Interaction between vitamin D level, antiseizure medications (ASM) and seizure control in epilepsy adult patients.

OBJECTIVE: To investigate vitamin D levels and factors associated with seizure control in adult patients with epilepsy (APE). METHOD: Cross-sectional study with APE in routine outpatient follow-up at a neurology clinic. Clinical variables, antiseizure medications (ASM) and vitamin D were investigated. Data were analyzed using the Chi2 or Fisher's exact tests, Mann-Whitney, Spearman's correlation coefficient, ROC curve and univariate and multiple logistic regression analysis. RESULTS: Mean age was 46.5±15.1 years and disease duration was 27.5±17.0 years; 52.7% (n=49) of patients used one ASM and 47.3% (n=44) used≥2 ASM. There was a significant difference in the level of vitamin D according to the number of ASM and it was higher in patients who used a single ASM (26.02±10.22 versus 22.50±8.69; P=0.048). In the logistic regression, when vitamin D level was set at 20ng/mL, the chance of seizure control for patients using a single ASM was 6.99 times greater than for those using≥2 ASM. When vitamin D level was set at 40ng/mL, the number of ASM did not modify seizure control. There was no correlation between vitamin D and disease duration, patient age and age at the time of the first seizure. In the logistic regression, it was observed that satisfactory levels of vitamin D did not modify potential seizure control. CONCLUSION: Thirty-three percent (33%) of patients presented with vitamin D deficiency (values below 20ng/mL) and 80% had vitamin D levels below what is recommended (30ng/mL). The use of ASM, when associated with different levels of vitamin D, modified the probability of seizure control in APE. Vitamin D levels and intrinsic epilepsy factors are associated with failure to effectively control seizures.

Subcellular localization of X-linked inhibitor of apoptosis protein (XIAP) in cancer: Does that matter?

X-linked inhibitor of apoptosis protein (XIAP) finely tunes the balance between survival and death to control homeostasis. XIAP is found aberrantly expressed in cancer, which has been shown to promote resistance to therapy-induced apoptosis and confer poor outcome. Despite its predominant cytoplasmic localization in human tissues, growing evidence implicates the expression of XIAP in other subcellular compartments in sustaining cancer hallmarks. Herein, we review our current knowledge on the prognostic role of XIAP localization and discuss molecular mechanisms underlying differential biological functions played in each compartment. The comprehension of XIAP subcellular shuttling and functional dynamics might provide the rationale for future anticancer therapeutics.

Mites (Mesostigmata: Melicharidae) associated with hummingbirds (Aves: Trochilidae) in Brazil

Mites of the family Melicharidae comprise 13 genera and 220 species often associated with edaphic environments and found in association with insects, birds and mammals. Two genera, Proctolaelaps and Tropicoseius, have been recorded in Brazil in association with birds and bromeliads. In this study, we add new locality and host-association records for Proctolaelaps superagui and Tropicoseius braziliensis in the country.

Ventromedial medullary pathway mediating cardiac responses evoked from periaqueductal gray.

Periaqueductal gray (PAG) is a midbrain region that projects to areas controlling behavioral and autonomic outputs and is involved in the behavioral and physiological components of defense reactions. Since Raphe Pallidus (RPa) is a medial medullary region comprising sympathetic premotor neurons governing heart function, it is worth considering the PAG-RPa path. We assessed: i) whether PAG projects to RPa; ii) the amplitude of cardiac responses evoked from PAG; iii) whether cardiovascular responses evoked from PAG rely on RPa. Experiments conducted in Wistar rats (±300 g) were approved by Ethics Committee CEUA-UFG (092/18). Firstly, (n = 3), monosynaptic retrograde tracer Retrobeads was injected into RPa; PAG slices were analyzed. Other two groups (n = 6 each) were anesthetized with urethane (1.4 g/kg) and chloralose (120 mg/kg) and underwent craniotomy, tracheostomy, catheterization of femoral artery and vein and of cardiac left ventricle. In one group, we injected the GABAA receptor antagonist, bicuculline methiodide (BMI - 40 pmol/100 nL) into lateral/dorsolateral PAG. Another group was injected (100 nL) with the GABAA receptor agonist muscimol (20 mM) into RPa, 20 min before BMI into PAG. The results were: i) retrogradely labelled neurons were found in PAG; ii) PAG activation by BMI caused positive chronotropism and inotropism, which were accompanied by afterload increases; iii) RPa inhibition with Muscimol reduced heart rate, arterial and ventricular pressures; iv) the subsequent PAG activation still increased arterial pressure, cardiac chronotropy and inotropy, but these responses were significantly attenuated. In conclusion, PAG activation increases cardiac chronotropy and inotropy, and these responses seem to rely on a direct pathway reaching ventromedial medullary RPa neurons.

