Infant Mortality in Novo Hamburgo: Associated Factors and Cardiovascular Causes

Background: Infant mortality has decreased in Brazil, but remains high as compared to that of other developing countries. In 2010, the Rio Grande do Sul state had the lowest infant mortality rate in Brazil. However, the municipality of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre metropolitan region. Objective: To describe the causes of infant mortality in the municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were related to heart diseases and if they were diagnosed in the prenatal period, and to assess the access to healthcare services. Methods: This study assessed infants of the municipality of Novo Hamburgo, who died, and whose data were collected from the infant death investigation records. Results: Of the 157 deaths in that period, 35.3% were reducible through diagnosis and early treatment, 25% were reducible through partnership with other sectors, 19.2% were non-preventable, 11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were reducible through appropriate delivery care, and 3.8% were ill defined. The major cause of death related to heart disease (13.4%), which was significantly associated with the variables ‘age at death’, ‘gestational age’ and ‘birth weight’. Regarding access to healthcare services, 60.9% of the pregnant women had a maximum of six prenatal visits. Conclusion: It is mandatory to enhance prenatal care and newborn care at hospitals and basic healthcare units to prevent infant mortality.

Prevalence of Risk for Obstructive Sleep Apnea Syndrome and Association With Risk Factors in Primary Care

Abstract Background: Obstructive sleep apnea syndrome (OSAS) is a chronic, progressive disease with high morbidity and mortality. It is underdiagnosed, especially among women. Objective: To study the prevalence of high risk for OSAS globally and for the Berlin Questionnaire (BQ) categories, and to evaluate the reliability of the BQ use in the population studied. Methods: Observational, cross-sectional study with individuals from the Niterói Family Doctor Program, randomly selected, aged between 45 and 99 years. The visits occurred between August/2011 and December/2012. Variables associated with each BQ category and with high risk for OSAS (global) were included in logistic regression models (p < 0.05). Results: Of the total (616), 403 individuals (65.4%) reported snoring. The prevalence of high risk for OSA was 42.4%, being 49.7% for category I, 10.2% for category II and 77.6% for category III. Conclusion: BQ showed an acceptable reliability after excluding the questions Has anyone noticed that you stop breathing during your sleep? and Have you ever dozed off or fallen asleep while driving?. This should be tested in further studies with samples mostly comprised of women and low educational level individuals. Given the burden of OSAS-related diseases and risks, studies should be conducted to validate new tools and to adapt BQ to better screen OSAS.

Exploration of the visual system : Part 2. In vivo analysis methods : virtual-reality optomotor system, fundus examination and fluorescent angiography

The mouse has emerged as an animal model for many diseases. At IRO, we have used this animal to understand the development of many eye diseases and treatment of some of them. Precise evaluation of vision is a prerequisite for both these approaches. In this unit we describe three ways to measure vision: testing the optokinetic response, and evaluating the fundus by direct observation and by fluorescent angiography.

Top Three Pharmacogenomics and Personalized Medicine Applications at the Nexus of Renal Pathophysiology and Cardiovascular Medicine.

Pharmacogenomics is a field with origins in the study of monogenic variations in drug metabolism in the 1950s. Perhaps because of these historical underpinnings, there has been an intensive investigation of 'hepatic pharmacogenes' such as CYP450s and liver drug metabolism using pharmacogenomics approaches over the past five decades. Surprisingly, kidney pathophysiology, attendant diseases and treatment outcomes have been vastly under-studied and under-theorized despite their central importance in maintenance of health, susceptibility to disease and rational personalized therapeutics. Indeed, chronic kidney disease (CKD) represents an increasing public health burden worldwide, both in developed and developing countries. Patients with CKD suffer from high cardiovascular morbidity and mortality, which is mainly attributable to cardiovascular events before reaching end-stage renal disease. In this paper, we focus our analyses on renal function before end-stage renal disease, as seen through the lens of pharmacogenomics and human genomic variation. We herein synthesize the recent evidence linking selected Very Important Pharmacogenes (VIP) to renal function, blood pressure and salt-sensitivity in humans, and ways in which these insights might inform rational personalized therapeutics. Notably, we highlight and present the rationale for three applications that we consider as important and actionable therapeutic and preventive focus areas in renal pharmacogenomics: 1) ACE inhibitors, as a confirmed application, 2) VDR agonists, as a promising application, and 3) moderate dietary salt intake, as a suggested novel application. Additionally, we emphasize the putative contributions of gene-environment interactions, discuss the implications of these findings to treat and prevent hypertension and CKD. Finally, we conclude with a strategic agenda and vision required to accelerate advances in this under-studied field of renal pharmacogenomics with vast significance for global public health.

Nutrition and acute schistosomiasis

In northeast Brazil, nutritional deficiency diseases and schistosomiasis mansoni overlap. An experimental model, wich reproduces the marasmatic clinical form of protein-energy malnutrition, was developed in this laboratory to study these interactions. Albino Swiss mice were fed with a food association ingested usually by human populations in northeast Brazil. This diet (Regional Basic Diet - RBD) has negative effects on the growth, food intake and protein utilization in infected mice (acute phase of murine schistosomiasis). Nitrogen balance studies have also shown that infection with Schistosoma mansoni has apparently no effect on protein intestinal absorption in well nourished mice. However, the lowest absorption ratios have been detected among RBD - fed infected animals, suggesting that suprerimposed schistosome infection aggravated the nutritional status of the undernourished host. The serum proteins electrophoretic pattern, as far as albumins are concerned, is quite similar for non-infected undernourished and infected well-fed animals. So, the significance of albumins as a biochemical indicator of the nutritional status of human populations residing in endemic foci of Manson's schistosomiasis, is discussable.

Is the thymus a target organ in infectious diseases?

The thymus is a central lymphoid organ, in wich T cell precursors differentiale and generate most of the so-called T cell reprtoire. Along with a variety of acute infectious diseases, we and others determined important changes in both microenvironmental and lymphoid compartments of the organ. For example, one major and common feature observed in acute viral, bacterial and parasitic diseases, is a depletion of cortical thymocytes, mostly those bearing the CD4-CD8 double positive phenotype. This occurs simmultaneously to the relative enrichment in medullary CD4 or CD8 single positive cells, expressing high densities of the CD3 complex. Additionally we noticed a variety of changes in the thymic microenvironment (and particularly is epithelial component), comprising abnormal location of thymic epithelial cell subsets as well has a denser Ia-bearing cellular network. Moreover, the extracellular matrix network was altered with an intralobular increase of basement membrane proteins that positively correlated with the degree of thymocyte death. Lastly, anti-thymic cell antibodies were detected in both human and animal models of infectious diseases, and in some of them a phenomenon of molecular mimicry could be evidenced. Taken together, the data receiwed herein clearly show that the thymus should be regarded as a target in infectious diseases.

Time-Course In Vivo Trafficking Pattern and Effector Function of Donor-Specific Regulatory T Cells in Response to an Allograft.

