Evolução tectónica mesozóica da Bacia Lusitaniana

The evolution of the Lusitanian Basin, localized on the western Iberian margin, is closely associated with the first opening phases of the North Atlantic. It persisted from the Late Triassic to the Early Cretaceous, more precisely until the end of the Early Aptian, and its evolution was conditioned by inherited structures from the variscan basement. The part played by the faults that establish its boundaries, as regards the geometric and kinematic evolution and the organization of the sedimentary bodies, is discussed here, as well as with respect to important faults transversal to the Basin. A basin evolution model is proposed consisting of four rifting episodes which show: i) periods of symmetrical (horst and graben organization) and asymmetrical (half graben organization) geometric evolution; ii) diachronous fracturing; iii) rotation of the main extensional direction; iv) rooting in the variscan basement of the main faults of the basin (predominantly thick skinned style). The analysis and regional comparison, particularly with the Algarve Basin, of the time intervals represented by important basin scale hiatuses near to the renovation of the rifting episodes, have led to assume the occurrence of early tectonic inversions (Callovian–Oxfordian and Tithonian–Berriasian). The latter, however, had a subsequent evolution distinct from the first: there is no subsidence renovation, which is discussed here, and it is related to a magmatic event. Although the Lusitanian Basin is located on a rift margin which is considered non-volcanic, the three magmatic cycles as defined by many authors, particularly the second (approx. 130 to 110 My ?), performed a fundamental part in the mobilization of the Hettangian evaporites, resulting in the main diapiric events of the Lusitanian Basin. The manner and time in which the basin definitely ends its evolution (Early Aptian) is discussed here. Comparisons are established with other west Iberian margin basins and with Newfoundland basins. A model of oceanization of this area of the North Atlantic is also presented, consisting of two events separated by approximately 10 My, and of distinct areas separated by the Nazaré fault. The elaboration of this synthesis was based on: - information contained in previously published papers (1990 – 2000); - field-work carried out over the last years, the results of which have not yet been published; - information gathered from the reinterpretation of geological mapping and geophysical (seismic and well logs) elements, and from generic literature concerning the Mesozoic of the west iberian margin.

Evaluation of a rapid dipstick test, Malar-CheckTM, for the diagnosis of Plasmodium falciparum malaria in Brazil

The present study was carried out to evaluate the Malar-CheckTM Pf test, an immunochromatographic assay that detects Plasmodium falciparum Histidine Rich Protein II, does not require equipment, and is easy and rapid to perform. In dilution assays performed to test sensitivity against known parasite density, Malar-CheckTMwere compared with thick blood smear (TBS), the gold standard for diagnosis. Palo Alto isolate or P. falciparum blood from patients with different parasitemias was used. The average cut-off points for each technique in three independent experiments were 12 and 71 parasites/mm³ (TBS and Malar-CheckTM, respectively). In the field assays, samples were collected from patients with fever who visited endemic regions. Compared to TBS, Malar-CheckTMyielded true-positive results in 38 patients, false-positive results in 3, true-negative results in 23, and false-negative result in 1. Malar-CheckTMperformed with samples from falciparum-infected patients after treatment showed persistence of antigen up to 30 days. Malar-CheckTM should aid the diagnosis of P. falciparum in remote areas and improve routine diagnosis even when microscopy is available. Previous P. falciparum infection, which can determine a false-positive test in cured individuals, should be considered. The prompt results obtained with the Malar-CheckTM for early diagnosis could avoid disease evolution to severe cases.

