378 research outputs found
Escenario económico postconvertibilidad: sus evidencias en la estructura empresaria neuquina
El presente documento analiza algunas de las cuestiones que vinculan los cambios en el escenario macroeconómico y el desenvolvimiento reciente de un conjunto de empresas neuquinas. Las mismas han sido objeto de un relevamiento realizado como parte de.una investigación exploratoria de mayor alcance.' La infonnación obtenida permite avanzar en la elaboración de hipótesis de investigación en la temática y en estrategias de intervención orientadas al desarrollo local y regional.Desde mediados de los años 80 y a lo largo de los 90, las actividades económicas de las distintas regiones, tanto como las PyMEs, han ganado una creciente presencia, tanto en los medios académicos como en los espacios donde se formulan políticas y programas, siendo consideradas elementos fundamentales para enfrentar los desafíos del desarrollo en la economía mundial y nacional. Tres elementos realzan su presencia en la economía contemporánea: el número de ellas en el total de establecimientos, la significativa participación sobre el total del empleo en todos los sectores, y el significativo aporte al Producto Bruto Interno de los diferentes países. (Todesca y Boceo, 2000
Blood–brain barrier impairment in patients living with hiv: Predictors and associated biomarkers
Despite the substantial changes resulting from the introduction of combination antiretroviral therapy (cART), the prevalence of HIV-associated neurocognitive disorders (HAND) remains substantial. Blood–brain barrier impairment (BBBi) is a frequent feature in people living with HIV (PLWH) and it may persist despite effective antiretroviral treatment. A cross-sectional study was performed in PLWH who underwent lumbar puncture for clinical reasons or research protocols and several cerebrospinal fluid biomarkers were studied. BBBi was defined as cerebrospinal fluid-to-serum albumin ratio (CSAR) >6.5 (<40 years) or >8 (>40 years). We included 464 participants: 147 cART-naïve and 317 on cART. Male sex was prevalent in both groups (72.1% and 72.2% respectively); median age was 44 (38–52) years in naïve and 49 (43–57) years in treated subjects. BBBi was observed in 35.4% naïve and in 22.7% treated participants; the use of integrase inhibitors was associated with a lower prevalence (18.3 vs. 30.9%, p = 0.050). At multivariate binary logistic regression (including age and sex) nadir CD4 cell count (p = 0.034), presence of central nervous system (CNS) opportunistic infections (p = 0.024) and cerebrospinal fluid (CSF) HIV RNA (p = 0.002) in naïve participants and male sex (p = 0.021), a history of CNS opportunistic infections (p = 0.001) and CSF HIV RNA (p = 0.034) in treated patients were independently associated with BBBi. CSF cells and neopterin were significantly higher in participants with BBBi. BBBi was prevalent in naïve and treated PLWH and it was associated with CSF HIV RNA and neopterin. Systemic control of viral replication seems to be essential for BBB integrity while sex and treatment influence need further studies
Epidemiological surveillance of trachoma in a school in an urban area in Southeastern Brazil
INTRODUCTION: Epidemiological surveillance activities undertaken after the detection of an active trachoma case in the APAE-SP are described. MATERIAL AND METHOD: A total of 1,009 pupils, employees and household contacts had an eye examination. Treatment control was carried out at the institution 4 times at 45 day-intervals. RESULTS: The overall prevalence was of 5.9%, 5.1% being of follicular trachoma (TF), 0.3% of intense trachoma (TF/TI) and 0.5% of cicatricial trachoma (TS). At the first control exercise 45.5% of the trachoma cases had no signs of the disease and 40.0% underwent treatment. At the last control exercise 20% were found to have been cured with no vestigial scars. Non-attendance was of 38.2%. The distribution of secondary cases showed great dispersion, suggesting dissemination throughout Greater S. Paulo . DISCUSSION AND CONCLUSIONS: The trachoma control activities do not show satisfactory results, perhaps due to the prolonged duration of the treatment and follow up. The development of strategies of clinical intervention should be implemented for better control of the disease.OBJETIVO: Verificar as condições de vigilância epidemiológica do tracoma desencadeadas a partir da detecção de um caso de tracoma inflamatório na APAE - SP. MATERIAL E MÉTODO: Foram submetidos a exame ocular 1.009 pessoas entre alunos, funcionários e comunicantes intradomiciliares. Os controles de tratamento foram realizados em uma instituição, por 4 vezes, em intervalos de 45 dias. RESULTADOS: A prevalência total foi de 5,9%, sendo 5,1% de tracoma folicular (TF), 0,3% de tracoma folicular intenso (TF/TI) e 0,5% de tracoma cicatricial (TS). No primeiro controle 45,5% dos casos apresentou alta clínica e 40,0% manteve tratamento. No último controle 20,0% apresentou alta curado sem cicatrizes. A taxa de faltosos alcançou 38,2%. A distribuição espacial dos casos secundários mostrou ampla dispersão na Grande São Paulo, indicando que o tracoma deve estar disseminado por toda a região. DISCUSSÃO/CONCLUSÕES: As ações de controle do tracoma não apresentaram resultados satisfatórios, provavelmente devido ao prolongado tempo de tratamento e acompanhamento. Estratégias de intervenção clínica devem ser desenvolvidas para melhor controle da doença.Secretaria de Estado da Saúde (SES). São PauloSES. São PauloUniversidade Federal de São Paulo (UNIFESP)APAESecretaria Municipal de Saúde. São PauloUNIFESPSciEL
A importância do Plano Nacional de Fertilizantes para o futuro do agronegócio e do Brasil.
