Dental Anomalies and Genetic Polymorphisms as Predictors of Maxillofacial Growth in Individuals Born with Cleft Lip and Palate.

Cleft lip and palate have a complex inheritance, and 90% of its variation in the population is due to genetic contributors. The impact of surgical procedures on maxillofacial growth is well known, but the interference of intrinsic factors in these growth outcomes is not elucidated. The present study aimed to analyze genetic polymorphisms and frequency of dental anomalies as predictors of maxillofacial growth in patients born with cleft lip with or without cleft palate. From a cohort of 537 individuals, operated on by the same surgeon, 121 were analyzed 2 times, to define changes in maxillary growth prognosis by occlusal scores in a minimum 4-y follow-up. In a second step, a subset of 360 individuals had maxillofacial growth outcomes evaluated using Wits, nasion perpendicular to point A, and occlusal scores. The markers MMP2 rs9923304, GLI2 rs3738880 and rs2279741, TGFA rs2166975, and FGFR2 rs11200014 and rs10736303 were genotyped, and frequency of dental anomalies and cleft severity were determined to define evidence of overrepresentation of alleles associated with maxillofacial growth outcomes. Age and age at primary surgical treatment, sex, and cleft laterality were variables adjusted in the analysis. We found an association between the frequency of dental anomalies and the maxillofacial growth in unilateral (P = 0.001) and bilateral (P = 0.03) individuals with clefts. MMP2 rs9923304 and maxillofacial growth were associated (P < 0.0001). There was also an association between GLI2 rs3738880 and TGFA rs2166975 and maxillary outcomes in individuals born with unilateral cleft lip and palate (P = 0.003 and P = 0.004, respectively), as well as between FGFR2 rs11200014 and maxillary outcomes regardless of cleft type (P = 0.005). Statistical evidence of an interaction between MMP2 rs9923304 and GLI2 rs3738880 was observed (P < 0.0001). Presence of dental anomalies and genetic variation in MMP2, GLI2, TGFA, and FGFR2 were associated with worse maxillofacial growth outcomes in individuals born with clefts.

Pulp enlargement in individuals born with cleft lip and palate pulp, a radiographic study from the cleft lip and palate service of paraiba, Brazil'.

PURPOSE: Pulp chamber enlargement impacts endodontic treatment planning. The aim of this study was to evaluate alterations in pulp chamber size of posterior teeth in individuals born with cleft lip with or without cleft palate. METHODS: Ninety individuals were treated at the Cleft Lip and Palate Service of the University Hospital Lauro Wanderley, Federal University of Paraíba, between the ages of 4 and 15 years born with cleft lip with or without cleft palate were selected. Ninety-nine patients from the archives of the residency program in Orthodontics of the Brazilian Dental Association (ABO) were paired by sex and age as a comparison group. Radiographs were evaluated by a single examiner, observing the presence/absence of an enlarged pulp chamber in the first and second permanent molars of all quadrants. Chi square or Fisher's exact tests were used (α = 0.05) in all comparisons. RESULTS: Pulp enlargement was more frequently found among individuals born with cleft lip with or without cleft palate (p = 0.0005). However, pulp enlargement frequency was different among subjects born with clefts (p = 0.0006). Pulp enlargement was more common in the maxilla, in both groups. Individuals born with cleft lip with or without cleft palate more often had six or more teeth affected (p = 0.02). Furthermore, individuals with a bilateral cleft more often had six or more teeth affected in comparison to unilateral cases (p = 0.002). CONCLUSION: Pulp enlargement is a frequent finding, particularly among individuals born with cleft lip with or without cleft palate, with a higher prevalence in the maxilla.

Initial Dynamic Susceptibility of Maghemite Nanoparticles Dispersed in Surface-Treated Polymeric Template.

Magnetic nanocomposites based on maghemite nanoparticles supported (ex situ route) on styrene- divinilbenzene (Sty-DVB) copolymer templates were produced and characterized for their structure and morphology. The as-produced nanocomposites were further chemically-treated with different oxidant agents and surface-coated with stearic acid. X-ray diffraction and transmission electron microscopy data show that the incorporated nanoparticles are preserved despite the aggressive chemical treatments employed. From the dynamical susceptibility measurements performed on the nanocomposites, the values of the saturation magnetization (76 emu/g) and the effective magnetic anisotropy (1.7 × 104 J/m³) were obtained, in excellent agreement with the values reported in the literature for maghemite. This finding strongly supports the preservation of the magnetic properties of the supported nanosized maghemite throughout the entire samples' processing.

COMT rs4818, pain sensitivity and duration, and alveolar bone grafting of oral clefts.

PURPOSE: Verifying whether the mutation in COMT rs4818 could be involved in pain modulation. METHODS: Thirty-two individuals born with cleft lip and palate that underwent bone graft from the iliac crest bone were assessed at 12, 24, 48, 72 h, and 7 days regarding their pain experience using a visual analogic scale. DNA from each participant was collected from saliva samples, and genotyping of rs4818 was performed using TaqMan chemistry. Overrepresentation of rs4818 alleles was tested using chi-square or Fisher's exact tests with an alpha of 0.05. RESULTS: Of the 32 individuals, eighteen reported long pain duration, nine reported high pain intensity, and fourteen low pain intensity up to 48 h. No differences were found in the distribution of individuals depending on the reported pain by sex (p = 0.12), age (p = 0.42), or cleft type (p = 0.5). The distribution of COMT r4818 alleles was different depending on the intensity and duration of pain. Carriers of the C wild-type allele were four times more likely to show high pain intensity and duration (odds ratio = 4.29, 95% confidence interval 1.13-16.18), meaning that the G variant allele is protective. CONCLUSION: COMT rs4818 is associated with postoperative pain after alveolar bone grafting.

Neurotoxicity in zebrafish exposed to carbon nanotubes: Effects on neurotransmitters levels and antioxidant system.

Given the increasing use of carbon nanotubes (CNT) in several industries and technological applications, it is essential to perform in vivo toxicological studies with these nanomaterials to evaluate their potential ecotoxicity. Dopamine (DA) and serotonin (5HT) are key neurotransmitters for brain functions and behavioral responses. Determination of DA and 5HT were performed in brain samples from zebrafish Danio rerio exposed i.p. to single-walled CNT (SWCNT), besides analyzing acetylcholinesterase (AChE) and ectonucleotidases activity, lipid peroxidation and total antioxidant capacity. Results showed that treatment with SWCNT increased between 3 and 6-fold the concentration of DA and 5HT (p < 0.05). Similarly, a significant reduction (p < 0.05) in AChE activity was observed in the brains of SWCNT exposed zebrafish when compared to the control groups. Cholinergic, serotonergic, and dopaminergic systems, through AChE activity and serotonin and dopamine levels, respectively were affected by SWCNT in the zebrafish brain. Alterations in these neurotransmitters can potentially affect several physiological and behavioral that they control.

Spin-Current to Charge-Current Conversion and Magnetoresistance in a Hybrid Structure of Graphene and Yttrium Iron Garnet.

The use of graphene in spintronic devices depends, among other things, on its ability to convert a spin excitation into an electric charge signal, a phenomenon that requires a spin-orbit coupling (SOC). Here we report the observation of two effects that show the existence of SOC in large-area CVD grown single-layer graphene deposited on a single crystal film of the ferrimagnetic insulator yttrium iron garnet (YIG). The first is a magnetoresistance of graphene induced by the magnetic proximity effect with YIG. The second is the detection of a dc voltage along the graphene layer resulting from the conversion of the spin current generated by spin pumping from microwave driven ferromagnetic resonance into a charge current, which is attributed to the inverse Rashba-Edelstein effect.

Correlation between (in)commensurate domains of multilayer epitaxial graphene grown on SiC(0001) and single layer electronic behavior.

