Detection of Citrus leprosis virus C using specific primers and TaqMan probe in one-step real-time reverse-transcription polymerase chain reaction assays.

Citrus leprosis virus C (CiLV-C), a causal agent of the leprosis disease in citrus, is mostly present in the South and Central America and spreading toward the North America. To enable better diagnosis and inhibit the further spread of this re-emerging virus a quantitative (q) real-time reverse transcription polymerase chain reaction (qRT-PCR) assay is needed for early detection of CiLV-C when the virus is present in low titer in citrus leprosis samples. Using the genomic sequence of CiLV-C, specific primers and probe were designed and synthesized to amplify a 73 nt amplicon from the movement protein (MP) gene.

Disruption of pre-B-cell receptor signaling jams the WNT/β-catenin pathway and induces cell death in B-cell acute lymphoblastic leukemia cell lines.

Targeting components of the B-cell receptor (BCR) pathway have dramatically improved clinical outcomes in a variety of B-cell malignancies. Despite the well-documented pathogenic role of BCR precursor (pre-BCR) pathway in B-cell acute lymphoblastic leukemia (B-ALL), there is limited available data of therapies that aim to disrupt this pathway. To investigate the role of protein kinase Cβ (PKCβ), a crucial mediator of BCR and pre-BCR signaling, in B-ALL survival, we studied the activity of the PKCβ selective inhibitor enzastaurin (ENZ) in seven B-ALL cell lines.

Regulatory risk assessment approaches for synthetic mineral fibres.

Exposure to synthetic mineral fibres (SMF) may occur in a number of workplace scenarios. To protect worker health, a number of different organisations worldwide have assessed the health risk of these materials and established workplace exposure limits. This paper outlines the basic principles of risk assessment and the scientific methods used to derive valid (justifiable) occupational exposure limits (OELs) and goes on to show how, for SMF, and particularly for refractory ceramic fibre (otherwise known as aluminosilicate wool, RCF/ASW), the methods used and the associated outcomes differ widely.

The future of nanosized radiation enhancers.

Radiotherapy has a universal and predictable mode of action, that is, a physical mode of action consisting of the deposit of a dose of energy in tissues. Tumour cell damage is proportional to the energy dose. However, the main limitation of radiotherapy is the lack of spatial control of the deposition of energy, that is, it penetrates the healthy tissues, damages them and renders unfeasible delivery of an efficient energy dose when tumours are close to important anatomical structures.

Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate.

Background: Treatment of moderate to severe atopic dermatitis (AD) is often inadequate.

Objective: We sought to evaluate the efficacy of the oral Janus kinase inhibitor tofacitinib citrate in the treatment of moderate to severe AD.

Methods: Six consecutive patients with moderate to severe AD who had failed standard treatment were treated with tofacitinib citrate.

Effects of Chemotherapy Regimen and Radiation Modality on Hematologic Toxicities in Patients Receiving Definitive Platinum-based Doublet Chemoradiation for Non-Small Cell Lung Cancer.

Objectives: Predictors of acute hematologic toxicities during definitive chemoradiation for non-small cell lung cancer (NSCLC) are incompletely defined.

Materials And Methods: We retrospectively analyzed 604 patients treated with definitive platinum-based doublet chemoradiation therapy for stage III NSCLC. The outcome of interest was grade ≥3 acute hematologic toxicities, specifically white blood cell, hemoglobin, platelet, neutrophil, and lymphocyte decrease during chemoradiation therapy.

Functional Characterization of a WWP1/Tiul1 Tumor-derived Mutant Reveals a Paradigm of Its Constitutive Activation in Human Cancer.

Although E3 ubiquitin ligases are deemed to play key roles in normal cell function and homeostasis, whether their alterations contribute to cancer pathogenesis remains unclear. In this study, we sought to investigate potential mechanisms that govern WWP1/Tiul1 (WWP1) ubiquitin ligase activity, focusing on its ability to trigger degradation of TGFβ type I receptor (TβRI) in conjunction with Smad7. Our data reveal that the WWP1 protein is very stable at steady states because its autopolyubiquitination activity is silenced due to an intra-interaction between the C2 and/or WW and Hect domains that favors WWP1 monoubiquitination at the expense of its polyubiquitination or polyubiquitination of TβRI.

