the opposite direction of a peripheral visual stimulus. Our findings are the following five points. First, ocular drift was slower when subjects prepared for targeting saccade initiation than when such preparation was unnecessary. Second, ocular drift was slowed down with elapsed time from fixation initiation, which was associated with the facilitation of targeting saccade initiation. Third, ocular drift was further slowed on correct antisaccade trials than when subjects failed to suppress targeting saccades toward peripheral stimuli. Fourth, such correlation with antisaccade performance was observed immediately after fixation initiation in ocular drift, but it emerged more slowly in the other fixational eye movements. Fifth, subjects with unstable fixation because of faster ocular drift had poorer antisaccade performance. We suggest that fixation stability measured by ocular drift can be used to decode the covert process of volitional action preparation along with the other fixational eye movements.
Cerebrospinal fluid changes following epileptic seizures unrelated to inflammation
Authors: Süße M. , Saathoff N. , Hannich M. , von Podewils F.
Published: February 2019

Background and purpose

Analyzing cerebrospinal fluid (CSF) is crucial in the diagnostic workup of epileptic seizures to rule out autoimmunity or infections as the underlying cause. Therefore, the description of post‐ictal changes in CSF is essential to differentiate between negligible and etiopathologically relevant changes in the CSF profile.

Methods

A retrospective analysis of 247 patients newly diagnosed with epileptic seizures and CSF analysis during diagnostic workup was conducted. Patients with possible or definitive autoimmune or infectious encephalitis were excluded. CSF results were evaluated for associations with seizure types, seizure etiology and electroencephalography (EEG) findings.

Results

An increased cell count (>4/μL) was found in 4% (n = 10), increased lactate concentration (>2.5 mmol/L) in 28% (n = 70), increased total protein (>500 mg/L) in 51% (n = 125) and a dysfunction of the blood–brain barrier in 29% (n = 71) of patients. Intrathecal immunoglobulin G production was observed in 5% (n = 12) of patients. Higher lactate concentrations were found in seizures with motor onset (P = 0.02) compared with those with non‐motor onset. Patients with generalized slow activity on EEG had significantly higher lactate values (P = 0.01) and albumin quotient (P = 0.05) than those with normal EEG.

Conclusions

Compared with mild pleocytosis and immunoglobulin synthesis, elevated lactate and total protein concentrations as well as blood–brain barrier dysfunction are frequently found following epileptic seizures. Our data suggest that seizure semiology might impact CSF profiles. The highest lactate concentrations were found following motor‐onset seizures. Our findings may help clinicians to avoid over‐interpretation of minor CSF changes; however, the exclusion of alternative causes should always be carefully considered, taking into account further clinical features.
No evidence for a BRD2 promoter hypermethylation in blood leukocytes of Europeans with juvenile myoclonic epilepsy
Authors: Schulz Herbert , Ruppert Ann‐Kathrin , Zara Federico , Madia Francesca , Iacomino Michele , S. Vari Maria , Balagura Ganna , Minetti Carlo , Striano Pasquale , Bianchi Amedeo , Marini Carla , Guerrini Renzo , Weber Yvonne G. , Becker Felicitas , Lerche Holger , Kapser Claudia , Schankin Christoph J. , Kunz Wolfram S. , Møller Rikke S. , Oliver Karen L. , Bellows Susannah T. , Mullen Saul A. , Berkovic Samuel F. , Scheffer Ingrid E. , Caglayan Hande , Ozbek Ugur , Hoffmann Per , Schramm Sara , Tsortouktzidis Despina , Becker Albert J. , Sander Thomas
Published: February 2019

Juvenile myoclonic epilepsy (JME) is a common syndrome of genetic generalized epilepsies (GGEs). Linkage and association studies suggest that the gene encoding the bromodomain‐containing protein 2 (BRD2) may increase risk of JME. The present methylation and association study followed up a recent report highlighting that the BRD2 promoter CpG island (CpG76) is differentially hypermethylated in lymphoblastoid cells from Caucasian patients with JME compared to patients with other GGE subtypes and unaffected relatives. In contrast, we found a uniform low average percentage of methylation (<4.5%) for 13 CpG76‐CpGs in whole blood cells from 782 unrelated European Caucasians, including 116 JME patients, 196 patients with genetic absence epilepsies, and 470 control subjects. We also failed to confirm an allelic association of the BRD2 promoter single nucleotide polymorphism (SNP) rs3918149 with JME (Armitage trend test, P = 0.98), and we did not detect a substantial impact of SNP rs3918149 on CpG76 methylation in either 116 JME patients (methylation quantitative trait loci [meQTL], P = 0.29) or 470 German control subjects (meQTL, P = 0.55). Our results do not support the previous observation that a high DNA methylation level of the BRD2 promoter CpG76 island is a prevalent epigenetic motif associated with JME in Caucasians.
The protective effect of acute pantoprazole pretreatment on renal ischemia/reperfusion injury in rats
Authors: Kohansal Parichehr , Rajai Nazanin , Dehpour Ahmad Reza , Rashidian Amir , Shafaroodi Hamed
Published: February 2019

Renal ischemia/reperfusion injury (IRI), which occurs in many pathological conditions, is associated with high rate of morbidity and mortality. Activation of inflammatory responses and oxidative stress contribute to induce organ damage following IRI. Pantoprazole, a proton pump inhibitor, which is mostly prescribed for gastroesophageal reflux disease (GERD) has been shown to exert anti‐inflammation effects. In order to evaluate the effects of pantoprazole on renal ischemia/reperfusion injury, four different doses of pantoprazole (4.5, 9, 18, and 36 mg/kg) were administered 30 min before the induction of IRI in male Wistar rats. Serum concentration of creatinine and blood urea nitrogen (BUN) were measured to assess renal function. Histopathological changes, malondialdehyde (MDA) level and toll‐like receptor 4 (TLR‐4) expression in renal tissue were determined and compared to control group. The results revealed that pretreatment with 18 and 36 mg/kg of pantoprazole leads to the significant decline in serum creatinine and BUN levels and the severity of necrosis grade in comparison with control group (P < 0.05). Pantoprazole also reduced the MDA level and TLR‐4 expression in renal tissue. In summary, pantoprazole attenuates renal injury following ischemia/reperfusion. This effect is mediated partially through inhibition of oxidative stress and TLR‐4 signaling pathway.