Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis.

Objective: The measure of serum proteome in the preclinical state of Crohn's disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort.

Design: In a nested case-control study within the Crohn's and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284).

Paediatric post-concussive symptoms: symptom clusters and clinical phenotypes.

Objective: To assess the co-occurrence and clustering of post-concussive symptoms in children, and to identify distinct patient phenotypes based on symptom type and severity.

Methods: We performed a secondary analysis of the prospective, multicentre Predicting and Preventing Post-concussive Problems in Pediatrics (5P) cohort study, evaluating children 5-17 years of age presenting within 48 hours of an acute concussion. Our primary outcome was the simultaneous occurrence of two or more persistent post-concussive symptoms on the Post-Concussion Symptom Inventory at 28 days post-injury.

Erratum to: Neonatal Microsurgical Repair of a Congenital Abdominal Aortic Aneurysm with a Cadaveric Graft.

[This corrects the article DOI: 10.1055/s-0041-1723019.].

Neonatal Microsurgical Repair of a Congenital Abdominal Aortic Aneurysm with a Cadaveric Graft.

Congenital abdominal aortic aneurysms (AAA) are an extremely rare entity. We present the case of a female fetus diagnosed with an AAA on routine prenatal ultrasound. A postnatal computed tomography angiogram revealed an infrarenal AAA with a narrow proximal neck.

Protocol for a randomised trial evaluating a preconception-early childhood telephone-based intervention with tailored e-health resources for women and their partners to optimise growth and development among children in Canada: a Healthy Life Trajectory Initiative (HeLTI Canada).

Introduction: The 'Developmental Origins of Health and Disease' hypothesis suggests that a healthy trajectory of growth and development in pregnancy and early childhood is necessary for optimal health, development and lifetime well-being. The purpose of this paper is to present the protocol for a randomised controlled trial evaluating a preconception-early childhood telephone-based intervention with tailored e-health resources for women and their partners to optimise growth and development among children in Canada: a Healthy Life Trajectory Initiative (HeLTI Canada). The primary objective of HeLTI Canada is to determine whether a 4-phase 'preconception to early childhood' lifecourse intervention can reduce the rate of child overweight and obesity.

Glomerular filtration rate in liver transplant for unresectable hepatoblastoma.

Most children with hepatoblastoma manifest, at the time of LT, a decrease in renal function due to chemotherapy that could be further deteriorated by the use of calcineurin inhibitors. The purpose of this work was to examine the long-term follow-up of renal function in a cohort of children transplanted for unresectable hepatoblastoma. We present a retrospective observational study of 10 pediatric patients who received a LT for unresectable hepatoblastoma between 1996 and 2016.

The Distinct Roles of CXCR3 Variants and Their Ligands in the Tumor Microenvironment.

First thought to orchestrate exclusively leukocyte trafficking, chemokines are now acknowledged for their multiple roles in the regulation of cell proliferation, differentiation, and survival. Dysregulation of their normal functions contributes to various pathologies, including inflammatory diseases and cancer. The two chemokine receptor 3 variants CXCR3-A and CXCR3-B, together with their cognate chemokines (CXCL11, CXCL10, CXCL9, CXCL4, and CXCL4L1), are involved in the control but also in the development of many tumors.

Exploring the Binding Interaction Mechanism of Taxol in β-Tubulin and Bovine Serum Albumin: A Biophysical Approach.

In this present study on understanding the taxol (PTX) binding interaction mechanism in both the β-tubulin and bovine serum albumin (BSA) molecule, various optical spectroscopy and computational techniques were used. The fluorescence steady-state emission spectroscopy result suggests that there is a static quenching mechanism of the PTX drug in both β-tubulin and BSA, and further time-resolved emission spectroscopy studies confirm that the quenching mechanism exists. The excitation-emission matrix (EEM), Fourier transform infrared, and resonance light scattering spectra (FT-IR) confirm that there are structural changes in both the BSA and β-tubulin molecule during the binding process of PTX.

Projecting social contact matrices to different demographic structures.

The modeling of large-scale communicable epidemics has greatly benefited in the last years from the increasing availability of highly detailed data. Particullarly, in order to achieve quantitative descriptions of the evolution of epidemics, contact networks and mixing patterns are key. These heterogeneous patterns depend on several factors such as location, socioeconomic conditions, time, and age.

Comparative Binding Analysis of N-Acetylneuraminic Acid in Bovine Serum Albumin and Human α-1 Acid Glycoprotein.

The present study focuses on the determination of the biologically significant N-acetylneuraminic acid (NANA) drug binding interaction mechanism between bovine serum albumin (BSA) and human α-1 acid glycoprotein (HAG) using various optical spectroscopy and computational methods. The steady state fluorescence spectroscopy result suggests that the fluorescence intensity of BSA and HAG was quenched by NANA in a static mode of quenching. Further time-resolved emission spectroscopy measurements confirm that mode of quenching mechanism of NANA in the BSA and HAG system.

Different contributions of chemokine N-terminal features attest to a different ligand binding mode and a bias towards activation of ACKR3/CXCR7 compared with CXCR4 and CXCR3.

