Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders.

Purpose: Copy-number variation is a common source of genomic variation and an important genetic cause of disease. Microarray-based analysis of copy-number variants (CNVs) has become a first-tier diagnostic test for patients with neurodevelopmental disorders, with a diagnostic yield of 10-20%. However, for most other genetic disorders, the role of CNVs is less clear and most diagnostic genetic studies are generally limited to the study of single-nucleotide variants (SNVs) and other small variants.

A Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Vedolizumab.

Vedolizumab is a humanized anti-αβ integrin monoclonal antibody that selectively blocks trafficking of memory T cells to inflamed gut tissue by inhibiting the αβ-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) interaction. Approved for treating patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD), vedolizumab is administered as a 300 mg intravenous infusion. Vedolizumab undergoes a rapid, saturable, non-linear, target-mediated elimination process at low concentrations and a slower, linear, non-specific elimination process at higher concentrations.

An unusual case of proximal humeral simple bone cyst in an adult from secondary cystic change.

Background: Simple bone cysts (SBC) have been documented to occur in adults with closed physeal plates, most commonly affecting the calcaneus in this patient subset. Although most authors theorize an association to trauma, etiology of simple bone cysts remains an enigma up to now.

Case Presentation: A 26-year-old kickboxing coach sought consult for a painful right shoulder which on radiographs and magnetic resonance (MR) imaging showed a proximal humeral lesion with signs of ossification.

Psychopathology and friendship in children and adolescents: disentangling the role of co-occurring symptom domains with serial mediation models.

The consolidation of social friendship groups is a vital part of human development. The objective of this study is to understand the direct and indirect influences of three major symptomatic domains-emotional, hyperkinetic, and conduct-on friendship. Specifically, we aim to study if the associations of one domain with friendship may be mediated by co-occurring symptoms from another domain.

A cross-cultural clinical comparison between subjects with obsessive-compulsive disorder from the United States and Brazil.

Although OCD is a global problem, the literature comparing, in a direct and standardized way, the manifestations across countries is scarce. Therefore, questions remain as to whether some important clinical findings are replicable worldwide, especially in the developing world. The objective of this study was to perform a clinical comparison of OCD patients recruited in the United States (U.

Persistent foot ulcer due to ruxolitinib therapy for primary myelofibrosis.

Primary myelofibrosis is characterized by bone marrow fibrosis, splenomegaly and presence of JAK-2 V617F mutation in more than 90% of patients. Ruxolitinib is a Janus kinase inhibitor used for the treatment of primary myelofibrosis. We describe herein a persistent foot ulcer development attributed to ruxolitinib therapy.

Safety, tolerability, pharmacokinetics, and activity of the novel long-acting antimalarial DSM265: a two-part first-in-human phase 1a/1b randomised study.

Background: DSM265 is a novel antimalarial that inhibits plasmodial dihydroorotate dehydrogenase, an enzyme essential for pyrimidine biosynthesis. We investigated the safety, tolerability, and pharmacokinetics of DSM265, and tested its antimalarial activity.

Methods: Healthy participants aged 18-55 years were enrolled in a two-part study: part 1, a single ascending dose (25-1200 mg), double-blind, randomised, placebo-controlled study, and part 2, an open-label, randomised, active-comparator controlled study, in which participants were inoculated with Plasmodium falciparum induced blood-stage malaria (IBSM) and treated with DSM265 (150 mg) or mefloquine (10 mg/kg).

Exposure-efficacy Relationships for Vedolizumab Induction Therapy in Patients with Ulcerative Colitis or Crohn's Disease.

Background And Aims: A positive relationship between vedolizumab trough serum concentrations and clinical outcomes in patients with ulcerative colitis [UC] or Crohn's disease [CD] has been reported. Here we further explore exposure-efficacy relationships for vedolizumab induction therapy in post hoc analyses of GEMINI study data.

Methods: Vedolizumab trough concentrations at Week 6 or 10 were grouped in quartiles and clinical outcome rates calculated.

