Rio de Janeiro, Brazil
Rio de Janeiro, Brazil

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Zin A.A.,Fernandes Figueira Institute | Moreira M.E.L.,Fernandes Figueira Institute | Bunce C.,Moorfields Eye Hospital | Darlow B.A.,University of Otago | Gilbert C.E.,London School of Hygiene and Tropical Medicine
Pediatrics | Year: 2010

OBJECTIVES: The goals were to determine optimal screening criteria for retinopathy of prematurity (ROP) in 7 neonatal units in Rio de Janeiro, Brazil, and to explore the workload implications of applying different criteria. METHODS: Infants with birth weights of ≤2000 g or gestational age of <37 weeks were examined by 3 ophthalmologists in 7 of the largest units in Rio de Janeiro, during a 34-month period. ROP was classified by using the international classification, and laser treatment was given to infants developing type 1 ROP. RESULTS: A total of 3437 (87%) of 3953 eligible infants were examined, of whom 124 (3.6% [range: 2.1%-7.8%]) were treated. Eleven infants were treated for aggressive posterior ROP. Appropriate screening criteria for the 2 NICUs with high survival rates (ie, ≥80% among infants with birth weights of <1500 g) would be ≤1500 g or <32 weeks. For NICUs with low survival rates (ie, <80%), appropriate criteria would be ≤1500 g or ≤35 weeks. UK, US, and previous Brazilian criteria would all miss infants needing treatment. CONCLUSIONS: ROP programs in Brazil should use the wider criteria of ≤1500 g or ≤35 weeks until further evidence-based criteria become available, although this would mean a slight increase in workload across the city, compared with use of the narrower criteria in the better units. Whether survival rates can be used as a proxy to indicate screening criteria requires further investigation. Copyright © 2010 by the American Academy of Pediatrics.


Lafouresse F.,French Institute of Health and Medical Research | Lafouresse F.,University Paul Sabatier | Lafouresse F.,French National Center for Scientific Research | Lafouresse F.,CNRS Institute of Pharmacology and Structural Biology | And 6 more authors.
Tissue Antigens | Year: 2013

T lymphocytes are key players of adaptive immune responses. Upon recognition of specific peptides presented by human leukocyte antigen (HLA) molecules on antigen presenting cells (APC), these cells execute subset-related functions such as killing, help and regulation. The ontogeny, the activation and the effector functions of T lymphocytes are all steps of T-lymphocyte life cycle that rely on high motility properties. These cells travel through the organism in a succession of steps, including entry into tissues, interstitial migration, APC scanning, synapse formation and tissue exit. Such ability is possible because of a plastic motility behavior, which is highly controlled in time and space. The molecular basis for the adaptable motility behavior of T lymphocytes is only starting to be unraveled. The scope of this review is to discuss recent data pointing to the key role of regulators of actin cytoskeleton remodeling in tuning distinct aspects of T-lymphocyte motility during their entry, residency and exit from tissues. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Steffen R.E.,Federal University of Rio de Janeiro | Caetano R.,State University of Rio de Janeiro | Pinto M.,Fernandes Figueira Institute | Chaves D.,Gama Filho University | And 6 more authors.
PLoS ONE | Year: 2013

Background: Latent tuberculosis infection (LTBI) is a reservoir for new TB cases. Isoniazid preventive therapy (IPT) reduces the risk of active TB by as much as 90%, but LTBI screening has limitations. Unlike tuberculin skin testing (TST), interferon-gamma release assays are not affected by BCG vaccination, and have been reported to be cost-effective in low-burden countries. The goal of this study was to perform a cost-effectiveness analysis from the health system perspective, comparing three strategies for LTBI diagnosis in TB contacts: tuberculin skin testing (TST), QuantiFERON®-TB Gold-in-Tube (QFT-GIT) and TST confirmed by QFT-GIT if positive (TST/QFT-GIT) in Brazil, a middle-income, high-burden country with universal BCG coverage. Methodology/Principal Findings: Costs for LTBI diagnosis and treatment of a hypothetical cohort of 1,000 adult immunocompetent close contacts were considered. The effectiveness measure employed was the number of averted TB cases in two years. Health system costs were US$ 105,096 for TST, US$ 121,054 for QFT-GIT and US$ 101,948 for TST/QFT-GIT; these strategies averted 6.56, 6.63 and 4.59 TB cases, respectively. The most cost-effective strategy was TST (US$ 16,021/averted case). The incremental cost-effectiveness ratio was US$ 227,977/averted TB case for QFT-GIT. TST/QFT-GIT was dominated. Conclusions: Unlike previous studies, TST was the most cost-effective strategy for averting new TB cases in the short term. QFT-GIT would be more cost-effective if its costs could be reduced to US$ 26.95, considering a TST specificity of 59% and US$ 18 considering a more realistic TST specificity of 80%. Nevertheless, with TST, 207.4 additional people per 1,000 will be prescribed IPT compared with QFT. © 2013 Steffen et al.


Cotta-de-Almeida V.,Oswaldo Cruz Institute | Dupre L.,French Institute of Health and Medical Research | Dupre L.,University Paul Sabatier | Dupre L.,French National Center for Scientific Research | And 4 more authors.
Frontiers in Immunology | Year: 2015

Over the last decades, research dedicated to the molecular and cellular mechanisms underlying primary immunodeficiencies (PID) has helped to understand the etiology of many of these diseases and to develop novel therapeutic approaches. Beyond these aspects, PID are also studied because they offer invaluable natural genetic tools to dissect the human immune system. In this review, we highlight the research that has focused over the last 20 years on T lymphocytes from Wiskott-Aldrich syndrome (WAS) patients. WAS T lymphocytes are defective for the WAS protein (WASP), a regulator of actin cytoskeleton remodeling. Therefore, study of WAS T lymphocytes has helped to grasp that many steps of T lymphocyte activation and function depend on the crosstalk between membrane receptors and the actin cytoskeleton. These steps include motility, immunological synapse assembly, and signaling, as well as the implementation of helper, regulatory, or cytotoxic effector functions. The recent concept that WASP also works as a regulator of transcription within the nucleus is an illustration of the complexity of signal integration in T lymphocytes. Finally, this review will discuss how further study of WAS may contribute to solve novel challenges of T lymphocyte biology. © 2015 Cotta-de-Almeida, Dupré, Guipouy and Vasconcelos.


PubMed | French Institute of Health and Medical Research, Fernandes Figueira Institute and Oswaldo Cruz Institute
Type: | Journal: Frontiers in immunology | Year: 2015

Over the last decades, research dedicated to the molecular and cellular mechanisms underlying primary immunodeficiencies (PID) has helped to understand the etiology of many of these diseases and to develop novel therapeutic approaches. Beyond these aspects, PID are also studied because they offer invaluable natural genetic tools to dissect the human immune system. In this review, we highlight the research that has focused over the last 20years on T lymphocytes from Wiskott-Aldrich syndrome (WAS) patients. WAS T lymphocytes are defective for the WAS protein (WASP), a regulator of actin cytoskeleton remodeling. Therefore, study of WAS T lymphocytes has helped to grasp that many steps of T lymphocyte activation and function depend on the crosstalk between membrane receptors and the actin cytoskeleton. These steps include motility, immunological synapse assembly, and signaling, as well as the implementation of helper, regulatory, or cytotoxic effector functions. The recent concept that WASP also works as a regulator of transcription within the nucleus is an illustration of the complexity of signal integration in T lymphocytes. Finally, this review will discuss how further study of WAS may contribute to solve novel challenges of T lymphocyte biology.


PubMed | Federal University of Rio de Janeiro and Fernandes Figueira Institute
Type: Journal Article | Journal: Journal of feline medicine and surgery | Year: 2016

Feline immunodeficiency virus (FIV) is a lentivirus that induces AIDS-like disease in cats. Some of the antiretroviral drugs available to treat patients with HIV type 1 are used to treat FIV-infected cats; however, antiretroviral therapy (ART) is not used in cats as a long-term treatment. In this study, the effects of long-term ART were evaluated in domestic cats treated initially with the nucleoside transcriptase reverse inhibitor (NTRI) zidovudine (AZT) over a period ranging from 5-6 years, followed by a regimen of the NTRI lamivudine (3TC) plus AZT over 3 years.Viral load, sequencing of pol (reverse transcriptase [RT]) region and CD4:CD8 lymphocyte ratio were evaluated during and after treatment. Untreated cats were evaluated as a control group.CD4:CD8 ratios were lower, and uncharacterized resistance mutations were found in the RT region in the group of treated cats. A slight increase in viral load was observed in some cats after discontinuing treatment.The data strongly suggest that treated cats were resistant to therapy, and uncharacterized resistance mutations in the RT gene of FIV were selected for by AZT. Few studies have been conducted to evaluate the effect of long-term antiretroviral therapy in cats. To date, resistance mutations have not been described in vivo.


