Population medical genetics: translating science to the community.

Rare genetic disorders are currently in the spotlight due to the elevated number of different conditions and significant total number of affected patients. The study of these disorders is extremely helpful for the elucidation of physiological processes related with complex disorders. Isolated populations are instrumental for the study of genetic disorders, considering their homogeneity and high proportion of affected patients in a small geographic area. These favorable conditions lead to the creation of a new discipline, known as "population medical genetics", which integrates medical genetics, population genetics, epidemiological genetics and community genetics. In order to develop practical activities in this new discipline, the National Institute of Population Medical Genetics (INaGeMP) was created in 2008 in Brazil. INaGeMP has developed several tools and funded numerous research activities. In this review, we highlight three successful projects developed in the first 10 years of INaGeMP activities (2008-2018): a newborn screening pilot study for MPS VI in Northeast Brazil, the study of Machado-Joseph disease in Brazilian families with Azorian ancestry, and the high twinning rate in a small town in southern Brazil. The results of these projects in terms of scientific output and contributions to the affected communities highlight the success and importance of INaGeMP.

Lack of association between genetic polymorphisms in IGF1 and IGFBP3 with twin births in a Brazilian population (Cândido Godói, Rio Grande do Sul).

Insulin-like growth factor (IGF-1) is an important peptide hormone involved in the reproduction and fetal development of mammals, and it is suggested that it may influence the human twinning rate. This study aimed to test such possible association, investigating the genetic polymorphisms IGF1 (CA)n and IGFBP3 rs2854744 in the population from Candido Godoi (CG), a small city located in the South of Brazil that has a high prevalence of twin births. A case-control study was performed comprising a total of 39 cases (representing about 40% of the mothers of twins who were born in CG after 1995) and 214 controls (mothers of non-twin children), 97 of whom were living in CG while 117 were living in Porto Alegre. DNA was extracted from blood leucocytes and genotyping was performed. According to the statistical analyses, there was no significant difference in the frequencies of both studied genetic polymorphisms when comparing case group with control group. Thus, our results pointed to a lack of association between IGF1 (CA)n and IGFBP3 rs2854744 polymorphisms and twin births in CG, but further investigations in other populations with different characteristics must be performed to confirm the role of IGF-I in human twinning.

How strong was the bottleneck associated to the peopling of the Americas? New insights from multilocus sequence data.

In spite of many genetic studies that contributed for a deep knowledge about the peopling of the Americas, no consensus has emerged about important parameters such as the effective size of the Native Americans founder population. Previous estimates based on genomic datasets may have been biased by the use of admixed individuals from Latino populations, while other recent studies using samples from Native American individuals relied on approximated analytical approaches. In this study we use resequencing data for nine independent regions in a set of Native American and Siberian individuals and a full-likelihood approach based on isolation-with-migration scenarios accounting for recent flow between Asian and Native American populations. Our results suggest that, in agreement with previous studies, the effective size of the Native American population was small, most likely in the order of a few hundred individuals, with point estimates close to 250 individuals, even though credible intervals include a number as large as ~4,000 individuals. Recognizing the size of the genetic bottleneck during the peopling of the Americas is important for determining the extent of genetic markers needed to characterize Native American populations in genome-wide studies and to evaluate the adaptive potential of genetic variants in this population.

Music genetics research: Association with musicality of a polymorphism in the AVPR1A gene.

Musicality is defined as a natural tendency, sensibility, knowledge, or talent to create, perceive, and play music. Musical abilities involve a great range of social and cognitive behaviors, which are influenced by both environmental and genetic factors. Although a number of studies have yielded insights into music genetics research, genes and biological pathways related to these traits are not fully understood. Our hypothesis in the current study is that genes associated with different behaviors could also influence the musical phenotype. Our aim was to investigate whether polymorphisms in six genes (AVPR1A, SLC6A4, ITGB3, COMT, DRD2 and DRD4) related to social and cognitive traits are associated with musicality in a sample of children. Musicality was assessed through an individualized music therapy assessment profile (IMTAP) which has been validated in Brazil to measure musical ability. We show here that the RS1 microsatellite of the AVPR1A gene is nominally associated with musicality, corroborating previous results linking AVPR1A with musical activity. This study is one of the first to investigate musicality in a comprehensive way, and it contributes to better understand the genetic basis underlying musical ability.

Distinct patterns of yeast cell morphology and host responses induced by representative strains of Paracoccidioides brasiliensis (Pb18) and Paracoccidioides lutzii (Pb01).

Paracoccidioidomycosis (PCM) is a systemic mycosis, widespread in Latin America. PCM is a granulomatous disease characterized by a polymorphism of lesions depending on the pathogen's virulence, the immune status of the host and its genetic susceptibility. The thermodimorphic fungus Paracoccidioides brasiliensis was considered the only etiologic agent of PCM, yet recent works have shown significant genetic diversity among different strains of P. brasiliensis. Therefore, it has been proposed for a new species within the Paracoccidioides genus, named Paracoccidioides lutzii. To better understand the fungus-host interactions elicited by strains Pb01 and Pb18 as key representatives of P. lutzii and P. brasiliensis, respectively, we carried out studies to investigate differences in morphology, induced immune response, virulence and pathology between these two Paracoccidioides species. Our results demonstrate distinct patterns of host-parasite interaction and pathology caused by Pb18 and Pb01. These results open up new fronts for NEW: clinical studies, which may result in significant consequences for the diagnosis and treatment of PCM. Considering that our results cannot be extended to all strains of both species, more studies about the virulence among Paracoccioides must be explored in the future.

So close, so far away: analysis of surnames in a town of twins (Cândido Godói, Brazil).

Cândido Godói is a small Brazilian town known for high rates of twin birth. In 2011, a genetic study showed that this localized high rate of twin births could be explained by a genetic founder effect. Here we used isonymic analysis and surname distribution to identify population subgroups within 5316 inhabitants and 665 different surnames. Four clusters were constructed based on different twin rates (P < 0.001; MRPP test). Fisher's α and consanguinity index showed low and high values, respectively, corresponding with observed values in isolated communities with high levels of genetic drift. Values of A and B estimators confirmed population isolation. Three boundaries were identified with Monmonier's maximum difference algorithm (P = 0.007). Inside the isolated sections, surnames of different geographic origins, language, and religion were represented. With an adequate statistical methodology, surname analyses provided a close approximation of historic and socioeconomic background at the moment of colony settlement. In this context, the maintenance of social and cultural practices had strong implications for the population's structure leading to drift processes in this small town, supporting the previous genetic study.

Polymorphisms in the endothelial nitric oxide synthase gene in thalidomide embryopathy.

Thalidomide is one of the most potent teratogens known to humans. It is currently used for many clinical situations such as treatment of leprosy reactions and multiple myeloma. However, the teratogenic mechanisms by which it produces morphological defects still remain unclear. One of the hypotheses is the blockage of angiogenesis by reduction of nitric oxide (NO). In this study, we evaluated two functional polymorphisms of the endothelial nitric oxide synthase (eNOS) gene which is a constitutively expressed enzyme responsible for production of NO. The promoter -786T>C exon 7 (896G>T) polymorphisms were genotyped using real-time PCR for 28 individuals with thalidomide embryopathy (TE), 27 first-degree relatives of these individuals, and 68 individuals from the general population. Their allele, genotypic, and haplotypic frequencies were compared. A significant difference was observed in the -786T>C polymorphism genotypes (p=0.03) between the groups affected by TE and those unaffected (non-relatives). The TT genotype of the 896G>T polymorphism was observed in 10.7% of those affected and 2.9% of those unaffected, but the difference was not statistically significant (p=0.09). The haplotypic analysis indicated that the wild haplotype -786T/896G was distributed differently in the affected and unaffected groups (p=0.004). These results indicate that the individuals with TE have a higher frequency of alleles associated with lower expression of eNOS, indicating that this may be a genotype susceptible to TE.

DNA-hsp65 vaccine as therapeutic strategy to treat experimental chromoblastomycosis caused by Fonsecaea pedrosoi.

Chromoblastomycosis (CBM) is a chronic subcutaneous mycosis, caused by several dimorphic, pigmented dematiaceous fungi. Patients with the disease are still considered a therapeutic challenge, mainly due to its recalcitrant nature. There is no "gold standard" treatment for this neglected mycosis, but rather there are several treatment options. Chemotherapy alternatives include 5-flucytosine, itraconazole, terbinafine, fluconazole, thiabendazole, ketoconazole and amphotericin B, although the healing of severe cases is still uncommon. However, several studies have reported the DNA vaccine to be promising in the treatment for fungal infections; this vaccine allows the host to restore depressed cellular immunity, minimizing the toxic effects from conventional antifungal therapies. This work was therefore carried out aiming to establish a suitable model for experimental CBM, suggesting also new therapies, including DNA-hsp65 vaccine. By analyzing the morphometrical and histopathological aspects and by quantifying the fungal burden, the results showed the establishment of a chronic, although transitory, experimental CBM model with lesions similar to those presented in humans. A treatment regimen using intralesional itraconazole or amphotericin B was effective in treating experimental CBM, as was a therapy using naked DNA-hsp65 vaccine. It has also been shown that chemotherapy associated with DNA-hsp65 vaccine is promising in the treatment for CBM.

ß2 Integrin-Mediated Susceptibility to Paracoccidioides brasiliensis Experimental Infection in Mice.

The earliest interaction between macrophages and Paracoccidioides brasiliensis is particularly important in paracoccidioidomycosis (PCM) progression, and surface proteins play a central role in this process. The present study investigated the contribution of ß2 integrin in P. brasiliensis-macrophage interaction and PCM progression. We infected ß2-low expression (CD18low) and wild type (WT) mice with P. brasiliensis 18. Disease progression was evaluated for fungal burden, lung granulomatous lesions, nitrate levels, and serum antibody production. Besides, the in vitro capacity of macrophages to internalize and kill fungal yeasts was investigated. Our results revealed that CD18low mice infected with Pb18 survived during the time analyzed; their lungs showed fewer granulomas, a lower fungal load, lower levels of nitrate, and production of high levels of IgG1 in comparison to WT animals. Our results revealed that in vitro macrophages from CD18low mice slowly internalized yeast cells, showing a lower fungal burden compared to WT cells. The migration capacity of macrophages was compromised and showed a higher intensity in the lysosome signal when compared with WT mice. Our data suggest that ß2 integrins play an important role in fungal survival inside macrophages, and once phagocytosed, the macrophage may serve as a protective environment for P. brasiliensis.

Genetic variants linked to folliculogenesis and successful pregnancy are not associated with twin births in a twins' town.

Background: Cândido Godói (CG) is a small city in South Brazil in which natural twin births (both monozygotic and dizygotic) occur at an unusually high rate and the twin trait runs through the local families, which are mostly European descendants. We have argued that a genetic founder effect must have occurred during the settlement of CG and that genetic factors may help to explain the familial aggregation of twinning in that city.Objective: The aim of this study was to evaluate single nucleotide polymorphisms (SNPs) related to folliculogenesis (rs6166:C > T in FSHR, rs11031006:G > A near FSHB, and rs17293443:T > C in SMAD3) and successful pregnancies (rs2010963:C > G in VEGFA, rs1800629:G > A in TNF, rs1801131:T > G and rs1801133:G > A in MTHFR) in mothers from CG.Study design: Forty-four mothers of twins (the case group) and 102 mothers of singletons (the control group) from CG were investigated. Genotypes were determined using real-time PCR (TaqMan® SNP Genotyping Assay).Results: For all SNPs, the distributions of the genotypic and allelic frequencies were similar between cases and controls. Interestingly, a deviation from the Hardy-Weinberg equilibrium was detected for SNP rs11031006:G > A near FSHB in the control population. Different combinations of risk alleles and haplotypic analyses were homogeneously distributed between cases and controls.Conclusion: These results suggest a lack of association between the seven studied SNPs and twin births in CG. However, we hypothesized that other genetic variants related to folliculogenesis or successful pregnancies may be involved in this phenomenon. Identifying such genetic components may be important not only for the Brazilian "Twins' Town" but also for a better understanding of twinning in general.

Bone regeneration in a mouse model of type 1 diabetes: Influence of sex, vitamin D3, and insulin.