Changes in the total ozone content over the period 2006 to 2100 and the effects on the erythemal and vitamin D effective UV doses for South America and Antarctica.

Recent studies show that the ozone layer will recover by the middle part of this century. This is a significant result arising from the Montreal Protocol, and highlights the success of this environmental protection agreement. Climate change projections show that Total Ozone Content (TOC) levels will increase significantly by the end of this century, mainly at higher latitudes. This increase may result in a reduction of the adverse effects of UV radiation overexposure. By contrast, reduced UV radiation levels at the surface of the Earth can result in reduced levels of vitamin D synthesis among the inhabitants of these regions. In this study we provide estimates for the UVI, erythemal, and vitamin-D weighted daily doses for ten different locations in South America and Antarctica. Our calculations were based on ozone projections provided by climate models set forth in the last IPCC report. Results show that the increase of TOC levels in middle and high latitude regions may result in decreased UVI and UV doses throughout the century. In high latitudes, erythemal doses and vitamin D synthesis doses may be reduced by up to 22 and 39%, respectively, if anthropogenic emissions continue to rise throughout the century. Furthermore, there may be reductions of up to 9 and 12%, respectively, in mid-latitudes (20°S to 35°S). Significant variations at Equatorial sites were not observed. In most of South America, the attenuation in UVR caused by increases in TOC during the 21st century is neither enough to promote protective effects from this radiation, nor for the lack of UVR for vitamin D synthesis. The incidence of UVR in tropical and sub-tropical areas of the continent will continue to be a public health risk for the entire 21st century during all seasons, regardless of the climatic scenarios. Our results can be used as an important tool for health studies focusing on the excess and/or lack of sun exposure.

Geographical Distribution of Schizotetranychus hindustanicus and Associated Mites in Roraima, Brazil.

The Hindustan citrus mite, Schizotetranychus hindustanicus Hirst (Acari: Tetranychidae), is a quarantine pest present in the state of Roraima, Brazil. This mite, which was described in India in 1924, was reported in 2002 in Venezuela and spread to Roraima, where it was reported in 2008, and to Colombia, where it was reported in 2010. Its possible spread to other regions of Brazil is a threat to Brazilian citriculture. This study reports the current distribution of S. hindustanicus and potential predators of this pest and other mites associated with citrus in Roraima. A survey was conducted in August and September 2015 in the 15 municipalities of the state. In each municipality, orchards and citrus plants in backyards and public areas along highways and in urban areas were sampled. Samples of leaves and fruits were collected to identify the mite and its natural enemies. Schizotetranychus hindustanicus was found in all 15 municipalities in the state of Roraima. In total, 308 associated mites were found, with S. hindustanicus being the most abundant phytophagous mite, followed by Brevipalpus yothersi Baker. Amblyseius aerialis (Muma) was the most abundant predator, followed by Iphiseiodes zuluagai Denmark and Muma and Euseius concordis (Chant). The broad dispersal of S. hindustanicus in Roraima increases the risks of this pest reaching the main citrus-producing regions in Brazil.

Population performance of Tetranychus evansi (Acari: Tetranychidae) on African tomato varieties and wild tomato genotypes.

The tomato red spider mite, Tetranychus evansi Baker & Pritchard, is one of the main pests of the tomato crop in several countries, mainly in Africa, where it can reduce tomato yield by up to 90%. The biotic potential of this mite is high and its control is difficult because of low efficiency of chemicals used and the rapid development of resistance to acaricides. We used the two-sex life table to evaluate the effect of two wild tomato genotypes (PI134417 and PI134418) and five tomato varieties widely grown in Benin (Kekefo, Akikon, TLCV15, Tounvi, and TOML4) on demographic characteristics of T. evansi under laboratory conditions. Tetranychus evansi did not develop on the genotypes PI134417 and PI134418, indicating their resistance to this mite. Developmental time of immature stages and female longevity were significantly higher on TLCV15 and Kekefo. Fecundity, net reproductive rate (R0), intrinsic rate of increase (r), and finite rate of increase (λ) of T. evansi on the African varieties were not statistically different among varieties. Generation time (T) was shorter on TOML4 than on TLCV15 and Tounvi. Thus, efforts should be made to prospect varieties with resistance characteristics or to develop other control means, to reduce the use of pesticides to control T. evansi in Africa.

A multi-biomarker approach to lambda-cyhalothrin effects on the freshwater teleost matrinxa Brycon amazonicus: single-pulse exposure and recovery.

Effects of the pyrethroid lambda-cyhalothrin (LCH) were investigated in matrinxa Brycon amazonicus, a non-target freshwater teleost. The fish were submitted to a single-pulse exposure (10% of LC50; 96 h, 0.65 µg L-1), followed by 7 days of recovery in clean water. Hematologic parameters indicated impairments in oxygen transport, which were not recovered. Plasma [Na+], [Cl-], and protein were diminished, and only [Na+] remained low after recovery. Gill Na+/K+ATPase activity was increased and recovered to basal values. Brain acetylcholinesterase activity was not responsive to LCH. Liver ascorbic acid concentration was not altered, and reduced glutathione levels remained augmented even after recovery. LCH inhibited hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, while glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) activities were steady. After recovery, SOD remained low, and GPx was augmented. Liver depicted lipid peroxidation, which was not observed after recovery. Hepatic morphology was affected by LCH and was not completely recovered. These responses, combined with the persistence of changes even after recovery span, clearly show the feasibility of these biomarkers in evaluating LCH toxic potential to non-target organisms, highlighting the importance of pyrethroids' responsible use.

Influence of hydrocolloids (galactomannan and xanthan gum) on the physicochemical and sensory characteristics of gluten-free cakes based on fava beans (Phaseolus lunatus).

Most gluten-free bakery formulations have starch sources of low nutritional value. The objective of this work was to use fava beans (Phaseolus lunatus) for the production of gluten-free sponge cakes, in addition to evaluating the effects of the partial substitution of fava bean flour by galactomannan and xanthan gum, isolated or mixed at 0.5 and 1.0% proportions, compared with a commercial reference. The properties such as viscosity, specific gravity and microscopy of the air bubbles were evaluated in the raw cakes, while the cooked cakes were analyzed according to physicochemical (chemical composition, specific volume, texture and color) and sensorial properties. Hydrocolloids increased the viscosity, specific gravity, and incorporation of air into the batters. Xanthan gum increased the cakes' firmness after cooking; in what concerns color parameters, hydrocolloids did not interfere. Cakes based on fava beans had better sensory acceptance with or without the presence of hydrocolloids and presented higher levels of moisture, proteins, lipids and ashes when compared to the commercial reference, proving to be an excellent food option without gluten and high nutritional value.

Phytoseiid mites (Acari: Phytoseiidae) from Chile, with descriptions of three new species and a redescription of Chileseius camposi.

A total of 40 phytoseiid species has been reported from Chile, including the two species (Neoseiulus californicus (McGregor) and Phytoseiulus persimilis (Athias-Henriot) most widely used worldwide for the biological control of the two-spotted spider mite, Tetranychus urticae Koch (Tetranychidae). In this paper we report nine other species found in new collecting conducted since 1989, including three new species: Amblyseius herbicolus (Chant), Amblyseius tamatavensis Blommers, Arrenoseius robertogonzalezi Trincado Martin n. sp., Neoseiulus anonymus (Chant Baker), Neoseiulus bicaudus (Wainstein), Neoseiulus viticolus Trincado Martin n. sp., Metaseiulus (Metaseiulus) camelliae (Chant Yoshida-Shaul), Metaseiulus (Metaseiulus) neoflumenis Moraes Kreiter and Metaseiulus (Metaseiulus) relictus Trincado Martin n. sp.. Chileseius camposi Gonzalez Schuster, 1962 is redescribed, and a list of all species presently known from Chile and a key to help in their separation are given. A new name, Proprioseiopsis kargi Trincado nom. nov., is a replacement name for Proprioseiopsis globosus Karg, 1976, a junior homonym of Proprioseiopsis globosus (Gonzalez Schuster, 1962).

