Identification and functional validation of a novel pathogenic germline variant p.G95V in familial melanoma.

variants have been identified in familial melanoma (FM) as well as a number of other germline and somatic malignancies. The functional validation of variants identified from the screening of patients with melanoma gene susceptibility panels is key to understanding the clinical significance of identified variants. Here we report a novel, likely pathogenic missense variant (p.

Environmental management of asthma in clinical practice: Results from the 2012 National Ambulatory Medical Care Survey.

Background: The National Asthma Education and Prevention Program guidelines emphasize environmental control as an integral part of asthma management; however, limited national-level data exist on how clinicians implement environmental control recommendations.

Objective: We analyzed data on clinicians' self-reported use of recommended environmental control practices in a nationally representative sample (n = 1645) of primary care physicians, asthma specialists, and advanced practice providers from the National Asthma Survey of Physicians, a supplemental questionnaire to the 2012 National Ambulatory Medical Care Survey.

Methods: We examined clinician and practice characteristics as well as clinicians' decisions and strategies regarding environmental trigger assessment and environmental control across provider groups.

Comparing post-concussion symptom reporting between adults with and without a TBI history within an adult male correctional facility.

Background: A higher proportion of people in prison have a history of traumatic brain injury (TBI) than the general population. However, little is known about potentially related persistent symptoms in this population.

Aims: To compare symptom reporting in men with and without a history of TBI following admission to a correctional facility.

An intervention to improve coping strategies in adult male prisoners with a history of traumatic brain injury: A pilot randomised clinical trial.

Objective: To determine whether a psychological intervention improves coping, post-concussion symptoms and decreases in-prison infractions in adult males with a history of traumatic brain injury.

Design: A single centre, randomised, wait-list, pilot study.

Setting: A high security prison in New Zealand.

Spectrum of mutational signatures in T-cell lymphoma reveals a key role for UV radiation in cutaneous T-cell lymphoma.

T-cell non-Hodgkin's lymphomas develop following transformation of tissue resident T-cells. We performed a meta-analysis of whole exome sequencing data from 403 patients with eight subtypes of T-cell non-Hodgkin's lymphoma to identify mutational signatures and associated recurrent gene mutations. Signature 1, indicative of age-related deamination, was prevalent across all T-cell lymphomas, reflecting the derivation of these malignancies from memory T-cells.

User testing a patient information resource about potential complications of vaginally inserted synthetic mesh.

Background: Vaginal mesh implants are medical devices used in a number of operations to treat stress urinary incontinence and pelvic organ prolapse. Although many of these operations have delivered good outcomes, some women have experienced serious complications that have profoundly affected their quality of life. To ensure that evolving patient information is up-to-date, accurate and appropriate, the Transvaginal Mesh Oversight Group 'user-tested' a newly developed Scottish patient resource, the first to focus exclusively on the issue of complications.

Frequent and Persistent PLCG1 Mutations in Sézary Cells Directly Enhance PLCγ1 Activity and Stimulate NFκB, AP-1, and NFAT Signaling.

Phospholipase C Gamma 1 (PLCG1) is frequently mutated in primary cutaneous T-cell lymphoma (CTCL). This study functionally interrogated nine PLCG1 mutations (p.R48W, p.

Contribution of STAT3 and RAD23B in Primary Sézary Cells to Histone Deacetylase Inhibitor FK228 Resistance.

FK228 (romidepsin) and suberoylanilide hydroxamic acid (vorinostat) are histone deacetylase inhibitors (HDACi) approved by the US Food and Drug Administration for cutaneous T-cell lymphoma (CTCL), including the leukemic subtype Sézary syndrome. This study investigates RAD23B and STAT3 gene perturbations in a large cohort of primary Sézary cells and the effect of FK228 treatment on tyrosine phosphorylation of STAT3 (pYSTAT3) and RAD23B expression. We report RAD23B copy number variation in 10% (12/119, P ≤ 0.

Clinician Agreement, Self-Efficacy, and Adherence with the Guidelines for the Diagnosis and Management of Asthma.

Background: The 2007 Guidelines for the Diagnosis and Management of Asthma provide evidence-based recommendations to improve asthma care. Limited national-level data are available about clinician agreement and adherence to these guidelines.

Objective: To assess clinician-reported adherence with specific guideline recommendations, as well as agreement with and self-efficacy to implement guidelines.

