Avaliação da vulnerabilidade sísmica do núcleo urbano antigo do Seixal

A avaliação do risco sísmico, tal como de outros fenómenos naturais, tem vindo a ganhar protagonismo ao longo das últimas décadas, sendo considerado primordial na definição de estratégias de planeamento e gestão urbana. A avaliação da vulnerabilidade sísmica de edifícios existentes, na perspectiva da mitigação do risco sísmico, deve colocar-se não só em relação aos edifícado monumental ou culturalmente valiosos, mas também em relação a aglomerados de edifícios em núcleos urbanos, particularmente nos núcleos urbanos antigos. A análise do desempenho de edifícios em sismos recentes tem permitido identificar quais os aspectos estruturais que mais influenciam a sua vulnerabilidade e o desenvolvimento de mecanismos de danos. Neste artigo analisam-se os resultados da avaliação da vulnerabilidade sísmica do núcleo urbano antigo do Seixal, obtidos através da aplicação de uma metodologia baseada num índice de vulnerabilidade. Através da avaliação da vulnerabilidade sísmica, esta metodologia permite ainda estimar dano e criar cenários de perda. Estes resultados serão apresentados tirando partido de uma ferramenta integrada num Sistema de Informação Geográfica (SIG)

Diagnostic value of distal colonic polyps for prediction of advanced proximal neoplasia in an average-risk population undergoing screening colonoscopy

For colorectal cancer screening, the predictive value of distal findings in the ascertainment of proximal lesions is not fully established. The aims of this study were to assess distal findings as predictors of advanced proximal neoplasia and to compare the predictive value of endoscopy alone vs. combined endoscopic and histopathologic data. METHODS: Primary colonoscopy screening was performed in 2210 consecutive, average-risk adults. Age, gender, endoscopic (size, number of polyps), and histopathologic distal findings were used as potential predictors of advanced proximal neoplasms (i.e., any adenoma > or =1 cm in size, and/or with villous histology, and/or with severe dysplasia or invasive cancer). Polyps were defined as distal if located in the descending colon, the sigmoid colon, or the rectum. Those in other locations were designated proximal. RESULTS: Neoplastic lesions, including 11 invasive cancers, were found in 617 (27.9%) patients. Advanced proximal neoplasms without any distal adenoma were present in 1.3% of patients. Of the advanced proximal lesions, 39% were not associated with any distal polyp. Older age, male gender, and distal adenoma were independent predictors of advanced proximal neoplasms. The predictive ability of a model with endoscopic data alone did not improve after inclusion of histopathologic data. In multivariate logistic regression analysis, the predictive ability of models that use age, gender, and any combination of distal findings was relatively low. The proportion of advanced proximal neoplasms identified if any distal polyp was an indication for colonoscopy was only 62%. CONCLUSIONS: A strategy in which colonoscopy is performed solely in patients with distal colonic findings is not effective screening for the detection of advanced proximal neoplasms in an average-risk populatio

Coxiella burnetii Phagocytosis Is Regulated by GTPases of the Rho Family and the RhoA Effectors mDia1 and ROCK

The GTPases belonging to the Rho family control the actin cytoskeleton rearrangements needed for particle internalization during phagocytosis. ROCK and mDia1 are downstream effectors of RhoA, a GTPase involved in that process. Coxiella burnetii, the etiologic agent of Q fever, is internalized by the host´s cells in an actin-dependent manner. Nevertheless, the molecular mechanism involved in this process has been poorly characterized. This work analyzes the role of different GTPases of the Rho family and some downstream effectors in the internalization of C. burnetii by phagocytic and non-phagocytic cells. The internalization of C. burnetii into HeLa and RAW cells was significantly inhibited when the cells were treated with Clostridium difficile Toxin B which irreversibly inactivates members of the Rho family. In addition, the internalization was reduced in HeLa cells that overexpressed the dominant negative mutants of RhoA, Rac1 or Cdc42 or that were knocked down for the Rho GTPases. The pharmacological inhibition or the knocking down of ROCK diminished bacterium internalization. Moreover, C. burnetii was less efficiently internalized in HeLa cells overexpressing mDia1-N1, a dominant negative mutant of mDia1, while the overexpression of the constitutively active mutant mDia1-ΔN3 increased bacteria uptake. Interestingly, when HeLa and RAW cells were infected, RhoA, Rac1 and mDia1 were recruited to membrane cell fractions. Our results suggest that the GTPases of the Rho family play an important role in C. burnetii phagocytosis in both HeLa and RAW cells. Additionally, we present evidence that ROCK and mDia1, which are downstream effectors of RhoA, are involved in that processFil: Salinas Ojeda, Romina Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Ortiz Flores, Rodolfo Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Distel, Jesús Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Aguilera, Milton Osmar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Colombo, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Beron, Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas.

