Immunohistochemistry and polymerase chain reaction on paraffin-embedded material improve the diagnosis of cutaneous leishmaniasis in the Amazon region

Background Recently, there has been an increase in the incidence of cutaneous leishmaniasis (CL), which represents an important health problem. This increase may be related to the epidemiologic expansion of the infective agent and the increase in tourism in tropical areas. The difficulty in clinical diagnosis, mainly in areas in which CL is not the first consideration of local physicians, has intensified efforts to describe diagnostic tests, which should be specific, sensitive, and practical. Amongst the new tests described are those including nucleic acid amplification (polymerase chain reaction, PCR) and immunohistochemistry (IHC). Methods In this study, we evaluated the sensitivity of a PCR based on small subunit (SSU) ribosomal DNA, in comparison with IHC using Leishmania spp. antibodies, in biopsies embedded in paraffin. Result The results indicated a total sensitivity of 96% (90.9% with PCR and 68.8% with IHC), showing the possibility of using paraffin-embedded biopsies to diagnose CL. Conclusion We propose the use of the two tests together as a routine protocol for diagnosis. This would require the provision of local medical services to perform molecular biology techniques and adequate Leishmania antibodies.

A defense of backwards in time causation models in quantum mechanics

This paper offers a defense of backwards in time causation models in quantum mechanics. Particular attention is given to Cramer's transactional account, which is shown to have the threefold virtue of solving the Bell problem, explaining the complex conjugate aspect of the quantum mechanical formalism, and explaining various quantum mysteries such as Schrodinger's cat. The question is therefore asked, why has this model not received more attention from physicists and philosophers? One objection given by physicists in assessing Cramer's theory was that it is not testable. This paper seeks to answer this concern by utilizing an argument that backwards causation models entail a fork theory of causal direction. From the backwards causation model together with the fork theory one can deduce empirical predictions. Finally, the objection that this strategy is questionable because of its appeal to philosophy is deflected.

Risk Estimates of Dengue in Travelers to Dengue Endemic Areas Using Mathematical Models

Dengue has emerged as a frequent problem in international travelers. The risk depends on destination, duration, and season of travel. However, data to quantify the true risk for travelers to acquire dengue are lacking. We used mathematical models to estimate the risk of nonimmune persons to acquire dengue when traveling to Singapore. From the force of infection, we calculated the risk of dengue dependent on duration of stay and season of arrival. Our data highlight that the risk for nonimmune travelers to acquire dengue in Singapore is substantial but varies greatly with seasons and epidemic cycles. For instance, for a traveler who stays in Singapore for 1 week during the high dengue season in 2005, the risk of acquiring dengue was 0.17%, but it was only 0.00423% during the low season in a nonepidemic year such as 2002. Risk estimates based on mathematical modeling will help the travel medicine provider give better evidence-based advice for travelers to dengue endemic countries.

MICROSURGICAL ANATOMY OF THE TEMPORAL LOBE: PART 2-SYLVIAN FISSURE REGION AND ITS CLINICAL APPLICATION

OBJECTIVE: We present observations of the anatomy of the sylvian fissure region and their clinical application in neuroimaging, microsurgery for middle cerebral artery aneurysms and insular lesions, frontobasal resections, and epilepsy Surgery. METHODS: Sixty adult cadaveric hemispheres and 12 adult cadaveric heads were studied after perfusion of the arteries and veins with colored latex. The anatomic information was applied in more than 200 microsurgeries in and around the sylvian fissure region in the past 15 years. RESULTS: The sylvian fissure extends from the basal to the lateral surface of the brain and presents 2 compartments on each surface, I superficial (temporal stem and its ramii) and 1 deep (anterior and lateral operculoinsular compartments). The temporal operculum is in opposition to the frontal and parietal opercula (planum polare versus inferior frontal and precentral gyri, Heschl`s versus postcentral gyri, planum temporale versus supramarginal gyrus). The inferior frontal, precentral, and postcentral gyri cover the anterior, middle, and posterior thirds of the lateral surface of the insula, respectively. The pars triangularis covers the apex of the insula, located immediately distal to the genu of the middle cerebral artery. The clinical application of the anatomic information presented in this article is in angiography, middle cerebral artery aneurysm surgery, insular resection, frontobasal resection, and amygdalohippocampectomy, and hemispherotomy. CONCLUSION: The anatomic relationships of the sylvian fissure region can be helpful in preoperative planning and can serve as reliable intraoperative navigation landmarks in microsurgery involving that region.

VKORC1 polymorphisms in Brazilians: comparison with the Portuguese and Portuguese-speaking Africans and pharmacogenetic implications

