PRELIMINARY REPORT ON THE PUTATIVE ASSOCIATION OF IL10 -3575 T/A GENETIC POLYMORPHISM WITH MALARIA SYMPTOMS

Only a small percentage of individuals living in endemic areas develop severe malaria suggesting that host genetic factors may play a key role. This study has determined the frequency of single nucleotide polymorphisms (SNPs) in some pro and anti-inflammatory cytokine gene sequences: IL6 (-174; rs1800795), IL12p40 (+1188; rs3212227), IL4 (+33; rs2070874), IL10 (-3575; rs1800890) and TGFb1 (+869; rs1800470), by means of PCR-RFLP. Blood samples were collected from 104 symptomatic and 37 asymptomatic subjects. Laboratory diagnosis was assessed by the thick blood smear test and nested-PCR. No association was found between IL6 (-174), IL12p40 (+1188), IL4 (+33), IL10 (- 3575), TGFb1 (+869) SNPs and malaria symptoms. However, regarding the IL10 -3575 T/A SNP, there were significantly more AA and AT subjects, carrying the polymorphic allele A, in the symptomatic group (c2 = 4.54, p = 0.01, OR = 0.40 [95% CI - 0.17- 0.94]). When the analysis was performed by allele, the frequency of the polymorphic allele A was also significantly higher in the symptomatic group (c2 = 4.50, p = 0.01, OR = 0.45 [95% CI - 0.21-0.95]). In conclusion, this study has suggested the possibility that the IL10 - 3575 T/A SNP might be associated with the presence and maintenance of malaria symptoms in individuals living in endemic areas. Taking into account that this polymorphism is related to decreased IL10 production, a possible role of this SNP in the pathophysiology of malaria is also suggested, but replication studies with a higher number of patients and evaluation of IL10 levels are needed for confirmation

Evaluation of the health-related quality of life of hematopoietic stem cell transplantation patients

This study evaluates the Health-Related Quality of Life of patients undergoing analogous and allogeneic transplantation at three different points in time: before, 30 and 180 days after transplantation, along with correlated clinical and socio-demographic data. Two questionnaires were used for data collection: the first addressed clinical and socio-demographic data and the second was the Functional Assessment Cancer Therapy translated and validated for Brazilian Portuguese. The initial sample was composed of 30 patients while 26 were ultimately evaluated at the three points. The set of results indicated a positive impact on Health-Related Quality of Life six months after transplantation. Despite the fact that there were additional concerns and some aspects such as physical and functional aspects were affected 30 days after the procedure, the Functional Assessment Cancer Therapy scores obtained six months after HSCT improved in all components, reaching levels above those prior to the procedure, especially physical and emotional aspects and the relationship with the physician.El objetivo de este estudio longitudinal consistió en evaluar la Calidad de Vida relacionada a la Salud de pacientes sometidos a trasplante autólogo y alogénico en tres momentos distintos: en el pre, 30 y 180 días postrasplante. Para la recolección de datos fueron utilizados dos cuestionarios: el primero para obtención de datos clínicos y sociodemográficos, y el segundo una escala específica el Functional Assesment Cancer Therapy. La muestra inicial fue constituida por 30 pacientes, siendo 26 evaluados en los tres momentos. El conjunto de resultados permitió visualizar un impacto positivo de la Calidad de Vida relacionada a la salud al final de los seis meses postrasplante, a pesar de algunas funciones presentarse más perjudicadas, como la función física, funcional y preocupaciones adicionales con 30 días, hubo mejoría en los puntajes del Functional Assesment Cancer Therapy en todos los componentes llegando a alcanzar niveles encima del pretrasplante, especialmente en los aspectos físicos y emocionales, y en la relación con el médico.O objetivo deste estudo longitudinal consistiu em se avaliar a qualidade de vida relacionada à saúde de pacientes submetidos ao transplante autólogo e alogênico, em três momentos distintos: no pré-transplante, 30 e 180 dias pós-transplante . Para a coleta de dados, foram utilizados dois questionários: o primeiro para obtenção de dados clínicos e sociodemográficos, e o segundo constituído por uma escala específica, o Functional Assessment Cancer Therapy. A amostra inicial foi constituída por 30 pacientes, sendo 26 avaliados nos três momentos. O conjunto de resultados permitiu visualizar impacto positivo da qualidade de vida relacionada à saúde, ao final dos seis meses pós-transplante. Apesar de algumas funções se apresentarem mais prejudicadas, como a função física, funcional e preocupações adicionais com 30 dias, houve melhora nos escores do Functional Assessment Cancer Therapy em todos os componentes, chegando-se a alcançar patamares acima dos encontrados na fase do pré-transplante, especialmente nos aspectos físicos, emocionais e relacionamento com o médico

