Blockage of longitudinal flow in Meniere's disease: A human temporal bone study

Conclusion: Blockage of the endolymphatic duct is a significant finding in Meniere's disease. The position of the utriculo-endolymphatic valve (UEV) and blockage of the ductus reuniens in the temporal bones were not found to be directly indicative of Meniere's disease. Objective: Comparison of blockage of the longitudinal flow of endolymph between ears affected by Meniere's disease and normal ears. Methods: We examined 21 temporal bones from 13 subjects who had Meniere's disease and 21 normal temporal bones from 12 controls. Results: The endolymphatic duct was blocked in five (23%) ears affected by Meniere's disease (p = 0.016). The utricular duct was blocked in 16 (76%) ears affected by Meniere's disease and 11 (52%) normal ears (p = 0.112). The saccular duct was blocked in 6 (28%) of ears affected by Meniere's disease and 16 (76%) normal ears (p = 0.001). The ductus reuniens was blocked in 10 (47%) ears affected by Meniere's disease and 10 (47%) normal ears (p = 1.000)

Electro-plating and characterisation of cadmium sulphide thin films using ammonium thiosulphate as the sulphur source

Cadmium sulphide (CdS) thin films have been successfully prepared from an aqueous electrolyte bath containing CdCl2 and ammonium thiosulphate ((NH4)2S2O3) using electrodeposition technique. The structural, compositional, optical, morphological and electrical properties of these thin films have been characterized using X-ray diffraction (XRD), Raman spectroscopy, energy dispersive X-ray spectroscopy, UV–Vis spectrophotometry, scanning electron microscopy (SEM), atomic force microscopy (AFM), photoelectrochemical cell and D.C. current–voltage (I–V) measurements. The optimum deposition cathodic potential has been observed at 1,455 mV, in a 2-electrode system with respect to carbon anode. Structural analysis using XRD shows a mixture of hexagonal and cubic phases in the as-deposited CdS samples and a phase transformation to the hexagonal structure occurred after heat treatment at 400 °C for 20 min. Optical studies demonstrate an improvement in the band edge, producing 2.42 eV for the band gap of the films after heat treatment. The heat treated CdS thin films show better transmission for wavelengths longer than 500 nm. SEM and AFM show that the heat-treated samples are more uniform, smoother and have larger grain size. Electrical studies confirm that the CdS thin films have n-type electrical conductivity and heat treated CdS thin films have resistivities of the order of 105 Ω cm

The variability and predictors of quality of AIDS care services in Brazil

Abstract Background Since establishing universal free access to antiretroviral therapy in 1996, the Brazilian Health System has increased the number of centers providing HIV/AIDS outpatient care from 33 to 540. There had been no formal monitoring of the quality of these services until a survey of 336 AIDS health centers across 7 Brazilian states was undertaken in 2002. Managers of the services were asked to assess their clinics according to parameters of service inputs and service delivery processes. This report analyzes the survey results and identifies predictors of the overall quality of service delivery. Methods The survey involved completion of a multiple-choice questionnaire comprising 107 parameters of service inputs and processes of delivering care, with responses assessed according to their likely impact on service quality using a 3-point scale. K-means clustering was used to group these services according to their scored responses. Logistic regression analysis was performed to identify predictors of high service quality. Results The questionnaire was completed by 95.8% (322) of the managers of the sites surveyed. Most sites scored about 50% of the benchmark expectation. K-means clustering analysis identified four quality levels within which services could be grouped: 76 services (24%) were classed as level 1 (best), 53 (16%) as level 2 (medium), 113 (35%) as level 3 (poor), and 80 (25%) as level 4 (very poor). Parameters of service delivery processes were more important than those relating to service inputs for determining the quality classification. Predictors of quality services included larger care sites, specialization for HIV/AIDS, and location within large municipalities. Conclusion The survey demonstrated highly variable levels of HIV/AIDS service quality across the sites. Many sites were found to have deficiencies in the processes of service delivery processes that could benefit from quality improvement initiatives. These findings could have implications for how HIV/AIDS services are planned in Brazil to achieve quality standards, such as for where service sites should be located, their size and staffing requirements. A set of service delivery indicators has been identified that could be used for routine monitoring of HIV/AIDS service delivery for HIV/AIDS in Brazil (and potentially in other similar settings). </jats:sec

