Two phase I, pharmacokinetic, and pharmacodynamic studies of DFP-10917, a novel nucleoside analog with 14-day and 7-day continuous infusion schedules.

Purpose DFP-10917 is a novel deoxycytidine analog with a unique mechanism of action. Brief exposure to high concentrations of DFP-10917 inhibits DNA polymerase resulting in S-phase arrest, while prolonged exposure to DFP-10917 at low concentration causes DNA fragmentation, G2/M-phase arrest, and apoptosis. DFP-10917 demonstrated activity in tumor xenografts resistant to other deoxycytidine analogs.

Cardiovascular Effects of Hookah Smoking: Potential Implications for Cardiovascular Risk.

Introduction: Smoking is a major cause of cardiovascular morbidity and mortality worldwide. Hookah (ie, waterpipe) smoking is a centuries-old revived yet understudied global epidemic of tobacco use. Because of the traditional set-up of a hookah-pipe, in addition to inhaling tobacco-combustion products, smokers are also exposed to large amounts of charcoal combustion products from the burning charcoal briquettes used to heat the hookah flavored tobacco.

An M2 Rather than a T2 Response Contributes to Better Protection against Latency Reactivation following Ocular Infection of Naive Mice with a Recombinant Herpes Simplex Virus 1 Expressing Murine Interleukin-4.

We found previously that altering macrophage polarization toward M2 responses by injection of colony-stimulating factor 1 (CSF-1) was more effective in reducing both primary and latent infections in mice ocularly infected with herpes simplex virus 1 (HSV-1) than M1 polarization by gamma interferon (IFN-γ) injection. Cytokines can coordinately regulate macrophage and T helper (T) responses, with interleukin-4 (IL-4) inducing type 2 T (T2) as well as M2 responses and IFN-γ inducing T1 as well as M1 responses. We have now differentiated the contributions of these immune compartments to protection against latency reactivation and corneal scarring by comparing the effects of infection with recombinant HSV-1 in which the latency-associated transcript (LAT) gene was replaced with either the (HSV-IL-4) or (HSV-IFN-γ) gene using infection with the parental (LAT-negative) virus as a control.

Beta blockers in critically ill patients with traumatic brain injury: Results from a multicenter, prospective, observational American Association for the Surgery of Trauma study.

Background: Beta blockers, a class of medications that inhibit endogenous catecholamines interaction with beta adrenergic receptors, are often administered to patients hospitalized after traumatic brain injury (TBI). We tested the hypothesis that beta blocker use after TBI is associated with lower mortality, and secondarily compared propranolol to other beta blockers.

Methods: The American Association for the Surgery of Trauma Clinical Trial Group conducted a multi-institutional, prospective, observational trial in which adult TBI patients who required intensive care unit admission were compared based on beta blocker administration.

Ovarian cancer risk, ALDH2 polymorphism and alcohol drinking: Asian data from the Ovarian Cancer Association Consortium.

The aldehyde dehydrogenase 2 (ALDH2) polymorphism rs671 (Glu504Lys) causes ALDH2 inactivation and adverse acetaldehyde exposure among Asians, but little is known of the association between alcohol consumption and rs671 and ovarian cancer (OvCa) in Asians. We conducted a pooled analysis of Asian ancestry participants in the Ovarian Cancer Association Consortium. We included seven case-control studies and one cohort study comprising 460 invasive OvCa cases, 37 borderline mucinous OvCa and 1274 controls of Asian descent with information on recent alcohol consumption.

p16(INK4A) expression in invasive laryngeal cancer.

We examined p16 expression in tumors from a population-based sample of laryngeal cancer cases diagnosed in the U.S. Samples had been previously genotyped for HPV DNA.

Emergency Department Care in the Postpartum Period: California Births, 2009-2011.

Objective: To use population data to identify patient characteristics associated with a postpartum maternal emergency department visit within 90 days of discharge after birth.

Methods: This retrospective cross-sectional study analyzed linked maternal discharge and emergency department data for all live California births from 2009 to 2011. The primary outcome was at least one emergency department visit within 90 days of hospital discharge after birth.

Do estrogens enhance activation of brown and beiging of adipose tissues?

Obesity and its associated co-morbidities are worldwide public health concerns. Obesity is characterized by excessive adipose tissue accumulation; however, it is important to recognize that human and rodent adipose tissues are made up of several distinct adipose tissue sub-types. White adipose tissue (WAT) is considered the prototypical fat cell, due to its capacity and capability to store large amounts of lipid.

Cross-sectional analysis of a large cohort with X-linked Charcot-Marie-Tooth disease (CMTX1).

Objective: To extend the phenotypic description of Charcot-Marie-Tooth disease (CMTX1) and to draw new genotype-phenotype relationships.

Methods: Mutations in cause the main X-linked form of CMTX (CMTX1). We report cross-sectional data from 160 patients (from 120 different families, with 89 different mutations) seen at the Inherited Neuropathies Consortium centers.

