Annual change in FEV in elderly 10-year survivors with established chronic obstructive pulmonary disease.

Long-term decline in lung function is generally considered to be progressive in individuals with established chronic obstructive pulmonary disease (COPD), despite the presence of intersubject variation. We hypothesized that the annualized rate of decline in forced expiratory volume in 1 second (FEV) would not be constant among different time periods in the natural history of established COPD. We compared the annual change rates in FEV during the first 5 years and the last 5 years, estimated separately using a linear mixed-effects model in 10-year survivors (n = 110).

Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation.

Background: Bradyarrhythmia is a common clinical manifestation. Although the majority of cases are acquired, genetic analysis of families with bradyarrhythmia has identified a growing number of causative gene mutations. Because the only ultimate treatment for symptomatic bradyarrhythmia has been invasive surgical implantation of a pacemaker, the discovery of novel therapeutic molecular targets is necessary to improve prognosis and quality of life.

Taurine improves glucose tolerance in STZ-induced insulin-deficient diabetic mice.

Blood glucose levels fluctuate considerably in diabetic patients with reduced secretion of endogenous insulin. We previously reported that glucagon is secreted excessively in these patients and that taurine increases glucagon secretion in vitro. Therefore, we hypothesized that glucose tolerance would further deteriorate when taurine was administered to diabetic mice incapable of insulin secretion.

Rapid Capture and Hydrolysis of a Sulfur Mustard Gas in Silver-Ion-Exchanged Zeolite Y.

Sulfur mustard gas, also called HD, is one of the main chemical warfare agents and has claimed thousands of lives and left many more contaminated. The development of functional materials to promptly capture and detoxify sulfur mustard within a few minutes is extremely important to save the lives of the affected people. This has motivated us to explore excellent detoxification systems that can be deployed in the field to rapidly capture and hydrolyze mustard gas in a short time.

Tumor Cell Subtypes Based on the Intracellular Hormonal Activity in KCNJ5-Mutated Aldosterone-Producing Adenoma.

Aldosterone-producing adenomas (APAs) harbor marked intratumoral heterogeneity in terms of morphology, steroidogenesis, and genetics. However, an association of biological significance of morphologically identified tumor cell subtypes and genotypes is virtually unknown. KCNJ5 mutation is most frequently detected and generally considered a curable phenotype by adrenalectomy.

Middle cerebral artery geometric features are associated with plaque distribution and stroke.

Objective: We aimed to investigate the geometric features of the middle cerebral artery (MCA) and their relevance to plaque distribution and ischemic stroke.

Methods: We reviewed our institutional vessel wall imaging database. Patients with symptomatic MCA atherosclerosis, asymptomatic MCA atherosclerosis, or without MCA atherosclerosis were included.

Reported Consumption of Low-Calorie Sweetener in Foods, Beverages, and Food and Beverage Additions by US Adults: NHANES 2007-2012.

Background: Low-calorie sweeteners (LCSs), artificial sweeteners, or high-intensity sweeteners are incorporated into foods, beverages, and food and beverage additions (FBAs). Many prior studies have focused on LCS beverage consumption, but not included LCS consumption from foods or FBAs.

Objectives: We aimed to describe the prevalence of LCS consumption by US adults, and to examine the relation between intake of products containing LCSs and macronutrients.

Information Geometric Approach on Most Informative Boolean Function Conjecture.

Let X n be a memoryless uniform Bernoulli source and Y n be the output of it through a binary symmetric channel. Courtade and Kumar conjectured that the Boolean function f : { 0 , 1 } n → { 0 , 1 } that maximizes the mutual information I ( f ( X n ) ; Y n ) is a dictator function, i.e.

A Phase 3 Trial of l-Glutamine in Sickle Cell Disease.

Background: Oxidative stress contributes to the complex pathophysiology of sickle cell disease. Oral therapy with pharmaceutical-grade l-glutamine (USAN, glutamine) has been shown to increase the proportion of the reduced form of nicotinamide adenine dinucleotides in sickle cell erythrocytes, which probably reduces oxidative stress and could result in fewer episodes of sickle cell-related pain.

Methods: In a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial, we tested the efficacy of pharmaceutical-grade l-glutamine (0.

Different surface plasmon coupling behaviors of a surface Al nanoparticle between TE and TM polarizations in a deep-UV light-emitting diode.