Recommendations for the Use of Ultrasound and Magnetic Resonance in Patients With Spondyloarthritis, Including Psoriatic Arthritis, and Patients With Juvenile Idiopathic Arthritis.

Objective: To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging in patients with spondyloarthritis, including psoriatic arthritis, and juvenile idiopathic arthritis.

Methods: Recommendations were generated following a nominal group technique. A panel of experts (15 rheumatologists and 3 radiologists) was established in the first panel meeting to define the scope and purpose of the consensus document, as well as chapters, potential recommendations and systematic literature reviews (we used and updated those from previous EULAR documents).

Associations of Timing of Sexual Orientation Developmental Milestones and Other Sexual Minority Stressors with Internalizing Mental Health Symptoms Among Sexual Minority Young Adults.

Sexual minorities (mostly heterosexual, bisexual, lesbian/gay) are more likely than heterosexuals to have adverse mental health, which may be related to minority stress. We used longitudinal data from 1461 sexual minority women and men, aged 22-30 years, from Wave 2010 of the Growing Up Today Study, to examine associations between sexual minority stressors and mental health. We hypothesized that sexual minority stressors (earlier timing of sexual orientation developmental milestones categorized into early adolescence, middle adolescence, late adolescence/young adulthood; greater sexual orientation mobility; more bullying victimization) would be positively associated with mental health outcomes (depressive and anxious symptoms).

Hospital Impact After a Chemical Spill That Compromised the Potable Water Supply: West Virginia, January 2014.

In January 2014, a chemical spill of 4-methylcyclohexanemethanol and propylene glycol phenyl ethers contaminated the potable water supply of approximately 300,000 West Virginia residents. To understand the spill's impact on hospital operations, we surveyed representatives from 10 hospitals in the affected area during January 2014. We found that the spill-related loss of potable water affected many aspects of hospital patient care (eg, surgery, endoscopy, hemodialysis, and infection control of Clostridium difficile).

Solitary thoracic intramedullary spinal neurofibroma microsurgically extirpated via recapping T-saw laminoplasty.

We report the case of a 40-year-old female presenting with back pain that was complicated by a solitary intramedullary spinal cord mass at the T10-11 levels, confirmed by magnetic resonance imaging and computed tomography myelography. Microsurgical en bloc extirpation of the tumor approached through a recapping T-saw laminoplasty of T10 was done, and histopathology findings revealed a diagnosis of neurofibroma. Solitary spinal neurofibroma is one of the rarest tumors involving the spinal cord and is very adherent for the lack of a well-defined capsule, requiring careful dissection under microscope magnification for successful en bloc resection.

Pathogenesis of Osteosclerotic Change Following Treatment with an Antibody Against RANKL for Giant Cell Tumour of the Bone.

Background: Giant cell tumours (GCTs) of the bone are intermediate tumours that are locally aggressive. Denosumab, an antibody against receptor activator of nuclear factor kappa-B ligand (RANKL), was recently developed; however, it induces osteosclerotic change through an unknown mechanism. We determined whether osteosclerotic change could be induced by neoplastic stromal cells of giant cell tumours (GCTs).

The Child Behavior Checklist-Obsessive-Compulsive Subscale Detects Severe Psychopathology and Behavioral Problems Among School-Aged Children.

Objective: The aims of this study were (1) to assess obsessive-compulsive symptoms (OCS) dimensionally in a school-aged community sample and to correlate them with clinical and demographical variables; (2) to determine a subgroup with significant OCS ("at-risk for OCD") using the Child Behavior Checklist (CBCL-OCS) and (3) to compare it with the rest of the sample; (4) To review the CBCL-OCS subscale properties as a screening tool for pediatric OCD.

Methods: Data from the Brazilian High Risk Cohort were analyzed. The presence and severity of OCS were assessed through the CBCL-OCS subscale.

Clinical trials in palliative care: a systematic review of their methodological characteristics and of the quality of their reporting.