AIM: This study set forth a question: are there any differences in bone responses to insulin and/or vitamin D3 treatment in female and male type 1 diabetic (T1D) mice? MAIN METHODS: To address this issue, a non-critical sized femur defect was created in streptozotocin (STZ)-T1D mice. Control non-diabetic and T1D female and male mice received: saline; vitamin D3; insulin; or vitamin D3 plus insulin, for 21 days. KEY FINDINGS: Female and male T1D mice showed impaired bone healing, as indicated by histological and micro-computed tomography (micro-CT) analysis. Vitamin D3 or insulin improved the bone regeneration in T1D mice, irrespective of sex. Vitamin D3 plus insulin did not exhibit any additional effects. There were no differences regarding the numbers of TRAP-stained osteoclasts in either evaluated groups. The osteoblast-related gene osterix was upregulated in vitamin D3-treated male T1D mice, as revealed by RT-qPCR. Female T1D mice treated with vitamin D3, insulin, or vitamin D3 plus insulin presented an increased expression of insulin growth factor-1 (IGF-1) mRNA. Conversely, IGF-1 mRNA levels were reduced by the same treatments in male TD1 mice. SIGNIFICANCE: Altogether, the results suggested that T1D similarly delayed the osseous healing in female and male mice, with beneficial effects for either vitamin D3 or insulin in T1D mice of both sexes. However, data indicated marked sex differences regarding the expression of genes implicated in bone formation, in T1D mice treated with vitamin D3 and/or insulin.

Improvement of Resveratrol Effects When Combined with Rice Oil in Rat Models of Inflammation.

This study investigated the effects of systemic treatment with a new formulation of resveratrol (RSV) vehicled in rice oil (RSVO) in experimental rat models of inflammation. Male Wistar rats were evaluated in the following in vivo models: carrageenan-induced acute edema, complete Freund's adjuvant (CFA)-evoked sub-chronic edema, and CFA-induced polyarthritis. The animals were treated orally with RSVO (10-15 mg/kg) or RSV (100-200 mg/kg), depending on the experimental protocol. RSV was more effective than RSVO in carrageenan-elicited acute edema when dosed in either prophylactic or therapeutic schemes of administration. However, the repeated RSVO administration, at 10-fold lower doses, exhibited superior anti-inflammatory actions in either the sub-chronic edema or the chronic polyarthritis model elicited by CFA, when compared with RSV. The novel formulation RSVO displayed a lower plasma biotransformation when compared with the RSV-treated group-46% versus 88% of metabolites, respectively. RSVO also prevented polyarthritis-related cartilage destruction, an effect that might rely on the inhibition of the pro-inflammatory cytokine interleukin-6 (IL-6), associated with an increase of the anti-inflammatory cytokine interleukin-10 (IL-10). Noteworthy, the long-term administration of RSVO did not elicit any gastrointestinal harm. Our study revealed that RSVO was notably effective in the long-term inflammatory and degenerative responses triggered by CFA. This innovative formulation might well represent a promising alternative for treating chronic inflammatory diseases, such as arthritis.

Inspiratory Muscle Training in the Severity of Obstructive Sleep Apnea, Sleep Quality and Excessive Daytime Sleepiness: A Placebo-Controlled, Randomized Trial.

PURPOSE: Exercise programs have been considered as an adjuvant treatment in obstructive sleep apnea (OSA). However, few studies have focused on the effects of the inspiratory muscle training (IMT) in reducing the severity and the symptoms of OSA. PATIENTS AND METHODS: A randomized controlled trial was conducted and approved by the local Ethics Committee. All subjects signed the informed consent form and were randomized into 2 groups: a) IMT group (n = 8), 8 weeks of IMT with 75% of maximal inspiratory pressure (MIP) and b) placebo group (n = 8): subjects performed IMT without load. RESULTS: IMT group showed reduction in the apnea-hypopnea index (AHI) (p = 0.01), in the Berlin questionnaire score (p = 0.001) and an increase in inspiratory muscle strength (p = 0.018). IMT group demonstrated a reduction in the AHI (31.7 ± 15.9 events/h vs 29.9 ± 15.8 events/h; p <0.001), in the Berlin questionnaire scores (2.6 ± 0.5 vs 1.2 ± 0.5; p = 0.016), Pittsburgh Sleep Quality Index (PSQI) score (7.2 ± 3.6 vs 3.7 ± 1.3; p = 0.008), in the Epworth Sleepiness Scale (ESS) (12.5 ± 4.0 vs 7.7 ± 3.0; p = 0.008) and increase in MIP (83.6 ± 26.5 cmH2O and 127.9 ± 32.5 cmH2O; p = 0.010). CONCLUSION: The IMT promotes discrete changes in the AHI and improves sleep quality and excessive daytime sleepiness in OSA. Moreover, IMT is a cheap, useful and simple home-based training program and can be considered as an adjunct therapy for OSA patients.