Carta da Agricultura
Seroprevalence of five neglected parasitic diseases among immigrants accessing five infectious and tropical diseases units in Italy: a cross-sectional study.
: This multicentre cross-sectional study aims to estimate the prevalence of five neglected tropical diseases (Chagas disease, filariasis, schistosomiasis, strongyloidiasis, toxocariasis) among immigrants accessing health care facilities in five Italian cities (Bologna, Brescia, Florence, Rome, Verona). : Individuals underwent a different set of serological tests, according to country of origin and presence of eosinophilia. Seropositive patients were treated and further followed up. : A total of 930 adult immigrants were enrolled: 477 men (51.3%), 445 women (47.9%), 8 transgender (0.8%); median age was 37.81 years (range 18-80). Most of them were coming from the African continent (405/930, 43.5%), the rest from East Europe, South America and Asia. A portion of 9.6% (89/930) were diagnosed with at least one of the infections under study. Seroprevalence of each specific infection varied from 3.9% (7/180) for Chagas diseases to 9.7% (11/113) for toxocariasis. Seropositive people were more likely to be 35 to 40 years-old male and to come from South East Asia, Sub-Saharan Africa or South America. : The results of our study confirm that neglected tropical diseases represent a substantial health problem among immigrants and highlight the need for addressing this emerging public health issue.<br/
Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE(TM) study in patients with previously treated CLL/SLL.
In the phase 3 RESONATE(TM) study, ibrutinib demonstrated superior progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) compared with ofatumumab in relapsed/refractory CLL patients with high-risk prognostic factors. We report updated results from RESONATE in these traditionally chemotherapy resistant high-risk genomic subgroups at a median follow-up of 19 months. Mutations were detected by Foundation One Heme Panel. Baseline mutations in the ibrutinib arm included TP53 (51%), SF3B1 (31%), NOTCH1 (28%), ATM (19%), and BIRC3 (14%). Median PFS was not reached, with 74% of patients randomized to ibrutinib alive and progression-free at 24 months. The improved efficacy of ibrutinib vs. ofatumumab continues in all prognostic subgroups including del17p and del11q. No significant difference within the ibrutinib arm was observed for PFS across most genomic subtypes, although a subset carrying both TP53 mutation and del17p had reduced PFS compared to patients with neither abnormality. Reduced PFS or OS was not evident in patients with only del17p. PFS was significantly better for ibrutinib-treated patients in second-line vs. later lines of therapy. The robust clinical activity of ibrutinib continues to show ongoing efficacy and acceptable safety consistent with prior reports, independent of various known high-risk mutations
Vigilância epidemiológica do tracoma em instituição de ensino na cidade de São Paulo, SP
INTRODUCTION: Epidemiological surveillance activities undertaken after the detection of an active trachoma case in the APAE-SP are described. MATERIAL AND METHOD: A total of 1,009 pupils, employees and household contacts had an eye examination. Treatment control was carried out at the institution 4 times at 45 day-intervals. RESULTS: The overall prevalence was of 5.9%, 5.1% being of follicular trachoma (TF), 0.3% of intense trachoma (TF/TI) and 0.5% of cicatricial trachoma (TS). At the first control exercise 45.5% of the trachoma cases had no signs of the disease and 40.0% underwent treatment. At the last control exercise 20% were found to have been cured with no vestigial scars. Non-attendance was of 38.2%. The distribution of secondary cases showed great dispersion, suggesting dissemination throughout Greater S. Paulo . DISCUSSION AND CONCLUSIONS: The trachoma control activities do not show satisfactory results, perhaps due to the prolonged duration of the treatment and follow up. The development of strategies of clinical intervention should be implemented for better control of the disease.OBJETIVO: Verificar as condições de vigilância epidemiológica do tracoma desencadeadas a