bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence Supporting Serology‐based Pathway for Diagnosing Celiac Disease in Asymptomatic Children From High‐risk Groups
Authors: Paul Siba Prosad , Sandhu Bhupinder Kaur , Spray Christine Helen , Basude Dharamveer , Ramani Pramila
Published: September 2017

Objective:

The European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines for diagnosing celiac disease (CD) in children were modified in 2012. They recommend that in symptomatic children with anti‐tissue transglutaminase antibody (anti‐tTG) titer of >10 times upper limit of normal (>10× ULN) and who have positive anti‐endomysial antibody and HLA‐DQ2/DQ8 haplotype, the diagnosis of CD can be based on serology. The aim of this study is to establish whether serology‐based pathway of the ESPGHAN guidelines could also be reliably applied to asymptomatic children from high‐risk groups.

Methods:

From March 2007 to February 2017, prospective data on anti‐tTG titer, age, sex, and reason for screening were collected at diagnostic endoscopy on all asymptomatic children being diagnosed as having CD. The relationship between modified Marsh‐Oberhuber classification histological grading and contemporaneous anti‐tTG titers was analyzed.

Results:

A total of 157 asymptomatic children were diagnosed as having CD. Eighty‐four of 157 (53.5%) had antitTG >10× ULN (normal <10 IU/mL) and 75 of 84 were from high‐risk groups. All 75 had definitive histological evidence (Marsh‐Oberhuber 3a‐3c) of small bowel enteropathy. Fifty‐three of 84 children had anti‐tTG >200 IU/mL and total villous atrophy was present in 29 of 53 (55%). Main reasons for serological screening were: type‐1 diabetes mellitus (n = 36) and first‐degree relatives with CD (n = 24). Mean age at diagnosis was 8.8 years. Serology‐based diagnosis is cost‐beneficial by around £1275 per child in the United Kingdom.

Conclusions:

All 75 asymptomatic children from high‐risk groups with anti‐tTG >10× ULN had histology‐proven CD. This study provides further evidence that the guidelines for diagnosing CD by the serology‐based pathway should be extended to these children.
Effects of modified constraint-induced movement therapy in the recovery of upper extremity function affected by a stroke: a single-blind randomized parallel trial-comparing group versus individual intervention
Authors: Doussoulin Arlette , Rivas Claudia , Rivas Rodrigo , Saiz José
Published: September 2017

An extensive corpus of literature supports the positive impact of constraint-induced movement therapy (CIMT) on neuroplasticity and the recovery of function. However, its clinical applicability is limited by the time of intervention and individual modality. We propose to assess the efficacy of modified CIMT protocols through a group therapy intervention. To determine the effectiveness of a group therapy, compared with individual modified CIMT, in increasing the use and functionality of movement of a paretic upper limb. The study was a single-blind, randomized parallel trial. Thirty-six patients who had had a stroke more than 6 months previously were divided randomly into two intervention groups. The independent variable was the implementation of group or individual modalities for 3 h for 10 consecutive days and the dependent variables were evaluated by the Motor Activity Log and Action Research Arm Test, at baseline (preintervention evaluation), end (postintervention evaluation), and 6 months after intervention (follow-up). By controlling the preintervention evaluations, analyses of covariance indicated that both dependent variables presented significant differences in favor of the group therapy at both the postintervention evaluation and the follow-up evaluations. Both types of intervention generated increases in the function and use of the upper extremity, with these increases being higher in the group therapy. The effects of the group therapy modality were maintained 6 months after the intervention ended.
Longitudinal Changes in Combat-Related Posttraumatic Stress Disorder Among Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Veterans With Hazardous Alcohol Use
Authors: Lee Joohyun , Possemato Kyle , Ouimette Paige C.
Published: September 2017

Military personnel who have experienced combat trauma are at risk for developing posttraumatic stress disorder (PTSD). A greater recognition of the complex array of vulnerability factors that contribute to PTSD severity has led researchers to examine other non–combat-related factors. This longitudinal study examined a number of pre-, peri-, and postdeployment factors hypothesized to contribute to PTSD symptomatology among returning Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn veterans presenting with at least subthreshold PTSD symptoms and hazardous alcohol use in a primary care setting. Purported risk factors included childhood family environment, severity of combat exposure, postdeployment social support, alcohol dependence severity, and an avoidant coping style. At baseline, postdeployment social support and avoidant coping contributed to PTSD severity. Only avoidant coping was associated with changes in PTSD symptom at 1-year follow-up. Reducing avoidant coping may deter the maintenance of PTSD among veterans with PTSD symptoms and hazardous alcohol use.
Effect of Cobicistat on Tenofovir Disoproxil Fumarate (TDF): What Is True for TAF May Also Be True for TDF
Authors: Cattaneo Dario , Minisci Davide , Baldelli Sara , Mazzali Cristina , Giacomelli Andrea , Milazzo Laura , Meraviglia Paola , Resnati Chiara , Rizzardini Giuliano , Clementi Emilio , Galli Massimo , Gervasoni Cristina
Published: September 2017

Background:

The dose of tenofovir alafenamide is reduced from 25 to 10 mg daily when given with boosting agents. However, such dose reduction has never been adopted for tenofovir disoproxil fumarate (TDF). In this study, we aim to quantify the effect of cobicistat (COBI) both on tenofovir concentrations and TDF durability in real life setting.