Comprehensive evolutionary and phylogenetic analysis of Hepacivirus N (HNV).

Hepaciviruses (HVs) have been detected in several domestic and wild animals and present high genetic diversity. The actual classification divides the genus Hepacivirus into 14 species (A-N), according to their phylogenetic relationships, including the bovine hepacivirus [Hepacivirus N (HNV)]. In this study, we confirmed HNV circulation in Brazil and sequenced the whole genome of two strains. Based on the current classification of HCV, which is divided into genotypes and subtypes, we analysed all available bovine hepacivirus sequences in the GenBank database and proposed an HNV classification. All of the sequences were grouped into a single genotype, putatively named 'genotype 1'. This genotype can be clearly divided into four subtypes: A and D containing sequences from Germany and Brazil, respectively, and B and C containing Ghanaian sequences. In addition, the NS3-coding region was used to estimate the time to the most recent common ancestor (TMRCA) of each subtype, using a Bayesian approach and a relaxed molecular clock model. The analyses indicated a common origin of the virus circulating in Germany and Brazil. Ghanaian sequences seemed to have an older TMRCA, indicating a long time of circulation of these viruses in the African continent.

Factors affecting prevailing population levels of Brevipalpus yothersi (Acari: Tenuipalpidae) in citrus areas affected by citrus leprosis in the State of Sao Paulo, Brazil.

Brevipalpus yothersi Baker (Acari: Tenuipalpidae) was recently confirmed as one of the main vectors of citrus leprosis. Knowledge about this mite's biology is essential to understand its population dynamics, in order to solve management issues in citrus orchards and explain why citrus leprosis is more severe in some regions. This paper aimed to study biological factors affecting prevailing population levels of B. yothersi and incidence of citrus leprosis. Mites were sampled from orchards in the south, north and northwestern regions of São Paulo State, Brazil. We assessed duration of the developmental stages, oviposition, incubation period, egg viability, longevity, net reproductive rate (Ro), mean generation time (T), intrinsic rate of increase (rm) and finite rate of increase (λ). There were small differences in parameter values between the three populations. Our results indicated that the various measures adopted in the control of the three populations did not lead to major biological differences between populations for the evaluated parameters.

HoBi-like is the most prevalent ruminant pestivirus in Northeastern Brazil.

The ruminant pestiviral species BVDV-1, BVDV-2 and BDV, along with the putative species HoBi-like, may cause substantial economic losses in cattle, sheep and goats. Brazil's large size, variable biomes and wide range of ruminant animal production within different geographic regions suggest that the presence and prevalence of ruminant pestivirus may differ by regions within Brazil. This study investigated the genetic diversity of ruminant pestiviruses and determined the frequency of active infections within two states of the Northeast Region of Brazil, Maranhão and Rio Grande do Norte. Serum samples from 16,621 cattle and 2,672 small ruminants from 569 different herds residing in this region were tested by RT-PCR followed by DNA sequencing. Seventeen positive cattle were detected (0.1%) from fifteen different herds (2.64%). All isolates were classified as HoBi-like pestiviruses based on phylogenetic analysis. All small ruminant samples tested negative. The findings presented herein suggest that the Northeast Region of Brazil has a uniquely high prevalence of HoBi-like viruses. The increasing reports of HoBi-like viruses detected in cattle in the field suggest that natural infection with these viruses may be more widespread than previously thought. The identification of HoBi-like viruses as the most prevalent type of ruminant pestivirus circulating in the Northeast Region of Brazil indicates the need for both continued monitoring and determination of the extent of economic losses associated with HoBi-like virus infections. In addition, it must be taken into account in the choice of diagnostic tests and in vaccine formulations.