Prevalence of Traumatic Brain Injury in a Male Adult Prison Population and Its Association with the Offence Type.

Background: The prevalence of traumatic brain injury (TBI) in prison populations has been found to vary considerably. This study aimed to determine the prevalence of TBI in a prison population in New Zealand and to identify whether age, ethnicity, offence type, security classification and sentence length were linked to TBI prevalence.

Methods: All offenders admitted to a new Corrections Facility over a 6-month period (May-November 2015) were screened to understand their history of TBI.

Candidate driver genes involved in genome maintenance and DNA repair in Sézary syndrome.

Sézary syndrome (SS) is a leukemic variant of cutaneous T-cell lymphoma (CTCL) and represents an ideal model for study of T-cell transformation. We describe whole-exome and single-nucleotide polymorphism array-based copy number analyses of CD4(+) tumor cells from untreated patients at diagnosis and targeted resequencing of 101 SS cases. A total of 824 somatic nonsynonymous gene variants were identified including indels, stop-gain/loss, splice variants, and recurrent gene variants indicative of considerable molecular heterogeneity.

Evaluation of Immunophenotypic and Molecular Biomarkers for Sézary Syndrome Using Standard Operating Procedures: A Multicenter Study of 59 Patients.

Differentiation between Sézary syndrome and erythrodermic inflammatory dermatoses can be challenging, and a number of studies have attempted to identify characteristic immunophenotypic changes and molecular biomarkers in Sézary cells that could be useful as additional diagnostic criteria. In this European multicenter study, the sensitivity and specificity of these immunophenotypic and recently proposed but unconfirmed molecular biomarkers in Sézary syndrome were investigated. Peripheral blood CD4(+) T cells from 59 patients with Sézary syndrome and 19 patients with erythrodermic inflammatory dermatoses were analyzed for cell surface proteins by flow cytometry and for copy number alterations and differential gene expression using custom-made quantitative PCR plates.

Independent Loss of Methylthioadenosine Phosphorylase (MTAP) in Primary Cutaneous T-Cell Lymphoma.

Methylthioadenosine phosphorylase (MTAP) and the tumor suppressor genes CDKN2A-CDKN2B are frequently deleted in malignancies. The specific role of MTAP in cutaneous T-cell lymphoma subgroups, mycosis fungoides (MF) and Sézary syndrome (SS), is unknown. In 213 skin samples from patients with MF/SS, MTAP copy number loss (34%) was more frequent than CDKN2A (12%) in all cutaneous T-cell lymphoma stages using quantitative reverse transcription PCR.

Explaining gender differences in jurors' reactions to child sexual assault cases.

In three experiments, we investigated the influence of juror, victim, and case factors on mock jurors' decisions in several types of child sexual assault cases (incest, day care, stranger abduction, and teacher-perpetrated abuse). We also validated and tested the ability of several scales measuring empathy for child victims, children's believability, and opposition to adult/child sex, to mediate the effect of jurors' gender on case judgments. Supporting a theoretical model derived from research on the perceived credibility of adult rape victims, women compared to men were more empathic toward child victims, more opposed to adult/child sex, more pro-women, and more inclined to believe children generally.

IgG4 subclass antibodies impair antitumor immunity in melanoma.

Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass antibodies are present in IL-10-driven Th2 immune responses in some inflammatory conditions. Since Th2-biased inflammation is a hallmark of tumor microenvironments, we investigated the presence and functional implications of IgG4 in malignant melanoma.

Solitary mycosis fungoides: a distinct clinicopathologic entity with a good prognosis: a series of 15 cases and literature review.

Background: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL), accounting for almost 50% of all primary cutaneous lymphomas. The occurrence of solitary lesions, which are clinically and histopathologically indistinguishable from classic MF has been described.

Objective: We describe 15 cases of solitary MF and discuss the relationship to classic MF, "reactive" processes and to other, rarer forms of CTCL that may present with solitary lesions.

Regulation of T-plastin expression by promoter hypomethylation in primary cutaneous T-cell lymphoma.

T-plastin (PLS3) is an actin-bundling protein normally expressed in epithelial cells but absent in cells of hematopoietic origin. Aberrant PLS3 expression has been demonstrated in lymphocytes from Sézary syndrome (SS) patients and has been proposed as a biomarker for SS; however, the mechanism underlying dysregulation of PLS3 has not been determined. In this study, PLS3 mRNA expression was demonstrated in 21/35 (60%) SS patients and in 3/8 (38%) mycosis fungoides patients, all of whom had clonal blood involvement.