Serological assessment of gastric mucosal atrophy in gastric cancer

<p>Abstract</p> <p>Background</p> <p>Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1 (PG1), pepsinogen 2 (PG2) and gastrin 17 (G17) offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia.</p> <p>Methods</p> <p>Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Laurén type, localisation), degree of mucosal abnormalities (intestinal metaplasia, atrophy) and serological parameters (PG1, PG2, PG1/2-ratio, G17, <it>H. pylori </it>IgG, CagA status). Association of the general factors to the different serological values have been statistically analyzed.</p> <p>Results</p> <p>Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (<it>p </it>= 0.003). The serum levels of PG2 itself and G17 were not significantly altered. <it>H. pylori </it>infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (<it>p </it>= 0.058). The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p < 0.01). Laurén-specific analysis revealed that this is only true for intestinal type tumors. Univariate ANOVA revealed atrophy and CagA-status as the only independent factors for low PG1 and a low PG1/2-ratio.</p> <p>Conclusions</p> <p>Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer.</p

Microarray analysis of DNA damage repair gene expression profiles in cervical cancer cells radioresistant to 252Cf neutron and X-rays

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to obtain stable radioresistant sub-lines from the human cervical cancer cell line HeLa by prolonged exposure to ²⁵²Cf neutron and X-rays. Radioresistance mechanisms were investigated in the resulting cells using microarray analysis of DNA damage repair genes.</p> <p>Methods</p> <p>HeLa cells were treated with fractionated ²⁵²Cf neutron and X-rays, with a cumulative dose of 75 Gy each, over 8 months, yielding the sub-lines HeLaNR and HeLaXR. Radioresistant characteristics were detected by clone formation assay, ultrastructural observations, cell doubling time, cell cycle distribution, and apoptosis assay. Gene expression patterns of the radioresistant sub-lines were studied through microarray analysis and verified by Western blotting and real-time PCR.</p> <p>Results</p> <p>The radioresistant sub-lines HeLaNR and HeLaXR were more radioresisitant to ²⁵²Cf neutron and X-rays than parental HeLa cells by detecting their radioresistant characteristics, respectively. Compared to HeLa cells, the expression of 24 genes was significantly altered by at least 2-fold in HeLaNR cells. Of these, 19 genes were up-regulated and 5 down-regulated. In HeLaXR cells, 41 genes were significantly altered by at least 2-fold; 38 genes were up-regulated and 3 down-regulated.</p> <p>Conclusions</p> <p>Chronic exposure of cells to ionizing radiation induces adaptive responses that enhance tolerance of ionizing radiation and allow investigations of cellular radioresistance mechanisms. The insights gained into the molecular mechanisms activated by these "radioresistance" genes will lead to new therapeutic targets for cervical cancer.</p

A Cell Permeable Peptide Inhibitor of NFAT Inhibits Macrophage Cytokine Expression and Ameliorates Experimental Colitis

Nuclear factor of activated T cells (NFAT) plays a critical role in the development and function of immune and non-immune cells. Although NFAT is a central transcriptional regulator of T cell cytokines, its role in macrophage specific gene expression is less defined. Previous work from our group demonstrated that NFAT regulates Il12b gene expression in macrophages. Here, we further investigate NFAT function in murine macrophages and determined the effects of a cell permeable NFAT inhibitor peptide 11R-VIVIT on experimental colitis in mice. Treatment of bone marrow derived macrophages (BMDMs) with tacrolimus or 11R-VIVIT significantly inhibited LPS and LPS plus IFN-γ induced IL-12 p40 mRNA and protein expression. IL-12 p70 and IL-23 secretion were also decreased. NFAT nuclear translocation and binding to the IL-12 p40 promoter was reduced by NFAT inhibition. Experiments in BMDMs from IL-10 deficient (Il10−/−) mice demonstrate that inhibition of IL-12 expression by 11R-VIVIT was independent of IL-10 expression. To test its therapeutic potential, 11R-VIVIT was administered systemically to Il10−/− mice with piroxicam-induced colitis. 11R-VIVIT treated mice demonstrated significant improvement in colitis compared to mice treated with an inactive peptide. Moreover, decreased spontaneous secretion of IL-12 p40 and TNF in supernatants from colon explant cultures was demonstrated. In summary, NFAT, widely recognized for its role in T cell biology, also regulates important innate inflammatory pathways in macrophages. Selective blocking of NFAT via a cell permeable inhibitory peptide is a promising therapeutic strategy for the treatment of inflammatory bowel diseases

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis