Unequal Impact of COL1A1 and COL1A2 Variants on Dentinogenesis Imperfecta.

Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by COL1A1 or COL1A2 heterozygous pathogenic variants. Its prevalence varies according to the studied population. Here, we report the molecular analysis of 81 patients with OI followed at reference centers in Brazil and France presenting COL1A1 or COL1A2 variants. Patients were submitted to clinical and radiographic dental examinations to diagnose the presence of DI. In addition, a systematic literature search and a descriptive statistical analysis were performed to investigate OI/DI phenotype-genotype correlation in a worldwide sample. In our cohort, 50 patients had COL1A1 pathogenic variants, and 31 patients had COL1A2 variants. A total of 25 novel variants were identified. Overall, data from a total of 906 individuals with OI were assessed. Results show that DI was more frequent in severe and moderate OI cases. DI prevalence was also more often associated with COL1A2 (67.6%) than with COL1A1 variants (45.4%) because COL1A2 variants mainly lead to qualitative defects that predispose to DI more than quantitative defects. For the first time, 4 DI hotspots were identified. In addition, we showed that 1) glycine substitution by branched and charged amino acids in the α2(I) chain and 2) substitutions occurring in major ligand binding regions-MLRB2 in α1(I) and MLBR 3 in α2(I)-could significantly predict DI (P < 0.05). The accumulated variant data analysis in this study provides a further basis for increasing our comprehension to better predict the occurrence and severity of DI and appropriate OI patient management.

Cobalamin F deficiency in a girl with severe skin hyperpigmentation and a homozygous LMBRD1 variant.

Cobalamin (vitamin B12) is important in gastrulation, nervous system development and haemoglobin formation. Mutations of the ABCD4 or LMBRD1 genes can lead to cobalamin-related disorders. We report a patient with disseminated skin hyperpigmentation caused by a homozygous LMBRD1 variant. Genetic disorders of cobalamin metabolism caused by variants in the ABCD4 or LMBRD1 genes should be considered in patients presenting with cutaneous hyperpigmentation. Click https://www.wileyhealthlearning.com/#/online-courses/a6ef1275-8325-4834-89d2-aa18fa31e63f for the corresponding questions to this CME article.

PIMA: A population informative multiplex for the Americas.

We describe an ancestry-informative autosomal SNP multiplex designed to be a small-scale, flexible panel that can complement uniparental markers in assessing the American variability (i.e. pre-Colombian) found in contemporary indigenous American populations. This study centered on choosing SNPs with the specific characteristics of: 1) extreme allele frequency differences between indigenous Americans and the African, European and East Asian population groups that contribute to present-day population variation in the Americas; 2) high informativeness-for-assignment In values; and 3) well-spaced genomic distribution and chromosomal separation from existing small-scale forensic ancestry marker sets. The resulting capillary electrophoresis SNaPshot single base extension test was named: PIMA (Population Informative Multiplex for the Americas), comprising 26 autosomal SNPs, a single X-chromosome SNP plus the amelogenin sex marker adapted for SNaPshot. PIMA complements the established 34plex forensic ancestry panel to provide a powerful and simple tool for the analysis of American populations, including those with admixed histories, commonly encountered in America. Comparing the results obtained with the combined marker panels of PIMA and 34plex to SNP data from a much larger ancestry panel allowed us to gauge their relative efficiency. PIMA+34plex gives equivalent power to the 314-SNP 'LACE' genomic ancestry control panel, while requiring a much smaller genotyping effort. The ancestry profiles and genetic structure of 22 populations spread across the American continent were estimated using PIMA+34plex data, and those estimates were contrasted with information provided by uniparental markers (mtDNA and Y-chromosome loci) for a small set of admixed individuals from Venezuela. Our results indicate that an American genetic component is efficiently detected in contemporary American populations using a small set of ancestry informative SNPs, and these co-ancestry estimates are consistent with the known history and demography of the Americas. The small scale and high population differentiation power of PIMA, particularly when combined with 34plex, provides a practical and powerful tool for genetic studies of American populations as well as forensic DNA analyses.

Potencial terapêutico e uso de plantas medicinais em uma área de Caatinga no estado do Ceará, nordeste do Brasil / Therapeutic potential and use of medicinal plants in an area of the Caatinga in the state of Ceará, northeastern Brazil

O presente trabalho visou o levantamento etnobotânico das plantas medicinais, verificando a versatilidade das espécies utilizadas e o consenso de uso e/ou conhecimento entre os informantes, do Distrito de Aratama, no Município de Assaré, Ceará. As informações etnobotânicas foram obtidas através de entrevistas estruturadas e semi-estruturadas com os moradores locais. Foram citadas 116 espécies com fins medicinais pertencentes a 103 gêneros e 58 famílias com destaque para Fabaceae (10ssp.), Asteraceae (7spp.) e Lamiaceae (6spp.). Entre as espécies levantadas, Mentha spicata L., Rosmarinus officinalis L., Allium sativum L., Bauhinia cheilantha (Bong.), Ximenea americana L., se destacaram como as mais versáteis dentro da comunidade. As indicações terapêuticas citadas foram agrupadas em 16 categorias de sistemas corporais, dos quais as Desordens mentais e comportamentais, as Afecções ou dores não definidas, os Transtornos do sistema respiratório, as Doenças de pele e do tecido celular subcutâneo, e os Transtornos do sistema sensorial (ouvidos), mostram maior concordância entre os informantes na utilização de espécies para tratar um sistema corporal especifico. Os resultados mostraram elevada riqueza da flora medicinal presente na caatinga. Neste sentido, torna-se necessária a intensificação de estudos que avaliem e consolidem as propriedades químicas e farmacológicas destas espécies.

This study is about an ethnobotanical survey of medicinal plants, checking the versatility of the species used and the consensus of use and/or knowledge among informants from the Aratama District, in the municipality of Assaré, state of Ceará, Brazil. The ethnobotanical information was obtained through structured interviews and semi-structured interviews with local residents. Approximately, 116 species were mentioned for medicinal purposes, belonging to 103 genera and 58 families, especially Fabaceae (10ssp.), Asteraceae (7spp.) and Lamiaceae (6spp.). Among the surveyed species, Mentha spicata L., Rosmarinus officinalis L., Allium sativum L. and Bauhinia cheilantha (Bong.) Ximenea americana L. stood out as the most versatile in the community. The therapeutic indications mentioned were grouped into 16 categories of body systems; the mental and behavioral disorders, disorders or pain not defined, disorder of the respiratory system, skin diseases and subcutaneous tissue disorder, and disorder of the sensory system (ears) showed greater agreement among informants in the use of species to treat a specific body system. The results showed a high species richness of the medicinal flora present in the Brazilian Caatinga. Thus, it is necessary to intensify and consolidate studies assessing the chemical and pharmacological properties of these species.

Exclusion of Class III malocclusion candidate loci in Brazilian families.

The role played by genetic components in the etiology of the Class III phenotype, a class of dental malocclusion, is not yet understood. Regions that may be related to the development of Class III malocclusion have been suggested previously. The aim of this study was to search for genetic linkage with 6 microsatellite markers (D1S234, D4S3038, D6S1689, D7S503, D10S1483, and D19S566), near previously proposed candidate regions for Class III. We performed a two-point parametric linkage analysis for 42 affected individuals from 10 Brazilian families with a positive Class III malocclusion segregation. Analysis of our data indicated that there was no evidence for linkage of any of the 6 microsatellite markers to a Class III locus at = zero, with data supporting exclusion for 5 of the 6 markers evaluated. The present work reinforces that Class III is likely to demonstrate locus heterogeneity, and there is a dependency of the genetic background of the population in linkage studies.

Evidence for an association between haptoglobin and MnSOD (Val9Ala) gene polymorphisms in essential hypertension based on a Brazilian case-control study.

Essential hypertension is a complex and multifactorial trait; genetic and environmental factors interact to produce the final phenotype. Studies have demonstrated association of hypertension with varied gene polymorphisms. However, demonstration of common genetic causes in the general population remains elusive. We investigated a possible association between hypertension and haptoglobin, angiotensin I-converting enzyme (ACE), glutathione S-transferases GSTM1 and GSTT1, MnSOD (Val9Ala), CAT (-21A/T), and GPX1 (Pro198Leu) gene polymorphisms in an urban Brazilian population group from Brasília. Although ACE has been reported to be one of the main polymorphisms associated with hypertension, we found no association with ACE's specific genotypes. However, a possible association with Hp1-1 and MnSOD Val/Ala genotypes suggests that, at least for the Brazilian population, polymorphisms related to oxidative stress should be more deeply investigated.

[The anatomical-functional characteristics of the pelvic floor and quality of life of women with stress urinary incontinence subjected to perineal exercises]. / Las características anatomofuncionales del suelo pélvico y la calidad de vida de mujeres con incontinencia urinaria de esfuerzo sometidas a ejercicios perineales.

OBJECTIVE: To determine the effects of exercise in anatomic abnormalities of the pelvic floor (SP) and the quality of life (QOL) of women with stress urinary incontinence (SUI). METHOD: An experimental study with 50 women with SUI, distributed randomly into two groups, experimental (GE, 49.24±7.37 years) and control group (CG; 45.25±5.60 years). The groups performed ultrasound evaluation of the SP, evidence of pelvic floor muscle strength by palpation bidigital, surface EMG motor activity and replied to the CV before and after treatment. The GE had 16 sessions of pelvic floor exercises twice a week for 30min. RESULTS: Comparison between the GE and GC revealed significant differences in favor of GE, namely: mobility of the bladder neck (Δ=-0.79mm, p=0.00), thickness of pelvic floor muscle (Δ=-0.04mm, p=0.00), EMG (Δ=0.05.V, p=0.00), muscle strength by the AFA (Δ=0.05 level, p=0.00), DOMI1 (Δ%=5.67%, p=0.00), DOMI2 (Δ%=18.00%, p=0.00), DOMI3 (Δ%=18.22%, p=0.00), DOMI4 (Δ%=4.45%, p=0.00), DOMI5 (Δ%=0.22%, p=0.00), DOMI6 (Δ%=2.00%, p=0.00), DOMI7 (Δ%=3.78%, p=0, 00), DOMI8 (Δ%=6.33%, p=0.00), DOMI9 (Δ%=4.03%, p=0.00). CONCLUSION: It was modified and improved anatomic features of the pelvic floor of women from GE through perineal exercises, which will positively influence the CV of these women.

Genetic polymorphisms in oestrogen metabolic pathway and breast cancer: a positive association with combined CYP/GST genotypes.

The cytochrome P450 family (CYPs) and the glutathione S-transferase (GSTs) enzymes play an important role in the metabolism of environmental carcinogens and of oestrogen and can affect breast cancer risk. In this study we examine the role of the genes CYP1A1, CYP17, CYP2D6, GSTM1, GSTP1 and GSTT1 in breast cancer risk in Brazilian women. The study population consisted of 102 incident breast cancer cases and 102 healthy controls. Genotyping analyses were performed by PCR-based methods. A significant finding was observed between GSTP1 Ile-Val polymorphism and breast cancer risk (OR = 1.81; CI 95% = 1.04-3.16). A significant association was observed between women with 0-2 risk genotypes and those with 4 or more risk genotypes (OR = 2.42; CI 95% = 1.13-5.18) when the potential combined effects of the risk genotypes were examined. No significant differences between cases and controls were found correlating the genotypes and the clinical-histopathological parameters. In conclusion, in our population only GSTP1 was associated with breast cancer risk. However, when the genes were tested in combination, a significant association in the breast cancer risk was observed.

Genetic variability in maned wolf based on heterologous short-tandem repeat markers from domestic dog.

The maned wolf (Chrysocyon brachyurus) is the largest South American canid. Habitat loss and fragmentation, due to agricultural expansion and predatory hunting, are the main threats to this species. It is included in the official list of threatened wildlife species in Brazil, and is also protected by IUCN and CITES. Highly variable genetic markers such as microsatellites have the potential to resolve genetic relationships at all levels of the population structure (among individuals, demes or metapopulations) and also to identify the evolutionary unit for strategies for the conservation of the species. Tests were carried out to verify whether a class of highly polymorphic tetranucleotide repeats described for the domestic dog effectively amplifies DNA in the maned wolf. All five loci studied were amplified; however, one of these, was shown to be monomorphic in 69 maned wolf samples. The average allele number and estimated heterozygosity per polymorphic locus were 4.3 and 67%, respectively. The genetic variability found for this species, which is considered threatened with extinction, showed similar results when compared to studies of other canids.

Genetic variability in maned wolf based on heterologous short-tandem repeat markers from domestic dog

The maned wolf (Chrysocyon brachyurus) is the largest South American canid. Habitat loss and fragmentation, due to agricultural expansion and predatory hunting, are the main threats to this species. It is included in the official list of threatened wildlife species in Brazil, and is also protected by IUCN and CITES. Highly variable genetic markers such as microsatellites have the potential to resolve genetic relationships at all levels of the population structure (among individuals, demes or metapopulations) and also to identify the evolutionary unit for strategies for the conservation of the species. Tests were carried out to verify whether a class of highly polymorphic tetranucleotide repeats described for the domestic dog effectively amplifies DNA in the maned wolf. All five loci studied were amplified; however, one of these, was shown to be monomorphic in 69 maned wolf samples. The average allele number and estimated heterozygosity per polymorphic locus were 4.3 and 67%, respectively. The genetic variability found for this species, which is considered threatened with extinction, showed similar results when compared to studies of other canids.

Group-specific component (GC) in Curiaú and Pacoval, two African-derived Brazilian populations.

The group-specific component (GC) system is of interest in anthropological genetic studies because the distribution of its subtypes distinguishes among major ethnic groups. The GC system was analyzed in Curiaú and Pacoval, two remnant Quilombo populations (African-derived populations) from the Brazilian Amazon. There was no significant statistical difference in allelic frequencies between the two populations or between them and three other African-derived Brazilian populations (Mimbó, Sítio Velho, and Gaucinha in Northeastern Brazil). These populations share similarities among themselves and with African populations (high frequencies of GC*1F and lower frequencies of GC*1S), which may reflect the influence of a high level of African contribution to their formation, but there is a clear difference between them and Europeans and South American Indians. It is suggested that the GC system is a useful marker for studying relationships between single populations and major ethnic groups, but does not discriminate between populations which share the same parental stock.

Granulated decidual cells in the mouse deciduoma: a putative source of decidual prolactin in mice.

Decidual cells are endometrial fibroblasts that redifferentiate during pregnancy in several species of mammals. In this work, we describe a subpopulation of resident decidual cells in the mouse endometrium that are joined by intercellular junctions and have cytoplasmic granules. Decidualization was induced in pseudopregnant mice on the 4th day of pseudopregnancy by injection of 30 microl of arachis oil into the uterine lumen. The uteri were collected on day 8 of pseudopregnancy (at 4 p.m., 8 p.m. and 11 p.m.) and on day 9 (at 8 a.m.). The tissues were fixed for light and electron microscopy. During day 8 of pseudopregnancy, granulated cells were present at the antimesometrial pole of the endometrium; they were concentrated at the periphery of the antimesometrial decidua and disappeared on day 9 of pseudopregnancy. The cytoplasm of the granulated decidual cells had acidophilic granules that stained also with periodic acid-Schiff (PAS). These granules stained with anti-rat prolactin antibody in both light and electron microscope immunocytochemical preparations. Vacuoles of various sizes were always present in the granulated cells. A PAS-positive and prolactin-stained material was often deposited at the periphery of the vacuoles. Our results indicate that the granulated decidual cells are the source of decidual prolactin which accumulates in cytoplasmic granules. These granulated cells therefore form a transient gland in the mouse antimesometrial endometrium (granulated decidual gland).

Organization of desmin-containing intermediate filaments during differentiation of mouse decidual cells.

Decidualization of the mouse endometrium consists of a redifferentiation of the endometrial stromal fibroblasts. During decidualization these fibroblasts undergo growth, change of shape, multinucleation, and establishment of intercellular junctions. One feature of rodent decidual cells is the accumulation of intermediate filaments. In spite of the fact that fibroblasts normally have vimentin intermediate filaments, they acquire a large amount of desmin intermediate filaments while they undergo decidualization. The light and electron microscope immunocytochemical results of the present work show that during the initial stages of decidual transformation the desmin intermediate filaments accumulate around the nuclei, often forming caps around the nuclear envelope. As the decidual cells grow, the filaments form bundles and nets that radiate from the nuclei toward the cell surface. During the final stages of differentiation, on day 8 of pregnancy, staining of differentiated decidual cells decreases and most filaments accumulate under the cell surface. A role for intermediate filaments is suggested for decidualization of mouse endometrial cells.

Advanced oviductal development, transport to the preferred implantation site, and attachment of the blastocyst in captive-bred, short-tailed fruit bats, Carollia perspicillata.

The final stages of embryonic development in the oviduct, transport of the embryo to the uterus, and the initial stages of implantation have been examined in captive-bred Carollia perspicillata at the light and electron microscopic levels. Development progressed to the expanded, zona pellucida-free, blastocyst stage in the oviduct. The abundance of microvilli on the exterior of the trophoblast varied with the degree of blastocyst expansion and cell shape, and may function in part as a membrane reservoir. Cells of the blastocyst also typically contained many lipid droplets and prominent areas of cytoplasm occupied by finely granular material (probably glycogen) instead of organelles. In most females, closure of the uterine lumen occurred prior to, or around the time of, transport of the blastocyst to the usual implantation site and appeared to play a role in preventing transport of the blastocyst too far distally in the uterus. This was associated with increased endometrial edema, particularly in the fundic region of the simplex uterus, and the extravasation of many erythrocytes into the endometrial stroma. Both of these changes began while the blastocyst was still being held in the oviduct and became pronounced during implantation. Engulfment of these erythrocytes by processes of the endometrial stromal cells and their phagocytosis by macrophages was also observed. Implantation was usually initiated within narrow tubular segments, lined by endometrium, that were located between the end of each oviduct and the main cavity of the uterus, or from immediately adjacent areas of the main cavity. During the early stages of implantation, the blastocyst was clasped by the endometrium at the implantation site, and this was associated with extensive interdigitation of the microvilli of the trophoblast and adjacent uterine epithelial cells. Initial adhesion of the trophoblast, which was still cellular rather than synctial, occurred over the apical intercellular junctions of the uterine epithelial cells.

Light and electron microscopic analysis of controlled injury to follicular unit grafts.

BACKGROUND: Careful manipulation of hair units is essential for a good yield of transplanted hair. OBJECTIVE: To analyze the morphology of dissected follicular units submitted to crushing, stretching, bending, and drying. METHODS: Follicular units were either crushed, bent, stretched with forceps, or left drying on surgical gloves for 3 minutes. The specimens were fixed and prepared for observation with light microscopy or transmission and scanning electron microscopy. RESULTS: No alterations were detected in follicular units that had been crushed, bent, or stretched. Major damage occurred in samples that were left to dry on gloves. CONCLUSION: Letting the follicular unit dry appears to be the worst mishandling to which the follicular units may be subjected during routine hair transplantation.

Coronary artery bypass graft surgery in patients with ischemic cardiomyopathy and severe left ventricular dysfunction: short and long-term results.

BACKGROUND: We evaluated the prognostic value of preoperative parameters, surgical risk, functional benefits and long-term survival after myocardial revascularization in patients with established ischemic cardiomyopathy. METHODS: Seventy-one patients with ischemic cardiomyopathy, severe left ventricular dysfunction (left ventricular ejection fraction < 30%), and myocardial perfusion evaluated by Thallium-201 scintigraphy, were studied before and after myocardial revascularization, during hospitalization and throughout 48 months (average) of late follow-up. RESULTS: The early postoperative mortality was 2.8% and the five-year survival rate was 62.8%. When the survival rate was studied, there was no correlation with 1) the presence of Q-waves on preoperative cardiogram, 2) the presence of ischemia on Tl-201 scintigraphy, 3) the degree of left ventricular ejection fraction, or 4) the presence of angina. There was a statistically significant difference for survivors and non-survivors in the following parameters: 1) functional class IV of CHF, and 2) the presence of left bundle-branch block (LBBB). CONCLUSIONS: Our surgical results confirm that myocardial revascularization is a safe procedure, and that it increases late survival and improves the quality of life in patients with ischemic cardiomyopathy and severe left ventricular dysfunction. We also observed that due to heterogeneous coronary and myocardial patterns of ischemic cardiomyopathy, preoperative prognostic parameters are difficult to establish. Preoperative functional class IV congestive heart failure, and LBBB were the main predictors of poor outcome following surgical revascularization for ischemic cardiomyopathy.