Methods:

HIV-positive patients receiving TDF-containing antiretroviral therapies with at least 1 assessment of tenofovir plasma trough concentrations were included in the study. Univariate and multivariate regression analyses were performed considering tenofovir concentration as the dependent variable and clinical characteristics as independent covariates. Subsequently, survival and Cox analyses were performed considering as the primary outcome TDF discontinuation for any reasons.

Results:

Patients were given TDF with protease inhibitors/ritonavir (n = 212), non–nucleoside reverse transcriptase inhibitors (n = 176), integrase inhibitors (dolutegravir or raltegravir, n = 46), or with elvitegravir/COBI (ELV/COBI) (n = 76). By multivariate analysis, concomitant antiretroviral therapies resulted significantly associated with tenofovir levels, with the highest drug concentrations measured in patients given ELV/COBI. By survival analysis, we found that patients given TDF with ELV/COBI had the lowest rate of drug durability. Overall, these patients had a 2.3-fold increased risk to experience TDF discontinuation.

Conclusions:

Coadministration with COBI resulted in significantly higher tenofovir concentrations and higher TDF discontinuation compared with other antiretroviral regimens. Accordingly, the possibility that the lack of proper dose adjustment for TDF when given with COBI might have biased the safety comparisons with tenofovir alafenamide during registrative trials cannot be ruled out.
Osteotomy Site Grafting in Bilateral Sagittal Split Surgery With Bioactive Glass S53P4 for Skeletal Stability
Authors: Stoor Patricia , Apajalahti Satu
Published: September 2017

In orthognathic surgery, the aim of the treatment is to achieve a good occlusion and a satisfying aesthetic outcome. In large mandibular advancements insufficient healing at the mandibular inferior border may lead to loss of support for the overlaying tissue at the osteotomy site. Augmentation can be performed to improve stability, bone regeneration, and the aesthetic outcome. The purpose of this prospective clinical study was to evaluate the use of a novel material for this indication; granules of the antibacterial, osteoconductive, and slowly resorbing bioactive glass S53P4 as filling material in large mandibular advancement in bilateral sagittal split osteotomies. The authors treated 25 patients who underwent bilateral sagittal split osteotomies due to class II dentoskeletal deformities. The mandibular osteotomy site defects (8–15 mm) were augmented with bioactive glass S53P4. The average clinical follow-up was 33 months and the average radiological follow-up with cone beam computerized tomography was 24 months. The clinical and radiological results were good with regard to healing, bone regeneration, and stability of the osteotomy sites. The recontouring of the inferior mandibular border provided a good soft tissue support followed by an excellent aesthetic outcome in 96% of the osteotomy sites. The occlusion was stable in 88% of the patients. The authors’ results show that bioactive glass S53P4 is a safe grafting material for osteotomy site defects in significant mandibular advancements with reliable bone regeneration, providing long-term stability at the osteotomy site and at the inferior mandibular border.
Intracranial Volume Measurement: A Systematic Review and Comparison of Different Techniques
Authors: Breakey William , Knoops Paul G.M. , Borghi Alessandro , Rodriguez-Florez Naiara , Dunaway David J. , Schievano Silvia , Jeelani Owase N.U.
Published: September 2017

The ability to calculate intracranial volume (ICV) from 3-dimensional imaging is a useful tool in a craniofacial team's armamentarium. Intracranial volume uses range from decision making to assessment. Various methods to calculate ICV exist including fully manual, semiautomatic, and fully automatic techniques and they are used with varying frequency in craniofacial centres globally.

This study aimed to systematically analyze and compare ICV calculations across the 3 methods and provide information to allow the reader to utilize these processes in practice.

Twenty-six computed tomography scans from Apert patients were used to compare ICV measurements calculated using the following techniques: fully manual segmentation with OsiriX (taken as the gold standard); semiautomatic segmentation using Simpleware ScanIP; and fully automatic segmentation using FSL neuroimaging software. In addition, to assess the effect that a reducing CT scan slice number had on ICV measurement, 13 scans were remeasured using half, quarter, and an eighth of the slices of the full scan.

The manual and semiautomatic techniques had intraclass correlation coefficients of 0.997, and 0.993 respectively. Intracranial volume measurements using the semi- and fully automatic techniques showed high linear correlation with manual techniques (R
2 = 0.993 and R
2 = 0.995). The coefficients of determination for full scan versus half, quarter, and eighth scan were R
2 = 0.98, 0.96, and 0.94 respectively.

