Variants in the promoter region of IKBL/NFKBIL1 gene may mark susceptibility to the development of chronic Chagas` cardiomyopathy among Trypanosoma cruzi-infected individuals

Chagas` disease, caused by Trypanosoma cruzi, is an inflammatory disorder leading to chronic Chagas cardiomyopathy (CCC). Only one third of T cruzi-infected individuals progress to CCC while the others are considered asymptomatic (ASY). The human inhibitory kappa B-like gene (KBLINFKBIL1), homologous to the I kappa B family of proteins that regulate the NF kappa B family of transcription factors, is suggested as a putative inhibitor of NFKB. We investigated two functional polymorphisms, -62A/T and -262A/G, in the promoter of IKBL by PCR-RFLP analysis in 169 patients with CCC and 76 ASY. Genotype distributions for both -62A/T and -262A/G differed between the CCC and ASY (X-2 = 7.3; P = 0.025 and X-2 = 6.8; P = 0.03, respectively). Subjects, homozygous for the -62A allele, had three-fold risk of developing CCC compared with those carrying the TT genotype (P = 0.0095; Odds Ratio [OR] = 2.9; [95% CI 1.2-7.3]). Similar trend was observed for the -262A homozygotes (P = 0.005; OR = 2.7 [95% CI 1.3-6.0]. The haplotype -262A -62A was prevalent in patients with CCC (40% versus 24%; OR 2.1 [95% C1 1.4-3.3j; Pc = 0.00 14). The I kappa BL locus itself or another critical gene in this region may confer susceptibility to the development of CCC. (C) 2007 Elsevier Ltd. All rights reserved.

Pathways to Melanoma Development: Lessons from the Mouse

Because of subtle differences between mouse and human skin, mice have traditionally not been an ideal model to study melanoma development. Understanding of the molecular mechanisms of melanoma predisposition, however, has been greatly improved by modeling various pathway defects in the mouse. This review analyzes the latest developments in mouse models of melanoma, and summarizes what these may indicate about the development of this neoplasm in humans. Mutations of genes involved in human melanoma have been recapitulated with some unexpected results, particularly with respect to the role of the two transcripts (Ink4a and Arf) encoded by the Cdkn2a locus. Both the Ink4a/pRb and Arf/p53 pathways are involved in melanoma development in mice, and possible mechanisms of cross-talk between the two pathways are discussed. We also know from mouse models that Ras/mitogen-activated protein kinase pathway activation is very important in melanoma development, either through direct activation of Ras (e.g., Hras G12V), or via activation of Ras-effector pathways by other oncogenes (e.g., Ret, Hgf/Sf). Ras can cooperate with the Arf/p53 pathway, and probably the Ink4a/Rb pathway, to induce melanoma. These three growth regulation pathways (Ink4a/pRb, Arf/p53, and Ras/mitogen-activated protein kinase) seem to represent three major axes of melanoma development in mice. Finally, we summarize experiments using genetically modified mice that have given indications of the intensity and timing of ultraviolet radiation exposure that may be most responsible for melanoma development.

A Devonian (Givetian) fore-reef slope sequence at Liangshuijing and implication for Devonian platform-to-depression development in Guilin, South China

Three Bahama-like carbonate plaforms-the Guilin, Yangshuo and Yanshan-occurred in Guilin and the surrounding regions during Middle and Late Devonian, which, at a broad scale, are part of an extensive carbonate platform (Xiangzhou carbonate platform) facies in South China. The intraplatform depression facies, a unique characteristic of the Chinese Devonian depositional sequence, separates Bahama-like (platform-to-depression) carbonate subplatfonns. Intraplatform depressions resulted from syndepositional faulting that cut the basement of carbonate subplatforms and affected further platform development. The Liangshuijing section, located between the Guilin platform in the north and the Yangshuo platform in the south, is representative of the fore-reef slope facies neighboring an intraplatform. depression. The South edge of the fore-reef slope lies adjacent to the Yangshuo reef carbonate platform, and the north edge graded into the Yangdi pelagic depression facies. A detailed sedimentary and microfacies analysis work done in this study at the Liangshuijing section shows a distinct vertical facies change from back-reef, restricted platform, hemipelagic, to fore-reefslope facies, differing from either shallow-water benthic facies or typical pelagic facies. Various benthic and pelagic lithofacies and their associations have been recognized in the Liangshuijing section, including dolomitic rudstone, gastropod wackestone, Amphipora floatstone, tentaculitoid wackestone, stromatolite and oncoid limestone, Amphipora grainstone, grain flows, laminated limestone, flat-pebble and brachiopod floatstone, and carbonate turbidites. Eight types of sedimentary cycles composed of two or three lithofacies have been distinguished, which are able to indicate environment changes. Stromatolites, oncoids, grain flows, carbonate turbidites, and tentaculitoid limestones characterize the slope and intraplatform depression lithofacies. Analysis of the vertical sedimentary cycles in the Liangshuijinag section and the lateral stratigraphic equivalents suggest the differing facies patterns occurred at the middle Varcus Zone (Givetian) of Middle Devonian, coeval with the development of fore-reef slope facies in the Guilin area in response to syndeposifional faulting.

Negative ion electrospray mass spectra of caerulein peptides: an aid to structural determination

MS/MS data derived from the [M-H](-) ions of desulfated caerulein peptides provide (i) sequencing information from a combination of alpha, beta and gamma backbone cleavages, and (ii) identification of specific amino acid side chains by side-chain cleavages [e.g. Ser (-CH2O), Thr (-CH3CHO) and Asp (-H2O)] (fragmentations having no counterparts in positive ion spectra). In addition, delta and/or gamma backbone cleavage ions from Asp residues identify the position of these residues in the peptide. In contrast, neither delta nor gamma cleavage ions are observed from either the Gln2 residue nor from Phe residues. Full structural information can be obtained from a consideration of the positive and negative ion MS/MS data in concert. Copyright (C) 2002 John Wiley Sons, Ltd.

A cognitive complexity metric applied to cognitive development

Two experiments tested predictions from a theory in which processing load depends on relational complexity (RC), the number of variables related in a single decision. Tasks from six domains (transitivity, hierarchical classification, class inclusion, cardinality, relative-clause sentence comprehension, and hypothesis testing) were administered to children aged 3-8 years. Complexity analyses indicated that the domains entailed ternary relations (three variables). Simpler binary-relation (two variables) items were included for each domain. Thus RC was manipulated with other factors tightly controlled. Results indicated that (i) ternary-relation items were more difficult than comparable binary-relation items, (ii) the RC manipulation was sensitive to age-related changes, (iii) ternary relations were processed at a median age of 5 years, (iv) cross-task correlations were positive, with all tasks loading on a single factor (RC), (v) RC factor scores accounted for 80% (88%) of age-related variance in fluid intelligence (compositionality of sets), (vi) binary- and ternary-relation items formed separate complexity classes, and (vii) the RC approach to defining cognitive complexity is applicable to different content domains. (C) 2002 Elsevier Science (USA). All rights reserved.

Cancer incidence projections for Lisbon and Santarém districts: an aid to radiotherapy services planning

Will the existing means in Radiotherapy respond to the needs of the potential user population in 2014 for Lisbon and Santarém districts? Number of treatment units? Number of Radiotherapy Technologists? Temporal variations of the dimension and age structure of the populations: Coastal areas/Interior areas, Urban areas/Rural areas. Temporal variations in the incidence of several types of cancer. Overall objectives: evaluate of the necessities of Radiotherapy for Lisbon and Santarém districts in 2014 and elaboration of proposals that aim the access/use for the potential user population.

Surveillance of mother-to-child HIV transmission: socioeconomic and health care coverage indicators

OBJECTIVE: To identify clustering areas of infants exposed to HIV during pregnancy and their association with indicators of primary care coverage and socioeconomic condition. METHODS: Ecological study where the unit of analysis was primary care coverage areas in the city of Porto Alegre, Southern Brazil, in 2003. Geographical Information System and spatial analysis tools were used to describe indicators of primary care coverage areas and socioeconomic condition, and estimate the prevalence of liveborn infants exposed to HIV during pregnancy and delivery. Data was obtained from Brazilian national databases. The association between different indicators was assessed using Spearman's nonparametric test. RESULTS: There was found an association between HIV infection and high birth rates (r=0.22, p<0.01) and lack of prenatal care (r=0.15, p<0.05). The highest HIV infection rates were seen in areas with poor socioeconomic conditions and difficult access to health services (r=0.28, p<0.01). The association found between higher rate of prenatal care among HIV-infected women and adequate immunization coverage (r=0.35, p<0.01) indicates that early detection of HIV infection is effective in those areas with better primary care services. CONCLUSIONS: Urban poverty is a strong determinant of mother-to-child HIV transmission but this trend can be fought with health surveillance at the primary care level.

HIV rapid testing as a key strategy for prevention of mother-to-child transmission in Brazil

OBJECTIVE: To assess the feasibility of HIV rapid testing for pregnant women at maternity hospital admission and of subsequent interventions to reduce perinatal HIV transmission. METHODS: Study based on a convenience sample of women unaware of their HIV serostatus when they were admitted to delivery in public maternity hospitals in Rio de Janeiro and Porto Alegre, Brazil, between March 2000 and April 2002. Women were counseled and tested using the Determine HIV1/2 Rapid Test. HIV infection was confirmed using the Brazilian algorithm for HIV infection diagnosis. In utero transmission of HIV was determined using HIV-DNA-PCR. There were performed descriptive analyses of sociodemographic data, number of previous pregnancies and abortions, number of prenatal care visits, timing of HIV testing, HIV rapid test result, neonatal and mother-to-child transmission interventions, by city studied. RESULTS: HIV prevalence in women was 6.5% (N=1,439) in Porto Alegre and 1.3% (N=3.778) in Rio de Janeiro. In Porto Alegre most of women were tested during labor (88.7%), while in Rio de Janeiro most were tested in the postpartum (67.5%). One hundred and forty-four infants were born to 143 HIV-infected women. All newborns but one in each city received at least prophylaxis with oral zidovudine. It was possible to completely avoid newborn exposure to breast milk in 96.8% and 51.1% of the cases in Porto Alegre and Rio de Janeiro, respectively. Injectable intravenous zidovudine was administered during labor to 68.8% and 27.7% newborns in Porto Alegre and Rio de Janeiro, respectively. Among those from whom blood samples were collected within 48 hours of birth, in utero transmission of HIV was confirmed in 4 cases in Rio de Janeiro (4/47) and 6 cases in Porto Alegre (6/79). CONCLUSIONS: The strategy proved feasible in maternity hospitals in Rio de Janeiro and Porto Alegre. Efforts must be taken to maximize HIV testing during labor. There is a need of strong social support to provide this population access to health care services after hospital discharge.

Social contextual factors contributing to child and adolescent labor: an ecological analysis

OBJECTIVE: To examine the relationship between social contextual factors and child and adolescent labor. METHODS: Population-based cohort study carried out with 2,512 families living in 23 subareas of a large urban city in Brazil from 2000 to 2002. A random one-stage cluster sampling was used to select families. Data were obtained through individual household interviews using questionnaires. The annual cumulative incidence of child and adolescent labor was estimated for each district. New child and adolescent labor cases were those who had their first job over the two-year follow-up. The annual cumulative incidence of child and adolescent labor was the response variable and predictors were contextual factors such as lack of social support, social deprivation, unstructured family, perceived violence, poor school quality, poor environment conditions, and poor public services. Pearson's correlation and multiple linear regression were used to assess the associations. RESULTS: There were selected 943 families corresponding to 1,326 non-working children and adolescents aged 8 to 17 years. Lack of social support, social deprivation, perceived violence were all positively and individually associated with the annual cumulative incidence of child and adolescent labor. In the multiple linear regression model, however, only lack of social support and perceived violence in the neighborhood were positively associated to child and adolescent labor. No effect was found for poor school quality, poor environment conditions, poor public services or unstructured family. CONCLUSIONS: Poverty reduction programs can reduce the contextual factors associated with child and adolescent labor. Violence reduction programs and strengthening social support at the community level may contribute to reduce CAL.

Design state exploration applied to the development of a remote lab for projectile launch experiments

This paper describes the application of Design State Exploration techniques in the development of a remote lab for projectile motion experiments. The application was enabled by the existence of two independent teams: one composed of a series of internships that started first and another with two grantees that started a few months later. The paper presents evidence on how this approach provided gains in the development process conducted by the second team that benefited from design state exploration studies performed by the first team. This particular aspect is highlighted in relation to the work already presented in the 10th Remote Engineering and Virtual Instrumentation (REV) conference.

ELEVATED ALANINE AMINOTRANSFERASE (ALT) IN BLOOD DONORS: AN ASSESSMENT OF THE MAIN ASSOCIATED CONDITIONS AND ITS RELATIONSHIP TO THE DEVELOPMENT OF HEPATITIS C

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.

Mother-to-child transmission of different HIV-1 subtypes among ARV Naïve infected pregnant women in Nigeria

The rate of mother-to-child transmission (MTCT) of HIV as well as the implications of the circulating multiple subtypes to MTCT in Nigeria are not known. This study was therefore undertaken to determine the differential rates of MTCT of HIV-1 subtypes detected among infected pregnant women before ARV intervention therapy became available in Nigeria. Twenty of the HIV-positive women who signed the informed consent form during pregnancy brought their babies for follow-up testing at age 18-24 months. Plasma samples from both mother and baby were tested for HIV antibody at the Department of Virology, UCH, Ibadan, Nigeria. All positive samples (plasma and peripheral blood mononuclear cells - PBMCs) were shipped to the Institute of Tropical Medicine, Antwerp, Belgium, where the subtype of the infecting virus was determined using the HMA technique. Overall, a mother-to-child HIV transmission rate of 45% was found in this cohort. Specifically, 36.4%, 66.7% and 100% of the women infected with HIV-1 CRF02 (IbNg), G and B, respectively, transmitted the virus to their babies. As far as it can be ascertained, this is the first report on the rate of MTCT of HIV in Nigeria. The findings reported in this paper will form a useful reference for assessment of currently available therapeutic intervention of MTCT in the country.