Spatial distribution of intestinal parasitic infections in a Kaingáng indigenous village from Southern Brazil

The spatial distribution of enteroparasitosis in an indigenous village from Paraná was evaluated to identify areas of risk for these infections. A cross-sectional study (from November 2010 to June 2011) was performed using Three Faecal Test^® and Kato &; Katz method and a questionnaire on housing and hygiene conditions was administered. Local geostatistical analyses were performed to determine the spatial distribution of intestinal parasitic infections. The overall prevalence of enteroparasites was 67.2?% (457/680), and the most prevalent taxa were Ascaris lumbricoides (48.8?%) and Trichuris trichiura (44.7?%). The prevalence of heavy infection by soil-transmitted helminths was 3.6?% and the families lived in houses with an average of 5.1 residents and < 2 bedrooms per household. The average number of species per individual present spatial heterogeneity with the highest values (≥0.8) in areas with high clustering of residences. The visualization of the spatial distribution of intestinal parasites in this indigenous village is an important contribution to determining health risk areas and planning decisions and services.     

Nonproportional hazards and unobserved heterogeneity in clustered survival data: When can we tell the difference?

Multivariate survival data are frequently encountered in biomedical applications in the form of clustered failures (or recurrent events data). A popular way of analyzing such data is by using shared frailty models, which assume that the proportional hazards assumption holds conditional on an unobserved cluster-specific random effect. Such models are often incorporated in more complicated joint models in survival analysis. If the random effect distribution has finite expectation, then the conditional proportional hazards assumption does not carry over to the marginal models. It has been shown that, for univariate data, this makes it impossible to distinguish between the presence of unobserved heterogeneity (eg, due to missing covariates) and marginal nonproportional hazards. We show that time-dependent covariate effects may falsely appear as evidence in favor of a frailty model also in the case of clustered failures or recurrent events data, when the cluster size or number of recurrent events is small. When true unobserved heterogeneity is present, the presence of nonproportional hazards leads to overestimating the frailty effect. We show that this phenomenon is somewhat mitigated as the cluster size grows. We carry out a simulation study to assess the behavior of test statistics and estimators for frailty models in such contexts. The gamma, inverse Gaussian, and positive stable shared frailty models are contrasted using a novel software implementation for estimating semiparametric shared frailty models. Two main questions are addressed in the contexts of clustered failures and recurrent events: whether covariates with a time-dependent effect may appear as indication of unobserved heterogeneity and whether the additional presence of unobserved heterogeneity can be detected in this case. Finally, the practical implications are illustrated in a real-world data analysis example.     

Characterization of the CXCR4 Signaling in Pancreatic Cancer Cells

CXCL12 and its receptor, CXCR4, are emerging as promising targets for modulating growth, angiogenesis, and metastasis in several human cancers. Indeed, blocking the receptor is sufficient to prevent metastasis and angiogenesis in experimental breast cancer xenografts. Recently, the biological effect of the CXCR4 in pancreatic cancer, one of the most deadly neoplastic diseases, has been reported. However, the molecular mechanism by which CXCR4 contributes to these properties is not completely understood. In this paper, we characterize the signaling pathways activated by CXCR4 in pancreatic cancer. We show that after CXCR4 activation, EGFR becomes tyrosine phosphorylated, and the kinase activity of this receptor, together with the activation of MMPs, Src, and PI3-Kinase, is required for CXCR4-mediated ERK activation. Analysis of this cascade in pancreatic cancer cells revealed that the ERK-mediated pathway regulates genes involved in angiogenesis, such as VEGF, CD44, HIF1α, and IL-8. Furthermore, ERK blockage inhibits the migration and tube formation of endothelial cells induced by CXCL12. Considering that inhibitors for several components of this pathway, including CXCR4 itself, are at different stages of clinical trials, this study provides theoretical justification for the clinical testing of these drugs in pancreatic cancer, thus extending the list of potential targets for treating this dismal disease.     

Liver transplant in a patient with a ventriculoperitoneal shunt.

There are no published accounts of patients with ventriculoperitoneal shunts undergoing liver transplantation in the literature. Because patients with ventriculoperitoneal shunts are prone to infections, this may be a theoretical contraindication to transplantation. We present a case of a patient with cirrhosis who had a ventriculoperitoneal shunt placed many years prior to transplantation. The patient had no neurological complications and the shunt was intact and functioning. Prior to transplantation, the patient underwent a ventriculoperitoneal to ventriculopleural shunt conversion that was reversed posttransplantation. Apart from some minor complications, the patient has done remarkably well from a graft and neurological perspective. In conclusion, patients who have ventriculoperitoneal shunts may be considered for liver transplantation as the risk of infectious and neurological complications is low and there are no deleterious effects on graft survival.     

