Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients.

BACKGROUND: Xeroderma pigmentosum (XP) patients present a high risk of developing skin cancer and other complications at an early age. This disease is characterized by mutations in the genes related to the DNA repair system. OBJECTIVES: To describe the clinical and molecular findings in a cohort of 32 Brazilian individuals who received a clinical diagnosis of XP. METHODS: Twenty-seven families were screened for germline variants in eight XP-related genes. RESULTS: All patients (N = 32) were diagnosed with bi-allelic germline pathogenic or potentially pathogenic variants, including nine variants previously undescribed. The c.2251-1G>C XPC pathogenic variant, reported as the founder mutation in Comorian and Pakistani patients, was observed in 15 cases in homozygous or compound heterozygous. Seven homozygous patients for POLH/XPV variants developed their symptoms by an average age of 7.7 years. ERCC2/XPD, DDB2/XPE and ERCC5/XPG variants were found in a few patients. Aside from melanoma and non-melanoma skin tumours, a set of patients developed skin sebaceous carcinoma, leiomyosarcoma, angiosarcoma, mucoepidermoid carcinoma, gastric adenocarcinoma and serous ovarian carcinoma. CONCLUSIONS: We reported a high frequency of XPC variants in 32 XP Brazilian patients. Nine new variants in XP-related genes, unexpected non-skin cancer lesions and an anticipation of the clinical manifestation in POLH/XPV cases were also described.

Latent class analysis of attention and white matter correlation in children with attention-deficit/hyperactivity disorder.

This study aimed to explore attentional patterns among children with inattentive attention-deficit/hyperactivity disorder (ADHD-I) and children with typical development (TD), using a latent class analysis (LCA). Patterns of brain connectivity were also explored. The sample comprised 29 ADHD-I and 29 TD matched children. An LCA was conducted to reclassify subjects according to their attentional performance, considering cognitive measures of attention and behavioral symptoms, regardless of group of origin. The new clusters were then compared in respect to brain white matter measurements (extracted from diffusion tensor imaging). Participants were rearranged in 2 new latent classes, according to their performance in an attention task and the results of behavioral scales, resulting in groups with more homogeneous attentional profiles. A comparison of the 2 new classes using the white matter measurements revealed increased fractional anisotropy in the left inferior fronto-occipital fasciculus and left inferior longitudinal fasciculus for the class composed by participants with a higher risk of attentional problems. The findings indicated that it was possible to observe variability regarding neuropsychological profile, accompanied by underpinning neurobiological differences, even among individuals with the same disorder subtype - inattentive ADHD. This specific data-driven clustering analysis may help to enhance understanding of the pathophysiology of the disorder's phenotypes.

Latent class analysis of attention and white matter correlation in children with attention-deficit/hyperactivity disorder

This study aimed to explore attentional patterns among children with inattentive attention-deficit/hyperactivity disorder (ADHD-I) and children with typical development (TD), using a latent class analysis (LCA). Patterns of brain connectivity were also explored. The sample comprised 29 ADHD-I and 29 TD matched children. An LCA was conducted to reclassify subjects according to their attentional performance, considering cognitive measures of attention and behavioral symptoms, regardless of group of origin. The new clusters were then compared in respect to brain white matter measurements (extracted from diffusion tensor imaging). Participants were rearranged in 2 new latent classes, according to their performance in an attention task and the results of behavioral scales, resulting in groups with more homogeneous attentional profiles. A comparison of the 2 new classes using the white matter measurements revealed increased fractional anisotropy in the left inferior fronto-occipital fasciculus and left inferior longitudinal fasciculus for the class composed by participants with a higher risk of attentional problems. The findings indicated that it was possible to observe variability regarding neuropsychological profile, accompanied by underpinning neurobiological differences, even among individuals with the same disorder subtype - inattentive ADHD. This specific data-driven clustering analysis may help to enhance understanding of the pathophysiology of the disorder's phenotypes.

A genetic cluster of patients with variant xeroderma pigmentosum with two different founder mutations.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare human syndrome associated with hypersensitivity to sunlight and a high frequency of skin tumours at an early age. We identified a community in the state of Goias (central Brazil), a sunny and tropical region, with a high incidence of XP (17 patients among approximately 1000 inhabitants). OBJECTIVES: To identify gene mutations in the affected community and map the distribution of the affected alleles, correlating the mutations with clinical phenotypes. METHODS: Functional analyses of DNA repair capacity and cell-cycle responses after ultraviolet exposure were investigated in cells from local patients with XP, allowing the identification of the mutated gene, which was then sequenced to locate the mutations. A specific assay was designed for mapping the distribution of these mutations in the community. RESULTS: Skin primary fibroblasts showed normal DNA damage removal but abnormal DNA synthesis after ultraviolet irradiation and deficient expression of the Polη protein, which is encoded by POLH. We detected two different POLH mutations: one at the splice donor site of intron 6 (c.764 +1 G>A), and the other in exon 8 (c.907 C>T, p.Arg303X). The mutation at intron 6 is novel, whereas the mutation at exon 8 has been previously described in Europe. Thus, these mutations were likely brought to the community long ago, suggesting two founder effects for this rare disease. CONCLUSIONS: This work describes a genetic cluster involving POLH, and, particularly unexpected, with two independent founder mutations, including one that likely originated in Europe.