PURPOSE: To evaluate the feasibility and safety of intratumoral injection of autologous dendritic cells (DCs) transfected with an adenovirus encoding interleukin-12 genes (AFIL-12) for patients with metastatic gastrointestinal carcinomas. Secondarily, we have evaluated biologic effects and antitumoral activity. PATIENTS AND METHODS: Seventeen patients with metastatic pancreatic (n = 3), colorectal (n = 5), or primary liver (n = 9) malignancies entered the study. DCs were generated from CD14+ monocytes from leukapheresis, cultured and transfected with AFIL-12 before administration. Doses from 10 x 10(6) to 50 x 10(6) cells were escalated in three cohorts of patients. Patients received up to three doses at 21-day intervals. RESULTS: Fifteen (88%) and 11 of 17 (65%) patients were assessable for toxicity and response, respectively. Intratumoral DC injections were mainly guided by ultrasound. Treatment was well tolerated. The most common side effects were lymphopenia, fever, and malaise. Interferon gamma and interleukin-6 serum concentrations were increased in 15 patients after each treatment, as well as peripheral blood natural killer activity in five patients. DC transfected with AFIL-12 stimulated a potent antibody response against adenoviral capsides. DC treatment induced a marked increase of infiltrating CD8+ T lymphocytes in three of 11 tumor biopsies analyzed. A partial response was observed in one patient with pancreatic carcinoma. Stable disease was observed in two patients and progression in eight patients, with two of the cases fast-progressing during treatment. CONCLUSION: Intratumoral injection of DC transfected with an adenovirus encoding interleukin-12 to patients with metastatic gastrointestinal malignancies is feasible and well tolerated. Further studies are necessary to define and increase clinical efficacy

Mechanistic model of natural killer cell proliferative response to IL-15 receptor stimulation

Natural killer (NK) cells are innate lymphocytes that provide early host defense against intracellular pathogens, such as viruses. Although NK cell development, homeostasis, and proliferation are regulated by IL-15, the influence of IL-15 receptor (IL-15R)-mediated signaling at the cellular level has not been quantitatively characterized. We developed a mathematical model to analyze the kinetic interactions that control the formation and localization of IL-15/IL-15R complexes. Our computational results demonstrated that IL-15/IL-15R complexes on the cell surface were a key determinant of the magnitude of the IL-15 proliferative signal and that IL-15R occupancy functioned as an effective surrogate measure of receptor signaling. Ligand binding and receptor internalization modulated IL-15R occupancy. Our work supports the hypothesis that the total number and duration of IL-15/IL-15R complexes on the cell surface crosses a quantitative threshold prior to the initiation of NK cell division. Furthermore, our model predicted that the upregulation of IL-15Rα on NK cells substantially increased IL-15R complex formation and accelerated the expansion of dividing NK cells with the greatest impact at low IL-15 concentrations. Model predictions of the threshold requirement for NK cell recruitment to the cell cycle and the subsequent exponential proliferation correlated well with experimental data. In summary, our modeling analysis provides quantitative insight into the regulation of NK cell proliferation at the receptor level and provides a framework for the development of IL-15 based immunotherapies to modulate NK cell proliferation