Quality measures in high-risk pregnancies: Executive Summary of a Cooperative Workshop of the Society for Maternal-Fetal Medicine, National Institute of Child Health and Human Development, and the American College of Obstetricians and Gynecologists.

Providers perceive current obstetric quality measures as imperfect and insufficient. Our organizations convened a "Quality Measures in High-Risk Pregnancies Workshop." The goals were to (1) review the current landscape regarding quality measures in obstetric conditions with increased risk for adverse maternal or fetal outcomes, (2) evaluate the available evidence for management of common obstetric conditions to identify those that may drive the highest impact on outcomes, quality, and value, (3) propose measures for high-risk obstetric conditions that reflect enhanced quality and efficiency, and (4) identify current research gaps, improve methods of data collection, and recommend means of change.

Injuries sustained during contact with law enforcement: An analysis from US trauma centers.

Background: Injuries sustained by civilians from interaction with police are a polarizing contemporary sociopolitical issue. Few comprehensive studies have been published using national hospital-based data. The aim of this study was to examine the epidemiology of these injuries to better understand this mechanism of injury.

Knowledge, Attitudes, and Beliefs Regarding Cardiovascular Disease in Women: The Women's Heart Alliance.

Background: Cardiovascular disease (CVD) is the number 1 killer of women in the United States, yet few younger women are aware of this fact. CVD campaigns focus little attention on physicians and their roles in assessing risk.

Objectives: In 2014, the Women's Heart Alliance (WHA) conducted a nationwide survey to determine barriers and opportunities for women and physicians with regard to CVD.

Evaluation of a Device Combining an Inferior Vena Cava Filter and a Central Venous Catheter for Preventing Pulmonary Embolism Among Critically Ill Trauma Patients.

Purpose: To evaluate efficacy and safety of a novel device that combines an inferior vena cava (IVC) filter and central venous catheter (CVC) for prevention of pulmonary embolism (PE) in critically ill patients.

Materials And Methods: In a multicenter, prospective, single-arm clinical trial, the device was inserted at the bedside without fluoroscopy and subsequently retrieved before transfer from the intensive care unit (ICU). The primary efficacy endpoint was freedom from clinically significant PE or fatal PE 72 hours after device removal or discharge, whichever occurred first.

Prevalence and orthopedic management of foot and ankle deformities in Charcot-Marie-Tooth disease.

Introduction: Foot deformities are frequent complications in Charcot-Marie-Tooth disease (CMT) patients, often requiring orthopedic surgery. However, there are no prospective, randomized studies on surgical management, and there is variation in the approaches among centers both within and between countries.

Methods: In this study we assessed the frequency of foot deformities and surgery among patients recruited into the Inherited Neuropathies Consortium (INC).

Incidental coronary calcifications on routine chest CT: Clinical implications.

Coronary artery calcification (CAC) is a marker of atherosclerosis and an independent risk factor for cardiac-related mortality, with much of the 50% decline in mortality over the past 30 years being attributed to early detection of coronary disease and intervention of modifiable risk factors. With over 10 million computed tomography (CT) examinations of the chest performed in the United States yearly, CAC can be identified in a very large number of patients. In this review, we discuss the clinical evidence underlying the relationship between radiologic identification of CAC, atherosclerosis, and cardiac outcomes and the implications of its assessment on standard chest CT.

Suppression of IL-12p70 formation by IL-2 or following macrophage depletion causes T-cell autoreactivity leading to CNS demyelination in HSV-1-infected mice.

We have established two mouse models of central nervous system (CNS) demyelination that differ from most other available models of multiple sclerosis (MS) in that they represent a mixture of viral and immune triggers. In the first model, ocular infection of different strains of mice with a recombinant HSV-1 that expresses murine IL-2 constitutively (HSV-IL-2) causes CNS demyelination. In the second model, depletion of macrophages causes CNS demyelination in mice that are ocularly infected with wild-type (WT) HSV-1.

Impact of Exercise on the Relationship Between CAC Scores and All-Cause Mortality.

Objectives: This study aims to assess the correlations among coronary artery calcium (CAC), self-reported exercise, and mortality in asymptomatic patients.

Background: The interaction between reported exercise habits and CAC scores for predicting clinical risk is not yet well known.

Methods: We followed 10,690 asymptomatic patients who underwent CAC scanning.

Roles of M1 and M2 Macrophages in Herpes Simplex Virus 1 Infectivity.

Macrophages are the predominant infiltrate in the corneas of mice that have been ocularly infected with herpes simplex virus 1 (HSV-1). However, very little is known about the relative roles of M1 (classically activated or polarized) and M2 (alternatively activated or polarized) macrophages in ocular HSV-1 infection. To better understand these relationships, we assessed the impact of directed M1 or M2 activation of RAW264.

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.