The formulations and numerical algorithms of a three-level model for studying the Purcell effect produced by the scattering of an air/AlGaN interface and the surface plasmon (SP) coupling effect induced by a surface Al nanoparticle in a two-polarization emission system to simulate the transverse-electric- (TE-) and transverse-magnetic- (TM-) polarized emissions in an AlGaN/AlGaN (y > x) quantum well (QW) are built. In reasonably selected ranges of Al content for an AlGaN QW to emit deep-ultraviolet (UV) light, the enhancement (suppression) of TE- (TM-) polarized emission is mainly caused by the SP-coupling (interface-scattering) effect. Different from a two two-level model, in the three-level model the TE- and TM-polarized emissions compete for electron in the shared upper state, which is used for simulating the conduction band, such that either interface-scattering or SP-coupling effect becomes weaker.

Ventricular Assist Device Utilization in Heart Transplant Candidates: Nationwide Variability and Impact on Waitlist Outcomes.

Background: Continuous-flow left ventricular assist devices (CF-LVADs) have become a standard treatment choice in advanced heart failure patients. We hypothesized that practice patterns with regards to CF-LVAD utilization vary significantly among transplant centers and impact waitlist outcomes.

Methods And Results: The United Network for Organ Sharing registry was queried to identify adult patients who were waitlisted for heart transplantation (HT) between 2008 and 2015.

Mechanical Circulatory Support Device Utilization and Heart Transplant Waitlist Outcomes in Patients With Restrictive and Hypertrophic Cardiomyopathy.

Background: Patients with restrictive cardiomyopathy (RCM) and hypertrophic cardiomyopathy (HCM) generally are considered poor candidates for mechanical circulatory support devices (MCSDs) and often not able to be bridged mechanically to heart transplantation. This study characterized MCSD utilization and transplant waitlist outcomes in patients with RCM/HCM under the current allocation system and discusses changes in the era of the new donor allocation system.

Methods And Results: Patients waitlisted from 2006 to 2016 in the United Network for Organ Sharing registry were stratified by RCM/HCM versus other diagnoses.

Socioeconomic Disparities in Adherence and Outcomes After Heart Transplant: A UNOS (United Network for Organ Sharing) Registry Analysis.

Background: There is mixed evidence of racial and socioeconomic disparities in heart transplant outcomes. Their underlying cause-and whether individual- or community-level traits are most influential-remains unclear. The current study aimed to characterize socioeconomic disparities in outcomes and identify time trends and mediators of these disparities.

Generation and Characterization of a Novel Small Biologic Alternative to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Antibodies, DS-9001a, Albumin Binding Domain-Fused Anticalin Protein.

Since it was recently reported that an antibody for proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces the risk of cardiovascular events in a clinical context, PCSK9 inhibition is thought to be an attractive therapy for dyslipidemia. In the present study, we created a novel small biologic alternative to PCSK9 antibodies called DS-9001a, comprising an albumin binding domain fused to an artificial lipocalin mutein (ABD-fused Anticalin protein), which can be produced by a microbial production system. DS-9001a strongly interfered with PCSK9 binding to low-density-lipoprotein receptor (LDL-R) and PCSK9-mediated degradation of LDL-R.

DOOB-MARTIN COMPACTIFICATION OF A MARKOV CHAIN FOR GROWING RANDOM WORDS SEQUENTIALLY.

We consider a Markov chain that iteratively generates a sequence of random finite words in such a way that the word is uniformly distributed over the set of words of length 2 in which letters are and letters are at each step an and a are shuffled in uniformly at random among the letters of the current word. We obtain a concrete characterization of the Doob-Martin boundary of this Markov chain and thereby delineate all the ways in which the Markov chain can be conditioned to behave at large times. Writing for the number of letters (equivalently, ) in the finite word , we show that a sequence ( ) of finite words converges to a point in the boundary if, for an arbitrary word there is convergence as tends to infinity of the probability that the selection of () letters and () letters uniformly at random from and maintaining their relative order results in .

Urban-rural differences in the association between access to healthcare and health outcomes among older adults in China.

Background: Studies have shown that inadequate access to healthcare is associated with lower levels of health and well-being in older adults. Studies have also shown significant urban-rural differences in access to healthcare in developing countries such as China. However, there is limited evidence of whether the association between access to healthcare and health outcomes differs by urban-rural residence at older ages in China.

Intake of high fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent coronary heart disease, in U.S. adults, ages 45-59 y.