Gestão integrada da doença : uma abordagem experimental de gestão em sa

RESUMO - Os sistemas de saúde deparam-se, actualmente, com novos paradigmas, ao nível da qualidade da prestação de cuidados de saúde, bem como no que se refere à necessidade de controlo dos custos com o sector da saúde, obrigando as organizações a adaptarem-se por forma a fornecerem a resposta mais adequada às crescentes necessidades dos indivíduos. O reconhecimento desta realidade tem levado os governos de muitos países a definir políticas orientadas para problemas de saúde específicos e a adoptar estratégias de intervenção que privilegiam uma abordagem integrada com o objectivo de melhorarem progressivamente o nível de saúde das populações, a qualidade dos cuidados prestados e a eficiência na utilização de recursos. Em Portugal, a aplicação dos princípios que estiveram na base dos modelos de gestão da doença, deu origem ao modelo experimental de Gestão Integrada da Doença, que incorpora a gestão clínica da doença, centrada no doente, com especial enfoque na sua autogestão e na clarificação das melhores práticas profissionais, visando a sua uniformização; a reorganização do modelo de prestação de cuidados, com a criação de Centros de Elevada Diferenciação e Centros de Tratamento, com especiais preocupações no que concerne à orientação do doente no sistema para que os cuidados lhe seja ministrados no nível mais adequado; um modelo de financiamento específico, indexado aos resultados, que reflicta a adopção das melhores práticas; um sistema de informação que permita a monitorização e avaliação constante deste processo. O desenvolvimento deste modelo organizacional tem-se revelado como uma estratégia inovadora e como uma ferramenta de elevado potencial para a melhoria da prestação de cuidados de saúde e para a promoção de uma maior efectividade e eficiência, tal como poderá, ainda, constituirse como um veículo, importante e permanente, de informação de apoio à decisão em Saúde. Este modelo visa, no fundo, promover uma acção concertada no sentido da obtenção de uma intervenção precisa, através da mobilização de recursos adequados, que permitam uma melhoria do estado de saúde, da qualidade de vida e do bem-estar global dos doentes. Esta abordagem passa pela colaboração e coordenação dos diferentes níveis de prestação de cuidados, no sentido de oferecerem cuidados integrados de saúde, com níveis de qualidade elevados em termos de prevenção, diagnóstico, tratamento, reabilitação e acompanhamento. ------------------------ --ABSTRACT – The health systems are faced with new paradigms, on one hand in the healthcare services delivered to the populations, and on the other hand, in the need to control costs in the health sector, forcing organizations to adapt and provide the most appropriate response to the individuals growing needs. The magnitude of this problem, in terms of public health, requires the adoption of a directed, targeted, planned and integrated action, based on clear and well defined strategies in order to obtain health gains, improving the quality of care and streamlining the costs. In Portugal, the application of those principles forming the basis of the disease management models, led to the Integrated Disease Management model which, apart from the clinical management of the disease, also incorporates the healthcare delivery structure reorganization, a specific financing model based on an information system that allows the process monitoring and evaluation. The development of Integrated Disease Management models is a central strategy and a tool for improving healthcare delivery, more effectively and efficiently, and can even be an important and permanent vehicle of information for health decision support. Therefore, it is important to promote a concerted action towards achieving a precise intervention, mobilizing the resources, improving the health status, quality of life and the overall patients’ wellbeing. This action means increasing collaboration and coordination of the different levels of care, offering integrated healthcare s

Efficacy of azithromycin in the treatment of cutaneous leishmaniasis

The present open pilot study was conducted to assess the efficacy of azithromycin for the treatment of patients with cutaneous leishmaniasis in Araçuaí and Varzelândia, MG. Twenty-four patients with less of six months of disease evolution were treated after clinical examination, Montenegro test and a biopsy. The treatment schemes consisted of oral doses of 500 mg per day for 3, 5 and 10 days and of 1000 mg for two days. A clinical control was performed monthly and treatment cycles were repeated when necessary until full reepithelialization of the lesions. On the occasion of the final evaluation, 20 patients had completed the study and 17 of them (85%) were cured. The time to obtain a cure was 60 days ifor 6 (30%) patients, 90 days for 7 (35%), and 120 for 4 (20%). The three patients with treatment failure received a pentavalent antimonial for 20 days. No adverse reactions to the medication were observed and a 14 month follow-up did not show recurrence in any patient. These results suggest that azithromycin can be a good therapeutic option for the treatment of cutaneous leishmaniasis caused by Leishmania Viannia brasiliensis.