partir da detecção de um caso de tracoma inflamatório na APAE - SP. MATERIAL E MÉTODO: Foram submetidos a exame ocular 1.009 pessoas entre alunos, funcionários e comunicantes intradomiciliares. Os controles de tratamento foram realizados em uma instituição, por 4 vezes, em intervalos de 45 dias. RESULTADOS: A prevalência total foi de 5,9%, sendo 5,1% de tracoma folicular (TF), 0,3% de tracoma folicular intenso (TF/TI) e 0,5% de tracoma cicatricial (TS). No primeiro controle 45,5% dos casos apresentou alta clínica e 40,0% manteve tratamento. No último controle 20,0% apresentou alta curado sem cicatrizes. A taxa de faltosos alcançou 38,2%. A distribuição espacial dos casos secundários mostrou ampla dispersão na Grande São Paulo, indicando que o tracoma deve estar disseminado por toda a região. DISCUSSÃO/CONCLUSÕES: As ações de controle do tracoma não apresentaram resultados satisfatórios, provavelmente devido ao prolongado tempo de tratamento e acompanhamento. Estratégias de intervenção clínica devem ser desenvolvidas para melhor controle da doença
Broad targeting of resistance to apoptosis in cancer
Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer
RESCUE OF HIPPO CO-ACTIVATOR YAP1 TRIGGERS DNA DAMAGE-INDUCED APOPTOSIS IN HEMATOLOGICAL CANCERS
Oncogene–induced DNA damage elicits genomic instability in epithelial cancer cells, but apoptosis is blocked through inactivation of the tumor suppressor p53. In hematological cancers, the relevance of ongoing DNA damage and mechanisms by which apoptosis is suppressed are largely unknown. We found pervasive DNA damage in hematologic malignancies including multiple myeloma, lymphoma and leukemia, which leads to activation of a p53–independent, pro-apoptotic network centered on nuclear relocalization of ABL1 kinase. Although nuclear ABL1 triggers cell death through its interaction with the Hippo pathway co–activator YAP1 in normal cells, we show that low YAP1 levels prevent nuclear ABL1–induced apoptosis in these hematologic malignancies. YAP1 is under the control of a serine–threonine kinase, STK4. Importantly, genetic inactivation of STK4 restores YAP1 levels, triggering cell death in vitro and in vivo. Our data therefore identify a novel synthetic–lethal strategy to selectively target cancer cells presenting with endogenous DNA damage and low YAP1 levels
Phenotype and immune function of lymph node and peripheral blood CLL cells are linked to transendothelial migration
everal lines of evidence suggest that homing of tumor cells to lymphoid tissue contributes to disease progression in chronic lymphocytic leukemia (CLL). Here, we demonstrate that lymph node (LN)-derived CLL cells possess a distinct phenotype, and exhibit enhanced capacity for T-cell activation and superior immune synapse formation when compared with paired peripheral blood (PB) samples. LN-derived CLL cells manifest a proliferative, CXCR4(dim)CD5(bright) phenotype compared with those in the PB and higher expression of T-cell activation molecules including CD80, CD86, and HLA-D-related (DR). In addition, LN-CLL cells have higher expression of α4β1 (CD49d) which, as well as being a co-stimulatory molecule, is required for CLL cells to undergo transendothelial migration (TEM) and enter the proliferation centers of the LNs. Using an in vitro system that models circulation and TEM, we showed that the small population of CLL cells that migrate are CXCR4(dim)CD5(bright) with higher CD49d, CD80, CD86, and HLA-DR compared with those that remain circulating; a phenotype strikingly similar to LN-derived CLL cells. Furthermore, sorted CD49d(hi) CLL cells showed an enhanced capacity to activate T cells compared with CD49d(lo) subpopulations from the same patient. Thus, although PB-CLL cells have a reduced capacity to form immune synapses and activate CD4(+) T cells, this was not the case for LN-CLL cells or those with the propensity to undergo TEM. Taken together, our study suggests that CLL cell immunologic function is not only modulated by microenvironmental interactions but is also a feature of a subpopulation of PB-CLL cells that are primed for lymphoid tissue homing and interaction with T cells
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