EPIGEN-Brazil Initiative resources: a Latin American imputation panel and the Scientific Workflow.

EPIGEN-Brazil is one of the largest Latin American initiatives at the interface of human genomics, public health, and computational biology. Here, we present two resources to address two challenges to the global dissemination of precision medicine and the development of the bioinformatics know-how to support it. To address the underrepresentation of non-European individuals in human genome diversity studies, we present the EPIGEN-5M+1KGP imputation panel-the fusion of the public 1000 Genomes Project (1KGP) Phase 3 imputation panel with haplotypes derived from the EPIGEN-5M data set (a product of the genotyping of 4.3 million SNPs in 265 admixed individuals from the EPIGEN-Brazil Initiative). When we imputed a target SNPs data set (6487 admixed individuals genotyped for 2.2 million SNPs from the EPIGEN-Brazil project) with the EPIGEN-5M+1KGP panel, we gained 140,452 more SNPs in total than when using the 1KGP Phase 3 panel alone and 788,873 additional high confidence SNPs (info score ≥ 0.8). Thus, the major effect of the inclusion of the EPIGEN-5M data set in this new imputation panel is not only to gain more SNPs but also to improve the quality of imputation. To address the lack of transparency and reproducibility of bioinformatics protocols, we present a conceptual Scientific Workflow in the form of a website that models the scientific process (by including publications, flowcharts, masterscripts, documents, and bioinformatics protocols), making it accessible and interactive. Its applicability is shown in the context of the development of our EPIGEN-5M+1KGP imputation panel. The Scientific Workflow also serves as a repository of bioinformatics resources.

GRPR/PI3Kγ: Partners in Central Transmission of Itch.

The gastrin-releasing peptide (GRP) and its receptor (GRPR) are important components of itch transmission. Upstream, but not downstream, aspects of GRPR signaling have been investigated extensively. We hypothesize that GRPR signals in part through the PI3Kγ/Akt pathway. We used pharmacological, electrophysiological, and behavioral approaches to further evaluate GRPR downstream signaling pathways. Our data show that GRP directly activates small-size capsaicin-sensitive DRG neurons, an effect that translates into transient calcium flux and membrane depolarization (∼ 20 mV). GRPR activation also induces Akt phosphorylation, a proxy for PI3Kγ activity, in ex vivo naive mouse spinal cords and in GRPR transiently expressing HEK293 cells. The intrathecal injection of GRP led to intense scratching, an effect largely reduced by either GRPR antagonists or PI3Kγ inhibitor. Scratching behavior was also induced by the intrathecal injection of an Akt activator. In a dry skin model of itch, we show that GRPR blockade or PI3Kγ inhibition reversed the scratching behavior. Altogether, these findings are highly suggestive that GRPR is expressed by the central terminals of DRG nociceptive afferents, which transmit itch via the PI3Kγ/Akt pathway. SIGNIFICANCE STATEMENT: Itch is the most common symptom of the skin and is related to noncutaneous diseases. It severely impairs patients' quality of life when it becomes chronic and there is no specific or effective available therapy, mainly because itch pathophysiology is not completely elucidated. Our findings indicate that the enzyme PI3Kγ is a key central mediator of itch transmission. Therefore, we suggest PI3Kγ as an attractive target for the development of new anti-pruritic drugs. With this study, we take a step forward in our understanding of the mechanisms underlying the central transmission of itch sensation.

Gate Control Theory Springs a Leak.

Sun and colleagues (2017) find that individual Grp+ spinal interneurons can respond to and distinguish between stimuli that provoke itch or pain. The nociceptive response is limited by enkaphalin-expressing interneurons that are connected synaptically to the Grp+ neurons.

Trachoma among the Yanomami Indians.