Splenectomy inhibits non-small cell lung cancer growth by modulating anti-tumor adaptive and innate immune response.

It has been shown that inhibitors of the immune system reside in the spleen and inhibit the endogenous antitumor effects of the immune system. We hypothesized that splenectomy would inhibit the growth of relatively large non-small lung cancer (NSCLC) tumors by modulating the systemic inhibition of the immune system, and in particular Myeloid Derived Suppressor Cells (MDSC). The effect of splenectomy was evaluated in several murine lung cancer models.

Cap-assisted colonoscopy and detection of Adenomatous Polyps (CAP) study: a randomized trial.

Background And Study Aim: Cap-assisted colonoscopy has improved adenoma detection in some but not other studies. Most previous studies have been limited by small sample sizes and few participating endoscopists. The aim of the current study was to evaluate whether cap-assisted colonoscopy improves adenoma detection in a two-center, multi-endoscopist, randomized trial.

The Scientific Basis of Uncertainty Factors Used in Setting Occupational Exposure Limits.

The uncertainty factor concept is integrated into health risk assessments for all aspects of public health practice, including by most organizations that derive occupational exposure limits. The use of uncertainty factors is predicated on the assumption that a sufficient reduction in exposure from those at the boundary for the onset of adverse effects will yield a safe exposure level for at least the great majority of the exposed population, including vulnerable subgroups. There are differences in the application of the uncertainty factor approach among groups that conduct occupational assessments; however, there are common areas of uncertainty which are considered by all or nearly all occupational exposure limit-setting organizations.

Implications of skeletal muscle loss for public health nutrition messages: a brief report.

Age-related skeletal muscle loss, sarcopenia, cachexia and wider malnutrition (under nutrition) are complex in aetiology with interaction of clinical, social and economic factors. Weight loss and loss of skeletal muscle mass in older people are associated with increased morbidity and mortality with implications for increasing health and social care costs. There is insufficient evidence to identify the ideal treatment options.

The Lys-Specific Molecular Tweezer, CLR01, Modulates Aggregation of the Mutant p53 DNA Binding Domain and Inhibits Its Toxicity.

The tumor suppressor p53 plays a unique role as a central hub of numerous cell proliferation and apoptotic pathways, and its malfunction due to mutations is a major cause of various malignancies. Therefore, it serves as an attractive target for developing novel anticancer therapeutics. Because of its intrinsically unstable DNA binding domain, p53 unfolds rapidly at physiological temperature.

Long-term outcomes after proton therapy, with concurrent chemotherapy, for stage II-III inoperable non-small cell lung cancer.

Purpose: We report long-term disease control, survival, and toxicity for patients with locally advanced non-small cell lung cancer prospectively treated with concurrent proton therapy and chemotherapy on a nonrandomized case-only observational study.

Methods: All patients received passive-scatter proton therapy, planned with 4D-CT-based simulation; all received proton therapy concurrent with weekly chemotherapy. Endpoints were local and distant control, disease-free survival (DFS), and overall survival (OS).

Transmission of Methicillin-Resistant Staphylococcus aureus (MRSA) to Healthcare Worker Gowns and Gloves During Care of Nursing Home Residents.

Objective: To estimate the frequency of methicillin-resistant Staphylococcus aureus (MRSA) transmission to gowns and gloves worn by healthcare workers (HCWs) interacting with nursing home residents to better inform infection prevention policies in this setting

Design: Observational study

Setting: Participants were recruited from 13 community-based nursing homes in Maryland and Michigan

Participants: Residents and HCWs from these nursing homes

Methods: Residents were cultured for MRSA at the anterior nares and perianal or perineal skin. HCWs wore gowns and gloves during usual care activities. At the end of each activity, a research coordinator swabbed the HCW's gown and gloves.

Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.

Background: Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia.

Methods: In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.

Translational toxicology in setting occupational exposure limits for dusts and hazard classification - a critical evaluation of a recent approach to translate dust overload findings from rats to humans.

Background: We analyze the scientific basis and methodology used by the German MAK Commission in their recommendations for exposure limits and carcinogen classification of "granular biopersistent particles without known specific toxicity" (GBS). These recommendations are under review at the European Union level. We examine the scientific assumptions in an attempt to reproduce the results.

