Secondhand Smoking Is Associated With Vascular Inflammation.

Background: The relative risk for cardiovascular diseases in passive smokers is similar to that of active smokers despite almost a 100-fold lower dose of inhaled cigarette smoke. However, the mechanisms underlying the surprising susceptibility of the vascular tissue to the toxins in secondhand smoke (SHS) have not been directly investigated. The aim of this study was to investigate directly vascular endothelial cell function in passive smokers.

Reduced Bone Density and Vertebral Fractures in Smokers. Men and COPD Patients at Increased Risk.

Rationale: Former smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered.

Objectives: To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women.

Intracardiac myocardial elastography in canines and humans in vivo.

Intracardiac echocardiography (ICE) is a useful imaging modality which is used during RF ablation procedures to identify anatomical structures. Utilizing ICE in conjunction with myocardial elastography (ME) can provide additional information on the mechanical properties of cardiac tissue and provide information on mechanical changes caused by ablation. The objective of this study was to demonstrate that ICE can be used at high frame rate using a diverging beam transmit sequence to image myocardial strain and differentiate myocardial tissue properties before, during, and after ablation for a clinical ablation procedure.

Help-seeking intentions and subsequent 12-month mental health service use in Chinese primary care patients with depressive symptoms.

Objective: To identify the factors associated with 12-month mental health service use in primary care patients with depressive symptoms.

Design: Cross-sectional followed by 12-month cohort study.

Setting And Participants: 10 179 adult patients were recruited from the waiting rooms of 59 primary care clinics across Hong Kong to complete a questionnaire which screened for depression.

Measuring in-home walking speed using wall-mounted RF transceiver arrays.

In this paper we present a new method for passively measuring walking speed using a small array of radio transceivers positioned on the walls of a hallway within a home. As a person walks between a radio transmitter and a receiver, the received signal strength (RSS) detected by the receiver changes in a repeatable pattern that may be used to estimate walking speed without the need for the person to wear any monitoring device. The transceivers are arranged as an array of 4 with a known distance between the array elements.

MobileRF: A Robust Device-Free Tracking System Based On a Hybrid Neural Network HMM Classifier.

We present a indoor tracking system that uses received signal strength (RSS) from radio frequency (RF) transceivers to estimate the location of a person. While many RSS-based tracking systems use a body-worn device or tag, this approach requires no such tag. The approach is based on the key principle that RF signals between wall-mounted transceivers reflect and absorb differently depending on a person's movement within their home.

Smoking-Associated Site-Specific Differential Methylation in Buccal Mucosa in the COPDGene Study.

DNA methylation is a complex, tissue-specific phenomenon that can reflect both endogenous factors and exogenous exposures. Buccal brushings represent an easily accessible source of DNA, which may be an appropriate surrogate tissue in the study of environmental exposures and chronic respiratory diseases. Buccal brushings were obtained from a subset of current and former smokers from the COPDGene study.

The PDZ motif of the α1C subunit is not required for surface trafficking and adrenergic modulation of CaV1.2 channel in the heart.

Voltage-gated Ca(2+) channels play a key role in initiating muscle excitation-contraction coupling, neurotransmitter release, gene expression, and hormone secretion. The association of CaV1.2 with a supramolecular complex impacts trafficking, localization, turnover, and, most importantly, multifaceted regulation of its function in the heart.

Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects.

Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing with the ACE Exome(TM) (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 cases) to sequence 28 patients with A/M and four patients with varied developmental eye defects. In the 28 patients with A/M, we identified de novo mutations in three patients (OTX2, p.

Mechanism of tumour vascularization in experimental lung metastases.

The appearance of lung metastases is associated with poor outcome and the management of patients with secondary pulmonary tumours remains a clinical challenge. We examined the vascularization process of lung metastasis in six different preclinical models and found that the tumours incorporated the pre-existing alveolar capillaries (ie vessel co-option). During the initial phase of vessel co-option, the incorporated capillaries were still sheathed by pneumocytes, but these incorporated vessels subsequently underwent different fates dependent on the model.

Global public health impact of recovered supplies from operating rooms: a critical analysis with national implications.

Background: In modern operating rooms, clean and unused medical supplies are routinely discarded and can be effectively recovered and redistributed abroad to alleviate the environmental burden of donor hospitals and to generate substantial health benefits at resource-poor recipient institutions.

Methods: We established a recovery and donation program to collect clean and unused supplies for healthcare institutions in developing nations. We analyzed items donated over a 3-year period (September 2010-November 2013) by quantity and weight, and estimated the projected value of the program under potential nationwide participation.

Visual Assessment of CT Findings in Smokers With Nonobstructed Spirometric Abnormalities in The COPDGene Study.

Within the COPD Genetic Epidemiology (COPDGene) study population of cigarette smokers, 9% were found to be unclassifiable by the Global Initiative for chronic Obstructive Lung Disease (GOLD) criteria. This study was to identify the differences in computed tomography (CT) findings between this nonobstructed (GOLDU) group and a control group of smokers with normal lung function. This research was approved by the institutional review board of each institution.

Phenotypic and genetic heterogeneity among subjects with mild airflow obstruction in COPDGene.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by marked phenotypic heterogeneity. Most previous studies have focused on COPD subjects with FEV1 < 80% predicted. We investigated the clinical and genetic heterogeneity in subjects with mild airflow limitation in spirometry grade 1 defined by the Global Initiative for chronic Obstructive Lung Disease (GOLD 1).

DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in subjects with moderate-to-severe airflow obstruction.

Epidemiology, genetics, and subtyping of preserved ratio impaired spirometry (PRISm) in COPDGene.

Background: Preserved Ratio Impaired Spirometry (PRISm), defined as a reduced FEV1 in the setting of a preserved FEV1/FVC ratio, is highly prevalent and is associated with increased respiratory symptoms, systemic inflammation, and mortality. Studies investigating quantitative chest tomographic features, genetic associations, and subtypes in PRISm subjects have not been reported.

Methods: Data from current and former smokers enrolled in COPDGene (n = 10,192), an observational, cross-sectional study which recruited subjects aged 45-80 with ≥10 pack years of smoking, were analyzed.

Novel mutations in PXDN cause microphthalmia and anterior segment dysgenesis.

We used exome sequencing to study a non-consanguineous family with two children who had anterior segment dysgenesis, sclerocornea, microphthalmia, hypotonia and developmental delays. Sanger sequencing verified two Peroxidasin (PXDN) mutations in both sibs--a maternally inherited, nonsense mutation, c.1021C>T predicting p.

Suppressive role of miR-502-5p in breast cancer via downregulation of TRAF2.

TRAF2 promotes cancer cell survival, proliferation and metastasis through the NF-κB pathway by directly interacting with various TNF recepors. However, the molecular mechanism of TRAF2 dysregulation in breast cancer remains to be elucidated. In the present study, miR-502-5p was predicted as a potential regulator of TRAF2.

The not-so-simple renal cyst.

Simple renal cysts are most commonly found in the elderly, male population. The majority of simple renal cysts remain untreated, except on the rare occasion when they become complicated with hemorrhage, infection or rupture. We present the case of a 31-year-old female with a simple renal cyst which was initially treated as acute pyelonephritis.

The clinical impact of non-obstructive chronic bronchitis in current and former smokers.

Background: As the clinical significance of chronic bronchitis among smokers without airflow obstruction is unclear, we sought to determine morbidity associated with this disorder.

Methods: We examined subjects from the COPDGene study and compared those with FEV1/FVC ≥ 0.70, no diagnosis of asthma and chronic bronchitis as defined as a history of cough and phlegm production for ≥ 3 months/year for ≥ 2 years (NCB) to non-obstructed subjects without chronic bronchitis (CB-).

The effect of VEGF-targeted therapy on biomarker expression in sequential tissue from patients with metastatic clear cell renal cancer.

Purpose: To investigate how biologically relevant markers change in response to antiangiogenic therapy in metastatic clear cell renal cancer (mRCC) and correlate these changes with outcome.

Experimental Design: The study used sequential tumor tissue and functional imaging (taken at baseline and 12-16 weeks) obtained from three similar phase II studies. All three studies investigated the role of VEGF tyrosine kinase inhibitors (TKI) before planned nephrectomy in untreated mRCC (n = 85).

Pulmonary function reduction in diabetes with and without chronic obstructive pulmonary disease.

Objective: Diabetes damages major organ systems through disrupted glycemic control and increased inflammation. The effects of diabetes on the lung have been of interest for decades, but the modest reduction in pulmonary function and its nonprogressive nature have limited its investigation. A recent systematic review found that diabetes was associated with reductions in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and diffusing capacity for carbon monoxide of the lung and increased FEV1/FVC.

Enhanced efferocytosis of apoptotic cardiomyocytes through myeloid-epithelial-reproductive tyrosine kinase links acute inflammation resolution to cardiac repair after infarction.

Rationale: Efficient clearance of apoptotic cells (efferocytosis) is a prerequisite for inflammation resolution and tissue repair. After myocardial infarction, phagocytes are recruited to the heart and promote clearance of dying cardiomyocytes. The molecular mechanisms of efferocytosis of cardiomyocytes and in the myocardium are unknown.

Diet-induced obesity causes long QT and reduces transcription of voltage-gated potassium channels.

In humans, obesity is associated with long QT, increased frequency of premature ventricular complexes, and sudden cardiac death. The mechanisms of the pro-arrhythmic electrophysiologic remodeling of obesity are poorly understood. We tested the hypothesis that there is decreased expression of voltage-gated potassium channels in the obese heart, leading to long QT.

Reduced vascular smooth muscle BK channel current underlies heart failure-induced vasoconstriction in mice.

Excessively increased peripheral vasoconstriction is a hallmark of heart failure (HF). Here, we show that in mice with systolic HF post-myocardial infarction, the myogenic tone of third-order mesenteric resistance vessels is increased, the vascular smooth muscle (VSM) membrane potential is depolarized by ~20 mV, and vessel wall intracellular [Ca(2+)] is elevated relative to that in sham-operated control mice. Despite the increased [Ca(2+)], the frequency and amplitude of spontaneous transient outward currents (STOCs), mediated by large conductance, Ca(2+)-activated BK channels, were reduced by nearly 80% (P<0.

Systemic steroid exposure is associated with differential methylation in chronic obstructive pulmonary disease.

Rationale: Systemic glucocorticoids are used therapeutically to treat a variety of medical conditions. Epigenetic processes such as DNA methylation may reflect exposure to glucocorticoids and may be involved in mediating the responses and side effects associated with these medications.

Objectives: To test the hypothesis that differences in DNA methylation are associated with current systemic steroid use.