Glucocorticoid-induced tumor necrosis factor receptor expression in patients with cervical human papillomavirus infection

Introduction The progression of human papillomavirus (HPV) infection in the anogenital tract has been associated with the involvement of cells with regulatory properties. Evidence has shown that glucocorticoid-induced tumor necrosis factor receptor (GITR) is an important surface molecule for the characterization of these cells and proposes that GITR ligand may constitute a rational treatment for many cancer types. We aimed to detect the presence of GITR and CD25 in cervical stroma cells with and without pathological changes or HPV infection to better understand the immune response in the infected tissue microenvironment. Methods We subjected 49 paraffin-embedded cervical tissue samples to HPV DNA detection and histopathological analysis, and subsequently immunohistochemistry to detect GITR and CD25 in lymphocytes. Results We observed that 76.9% of all samples with high GITR expression were HPV-positive regardless of histopathological findings. High GITR expression (77.8%) was predominant in samples with ≥1,000 RLU/PCB. Of the HPV-positive samples negative for intraepithelial lesion and malignancy, 62.5% had high GITR expression. High GITR expression was observed in both carcinoma and high-grade squamous intraepithelial lesion (HSIL) samples (p = 0.16). CD25 was present in great quantities in all samples. Conclusions The predominance of high GITR expression in samples with high viral load that were classified as HSIL and carcinoma suggests that GITR+ cells can exhibit regulatory properties and may contribute to the progression of HPV-induced cervical neoplasia, emphasizing the importance of GITR as a potential target for immune therapy of cervical cancer and as a disease evolution biomarker.

Comparative study of lymphocytes from individuals that were vaccinated and unvaccinated against the pandemic 2009-2011 H1N1 influenza virus in Southern Brazil

ABSTRACTINTRODUCTION:While no single factor is sufficient to guarantee the success of influenza vaccine programs, knowledge of the levels of immunity in local populations is critical. Here, we analyzed influenza immunity in a population from Southern Brazil, a region with weather conditions that are distinct from those in the rest of country, where influenza infections are endemic, and where greater than 50% of the population is vaccinated annually.METHODS:Peripheral blood mononuclear cells were isolated from 40 individuals. Of these, 20 had received the H1N1 vaccine, while the remaining 20 were unvaccinated against the disease. Cells were stimulated in vitro with the trivalent post-pandemic influenza vaccine or with conserved major histocompatibility complex I (MHC I) peptides derived from hemagglutinin and neuraminidase. Cell viability was then analyzed by [3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide)]-based colorimetric assay (MTT), and culture supernatants were assayed for helper T type 1 (Th1) and Th2-specific cytokine levels.RESULTS:Peripheral blood lymphocytes from vaccinated, but not unvaccinated, individuals exhibited significant proliferation in vitro in the presence of a cognate influenza antigen. After culturing with vaccine antigens, cells from vaccinated individuals produced similar levels of interleukin (IL)-10 and interferon (IFN)-γ, while those from unvaccinated individuals produced higher levels of IFN-γ than of IL-10.CONCLUSIONS:Our data indicate that peripheral blood lymphocytes from vaccinated individuals are stimulated upon encountering a cognate antigen, but did not support the hypothesis that cross-reactive responses related to previous infections can ameliorate the immune response. Moreover, monitoring IL-10 production in vaccinated individuals could comprise a valuable tool for predicting disease evolution.

99mTc-sestamibi imaging and bone marrow karyotyping in the assessment of multiple myeloma and MGUS