1, 25-dihidroxivitamina-D 3 sobre as características ósseas de frangos de corte fêmeas / 1, 25-dihydroxyvitamin-D3 over bony characteristics of female broilers

Objetivou-se avaliar as características dos tibiotarsos de frangos de corte fêmeas. As variáveis analisadas foram os pesos in natura, secos e desengordurados, o comprimento, os diâmetros, a resistência óssea, o índice de Seedor (IS), os percentuais de proteínas colagenosas (PC), as proteínas não colagenosas (PNC), os minerais (cálcio, fósforo, potássio e sódio) e as cinzas. Foram utilizadas 648 aves, da marca comercial Cobb®, em um delineamento em blocos ao acaso, com seis tratamentos e seis repetições, com 18 aves por unidade experimental. Os tratamentos consistiram na suplementação de 0,00; 0,50; 1,00; 1,50; 2,00 e 2,50 µg de 1,25-dihidroxivitamina-D3 (1,25(OH)2D3)/kg de ração. Aos 21 e 35 dias de idade, as aves foram pesadas e uma ave por unidade experimental (UE) com o peso médio da UE foi eutanasiada para a obtenção dos tibiotarsos e subsequente análise dos parâmetros ósseos. As variáveis métricas, bem como a composição orgânica (PC), a densidade (IS) e a resistência à quebra dos ossos das aves, não foram influenciadas pelos tratamentos. No recebimento de 2,50 µg de 1,25(OH)2D3/kg de ração, observou-se maior retenção mineral (cinzas) nos ossos das aves aos 35 dias de idade.(AU)

This study aimed to evaluate the characteristics of tibiotarsus of female broilers. The variables analyzed were the weights in natura, dry and degreased, length, diameter, bone strength, Seedor index, percentage of collagenous protein (CP), non-collagenous proteins (NCP), minerals (calcium, phosphorus, potassium and sodium), and ash. Six hundred forty-eight, Cobb® birds were used, a design of randomized blocks with six treatments and six replicates of 18 birds each. The treatments consisted of supplementation of 0.00; 0.50; 1.00; 1.50; 2.00 to 2.50 µg of 1,25-dihydroxyvitamin-D3 (1,25(OH)2D3)/kg of ration. At 21 and 35 days of age the birds were weighed and a unit/experimental unit (EU) with the EU average weight was euthanized to obtain the tibiotarsos and subsequent analysis of the bone parameters. The metric variables, as well as the organic composition (CP), density (IS) and resistance to breakage of the bones of the birds were not affected by treatments. Upon reception of 2.50 µg of 1,25(OH)2D3/kg ration, there was a higher mineral retention (ashes) in the bones of female broilers at 35 days of age.(AU)

Changes in gene expression and catalase activity in Oryza sativa L. under abiotic stress.

Different rice (Oryza sativa L.) genotypes were subjected to high salinity and low temperature (150 mM NaCl and 13°C, respectively) for 0, 6, 24, 48, or 72 h. We evaluated the simultaneous expression of the genes OsCATA, OsCATB, and OsCATC, correlated gene expression with enzyme activity, and verified the regulation of these genes through identification of cis-elements in the promoter region. The hydrogen peroxide content increased in a tolerant genotype and decreased in a sensitive genotype under both stress conditions. Lipid peroxidation increased in the tolerant genotype when exposed to cold, and in the sensitive genotype when exposed to high salinity. Catalase activity significantly increased in both genotypes when subjected to 13°C. In the tolerant genotype, OsCATA and OsCATB were the most responsive to high salinity and cold, while in the sensitive genotype, OsCATA and OsCATC responded positively to saline stress, as did OsCATA and OsCATB to low temperature. Cis-element analysis identified different regulatory sequences in the catalase promoter region of each genotype. The sensitive genotype maintained a better balance between hydrogen oxyacid levels, catalase activity, and lipid peroxidation under low temperature than the resistant genotype. OsCATA and OsCATB were the most responsive in the salt-tolerant genotype to cold, OsCATA and OsCATC were the most responsive to saline stress, and OsCATA and OsCATB were the most responsive to chilling stress in the sensitive genotype. There were positive correlations between catalase activity and OsCATB expression in the tolerant genotype under saline stress and in the sensitive genotype under cold stress.