Oxlade O.,Harvard University | Pinto M.,Fernandes Figueira Institute | Trajman A.,Gama Filho University | Trajman A.,McGill University | Menzies D.,McGill University
PLoS ONE | Year: 2013

Introduction: Cost effectiveness analyses (CEA) can provide useful information on how to invest limited funds, however they are less useful if different analysis of the same intervention provide unclear or contradictory results. The objective of our study was to conduct a systematic review of methodologic aspects of CEA that evaluate Interferon Gamma Release Assays (IGRA) for the detection of Latent Tuberculosis Infection (LTBI), in order to understand how differences affect study results. Methods: A systematic review of studies was conducted with particular focus on study quality and the variability in inputs used in models used to assess cost-effectiveness. A common decision analysis model of the IGRA versus Tuberculin Skin Test (TST) screening strategy was developed and used to quantify the impact on predicted results of observed differences of model inputs taken from the studies identified. Results: Thirteen studies were ultimately included in the review. Several specific methodologic issues were identified across studies, including how study inputs were selected, inconsistencies in the costing approach, the utility of the QALY (Quality Adjusted Life Year) as the effectiveness outcome, and how authors choose to present and interpret study results. When the IGRA versus TST test strategies were compared using our common decision analysis model predicted effectiveness largely overlapped. Implications: Many methodologic issues that contribute to inconsistent results and reduced study quality were identified in studies that assessed the cost-effectiveness of the IGRA test. More specific and relevant guidelines are needed in order to help authors standardize modelling approaches, inputs, assumptions and how results are presented and interpreted. © 2013 Oxlade et al.


Fontenelle E.,Fernandes Figueira Institute | de Almeida A.P.M.,Teaching Hospital Alvaro Alvim | Souza G.M.A.A.,Dermatologist of the Military Firefighters Corporation of the State of Rio de Janeiro
Anais Brasileiros de Dermatologia | Year: 2013

Marshall ́s syndrome is a form of acquired cutis laxa without systemic involvement, which is preceded by an inflammatory dermatitis with a neutrophilic component. We report a case of a 6-year-old boy with clinical and histopathological features of this syndrome. The etiology remains unknown and there is no definitive treatment. © 2013 by Anais Brasileiros de Dermatologia.


PubMed | Fernandes Figueira Institute
Type: Journal Article | Journal: Twin research and human genetics : the official journal of the International Society for Twin Studies | Year: 2016

A dramatic increase in twin pregnancies has been observed in the past few decades, primarily related to assisted reproductive techniques (ART) and increased average maternal age during pregnancy. Multiple pregnancies, compared to singleton pregnancies, are associated with greater perinatal morbidity and mortality. The present study evaluated the perinatal outcomes of pregnancies with discordant anomalous twins in a tertiary maternity ward in a developing country. Data were retrospectively collected from the Instituto Fernandes Figueira/FIOCRUZ, Brazil between January 2002 and December 2014. We identified 74 twin pregnancies with discordant anomalous twins. Final data analysis was based on 40 pregnancies. Congenital defects were classified according to the International Classification of Diseases: ICD-10: the digestive system was responsible in 27 (34%) cases; the central nervous system was responsible in 18 (22%) cases; the urinary tract was responsible in 14 (17%) cases; and the circulatory system was responsible in 14 (17%) cases. A total of 19 deaths occurred during the study period, and delivery before 30.4 weeks was a significant prediction of fetal death (p = .01). The presence of hydrops in the affected fetus was related to a higher number of deaths in healthy fetuses and contributed to a worse prognosis. The presence of this condition was the cause of 12 (55.6%) deaths in healthy fetuses. A 10 times higher risk of death of a normal co-twin was observed in cases of death of the anomalous twin (p = .002, OR 10.55, 95% CI: 1.9-58.52).


PubMed | Secretaria de Atencao a Saude, Fernandes Figueira Institute and University of Brasilia
Type: Journal Article | Journal: Revista brasileira de epidemiologia = Brazilian journal of epidemiology | Year: 2016

The article assessed the overall mortality in Brazil in 2000 and 2010.Data source was the Mortality Information System from Ministry of Health of Brazil.The data show the high rate of mortality among men compared to women between ages of 20 to 59 years and an expressive lower life expectancy by this population. The main groups of death were: external causes; diseases of the circulatory system, diseases of the digestive system, infectious and parasitic diseases, diseases of the respiratory system; mental and behavioral disorders; diseases of the nervous system; endocrine, nutritional and metabolic diseases; neoplasia and diseases of the genitourinary system.Unequal gender relations and distinct characteristics of exposure to risk factors can explain this mortality, highlighting the need to bring critical incorporation of relational gender perspective by public health policies.

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