A systematic study of the evolution of the electronic behavior and atomic structure of multilayer epitaxial graphene (MEG) as a function of growth time was performed. MEG was obtained by sublimation of a 4H-SiC(0001(-)) substrate in an argon atmosphere. Raman spectroscopy and x-ray diffraction were carried out in samples grown for different times. For 30 min of growth the sample Raman signal is similar to that of graphite, while for 60 min the spectrum becomes equivalent to that of exfoliated graphene. Conventional x-ray diffraction reveals that all the samples have two different (0001) lattice spacings. Grazing incidence x-ray diffraction shows that thin films are composed of rotated (commensurate) structures formed by adjacent graphene layers. Thick films are almost completely disordered. This result can be directly correlated to the single layer electronic behavior of the films as observed by Raman spectroscopy. Finally, to understand the change in lattice spacings as a result of layer rotation, we have carried out first principles calculations (using density functional theory) of the observed commensurate structures.

Dermatofilose em ovinos da raça Santa Inês no Distrito Federal / Dermatophylosis in Santa Inês sheep from Distrito Federal

Relataram-se quatro casos de dermatofilose em ovinos da raça Santa Inês, no período de um ano. Microscopicamente observaram-se filamentos na forma de "trilho de bonde" e zoósporos nos quatro casos. A tentativa do isolamento do microrganismo foi realizada por meio do método de Haalstra e em apenas um caso obteve-se sucesso, observando-se colônias de aparência lisa, formato circular, cor amarelada e hemolítica em ágar sangue. O exame direto com coloração de Gram mostrou-se um método bastante eficiente na confirmação da presença do microrganismo afetando a epiderme em razão da morfologia típica do agente.

Four cases of dermatophylosis were reported in Santa Inês sheep in a study period of one year. Microscopically, septate filaments and coccoid forms zoospores were observed. Attempts to isolate the microorganisms were accomplished using Haastra's method and it was successful in only one case. Dermatophilus congolensis samples have grown on blood agar, colonies where hemolytic, small, round and pigmentation vary from yellow to orange. The gram staining method was efficient to confirm the presence of the microorganism affecting the epidermis due to typical morphology of the agent.

Metastable phase formation and structural evolution of epitaxial graphene grown on SiC(100) under a temperature gradient.

Multilayer epitaxial graphene was obtained from a 6H-SiC(001) substrate subjected to a temperature gradient from 1250 to 1450 °C. Scanning tunneling microscopy and x-ray diffraction were used to identify the structure and morphology of the surface, from which the formation of a metastable phase was inferred. By a comparison between microscopy and diffraction data, we report the appearance of misoriented Si-doped graphene in cold regions (1250 °C) of the substrate. This metastable phase occurs in domains where silicon sublimation is incomplete and it coexists with small domains of epitaxial graphene. At 1350 °C this phase disappears and one observes complete graphene-like layers (although misoriented), where rotational registry between the underlying epitaxial graphene and additional layers is absent. At 1450 °C the stacking among layers is established and the formation of highly oriented single crystalline graphite is complete. The stability of this Si-rich metastable phase at 1250 °C was confirmed by first-principles calculations based on the density functional theory.

A possible role of a cerebral energy gene in alcoholism.

We examined a possible relationship between genes responsible for energy metabolism of the brain and addictive behavior in an animal model. We used non-inbred, Swiss mice exposed to a three-bottle free-choice model [water, 5% (v/v) ethanol, and 10% (v/v) ethanol] over a 16-week period, consisting of four phases: acquisition, withdrawal, reexposure, and quinine-adulteration. The mice were then behaviorally classified into three groups: loss-of-control-drinker (preference for ethanol and high levels of consumption during all phases, N = 6), heavy-drinker (preference for ethanol and high levels of consumption during acquisition and reduction during quinine-adulteration, N = 7), and light-drinker (preference for water during all phases, N = 10). Another group only received tap water (ethanol-naive control mice, N = 9). Further analysis using quantitative real-time PCR showed that in mice behaviorally classified as loss-of-control-drinkers, there was a significant inverse correlation between transcript levels of the Hadh gene and those of other energy metabolism genes in the nucleus of the amygdala, suggesting that this pathway may contribute to ethanol consumption in these mice. We conclude that cerebral energy metabolism is involved with ethanol addiction, meriting further study.

Hydrogen sensing in titanate nanotubes associated with modulation in protonic conduction.

Hydrogen/sodium titanate nanotubes (TNTs) were investigated as hydrogen (H(2)) sensors. TNT films exhibit good sensing properties and a large response, in particular at room temperature. Electrical conductivity measurements performed under different atmospheres from 25 to 300 °C indicate that, for T > 100 °C, conduction is thermally activated and can be attributed to electronic transport, whereas for T < 100 °C conduction is dominated by protonic transport. The T dependence of the H(2) sensitivity was determined and related to this variation in the dominant transport mechanism. For low T, H(2) sensing originates from the modulation in protonic conduction. Such modulation was attributed to the creation/destruction of surface hydroxyl groups.

New material for low-dose brachytherapy seeds: Xe-doped amorphous carbon films with post-growth neutron activated 125I.

We report a novel material for use in (125)I brachytherapy that consists of amorphous carbon films grown by ion-beam-assisted deposition and doped with Xe (5 at%) by implantation. Samples of these films grown on Si substrates were irradiated with neutrons in a TRIGA-I nuclear reactor for the production (125)Xe, and latter characterized by gamma spectroscopy. The results indicate that the (124)Xe was efficiently converted into (125)Xe, the precursor of (125)I, and support the activity calculations for a model brachytherapy seed.

Highly efficient siRNA delivery system into human and murine cells using single-wall carbon nanotubes.

Development of RNA interference (RNAi) technology utilizing short interfering RNA sequences (siRNA) has focused on creating methods for delivering siRNAs to cells and for enhancing siRNA stability in vitro and in vivo. Here, we describe a novel approach for siRNA cellular delivery using siRNA coiling into carboxyl-functionalized single-wall carbon nanotubes (SWCNTs). The CNT-siRNA delivery system successfully demonstrates nonspecific toxicity and transfection efficiency greater than 95%. This approach offers the potential for siRNA delivery into different types of cells, including hard-to-transfect cells, such as neuronal cells and cardiomyocytes. We also tested the CNT-siRNA system in a non-metastatic human hepatocellular carcinoma cell line (SKHep1). In all types of cells used in this work the CNT-siRNA delivery system showed high efficiency and apparent no side effects for various in vitro applications.

Eritrograma e variantes de hemoglobina em caprinos da raça Canindé / Erythrogram and hemoglobin types in Canindé goats

The erythrogram and hemoglobin types in Canindé goats were determined. Twenty blood samples were collected from the animals and used for determination of packed cell volume (PCV), erythrocytes counts, hemoglobin concentration, calculation of mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC), and electrophoretic separation of hemoglobin types. The values for erythrogram were: PCV 34.6±4.62 percent, hemoglobin 10.1±1.05mg/dl, erythrocytes 15.3±4.54x106/mm3, MCV 24.0±5.83fl, and MCHC 29.3±2.44g/dl. Electrophoretic separation of hemoglobin types revealed only one type characterized as hemoglobin A (HbAA).

Deformação relativa e frouxidão do tendão calcanear durante mobilização articular passiva através de ultra-sonografia por imagem / Strain and slackness of achilles tendon during passive joint mobilization via imaging ultrasonography

CONTEXTUALIZAÇÃO: O estudo do comportamento das propriedades mecânicas do tendão in vivo pode trazer avanços na avaliação do impacto de programas de intervenção para flexibilidade e força, nas áreas clínica e desportiva. OBJETIVO: O objetivo deste trabalho foi quantificar a deformação (strain) e a frouxidão (slackness) relativas do tendão calcanear, durante mobilização passiva para quatro ângulos articulares do tornozelo e dois do joelho. MATERIAIS E MÉTODOS: O deslocamento da junção miotendínea foi quantificado através de imagens ultra-sonográficas capturadas durante a mobilização passiva do tornozelo, com o auxílio de um eletrogoniômetro e um eletromiógrafo, para garantir as angulações requeridas e a inatividade muscular, respectivamente. RESULTADOS: Os valores de deformação relativa encontrados variaram de 4,28±2,37 a -0,94±1,58 por cento para o joelho estendido e de 2,38±1,63 a -2,32±2,16 por cento para o joelho fletido. CONCLUSÕES: Os valores encontrados ratificam os da literatura, demonstrando a participação do tendão calcanear na variação do comprimento da unidade músculo-tendão, durante movimentação passiva. Estes resultados sugerem que as propriedades mecânicas dos tecidos tendinosos afetam a relação entre o comprimento das fibras e o ângulo articular, até mesmo nesse tipo de movimento.

BACKGROUND: In vivo study of the mechanical behavior of tendons may bring advances in evaluating the impact of intervention programs for flexibility and strength, in clinical practice and sports. OBJECTIVE: The aim of this study was to quantify the relative strain and slackness of achilles tendons during passive mobilization, for four ankle joint angles and two knee angles. METHODS: The displacement of the muscle-tendon junction was quantified by means of ultrasound images acquired during passive ankle mobilization, with the aid of an electrogoniometer and an electromyograph to ensure the achievement of the required angles and muscle inactivity, respectively. RESULTS: The strain values ranged from 4.28 percent±2.37 to -0.94 percent±1.58 for the fully extended knee, and from 2.38 percent±1.63 to -2.32 percent±2.16 percent for the flexed knee. CONCLUSIONS: The values found in this study confirm those in the literature and demonstrate how the Achilles tendon participates in length changes in the muscle-tendon unit during passive movement. These results suggest that the mechanical properties of tendinous tissues affect the relationship between the length of muscle fibers and the joint angle, even during this type of movement.

Lack of relation between drug-seeking behavior in an addiction model and the expression of behavioral sensitization in response to ethanol challenge in mice.

Drug-induced sensitization has been associated with enhanced self-administration and may contribute to addiction. The possible association between sensitization and voluntary ethanol consumption using an addiction model was investigated. Mice (n = 60) were individually housed with ad libitum access to food and had free choice between ethanol (5% and 10%) and water in a four-phase paradigm: free choice (12 weeks), withdrawal (2 weeks), re-exposure (2 weeks), and quinine-adulteration (2 weeks). Control mice (n = 10) had access to water. Mice were characterized as addicted (n = 10, ethanol preference without reducing intake with adulterated ethanol), heavy (n = 22, ethanol preference but reduced intake with adulterated ethanol), and light (n = 21, water preference). Oral ethanol then was withdrawn, and 24 h later mice received a 2 g/kg ethanol (i.p.) challenge dose or saline, and ambulation was evaluated 10 min later. Half of the classified mice received daily 2 g/kg ethanol injections for 14 days, and ambulation was assessed 10 min after the last dose. Acute ethanol increased ambulation in all groups compared to the control group, and chronic ethanol induced sensitization, showing no difference among ethanol-treated mice. The data suggest that independent neural mechanisms are responsible for the development of addiction and sensitization.

Serotonin 5-HT2 receptor antagonist does not reverse established ethanol-induced sensitization but blocks its development and expression.

Several substances that inhibit the induction or expression of behavioral sensitization have been proposed, but patients who present for treatment often have already an established sensitized drug response. Serotonergic agents, including serotonin-2 (5-HT(2)) antagonists, reverse cocaine sensitization, but there is no evidence for the same effect with ethanol, although serotonin involvement in ethanol sensitization has been well reported. To evaluate a 5-HT(2C) antagonist effect on reversing established ethanol sensitization, three experiments were performed assessing locomotor activity of mice under different treatments. First, mice received daily intraperitoneal saline (S), mianserin 10 (M1) or 20 mg/kg (M2), ethanol 2 g/kg (E), or ethanol+mianserin for 21 days. Then, each treatment was withdrawn for 3 days, and mice were randomly challenged with S, E, M1, or M2. During the next 7 days, S and E groups were subjected to daily treatment with S, E, M1, or M2. On the eighth day, all rats were tested under ethanol challenge. The saline group expressed sensitization under ethanol challenge similarly to the ethanol group. Mianserin+ethanol blocked the development of sensitization, suggesting an involvement of the 5-HT(2C) receptor subtype on ethanol-induced sensitization. Ethanol challenge to the chronic mianserin group did not express sensitization, implicating a role for mianserin in protection against stress. Mianserin did not reverse established ethanol sensitization, suggesting that cocaine- and ethanol-induced sensitization involved different mechanisms.