Influence of CYP2C19 on Helicobacter pylori eradication in Brazilian patients with functional dyspepsia.

The aim of this study was to examine the effect of polymorphisms in the cytochrome P450 (CYP) 2C19 gene (CYP2C19) on the Helicobacter pylori eradication rate in Brazilian patients with functional dyspepsia. Adults diagnosed with functional dyspepsia based on the ROME III criteria and infected with H. pylori were recruited to this study. The patients were subjected to gastrointestinal endoscopy and the H. pylori status was defined when both urease test and histopathology results were negative or positive. The patients were treated with proton pump inhibitor-based triple therapy (omeprazole, amoxicillin, and clarithromycin). CYP2C19*2 and CYP2C19*3 were genotyped by polymerase chain reaction-restriction fragment length polymorphism. One hundred and forty-eight patients (81.8% women) with a mean (± SD) age of 46.1 (12.2) years were included in this study. Based on the CYP2C19 genotypes, the patients were classified as homozygous extensive metabolizer (HomEM; 67.6%), heterozygous extensive metabolizer (HetEM; 26.3%), or poor metabolizer (PM; 6.1%). The H. pylori eradication rates in patients with HomEM, HetEM, and PM were 85.0, 89.7, and 100.0% (P = 0.376), respectively. The included study population comprised a high frequency of patients carrying the HomEM genotype. Although the genotypes of CYP2C19 variants were not statistically significant, the results of this study suggest a possible effect of the PM genotype on the efficacy of H. pylori eradication.

Glycolysis and gluconeogenesis in the liver of catfish fed with different concentrations of proteins, lipids and carbohydrates / Glicólise e gliconeogênese no fígado de jundiá alimentado com diferentes concentrações de proteínas, lipídeos e carboidratos

The activities of enzymes from a number of metabolic pathways have been used as a tool to evaluate the best use of nutrients on fish performance. In the present study the catfish Rhamdia quelen was fed with diets containing crude protein-lipid-carbohydrate (%) as follows: treatment (T) T1: 19-19-44; T2: 26-15-39; T3: 33-12-33; and T4: 40-10-24. The fish were held in tanks of re-circulated, filtered water with controlled temperature and aeration in 2000L experimental units. The feeding experiment lasted 30 days. The following enzymes of the carbohydrate metabolism were determined: Glucokinase (GK), Phosphofructokinase 1 (PFK-1), Pyruvate kinase (PK), Fructose-1,6-biphosphatase 1 (FBP-1). The activities of 6 phosphogluconate dehydrogenase (6PGDH) and glucose 6 phosphate dehydrogenase (G6PDH) were also assayed. The influence of nutrient levels on the enzyme activities is reported. The increase of dietary protein plus reduction of carbohydrates and lipids attenuates the glycolytic activity and induces hepatic gluconeogenesis as a strategy to provide metabolic energy from amino acids. The fish performance was affected by the concentrations of protein, lipid and carbohydrates in the diet. The greatest weight gain was obtained in fish fed diet T4 containing 40.14% of crude protein, 9.70% of lipids, and 24.37% of carbohydrate, respectively.(AU)