The Yanomami are one of the last primitive groups of Indians living in Brazil. They have almost no contact with other cultures. The epidemiology of eye disease among Yanomami is virtually unknown. For the first time, a trachoma survey was conducted among Yanomami Indians in the State of Amazonas near the Venezuelan border of the Brazilian rain forest. Ophthalmic examination was carried out on a total of 613 individuals (338 males and 275 females) from eight Yanomami villages along the Maraui River located in the upper Rio Negro Basin. Age was classified into three categories (children, adults, and elderly) and trachoma was classified into five grades: follicular, inflammatory intense, cicatricial, trichiasis, and corneal opacity. Trachoma was endemic in all villages visited. Overall, 30.3% of the subjects had trachoma. Females were significantly more affected (37.4%) than males (23.9%). The inflammatory trachoma rate reached 24.9% in children and the cicatricial form increased with age, reaching 13.9% among adults and 35.21% among the elderly. Trichiasis or corneal opacities were not detected and treatment of the entire population was initiated with 1 g azithromycin. The detection of endemic trachoma among the Yanomami is relevant for the understanding of the epidemiology of this disease in the Brazilian rain forest and underscores the necessity for a program of trachoma control in this region.

Association between oral health-related quality of life and atraumatic restorative treatment in school children: an exploratory study.

BACKGROUND: The present study's objectives were to compare the perceptions of oral health-related quality of life (OHRQoL) among school children presents dental caries with that of caries-free school children, and to evaluate the subjective impact of atraumatic restorative treatment (ART) on the OHRQoL of school children. DESIGN: Exploratory study. SETTING: Public school in Piracicaba, Brazil. MATERIALS AND METHODS: The sample was composed of 30 children in the age-group of 8-10 years. The children were divided into two groups: one with caries and other without caries. The information related to OHRQoL was obtained through the administration of the Child Perceptions Questionnaires (CPQ 8-10 ). To evaluate the impact of ART on the school children's OHRQoL, the CPQ 8-10 was re-administered 4 weeks after the initial treatment. For statistical analysis we used the nonparametric Wilcoxon test for two dependent variables (test and re-test groups) and the nonparametric Mann-Whitney test for independent variables (test and control groups). RESULTS: It was observed that children with dental caries reported larger impact of oral health conditions on the quality of life when compared with the caries-free group, especially in the emotional and social well-being domains ( P ≤.05). After the school children who presented with dental caries received ART, there was improvement in the median scores of CPQ 8-10 in all of the domains, but particularly in the functional limitation domain ( P ≤.05). CONCLUSION: Dental caries exerts a strong influence on the OHRQoL of children. ART was shown to be a simple and painless caries management approach that could improve the OHRQoL of school children.

Rabbit rubeosis iridis induced by intravitreal latex-derived angiogenic fraction.

PURPOSE: To describe the presence of iris neovascularization in a rabbit-model of retinal neovascularization induced by the intravitreal injection of latex-derived angiogenic fraction microspheres (LAF). MATERIALS AND METHODS: Eight New Zealand rabbits received one intravitreal injection of PLGA (L-lactide-co-glycolide) microspheres with 50 ug of LAF in the right eye (Group A). Microspheres without the LAF (0.1 ml) were injected in controls (Group B; n = 8). Follow-up with clinical evaluation and iris fluorescein angiography was performed after 4 weeks when eyes were processed for light microscopy. RESULTS: All eyes from Group A showed significant vascular dilation, conjunctival hyperemia and neovascularization on the iris surface, after LAF injection. No vascular changes were observed in Group B. CONCLUSIONS: The intravitreal injection of microspheres containing the LAF can induce rubeosis iridis in rabbits and could be used as a simple experimental model for iris neovascularization.

Prevalence of pterygium and cataract in indigenous populations of the Brazilian Amazon rain forest.

PURPOSE: To compare the prevalence of pterygium and cataract in four indigenous populations of the Brazilian Amazonian rain forest (Arawak, Tukano, Maku, and Yanomami) with different ethnic and social behaviour backgrounds. METHODS: A cross-sectional pterygium and cataract survey was performed in 624 adult Indians of the Brazilian rain forest belonging to four different ethnic groups. The Indians were classified according to their social behaviour in two groups: Arawak and Tukano (group 1) and Maku and Yanomami (group 2). Slit-lamp biomicroscopy was employed to examine the entire sample. All subjects were classified as 1 or 0 according to the presence or absence pterygium and cataract. Sex and age were also recorded. RESULTS: chi(2)-tests revealed that the prevalence of pterygium and cataract differed significantly between groups 1 and 2. For pterygia: 36.6% (97/265) and 5.0% (18/359), respectively (chi(2)=101.2, P<0.0001), and for cataracts: 24.5% (65/265) and 13.7% (49/359) respectively (chi(2)=12.09, P=0.0005). Gender was not associated with pterygium (P=0.1326) and cataract (P=0.2263) in both groups. Elderly subjects showed a significantly higher prevalence of cataract (P<0.0001). The prevalence of pterygia did not increase with age (P=0.8079) in both groups. CONCLUSION: Indians of group 1 have higher prevalence of pterygia and cataract than Indians of group 2. Social behaviour, especially the rate of sun exposure, appears to be the main factor for the different rates of pterygium and cataract displayed by these indigenous people of the Brazilian rain forest.

Nitric oxide is involved in the lesions of the peripheral autonomic neurons observed in the acute phase of experimental Trypanosoma cruzi infection.

Our aim was to investigate the possible involvement of nitric oxide (NO) in peripheral denervation during the acute phase of murine experimental Trypanosoma cruzi infection. Wistar male rats were infected with the Y strain of T. cruzi. One group of animals was also treated with the NO synthase inhibitor N-nitro-l-arginine. A group of uninfected animals was the control. At the 18th day of infection the animals were sacrificed. Quantification of neurons in the colon and heart and tissue parasitism in the heart was performed. Serum concentration of nitrate was measured and a histochemical technique for assessing NADPH-diaphorase activity in the colon was also performed. The infected animals presented a statistically significant decrease in the number of peripheral neurons in the colon and heart and a 2-fold increase in serum NO(3) concentration compared with controls. The animals treated with N-nitro-l-arginine showed almost an absence of NO(3) concentration in the serum and did not show loss of neurons compared with controls. These treated animals displayed a 15-fold increase in tissue parasitism compared with nontreated infected animals. The NADPH-diaphorase activity was much more intense in the muscle layers of the colon of the infected animals than in those of the controls. Taken together, these data suggest that NO is involved in the peripheral denervation observed in the acute phase of experimental T. cruzi infection.

Trachoma among the Yanomami Indians

The Yanomami are one of the last primitive groups of Indians living in Brazil. They have almost no contact with other cultures. The epidemiology of eye disease among Yanomami is virtually unknown. For the first time, a trachoma survey was conducted among Yanomami Indians in the State of Amazonas near the Venezuelan border of the Brazilian rain forest. Ophthalmic examination was carried out on a total of 613 individuals (338 males and 275 females) from eight Yanomami villages along the Marauiá River located in the upper Rio Negro Basin. Age was classified into three categories (children, adults, and elderly) and trachoma was classified into five grades: follicular, inflammatory intense, cicatricial, trichiasis, and corneal opacity. Trachoma was endemic in all villages visited. Overall, 30.3 percent of the subjects had trachoma. Females were significantly more affected (37.4 percent) than males (23.9 percent). The inflammatory trachoma rate reached 24.9 percent in children and the cicatricial form increased with age, reaching 13.9 percent among adults and 35.21 percent among the elderly. Trichiasis or corneal opacities were not detected and treatment of the entire population was initiated with 1 g azithromycin. The detection of endemic trachoma among the Yanomami is relevant for the understanding of the epidemiology of this disease in the Brazilian rain forest and underscores the necessity for a program of trachoma control in this region