Background: Intake of high excess free fructose (EFF) beverages, including high fructose corn syrup (HFCS), sweetened soft drinks, fruit drinks, and apple juice, may be associated with childhood asthma, adult idiopathic chronic bronchitis/ COPD, and autoimmune arthritis, possibly due to underlying fructose malabsorption. Fructose malabsorption may contribute to the intestinal in situ formation of advanced glycation end-products (enFruAGEs) that travel to other tissues and promote inflammation. Chronic respiratory conditions and arthritis are comorbidities of coronary heart disease (CHD).

Formal Reduction Potentials of Difluorotyrosine and Trifluorotyrosine Protein Residues: Defining the Thermodynamics of Multistep Radical Transfer.

Redox-active tyrosines (Ys) play essential roles in enzymes involved in primary metabolism including energy transduction and deoxynucleotide production catalyzed by ribonucleotide reductases (RNRs). Thermodynamic characterization of Ys in solution and in proteins remains a challenge due to the high reduction potentials involved and the reactive nature of the radical state. The structurally characterized αY model protein has allowed the first determination of formal reduction potentials (E°') for a Y residing within a protein (Berry, B.

Stromal cues regulate the pancreatic cancer epigenome and metabolome.

A fibroinflammatory stromal reaction cooperates with oncogenic signaling to influence pancreatic ductal adenocarcinoma (PDAC) initiation, progression, and therapeutic outcome, yet the mechanistic underpinning of this crosstalk remains poorly understood. Here we show that stromal cues elicit an adaptive response in the cancer cell including the rapid mobilization of a transcriptional network implicated in accelerated growth, along with anabolic changes of an altered metabolome. The close overlap of stroma-induced changes in vitro with those previously shown to be regulated by oncogenic Kras in vivo suggests that oncogenic Kras signaling-a hallmark and key driver of PDAC-is contingent on stromal inputs.

The influence of ultra-pasteurization by indirect heating versus direct steam injection on skim and 2% fat milks.

Fluid milk is traditionally pasteurized by high temperature, short time (HTST) pasteurization, which requires heating to at least 72°C for 15 s. Ultra-pasteurization (UP) extends milk shelf life and is defined as heating to at least 138°C for 2 s. The UP process can be done by indirect heating (IND) or by direct steam injection (DSI).

Preoperative Proteinuria and Reduced Glomerular Filtration Rate Predicts Renal Replacement Therapy in Patients Supported With Continuous-Flow Left Ventricular Assist Devices.

Background: Renal failure requiring renal replacement therapy (RRT) has detrimental effects on quality of life and survival of patients with continuous-flow left ventricular assist devices (CF-LVADs). Current guidelines do not offer a decision-making algorithm for CF-LVAD candidates with poor baseline renal function. Objective of this study was to identify risk factors associated with RRT after CF-LVAD implantation.

Transradial Approach for Hepatic Radioembolization: Initial Results and Technique.

Objective: The transradial approach (TRA) has been shown to reduce the morbidity and mortality associated with arterial coronary interventions. Selective internal radiation therapy (SIRT) performed via the TRA can enhance patient comfort, compared with the traditional transfemoral approach (TFA), by allowing immediate ambulation and precluding potential complications associated with the TFA, such as closure device injury or retroperitoneal hematoma. We report our initial experience with and technique for using the TRA for SIRT.

Impact of Socioeconomic Status on Patients Supported With a Left Ventricular Assist Device: An Analysis of the UNOS Database (United Network for Organ Sharing).

Background: Low socioeconomic status (SES) is a known risk factor for heart failure, mortality among those with heart failure, and poor post heart transplant (HT) outcomes. This study sought to determine whether SES is associated with decreased waitlist survival while on left ventricular assist device (LVADs) support and after HT.

Methods And Results: A total of 3361 adult patients bridged to primary HT with an LVAD between May 2004 and April 2014 were identified in the UNOS database (United Network for Organ Sharing).

Surface Chemistry of Semiconducting Quantum Dots: Theoretical Perspectives.

Colloidal quantum dots (QDs) are near-ideal nanomaterials for energy conversion and lighting technologies. However, their photophysics exhibits supreme sensitivity to surface passivation and defects, of which control is problematic. The role of passivating ligands in photodynamics remains questionable and is a focus of ongoing research.

Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis.

Purpose: KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 and .