The natural history of prenatally diagnosed congenital cystic lung lesions: long-term follow-up of 119 cases.

Background: A paucity of evidence regarding the natural history of congenital pulmonary airway malformations (CPAMs) and pulmonary sequestration (PS) has resulted in a divergence in management strategy of asymptomatic cases.

Methods: We describe the long-term clinical course of 119 children diagnosed with these lesions treated at Great Ormond Street Hospital (GOSH). Cases were identified via the GOSH patient database.

New Molecular Assay for the Proliferation Signature in Mantle Cell Lymphoma Applicable to Formalin-Fixed Paraffin-Embedded Biopsies.

Purpose Mantle cell lymphoma is an aggressive B-cell neoplasm that displays heterogeneous outcomes after treatment. In 2003, the Lymphoma/Leukemia Molecular Profiling Project described a powerful biomarker-the proliferation signature-using gene expression in fresh frozen material. Herein, we describe the training and validation of a new assay that measures the proliferation signature in RNA derived from routinely available formalin-fixed paraffin-embedded (FFPE) biopsies.

Rare and low-frequency coding variants alter human adult height.

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk.

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci.

E1A enhances cellular sensitivity to DNA-damage-induced apoptosis through PIDD-dependent caspase-2 activation.

Expression of the adenoviral protein, E1A, sensitizes mammalian cells to a wide variety of apoptosis-inducing agents through multiple cellular pathways. For example, E1A sensitizes cells to apoptosis induced by TNF-superfamily members by inhibiting NF-kappa B (NF-B)-dependent gene expression. In contrast, E1A sensitization to nitric oxide, an inducer of the intrinsic apoptotic pathway, is not dependent upon repression of NF-B-dependent transcription but rather is dependent upon caspase-2 activation.

Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.

Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1.

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication.

The Epidemiology of Urolithiasis in an Ethnically Diverse Population Living in The Same Area.

Purpose: Little is known about whether migrants retain the risk of urolithiasis seen in their indigenous populations. We sought to evaluate the risk of renal colic between different ethnic groups among a diverse population in London.

Materials And Methods: Data on a cohort of 100 consecutive patients presenting to our emergency department with acute renal colic over a 6 month period was collected retrospectively.

BioCartilage Improves Cartilage Repair Compared With Microfracture Alone in an Equine Model of Full-Thickness Cartilage Loss.

Background: Microfracture (MFx) remains a dominant treatment strategy for symptomatic articular cartilage defects. Biologic scaffold adjuncts, such as particulated allograft articular cartilage (BioCartilage) combined with platelet-rich plasma (PRP), offer promise in improving clinical outcomes as an adjunct to MFx.

Purpose: To evaluate the safety, biocompatibility, and efficacy of BioCartilage and PRP for cartilage repair in a preclinical equine model of full-thickness articular cartilage loss.

Do 25-Hydroxyvitamin D Levels Correlate With Fracture Complications?

Objectives: To determine the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and the likelihood of postoperative complications and fracture reoperation rate in orthopaedic trauma patients receiving vitamin D and calcium supplementation.

Design: Retrospective case series.

Setting: Level I trauma center, Midwestern United States.

US Intergroup Trial of Response-Adapted Therapy for Stage III to IV Hodgkin Lymphoma Using Early Interim Fluorodeoxyglucose-Positron Emission Tomography Imaging: Southwest Oncology Group S0816.

Purpose: Four US National Clinical Trials Network components (Southwest Oncology Group, Cancer and Leukemia Group B/Alliance, Eastern Cooperative Oncology Group, and the AIDS Malignancy Consortium) conducted a phase II Intergroup clinical trial that used early interim fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to determine the utility of response-adapted therapy for stage III to IV classic Hodgkin lymphoma.

Patients And Methods: The Southwest Oncology Group S0816 (Fludeoxyglucose F 18-PET/CT Imaging and Combination Chemotherapy With or Without Additional Chemotherapy and G-CSF in Treating Patients With Stage III or Stage IV Hodgkin Lymphoma) trial enrolled 358 HIV-negative patients between July 1, 2009, and December 2, 2012. A PET scan was performed after two initial cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and was labeled PET2.

A Stromal Cell-Derived Factor 1α Analogue Improves Endothelial Cell Function in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome.

Endothelial cell (EC) dysfunction is a critical mediator of the acute respiratory distress syndrome (ARDS). Recent studies have demonstrated that stromal cell-derived factor 1α (SDF-1α) promotes EC barrier integrity. Our previous studies used a SDF-1α analogue CTCE-0214 (CTCE) in experimental sepsis and demonstrated that it attenuated vascular leak and modulated microRNA (miR) levels.

Acute Management of Anterior Cruciate Ligament Injuries Using Novel Canine Models.

The objective of this study was to compare treatment options for acute management of anterior cruciate ligament (ACL) injuries using preclinical models. Twenty-seven adult purpose-bred research hounds underwent knee surgery (sham control, exposed ACL, or partial-tear ACL) and were assessed over the following 8 weeks. Dogs were randomized into three treatment groups: standard of care (i.

Cytokine preconditioning of engineered cartilage provides protection against interleukin-1 insult.

Background: During osteoarthritis and following surgical procedures, the environment of the knee is rich in proinflammatory cytokines such as IL-1. Introduction of tissue-engineered cartilage constructs to a chemically harsh milieu may limit the functionality of the implanted tissue over long periods. A chemical preconditioning scheme (application of low doses of IL-1) was tested as a method to prepare developing engineered tissue to withstand exposure to a higher concentration of the cytokine, known to elicit proteolysis as well as rapid degeneration of cartilage.

Low-Level Expression of the E1B 20-Kilodalton Protein by Adenovirus 14p1 Enhances Viral Immunopathogenesis.

Adenovirus 14p1 (Ad14p1) is an emergent variant of Ad serotype 14 (Ad14) that has caused increased severity of respiratory illnesses during globally distributed outbreaks, including cases of acute respiratory distress syndrome and death. We found that human cell infection with Ad14p1 results in markedly decreased expression of the E1B 20-kilodalton (20K) protein compared to that with infection with wild-type (wt) Ad14. This reduced Ad14p1 E1B 20K expression caused a loss-of-function phenotype of Ad-infected cell corpses that, in contrast to cells infected with wt Ad14, either failed to repress or increased NF-κB-dependent, proinflammatory cytokine responses of responder human alveolar macrophages.

Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank.

Background: Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.

Methods: We sampled individuals of European ancestry from UK Biobank, from the middle and extremes of the forced expiratory volume in 1 s (FEV1) distribution among heavy smokers (mean 35 pack-years) and never smokers.

Clinical outcomes associated with the initial use of the Canine Unicompartmental Elbow (CUE) Arthroplasty System(®).

We evaluated mid- to long-term outcomes with respect to function and complications in dogs undergoing canine unicompartmental elbow (CUE) arthroplasty for treatment of medial compartment disease of the elbow. This prospective multicenter case series is the first group of clinical cases to receive CUE arthroplasty. Cases (each elbow that underwent CUE performed by a participating surgeon) were enrolled into an electronic database and prospectively followed to determine and record all associated complications, as well as functional outcomes.

Regulating anxiety with extrasynaptic inhibition.

Aversive experiences can lead to complex behavioral adaptations including increased levels of anxiety and fear generalization. The neuronal mechanisms underlying such maladaptive behavioral changes, however, are poorly understood. Here, using a combination of behavioral, physiological and optogenetic approaches in mouse, we identify a specific subpopulation of central amygdala neurons expressing protein kinase C δ (PKCδ) as key elements of the neuronal circuitry controlling anxiety.

Identification of Primary Mediastinal Large B-cell Lymphoma at Nonmediastinal Sites by Gene Expression Profiling.

Mediastinal involvement is considered essential for the diagnosis of primary mediastinal large B-cell lymphoma (PMBL). However, we have observed cases of diffuse large B-cell lymphoma (DLBCL) with features of PMBL but without detectable mediastinal involvement. The goal was to assess our previously established gene expression profiling (GEP) signature for PMBL in classifying these cases.

A Conceptual Model of Irritability Following Traumatic Brain Injury: A Qualitative, Participatory Research Study.

Background: Individuals with a history of traumatic brain injury (TBI) may have chronic problems with irritability, which can negatively affect their lives.

Objectives: (1) To describe the experience (thoughts and feelings) of irritability from the perspectives of multiple people living with or affected by the problem, and (2) to develop a conceptual model of irritability.

Design: Qualitative, participatory research.

Social pedagogy as a model to provide support for siblings of children with intellectual disabilities: A report of the views of the children and young people using a sibling support group.

The experiences of non-disabled children growing up with a sibling with an intellectual disability vary considerably, with reported impact ranging from increased mental health problems through evaluations of life enhancement. However, there is evidence that the net impact is neutral to positive, which was supported by the findings of this report of a service evaluation survey. The value of providing support to those young siblings is however clear.