Incidence and transmission patterns of tuberculosis among indigenous populations in Brazil

Approximately 10% of the Brazilian indigenous population lives in the state of Mato Grosso do Sul (MS), where a large number of new cases of tuberculosis (TB) are reported. This study was conducted to assess TB occurrence, transmission and the utility of TB diagnosis based on the Ogawa-Kudoh (O-K) culture method in this remote population. The incidence of TB was estimated by a retrospective review of the surveillance data maintained by the Notifiable Diseases Surveillance System for the study region. The TB transmission pattern among indigenous people was assessed by genotyping Mycobacterium tuberculosis isolates using the IS 6110restriction fragment length polymorphism (RFLP) technique. Of the 3,093 cases identified from 1999-2001, 610 (~20%) were indigenous patients (average incidence: 377/100,000/year). The use of the O-K culture method increased the number of diagnosed cases by 34.1%. Of the genotyped isolates from 52 indigenous patients, 33 (63.5%) belonged to cluster RFLP patterns, indicating recently transmitted TB. These results demonstrate high, on-going TB transmission rates among the indigenous people of MS and indicate that new efforts are needed to disrupt these current transmissions.

Accompagnement thérapeutique : le chemin du suivi à long terme [Patient education: the way for long-term follow up]

L'éducation thérapeutique du patient est maintenant parfaitement intégrée dans les soins. Son champ d'application se situe essentiellement dans le domaine des maladies chroniques pour l'acquisition de compétences dans la gestion du traitement, en coopération avec les professionnels. En médecine ambulatoire, patients et soignants se heurtent actuellement aux difficultés du suivi avec sa part d'incertitude, lassitude et de pression économique. La médecine fondée sur les preuves (EBM) et les différents modèles en psychologie de la santé ne nous éclairent que partiellement le chemin. Un nouveau type de démarche réflexive est en train d'émerger. Cette réflexion devrait placer en son centre la notion de relation thérapeutique : entre science et existence. Nous résumons ici ce processus réflexif en cours d'une équipe interdisciplinaire regroupant sciences humaines, art et médecine. Therapeutic education is now perfectly integrated in caring and medicine. Its field of application is primarily in chronic diseases for the acquisition of competences in the management of treatments, in co-operation with health professionals. In ambulatory medicine, patients and health professionals are currently running up against the difficulties of the long-term follow-up with its part of uncertainty, lassitude and economic pressure. EBM and the various models of health psychology light us only partially the way. A new type of reflexive step is emerging. This way of thinking should place in its center the concept of therapeutic relation: between science and being. We summarize here our reflexive process in the course of an interdisciplinary team gathering social sciences, art and medicine

A decade of malaria during pregnancy in Brazil: what has been done concerning prevention and management

In Brazil, malaria remains a disease of major epidemiological importance because of the high number of cases in the Amazonian Region. Plasmodium spp infections during pregnancy are a significant public health problem with substantial risks for the pregnant woman, the foetus and the newborn child. In Brazil, the control of malaria during pregnancy is primarily achieved by prompt and effective treatment of the acute episodes. Thus, to assure rapid diagnosis and treatment for pregnant women with malaria, one of the recommended strategy for low transmission areas by World Health Organization and as part of a strategy by the Ministry of Health, the National Malaria Control Program has focused on integrative measures with woman and reproductive health. Here, we discuss the approach for the prevention and management of malaria during pregnancy in Brazil over the last 10 years (2003-2012) using morbidity data from Malaria Health Information System. Improving the efficiency and quality of healthcare and education and the consolidation of prevention programmes will be challenges in the control of malaria during pregnancy in the next decade.

Education and male-female differences in later-life cognition: international evidence from latin america and the Caribbean.

This study explores the role of early-life education for differences in cognitive functioning between men and women aged 60 and older from seven major urban areas in Latin America and the Caribbean. After documenting statistically significant differences in cognitive functioning between men and women for six of the seven study sites, I assess the extent to which these differences can be explained by prevailing male-female differences in education. I decompose predicted male-female differences in cognitive functioning based on various statistical models for later-life cognition and find robust evidence that male-female differences in education are a major driving force behind cognitive functioning differences between older men and women. This study therefore suggests that early-life differences in educational attainment between boys and girls during childhood have a lasting impact on gender inequity in cognitive functioning at older ages. Increases in educational attainment and the closing of the gender gap in education in many countries in Latin America and the Caribbean may thus result in both higher levels and a more gender-equitable distribution of later-life cognition among the future elderly in those countries.