Functionally active cardiac antibodies in chronic Chagas' disease are specifically blocked by Trypanosoma cruzi antigens.

Antibodies of chronic chagasic patients have been shown to interfere with electric and mechanical activities of cardiac embryonic myocytes in culture and with whole mammalian hearts. A mechanism proposed for this effect involves interaction of the antibodies with G-protein-linked membrane receptors, thus leading to activation of beta adrenergic and muscarinic receptors; more specifically, IgG of chagasic patients would interact with the negatively charged regions of the second extracellular loop of these receptors. We performed competition experiments to test this hypothesis. We evaluated the effect of sera/IgG from patients previously known to depress electrogenesis and/or atrioventricular conduction in isolated rabbit hearts after incubation with live and lysed parasites, the peptide corresponding to the second extracellular loop (O2) of the M2 receptor, and different peptides derived from two ribosomal proteins of T. cruzi: P0 and P2beta. Our results indicate that 1) the antigenic factor inducing the functionally active IgGs in the chagasic patients is probably an intracellular T. cruzi antigen; 2) IgG/serum is interacting with the O2 region of the M2 receptor in the rabbit heart; and 3) the negative charges present in the ribosomal proteins of T. cruzi are important in mediating the interaction between the patients' serum/IgG and the receptor.

Autoradiography reveals regional metabolic differences in the endometrium of pregnant and nonpregnant mice.

The rodent endometrium undergoes remarkable modifications during pregnancy, resulting from a redifferentiation of its fibroblasts. During this modification (decidualization), the fibroblasts transform into large, polyhedral cells that establish intercellular junctions. Decidualization proceeds from the subepithelial stroma towards the deep stroma situated next to the myometrium and creates regions composed of cells in different stages of differentiation. We studied by autoradiography whether cells of these different regions have different levels of macromolecular synthesis. Radioactive amino acids or radioactive sulfate were administered to mice during estrus or on different days of pregnancy. The animals were killed 30 min after injection of the precursors and the uteri were processed for light microscope autoradiography. Silver grains were counted over cells of different regions of the endometrium and are reported as the number of silver grains per area. Higher levels of incorporation of amino acids were found in pregnant animals as compared to animals in estrus. In pregnant animals, the region of decidual cells or the region of fibroblasts transforming into decidual cells showed the highest levels of synthesis. Radioactive sulfate incorporation, on the other hand, was generally higher in nonpregnant animals. Animals without decidual cell transformation (nonpregnant and 4th day of pregnancy) showed a differential incorporation by subepithelial and deep stroma fibroblasts. This study shows that regional differences in synthetic activity exist in cells that are in different stages of transformation into decidual cells as well as in different regions of the endometrium of nonpregnant mice.

The Awá-Guajá Indians of the Brazilian Amazon. Demographic data, serum protein markers and blood groups.

The South-American Indian group Awá-Guajá, currently living in the State of Maranhão (Northeastern Brazil), is one of the most recently contacted Indian groups of the Brazilian Amazon. This group is made up by three partially isolated villages named Awá, Guajá and Juriti, and is characterized by having a young population, in which 47.6% of the individuals range from 0 to 14 years old. The sex ratios (male/female) for people of reproductive age are 1.13 for Awá village, 2.00 for Guajá, 3.33 for Juriti and 1.61 for the tribe as a whole. Fst and heterogeneity analysis show that, despite the small differences observed among villages for the eight genetic systems analyzed, the Awá-Guajá tribe is constituted of only one population. Furthermore, comparisons between Awá-Guajá and Urubú-Kaapor tribes indicate that they are still isolated genetically, in spite of the fact that they share territories.