An experimental model for the study of craniofacial deformities

PURPOSE: To develop an experimental surgical model in rats for the study of craniofacial abnormalities. METHODS: Full thickness calvarial defects with 10x10-mm and 5x8-mm dimensions were created in 40 male NIS Wistar rats, body weight ranging from 320 to 420 g. The animals were equally divided into two groups. The periosteum was removed and dura mater was left intact. Animals were killed at 8 and 16 weeks postoperatively and cranial tissue samples were taken from the defects for histological analysis. RESULTS: Cranial defects remained open even after 16 weeks postoperatively. CONCLUSION: The experimental model with 5x8-mm defects in the parietal region with the removal of the periosteum and maintenance of the integrity of the dura mater are critical and might be used for the study of cranial bone defects in craniofacial abnormalities.

Regimes de precipitação na América do Sul: uma revisão bibliográfica

Como a América do Sul se estende por diferentes latitudes e possui formas de relevo variadas, proporciona a atuação e o desenvolvimento de diferentes sistemas atmosféricos, os quais contribuem para a não homogeneidade climática da região. Portanto o objetivo deste estudo é apresentar uma revisão dos sistemas atmosféricos que atuam nos diferentes setores do continente sul-americano e que contribuem para a precipitação.

Histological and radiological changes in cranial bone in the presence of bone wax

PURPOSE: To quantify the amount of bone formation in the calvarial region of Wistar rats after craniotomy using bone wax as a haemostatic agent. METHODS: Surgery to produce bilateral, symmetric, full-thickness cranial defects (area: 18 mm²) was performed in eight animals. The right side of the cranium remained open and the edges of the left side osseous defect was covered with bone wax. Calvaria were imaged immediately after surgery and 12 weeks postoperatively by computerized tomography. The areas of the bone defects were measured in three-dimensional images using Magics 13.0 (Materialise-Belgic, software CAD). RESULTS: The average amount of bone formation on the left and right side respectively was 4.85 mm² and 8.16 mm². Statistically significant differences between the amount of bone formation on the left and right sides were seen. CONCLUSIONS: Bone wax significantly diminishes the rate of bone formation in calvarial defects in a rat model.

Effects of uterine cervix constriction on Wistar rats

PURPOSE: To verify if uterine cerclage can induce craniosynostosis or any cranial deformity in new born Wistar rats. METHODS: One pregnant female Wistar rat underwent laparotomy on day 18 of gestation and the uterus cervix was closed with a 3-0 nylon suture to avoid delivery, that occurs normally on the 21 day. The suture was released after 48 hours beyond the normal gestation period. The female rat delivered 11 pups. Six surviving rats from the delivery (group A - constrained group). Two rats were born from another mother and in the same age were used as control group (group B - 2 nonconstrained controls) were allowed to grow. They were sacrificed 1.2 years after their birth all the eight animals. Linear measurement, routine histology and computed tomography of the skull were performed at the time of their death to evaluate the cranial asymmetries by mesurements of the anatomical landmarks of the craniofacial skeleton of the rats on the two groups and compared then. RESULTS: We did not observe statistically significant differences in any of the compared measurements (p>0.05) obtained through the morphologic and radiologic methods. Histologic examinations did not reveal any sign of premature fusion or suture imbrications. Critical decrease in longitudinal body size was noticed as the limbs too in all the animals of group A. CONCLUSION: Constriction of uterine cervix leads to fetus suffering, even death for a few animals, associated to small body size, but not to craniosynostosis.

Alveolar osseous defect in rat for cell therapy: preliminary report

PURPOSE: To study were to reproduce an alveolar bone defect model in Wistar rats to be used for testing the efficacy of stem cell therapies. Additionally, we also aimed to determine the osteogenesis process of this osseous defect in the 1 month period post-surgery. METHODS: The animals were randomly divided into two groups of 7 animals each. A gingivobuccal incision was made, and a bone defect of 28 mm² of area was performed in the alveolar region. Animals were killed at 2 weeks after surgery (n=7) and 4 weeks after surgery (n=7). RESULTS: The average area of the alveolar defect at time point of 2 weeks was 22.27 ± 1.31 mm² and the average area of alveolar defect at time point of 4 weeks was 9.03 ± 1.17 mm². The average amount of bone formation at time point of 2 weeks was 5.73 ± 1.31 mm² and the average amount of bone formation at time point of 4 weeks was 19 ± 1.17 mm². Statistically significant differences between the amount of bone formation at 2 weeks and 4 weeks after surgery were seen (p=0.003). CONCLUSION: The highest rate of ossification occurred mostly from 2 to 4 weeks after surgery. This observation suggests that 4 weeks after the bone defect creation should be a satisfactory timing to assess the potential of bone inductive stem cells to accelerate bone regeneration in Wistar rats.

Controle da adipogênese por ácidos graxos

A obesidade é um dos principais problemas de saúde pública. Indivíduos obesos são mais suscetíveis a desenvolver doenças cardiovasculares e diabetes melito tipo 2. A obesidade resulta do aumento no tamanho e no número de adipócitos. O balanço entre adipogênese e adiposidade determina o grau de obesidade do indivíduo. Adipócitos maduros secretam adipocinas, tais como TNFα, IL-6, leptina e adiponectina, e lipocina, o ácido palmitoleico ω-7. A produção de adipocinas é maior na obesidade, o que contribui para o estabelecimento de resistência periférica à insulina. O conhecimento dos eventos moleculares que regulam a diferenciação dos pré-adipócitos e de células-tronco mesenquimais em adipócitos (adipogênese) é importante para o entendimento da gênese da obesidade. A ativação do fator de transcrição PPARγ é essencial na adipogênese. Certos ácidos graxos são ligantes de PPARγ e podem, assim, controlar a adipogênese. Além disso, alguns ácidos graxos atuam como moléculas sinalizadoras em adipócitos, regulando sua diferenciação ou morte. Dessa forma, a composição lipídica da dieta e os agonistas de PPARγ podem regular o balanço entre adipogênese e morte de adipócitos e, portanto, a obesidade.

Nutraceuticals in reproduction of bulls and stallions

The industry has made available in the market a series of substances (nutraceuticals) which intent would be to optimize the use of nutrients in some metabolic paths, influencing positively reproductive performance in animals. However, the response to the use of nutraceuticals varies according to the animal. As the organism is highly complex and in order to achieve a perfect activity of the hypothalamic-pituitary-gonadal axis, an ideal interaction in molecular basis is needed, where the nutraceuticals can have their direct action. The aim of this study was to review the function and research results using the main nutraceuticals (β carotene, vitamin A, L-carnitine, omegas 3, 6 and 9 and Gamma-oryzanol) on reproductive characteristics of bulls and stallions.

Cross-national epidemiology of DSM-IV major depressive episode

Background: Major depression is one of the leading causes of disability worldwide, yet epidemiologic data are not available for many countries, particularly low- to middle-income countries. In this paper, we present data on the prevalence, impairment and demographic correlates of depression from 18 high and low-to middle-income countries in the World Mental Health Survey Initiative. Methods: Major depressive episodes (MDE) as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DMS-IV) were evaluated in face-to-face interviews using the World Health Organization Composite International Diagnostic Interview (CIDI). Data from 18 countries were analyzed in this report (n = 89,037). All countries surveyed representative, population-based samples of adults. Results: The average lifetime and 12-month prevalence estimates of DSM-IV MDE were 14.6% and 5.5% in the ten high-income and 11.1% and 5.9% in the eight low- to middle-income countries. The average age of onset ascertained retrospectively was 25.7 in the high-income and 24.0 in low- to middle-income countries. Functional impairment was associated with recency of MDE. The female: male ratio was about 2: 1. In high-income countries, younger age was associated with higher 12-month prevalence; by contrast, in several low-to middle-income countries, older age was associated with greater likelihood of MDE. The strongest demographic correlate in high-income countries was being separated from a partner, and in low- to middle-income countries, was being divorced or widowed. Conclusions: MDE is a significant public-health concern across all regions of the world and is strongly linked to social conditions. Future research is needed to investigate the combination of demographic risk factors that are most strongly associated with MDE in the specific countries included in the WMH.