Similar ICV results can be obtained using manual, semiautomatic, or automatic techniques with decreasing amount of time required to perform each method. Command line code for the fully automatic method is provided.
Twenty-Year Review of a Single Surgeon's Experience Using a Unique Surgical Technique to Correct Lambdoidal Synostosis
Authors: Rodriguez-Feo Charles , Winocour Julian , Ramirez Roberto , Spear Marcia , Kelly Kevin
Published: September 2017

Background:

Numerous techniques for the surgical management of lambdoidal synostosis have been previously described; however, no best practice technique currently exists. Surgical procedures range from complete posterior calvarial reconstruction to distraction osteogenesis techniques. Our primary purpose is to describe a novel approach to correct unilateral or bilateral lambdoidal synostosis.

Methods:

A retrospective review was performed on a single surgeon's experience with craniosynostosis (1994–2014). Specifically, craniosynostosis cases involving the lambdoidal suture, which were repaired using a novel ‘tongue and groove’ technique, were identified.

Results:

A total of 664 craniosynostosis cases were retrieved, with 21 primarily involving the lambdoidal suture (3.2%). Of these, 18 were unilateral and 3 were bilateral lambdoidal synostosis. Male-to-female ratio was 3:1. Average age of first encounter with a craniofacial physician was 33 weeks (8 months). Average age at time of surgery was 43 weeks (10.75 months). Complications of this technique included 1 patient who experienced refusion of his lambdoidal suture and fusion of his sagittal suture, and 4 who returned for bone graft coverage of full-thickness calvarial defects owing to a lack of complete reossification.

Conclusion:

The “tongue and groove” technique represents a novel method for the management of lambdoidal synostosis with good esthetic outcomes, allowing immediate cranial stabilization with increased skull volume. This technique, used by the senior author for >20 years, provides a reproducible and reliable method of correcting lambdoidal synostosis.
A Comparison of Bowel Preparations for Colonoscopy in Constipated Adults
Authors: Kunz Lisa , Gillespie Debra
Published: September 2017

Clinical practice shows that patients with constipation are more likely to have a poor bowel preparation for colonoscopy. Consequences of poor bowel preparation include missed lesions, increased complication rates, and higher costs. Research on preparing constipated patients for colonoscopy with Food and Drug Administration-approved medications is scarce. This study included 372 patients and compared the effectiveness of high-volume (4 L) polyethylene glycol solution (GoLYTELY) with low-volume (2 L) polyethylene glycol solution with ascorbate (MoviPrep) in constipated and nonconstipated adults. Patients were considered constipated if constipation was recently documented in their medical history, they self-reported constipation, and/or they met Rome III criteria for constipation. Quality of bowel preparation was rated with the Aronchick scale. Of the 372 patients enrolled, 65 (17.5%) were constipated. Among those with constipation, 26.1% (n = 17) had a bowel preparation rated fair or poor. There was no statistically significant difference in quality of bowel preparation between GoLYTELY and MoviPrep in chronically constipated adults (p = .27). This study concluded that patients with constipation were more likely than nonconstipated patients to have poor bowel preparation, and there was no statistically significant difference between GoLYTELY and MoviPrep. Further study is needed to determine an adequate preparation regimen.
New evidence of a rhythmic priming effect that enhances grammaticality judgments in children
Authors: Chern Alexander , Tillmann Barbara , Vaughan Chloe , Gordon Reyna L.
Published: September 2017

Musical rhythm and the grammatical structure of language share a surprising number of characteristics that may be intrinsically related in child development. The present study aimed to understand the potential influence of musical rhythmic priming on subsequent spoken grammar task performance in children with typical development who were native speakers of English. Participants (ages 5 to 8 years) listened to rhythmically regular and irregular musical sequences (within-subjects design) followed by blocks of grammatically correct and incorrect sentences upon which they were asked to perform a grammaticality judgment task. Rhythmically regular musical sequences improved performance in grammaticality judgment compared to rhythmically irregular musical sequences. No such effect of rhythmic priming was found in two non-linguistic control tasks, suggesting a neural overlap between rhythm processing and mechanisms recruited during grammar processing. These findings build on previous research investigating the effect of rhythmic priming by extending the paradigm to a different language, testing a younger population, and employing non-language control tasks. These findings of an immediate influence of rhythm on grammar states (temporarily augmented grammaticality judgment performance) also converge with previous findings of associations between rhythm and grammar traits (stable, generalized grammar abilities) in children. Taken together, this study provides additional evidence for shared neural processing for language and music, and warrants future investigations of potentially beneficial effects of innovative musical material on language processing.
Age at first birth in women is genetically associated with increased risk of schizophrenia
Authors: Ni Guiyan , Gratten Jacob ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Wray Naomi R. , Hong Lee S.
Published: September 2017

Previous studies have shown an increased risk for a range of mental health issues in children born to both younger and older parents compared to children of average-aged parents. However, until recently, it was not clear if these increased risks are due to psychosocial factors associated with age or if parents at higher genetic risk for psychiatric disorders tend to have children at an earlier or later age. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age of mothers at the birth of their first child (AFB). Here, we use independent data from the UK Biobank (N=38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, end to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value=1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value=3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE=0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE=0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.
MACS – a new SPM toolbox for model assessment, comparison and selection
Authors: Soch Joram , Allefeld Carsten
Published: September 2017

Background

In cognitive neuroscience, functional magnetic resonance imaging (fMRI) data are widely analyzed using general linear models (GLMs). However, model quality of GLMs for fMRI is rarely assessed, in part due to the lack of formal measures for statistical model inference.

