Craniometaphyseal Dysplasia With Severe Craniofacial Involvement Shows Homozygosity at 6q21-22.1 Locus

Craniotubular dysplasias (CTD) are a heterogeneous group of genetic disorders of skeletal development, whose clinical and etiological classification is still much debated. One of the most common form is the autosomal dominant craniometaphyseal dysplasia (CMD) which is associated with mutation in the ANKH gene. In the literature a few families are reported with CMD phenotype that suggest an autosomal recessive (AR) pattern of inheritance. A candidate locus at 6q21-22 has been mapped in a large inbred Brazilian family, but the gene of the recessive form is still unknown. Our data on a female patient with CMD phenotype, born from healthy first degree cousins and displaying homozygosity for polymorphic markers at the 6q21-22 locus, further support the existence of an AR CMD, expanding its clinical spectrum to a more severe phenotype. (C) 2011 Wiley-Liss, Inc.

Spastic Paraplegia, Optic Atrophy, and Neuropathy: New Observations, Locus Refinement, and Exclusion of Candidate Genes

SPOAN is an autosomal recessive neurodegenerative disorder which was recently characterized by our group in a large inbred Brazilian family with 25 affected individuals. This condition is clinically defined by: 1. congenital optic atrophy; 2. progressive spastic paraplegia with onset in infancy; and 3. progressive motor and sensory axonal neuropathy. Overall, we are now aware of 68 SPOAN patients (45 females and 23 males, with age ranging from 5 to 72 years), 44 of which are presented here for the first time. They were all born in the same geographic micro region. Those 68 patients belong to 43 sibships, 40 of which exhibit parental consanguinity. Sixty-one patients were fully clinically evaluated and 64 were included in the genetic investigation. All molecularly studied patients are homozygotes for D11S1889 at 11q13. This enabled us to reduce the critical region for the SPOAN gene from 4.8 to 2.3 Mb, with a maximum two point lod score of 33.2 (with marker D11S987) and of 27.0 (with marker D11S1889). Three genes located in this newly defined critical region were sequenced, but no pathogenic mutation was detected. The gene responsible for SPOAN remains elusive.

Skipping of exon 30 in C5 gene results in complete human C5 deficiency and demonstrates the importance of C5d and CUB domains for stability

The deficiency of complement C5 is rare and frequently associated with severe and recurrent infections, especially caused by Neisseria spp. We observed the absence of component C5 in the serum of 3 siblings from a Brazilian family with history of consanguinity. The patients had suffered from recurrent episodes of meningitis and other less severe infections. Sera from these patients were unable to mediate hemolytic activity either by the classical or alternative pathways and presented extremely low levels of C5 protein (13, 0.9 and 1.0 mu g/ml-normal range: 45-190 mu g/ml). Hemolytic activity could be restored by the addition of purified C5 to deficient serum. Sequencing of sibling C5 cDNA revealed a homozygous 153 bp deletion that corresponds precisely to exon 30. The parents carried the same deletion but only in one allele. Sequencing of the corresponding region in the genomic DNA revealed a C to C substitution within intron 30 and, most significantly, the substitution of GAG(4028) for GAA(4028) at the 3` end of exon 30 which is most likely responsible for skipping of exon 30. The resulting in-frame deletion in the C5 mRNA codes for a mutant C5 protein lacking residues 1289-1339. These residues map to the CUB and C5d domains of the C5 alpha chain. This deletion is expected to produce a non-functional and unstable C5 protein which is more susceptible to degradation. (C) 2009 Published by Elsevier Ltd.