Coordinated brain development: exploring the synchrony between changes in grey and white matter during childhood maturation.

Brain development during childhood and early adolescence is characterized by global changes in brain architecture. Neuroimaging studies have revealed overall decreases in cortical thickness (CT) and increases in fractional anisotropy (FA). Furthermore, previous studies have shown that certain cortical regions display coordinated growth during development. However, there is significant heterogeneity in the timing and speed of these developmental transformations, and it is still unclear whether white and grey matter changes are co-localized. In this multimodal neuroimaging study, we investigated the relationship between grey and white matter developmental changes and asynchronous maturation within brain regions in 249 normally developing children between the ages 7-14. We used structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to analyze CT and FA, respectively, as well as their covariance across development. Consistent with previous studies, we observed overall cortical thinning with age, which was accompanied by increased FA. We then compared the coordinated development of grey and white matter as indexed by covariance measures. Covariance between grey matter regions and the microstructure of white matter tracts connecting those regions were highly similar, suggesting that coordinated changes in the cortex were mirrored by coordinated changes in their respective tracts. Examining within-brain divergent trajectories, we found significant structural decoupling (decreased covariance) between several brain regions and tracts in the 9- to 11-year-old group, particularly involving the forceps minor and the regions that it connects to. We argue that this decoupling could reflect a developmental pattern within the prefrontal region in 9- and 11-year-old children, possibly related to the significant changes in cognitive control observed at this age.

Diallel analysis to choose parents for black bean (Phaseolus vulgaris L.) breeding.

In this study, conducted in two different seasons, we aimed to choose parents to obtain promising segregating populations for the extraction of black bean (Phaseolus vulgaris L.) lines that are superior in terms of disease resistance, plant architecture, and grain yield. Twelve parents were arranged in two groups to compose a partial diallel in a 5 x 7 scheme. Group 1 was composed of parents with black grains and erect plant architecture, while group 2 was composed of parents that had carioca grains and were resistant to the main fungal diseases that occur in the common bean. The following traits were evaluated: severity of angular leaf spot (ALS), plant architecture (PAG), and grain yield (YIELD). The data were analyzed according to a partial diallel model using parents and F1 hybrids. In the genetic control of ALS and PAG, additive effects were predominant, while for YIELD, additive effects were predominant in one season and dominance effects were in another season, because it is a more complex trait than ALS and PAG. For YIELD, we observed an interaction between general combining ability and specific combining ability between seasons. The genes that control ALS, PAG, and YIELD were in eight of the 12 parents evaluated in the diallel. The cultivar 'BRS Estilo' is suitable to use as a parent in common bean breeding in terms of ALS, PAG and YIELD. Recurrent selection is the most recommended option for simultaneously breeding for PAG, YIELD, and resistance to angular leaf spot in bean culture.

Genetic progress resulting from forty-three years of breeding of the carioca common bean in Brazil.

We aimed to evaluate 40 common bean cultivars recommended by various Brazilian research institutions between 1970 and 2013 and estimate the genetic progress obtained for grain yield and other agronomic traits. Additionally, we proposed a bi-segmented nonlinear regression model to infer the year in which breeding began to show significant gains in Brazil. The experiment was carried out in Viçosa/MG and Coimbra/MG, in the dry and winter seasons of 2013. For this, a randomized complete block design with three replications was employed. The following traits were evaluated: number of pods per plant (NPP); number of seeds per pod (NSP); 1000-seed weight (W1000); grain yield (Yield); plant architecture (Arch); and grain aspect (GA). Genotypic means were estimated over years using linear mixed models, and genetic gains were estimated using bi-segmented nonlinear regression models. In summary, the methodology proposed in the present study indicated that bean breeding programs in Brazil began to influence Yield beginning in 1990, resulting in a gain of 6.74% per year (68.15 kg/ha per year). The years from which estimated genetic progress for NPP (5.62% per year), NSP (4.59% per year), W1000 (2.08% per year), and GA (1.36% per year) began to increase were 1994, 1990, 1989, and 1986, respectively.

Effect of generations and environments in the analysis of a partial diallel to improve bean earliness.

The objective of this study was to select genitors based on F1 and F2 generations, evaluated in different environments, to obtain segregating populations for the identification of strains showing improved earliness, yield, and carioca-type grains. Nine bean strains were crossed in a partial diallel scheme (4 x 5), in which group 1 included 4 strains with early cycles and group 2 included 5 elite strains. The F1 and F2 generations and the genitors were assessed in Coimbra and Viçosa in randomized blocks with 3 replications. The following characteristics were evaluated: days between sowing and emergence, and grain yield. We observed an interaction between the effects of general combining ability and specific combining ability with the environments (crop, location, and generation) for both grain earliness and yield. Genetic analysis of earliness revealed a predominance of additive effects and grain yield dominance effects. The strain Goiano Precoce may be used as a genitor in breeding programs to improve earliness, while strains RP1 and VC33 can be used to increase grain yield. We observed genetic complementation between strains Goiano Precoce and RP1, BRSMG Madrepérola and BRS Estilo for earliness and between RP1 and Rosinha Precoce for grain yield.

Distribution of rotavirus genotypes after vaccine introduction in the Triângulo Mineiro region of Brazil: 4-Year follow-up study.

BACKGROUND: Rotaviruses are the major cause of diarrhea in children for which a monovalent G1P[8] vaccine has been provided free for all Brazilian infants since March 2006. OBJECTIVES: To investigate prevalence and genotypes of rotavirus strains causing diarrhea in children in Triângulo Mineiro, Minas Gerais, during 2007-2010, and to assess local vaccine impact. STUDY DESIGN: Fecal specimens were analyzed for rotavirus detection and characterization by PAGE, RT-PCR and PCR-genotyping assays. RESULTS: Overall, rotavirus was diagnosed in 12.1% (76/630) cases, accounting for 35.8% of the hospitalizations and 6.5% of outpatient attendance due to diarrhea. A trend in rotavirus disease reduction occurred in both cities (71.8% and 83.4% in Uberaba; 95.3% in Uberlândia) up to 2009, but it reversed in 2010 with increased rotavirus cases in Uberlândia. Short pattern G2P[4] strains were detected in all but three (96%) cases of mixed/P[NT] infections with long electropherotypes. CONCLUSIONS: This 4-year follow-up study showed a reduction in rotavirus-related diarrhea and even skipped a rotavirus season, which is consistent with vaccine mediated protection. The 2007-2010 rotavirus epidemic curve reflected the natural cyclic fluctuation of the single G2P[4] genotype, with sharp reduction of cases in 2008 leading to lack of a rotavirus 2009 season (both cases and hospitalizations) followed by its come back in 2010. Diarrhea cases related to either vaccine serotype/genotype (G1 or P[8]) were not detected. Thus, a new scenario emerged with a single epidemic genotype replacing the cocirculation of great diversity of genotypes, thus far, a hallmark of the epidemiology of rotavirus in Brazil.

Morphine infusions into the rostrolateral periaqueductal gray affect maternal behaviors

It is well established that morphine inhibits maternal behaviors. Previous studies by our group have shown activation of the rostrolateral periaqueductal gray (rlPAG) upon inhibition-intended subcutaneous injections of morphine. In this context, we demonstrated that a single naloxone infusion into the rlPAG, following this opioid-induced inhibition, reactivated maternal behaviors. Since these data were obtained by using peripheral morphine injections, the present study was designed to test whether morphine injected directly into the rlPAG would affect maternal behaviors. Our hypothesis that morphine acting through the rlPAG would disrupt maternal behaviors was confirmed with a local infusion of morphine. The mothers showed shorter latency for locomotor behavior to explore the home cage (P = 0.049). Inhibition was especially evident regarding retrieving (P = 0.002), nest building (P = 0.05) and full maternal behavior (P = 0.023). These results support the view that opioidergic transmission plays a behaviorally meaningful inhibitory role in the rostrolateral PAG.

Morphine infusions into the rostrolateral periaqueductal gray affect maternal behaviors.

It is well established that morphine inhibits maternal behaviors. Previous studies by our group have shown activation of the rostrolateral periaqueductal gray (rlPAG) upon inhibition-intended subcutaneous injections of morphine. In this context, we demonstrated that a single naloxone infusion into the rlPAG, following this opioid-induced inhibition, reactivated maternal behaviors. Since these data were obtained by using peripheral morphine injections, the present study was designed to test whether morphine injected directly into the rlPAG would affect maternal behaviors. Our hypothesis that morphine acting through the rlPAG would disrupt maternal behaviors was confirmed with a local infusion of morphine. The mothers showed shorter latency for locomotor behavior to explore the home cage (P = 0.049). Inhibition was especially evident regarding retrieving (P = 0.002), nest building (P = 0.05) and full maternal behavior (P = 0.023). These results support the view that opioidergic transmission plays a behaviorally meaningful inhibitory role in the rostrolateral PAG.

[Epidemiological profile of elderly HIV/AIDS patients]. / Perfil epidemiológico dos clientes HIV/AIDS na terceira idade.

The present study is the result of an experience in the hospital Correia Picanço in Recife, Pernambuco Federal State, a reference hospital for HIV patients. The objective of this investigation is to supply the discrepancy of information on elderly carriers of HIV. This is a quantitative, transversal and retrospective research. A diagram form was used to organize the data collected from 46 medical records. Results showed that there was an increase on the number of women, especially married women, heterosexuals, and elderly infected by HIV. The study also showed an increase on the number of infections through sexual contact and the predominance of carriers who were undereducated. It was also observed that the medical records were incomplete. The conclusion was that preventive education programs have to be elaborated in order to reach the population in general, including the elderly.