New Method

We introduce a new SPM toolbox for model assessment, comparison and selection (MACS) of GLMs applied to fMRI data. MACS includes classical, information-theoretic and Bayesian methods of model assessment previously applied to GLMs for fMRI as well as recent methodological developments of model selection and model averaging in fMRI data analysis.

Results

The toolbox – which is freely available from GitHub – directly builds on the Statistical Parametric Mapping (SPM) software package and is easy-to-use, general-purpose, modular, readable and extendable. We validate the toolbox by reproducing model selection and model averaging results from earlier publications.

Comparison with Existing Methods

A previous toolbox for model diagnosis in fMRI has been discontinued and other approaches to model comparison between GLMs have not been translated into reusable computational resources in the past.

Conclusions

Increased attention on model quality will lead to lower false-positive rates in cognitive neuroscience and increased application of the MACS toolbox will increase the reproducibility of GLM analyses and is likely to increase the replicability of fMRI studies.
Small RNAs are trafficked from the epididymis to developing mammalian sperm
Authors: Sharma Upasna , Sun Fengyun , Reichholf Brian , Herzog Veronika A. , Ameres Stefan L. , Rando Oliver J.
Published: September 2017

RNAs present in mature mammalian sperm are delivered to the zygote at fertilization, where they have the potential to affect early development. The biogenesis of the small RNA payload of mature sperm is therefore of great interest, as it may be a target of signaling pathways linking paternal conditions to offspring phenotype. Recent studies have suggested the surprising hypothesis that the small RNA payload carried by mature sperm may include RNAs that were not synthesized during testicular spermatogenesis, but that are instead delivered to sperm during the process of post-testicular maturation in the epididymis. To further test this hypothesis, we characterized small RNA dynamics during testicular and post-testicular germ cell maturation in mice. We show that purified testicular germ cell populations, including mature testicular spermatozoa, carry extremely low levels of tRNA fragments (tRFs), and that tRFs become highly abundant only after sperm have entered the epididiymis. The process of small RNA delivery to sperm can be recapitulated in vitro, as caput epididymosomes deliver small RNAs including tRFs and microRNAs to mature testicular spermatozoa. Finally, to definitively identify the tissue of origin for small RNAs in sperm, we carried out tissue-specific metabolic labeling of RNAs in intact mice, finding that mature sperm carry small RNAs that were originally synthesized in the somatic cells of the epididymis. Taken together, our data demonstrates that soma-germline small RNA transfer occurs in male mammals, most likely via vesicular transport from the epididymis to maturing sperm.
Assessing the quality of supplementary sensory feedback using a crossmodal congruency task
Authors: Blustein Daniel , Wilson Adam , Sensinger Jon
Published: September 2017

Peripheral nerve interfaces show promise in making prosthetic limbs more biomimetic and ultimately more intuitive and useful for patients. However, approaches to assess these emerging technologies are limited in their scope and the insight they provide. When outfitting a prosthesis with a new feedback system it would be helpful to quantify its physiological correspondence, i.e. how well the experimental feedback mimics the perceived feedback in an intact limb. Here we present an approach to quantify physiological correspondence using a modified crossmodal congruency task. We trained 60 able-bodied subjects to control a bypass prosthesis under different feedback conditions and training durations. We find that the crossmodal congruency effect (CCE) score is sensitive to changes in feedback modality (multi-way ANOVA; F(2,48) = 6.02, p<0.05). After extended training, the CCE score increased as the spatial separation between expected and perceived feedback decreased (unpaired t-test, p<0.05). We present a model that can quantitatively estimate physiological correspondence given the CCE result and the measured spatial separation of the feedback. This quantification approach gives researchers a tool to assess an aspect of emerging augmented feedback systems that is not measurable with current motor assessments.
Intragenus variation in a Chemokine Receptor Gene (CCR5) in Homo
Authors: Hoover Kara C.
Published: September 2017

In comparison to non-human primates, humans have a notable increase in polymorphisms of the regulatory regions of the CCR5 gene, an immune system gene with both general and specific functions. This particular pattern of variation is interpreted as allowing flexibility and diversity of gene expression in response to varying disease loads. A broad expression repertoire is useful to humans, the only globally distributed primate, due to unique cultural interventions that increase pathogen exposure and disease loads (e.g., sedentism, subsistence practices). The main objective of the study is to determine if the pattern of variation observed in humans extends to other members of the genus. The data for this study are mined from the published genomes of extinct hominins (Altai Neandertal, Denisova), an ancient human (Ust-Ishim), and modern humans (1000 Genomes) using a variant call bioinformatics pipeline. No strong evidence for introgression was found to explain shared patterns of variation. Of the 21 polymorphisms identified in paleogenomes, 20 were previously found in modern humans and one is novel in Denisova. Despite introgression of haplotypes with variation in regulatory regions from extinct hominins, the pattern is not upheld in CCR5. While humans (ancient and modern) tend to have more polymorphisms in regulatory regions of the gene, neither the average number of polymorphisms per individual nor the distribution of polymorphisms across gene regions are not significantly different across members of the genus Homo. Thus, humans are not unique with regards to the increased frequency of regulatory polymorphisms and the evolution of variation patterns across CCR5 gene appears to have originated within the genus. A broader evolutionary perspective on regulatory flexibility may be that it provided an advantage during the transition to confrontational foraging (and later hunting) that altered human-environment interaction as well as during migration to Eurasia and encounters with novel pathogens.
Inter-play(ing) – embodied and relational possibilities of “serious play” at work
Authors: Küpers Wendelin
Published: October 2017