As atividades de enzimas das vias metabólicas têm sido utilizadas como uma ferramenta para avaliar a melhor utilização dos nutrientes e o desempenho dos peixes. No presente estudo, o jundiá foi alimentado com rações contendo diferentes concentrações de proteína bruta, lipídeos e carboidratos (%), da seguinte forma: tratamento (T) T1: 19-19-44; T2: 26-15-39; T3: 33-12-33; e T4: 40-10-24. Os peixes foram mantidos em tanques de recirculação, com água filtrada, temperatura controlada e aeração em unidades experimentais de 2.000L. O período experimental foi de 30 dias. Foram aferidas as atividades das enzimas glicoquinase (GK), fosfofrutoquinase 1 (PFK-1), piruvato quinase (PK) e frutose-1,6-difosfatase (FBP-1). Também foram aferidas as atividades da 6-fosfogluconato desidrogenase (6PGDH) e glicose-6-fosfato desidrogenase (G6PDH) da via das pentoses. É relatado que níveis de nutrientes influenciam as atividades enzimáticas das vias metabólicas. No presente estudo, o aumento da proteína da dieta e a redução de hidratos de carbono e lipídeos reduziram a atividade glicolítica e induziram a gliconeogênese hepática como uma estratégia para fornecer energia pelos aminoácidos. O desempenho dos peixes foi afetado pelas concentrações de proteínas, lipídeos e carboidratos na dieta. O maior ganho de peso foi obtido em peixes alimentados com dieta T4 contendo 40,14% de proteína bruta, 9,70% de lipídeos, e 24,37% de carboidratos, respectivamente.(AU)

Prosthetic Oral Rehabilitation of a Child With S-ECC: A Case Report with Histopathologic Analysis.

The aim of this case report is to describe the treatment planning of a young child with severe early childhood caries (S-ECC) as well as the prosthetic rehabilitation technique. A 3-year-old female child was referred to the pediatric dentistry clinic with the chief complaint of tooth pain, difficulty in eating and recurrent hospitalizations caused by dental infections. The mother reported intermittent episodes of fever and recurrent swelling of child's face. The girl presented angular cheilitis and was referred to a dietitian. The treatment plain consisted on a behavior changes in oral hygiene habits, exodontias of all primary teeth and oral rehabilitation with a prosthesis. The extracted teeth with periapical lesions were submitted to histopathologic analysis (hematoxilin and eosin staining) and revealed an inflammatory infiltrate. The aesthetic requirement of children with S-ECC has been a challenge to pediatric dentists. In the present case, the oral rehabilitation provided for the children better aesthetic, nutrition, phonation, and functional conditions.

Forkhead box K2 modulates epirubicin and paclitaxel sensitivity through FOXO3a in breast cancer.

The forkhead transcription factor FOXK2 has recently been implicated in cancer cell proliferation and survival, but a role in cancer chemotherapeutic drug resistance has hitherto not been explored. Here we demonstrate that FOXK2 has a central role in mediating the cytotoxic drug response in breast cancer. Clonogenic and cell viability assays showed that enhanced FOXK2 expression sensitizes MCF-7 breast cancer cells to paclitaxel or epirubicin treatment, whereas FOXK2 depletion by small interfering RNAs (siRNAs) confers drug resistance. Our data also showed that the activation of the tumour suppressor FOXO3a by paclitaxel and epirubicin is mediated through the induction of FOXK2, as depletion of FOXK2 by siRNA limits the induction of FOXO3a by these drugs in MCF-7 cells. Chromatin immunoprecipitation (ChIP) analysis showed that in response to drug treatment, FOXK2 accumulates and binds to the proximal FOXO3a promoter region in MCF-7 cells. Furthermore, we also uncovered that FOXK2 is deregulated and, therefore, can express at high levels in the nucleus of both the paclitaxel and epirubicin drug-resistant MCF-7 cells. Our results showed that ectopically overexpressed FOXK2 accumulates in the nuclei of drug-resistant MCF-7 cells but failed to be recruited to target genes, including FOXO3a. Crucially, we found that FOXO3a is required for the anti-proliferative and epirubicin-induced cytotoxic function of FOXK2 in MCF-7 cells by sulphorhodamine and clonogenic assays. The physiological importance of the regulation of FOXO3a by FOXK2 is further confirmed by the significant correlations between FOXO3a and FOXK2 expression in breast carcinoma patient samples. Further survival analysis also reveals that high nuclear FOXK2 expression significantly associates with poorer clinical outcome, particularly in patients who have received conventional chemotherapy, consistent with our finding that FOXK2 is deregulated in drug-resistant cells. In summary, our results suggest that paclitaxel and epirubicin target the FOXK2 to modulate their cytotoxicity and deregulated FOXK2 confers drug resistance.