Inequalities in dental services utilization among Brazilian low-income children: the role of individual determinants

Objectives: To assess the role of the individual determinants on the inequalities of dental services utilization among low-income children living in the working area of Brazilian`s federal Primary Health Care program, which is called Family Health Program (FHP), in a big city in Southern Brazil. Methods: A cross-sectional population-based study was performed. The sample included 350 children, ages 0 to 14 years, whose parents answered a questionnaire about their socioeconomic conditions, perceived needs, oral hygiene habits, and access to dental services. The data analysis was performed according to a conceptual framework based on Andersen`s behavioral model of health services use. Multivariate models of logistic regression analysis instructed the hypothesis on covariates for never having had a dental visit. Results: Thirty one percent of the surveyed children had never had a dental visit. In the bivariate analysis, higher proportion of children who had never had a dental visit was found among the very young, those with inadequate oral hygiene habits, those without perceived need of dental care, and those whose family homes were under absent ownership. The mechanisms of social support showed to be important enabling factors: children attending schools/kindergartens and being regularly monitored by the FHP teams had higher odds of having gone to the dentist, even after adjusting for socioeconomic, demographic, and need variables. Conclusions: The conceptual framework has confirmed the presence of social and psychosocial inequalities on the utilization pattern of dental services for low-income children. The individual determinants seem to be important predictors of access.

Risks Associated With Tendinitis: Effects From Demographic, Socioeconomic, and Psychological Status Among Brazilian Workers

Background Self-reported tendinitis/tenosynovitis was evaluated by gender, age group, skin color, family income, and educational and psychological status. Methods The study was carried out in a representative sample of formally contracted Brazilian workers from a household survey. A total of 54,660 participants were included. Occupations were stratified according to estimated prevalences of self-reported injuries. Non-conditional logistic regression was performed, and all variables were analyzed in two occupational groups. Results The overall prevalence rate of tendinitis/tenosynovitis was 3.1%: 5.5% in high-prevalence occupations (n=10,726); and 2.5% in low-prevalence occupations (n=43,934). White female workers between the ages of 45 and 64 years and at a higher socioeconomic level were more likely to report tendinitis/tenosynovitis regardless of their occupational category. An adjusted OR = 3.59 [95% CI: 3.15-4.09] was found between tendinitis/tenosynovitis and psychological status. Conclusion Among formally contracted Brazilian workers, higher income can imply greater physical and psychological demands that, regardless of occupational stratum, increase the risk of tendinitis/tenosynovitis. Am. J. Ind. Med. 53:72-79, 2010. (C) 2009 Wiley-Liss, Inc.

Narrowing socioeconomic inequality in child stunting: the Brazilian experience, 1974-2007

Objective To assess trends in the prevalence and social distribution of child stunting in Brazil to evaluate the effect of income and basic service redistribution policies implemented in that country in the recent past. Methods The prevalence of stunting (height-for-age z score below 2 using the Child Growth Standards of the World Health Organization) among children aged less than 5 years was estimated from data collected during national household surveys carried out in Brazil in 1974-75 (n = 34 409), 1989 (n = 7374), 1996 (n = 4149) and 2006-07 (n = 4414). Absolute and relative socioeconomic inequality in stunting was measured by means of the slope index and the concentration index of inequality, respectively. Findings Over a 33-year period, we documented a steady decline in the national prevalence of stunting from 37.1% to 7.1%. Prevalence dropped from 59.0% to 11.2% in the poorest quintile and from 12.1% to 3.3% among the wealthiest quintile. The decline was particularly steep in the last 10 years of the period (1996 to 2007), when the gaps between poor and wealthy families with children under 5 were also reduced in terms of purchasing power; access to education, health care and water and sanitation services; and reproductive health indicators. Conclusion In Brazil, socioeconomic development coupled with equity-oriented public policies have been accompanied by marked improvements in living conditions and a substantial decline in child undernutrition, as well as a reduction of the gap in nutritional status between children in the highest and lowest socioeconomic quintiles. Future studies will show whether these gains will be maintained under the current global economic crisis.