Background: Experimental data have suggested that adoptive transfer of CD4+CD25+Foxp3+ regulatory T cells (Tregs), capable of controlling immune responses to specifi c auto- or alloantigens, could be used as a therapeutic strategy to promote specifi c tolerance in T-cell mediated diseases and in organ transplantation (Tx). However, before advocating the application of immunotherapy with Tregs in Tx, we need to improve our understanding of their in vivo homeostasis, traffi cking pattern and effector function in response to alloantigens. Methods : Donor-antigen specifi c murine Tregs were generated and characterized in vitro following our described protocols. Using an adoptive transfer and skin allotransplantation model, we have analyzed the in vivo expansion and homing of fl uorescent-labeled effector T cells (Teff) and Tregs, at different time-points after Tx, using fl ow-cytometry as well as fl uorescence microscopy techniques. Results: Tregs expressed CD62L, CCR7 and CD103 allowing their homing into lymphoid and non-lymphoid tissues (gut, skin) after intravenous injection. While hyporesponsive to TCR stimulation in vitro, transferred Tregs survived, migrated to secondary lymphoid organs and preferentially expanded within the allograft draining lymph nodes. Furthermore, Foxp3+ cells could be detected inside the allograft as early as day 3-5 after Tx. At a much later time-point (day 60 after Tx), graft-infi ltrating Foxp3+ cells were also detectable in tolerant recipients. When transferred alone, CD4+CD25- Teff cells expanded within secondary lymphoid organs and infi ltrated the allograft by day 3-5 after Tx. The co-transfer of Tregs limited the expansion of alloreactive Teff cells as well as their recruitment into the allograft. The promotion of graft survival observed in the presence of Tregs was in part mediated by the inhibition of the production of effector cytokines by CD4+CD25- T cells. Conclusion: Taken together, our results suggest that the suppression of allograft rejection and the induction of Tx tolerance are in part dependant on the alloantigendriven homing and expansion of Tregs. Thus, the appropriate localization of Tregs may be critical for their suppressive function in vivo.

The role of the eosinophil-selective chemokine, eotaxin, in allergic and non-allergic airways inflammation

Blood eosinophilia and tissue infiltration by eosinophils are frequently observed in allergic inflammation and parasitic infections. This selective accumulation of eosinophils suggested the existence of endogenous eosinophil-selective chemoattractants. We have recently discovered a novel eosinophil-selective chemoattractant which we called eotaxin in an animal model of allergic airways disease. Eotaxin is generated in both allergic and non-allergic bronchopulmonary inflammation. The early increase in eotaxin paralled eosinophil infiltration in the lung tissue in both models. An antibody to IL-5 suppressed lung eosinophilia, correlating with an inhibition of eosinophil release from bone marrow, without affecting eotaxin generation. This suggests that endogenous IL-5 is important for eosinophil migration but does not appear to be a stimulus for eotaxin production. Constitutive levels of eotaxin observed in guinea-pig lung may be responsible for the basal lung eosinophilia observed in this species. Allergen-induced eotaxin was present mainly in the epithelium and alveolar macrophages, as detected by immunostaining. In contrast there was no upregulation of eotaxin by the epithelial cells following the injection of Sephadex beads and the alveolar macrophage and mononuclear cells surrounding the granuloma were the predominant positive staining cells. Eotaxin and related chemokines acting through the CCR3 receptor may play a major role in eosinophil recruitment in allergic inflammation and parasitic diseases and thus offer an attractive target for therapeutic intervention.

Framework for Preventing and Addressing Overweight and Obesity in Northern Ireland 2012-2022: A Fitter Future for All (PDF 1MB)

A Framework for Preventing and Addressing Overweight and Obesity in NI 2012-2022 This Framework aims to “empower the population of Northern Ireland to make healthy choices, reduce the risk of overweight and obesity related diseases and improve health and wellbeing, by creating an environment that supports and promotes a physically active lifestyle and a healthy diet”. In addition, the following overarching targets have been set: Adults • To reduce the level of obesity by 4% and overweight and obesity by 3% by 2022. Children • A 3% reduction of obesity and 2% reduction of overweight and obesity by 2022åÊThe target is in two parts; the proportion that are obese and the proportion that are overweight and obese. Prevention is typically taken forward through action to address two main areas – improving diet and nutrition, and increasing participation in physical activity. Acknowledging this, two overarching objectives for the Framework have been set: to increase the percentage of people eating a healthy, nutritionally balanced diet; and to increase the percentage of the population meeting the CMO guidelines on physical activity.