A putative gene located at the MHC class I region around the D6S105 marker contributes to the setting of CD8+ T-lymphocyte numbers in humans.

Significant associations between human leucocyte antigen (HLA)-A and -B alleles and CD8+ T-lymphocyte numbers have been reported in the literature in both healthy populations and in HFE-haemochromatosis patients. In order to address whether HLA alleles themselves or alleles at linked genes are responsible for these associations, several genetic markers at the MHC class I region were typed on a population of 147 apparently healthy unrelated subjects phenotypically characterized for their CD8+ and CD4+ T-lymphocyte numbers. By using a machine learning approach, a set of rules was generated that predict the number of CD8+ T-lymphocyte numbers on the basis of the information of the D6S105 microsatellite alleles only. We demonstrate that the previously reported associations with HLA-A and -B alleles are due to the presence of common long (up to 4 megabases long) haplotypes that increased in frequency recently due to positive selection and that encompass a region where a putative gene contributing to the setting of CD8+ T lymphocytes is located, in the neighbourhood of microsatellite locus D6S105, in the 6p21.3 region.

Development of a mouse model of ethanol addiction: naltrexone efficacy in reducing consumption but not craving.

The aim of the present study was validating pharmacologically a mouse model of alcohol addiction. Mice (n = 60) were offered ethanol (5% and 10%) and water in a free choice paradigm consisting of four phases: free choice (10 weeks), withdrawal (2 weeks), re-exposure (2 weeks) and quinine- adulteration (2 weeks). Control mice (n = 10) had access to water. They were housed individually with food ad libitum. The animals' behaviour was evaluated at the beginning of the treatment and during the withdrawal period. After the exposure to the model, mice received i.p. naltrexone (0.0; 0.125; 2.0 and 16.0 mg/kg) or saline. Mice were characterized as: addicted (n = 15, preference for ethanol without reducing intake when ethanol were adulterated with quinine); heavy drinker (n = 14, preference for ethanol but reduced intake when ethanol were adulterated); and light drinker (n = 16, no preference for ethanol). Naltrexone reduced ethanol intake in the heavy and light groups (p

Influence of fluoxetine and paroxetine in behavioral sensitization induced by ethanol in mice.

The serotonergic system is involved in depression, anxiety and alcoholism. The rewarding properties of ethanol, mainly its anxiolytic and stimulant effects, as well as the development of dependence on ethanol have been related to the serotonergic system. Consequently, the use of selective serotonergic reuptake inhibitors (SSRI) has been proposed in the treatment of alcoholism. In this study we investigated whether acute administration of the SSRIs fluoxetine or paroxetine is able to (i) reverse the behavioral effects induced by chronic ethanol consumption, and conversely, (ii) to determine whether acute ethanol is able to substitute for the chronically induced behavioral effects of fluoxetine or paroxetine. Four groups of male Swiss mice (n=60/group) received daily i.p. saline, ethanol (2 g/kg), fluoxetine (10 mg/kg) or paroxetine (5 mg/kg) for 27 days. On the 28th day, each group was challenged with saline, ethanol, fluoxetine or paroxetine. The 14 groups (SS, SE, SP, SF, EE, ES, EP, EF, PP, PE, PS, FF, FE, and FS) were then tested in open field, activity cage and plus-maze. EP and EF groups were able to reverse the behavioral sensitization to the psychomotor stimulant effects of chronic ethanol administration. In contrast, a sensitized stimulatory effect was observed in chronically fluoxetine- or paroxetine treated mice challenged with ethanol (PE and FE). An anxiolytic effect was observed whether ethanol was substituted for SSRI or, conversely, SSRI was substituted for ethanol. SSRIs facilitated ethanol-induced locomotor sensitization, although SSRIs by themselves are unable to produce the locomotor stimulation similar to that induced by ethanol. Finally, SSRIs are unable to interfere in the ethanol anxiolytic effect.