Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome.

Aims: Triple-negative breast cancer (TNBC) patients generally have a poor outcome; there is a pressing need to identify more effective therapeutic strategies. Clinical trials targeting programmed death 1/programmed death ligand 1 (PD1/PDL1) in melanoma and non-small-cell lung cancer have reported high response rates, and tumoral PDL1 expression has been suggested as a potential biomarker to enrich for patient response to these treatments. There are only very limited data to date reporting the expression of PDL1 in TNBC.

MicroRNA-Related DNA Repair/Cell-Cycle Genes Independently Associated With Relapse After Radiation Therapy for Early Breast Cancer.

Purpose: Local recurrence and distant failure after adjuvant radiation therapy for breast cancer remain significant clinical problems, incompletely predicted by conventional clinicopathologic markers. We had previously identified microRNA-139-5p and microRNA-1274a as key regulators of breast cancer radiation response in vitro. The purpose of this study was to investigate standard clinicopathologic markers of local recurrence in a contemporary series and to establish whether putative target genes of microRNAs involved in DNA repair and cell cycle control could better predict radiation therapy response in vivo.

Sex-Specific Differences in Hepatic Fat Oxidation and Synthesis May Explain the Higher Propensity for NAFLD in Men.

Context And Objective: In most populations a greater proportion of men have hepatic steatosis than women. Sex-specific differences in hepatic dietary fatty acid (FA) metabolism have not been well characterized. We compared fasting and postprandial hepatic FA synthesis (de novo lipogenesis [DNL]) and oxidation in men and women.

Healthful Nutrition of Foods in Navajo Nation Stores: Availability and Pricing.

Purpose: Low availability and affordability of healthier foods in food stores on the Navajo Nation (NN) may be a community-level risk factor for the high prevalence of obesity among the Navajo people. This study assessed the availability and pricing of foods and beverages in supermarkets and convenience stores throughout the NN.

Design: Descriptive study design using the Nutrition Environment Measurement Survey in Stores audit tool.

Vascular Risk Factors in Patients with Different Subtypes of Ischemic Stroke May Affect Their Outcome after Intravenous tPA.

Intravenous (i.v.) tissue-type plasminogen activator (tPA) is the only approved noninvasive therapy for acute ischemic stroke (AIS).

Novel Ranking System for Identifying Efficacious Anti-Influenza Virus PB2 Inhibitors.

Through antigenic drift and shifts, influenza virus infections continue to be an annual cause of morbidity in healthy populations and of death among elderly and at-risk patients. The emergence of highly pathogenic avian influenza viruses such as H5N1 and H7N9 and the rapid spread of the swine-origin H1N1 influenza virus in 2009 demonstrate the continued need for effective therapeutic agents for influenza. While several neuraminidase inhibitors have been developed for the treatment of influenza virus infections, these have shown a limited window for treatment initiation, and resistant variants have been noted in the population.

Genome-wide association study of colorectal cancer identifies six new susceptibility loci.

Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.

Intravenous Tissue Plasminogen Activator Can Be Safely Given without Complete Blood Count Results Back.

Introduction: It is well known that the efficacy of intravenous (i.v.) tissue plasminogen activator (tPA) is time-dependent when used to treat patients with acute ischemic strokes.

Pembrolizumab for the treatment of melanoma.

The immune system plays a vital role in regulating tumor growth, and the oncology community has witnessed an exciting resurgence in clinical research to develop effective immunotherapeutic strategies. The utility of these strategies in advanced melanoma has been at the forefront of these developments. In particular, blockade of programmed cell death protein 1 (PD-1) in advanced melanoma has proven to be a most promising new anticancer strategy.

Characterization of lipid metabolism in a novel immortalized human hepatocyte cell line.

The development of hepatocyte cell models that represent fatty acid partitioning within the human liver would be beneficial for the study of the development and progression of nonalcoholic fatty liver disease (NAFLD). We sought to develop and characterize a novel human liver cell line (LIV0APOLY) to establish a model of lipid accumulation using a physiological mixture of fatty acids under low- and high-glucose conditions. LIV0APOLY cells were compared with a well-established cell line (HepG2) and, where possible, primary human hepatocytes.

Rationale and Considerations for the Internet-Based Delivery of Parent-Child Interaction Therapy.

Given the enormous individual, familial, and societal costs associated with early disruptive behavior disorders, transformative efforts are needed to develop innovative options for overcoming traditional barriers to effective care and for broadening the availability of supported interventions. This paper presents the rationale and key considerations for a promising innovation in the treatment of early-onset disruptive behavior disorders-that is, the development of an Internet-based format for the delivery of Parent-Child Interaction Therapy (PCIT) directly to families in their own homes. Specifically, we consider traditional barriers to effective care, and discuss how technological innovations can overcome problems of treatment availability, accessibility, and acceptability.

Blood flow and muscle oxygenation during low, moderate, and maximal sustained isometric contractions.

A reduction of blood flow to active muscle will precipitate fatigue, and sustained isometric contractions produce intramuscular and compartmental pressures that can limit flow. The present study explored how blood flow and muscle oxygenation respond to isometric contractions at low, moderate, and maximal intensities. Over two visits, 10 males (26 ± 2 yr; means ± SD) performed 1-min dorsiflexion contractions at 30, 60, and 100% of maximal voluntary contraction (MVC) torque.

Community rabies knowledge and pet vaccination practices after a skunk rabies outbreak in Eddy County, New Mexico.

Objective: To determine percentages of domestic cats and dogs vaccinated against rabies, identify barriers to vaccination, and assess knowledge about rabies in a semirural New Mexico community after a skunk rabies outbreak.

Design: Cross-sectional, door-to-door, bilingual, community-based participatory survey.

Sample: 366 residential properties in Eddy County, NM.

Pembrolizumab versus Ipilimumab in Advanced Melanoma.

Background: The immune checkpoint inhibitor ipilimumab is the standard-of-care treatment for patients with advanced melanoma. Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma.

Methods: In this randomized, controlled, phase 3 study, we assigned 834 patients with advanced melanoma in a 1:1:1 ratio to receive pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks.

Equivocal ALK fluorescence in-situ hybridization (FISH) cases may benefit from ancillary ALK FISH probe testing.

Aims: Accurate assessment of anaplastic lymphoma kinase (ALK) gene rearrangement in non-small-cell lung cancers (NSCLCs) is critical to identify patients who are likely to respond to crizotinib. The aim of this study was to evaluate the ALK/EML4 TriCheck FISH probe in a series of NSCLCs enriched for tumours with equivocal ALK status.

Methods And Results: ALK FISH was prospectively performed on 45 NSCLCs with the ALK/EML4 TriCheck probe (ZytoVision) and the Vysis ALK break-apart probe (Abbott Molecular).

Bedside rounds versus board rounds in an emergency department.

Background: Our objective was to gain insight into whether bedside rounding at shift turnover in the emergency department improved education quality, as compared with board rounds. Board rounds are commonly used in the emergency department, where the teams review the patient and transfer care near a computer screen or written board, rather than at the patient's bedside. The impact on teaching or patient care has not been extensively compared between the two approaches.

Demographic trends of sick leave absenteeism among civil service employees at a federal agency from 2004 to 2012.

Objective: To investigate the associations between demographic variables and sick leave use.

Methods: We analyzed sick leave use among civil servants at a federal agency (FA) from 2004 to 2012 by demographic and FA-specific variables. We used a mixed methods approach and type III analysis to build a descriptive model of sick leave proportions and demographic variables.

Improvement in Bone Mineral Density and Architecture in a Patient with Gaucher Disease Using Teriparatide.

Gaucher disease is an autosomal recessive lysosomal storage disorder caused by deficiency of the enzyme acid beta-glucosidase (glucocerebrosidase) due to mutations in the GBA gene. The most common form (type I) is associated with severe hematologic, visceral and bone disease. Disease-modifying treatments, such as enzyme replacement therapy and substrate reduction therapy, can improve the hematologic and visceral aspects of the disease but success with improving severe osteopenia, which can increase the risk of fractures, is limited.

Implementation of Parent Child Interaction Therapy Within Foster Care: An Attempt to Translate an Evidence-Based Program Within a Local Child Welfare Agency.

This paper describes an innovative adaptation of an evidence-based intervention - Parent Child Interaction Therapy or PCIT - to foster parent training services. The authors faced multiple problems that commonly plague translational child welfare research as they developed, implemented and tested their model. The paper discusses how the authors addressed these problems when: 1) specifying the child welfare context in which the intervention model was implemented and tested, choosing an intervention model that responded to child welfare service needs, and tailoring the model for a child welfare context; 2) securing external funding and initiating sustainability plans for model uptake; and 3) forging a university-community partnership to overcome logistical and ethical obstacles.

Oxidized LDL activates blood platelets through CD36/NOX2-mediated inhibition of the cGMP/protein kinase G signaling cascade.

Oxidized low-density lipoprotein (oxLDL) promotes unregulated platelet activation in dyslipidemic disorders. Although oxLDL stimulates activatory signaling, it is unclear how these events drive accelerated thrombosis. Here, we describe a mechanism for oxLDL-mediated platelet hyperactivity that requires generation of reactive oxygen species (ROS).

Ipilimumab-induced toxicities and the gastroenterologist.

Ipilimumab has been shown to improve overall survival in patients with advanced melanoma. Ipilimumab acts through immune-modulation, and is recognized to cause potentially severe immune-related adverse events (irAEs) including dermatitis, colitis, thyroiditis, hypophysitis, and hepatitis. The acceptance of ipilimumab as a treatment for metastatic melanoma means patients will continue to be treated with this agent and gastroenterologists will be increasingly called upon to assist in managing severe autoimmune-related hepatitis and colitis.