Current millennium biotechniques for biomedical research on parasites and host-parasite interactions

The development of biotechnology in the last three decades has generated the feeling that the newest scientific achievements will deliver high standard quality of life through abundance of food and means for successfully combating diseases. Where the new biotechnologies give access to genetic information, there is a common belief that physiological and pathological processes result from subtle modifications of gene expression. Trustfully, modern genetics has produced genetic maps, physical maps and complete nucleotide sequences from 141 viruses, 51 organelles, two eubacteria, one archeon and one eukaryote (Saccharomices cerevisiae). In addition, during the Centennial Commemoration of the Oswaldo Cruz Institute the nearly complete human genome map was proudly announced, whereas the latest Brazilian key stone contribution to science was the publication of the Shillela fastidiosa genomic sequence highlythed on a Nature cover issue. There exists a belief among the populace that further scientific accomplishments will rapidly lead to new drugs and methodological approaches to cure genetic diseases and other incurable ailments. Yet, much evidence has been accumulated, showing that a large information gap exists between the knowledge of genome sequence and our knowledge of genome function. Now that many genome maps are available, people wish to know what are we going to do with them. Certainly, all these scientific accomplishments will shed light on many more secrets of life. Nevertheless, parsimony in the weekly announcements of promising scientific achievements is necessary. We also need many more creative experimental biologists to discover new, as yet un-envisaged biotechnological approaches, and the basic resource needed for carrying out mile stone research necessary for leading us to that "promised land"often proclaimed by the mass media.

Hyperglycemia-induced abnormalities in rat and human corneas: the potential of second harmonic generation microscopy.

BACKGROUND: Second Harmonic Generation (SHG) microscopy recently appeared as an efficient optical imaging technique to probe unstained collagen-rich tissues like cornea. Moreover, corneal remodeling occurs in many diseases and precise characterization requires overcoming the limitations of conventional techniques. In this work, we focus on diabetes, which affects hundreds of million people worldwide and most often leads to diabetic retinopathy, with no early diagnostic tool. This study then aims to establish the potential of SHG microscopy for in situ detection and characterization of hyperglycemia-induced abnormalities in the Descemet's membrane, in the posterior cornea. METHODOLOGY/PRINCIPAL FINDINGS: We studied corneas from age-matched control and Goto-Kakizaki rats, a spontaneous model of type 2 diabetes, and corneas from human donors with type 2 diabetes and without any diabetes. SHG imaging was compared to confocal microscopy, to histology characterization using conventional staining and transmitted light microscopy and to transmission electron microscopy. SHG imaging revealed collagen deposits in the Descemet's membrane of unstained corneas in a unique way compared to these gold standard techniques in ophthalmology. It provided background-free images of the three-dimensional interwoven distribution of the collagen deposits, with improved contrast compared to confocal microscopy. It also provided structural capability in intact corneas because of its high specificity to fibrillar collagen, with substantially larger field of view than transmission electron microscopy. Moreover, in vivo SHG imaging was demonstrated in Goto-Kakizaki rats. CONCLUSIONS/SIGNIFICANCE: Our study shows unambiguously the high potential of SHG microscopy for three-dimensional characterization of structural abnormalities in unstained corneas. Furthermore, our demonstration of in vivo SHG imaging opens the way to long-term dynamical studies. This method should be easily generalized to other structural remodeling of the cornea and SHG microscopy should prove to be invaluable for in vivo corneal pathological studies.

Developmental and pathological lymphangiogenesis: from models to human disease.

The lymphatic vascular system, the body's second vascular system present in vertebrates, has emerged in recent years as a crucial player in normal and pathological processes. It participates in the maintenance of normal tissue fluid balance, the immune functions of cellular and antigen trafficking and absorption of fatty acids and lipid-soluble vitamins in the gut. Recent scientific discoveries have highlighted the role of lymphatic system in a number of pathologic conditions, including lymphedema, inflammatory diseases, and tumor metastasis. Development of genetically modified animal models, identification of lymphatic endothelial specific markers and regulators coupled with technological advances such as high-resolution imaging and genome-wide approaches have been instrumental in understanding the major steps controlling growth and remodeling of lymphatic vessels. This review highlights the recent insights and developments in the field of lymphatic vascular biology.