Markers of atherosclerosis and of inflammation for prediction of coronary heart disease in older adults

BACKGROUND: Several markers of atherosclerosis and of inflammation have been shown to predict coronary heart disease (CHD) individually. However, the utility of markers of atherosclerosis and of inflammation on prediction of CHD over traditional risk factors has not been well established, especially in the elderly. METHODS: We studied 2202 men and women, aged 70-79, without baseline cardiovascular disease over 6-year follow-up to assess the risk of incident CHD associated with baseline noninvasive measures of atherosclerosis (ankle-arm index [AAI], aortic pulse wave velocity [aPWV]) and inflammatory markers (interleukin-6 [IL-6], C-reactive protein [CRP], tumor necrosis factor-a [TNF-a]). CHD events were studied as either nonfatal myocardial infarction or coronary death ("hard" events), and "hard" events plus hospitalization for angina, or the need for coronary-revascularization procedures (total CHD events). RESULTS: During the 6-year follow-up, 283 participants had CHD events (including 136 "hard" events). IL-6, TNF-a and AAI independently predicted CHD events above Framingham Risk Score (FRS) with hazard ratios [HR] for the highest as compared with the lowest quartile for IL-6 of 1.95 (95%CI: 1.38-2.75, p for trend<0.001), TNF-a of 1.45 (95%CI: 1.04-2.02, p for trend 0.03), of 1.66 (95%CI: 1.19-2.31) for AAI £0.9, as compared to AAI 1.01-1.30. CRP and aPWV were not independently associated with CHD events. Results were similar for "hard" CHD events. Addition of IL-6 and AAI to traditional cardiovascular risk factors yielded the greatest improvement in the prediction of CHD; C-index for "hard"/total CHD events increased from 0.62/0.62 for traditional risk factors to 0.64/0.64 for IL-6 addition, 0.65/0.63 for AAI, and 0.66/0.64 for IL-6 combined with AAI. Being in the highest quartile of IL-6 combined with an AAI £ 0.90 or >1.40 yielded an HR of 2.51 (1.50-4.19) and 4.55 (1.65-12.50) above FRS, respectively. With use of CHD risk categories, risk prediction at 5 years was more accurate in models that included IL-6, AAI or both, with 8.0, 8.3 and 12.1% correctly reclassified respectively. CONCLUSIONS: Among older adults, markers of atherosclerosis and of inflammation, particularly IL-6 and AAI, are independently associated with CHD. However, these markers only modestly improve cardiovascular risk prediction beyond traditional risk factors. Acknowledgments: This study was supported by Contracts NO1-AG-6-2101, NO1-AG-6- 2103, and NO1-AG-6-2106 of the National Institute on Aging. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.

Framingham risk score and alternatives for prediction of coronary heart disease in older adults.

BACKGROUND: Guidelines for the prevention of coronary heart disease (CHD) recommend use of Framingham-based risk scores that were developed in white middle-aged populations. It remains unclear whether and how CHD risk prediction might be improved among older adults. We aimed to compare the prognostic performance of the Framingham risk score (FRS), directly and after recalibration, with refit functions derived from the present cohort, as well as to assess the utility of adding other routinely available risk parameters to FRS.¦METHODS: Among 2193 black and white older adults (mean age, 73.5 years) without pre-existing cardiovascular disease from the Health ABC cohort, we examined adjudicated CHD events, defined as incident myocardial infarction, CHD death, and hospitalization for angina or coronary revascularization.¦RESULTS: During 8-year follow-up, 351 participants experienced CHD events. The FRS poorly discriminated between persons who experienced CHD events vs. not (C-index: 0.577 in women; 0.583 in men) and underestimated absolute risk prediction by 51% in women and 8% in men. Recalibration of the FRS improved absolute risk prediction, particulary for women. For both genders, refitting these functions substantially improved absolute risk prediction, with similar discrimination to the FRS. Results did not differ between whites and blacks. The addition of lifestyle variables, waist circumference and creatinine did not improve risk prediction beyond risk factors of the FRS.¦CONCLUSIONS: The FRS underestimates CHD risk in older adults, particularly in women, although traditional risk factors remain the best predictors of CHD. Re-estimated risk functions using these factors improve accurate estimation of absolute risk.