Amphotericin B in poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) nanoparticles against paracoccidioidomycosis.

OBJECTIVES: The present study reports on the preparation and testing of a desoxycholate amphotericin B (D-AMB) sustained delivery system based on poly(lactic-co-glycolic acid) (PLGA) and dimercaptosuccinic acid (DMSA) polymeric blends (Nano-D-AMB) aimed at reducing the number of AMB administrations required to treat mycosis. METHODS: BALB/c mice were infected with the yeast Paracoccidioides brasiliensis intravenously to mimic the chronic form of paracoccidioidomycosis. At 30 days post-infection, the animals were treated with Nano-D-AMB [6 mg/kg of encapsulated D-AMB, intraperitoneally (ip), interval of 72 h] or D-AMB (2 mg/kg, ip, interval of 24 h). Drug efficacy was investigated by the fungal burden recovery from tissues. Toxicity was assessed by renal and hepatic biochemical parameters, physical appearance of the animals and haematological investigation. The control groups used were non-infected and the infected mice mock treated with PBS. RESULTS: Nano-D-AMB presented results comparable to free D-AMB, with a marked antifungal efficacy. The Nano-D-AMB-treated group presented lower loss of body weight and absence of stress sign (piloerection and hypotrichosis) observed after D-AMB treatment. No renal [blood urea nitrogen (BUN), creatinine] or hepatic (pyruvic and oxalacetic glutamic transaminases) biochemical abnormalities were found. The micronucleus assay showed no significant differences in both the micronucleus frequency and percentage of polychromatic erythrocytes for Nano-D-AMB, indicating the absence of genotoxicity and cytotoxic effects. CONCLUSIONS: The D-AMB-coated PLGA-DMSA nanoparticle showed antifungal efficacy, fewer undesirable effects and a favourable extended dosing interval. Nano-D-AMB comprises an AMB formulation able to lessen the number of drug administrations. Further studies would elucidate whether Nano-D-AMB would be useful to treat systemic fungal infections such as paracoccidioidomycosis, candidiasis, aspergillosis and cryptococcosis.

Publicações científicas sobre direção veicular por pessoas idosas: revisão de escopo / Scientific publications on driving by older adults: scope review

Resumo Objetivo Mapear evidências científicas nacionais e internacionais sobre a condução veicular por pessoas idosas. Método Revisão de escopo baseada no manual proposto pelo Joanna Briggs Institute. Para as buscas foram acessadas as bases MEDLINE, Web of Science, Scopus, SciELO e a literatura cinzenta, por meio do Google Scholar. Resultados Dos 1.194 estudos encontrados, selecionaram-se 189 artigos submetidos aos critérios de elegibilidade. Os países precursores nas publicações foram Austrália e Estados Unidos, e o ápice das pesquisas ocorreu entre 2013 e 2014. Os participantes dos estudos eram pessoas idosas saudáveis, 63,49% (120); seguidos de 17,46% (33) com doença de Alzheimer; 11,11% (21) com Transtorno Neurocognitivo Leve; 6,88% (13) com doença de Parkinson; e 19,58% (37) com outras comorbidades. Diferentes tipos de intervenções foram identificadas nos estudos, destas, 94,02% (178) avaliaram a eficácia de instrumentos que mensuram a aptidão do motorista idoso. Conclusão Houve predominância de estudos na busca de instrumentos de avaliação que mensurassem a funcionalidade do condutor idoso. Esse fato ratifica a importância de avaliação padronizada, validada e economicamente viável que colabore na identificação do motorista em risco. Evidenciou-se a necessidade de intervenções para a prática da geriatria e gerontologia, por meio de ações para formação de equipe multidisciplinar especializada em condução veicular, de modo a adequar as diretrizes de licenciamento a fim de atender às especificidades dos condutores idosos, considerando os aspectos sociais, econômicos, políticos e educacionais, especialmente nos departamentos de trânsito brasileiro.