Prevalence of hepatitis B and C virus markers among malaria-exposed gold miners in Brazilian Amazon

Hepatitis B and C virus markers were assessed during a survey on malaria in gold mine camps in southern Brazilian Amazon in order to identify risk factors associated to these viral diseases. The study comprised 520 subjects, most of them were gold miners. Missing subjects totaled 49 (8.6%). Among these 520, 82.9% had HBV markers and 7.1% were HBsAg positive. Previous hospitalization, surgery, sexually transmitted diseases and incarceration were quite common among surveyed people, but there is no association between total HBV markers and these factors. On other hand, HBsAg was independently associated to history of sexually transmitted diseases and history of surgery after adjustment. The most frequent HBsAg subtypes identified, adw2 (59%), predominates in populations of Northeast Brazil. The most surveyed people were immigrants coming from that area suggesting that immigrants carried HBV themselves to the study area. Immunoblot (RIBA) confirmed-anti-HCV were found in 2.1%. The only variable associated to anti-HCV in multivariate analysis was illicit intravenous drug. Lack of HCV infection in subjects with such a high HBV markers prevalence reinforces the opinion that HCV is transmitted by restricted routes when compared to HBV. Furthermore, gold miners in Amazon may be considered as a risk group for HBV infection, but not for HCV.

An alternative plate tectonic model for the Palaeozoic-Early Mesozoic Palaeotethyan evolution of Southeast Asia (northern Thailand-Myanmar)

An alternative model for the geodynamic evolution of Southeast Asia is proposed and inserted in a modern plate tectonic model. The reconstruction methodology is based on dynamic plate boundaries, constrained by data such as spreading rates and subduction velocities; in this way it differs from classical continental drift models proposed so far. The different interpretations about the location of the Palaeotethys suture in Thailand are revised, the Tertiary Mae Yuam fault is seen as the emplacement of the suture. East of the suture we identify an Indochina derived terrane for which we keep the name Shan-Thai, formerly used to identify the Cimmerian block present in Southeast Asia, now called Sibumasu. This nomenclatural choice was made on the basis of the geographic location of the terrane (Eastern Shan States in Burma and Central Thailand) and in order not to introduce new confusing terminology. The closure of the Eastern Palaeotethys is related to a southward subduction of the ocean, that triggered the Eastern Neotethys to open as a back-arc, due to the presence of Late Carboniferous-Early Permian arc magmatism in Mergui (Burma) and in the Lhasa block (South Tibet), and to the absence of arc magmatism of the same age East of the suture. In order to explain the presence of Carboniferous-Early Permian and Permo-Triassic volcanic arcs in Cambodia, Upper Triassic magmatism in Eastern Vietnam and Lower Permian-Middle Permian arc volcanites in Western Sumatra, we introduce the Orang Laut terranes concept. These terranes were detached from Indochina and South China during back-arc opening of the Poko-Song Ma system, due to the westward subduction of the Palaeopacific. This also explains the location of the Cathaysian West Sumatra block to the West of the Cimmerian Sibumasu block.

Proteomics of blood and derived products: what's next?

Proteomics has changed the way proteins are analyzed in living systems. This approach has been applied to blood products and protein profiling has evolved in parallel with the development of techniques. The identification of proteins belonging to red blood cell, platelets or plasma was achieved at the end of the last century. Then, the questions on the applications emerged. Hence, several studies have focused on problems related to blood banking and products, such as the aging of blood products, identification of biomarkers, related diseases and the protein-protein interactions. More recently, a mass spectrometry-based proteomics approach to quality control has been applied in order to offer solutions and improve the quality of blood products. The current challenge we face is developing a closer relationship between transfusion medicine and proteomics. In this article, these issues will be approached by focusing first on the proteome identification of blood products and then on the applications and future developments within the field of proteomics and blood products.