Modification of the Perrine-Baum diagram to improve the calculation of high voltage electric lines

Through the history of Electrical Engineering education, vectorial and phasorial diagrams have been used as a fundamental learning tool. At present, computational power has replaced them by long data lists, the result of solving equation systems by means of numerical methods. In this sense, diagrams have been shifted to an academic background and although theoretically explained, they are not used in a practical way within specific examples. This fact may be against the understanding of the complex behavior of the electrical power systems by students. This article proposes a modification of the classical Perrine-Baum diagram construction to allowing both a more practical representation and a better understanding of the behavior of a high-voltage electric line under different levels of load. This modification allows, at the same time, the forecast of the obsolescence of this behavior and line’s loading capacity. Complementary, we evaluate the impact of this tool in the learning process showing comparative undergraduate results during three academic years

Risk factors of obesity and their determinants in preschool children (the Swiss Ballabeina study)

This thesis has been conducted in the context of a lifestyle intervention in 40 Swiss kindergarten classes in the cantons St. Gallen and Vaud, in areas with a high migrant prevalence (Ballabeina study). The main objective of this work was to fill certain gaps of the literature and to bring a better understanding of the risk factors of overweight and obesity and their determinants in preschool children. Our data show that parental migrant status and educational level influence independently of each other adiposity and/or eating habits in these children. In addition, sports club participation at this young age seems to be a better indicator of healthy lifestyle characteristics in terms of physical activity, sedentary behaviour and eating habits than weight status. Finally, we found that in this population higher scores of hyperactivity/inattention are associated with lower adiposity and with both healthy (more physical activity and less sedentary activity) and unhealthy (more television viewing and more unhealthy eating habits) lifestyle characteristics. Thus, our findings can be used by different actors of health and education system to better target their preventive actions and can serve as a basis for future complementary researches. - Cette thèse a été réalisée dans le cadre d'un projet de promotion de la santé mené dans 40 classes enfantines suisses issues de régions à forte prévalence migrante des cantons de St. Gall et de Vaud (étude Ballabeina). L'objectif principal de ce travail était de combler certaines lacunes de la littérature et d'approfondir nos connaissances sur les facteurs de risque du surpoids et de l'obésité et de leurs déterminants chez les enfants d'âge préscolaire. Nos analyses montrent que le statut de migrant des parents et leur niveau d'éducation influencent indépendamment l'un de l'autres l'adiposité et les habitudes alimentaires chez ces enfants. De plus, à ce jeune âge la participation dans un club de sport semble être un meilleur indicateur de style de vie sain en termes d'activité physique, de comportements sédentaires et d'habitudes alimentaires que le statut pondéral. Nous avons également trouvé que dans cette population, un score plus élevé d'hyperactivité/inattention est associé aussi bien à des caractéristiques de style de vie saines (plus d'activité physique, moins d'activité sédentaire) que malsaines (plus de consommation de télévision et moins bonnes habitudes alimentaire. Ainsi, nos résultats peuvent aider les différents acteurs de la santé et de l'éducation à mieux cibler leurs actions de prévention et servir de base à de futures recherches complémentaires.

Epidemiology of inflammatory bowel disease: Is there a shift towards onset at a younger age?

OBJECTIVES: Increasing numbers of paediatric and adolescent patients with Crohn disease (CD) and ulcerative colitis (UC) are reported. To determine whether this observation is a consequence of a shift towards onset at a younger age, we analysed retrospective data from patients enrolled in the Swiss IBD Cohort Study (SIBDCS). PATIENTS AND METHODS: The SIBDCS is a disease-based cohort in Switzerland, which collects retrospective and prospective data on a large sample of patients with inflammatory bowel disease (IBD). Patients, diagnosed from 1980, were stratified according to diagnosis of CD and UC. Age at disease onset (age at first symptoms and age at diagnosis) was analysed in relation to calendar year of disease onset. Data were extracted from physician and patient questionnaires. Linear regressions of age at disease onset by calendar year of disease onset adjusted by sex, country of birth, and education were performed. RESULTS: Adjusted regression coefficients for CD and UC were significantly positive, that is, age at disease onset has increased with time. Male sex was associated with an increase in age at disease onset, and birth in Switzerland with a decrease. These associations were statistically significant. CONCLUSIONS: The results from the SIBDCS do not support the hypothesis that disease onset of both CD and UC occur today at a younger age. On the contrary, our results show that there is a significant trend for age at disease onset occurring at an older age today as compared with recent decades. We conclude that the observation of increasing numbers of paediatric and adolescent patients with IBD is not caused by a trend towards disease onset at a younger age, but that this may rather be a consequence of the overall increasing incidence of these conditions.