Abstract Objective To map national and international scientific evidence regarding driving by older adults. Method Scope review based on the manual proposed by the Joanna Briggs Institute. Searches were conducted in the MEDLINE, Web of Science, Scopus, SciELO databases, and grey literature through Google Scholar. Results Out of 1,194 studies identified, 189 papers meeting eligibility criteria were selected. Pioneering countries in publications were Australia and the United States, with the peak of research occurring between 2013 and 2014. Study participants included healthy older adults (63.49%, 120), followed by those with Alzheimer's disease (17.46%, 33), Mild Neurocognitive Disorder (11.11%, 21), Parkinson's disease (6.88%, 13), and other comorbidities (19.58%, 37). Various interventions were identified, with 94.02% (178) assessing the effectiveness of instruments measuring the fitness of older drivers. Conclusion There was a prevalence of studies aimed at identifying assessment tools to measure the functionality of older drivers. This underscores the importance of standardized, validated, and economically viable assessments that contribute to identifying at-risk drivers. The need for interventions in geriatrics and gerontology was evident, emphasizing the necessity for actions to establish a specialized multidisciplinary team in vehicular driving. This approach seeks to align licensing guidelines with the specific needs of older drivers, taking into account social, economic, political, and educational aspects, particularly within the Brazilian traffic departments.

Olfactory stimulus as environmental enrichment for shelter dogs: a pilot study / Estímulo olfativo como enriquecimento ambiental para cães de abrigo: um estudo piloto

Environmental enrichment techniques include olfactory stimuli for improving animal welfare. This study aimed to analyze the reactions of 41 shelter dogs exposed to odorous stimuli, such as the method used in another study on wild canids. The focal animal method analyzed the dogs' reactions, with all behaviors recorded. Behavioral responses were classified as positive (P+), negative (N-), or other (Ot). Independent variables were all dogs and the size of the packs. The behavior between the basal (without stimulus), exposure, and after-stimulus withdrawal was analyzed. For all dogs, olfactory stimuli significantly increased P+ (P=0.001) and N- (P=0.004), contrasting with the decrement of Ot behaviors (P=0.001) from the basal to the exposure phase. After the withdrawal of the stimuli, P+, N-, and Ot behaviors returned to basal levels (P>0.05). There were no significant differences (P>0.05) in the conduct of small or large packs exposed to stimuli. Dogs are sensitive to olfactory stimuli, but arousal is generalized to P+ and N-. It is undesirable to an N- increase for improvement of animal welfare. Contrary to what was observed in a study with wild canids, the method failed in shelter dogs because N- was increased. The introduction of sudden novelty (olfactory stimulus) in an impoverished shelter environment may have caused excitement in the dogs. It is suggested that changes in the method, such as stimuli exposition to each dog in an isolated room, are necessary to increase sheltered dog well-being.(AU)

As técnicas de enriquecimento ambiental incluem estímulos olfativos para aumentar o bem-estar animal. O objetivo deste estudo foi analisar as reações de 41 cães de abrigo expostos a estímulos odoríferos, como o método utilizado em outro estudo com canídeos selvagens. As reações dos cães foram analisadas pelo método animal focal, com todos os comportamentos registrados. As respostas comportamentais foram classificadas como positivas (P+), negativas (N-) ou outras (Ot). As variáveis independentes foram todos os cães e o tamanho das matilhas. Foi analisado o comportamento entre o basal (sem estímulo), exposição e após a retirada do estímulo. Para todos os cães, os estímulos olfativos aumentaram significativamente P+ (P=0,001) e N- (P=0,004), contrastando com a diminuição dos comportamentos Ot (P=0,001) da fase basal para a de exposição. Após a retirada dos estímulos, os comportamentos P+, N- e Ot retornaram aos níveis basais (P>0,05). Não houve diferenças significativas (P>0,05) no comportamento de matilhas pequenas ou grandes expostas a estímulos. Os cães são sensíveis a estímulos olfativos, mas a excitação parece ser generalizada para ambos, P+ e N-. É indesejável um aumento de N- para melhoria do bem-estar animal. Ao contrário do que foi observado em um estudo com canídeos selvagens, o método falhou em abrigar cães porque o N- foi aumentado. A introdução de uma novidade repentina (estímulo olfativo) em um ambiente de abrigo empobrecido, pode ter causado excitação exagerada nos cães. Sugere-se alterações no método, como a exposição de estímulos a cada cão em uma sala isolada necessária para aumentar o bem-estar do cão abrigado.(AU)

DNAhsp65 Vaccine as Therapy against Paracoccidioidomycosis.

