Robersonkrabbe5346
Several databases of epidemiologic studies in patients with idiopathic pulmonary fibrosis (IPF) have been analyzed in the Western community. However, few studies have been reported in Asia. The objective of this study was to investigate the epidemiology of IPF in Taiwan. We collected and analyzed patients with IPF from the Taiwan National Health Insurance Research Database from 2001 to 2011. We estimated the annual incidence and cumulative prevalence of IPF and mean survival time of patients and determined the causes of death. The annual incidence rates of IPF remained stable after 2005, ranging from 0.7 to 1.3 cases per 100,000 people per year, whereas the cumulative prevalence rates increased steadily from 3.1 to 6.4 cases per 100,000 people per year during 2006-2011 based on a narrow case definition. Men older than 75 years had higher incidence compared with other age groups. The mean survival after diagnosis was 6.9 years. Old age, male sex, and respiratory hospitalization were associated with shorter survival time after diagnosis. Both the incidence and prevalence rates of IPF were lower in Taiwanese patients than Western ones. Moreover, the survival time was higher in the Asian population compared with the Western population. These results may suggest the heterogeneity of the IPF definition in different study populations and geographic locations.There are two well-characterized cannabinoid receptors (CB1R and CB2R and other candidates) the central nervous system (CNS) enriched CB1R and peripheral tissue enriched CB2R with a wide dynamic range of expression levels in different cell types of human tissues. Hepatocytes and neurons express low baseline CB1R and CB2R, respectively, and their cell-type-specific functions are not well defined. Here we report inducible expression of CB1R in the liver by high-fat and high sugar diet and CB2R in cortical neurons by methamphetamine. While there is less controversy about hepatocyte CB1R, the presence of functional neuronal CB2R is still debated to date. We found that neuron CB2R basal expression was higher than that of hepatocyte CB1R by measuring mRNA levels of specific isoform CB2A in neurons isolated by fluorescence-activated cell sorting (FACS) and CB1A in hepatocytes isolated by collagenase perfusion of liver. find more For in vivo studies, we generated hepatocyte, dopaminergic neuron, and microglia-specific conditional knockout mice (Abl-Cnr1Δ, Dat-Cnr2Δ, and Cx3cr1-Cnr2Δ) of CB1R and CB2R by crossing Cnr1f/f and Cnr2f/f strains to Abl-Cre, Dat-Cre, and Cx3cr1-Cre deleter mouse strains, respectively. Our data reveals that neuron and microglia CB2Rs are involved in the "tetrad" effects of the mixed agonist WIN 55212-2, CB1R selective agonist arachidonyl-2'-chloroethylamide (ACEA), and CB2R selective agonist JWH133. Dat-Cnr2Δ and Cx3cr1-Cnr2Δ mice showed genotypic differences in hypomobility, hypothermia, analgesia, and catalepsy induced by the synthetic cannabinoids. Alcohol conditioned place preference was abolished in DAT-Cnr2Δ mice and remained intact in Cx3cr1-Cnr2Δ mice in comparison to WT mice. These Cre-loxP recombinant mouse lines provide unique approaches in cannabinoid research for dissecting the complex endocannabinoid system that is implicated in many chronic disorders.This paper presents a 0.5 V fifth-order Butterworth low-pass filter based on multiple-input operational transconductance amplifiers (OTA). The filter is designed for electrocardiogram (ECG) acquisition systems and operates in the subthreshold region with nano-watt power consumption. The used multiple-input technique simplifies the overall structure of the OTA and reduces the number of active elements needed to realize the filter. The filter was designed and simulated in the Cadence environment using a 0.18 µm Complementary Metal Oxide Semiconductor (CMOS) process from Taiwan Semiconductor Manufacturing Company (TSMC). Simulation results show that the filter has a bandwidth of 250 Hz, a power consumption of 34.65 nW, a dynamic range of 63.24 dB, attaining a figure-of-merit of 0.0191 pJ. The corner (process, voltage, temperature PVT) and Monte Carlo (MC) analyses are included to prove the robustness of the filter.Apremilast (APR) is a selective phosphodiesterase 4 inhibitor administered orally in the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. The low solubility and permeability of this drug hinder its dermal administration. The purpose of this study was to design and characterize an apremilast-loaded microemulsion (APR-ME) as topical therapy for local skin inflammation. Its composition was determined using pseudo-ternary diagrams. Physical, chemical and biopharmaceutical characterization were performed. Stability of this formulation was studied for 90 days. Tolerability of APR-ME was evaluated in healthy volunteers while its anti-inflammatory potential was studied using in vitro and in vivo models. A homogeneous formulation with Newtonian behavior and droplets of nanometric size and spherical shape was obtained. APR-ME released the incorporated drug following a first-order kinetic and facilitated drug retention into the skin, ensuring a local effect. Anti-inflammatory potential was observed for its ability to decrease the production of IL-6 and IL-8 in the in vitro model. This effect was confirmed in the in vivo model histologically by reduction in infiltration of inflammatory cells and immunologically by decrease of inflammatory cytokines IL-8, IL-17A and TNFα. Consequently, these results suggest that this formulation could be used as an attractive topical treatment for skin inflammation.In this study, HER2 RNA aptamers were conjugated to mertansine (DM1) and the anti-cancer effectiveness of the conjugate was evaluated in HER2-overexpressing breast cancer models. The conjugate of HER2 aptamer and anticancer drug DM1 (aptamer-drug conjugate, ApDC) was prepared and analyzed using HPLC and mass spectrometry. The cell-binding affinity and cytotoxicity of the conjugate were determined using confocal microscopy and WST-1 assay. The in vivo anti-tumoral efficacy of ApDC was also evaluated in mice carrying BT-474 breast tumors overexpressing HER2. The synthesized HER2-specific RNA aptamers were able to specifically and efficiently bind to HER-positive BT-474 breast cancer cells, but not to HER2-negative MDA-MB-231 breast cancer cells. Also, the HER2-specific ApDC showed strong toxicity to the target cells, BT-474, but not to MDA-MB-231 cells. According to the in vivo analyses drawn from the mouse xenografts of BT-747 tumor, the ApDC was able to more effectively inhibit the tumor growth. Compared to the control group, the mice treated with the ApDC showed a significant reduction of tumor growth.