Purpose

The purpose of this paper is to analyze the role of embodied dimensions and relational possibilities of (serious) play at work. It shows how a phenomenological and processual approach can help in developing an integral understanding of (serious) play and its paradox in relation to work and practical wisdom and professional artistry in organizations.

Design/methodology/approach

Based on the literature review and phenomenology, the role of embodied dimension, and the nexus of playful practitioners, practices and playgrounds are discussed. Systematically, then the concept of “inter-playing” is proposed as a specific embodied and processual practice. Subsequently, the in-between is shown to be a medium and transrelational nexus for (serious) play that allows a more comprehensive understanding and implications.

Findings

Based on the phenomenological and relational approach, the concept of (inter-)play allows an extended understanding of serious play and its paradox as a form of an inter-practice. The mediating in-(ter-)between is revealed as decisive for playful practices and playgrounds in organizations. Serious play is linked to practical wisdom and professional artistry in organizations.

Research limitations/implications

Specific theoretical and methodological implications for exploring and enacting play are offered. It is suggested to take research itself as a form of inter-practice and to enact a more integral epistemology and methodological pluralism, including body-related and art-based approaches and critical issues.

Practical implications

Some specific practical implications are provided that facilitate and enable embodied play and play-spaces in an ongoing, arts-based learning and development process in organizational and educational contexts.

Social implications

The corporeality of responsive inter-play is seen as connected to sociality and social interaction as self and others are considered as a nexus. In particular, poetic phrónêsis in professional playful practice is linked to social creativity that includes attention and recognition of others and otherness as well as social inclusivity.

Originality/value

By extending the existing discourse and using an embodied approach, the paper proposes a novel orientation for re-interpreting serious play. Equally, it offers the new processual concepts of inter-play and inter-practice that allow more explorations and connections to discourses and practices of phronesis and art(istry).
Sex‐biased seed predation in gynodioecious Dianthus superbus var. longicalycinus (Capryophyllaceae) and differential influence of two seed predator species on the floral traits
Authors: Miyake Takashi , Satake Ikue , Miyake Keiko
Published: September 2017

Gynodioecy, the co‐occurrence of hermaphrodite and female individuals within a species, is maintained by differential reproductive success between sexes. Recently, researchers recognized that not only pollinators but also herbivores are important agents in the evolution and maintenance of gynodioecy, when herbivory is hermaphrodite biased. In this study, we investigated whether there is hermaphrodite‐biased herbivory in a gynodioecious plant, Dianthus superbus var. longicalycinus, and if so, what floral traits influenced hermaphrodite‐biased herbivory. We measured flower morphology (flower diameter, calyx tube length, corolla height and petal width) and phenology of flowers of female individuals, hermaphrodites and gynomonoecious individuals in a natural population. We also investigated seed predation and predator species. At the study site, Sibinia weevils (Curculionidae; Coleoptera) and Coleophora moths (Coleophoridae; Lepidoptera) were common pre‐dispersal seed predators in this species. The weevil appeared early in the flowering season, and weevil predation correlated with flower phenology. Because female individuals did not flower early in the season, weevil predation was less frequent in female individuals. Moth predation correlated with calyx length. The calyx length of flowers of female individuals was smaller than those of hermaphrodites, but a direct comparison of moth predation rates failed to find a significant difference among sex morphs. We found that the two seed predators had different effects on floral traits in D. superbus var. longicalycinus. We suggest that weevil predation contributes to the maintenance of gynodioecy because female individuals successfully escaped weevil predation by flowering late. It remains unclear why flower phenology is different among sex morphs.
Adsorption of Nafamostat Mesilate on AN69ST Membranes: A Single‐Center Retrospective and In Vitro Study
Authors: Nakamura Yoshihiko , Hara Shuuji , Hatomoto Hiroki , Yamasaki Shintaro , Nakano Takafumi , Miyazaki Motoyasu , Matsumoto Norihiko , Irie Yuhei , Ishikura Hiroyasu
Published: September 2017