The conventional treatment for fungal diseases usually shows long periods of therapy and the high frequency of relapses and sequels. New strategies of the treatment are necessary. We have shown that the Mycobacterium leprae HSP65 gene can be successfully used as therapy against murine Paracoccidioidomycosis (PCM). Here, we described the methodology of DNAhsp65 immunotherapy in mice infected with the dimorphic fungus Paracoccidioides brasiliensis, one of PCM agent, evaluating cytokines levels, fungal burden, and lung injury. Our results provide a new prospective on the immunotherapy of mycosis.

Salivary Gland Tumors: a Ten-Year Retrospective Analysis in a Brazilian Teaching Hospital / Tumores de las Glándulas Salivales: Análisis Retrospectivo de Diez Años en un Hospital de Enseñanza Brasileño / Tumores de Glândulas Salivares: Análise Retrospectiva de Dez Anos em um Hospital Escola Brasileiro

Introduction: The tumors affecting salivary glands have a wide morphological diversity. Objective: This study aimed to examine the prevalence of salivary gland tumors in patients treated at São Lucas Teaching Hospital at the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS), in Porto Alegre (RS), Brazil, from 2007 to 2016. Method: A retrospective study analyzing 201 files from the Department of Pathology at the HSL-PUCRS was carried out, by revising the medical records. Results: Seventy-three cases of salivary gland tumors were found, and their electronic and physical medical records were analyzed. Of the 73 cases, 56 (76.7%) were benign tumors and 17 (23.3%) were malignant tumors. The age group with the highest number of cases was between 41 and 60 years of age and the highest prevalence was found in females, with 54.8% of the cases. The parotid gland presented the highest prevalence, accounting for 72.6% of the cases. The predominant neoplasia was the pleomorphic adenoma, accounting for 53.4% of the tumors. The standard of distribution of neoplasms of salivary glands was similar to the encountered in other Brazilian regions. Conclusion: The largest salivary glands were the most affected by neoplastic processes. Pleomorphic adenoma and adenoid cystic carcinoma were the most frequent benign and malignant tumors, respectively, and parotid gland was the most affected site. In the light of previous literature data, the results allow to infer that some demographic characteristics (for example, sex and age) vary among the different geographic regions

Introducción: Los tumores que afectan a las glándulas salivales tienen una amplia diversidad morfológica. Objetivo: Identificar la prevalencia de neoplasias de glándulas salivales en pacientes atendidos en el Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (HSLPUCRS), en Porto Alegre (RS), desde 2007 hasta 2016. Método: Estudio retrospectivo mediante el análisis de 201 registros del Departamento de Patología de HSL-PUCRS. Resultados: Se encontraron 73 casos de neoplasias de glándulas salivales y se analizaron los registros electrónicos y físicos de los casos seleccionados. De los 73 casos, 56 (76,7%) fueron de neoplasias benignas y 17 (23,3%) de neoplasias malignas. El grupo de edad con mayor número de casos fue el de 41 a 60 años, y la mayor prevalencia en mujeres, con 54,8%. La glándula parótida tuvo una mayor prevalencia, constituyendo 72,6% de los casos. El tipo neoplásico más prevalente fue el adenoma pleomorfo, con 53,4%. El patrón de distribución de las neoplasias de glándulas salivales fue similar al encontrado en otras regiones de Brasil. Conclusión: Las glándulas salivales mayores fueron las glándulas más afectadas por procesos neoplásicos. El adenoma pleomórfico y el carcinoma adenoide quístico fueron los tumores benignos y malignos más frecuentes, respectivamente y el sitio más afectado fue la glándula parótida. Con base en la literatura previa, estos resultados permiten inferir que algunas características demográficas (por ejemplo, sexo y edad) varían entre las distintas regiones geográficas