Interaction among apoptosis-associated sequence variants and joint effects on aggressive prostate cancer

<p>Abstract</p> <p>Background</p> <p>Molecular and epidemiological evidence demonstrate that altered gene expression and single nucleotide polymorphisms in the apoptotic pathway are linked to many cancers. Yet, few studies emphasize the interaction of variant apoptotic genes and their joint modifying effects on prostate cancer (PCA) outcomes. An exhaustive assessment of all the possible two-, three- and four-way gene-gene interactions is computationally burdensome. This statistical conundrum stems from the prohibitive amount of data needed to account for multiple hypothesis testing.</p> <p>Methods</p> <p>To address this issue, we systematically prioritized and evaluated individual effects and complex interactions among 172 apoptotic SNPs in relation to PCA risk and aggressive disease (i.e., Gleason score ≥ 7 and tumor stages III/IV). Single and joint modifying effects on PCA outcomes among European-American men were analyzed using statistical epistasis networks coupled with multi-factor dimensionality reduction (SEN-guided MDR). The case-control study design included 1,175 incident PCA cases and 1,111 controls from the prostate, lung, colo-rectal, and ovarian (PLCO) cancer screening trial. Moreover, a subset analysis of PCA cases consisted of 688 aggressive and 488 non-aggressive PCA cases. SNP profiles were obtained using the NCI Cancer Genetic Markers of Susceptibility (CGEMS) data portal. Main effects were assessed using logistic regression (LR) models. Prior to modeling interactions, SEN was used to pre-process our genetic data. SEN used network science to reduce our analysis from > 36 million to < 13,000 SNP interactions. Interactions were visualized, evaluated, and validated using entropy-based MDR. All parametric and non-parametric models were adjusted for age, family history of PCA, and multiple hypothesis testing.</p> <p>Results</p> <p>Following LR modeling, eleven and thirteen sequence variants were associated with PCA risk and aggressive disease, respectively. However, none of these markers remained significant after we adjusted for multiple comparisons. Nevertheless, we detected a modest synergistic interaction between <it>AKT3 rs2125230-PRKCQ rs571715 </it>and disease aggressiveness using SEN-guided MDR (p = 0.011).</p> <p>Conclusions</p> <p>In summary, entropy-based SEN-guided MDR facilitated the logical prioritization and evaluation of apoptotic SNPs in relation to aggressive PCA. The suggestive interaction between <it>AKT3-PRKCQ </it>and aggressive PCA requires further validation using independent observational studies.</p

Pathogenesis of Streptococcus urinary tract infection depends on bacterial strain and β-hemolysin/cytolysin that mediates cytotoxicity, cytokine synthesis, inflammation and virulence

Streptococcus agalactiae can cause urinary tract infection (UTI) including cystitis and asymptomatic bacteriuria (ABU). The early host-pathogen interactions that occur during S. agalactiae UTI and subsequent mechanisms of disease pathogenesis are poorly defined. Here, we define the early interactions between human bladder urothelial cells, monocyte-derived macrophages, and mouse bladder using uropathogenic S. agalactiae (UPSA) 807 and ABU-causing S. agalactiae (ABSA) 834 strains. UPSA 807 adhered, invaded and killed bladder urothelial cells more efficiently compared to ABSA 834 via mechanisms including low-level caspase-3 activation, and cytolysis, according to lactate dehydrogenase release measures and cell viability. Severe UPSA 807-induced cytotoxicity was mediated entirely by the bacterial β-hemolysin/cytolysin (β-H/C) because an β-H/C-deficient UPSA 807 isogenic mutant, UPSA 807ΔcylE, was not cytotoxic in vitro; the mutant was also significantly attenuated for colonization in the bladder in vivo. Analysis of infection-induced cytokines, including IL-8, IL-1β, IL-6 and TNF-α in vitro and in vivo revealed that cytokine and chemokine responses were dependent on expression of β-H/C that also elicited severe bladder neutrophilia. Thus, virulence of UPSA 807 encompasses adhesion to, invasion of and killing of bladder cells, pro-inflammatory cytokine/ chemokine responses that elicit neutrophil infiltration, and β-H/C-mediated subversion of innate immune-mediated bacterial clearance from the bladder.Full Tex