We examined whether AN69ST (acrylonitrile and methallyl sulfonate copolymer) membranes adsorb nafamostat mesilate. This study retrospectively analyzed 87 continuous hemodiafiltration sessions in vivo. We divided the continuous hemodiafiltration sessions into AN69ST and non‐AN69ST groups using the nafamostat mesilate dose and activated clotting time as indicators of nafamostat mesilate adsorption onto the membrane. Furthermore, we studied the in vitro adsorption of nafamostat mesilate from nafamostat mesilate solutions onto four different hemodialysis membranes. This in vivo study shows that nafamostat mesilate doses were significantly higher, but activated clotting times were shorter (P < 0.001) in the AN69ST group than in the non‐AN69ST group. These results suggest that AN69ST adsorbs nafamostat mesilate. Further, the in vitro experiments show that nafamostat mesilate adsorbs AN69ST on membranes significantly more than the other membranes tested. These in vitro and clinical findings provide evidence that AN69ST may adsorb nafamostat mesilate.
Return Visit Admissions May Not Indicate Quality of Emergency Department Care for Children
Authors: Sills Marion R. , Macy Michelle L. , Kocher Keith E. , Sabbatini Amber K.
Published: September 2017

Objective

The objective was to test the hypothesis that in‐hospital outcomes are worse among children admitted during a return ED visit than among those admitted during an index ED visit.

Methods

This was a retrospective analysis of ED visits by children age 0 to 17 to hospitals in Florida and New York in 2013. Children hospitalized during an ED return visit within 7 days were classified as “ED return admissions” (discharged at ED index visit and admitted at return visit) or “readmissions” (admission at both ED index and return visits). In‐hospital outcomes for ED return admissions and readmissions were compared to “index admissions without return admission” (admitted at ED index visit without 7‐day return visit admission).

Results

Among 1,886,053 index ED visits to 321 hospitals, 75,437 were index admissions without return admission, 7,561 were ED return admissions, and 1,333 were readmissions. ED return admissions had lower intensive care unit admission rates (11.0% vs. 13.6%; adjusted odds ratio = 0.78; 95% confidence interval [CI] = 0.71 to 0.85), longer length of stay (3.51 days vs. 3.38 days; difference = 0.13 days; incidence rate ratio = 1.04; 95% CI = 1.02 to 1.07), but no difference in mean hospital costs (($7,138 vs. $7,331; difference = –$193; 95% CI = –$479 to $93) compared to index admissions without return admission.

Conclusions

Compared with children who experienced index admissions without return admission, children who are initially discharged from the ED who then have a return visit admission had lower severity and similar cost, suggesting that ED return visit admissions do not involve worse outcomes than do index admissions.
CREB Protein Mediates Alcohol‐Induced Circadian Disruption and Intestinal Permeability
Authors: Davis Booker T , Voigt Robin M. , Shaikh Maliha , Forsyth Christopher B. , Keshavarzian Ali
Published: September 2017

Background

Alcoholic liver disease (ALD) is commonly associated with intestinal permeability. An unanswered question is why only a subset of heavy alcohol drinkers develop endotoxemia. Recent studies suggest that circadian disruption is the susceptibility factor for alcohol‐induced gut leakiness to endotoxins. The circadian protein PER2 is increased after exposure to alcohol and siRNA knockdown of PER2 in vitro blocks alcohol‐induced intestinal barrier dysfunction. We have shown that blocking CYP2E1 (i.e., important for alcohol metabolism) with siRNA inhibits the alcohol‐induced increase in PER2 and suggesting that oxidative stress may mediate alcohol‐induced increase in PER2 in intestinal epithelial cells. The aim of this study was to elucidate whether a mechanism incited by alcohol‐derived oxidative stress mediates the transcriptional induction of PER2 and subsequent intestinal hyperpermeability.

Methods

Caco‐2 cells were exposed to 0.2% alcohol with or without pretreatment with modulators of oxidative stress or PKA activity. Permeability of the Caco‐2 monolayer was assessed by transepithelial electrical resistance. Protein expression was measured by Western blot and mRNA with real‐time polymerase chain reaction. Wild‐type C57BL/6J mice were fed with alcohol diet (29% of total calories, 4.5% v/v) for 8 weeks. Western blot was used to analyze PER2 expression in mouse proximal colon tissue.

Results

Alcohol increased oxidative stress, caused Caco‐2 cell monolayer dysfunction, and increased levels of the circadian clock proteins PER2 and CLOCK. These effects were mitigated by pretreatment of Caco‐2 cells with an antioxidant scavenger. Alcohol‐derived oxidative stress activated cAMP response element‐binding (CREB) via the PKA pathway and increased PER2 mRNA and protein. Inhibiting CREB prevented the increase in PER2 and Caco‐2 cell monolayer hyperpermeability.

Conclusions

Taken together, these data suggest that strategies to reduce alcohol‐induced oxidative stress may alleviate alcohol‐mediated circadian disruption and intestinal leakiness, critical drivers of ALD.
The sex‐shift in single disease and multimorbid asthma and rhinitis during puberty ‐ a study by MeDALL
Authors: Keller T. , Hohmann C. , Standl M. , Wijga A. H. , Gehring U. , Melén E. , Almqvist C. , Lau S. , Eller E. , Wahn U. , Christiansen E. S. , von Berg A. , Heinrich J. , Lehmann I. , Maier D. , Postma D. S. , Antó J. M. , Bousquet J. , Keil T. , Roll S.
Published: September 2017

Background

Cross‐sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear whether this inequality changes after puberty. We examined the sex‐specific prevalence of asthma and rhinitis as single and as multimorbid diseases before and after puberty onset in longitudinal cohort data.