Aims: The heterogeneity of the Brazilian population renders the extrapolation of pharmacogenomic data derived from well-defined ethnic groups inappropriate. We investigated the influence of self-reported `race/color`, geographical origin and genetic ancestry on the distribution of four VKORC1 SNPs and haplotypes in Brazilians. Comparative data were obtained from two major ancestral roots of Brazilians: Portuguese and Africans from former Portuguese colonies. Materials & methods: A total of 1037 healthy adults Brazilians, recruited at four different geographical regions and self identified as white, brown or black (race/color categories), 89 Portuguese and 216 Africans from Angola and Mozambique were genotyped for the VKORC1 3673G>A (rs9923231), 5808T>G (rs2884737), 6853G>C (rs8050894) and 9041G>A (rs7294) polymorphisms using TaqMan (R) (Applied Biosystems, CA, USA) assays. VKORC1 haplotypes were statistically inferred using the haplo.stats software. We inferred the statistical association between the distribution of the VKORC1 polymorphisms among Brazilians and self-reported color, geographical region and genetic ancestry by fitting multinomial log linear models via neural networks. Individual proportions of European and African ancestry were used to assess the impact of genetic admixture on the frequency distribution of VKORC1 polymorphisms among Brazilians, and for the comparison of Brazilians with Portuguese and Africans. Results: The frequency distribution of the 3673G>A and 5808T>G polymorphisms, and VKORC1 haplotypes among Brazilians varies across geographical regions, within self-reported color categories and according to the individual proportions of European and African genetic ancestry. Notably, the frequency of the warfarin sensitive VKORC1 3673A allele and the distribution of VKORC1 haplotypes varied continuously as the individual proportion of European ancestry increased in the entire cohort, independently of race/color categorization and geographical origin. Brazilians with more than 80% African ancestry differ significantly from Angolans and Mozambicans in frequency of the 3673G>A, 5808T>G and 6853G>C polymorphisms and haplotype distribution, whereas no such differences are observed between Brazilians with more than 90% European ancestry and Portuguese individuals. Conclusion: The diversity of the Brazilian population, evident in the distribution of VKORC1 polymorphisms, must be taken into account in the design of pharmacogenetic clinical trials and dealt with as a continuous variable. Warfarin dosing algorithms that include `race` terms defined for other populations are clearly not applicable to the heterogeneous and extensively admixed Brazilian population.

A prospective study on the dynamics of the clinical and immunological evolution of human Leishmania (L.) infantum chagasi infection in the Brazilian Amazon region

This prospective study was carried out from October 2003 to December 2005 and involved a cohort of 946 individuals of both genders, aged 1-89 years, from an endemic area for American visceral leishmaniasis (AVL), in Para State, Brazil. The aim of the study was to analyze the dynamics of the clinical and immunological evolution of human Leishmania ( L.) infantum chagasi infection represented by the following clinical-immunological profiles: asymptomatic infection (AI); symptomatic infection (SI = AVL); subclinical oligosymptomatic infection (SOI); subclinical resistant infection (SRI); and indeterminate initial infection (III). Infection diagnosis was determined by the indirect fluorescent antibody test and leishmanin skin test. In total, 231 cases of infection were diagnosed: the AI profile was the most frequent (73.2%), followed by SRI (12.1%), III (9.9%), SI (2.6%) and SOI (2.2%). The major conclusion regarding evolution dynamics was that the III profile plays a pivotal role from which the cases evolve to either the resistant, SRI and AI, or susceptible, SOI and SI, profiles; only one of the 23 III cases evolved to SI, while most evolved to either SRI (nine cases) or SOI (five cases) and eight cases remained as III. (C) 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

A cross-sectional study on the clinical and immunological spectrum of human Leishmania (L.) infantum chagasi infection in the Brazilian Amazon region

The objectives of this study were to identify individuals with symptomatic and/or asymptomatic infection due to Leishmania (L.) infantum chagasi; to study the two types of infection, both clinically and immunologically, and to determine the prevalence rate of infection at the beginning of the study. This was a cross-sectional study with a cohort of 946 individuals, of both genders, from the age of 1 year, living in the municipality of Barcarena, PA, Brazil, an area endemic for American visceral leishmaniasis (AVL). The leishmanin skin test (LST) and the indirect fluorescent test (IFAT), were used for the diagnosis of infection. One hundred and twenty cases of infection were diagnosed, with a prevalence rate of 12.6%; eight cases showed high seroreactivity (1280-10240, IgG) in IFAT and no LST reaction; four of these cases were typical AVL and four had subclinical oligosymptomatic infection. Using two immunological methods with a clinical examination of the infected individuals enabled the identification of five clinical-immunological profiles which may promote a better understanding of the interaction between L. (L.) i. chagasi and the human immune response: asymptomatic infection (AI) 73.4%; subclinical resistant infection (SRI) 15%; subclinicat oligosymptomatic infection (SOI) 3%; symptomatic infection (AVL) 3% and indeterminate initial infection (III) 5%. (C) 2009 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Childhood adversities as risk factors for onset and persistence of suicidal behaviour

Background Suicide is a leading cause of death worldwide, but the precise effect of childhood adversities as risk factors for the onset and persistence of suicidal behaviour (suicide ideation, plans and attempts) are not well understood. Aims To examine the associations between childhood adversities as risk factors for the onset and persistence of suicidal behaviour across 21 countries worldwide. Method Respondents from nationally representative samples (n = 55 299) were interviewed regarding childhood adversities that occurred before the age of 18 years and lifetime suicidal behaviour. Results Childhood adversities were associated with an increased risk of suicide attempt and ideation in both bivariate and multivariate models (odds ratio range 1.2-5.7). The risk increased with the number of adversities experienced, but at a decreasing rate. Sexual and physical abuse were consistently the strongest risk factors for both the onset and persistence of suicidal behaviour, especially during adolescence. Associations remained similar after additional adjustment for respondents` lifetime mental disorder status. Conclusions Childhood adversities (especially intrusive or aggressive adversities) are powerful predictors of the onset and persistence of suicidal behaviours.