Clinical risk factors for osteoporotic fractures in Brazilian women and men: the Brazilian Osteoporosis Study (BRAZOS)

The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older. The prevalence of fragility fractures is about 15.1% in the women and 12.8% in the men. Moreover, advanced age, sedentarism, family history of hip fracture, current smoking, recurrent falls, diabetes mellitus and poor quality of life are the main clinical risk factors associated with fragility fractures. The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older with the purpose of identifying the prevalence and the main clinical risk factors (CRF) associated with osteoporotic fracture in our population. A total of 2,420 individuals (women, 70%) from 150 different cities in the five geographic regions in Brazil, and all different socio-economical classes were selected to participate in the present survey. Anthropometrical data as well as life habits, fracture history, food intake, physical activity, falls and quality of life were determined by individual quantitative interviews. The representative sampling was based on Brazilian National data provided by the 2000 and 2003 census. Low trauma fracture was defined as that resulting of a fall from standing height or less in individuals 50 years or older at specific skeletal sites: forearm, femur, ribs, vertebra and humerus. Sampling error was 2.2% with 95% confidence intervals. Logistic regression analysis models were designed having the fragility fracture as the dependent variable and all other parameters as the independent variable. Significance level was set as p < 0.05. The average of age, height and weight for men and women were 58.4 +/- 12.8 and 60.1 +/- 13.7 years, 1.67 +/- 0.08 and 1.56 +/- 0.07 m and 73.3 +/- 14.7 and 64.7 +/- 13.7 kg, respectively. About 15.1% of the women and 12.8% of the men reported fragility fractures. In the women, the main CRF associated with fractures were advanced age (OR = 1.6; 95% CI 1.06-2.4), family history of hip fracture (OR = 1.7; 95% CI 1.1-2.8), early menopause (OR = 1.7; 95% CI 1.02-2.9), sedentary lifestyle (OR = 1.6; 95% CI 1.02-2.7), poor quality of life (OR = 1.9; 95% CI 1.2-2.9), higher intake of phosphorus (OR = 1.9; 95% CI 1.2-2.9), diabetes mellitus (OR = 2.8; 95% CI 1.01-8.2), use of benzodiazepine drugs (OR = 2.0; 95% CI 1.1-3.6) and recurrent falls (OR = 2.4; 95% CI 1.2-5.0). In the men, the main CRF were poor quality of life (OR = 3.2; 95% CI 1.7-6.1), current smoking (OR = 3.5; 95% CI 1.28-9.77), diabetes mellitus (OR = 4.2; 95% CI 1.27-13.7) and sedentary lifestyle (OR = 6.3; 95% CI 1.1-36.1). Our findings suggest that CRF may contribute as an important tool to identify men and women with higher risk of osteoporotic fractures and that interventions aiming at specific risk factors (quit smoking, regular physical activity, prevention of falls) may help to manage patients to reduce their risk of fracture.

Contraceptive methods with male participation: a perspective of Brazilian couples

Objective: To assess the perspectives of couples who requested vasectomy in a public health service on the use of male participation contraceptive methods available in Brazil: male condoms, natural family planning/calendar, coitus interruptus and vasectomy. Methods: A qualitative study with semi-structured interviews was held with 20 couples who had requested vasectomy at the Human Reproduction Unit of the Universidade Estadual de Campinas, Brazil. Data analysis was carried out through thematic content analysis. Findings: The couples did not, in general, know any effective contraceptive options for use by men and/or participating in their use, except for vasectomy. The few methods with male participation that they knew of were perceived to interfere in spontaneity and in pleasure of intercourse. Men accepted that condom use in extra-conjugal relations offered them protection from sexually transmitted diseases; that their wives might also participate in extra-marital relationships was not considered. Discussion: The few contraceptive options with male participation lead to difficulty in sharing responsibilities between men and women. On the basis of perceived gender roles, women took the responsibility for contraception until the moment when the situation became untenable, and they faced the unavoidable necessity of sterilization. Conclusion: Specific actions are necessary for men to achieve integral participation in relation to reproductive sexual health. These include education and discussions on gender roles, leading to greater awareness in men of the realities of sexual and reproductive health.