Methods

In six European population‐based birth cohorts of MeDALL, we assessed the outcomes: current rhinitis, current asthma, current allergic multimorbidity (ie, concurrent asthma and rhinitis), puberty status and allergic sensitization by specific serum antibodies (immunoglobulin E) against aero‐allergens. With generalized estimating equations, we analysed the effects of sex, age, puberty (yes/no) and possible confounders on the prevalence of asthma and rhinitis, and allergic multimorbidity in each cohort separately and performed individual participant data meta‐analysis.

Findings

We included data from 19 013 participants from birth to age 14‐20 years. Current rhinitis only affected girls less often than boys before and after puberty onset: adjusted odds ratio for females vs males 0.79 (95%‐confidence interval 0.73‐0.86) and 0.86 (0.79‐0.94), respectively (sex‐puberty interaction P = .089). Similarly, for current asthma only, females were less often affected than boys both before and after puberty onset: 0.71, 0.63‐0.81 and 0.81, 0.64‐1.02, respectively (sex‐puberty interaction P = .327). The prevalence of allergic multimorbidity showed the strongest sex effect before puberty onset (female‐male‐OR 0.55, 0.46‐0.64) and a considerable shift towards a sex‐balanced prevalence after puberty onset (0.89, 0.74‐1.04); sex‐puberty interaction: P < .001.

Interpretation

The male predominance in prevalence before puberty and the “sex‐shift” towards females after puberty onset were strongest in multimorbid patients who had asthma and rhinitis concurrently.
Expression of CD markers' in immune thrombocytopenic purpura: prognostic approaches
Authors: Behzad Masumeh Maleki , Asnafi Ali Amin , Jaseb Kaveh , Jalali Far Mohammad Ali , Saki Najmaldin
Published: September 2017

Immune Thrombocytopenic Purpura (ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto‐Abs) are produced against platelet GPIIb/GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990–2016) of English‐language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self‐tolerance dysfunction, as well as induction of Auto‐Abs against platelet glycoproteins (PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients.
Large‐scale network functional interactions during distraction and reappraisal in remitted bipolar and unipolar patients
Authors: Lois Giannis , Gerchen Martin F , Kirsch Peter , Kanske Philipp , Schönfelder Sandra , Wessa Michèle
Published: September 2017

Objectives

The human brain is organized into large‐scale networks that dynamically interact with each other. Extensive evidence has shown characteristic changes in certain large‐scale networks during transitions from internally directed to externally directed attention. The aim of the present study was to compare these context‐dependent network interactions during emotion regulation and to examine potential alterations in remitted unipolar and bipolar disorder patients.

Methods

We employed a multi‐region generalized psychophysiological interactions analysis to quantify connectivity changes during distraction vs reappraisal pair‐wise across 90 regions placed throughout the four networks of interest (default‐mode, frontoparietal, salience, and dorsal attention networks). Using network contingency analysis and permutation testing, we estimated the likelihood that the number of significant condition‐dependent connectivity changes in every pair of networks exceeds the number expected by chance. We first examined the pattern of functional connectivity in 42 healthy subjects (sample I) and then compared these connectivity patterns across healthy individuals (n=23) and remitted bipolar (n=21) and unipolar disorder patients (n=21) in an independent sample II.

Results

In sample I, distraction compared to reappraisal was characterized by reduced connectivity within the default‐mode network and between the default‐mode and two cognitive control networks and increased connectivity among the cognitive control networks. In sample II, both patient groups exhibited abnormally increased default‐mode intra‐ and inter‐network connectivity during distraction compared to reappraisal.

Conclusions

The present study highlights the role of large‐scale network interactions in emotion regulation and provides preliminary evidence of default‐mode inter‐ and intra‐network connectivity impairments in remitted bipolar and unipolar patients during emotion regulation.
Modeling the Causal Effect of Treatment Initiation Time on Survival: Application to HIV/TB Co-infection
Authors: Hu Liangyuan , Hogan Joseph W. , Mwangi Ann W. , Siika Abraham
Published: September 2017

The timing of antiretroviral therapy (ART) initiation for HIV and tuberculosis (TB) co-infected patients needs to be considered carefully. CD4 cell count can be used to guide decision making about when to initiate ART. Evidence from recent randomized trials and observational studies generally supports early initiation but does not provide information about effects of initiation time on a continuous scale. In this article, we develop and apply a highly flexible structural proportional hazards model for characterizing the effect of treatment initiation time on a survival distribution. The model can be fitted using a weighted partial likelihood score function. Construction of both the score function and the weights must accommodate censoring of the treatment initiation time, the outcome, or both. The methods are applied to data on 4903 individuals with HIV/TB co-infection, derived from electronic health records in a large HIV care program in Kenya. We use a model formulation that flexibly captures the joint effects of ART initiation time and ART duration using natural cubic splines. The model is used to generate survival curves corresponding to specific treatment initiation times; and to identify optimal times for ART initiation for subgroups defined by CD4 count at time of TB diagnosis. Our findings potentially provide ‘higher resolution’ information about the relationship between ART timing and mortality, and about the differential effect of ART timing within CD4 subgroups.
Requisite role of vasohibin‐2 in spontaneous gastric cancer formation and accumulation of cancer‐associated fibroblasts
Authors: Suzuki Yasuhiro , Kitahara Shuji , Suematsu Takuya , Oshima Masanobu , Sato Yasufumi
Published: September 2017

