Epicardial fat thickness in patients with rheumatoid arthritis

Background: Epidemiologic data indicates that rheumatoid arthritis is an independent risk factor for cardiovascular disease. Epicardial adipose tissue is a novel cardio-metabolic risk factor. Our aim was to evaluate epicardial fat thickness (EFT) using echocardiography in patients with rheumatoid arthritis compared to healthy control subjects. Secondly, we investigated relationship between epicardial fat thickness and clinical and echocardiographic parameters in patients with rheumatoid arthritis.Method: The study population included 76 consecutive patients with rheumatoid arthritis (64 female; mean age, 53 ±11 years, median disease duration, 7.8 years) and 50 healthy subjects as controls (39 female; mean age, 52 ± 6 years). All patients underwent echocardiography to assess left ventricular diastolic dysfunction, left ventricular hypertrophy and EFT. All values were compared between groups.Results: EFT was higher in rheumatoid arthritis patients than in healthy controls (0.66±0.20 vs. 0.54±0.18; p= 0.003). Thickness of Intra Ventricular Septum (IVS) (1.1±0.06 and 9.8±0.08; p=0.001) and posterior wall (PW) (0.98±0.05 and 0.93±0.08; p=0.015) was higher in patients with rheumatoid arthritis compared to healthy controls. Early diastolic myocardiac peak velocity or late diastolic mitral peak velocity (E/A) ratio was lower in rheumatoid arthritis patients compared to healthy patients (1.1 ±0.8 and 1.24±0.1 p=0.001) as well as, E/e’ was higher in Rheumatoid arthritis (RA) patients than healthy patients. (E/e’:8.7±1.6 and 8.0±1.4 p=0.020). In patients with rheumatoid arthritis, EFT was positively correlated with hypertension and duration of disease and E/e’ (r: 0.10, p: 0.010, r: 0.306, p: 0.004 and r: 0.465 p: 0.007 respectively) and EFT was negatively correlated with E/A (r: -.262 p:0.022 )Conclusion: To our knowledge, this is the first report about epicardial adipose tissue in rheumatoid arthritis patients. Epicardial fat thickness as an indicator of cardiovascular involvement was higher in rheumatoid arthritis patients.Keywords: Rheumatoid arthritis, epicardial fat thickness, cardiac involvemen

Syysviljojen talvituhosienien torjunta PCNB:llä

Tehdyissä kokeissa vuosina 1966—69 on Kotkaniemen koetilalla Vihdissä saatu PCNB-käsittelyllä useimmiten huomattavia sadonlisäyksiä rukiilla ja syysvehnällä. Alustavat kokeet osoittavat, että 50 %:sen PCNB-ruiskutejauheen, joka sisältää täyteaineena ammoniumsulfaattia, levitys alkutalven löyhälle lumelle tai sijoitus lumen läpi rivilannoituskoneella lannoitteeseen sekoitettuna maan pinnalle, antaa yhtä hyviä tuloksia kuin ennen lumen tuloa tapahtunut levityskin

Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed

Understanding the Differences Between Vendor Types in Local Governance

It is commonly posited that for-profit, nonprofit, and other government vendors have fundamental differences, which make one or the other the superior choice depending on the circumstances of service delivery. Past research, focusing on service and market characteristics, finds support for this proposition. In this article, we investigate not only the typical theoretical expectations regarding vendor traits, service characteristics, and market conditions associated with the sectors, but also the presumed trustworthiness and management practices that are argued to differentiate them in an effort to better understand the roles played by each in local government contracting. Our findings indicate that as expected, nonprofits are most commonly employed when dealing with hard to define, “soft” services with weak markets. However, contrary to expectations, nonprofits are not generally considered more trustworthy than for-profits and are not managed more “loosely” (i.e., more ambiguous contracts, more discretion exercised in sanctioning) than their for-profit peers. Rather, public vendors seem to be the most trusted and are managed less rigidly than contractors from the other sectors.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Bioinformatic analyses identifies novel protein-coding pharmacogenomic markers associated with paclitaxel sensitivity in NCI60 cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Paclitaxel is a microtubule-stabilizing drug that has been commonly used in treating cancer. Due to genetic heterogeneity within patient populations, therapeutic response rates often vary. Here we used the NCI60 panel to identify SNPs associated with paclitaxel sensitivity. Using the panel's GI50 response data available from Developmental Therapeutics Program, cell lines were categorized as either sensitive or resistant. PLINK software was used to perform a genome-wide association analysis of the cellular response to paclitaxel with the panel's SNP-genotype data on the Affymetrix 125 k SNP array. FastSNP software helped predict each SNP's potential impact on their gene product. mRNA expression differences between sensitive and resistant cell lines was examined using data from BioGPS. Using Haploview software, we investigated for haplotypes that were more strongly associated with the cellular response to paclitaxel. Ingenuity Pathway Analysis software helped us understand how our identified genes may alter the cellular response to paclitaxel.</p> <p>Results</p> <p>43 SNPs were found significantly associated (FDR < 0.005) with paclitaxel response, with 10 belonging to protein-coding genes (<it>CFTR</it>, <it>ROBO1</it>, <it>PTPRD</it>, <it>BTBD12</it>, <it>DCT</it>, <it>SNTG1</it>, <it>SGCD</it>, <it>LPHN2</it>, <it>GRIK1</it>, <it>ZNF607</it>). SNPs in <it>GRIK1</it>, <it>DCT</it>, <it>SGCD </it>and <it>CFTR </it>were predicted to be intronic enhancers, altering gene expression, while SNPs in <it>ZNF607 </it>and <it>BTBD12 </it>cause conservative missense mutations. mRNA expression analysis supported these findings as <it>GRIK1</it>, <it>DCT</it>, <it>SNTG1</it>, <it>SGCD </it>and <it>CFTR </it>showed significantly (p < 0.05) increased expression among sensitive cell lines. Haplotypes found in <it>GRIK1, SGCD, ROBO1, LPHN2</it>, and <it>PTPRD </it>were more strongly associated with response than their individual SNPs.</p> <p>Conclusions</p> <p>Our study has taken advantage of available genotypic data and its integration with drug response data obtained from the NCI60 panel. We identified 10 SNPs located within protein-coding genes that were not previously shown to be associated with paclitaxel response. As only five genes showed differential mRNA expression, the remainder would not have been detected solely based on expression data. The identified haplotypes highlight the role of utilizing SNP combinations within genomic loci of interest to improve the risk determination associated with drug response. These genetic variants represent promising biomarkers for predicting paclitaxel response and may play a significant role in the cellular response to paclitaxel.</p