Mesenchymal stem cells mediate the clinical phenotype of inflammatory breast cancer in a preclinical model.

Introduction: Inflammatory breast cancer (IBC) is an aggressive type of breast cancer, characterized by very rapid progression, enlargement of the breast, skin edema causing an orange peel appearance (peau d'orange), erythema, thickening, and dermal lymphatic invasion. It is characterized by E-cadherin overexpression in the primary and metastatic disease, but to date no robust molecular features that specifically identify IBC have been reported. Further, models that recapitulate all of these clinical findings are limited and as a result no studies have demonstrated modulation of these clinical features as opposed to simply tumor cell growth.

TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis.

Many types of human cancers having hyperactivated Wnt signaling display no causative alterations in known effectors of this pathway. Here, we report a function of TGIF in Wnt signaling. TGIF associates with and diverts Axin1 and Axin2 from the β-catenin destruction complex, therefore allowing β-catenin accrual.

The role of podiatric medicine in the health-care team. A paradigm shift.

As physicians, podiatric medical doctors should not define themselves as medical professionals who treat the foot and ankle but rather as medical professionals who prevent, diagnose, and treat people who have foot and ankle problems. Patients who come to see podiatric physicians often have other health-care issues, and because of the education and training that doctors of podiatric medicine receive, they are uniquely qualified to identify and respond to findings not only related to the pedal extremity but also that may affect overall health, have a major effect on quality of life, and even help reduce overall health-care costs. The role of podiatric medicine as a truly integrated branch of medical care needs to be reassessed.

Delivering nanomedicines to patients: a practical guide.

Unlabelled: This is a perspective on the current state of development of nanomedicines in Europe. The view is expressed that a much higher translational success rate could be achieved, with rewards for all stakeholders, if researchers understood the industrial decision points required for new drugs. Getting a drug through the clinic will not help patients unless it is developable by industry.

Disruption of the PHRF1 Tumor Suppressor Network by PML-RARα Drives Acute Promyelocytic Leukemia Pathogenesis.

PHRF1 functions as an essential component of the TGF-β tumor suppressor pathway by triggering degradation of the homeodomain repressor factor TGIF. This leads to redistribution of cPML into the cytoplasm, where it coordinates phosphorylation and activation of Smad2 by the TGF-β receptor. In acute promyelocytic leukemia (APL), acquisition of PML-RARα is known to impede critical aspects of TGF-β signaling, including myeloid differentiation.

Merkel cell carcinoma of the head and neck: Favorable outcomes with radiotherapy.

Background: The purpose of this study was to report the outcomes of patients with Merkel cell carcinoma (MCC) of the head and neck using a radiation-based treatment approach.

Methods: We reviewed records of 106 consecutive patients with MCC of the head and neck treated with radiation therapy (RT) at our institution between 1988 and 2011. The Kaplan-Meier method was used to estimate outcomes and hazard ratios (HRs) were calculated.

Concurrent alcohol and tobacco treatment: Effect on daily process measures of alcohol relapse risk.

Objective: The aim of this study was to compare the effects of alcohol treatment along with concurrent smoking treatment or delayed smoking treatment on process measures related to alcohol relapse risk.

Method: Alcohol dependent smokers (N = 151) who were enrolled in an intensive outpatient alcohol treatment program and were interested in smoking cessation were randomized to a concurrent smoking cessation (CSC) intervention or to a waiting list for delayed smoking cessation (DSC) intervention scheduled to begin 3 months later. Daily assessments of relapse process measures were obtained using an Interactive Voice Response (IVR) system for 12 weeks after the onset of smoking treatment in the CSC condition, and before beginning smoking treatment in the DSC condition.

Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer.

Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs) that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs).

Use of simultaneous radiation boost achieves high control rates in patients with non-small-cell lung cancer who are not candidates for surgery or conventional chemoradiation.

Background: Intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) has improved the local disease control at a variety of anatomic sites. However, little is known about its use in lung cancer, especially in the context of shorter treatment schedules (hypofractionation). We analyzed the feasibility, toxicity, and patterns of failure of this approach for patients with non-small-cell lung cancer (NSCLC) who were not candidates for surgery or standard concurrent chemoradiation therapy.