The vasohibin (VASH) family consists of two genes, VASH1 and VASH2. VASH1 is mainly expressed in vascular endothelial cells and suppresses angiogenesis in an autocrine manner, whereas VASH2 is mainly expressed in cancer cells and exhibits pro‐angiogenic activity. Employing adenomatous polyposis coli gene mutant mice, we recently reported on the role of Vash2 in the spontaneous formation of intestinal tumors. In this study, we used K19‐Wnt1/C2mE (Gan) mice and examined the role of Vash2 in spontaneous gastric cancer formation. Gan mice spontaneously develop gastric tumors by activation of Wnt and prostaglandin E2 signaling pathways in gastric mucosa after 30 weeks of age. Expression of Vash2 mRNA was significantly increased in gastric tumor tissues compared with normal stomach tissues. When Gan mice were crossed with the Vash2‐deficient (Vash2LacZ/LacZ) strain, gastric cancer formation was significantly suppressed in Vash2LacZ/LacZ Gan mice. Normal composition of gastric mucosa was partially maintained in Vash2LacZ/LacZ Gan mice. Knockout of Vash2 caused minimal reduction of tumor angiogenesis but a significant decrease in cancer‐associated fibroblasts (CAF) in tumor stroma. DNA microarray analysis and real‐time RT‐PCR showed that mRNA levels of epiregulin (Ereg) and interleukin‐11 (Il11) were significantly downregulated in gastric tumors of Vash2LacZ/LacZ Gan mice. Furthermore, conditioned medium of gastric cancer cells stimulated migration of and α‐smooth muscle actin expression in fibroblasts, whereas conditioned medium of VASH2 knockdown cells attenuated these effects in vitro. These results suggest that VASH2 plays an important role in gastric tumor progression via the accumulation of CAF accompanying upregulation of EREG and IL‐11 expression.
Multigenerational Effects on Children's Cognitive and Socioemotional Outcomes: A Within‐Child Investigation
Authors: Tanskanen Antti O. , Danielsbacka Mirkka
Published: September 2017

Associations between grandparental investment and child outcomes were investigated using three waves of a longitudinal British Millennium Cohort Study that included children between the ages of 9 months and 5 years (n = 24,614 person‐observations from 13,744 children). Grandparental investment was measured by parent–grandparent contact frequency and grandparental financial support. Child cognitive development was measured using the British Ability Scale and socioemotional outcomes using the Strength and Difficulties Questionnaire. Grandparental investment was associated with improved cognitive and socioemotional outcomes among children. However, these associations occurred because of between‐person effects and did not exist in within‐person analyses that compared the same children over time. The results are discussed in terms of their contribution to multigenerational relationships research.
Alterations in circulating lymphoid cell populations in systemic small vessel vasculitis are non-specific manifestations of renal injury
Authors: Fazekas B , Moreno-Olivera A , Kelly Y , O'Hara P , Murray S , Kennedy A , Conlon N , Scott J , Melo A M , Hickey F B , Dooley D , O'Brien E C , Moran S , Doherty D G , Little M A
Published: September 2017

Innate lymphocyte populations, such as innate lymphoid cells (ILCs), γδ T cells, invariant natural killer T (iNK T) cells and mucosal-associated invariant T (MAIT) cells are emerging as important effectors of innate immunity and are involved in various inflammatory and autoimmune diseases. The aim of this study was to assess the frequencies and absolute numbers of innate lymphocytes as well as conventional lymphocytes and monocytes in peripheral blood from a cohort of anti-neutrophil cytoplasm autoantibody (ANCA)-associated vasculitis (AAV) patients. Thirty-eight AAV patients and 24 healthy and disease controls were included in the study. Patients with AAV were sampled both with and without immunosuppressive treatment, and in the setting of both active disease and remission. The frequencies of MAIT and ILC2 cells were significantly lower in patients with AAV and in the disease control group compared to healthy controls. These reductions in the AAV patients remained during remission. B cell count and frequencies were significantly lower in AAV in remission compared to patients with active disease and disease controls. Despite the strong T helper type 2 (Th) preponderance of eosinophilic granulomatosis with polyangiitis, we did not observe increased ILC2 frequency in this cohort of patients. The frequencies of other cell types were similar in all groups studied. Reductions in circulating ILC2 and MAIT cells reported previously in patients with AAV are not specific for AAV, but are more likely to be due to non-specific manifestations of renal impairment and chronic illness. Reduction in B cell numbers in AAV patients experiencing remission is probably therapy-related.