Evaluating microfossil content of dental calculus from Brazilian sambaquis

To date, limited numbers of dental calculus samples have been analyzed by researchers in diverse parts of the world. The combined analyses of these have provided some general guidelines for the analysis of calculus that is non-destructive to archaeological teeth. There is still a need for a quantitative study of large numbers of calculus samples to establish protocols, assess the level of contamination, evaluate the quantity of microfossils in dental calculus, and to compare analysis results with the literature concerning the biology of calculus formation. We analyzed dental calculus from 53 teeth from four Brazilian sambaquis. Sambaquis are the shell-mounds that were established prehistorically along the Brazilian coast. The analysis of sambaqui dental calculi shows that there are relatively high concentrations of microfossils (phytoliths and starch), mineral fragments, and charcoal in dental calculus. Mineral fragments and charcoal are possibly contaminants. The largest dental calculi have the lowest concentrations of microfossils. Biologically, this is explained by individual variation in calculus formation between people. Importantly, starch is ubiquitous in dental calculus. The starch and phytoliths show that certainly Dioscorea (yam) and Araucaria angustifolia (Parana pine) were eaten by sambaqui people. Araceae (arum family), Ipomoea batatas (sweet potato) and Zea mays (maize) were probably in their diet. (C) 2009 Elsevier Ltd. All rights reserved.

Cutaneous Resistance to Evaporative Water Loss in Brazilian Rhinella (Anura: Bufonidae) from Contrasting Environments

Influenced by taxonomic position. For example, bufonids are regarded as exhibiting a permeable skin that seems typical for terrestrial anurans. However, this assumption is supported by information on only four bufonid species; therefore, the enormous ecological diversity of the family remains poorly Investigated. To assess whether variation in R(s) within related bufonids correlates with environmental aridity, we measured area-specific rates of EWL of two Brazilian populations of Rhinella granulosa (previously Bufo granulosus), one from the Atlantic Forest and other from the semi-arid Caatinga, and compared both with the forest species R. ornato. Rhinella granulosa from the Atlantic Forest had higher cutaneous resistance than conspecifics from Caatinga and R. ornata. Rhinella ornato presented the lowest cutaneous resistance values. However, Rs were very close to zero In all three populations. We conclude that enhanced Rs is not part of the suite of traits allowing R. granulosa to exploit the Caatinga, and that variation in R(s) within bufonids may relate to traits other than water conservation. Some Information on microhabitat occupation and ventral skin morphology supports the idea that exceptional abilities for detecting and taking up water may be the key factors enhancing the survival of R. granulosa, and possibly other bufonids, in xeric environments.

Canga renatae, a new genus and species of Cyphophthalmi from Brazilian Amazon caves (Opiliones: Neogoveidae)

A new genus and species of Cyphophthalmi, Canga renatae gen. nov., sp. nov., is described in the family Neogoveidae from a system of caves in the Serra de Carajas, Para State, Brazil. Canga can be easily distinguished from other neogoveid genera by the presence of a dentate claw on leg I, a unique character among known cyphophthalmid species, and by the free coxa II, which is fused to coxae III and IV in all the other neogoveid species except for the North American Metasiro. The new genus also differs from other Neotropical neogoveids in the lack of a dorsal crest on the chelicerae and in the lack of opisthosomal glands. The finding of a neogoveid in the Para State greatly increases the known distribution of South American cyphophtalmids into the Eastern Brazilian Amazon forest.

HTR1B and HTR2C in autism spectrum disorders in Brazilian families

Autism spectrum disorders (ASD) is a group of behaviorally defined neuro developmental disabilities characterized by multiple genetic etiologies and a complex presentation. Several studies suggest the involvement of the serotonin system in the development of ASD, but only few have investigated serotonin receptors. We have performed a case-control and a family-based study with 9 polymorphisms mapped to two serotonin receptor genes (HTR1B and HTR2C) in 252 Brazilian male ASD patients of European ancestry. These analyses showed evidence of undertransmission of the HTR1B haplotypes containing alleles -161G and -261A at HTR1B gene to ASD (P=0.003), but no involvement of HTR2C to the predisposition to this disease. Considering the relatively low level of statistical significance and the power of our sample, further studies are required to confirm the association of these serotonin-related genes and ASD. (C) 2008 Elsevier B.V. All rights reserved.

Unexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness

Nonsyndromic autosomal recessive deafness accounts for 80% of hereditary deafness. To date, 52 loci responsible for autosomal recessive deafness have been mapped and 24 genes identified. Here, we report a large inbred Brazilian pedigree with 26 subjects affected by prelingual deafness. Given the extensive consanguinity found in this pedigree, the most probable pattern of inheritance is autosomal recessive. However, our linkage and mutational analysis revealed, instead of an expected homozygous mutation in a single gene, two different mutant alleles and a possible third undetected mutant allele in the MYO15A gene (DFNB3 locus), as well as evidence for other causes for deafness in the same pedigree. Among the 26 affected subjects, 15 were homozygous for the novel c.10573delA mutation in the MYO15A gene, 5 were compound heterozygous for the mutation c.10573delA and the novel deletion c.9957_9960delTGAC and one inherited only a single c.10573delA mutant allele, while the other one could not be identified. Given the extensive consanguinity of the pedigree, there might be at least one more deafness locus segregating to explain the condition in some of the subjects whose deafness is not clearly associated with MYO15A mutations, although overlooked environmental causes could not be ruled out. Our findings illustrate a high level of etiological heterogeneity for deafness in the family and highlight some of the pitfalls of genetic analysis of large genes in extended pedigrees, when homozygosity for a single mutant allele is expected.

Contributions to the taxonomy of the Normanellidae (Copepoda, Harpacticoida): description of a new genus from the Brazilian continental shelf and re-assignment of Pseudocletodes vararensis Scott & Scott, 1893 (ex Nannopodidae)

A new genus and species of Normanellidae (Copepoda, Harpacticoida), Paranaiara inajae gen. et sp. nov., is described from the continental shelf off the northern coast of Sao Paulo State, Brazil. The new genus differs from the type genus Normanella Brady, 1880 and Sagamiella Lee & Huys, 1999 in its presence of lamelliform caudal rami, a maxillulary endopod represented by 2 setae, an unarmed maxillipedal syncoxa, and reduced setation on P2 enp-2 (without outer spine) and P3 enp-2 (with only 2 inner setae). All these apomorphic character states are shared with the genus Pseudocletodes Scott & Scott, 1893, formerly placed in the family Nannopodidae (ex Huntemanniidae) and here assigned to the Normanellidae. Pseudocletodes can be differentiated from Paranaiara by the loss of the P1 endopod and of the inner seta on P2-P4 enp-1, the presence of only 2 inner setae on P2 enp-2 (instead of 3) and only 1 inner seta on P4 exp-3 (instead of 2), the presence of a second inner seta on P4 enp-2 (instead of 1), the morphology of the fifth pair of legs which are not medially fused and have only 3 endopodal elements (instead of 4) in the male, and the well developed caudal ramus seta V (instead of rudimentary). It is postulated that prehensility of the P1 endopod was secondarily lost in the common ancestor of Paranaiara and Pseudocletodes. An updated family diagnosis of the Normanellidae and a dichotomous identification key to the 22 currently valid species are presented.

The effect of sixteen medicinal plants used in the Brazilian pharmacopoeia on the expression and activity of glutathione S-transferase in hepatocytes and leukemia cells

Glutathione S-transferase (GST) is a family of enzymes involved in the detoxification of electrophilic compounds. Different classes of GST are expressed in various organs, such as liver, lungs, stomach and others. Expression of GST can be modulated by diet components and plant-derived compounds. The importance of controlling GST expression is twofold: increasing levels of GST are beneficial to prevent deleterious effects of toxic and carcinogenic compounds, while inhibition of GST in tumor cells may help overcoming tumor resistance to chemotherapy. A screening of 16 plants used in the Brazilian pharmacopoeia tested their effects on GST expression in hepatocytes and Jurkat (leukemia) T-cells. The methanol extracts of five plants inhibited GST expression in hepatocytes. Three plants significantly inhibited and four others induced GST expression in Jurkat cells. Among these, the extracts of Bauhinia forficata Link. (Leguminosae) and Cecropia pachystachya Trec. (Urticaceae) inhibited GST expression at relatively low concentrations. With the exception of B. forficata, all plants were cytotoxic when administered to Jurkat cells at high doses (1 mg/mL) and some extracts were considerably cytotoxic even at lower concentrations.