Background: Over the past decades there has been a significant increase in the number of published clinical trials in palliative care. However, empirical evidence suggests that there are methodological problems in the design and conduct of studies, which raises questions about the validity and generalisability of the results and of the strength of the available evidence. We sought to evaluate the methodological characteristics and assess the quality of reporting of clinical trials in palliative care.

A Model of Female Sexual Desire: Internalized Working Models of Parent-Child Relationships and Sexual Body Self-Representations.

The etiology of low female sexual desire, the most prevalent sexual complaint in women, is multi-determined, implicating biological and psychological factors, including women's early parent-child relationships and bodily self-representations. The current study evaluated a model that hypothesized that sexual body self-representations (sexual subjectivity, self-objectification, genital self-image) explain (i.e.

Primary squamous cell carcinoma of the thyroid with complete response to radical radiotherapy and concurrent cisplatin-based chemotherapy.

Chemoradiotherapy and/or surgery are both potentially radical treatments for squamous cell carcinomas. Squamous cell carcinomas are considered chemosensitive tumours compared to adenocarcinomas or anaplastic thyroid malignancies. A 76-year-old man was found to have T4bN0M0 primary squamous cell carcinoma of the thyroid with encasement of the internal carotid artery.

Corrigendum: 2016 ACG Abstracts-Inflammatory Bowel Disease.

This corrects the article DOI: 10.1038/ajg.2016.

Functional and radiological outcomes of a minimally invasive surgical approach to monostotic fibrous dysplasia.

Background: Reports showing high recurrence rates for intralesional curettage and bone grafting have made the current treatment principle for fibrous dysplasia controversial. This study aimed to report the postoperative clinical outcomes from three minimally invasive surgical strategies we use for monostotic fibrous dysplasia (MFD).

Patients And Methods: Twelve patients with MFD presenting with no pathologic fracture or deformity and treated with one of three surgical strategies-plain open biopsy, plain alpha-tricalcium phosphate (ATP) reconstruction, and prophylactic bridge plating-were included.

Recommendations for the use of ultrasound and magnetic resonance in patients with rheumatoid arthritis.

Objective: To develop evidence-based recommendations on the use of ultrasound (US) and magnetic resonance imaging (MRI) in patients with rheumatoid arthritis (RA).

Methods: Recommendations were generated following a nominal group technique. A panel of experts, consisting of 15 rheumatologists and 3 radiologists, was established in the first panel meeting to define the scope and purpose of the consensus document, as well as chapters, potential recommendations and systematic literature reviews (we used and updated those from previous EULAR documents).

A case of infected schwannoma mimicking malignant tumor.

Background: Infected schwannoma has been reported, this being one of the four cases published in the literature. Infected schwannoma has proven to be a tough diagnostic challenge to the treating tumor surgeon, mimicking infectious entities and most essentially, a malignant tumor.

Case Presentation: The authors report the case of a 64-year-old male with a soft tissue mass in his right gluteal area that presented initially with right leg pain, then later with signs of inflammation on the tumor area.

Cytokine-Induced Memory-Like Differentiation Enhances Unlicensed Natural Killer Cell Antileukemia and FcγRIIIa-Triggered Responses.

Cytokine-induced memory-like natural killer (NK) cells differentiate after short-term preactivation with IL-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks after the initial preactivation. Conventional NK cell function depends on a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown.

Lesbian, Gay, Bisexual, and Transgender Youth and Family Acceptance.

In this article, we address theories of attachment and parental acceptance and rejection, and their implications for lesbian, gay, bisexual, and transgender (LGBT) youths' identity and health. We also provide 2 clinical cases to illustrate the process of family acceptance of a transgender youth and a gender nonconforming youth who was neither a sexual minority nor transgender. Clinical implications of family acceptance and rejection of LGBT youth are discussed.

Hydration affects the physical and mechanical properties of baleen tissue.

Baleen, an anisotropic oral filtering tissue found only in the mouth of mysticete whales and made solely of alpha-keratin, exhibits markedly differing physical and mechanical properties between dried or (as in life) hydrated states. On average baleen is 32.35% water by weight in North Atlantic right whales () and 34.