Reduced transcription of TCOF1 in adult cells of Treacher Collins syndrome patients

Background: Treacher Collins syndrome (TCS) is an autosomal dominant craniofacial disorder caused by frameshift deletions or duplications in the TCOF1 gene. These mutations cause premature termination codons, which are predicted to lead to mRNA degradation by nonsense mediated mRNA decay (NMD). Haploinsufficiency of the gene product (treacle) during embryonic development is the proposed molecular mechanism underlying TCS. However, it is still unknown if TCOF1 expression levels are decreased in postembryonic human cells. Methods: We have estimated TCOF1 transcript levels through real time PCR in mRNA obtained from leucocytes and mesenchymal cells of TCS patients (n = 23) and controls (n = 18). Mutational screening and analysis of NMD were performed by direct sequencing of gDNA and cDNA, respectively. Results: All the 23 patients had typical clinical features of the syndrome and pathogenic mutations were detected in 19 of them. We demonstrated that the expression level of TCOF1 is 18-31% lower in patients than in controls (p < 0.05), even if we exclude the patients in whom we did not detect the pathogenic mutation. We also observed that the mutant allele is usually less abundant than the wild type one in mesenchymal cells. Conclusions: This is the first study to report decreased expression levels of TCOF1 in TCS adult human cells, but it is still unknown if this finding is associated to any phenotype in adulthood. In addition, as we demonstrated that alleles harboring the pathogenic mutations have lower expression, we herein corroborate the current hypothesis of NMD of the mutant transcript as the explanation for diminished levels of TCOF1 expression. Further, considering that TCOF1 deficiency in adult cells could be associated to pathologic clinical findings, it will be important to verify if TCS patients have an impairment in adult stem cell properties, as this can reduce the efficiency of plastic surgery results during rehabilitation of these patients.

Spatio-Temporal Tracking and Phylodynamics of an Urban Dengue 3 Outbreak in Sao Paulo, Brazil

The dengue virus has a single-stranded positive-sense RNA genome of similar to 10.700 nucleotides with a single open reading frame that encodes three structural (C, prM, and E) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins. It possesses four antigenically distinct serotypes (DENV 1-4). Many phylogenetic studies address particularities of the different serotypes using convenience samples that are not conducive to a spatio-temporal analysis in a single urban setting. We describe the pattern of spread of distinct lineages of DENV-3 circulating in Sao Jose do Rio Preto, Brazil, during 2006. Blood samples from patients presenting dengue-like symptoms were collected for DENV testing. We performed M-N-PCR using primers based on NS5 for virus detection and identification. The fragments were purified from PCR mixtures and sequenced. The positive dengue cases were geo-coded. To type the sequenced samples, 52 reference sequences were aligned. The dataset generated was used for iterative phylogenetic reconstruction with the maximum likelihood criterion. The best demographic model, the rate of growth, rate of evolutionary change, and Time to Most Recent Common Ancestor (TMRCA) were estimated. The basic reproductive rate during the epidemics was estimated. We obtained sequences from 82 patients among 174 blood samples. We were able to geo-code 46 sequences. The alignment generated a 399-nucleotide-long dataset with 134 taxa. The phylogenetic analysis indicated that all samples were of DENV-3 and related to strains circulating on the isle of Martinique in 2000-2001. Sixty DENV-3 from Sao Jose do Rio Preto formed a monophyletic group (lineage 1), closely related to the remaining 22 isolates (lineage 2). We assumed that these lineages appeared before 2006 in different occasions. By transforming the inferred exponential growth rates into the basic reproductive rate, we obtained values for lineage 1 of R(0) = 1.53 and values for lineage 2 of R(0) = 1.13. Under the exponential model, TMRCA of lineage 1 dated 1 year and lineage 2 dated 3.4 years before the last sampling. The possibility of inferring the spatio-temporal dynamics from genetic data has been generally little explored, and it may shed light on DENV circulation. The use of both geographic and temporally structured phylogenetic data provided a detailed view on the spread of at least two dengue viral strains in a populated urban area.

Cross-National Analysis of the Associations between Traumatic Events and Suicidal Behavior: Findings from the WHO World Mental Health Surveys

Background: Community and clinical data have suggested there is an association between trauma exposure and suicidal behavior (i.e., suicide ideation, plans and attempts). However, few studies have assessed which traumas are uniquely predictive of: the first onset of suicidal behavior, the progression from suicide ideation to plans and attempts, or the persistence of each form of suicidal behavior over time. Moreover, few data are available on such associations in developing countries. The current study addresses each of these issues. Methodology/Principal Findings: Data on trauma exposure and subsequent first onset of suicidal behavior were collected via structured interviews conducted in the households of 102,245 (age 18+) respondents from 21 countries participating in the WHO World Mental Health Surveys. Bivariate and multivariate survival models tested the relationship between the type and number of traumatic events and subsequent suicidal behavior. A range of traumatic events are associated with suicidal behavior, with sexual and interpersonal violence consistently showing the strongest effects. There is a dose-response relationship between the number of traumatic events and suicide ideation/attempt; however, there is decay in the strength of the association with more events. Although a range of traumatic events are associated with the onset of suicide ideation, fewer events predict which people with suicide ideation progress to suicide plan and attempt, or the persistence of suicidal behavior over time. Associations generally are consistent across high-, middle-, and low-income countries. Conclusions/Significance: This study provides more detailed information than previously available on the relationship between traumatic events and suicidal behavior and indicates that this association is fairly consistent across developed and developing countries. These data reinforce the importance of psychological trauma as a major public health problem, and highlight the significance of screening for the presence and accumulation of traumatic exposures as a risk factor for suicide ideation and attempt.