AIM: The first pathogenetic step in multiple myeloma is the emergence of a limited number of clonal plasma cells, clinically known as monoclonal gammopathy of undetermined significance (MGUS). Patients with MGUS do not have symptoms or end-organ damage but they do have a 1% annual risk of progression to multiple myeloma or related malignant disorders. With progression of MGUS to multiple myeloma, complex genetic events occur in the neoplastic plasma cell. Karyotyping and fluorescence in-situ hybridization (FISH) were shown to be of prognostic value in patients with multiple myeloma. Tc-sestamibi imaging reflects myeloma disease activity in bone marrow with very high sensitivity and specificity predicting disease evolution. This study was undertaken to evaluate the role of Tc-sestamibi imaging and cytogenetic analysis in prognosis prediction of MGUS and multiple myeloma. METHODS: We enrolled 30 consecutive patients with a confirmed diagnosis of multiple myeloma or MGUS. Bone marrow biopsy and biochemical staging according to the International Staging System (ISS) were performed in all cases. Karyotype analysis and FISH were performed in 11 of 12 patients with MGUS and in 17 of 18 patients with multiple myeloma having adequate metaphases. RESULTS: The karyotype was abnormal in four of 11 MGUS and in six of 17 multiple myeloma. Abnormalities of chromosome 13 were present in one case of MGUS and in six cases of multiple myeloma whereas the involvement of immunoglobulin was observed in one case of multiple myeloma. An abnormal FISH panel was found in four MGUS and nine multiple myeloma patients. All patients with MGUS showed a normal MIBI scan (score 0). Among patients with multiple myeloma only three, all with ISS stage I, showed a normal scan while a positive scan was obtained in others (score range, 1-7). The MIBI uptake was strongly related to the bone marrow plasma cell infiltration and to cytogenetic abnormalities. Particularly, a MIBI uptake score above 5 identified patients with poor prognosis encompassing all stage III multiple myeloma and three of seven stage II multiple myeloma. On the other hand all stage I and II patients having a MIBI score less than 5 showed a good prognosis. CONCLUSION: Both cytogenetic analysis and a MIBI scan add no relevant prognostic information to the ISS in patients with stage I and III multiple myeloma. The MIBI scan was of prognostic value in stage II multiple myeloma patients. Additionally, MIBI imaging may be useful to guide bone marrow biopsy in order to obtain adequate samples for cytogenetic analysis.

Evidence for mantle exhumation along the Arabian margin in the Zagros (Kermanshah area, Iran)

The Kermanshah Crush Zone (Zagros, Iran) comprises elements from the Tethys Ocean and the former ocean-continent transition. Serpentinites and gabbros exposed in this area were formerly interpreted as originated from Tethys ocean and other residual Tethys oceanic domains all situated northeast of the Bisotoun platform. However, the structural relationships between these ultramafic units remained unclear. New field work in the Kermanshah-Harsin area led to the description of detachment faults over serpentinised mantle. ``Mid-Cretaceous'' carbonate ``extensional allochthons'' (pre-rift) and pelagic sediments (syn- to post-rift) dated from the Liassic are exposed above these detachments. Such an age mismatch can be explained by a polyphased mantle exhumation in a narrow basin along the Arabian margin with the assumption that no radiolarite nappe has been thrusted over the Bisotoun. Another detachment has been identified further to the NE on Eocene gabbro. So far, this one is considered as an intra-oceanic detachment from the residual Tethys. A first evolution model is proposed from early Jurassic to late Cretaceous obduction along with how this interpretation may be improved by future field work.

Conserved chromosomal clustering of genes governed by chromatin regulators in Drosophila

BACKGROUND: The trithorax group (trxG) and Polycomb group (PcG) proteins are responsible for the maintenance of stable transcriptional patterns of many developmental regulators. They bind to specific regions of DNA and direct the post-translational modifications of histones, playing a role in the dynamics of chromatin structure. RESULTS: We have performed genome-wide expression studies of trx and ash2 mutants in Drosophila melanogaster. Using computational analysis of our microarray data, we have identified 25 clusters of genes potentially regulated by TRX. Most of these clusters consist of genes that encode structural proteins involved in cuticle formation. This organization appears to be a distinctive feature of the regulatory networks of TRX and other chromatin regulators, since we have observed the same arrangement in clusters after experiments performed with ASH2, as well as in experiments performed by others with NURF, dMyc, and ASH1. We have also found many of these clusters to be significantly conserved in D. simulans, D. yakuba, D. pseudoobscura and partially in Anopheles gambiae. CONCLUSION: The analysis of genes governed by chromatin regulators has led to the identification of clusters of functionally related genes conserved in other insect species, suggesting this chromosomal organization is biologically important. Moreover, our results indicate that TRX and other chromatin regulators may act globally on chromatin domains that contain transcriptionally co-regulated genes.

Experimental endocarditis following dental extractions in rats with periodontitis.

This study analyzed the development of bacterial endocarditis following dental extraction in rats with periodontal disease. Periodontal disease was produced in rats by tying silk ligatures around the two maxillary first molars, and placing the animals on a high sucrose diet. Sterile aortic valve vegetations were produced by means of a transaortic catheter, and 24 hours later the maxillary first molars were extracted. The animals were killed 72 hours after the extractions. In rats with periodontal disease induced for 10 and 14 weeks, extractions resulted in an incidence of bacterial endocarditis of 24% and 50%, respectively, most of which were due to streptococcal species (two were caused by Staphylococcus [corrected] aureus). The difference, though not statistically significant (p = 0.10, chi 2 with Yates correction), shows a trend toward increased incidence of endocarditis with increasing severity of periodontal disease. This model demonstrates that one can reliably induce bacterial endocarditis after dental extractions in rats with periodontal disease.

Fluorescein and indocyanine-green angiography in ocular syphilis: an exploratory study.

BACKGROUND: Fluorescein (FA) and indocyanine-green angiography (ICGA) may offer valuable information concerning disease severity and prognosis in ocular syphilis. The aim of the present study is to describe angiographic patterns encountered in the context of ocular syphilis, and to explore the associations between specific angiographic manifestations and severity of disease presentation, as well as disease evolution after treatment. METHODS: We performed a retrospective institutional study with the inclusion of 23 patients with ocular syphilis presenting to the uveitis clinic of the Jules-Gonin Eye Hospital in a 10-year period. FA and ICGA were performed following a standard protocol for posterior uveitis. Patterns of fluorescence were noted, and statistical associations between each angiographic pattern and any demographic, clinical, or laboratory parameter at baseline and after treatment were sought. RESULTS: The presence of any dark dots in ICGA was significantly associated with anterior uveitis (p = 0.031). The presence of hot spots in ICGA was significantly associated with longer duration of symptoms prior to initial visit (p = 0.032) and with male gender (p = 0.012). Weak non-significant trends were found associating vascular staining in FA with anterior uveitis (p = 0.066), vitritis (p = 0.069), and younger age (p = 0.061), as well as disc hyperfluorescence in FA with seropositivity for HIV (p = 0.089) and macular edema in FA with longer disease duration (p = 0.061). The presence of any dark dots in ICGA exhibited a weak trend of association with anterior uveitis and/or vitritis (p = 0.079). CONCLUSIONS: Out of the several associations identified implicating specific angiographic features, we underline the possible role of the presence of dark dots in ICGA for identifying active inflammation, and the role of hot spots in ICGA as markers of long-standing disease. Vascular staining in FA appears to be more common in patients with severe ocular inflammation with presence of anterior uveitis and/or vitritis.

Fibrinogen and fibronectin binding cooperate for valve infection and invasion in Staphylococcus aureus experimental endocarditis.

The expression of Staphylococcus aureus adhesins in Lactococcus lactis identified clumping factor A (ClfA) and fibronectin-binding protein A (FnBPA) as critical for valve colonization in rats with experimental endocarditis. This study further analyzed their role in disease evolution. Infected animals were followed for 3 d. ClfA-positive lactococci successfully colonized damaged valves, but were spontaneously eradicated over 48 h. In contrast, FnBPA-positive lactococci progressively increased bacterial titers in vegetations and spleens. At imaging, ClfA-positive lactococci were restricted to the vegetations, whereas FnBPA-positive lactococci also invaded the adjacent endothelium. This reflected the capacity of FnBPA to trigger cell internalization in vitro. Because FnBPA carries both fibrinogen- and fibronectin-binding domains, we tested the role of these functionalities by deleting the fibrinogen-binding domain of FnBPA and supplementing it with the fibrinogen-binding domain of ClfA in cis or in trans. Deletion of the fibrinogen-binding domain of FnBPA did not alter fibronectin binding and cell internalization in vitro. However, it totally abrogated valve infectivity in vivo. This ability was restored in cis by inserting the fibrinogen-binding domain of ClfA into truncated FnBPA, and in trans by coexpressing full-length ClfA and truncated FnBPA on two separate plasmids. Thus, fibrinogen and fibronectin binding could cooperate for S. aureus valve colonization and endothelial invasion in vivo.