Polyhalide derivatives of poly[N-(2-aminoethyl)-acrylamido]triethylammonium resins as iodinating reagents

Poly[N-(2-aminoethyl)acrylamido]triethylammonium dichloroiodate, tetrachloroiodate and dibromoiodate resins have been developed as a new class of heterogeneous reagents. The use of the polyhalide derivatives for the selective iodination of aromatic amines and phenols is described. The influence of the various reaction parameters including nature of the solvent, effective molar concentration of the reagent and temperature were investigated to find out the optimum reaction conditions for achiveing selectivity for monoiodination.     

Development of a recombinant human collagen-type III based hemostat

Animal-tissue-derived collagen, containing mostly type I collagen with a minor amount of type III collagen, has been widely used in the production of hemostats for many decades, although it has been known for a long time that type III collagen is more likely to induce platelet aggregation in vitro. Because it is hard to purify type III from animal tissue, it has not been possible to correlate this finding with in vivo data. In this report, it is demonstrated that recombinant human collagen III fibrils are more capable of inducing platelet aggregation in vitro than those comprised of bovine collagen I, in agreement with previously published data on tissue-derived type III collagen. When formed into three-dimensional matrices, the use of type III collagen results in formulations with better mechanical integrity, larger surface area, and higher hemostatic activity in a rabbit spleen injury model as compared with commercially available hemostats formed from bovine type I collagen.     

Distinctive gene expression profiles by cDNA microarrays in endometrioid and serous carcinomas of the endometrium.

Endometrial carcinomas are classified by their morphology into two major subtypes. Endometrioid carcinomas (type I) are generally estrogen dependent, well-differentiated, superficially invasive, and have a good outcome. Serous carcinomas (type II) are hormone independent, frequently deeply invasive and widely metastatic, and have a poor prognosis. Microarray technology and analysis allows us to determine if the global gene expression profiles of these two subtypes correlate with their morphologic phenotype. Fresh tissue from 18 endometrial carcinomas was studied: 7 well-, 2 moderately, and one poorly differentiated endometrioid, 4 serous carcinomas, and 4 high-grade mixed endometrioid-serous carcinomas. Labeled cDNA probes were synthesized (Cy5 for tumor, Cy3 for reference) and applied to microarrays containing 18,098 cDNA clones or ESTs. A pool of equal amounts of total RNA from each tumor served as the reference RNA. By unsupervised cluster analysis, the endometrioid carcinomas clustered together and were separate from the serous carcinomas. The high-grade mixed carcinomas clustered with the serous carcinomas. Using a statistical algorithm based on gene expression pattern and conducting a supervised analysis of the two defined groups, we have identified 315 genes that statistically differentiate type I from type II endometrial carcinomas. In addition to corroborating the predicted overexpression of known markers (e.g., ras and catenin in endometrioid carcinomas), the cDNA microarray technique has revealed novel alterations in gene expression relevant to cell cycle, cell adhesion, signal transduction, apoptosis, and tumor progression not previously implicated in endometrial carcinomas. For serous carcinomas, these include aldolase, desmoplakin, integrin-linked kinase, PKC, and metallopeptidase. In conclusion, the gene expression profiles of type I and type II endometrial carcinomas are different. Refinement of these profiles will permit more accurate diagnostic tumor classification and the development of prognosis assays.     

Zinc-mediated carboxylations of allylic and propargylic halides in flow: synthesis of β-lactones via subsequent bromolactonization

Zinc-mediated carboxylation of allylic halides under flow conditions delivered β,γ-unsaturated carboxylic acids and subsequent bromolactonization provides a streamlined process for the synthesis of γ-bromo-β-lactones. The described process further demonstrates the utility of organozinc reagents prepared by passage of allylic halides through a metallic zinc column integrated into a flow process. Use of a tube-in-tube reactor for efficient CO₂ introduction led to improvements in conversion compared to a batch process and improved overall yields of β-lactones. The described flow process was also applied to propargylic bromides for the synthesis of allenic and propargylic acids.

Zinc-mediated carboxylation of allylic halides under flow conditions delivered β,γ-unsaturated carboxylic acids and subsequent bromolactonization provides a streamlined process for the synthesis of γ-bromo-β-lactones.