New Source of Muscle-Derived Stem Cells with Potential for Alveolar Bone Reconstruction in Cleft Lip and/or Palate Patients

Cleft lip and palate (CLP), one of the most frequent congenital malformations, affects the alveolar bone in the great majority of the cases, and the reconstruction of this defect still represents a challenge in the rehabilitation of these patients. One of the current most promising strategy to achieve this goal is the use of bone marrow stem cells (BMSC); however, isolation of BMSC or iliac bone, which is still the mostly used graft in the surgical repair of these patients, confers site morbidity to the donor. Therefore, in order to identify a new alternative source of stem cells with osteogenic potential without conferring morbidity to the donor, we have used orbicular oris muscle (OOM) fragments, which are regularly discarded during surgery repair (cheiloplasty) of CLP patients. We obtained cells from OOM fragments of four unrelated CLP patients (CLPMDSC) using previously described preplating technique. These cells, through flow cytometry analysis, were mainly positively marked for five mesenchymal stem cell antigens (CD29, CD90, CD105, SH3, and SH4), while negative for hematopoietic cell markers, CD14, CD34, CD45, and CD117, and for endothelial cell marker, CD31. After induction under appropriate cell culture conditions, these cells were capable to undergo chondrogenic, adipogenic, osteogenic, and skeletal muscle cell differentiation, as evidenced by immunohistochemistry. We also demonstrated that these cells together with a collagen membrane lead to bone tissue reconstruction in a critical-size cranial defects previously induced in non-immunocompromised rats. The presence of human DNA in the new bone was confirmed by PCR with human-specific primers and immunohistochemistry with human nuclei antibodies. In conclusion, we showed that cells from OOM have phenotypic and behavior characteristics similar to other adult stem cells, both in vitro and in vivo. Our findings suggest that these cells represent a promising source of stem cells for alveolar bone grafting treatment, particularly in young CLP patients.

Transiting exoplanets from the CoRoT space mission XVI. CoRoT-14b: an unusually dense very hot Jupiter

In this paper, the CoRoT Exoplanet Science Team announces its 14th discovery. Herein, we discuss the observations and analyses that allowed us to derive the parameters of this system: a hot Jupiter with a mass of 7.6 +/- 0.6 Jupiter masses orbiting a solar-type star (F9V) with a period of only 1.5 d, less than 5 stellar radii from its parent star. It is unusual for such a massive planet to have such a small orbit: only one other known higher mass exoplanet orbits with a shorter period.

Discovery of VVV CL001 A low-mass globular cluster next to UKS 1 in the direction of the Galactic bulge

Context. It is not known how many globular clusters may remain undetected towards the Galactic bulge. Aims. One of the aims of the VISTA Variables in the Via Lactea (VVV) Survey is to accurately measure the physical parameters of the known globular clusters in the inner regions of the Milky Way and search for new ones, hidden in regions of large extinction. Methods. From deep near-infrared images, we derive deep JHK(S)-band photometry of a region surrounding the known globular cluster UKS 1 and reveal a new low-mass globular cluster candidate that we name VVV CL001. Results. We use the horizontal-branch red clump to measure E(B-V) similar to 2.2 mag, (m - M)(0) = 16.01 mag, and D = 15.9 kpc for the globular cluster UKS 1. On the basis of near-infrared colour-magnitude diagrams, we also find that VVV CL001 has E(B-V) similar to 2.0, and that it is at least as metal-poor as UKS 1, although its distance remains uncertain. Conclusions. Our finding confirms the previous projection that the central region of the Milky Way harbours more globular clusters. VVV CL001 and UKS 1 are good candidates for a physical cluster binary, but follow-up observations are needed to decide if they are located at the same distance and have similar radial velocities.