Introdução: Os tumores que afetam as glândulas salivares apresentam vasta diversidade morfológica. Objetivo: Identificar a prevalência de neoplasias de glândulas salivares em pacientes atendidos no Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (HSL-PUCRS), em Porto Alegre (RS), no período de 2007 a 2016. Método: Estudo retrospectivo por meio da análise de 201 arquivos do Departamento de Patologia do HSL-PUCRS. Resultados: Foram encontrados 73 casos de neoplasias de glândulas salivares e os prontuários eletrônicos e físicos dos casos selecionados foram analisados. Dos 73 casos, 56 (76,7%) eram de neoplasias benignas e 17 (23,3%) de neoplasias malignas. A faixa etária com maior número de casos foi entre 41 e 60 anos e o sexo feminino apresentou a maior prevalência com 54,8%. A glândula parótida apresentou maior prevalência, perfazendo 72,6% dos casos. O tipo neoplásico mais prevalente foi o adenoma pleomórfico, com 53,4%. O padrão de distribuição das neoplasias de glândulas salivares foi semelhante ao encontrado em outras Regiões do Brasil. Conclusão: As glândulas salivares maiores foram as mais afetadas pelos processos neoplásicos. Adenoma pleomórfico e carcinoma adenoide cístico foram os tumores benignos e malignos mais frequentes, respectivamente, e a glândula parótida foi o local mais acometido. Com base na literatura prévia, esses resultados permitem inferir que algumas características demográficas (por exemplo, sexo e idade) variam entre as diferentes Regiões geográficas

Genomic and in silico analyses of CRBN gene and thalidomide embryopathy in humans.

Thalidomide causes Thalidomide Embryopathy (TE), but is largely used to treat several conditions. Investigations with Cereblon, a thalidomide target protein encoded by CRBN gene, have helped to understand thalidomide therapeutic and teratogenic properties. We sequenced CRBN-thalidomide binding region in 38 TE individuals and 136 Brazilians without congenital anomalies, and performed in silico analyses. Eight variants were identified, seven intronic and one in 3'UTR. TE individuals had rare variants in higher frequency than the non-affected group (p=0.04). The genotype rs1620675 CC was related to neurological anomalies in TE individuals (p=0.004). Bioinformatics analysis suggested this genotype leads to potential alterations in splicing sites and binding to transcription factors. Comparison of the Cereblon-thalidomide binding domains in mammals demonstrated that CRBN is highly conserved across species. All the variants require evaluation in functional assays in order to understand their role in Cereblon-thalidomide binding and complex interactions that lead to TE.

Decifrando o "mistério dos gêmeos": vinte anos de pesquisa em Cândido Godói, Rio Grande do Sul / Solving the "twins mystery": twenty years of research in Cândido Godói, Rio Grande do Sul state

Cândido Godói (CG) é um pequeno município brasileiro localizado no noroeste do Rio Grande do Sul e é conhecido como "Cidade dos Gêmeos" devido à alta taxa de nascimentos gemelares na região. Diante de um fato tão notável, muitas explicações foram sugeridas. Entre estas teorias, a que mais recebeu atenção da mídia, mesmo sem base científica, foi a de que a gemelaridade seria fruto de experimentos de um médico nazista alemão foragido após a Segunda Guerra Mundial. A convite da própria comunidade de CG, nosso grupo de pesquisa trabalha para resolver este mistério desde 1994, analisando diferentes fatores possivelmente relacionados, em especial suas características genéticas. Aqui, nós sumarizamos os principais resultados obtidos em mais de duas décadas de pesquisa, com foco nas particularidades do processo de comunicação dos resultados, aspectos éticos e como os achados científicos naquela comunidade contribuem não apenas com a resolução de um mistério histórico e local, mas também com o estudo de outras questões, como a reprodução humana e as bases biológicas da gemelaridade. (AU)

Cândido Godói (CG) is a small town located in the northwest region of Rio Grande do Sul state which is known as "Town of Twins" because of the high rate of twin births. Many explanations have been suggested for such a noteworthy fact. The theory that has received most attention from the press, despite a lack of scientific evidence, was that twinning would result from experiments conducted by a Nazi German physician who had been a fugitive after World War II. Invited by the local community, our research team has been dedicated to solving this mystery since 1994 by analyzing different possibly related factors, especially genetic characteristics. In this paper, we summarize the main results obtained in more than two decades of research, focusing on the particular communication process of the results, ethical aspects, and how the scientific findings in that community have contributed not only to the resolution of a historical and localized mystery, but also with the study of other issues such as human reproduction and biological basis of the twinning process. (AU)