Survival outcomes and prognostic factors in mycosis fungoides/Sézary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal.

Purpose: We have analyzed the outcome of mycosis fungoides (MF) and Sézary syndrome (SS) patients using the recent International Society for Cutaneous Lymphomas (ISCL)/European Organisation for Research and Treatment of Cancer (EORTC) revised staging proposal.

Patients And Methods: Overall survival (OS), disease-specific survival (DSS), and risk of disease progression (RDP) were calculated for a cohort of 1,502 patients using univariate and multivariate models.

Results: The mean age at diagnosis was 54 years, and 71% of patients presented with early-stage disease.

MicroRNA expression in Sezary syndrome: identification, function, and diagnostic potential.

MicroRNAs are commonly aberrantly expressed in many cancers. Very little is known of their role in T-cell lymphoma, however. We therefore elucidated the complete miRNome of purified T cells from 21 patients diagnosed with Sézary Syndrome (SzS), a rare aggressive primary cutaneous T-cell (CD4(+)) lymphoma.

Downregulation of Fas gene expression in Sézary syndrome is associated with promoter hypermethylation.

Sézary Syndrome (SS) is an aggressive leukemic variant of primary cutaneous T-cell lymphoma characterized by the presence of tumor or Sézary cells that generally display a mature memory T-cell immunophenotype. Sézary cells proliferate poorly and therefore their accumulation may be due to defective T-cell homeostasis involving resistance to apoptosis. In this study, we analyzed Fas expression in CD4+ lymphocytes at the mRNA and protein levels in a large cohort of SS patients as compared with healthy controls.

Low-grade B-cell proliferation progressing to high-grade B-cell lymphoma.

We present a case of a primary cutaneous lymphoproliferative process, originally diagnosed as cutaneous lymphoid hyperplasia, which progressed to a nodal high-grade diffuse large B-cell lymphoma 3 years after the initial diagnosis. The 2 processes were related by the presence of the same lymphoid clone in the cutaneous and the nodal proliferation.

Fine-mapping chromosomal loss at 9p21: correlation with prognosis in primary cutaneous diffuse large B-cell lymphoma, leg type.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT) is the most aggressive type of primary cutaneous B-cell lymphoma. In a recent study on 12 patients it was found that inactivation of CDKN2A by either deletion of 9p21.3 or promoter hypermethylation is correlated with a worse prognosis.

A genomic and expression study of AP-1 in primary cutaneous T-cell lymphoma: evidence for dysregulated expression of JUNB and JUND in MF and SS.

Activator protein 1 (AP-1) consists of a group of transcription factors including the JUN and FOS family proteins with diverse biological functions. This study assessed the genomic and expression status of the AP-1 transcription factors in primary cutaneous T-cell lymphoma (CTCL) by using immunohistochemistry (IHC), Affymetrix expression microarray, real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescent in situ hybridization (FISH). IHC showed JUNB protein expression in tumor cells from 17 of 33 cases of Sezary syndrome (SS) and JUND protein expression in 16 of 23 mycosis fungoides cases.

Molecular analysis of T-cell receptor beta genes in cutaneous T-cell lymphoma reveals Jbeta1 bias.

Molecular characterization of T-cell receptor junctional region sequences in cutaneous T-cell lymphoma had not been previously reported. We have examined in detail the features of the T-cell receptor beta (TCRB) gene rearrangements in 20 individuals with well-defined stages of cutaneous T-cell lymphoma (CTCL) comprising 10 cases with early-stage mycosis fungoides (MF) and 10 cases with late-stage MF or Sezary syndrome. Using BIOMED-2 PCR primers, we detected a high frequency of clonally rearranged TCR gamma and TCRB genes (17/20 and 15/20 cases, respectively).

Lack of suppressive CD4+CD25+FOXP3+ T cells in advanced stages of primary cutaneous T-cell lymphoma.

Mycosis fungoides and its leukemic variant, Sezary syndrome, are the most common primary cutaneous T-cell lymphomas (CTCLs). In an ex vivo study, we investigated the percentage, phenotype, and suppressive function of CD4+CD25+ regulatory T cells (Tregs) from peripheral blood of CTCL patients. The percentage of Tregs did not differ significantly between patients and controls.