Background And Purpose: Chemokines and their receptors form an intricate interaction and signalling network that plays critical roles in various physiological and pathological cellular processes. The high promiscuity and apparent redundancy of this network makes probing individual chemokine/receptor interactions and functional effects, as well as targeting individual receptor axes for therapeutic applications, challenging. Despite poor sequence identity, the N-terminal regions of chemokines, which play a key role in their activity and selectivity, contain several conserved features.

Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study.

Background: Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined.

Objective: This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors.

Ligand-specific conformational transitions and intracellular transport are required for atypical chemokine receptor 3-mediated chemokine scavenging.

The atypical chemokine receptor ACKR3 contributes to chemotaxis by binding, internalizing, and degrading the chemokines CXCL11 and CXCL12 to shape and terminate chemotactic gradients during development and immune responses. Although unable to trigger G protein activation, both ligands activate G protein-independent ACKR3 responses and prompt arrestin recruitment. This offers a model to specifically study ligand-specific receptor conformations leading to G protein-independent signaling and to functional parameters such as receptor transport and chemokine degradation.

Clinical trial of L-Carnitine and valproic acid in spinal muscular atrophy type I.

Introduction: The aim of this study was to determine the safety and therapeutic potential of L-carnitine and valproic acid (VPA) in infants with spinal muscular atrophy (SMA).

Methods: Our investigation was an open-label phase 2 multicenter trial of L-carnitine and VPA in infants with SMA type I with retrospective comparison to an untreated, matched cohort. Primary outcomes were: safety and adverse events; secondary outcomes were survival, time to death/>16 hours/day of ventilator support; motor outcomes; and maximum ulnar compound motor action potential amplitude.

Advanced neonatal medicine in China: a quantitative analysis of research productivity and impact factors.

Objectives: To summarize academic productivity of neonatal medicine in China and explore its relationship with health care workforce and activities.

Methods: We retrospectively extracted data from national key clinical subspecialty proposals, and used accessible databases as Science Citation Index (SCI), PubMed, and National Natural Science Foundation of China.

Results: Between 2008 and 2010, 61 newborn units at the most advanced level in 31 cities from 28 of 31 provincial districts in mainland China were included.

Advanced Neonatal Medicine in China: A National Baseline Database.

Previous surveys of neonatal medicine in China have not collected comprehensive information on workforce, investment, health care practice, and disease expenditure. The goal of the present study was to develop a national database of neonatal care units and compare present outcomes data in conjunction with health care practices and costs. We summarized the above components by extracting data from the databases of the national key clinical subspecialty proposals issued by national health authority in China, as well as publicly accessible databases.

Mutational Analysis of Atypical Chemokine Receptor 3 (ACKR3/CXCR7) Interaction with Its Chemokine Ligands CXCL11 and CXCL12.

Atypical chemokine receptors do not mediate chemotaxis or G protein signaling, but they recruit arrestin. They also efficiently scavenge their chemokine ligands, thereby contributing to gradient maintenance and termination. ACKR3, also known as CXCR7, binds and degrades the constitutive chemokine CXCL12, which also binds the canonical receptor CXCR4, and CXCL11, which also binds CXCR3.

Secular Trends in Preeclampsia Incidence and Outcomes in a Large Canada Database: A Longitudinal Study Over 24 Years.

Background: The incidence of preeclampsia is increasing, but effects on women and infants are unclear. We measured the incidence of preeclampsia over time in a large Canadian population, and assessed trends in maternal and infant morbidity and mortality.

Methods: We carried out a population-based study of 1,901,376 linked hospital discharge abstracts for all deliveries in the province of Quebec, Canada from 1989 through 2012.

New modes in non-invasive ventilation.

Non-invasive ventilation is useful to treat some forms of respiratory failure. Hence, the number of patients receiving this treatment is steadily increasing. Considerable conceptual and technical progress has been made in the last years by manufacturers concerning this technique.

Genome-Wide Association Studies of the Human Gut Microbiota.

The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both).

Inherited CARD9 deficiency in otherwise healthy children and adults with Candida species-induced meningoencephalitis, colitis, or both.

Background: Invasive infections of the central nervous system (CNS) or digestive tract caused by commensal fungi of the genus Candida are rare and life-threatening. The known risk factors include acquired and inherited immunodeficiencies, with patients often displaying a history of multiple infections. Cases of meningoencephalitis, colitis, or both caused by Candida species remain unexplained.

Vitamin D and pregnancy outcomes.

Purpose Of Review: This article presents an overview of the most recent scientific evidence of the role of maternal vitamin D on pregnancy outcomes, with a particular emphasis on those articles in the English-language literature published between 1 January 2013 and 1 July 2014 in PubMed.

Recent Findings: Low levels of vitamin D status, as measured by 25-hydroxyvitamin D [25(OH)D], are common in pregnant women. Meta-analysis of observational studies has demonstrated positive associations between vitamin D status and adverse pregnancy outcomes such as preeclampsia, gestational diabetes mellitus, preterm birth and small-for-gestational age.

Head and trunk segment moments of inertia estimation using angular momentum technique: validity and sensitivity analysis.

Classical models to estimate the head and trunk (HT) moments of inertia (I) are limited to populations from which the anthropometric measures were obtained. The purposes of this study were to determine if the angular momentum technique can be used to estimate subject-specific HT's I values and test its validity and sensitivity. Twenty-three adults who participated in this study were divided into three morphological groups according to their body mass index (BMI).