Medicine and Science in a New Medical-surgical Context: The Royal College of Surgery of Barcelona (1760–1843)

Taking the Royal College of Barcelona (1760 -1843) as a case study this paper shows the development of modern surgery in Spain initiated by Bourbon Monarchy founding new kinds of institutions through their academic activities of spreading scientific knowledge. Antoni Gimbernat was the most famousinternationally recognised Spanish surgeon. He was trained as a surgeon at the Royal College of Surgery in Cadiz and was later appointed as professor of theAnatomy in the College of Barcelona. He then became Royal Surgeon of King Carlos IV and with that esteemed position in Madrid he worked resiliently to improve the quality of the Royal colleges in Spain. Learning human bodystructure by performing hands-on dissections in the anatomical theatre has become a fundamental element of modern medical education. Gimbernat favoured the study of natural sciences, the new chemistry of Lavoisier and experimental physics in the academic programs of surgery. According to the study of a very relevant set of documents preserved in the library, the so-called “juntas literarias”, among the main subjects debated in the clinical sessions was the concept of human beings and diseases in relation to the development of the new experimental sciences. These documents showed that chemistry andexperimental physics were considered crucial tools to understand the unexplained processes that occurred in the diseased and healthy human bodyand in a medico-surgical context. It is important to stress that through these manuscripts we can examine the role and the reception of the new sciences applied to healing arts.

Network-guided analysis of genes with altered somatic copy number and gene expression reveals pathways commonly perturbed in metastatic melanoma.

Cancer genomes frequently contain somatic copy number alterations (SCNA) that can significantly perturb the expression level of affected genes and thus disrupt pathways controlling normal growth. In melanoma, many studies have focussed on the copy number and gene expression levels of the BRAF, PTEN and MITF genes, but little has been done to identify new genes using these parameters at the genome-wide scale. Using karyotyping, SNP and CGH arrays, and RNA-seq, we have identified SCNA affecting gene expression ('SCNA-genes') in seven human metastatic melanoma cell lines. We showed that the combination of these techniques is useful to identify candidate genes potentially involved in tumorigenesis. Since few of these alterations were recurrent across our samples, we used a protein network-guided approach to determine whether any pathways were enriched in SCNA-genes in one or more samples. From this unbiased genome-wide analysis, we identified 28 significantly enriched pathway modules. Comparison with two large, independent melanoma SCNA datasets showed less than 10% overlap at the individual gene level, but network-guided analysis revealed 66% shared pathways, including all but three of the pathways identified in our data. Frequently altered pathways included WNT, cadherin signalling, angiogenesis and melanogenesis. Additionally, our results emphasize the potential of the EPHA3 and FRS2 gene products, involved in angiogenesis and migration, as possible therapeutic targets in melanoma. Our study demonstrates the utility of network-guided approaches, for both large and small datasets, to identify pathways recurrently perturbed in cancer.

Systematic Identification of High Crash Locations Final Report, 2001

Federal and state policy makers increasingly emphasize the need to reduce highway crash rates. This emphasis is demonstrated in Iowa’s recently released draft Iowa Strategic Highway Safety Plan and by the U.S. Department of Transportation’s placement of “improved transportation safety” at the top of its list of strategic goals. Thus, finding improved methods to enhance highway safety has become a top priority at highway agencies. The objective of this project is to develop tools and procedures by which Iowa engineers can identify potentially hazardous roadway locations and designs, and to demonstrate the utility of these tools by developing candidate lists of high crash locations in the State. An initial task, building an integrated database to facilitate the tools and procedures, is an important product, in and of itself. Accordingly, the Iowa Department of Transportation (Iowa DOT) Geographic Information Management System (GIMS) and Geographic Information System Accident Analysis and Location System (GIS-ALAS) databases were integrated with available digital imagery. (The GIMS database contains roadway characteristics, e.g., lane width, surface and shoulder type, and traffic volume, for all public roadways. GIS-ALAS records include data, e.g., vehicles, drivers, roadway conditions, and the crash severity, for crashes occurring on public roadways during then past 10 years.)

Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders

Genetic and functional data indicate that variation in the expression of the neurotrophin-3 receptor gene (NTRK3) may have an impact on neuronal plasticity, suggesting a role for NTRK3 in the pathophysiology of anxiety disorders. MicroRNA (miRNA) posttranscriptional gene regulators act by base-pairing to specific sequence sites, usually at the 3'UTR of the target mRNA. Variants at these sites might result in gene expression changes contributing to disease susceptibility. We investigated genetic variation in two different isoforms of NTRK3 as candidate susceptibility factors for anxiety by resequencing their 3'UTRs in patients with panic disorder (PD), obsessive-compulsive disorder (OCD), and in controls. We have found the C allele of rs28521337, located in a functional target site for miR-485-3p in the truncated isoform of NTRK3, to be significantly associated with the hoarding phenotype of OCD. We have also identified two new rare variants in the 3'UTR of NTRK3, ss102661458 and ss102661460, each present only in one chromosome of a patient with PD. The ss102661458 variant is located in a functional target site for miR-765, and the ss102661460 in functional target sites for two miRNAs, miR-509 and miR-128, the latter being a brain-enriched miRNA involved in neuronal differentiation and synaptic processing. Interestingly, these two variants significantly alter the miRNA-mediated regulation of NTRK3, resulting in recovery of gene expression. These data implicate miRNAs as key posttranscriptional regulators of NTRK3 and provide a framework for allele-specific miRNA regulation of NTRK3 in anxiety disorders.

HER2 shedding and serum HER2 extracellular domain: Biology and clinical utility in breast cancer.

The transmembrane protein HER2 is over-expressed in approximately 15% of invasive breast cancers as a result of HER2 gene amplification. HER2 proteolytic cleavage (HER2 shedding) generates soluble truncated HER2 molecules that include only the extracellular domain and the concentration of which can be measured in the serum fraction of blood. HER2 shedding also generates a constitutively active truncated intracellular receptor of 95kDa (p95(HER2)). Another soluble truncated HER2 protein (Herstatin), which can also be found in serum, is the product of an alternatively spliced HER2 transcript. Recent preclinical findings may provide crucial insights into the biological and clinical relevance of increased sHER2 concentrations for the outcome of HER2-positive breast cancer and sensitivity to trastuzumab and lapatinib treatment. We present here the most recent findings about the role and biology of sHER2 based on data obtained using a standardized test, which has been cleared by FDA in 2000, for measuring sHER2. This test includes quality control assessments and has been already widely used to evaluate the clinical utility of sHER2 as a biomarker in breast cancer. We will describe in detail data concerning the assessment of sHER2 as a surrogate maker to optimize the evaluation of the HER2 status of a primary tumor and as a prognosis and predictive marker of response to therapies, both in early and metastatic breast cancer.

Variability of voriconazole plasma levels measured by new high-performance liquid chromatography and bioassay methods.

Voriconazole (VRC) is a broad-spectrum antifungal triazole with nonlinear pharmacokinetics. The utility of measurement of voriconazole blood levels for optimizing therapy is a matter of debate. Available high-performance liquid chromatography (HPLC) and bioassay methods are technically complex, time-consuming, or have a narrow analytical range. Objectives of the present study were to develop new, simple analytical methods and to assess variability of voriconazole blood levels in patients with invasive mycoses. Acetonitrile precipitation, reverse-phase separation, and UV detection were used for HPLC. A voriconazole-hypersusceptible Candida albicans mutant lacking multidrug efflux transporters (cdr1Delta/cdr1Delta, cdr2Delta/cdr2Delta, flu1Delta/flu1Delta, and mdr1Delta/mdr1Delta) and calcineurin subunit A (cnaDelta/cnaDelta) was used for bioassay. Mean intra-/interrun accuracies over the VRC concentration range from 0.25 to 16 mg/liter were 93.7% +/- 5.0%/96.5% +/- 2.4% (HPLC) and 94.9% +/- 6.1%/94.7% +/- 3.3% (bioassay). Mean intra-/interrun coefficients of variation were 5.2% +/- 1.5%/5.4% +/- 0.9% and 6.5% +/- 2.5%/4.0% +/- 1.6% for HPLC and bioassay, respectively. The coefficient of concordance between HPLC and bioassay was 0.96. Sequential measurements in 10 patients with invasive mycoses showed important inter- and intraindividual variations of estimated voriconazole area under the concentration-time curve (AUC): median, 43.9 mg x h/liter (range, 12.9 to 71.1) on the first and 27.4 mg x h/liter (range, 2.9 to 93.1) on the last day of therapy. During therapy, AUC decreased in five patients, increased in three, and remained unchanged in two. A toxic encephalopathy probably related to the increase of the VRC AUC (from 71.1 to 93.1 mg x h/liter) was observed. The VRC AUC decreased (from 12.9 to 2.9 mg x h/liter) in a patient with persistent signs of invasive aspergillosis. These preliminary observations suggest that voriconazole over- or underexposure resulting from variability of blood levels might have clinical implications. Simple HPLC and bioassay methods offer new tools for monitoring voriconazole therapy.