Aggregation of liposomes induced by calcium: A structural and kinetic study

In this work, the calcium-induced aggregation of phosphatidylserine liposomes is probed by means of the analysis of the kinetics of such process as well as the aggregate morphology. This novel characterization of liposome aggregation involves the use of static and dynamic light-scattering techniques to obtain kinetic exponents and fractal dimensions. For salt concentrations larger than 5 mM, a diffusion-limited aggregation regime is observed and the Brownian kernel properly describes the time evolution of the diffusion coefficient. For slow kinetics, a slightly modified multiple contact kernel is required. In any case, a time evolution model based on the numerical resolution of Smoluchowski's equation is proposed in order to establish a theoretical description for the aggregating system. Such a model provides an alternative procedure to determine the dimerization constant, which might supply valuable information about interaction mechanisms between phospholipid vesicles.

A two-phase composite in simple shear: Effective mechanical anisotropy development and localization potential

We present a combined shape and mechanical anisotropy evolution model for a two-phase inclusion-bearing rock subject to large deformation. A single elliptical inclusion embedded in a homogeneous but anisotropic matrix is used to represent a simplified shape evolution enforced on all inclusions. The mechanical anisotropy develops due to the alignment of elongated inclusions. The effective anisotropy is quantified using the differential effective medium (DEM) approach. The model can be run for any deformation path and an arbitrary viscosity ratio between the inclusion and host phase. We focus on the case of simple shear and weak inclusions. The shape evolution of the representative inclusion is largely insensitive to the anisotropy development and to parameter variations in the studied range. An initial hardening stage is observed up to a shear strain of gamma = 1 irrespective of the inclusion fraction. The hardening is followed by a softening stage related to the developing anisotropy and its progressive rotation toward the shear direction. The traction needed to maintain a constant shear rate exhibits a fivefold drop at gamma = 5 in the limiting case of an inviscid inclusion. Numerical simulations show that our analytical model provides a good approximation to the actual evolution of a two-phase inclusion-host composite. However, the inclusions develop complex sigmoidal shapes resulting in the formation of an S-C fabric. We attribute the observed drop in the effective normal viscosity to this structural development. We study the localization potential in a rock column bearing varying fraction of inclusions. In the inviscid inclusion case, a strain jump from gamma = 3 to gamma = 100 is observed for a change of the inclusion fraction from 20% to 33%.

Evolutionary fate of retroposed gene copies in the human genome.

Given that retroposed copies of genes are presumed to lack the regulatory elements required for their expression, retroposition has long been considered a mechanism without functional relevance. However, through an in silico assay for transcriptional activity, we identify here >1,000 transcribed retrocopies in the human genome, of which at least approximately 120 have evolved into bona fide genes. Among these, approximately 50 retrogenes have evolved functions in testes, more than half of which were recruited as functional autosomal counterparts of X-linked genes during spermatogenesis. Generally, retrogenes emerge "out of the testis," because they are often initially transcribed in testis and later evolve stronger and sometimes more diverse spatial expression patterns. We find a significant excess of transcribed retrocopies close to other genes or within introns, suggesting that retrocopies can exploit the regulatory elements and/or open chromatin of neighboring genes to become transcribed. In direct support of this hypothesis, we identify 36 retrocopy-host gene fusions, including primate-specific chimeric genes. Strikingly, 27 intergenic retrogenes have acquired untranslated exons de novo during evolution to achieve high expression levels. Notably, our screen for highly transcribed retrocopies also uncovered a retrogene linked to a human recessive disorder, gelatinous drop-like corneal dystrophy, a form of blindness. These functional implications for retroposition notwithstanding, we find that the insertion of retrocopies into genes is generally deleterious, because it may interfere with the transcription of host genes. Our results demonstrate that natural selection has been fundamental in shaping the retrocopy repertoire of the human genome.