NCI60 Cancer Cell Line Panel Data and RNAi Analysis Help Identify EAF2 as a Modulator of Simvastatin and Lovastatin Response in HCT-116 Cells

Simvastatin and lovastatin are statins traditionally used for lowering serum cholesterol levels. However, there exists evidence indicating their potential chemotherapeutic characteristics in cancer. In this study, we used bioinformatic analysis of publicly available data in order to systematically identify the genes involved in resistance to cytotoxic effects of these two drugs in the NCI60 cell line panel. We used the pharmacological data available for all the NCI60 cell lines to classify simvastatin or lovastatin resistant and sensitive cell lines, respectively. Next, we performed whole-genome single marker case-control association tests for the lovastatin and simvastatin resistant and sensitive cells using their publicly available Affymetrix 125K SNP genomic data. The results were then evaluated using RNAi methodology. After correction of the p-values for multiple testing using False Discovery Rate, our results identified three genes (NRP1, COL13A1, MRPS31) and six genes (EAF2, ANK2, AKAP7, STEAP2, LPIN2, PARVB) associated with resistance to simvastatin and lovastatin, respectively. Functional validation using RNAi confirmed that silencing of EAF2 expression modulated the response of HCT-116 colon cancer cells to both statins. In summary, we have successfully utilized the publicly available data on the NCI60 cell lines to perform whole-genome association studies for simvastatin and lovastatin. Our results indicated genes involved in the cellular response to these statins and siRNA studies confirmed the role of the EAF2 in response to these drugs in HCT-116 colon cancer cells

Type-II Colloidal Quantum Wells: CdSe/CdTe Core/Crown Heteronanoplatelets

Solution-processed quantum wells, also known as colloidal nanoplatelets (NPLs), are emerging as promising materials for colloidal optoelectronics. In this work, we report the synthesis and characterization of CdSe/CdTe core/crown NPLs exhibiting a Type-II electronic structure and Type-II specific optical properties. Here, based on a core-seeded approach, the CdSe/CdTe core/crown NPLs were synthesized with well-controlled CdTe crown coatings. Uniform and epitaxial growth of CdTe crown region was verified by using structural characterization techniques including transmission electron microscopy (TEM) with quantitative EDX analysis and X-ray diffraction (XRD). Also the optical properties were systematically studied in these Type-II NPLs that reveal strongly red-shifted photoluminescence (up to similar to 150 nm) along with 2 orders of magnitude longer fluorescence lifetimes (up to 190 ns) compared to the Type-I NPLs owing to spatially indirect excitons at the Type-II interface between the CdSe core and the CdTe crown regions. Photoluminescence excitation spectroscopy confirms that this strongly red-shifted emission actually arises from the CdSe/CdTe NPLs. In addition, temperature-dependent time-resolved fluorescence spectroscopy was performed to reveal the temperature-dependent fluorescence decay kinetics of the Type-II NPLs exhibiting interesting behavior. Also, water-soluble Type-II NPLs were achieved via ligand exchange of the CdSe/CdTe core/crown NPLs by using 3-mercaptopropionic acid (MPA), which allows for enhanced charge extraction efficiency owing to their shorter chain length and enables high quality film formation by layer-by-layer (LBL) assembly. With all of these appealing properties, the CdSe/CdTe core/crown heterostructures having Type-II electronic structure presented here are highly promising for light-harvesting applications

Systematic Review and Meta-Analysis of Randomized Clinical Trials in the Treatment of Human Brucellosis

BACKGROUND: Brucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance. METHODS AND FINDINGS: A search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified. Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05-4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81-4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63-2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future. CONCLUSIONS: Although the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current treatment of choice