Gastroduodenal injury after radioembolization of hepatic tumors

Radioembolization is a new tool for the treatment of hepatic tumors that consists in the injection of biocompatible microspheres carrying radioisotopes into the hepatic artery or its branches. METHODS: We have performed radioembolization in 78 patients with hepatic tumors using resin-based microspheres loaded with yttrium-90. All patients were previously evaluated to minimize the risk of hazardous irradiation to nontarget organs and to obtain the data needed for dose calculation. RESULTS: We report a complication found in three cases (3.8%) that consists of abdominal pain resulting from gastroduodenal lesions and that had a chronic, insidious course. Microscopically, microspheres were detected in the specimens obtained from all affected gastric areas. Since these gastroduodenal lesions do not appear when nonradiating microspheres are injected in animals, lesions are likely to be due to radiation and not to an ischemic effect of vascular occlusion by spheres. CONCLUSIONS: We believe that a pretreatment evaluation that includes a more thorough scrutiny of the hepatic vascularization in search of small collaterals connecting to the gastroduodenal tract can help prevent this awkward complicatio

Use of colonoscopy as a primary screening test for colorectal cancer in average risk people

The use of colonoscopy as a primary screening test for colorectal cancer (CRC) in average risk adults is a subject of controversy. Our primary objective was to build a predictive model based on a few simple variables that could be used as a guide for identifying average risk adults more suitable for examination with colonoscopy as a primary screening test. METHODS: The prevalence of advanced adenomas was assessed by primary screening colonoscopy in 2210 consecutive adults at least 40 yr old, without known risk factors for CRC. Age, gender, and clinical and biochemical data were compared among people without adenomas, those with non-advanced adenomas, and those with any advanced neoplasm. A combined score to assess the risk of advanced adenomas was built with the variables selected by multiple logistic regression analysis. RESULTS: Neoplastic lesions were found in 617 subjects (27.9%), including 259 with at least one neoplasm that was 10 mm or larger, villous, or with moderate-to-severe dysplasia, and 11 with invasive cancers. Advanced lesions were more frequent among men, older people, and those with a higher body mass index (BMI). These three variables were independent predictors of advanced adenomas in multivariate analysis. A score combining age, sex, and BMI was developed as a guide for identifying individuals more suitable for screening colonoscopy. CONCLUSIONS: Age, gender, and BMI can be used to build a simple score to select those average risk adults who might be candidates for primary screening colonoscop

Water protection after tympanostomy (Shepard) tubes does not decrease otorrhea incidence - retrospective cohort study

INTRODUCTION: Myringotomy for tube insertion is the most common otologic surgery. Otorrhea is a frequent complication of this procedure and, to prevent it, most surgeons strongly recommend avoiding contact with water as this is thought to adversely impact on post-operative quality of life. OBJECTIVE: To understand the benefit of this recommendation. METHODS: Observational study - retrospective cohort study comparing the incidence of post-operative otorrhea and its impact on patients' quality of life, in two groups of patients comprising children under 10 years of age who underwent bilateral myringotomy and tube placement for chronic otitis media with effusion between May 2011 and May 2012. One group received water protection care after surgery, the other did not. Data was collected through telephonic interview, after one year of follow up (one year after the procedure). Water exposure without protection was considered the exposure event. Incidence of otorrhea and perceived impact on quality of life were the outcome measures. Results were compared after logistic regression. RESULTS: We included 143 children: 116 were not exposed to water without protection and 27 were exposed. In the not exposed group 36.2% had at least one episode of otorrhea, compared to 40.0% of the exposed group. Odds ratio for otorrhea on exposed was 1.21 (95% CI 0.51-2.85, p=0.6). Negative impact on quality of life was reported by parents of 48.2% on the not exposed children, compared to 40.7% on the exposed group. This difference was not significant (p=0.5). CONCLUSION: We found that recommending water protection did not have beneficial effect on the incidence of otorrhea after myringotomy with tubes on chronic otitis media with effusion. However, such measures did not appear to have a negative impact on quality of life. This is a populational observational study with few cases (143 cases); these final statements would be better stated by a very large populational study with another large control group.info:eu-repo/semantics/publishedVersio

Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria

Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection