Gene Dosage Effects of the Imprinted Delta-Like Homologue 1 (Dlk1/Pref1) in Development: Implications for the Evolution of Imprinting

Genomic imprinting is a normal process that causes genes to be expressed according to parental origin. The selective advantage conferred by imprinting is not understood but is hypothesised to act on dosage-critical genes. Here, we report a unique model in which the consequences of a single, double, and triple dosage of the imprinted Dlk1/Pref1, normally repressed on the maternally inherited chromosome, can be assessed in the growing embryo. BAC-transgenic mice were generated that over-express Dlk1 from endogenous regulators at all sites of embryonic activity. Triple dosage causes lethality associated with major organ abnormalities. Embryos expressing a double dose of Dlk1, recapitulating loss of imprinting, are growth enhanced but fail to thrive in early life, despite the early growth advantage. Thus, any benefit conferred by increased embryonic size is offset by postnatal lethality. We propose a negative correlation between gene dosage and survival that fixes an upper limit on growth promotion by Dlk1, and we hypothesize that trade-off between growth and lethality might have driven imprinting at this locus

Biofilm disclosing agents in complete denture: clinical and antimicrobial evaluation

Este trabalho avaliou a capacidade em corar, a facilidade de remoção e a ação antimicrobiana de evidenciadores de biofilme dental em prótese total. A capacidade em corar foi avaliada por método visual aplicando-se evidenciadores sobre a superfície interna da prótese total superior. Após fotografia, as próteses coradas foram escovadas (escova e dentifrício específicos para prótese total) e novamente fotografadas. Os diapositivos foram projetados em folhas de papel (aumento de 10 X); as áreas total e corada das próteses contornadas com grafite, recortadas e pesadas, para obtenção, em porcentagem, dos resultados da facilidade de remoção. A ação antimicrobiana foi avaliada pelo método de difusão em ágar e os resultados obtidos pela medida dos aros e halos de inibição formados. A melhor capacidade em corar foi apresentada pelo azul de metileno (0,05%), eritrosina (5%), fluoresceína sódica (1%), Replak e vermelho neutro (1%). Eosina (1%), fluoresceína sódica (1%) e eritrosina (5%) apresentaram a maior facilidade de remoção. Não apresentaram ação antimicrobiana eosina (1%), eritrosina (5%), fluoresceína sódica (1%), proflavina (0,3%), Replak e vermelho neutro (1%). As soluções que apresentaram maior capacidade de corar, facilidade de remoção e ausência de ação antimicrobiana, requisitos necessários para auxiliar estudos que avaliam métodos de higiene e de orientação aos pacientes, foram eosina (1%), vermelho neutro (1%) e eritrosina (5%).This study evaluated the disclosing ability, removal facility and antimicrobial effect of biofilm disclosing agents applied on complete dentures. Disclosing ability was evaluated by means of the visual method. The solutions were applied on the internal surface of dentures. After being photographed, the dentures were brushed with denture-specific brush and dentifrice and photographed again. The obtained slides were projected on paper (10 X amplification) and the total and stained surfaces were outlined with graphite, cut off and weighed, in order to assess removal facility. The evaluation of antimicrobial effects was carried out by means of the method of diffusion in agar, and the results were obtained by measuring the length of the halos and rings. In terms of disclosing ability, the best solutions were 0.05% methylene blue, 5% erythrosin, 1% sodic fluorescein, Replak and 1% neutral red. One percent eosin, 1% sodic fluorescein and 5% erythrosin were the most easily removed solutions. One percent eosin, 5% erythrosin, 1% sodic fluorescein, 0.3% proflavine, Replak and 1% neutral red presented no antimicrobial effect. The solutions which presented the greatest disclosing ability and removal facility as well as absence of antimicrobial effect - which are essential requirements in the assessment of hygiene methods and guidance on oral health - were 1% eosin, 1% neutral red and 5% erythrosin

Clinical and antimicrobial efficacy of NitrAdineTM-based disinfecting cleaning tablets in complete denture wearers

OBJECTIVE: This study evaluated the efficacy of NitrAdineTM-based disinfecting cleaning tablets for complete denture, in terms of denture biofilm removal and antimicrobial action. MATERIAL AND METHODS: Forty complete denture wearers (14 men and 26 women) with a mean age of 62.3±9.0 years were randomly assigned to two groups and were instructed to clean their dentures according to two methods: brushing (control) - 3 times a day with denture brush and tap water following meals; brushing and immersion (Experimental) - brushing the denture 3 times a day with denture brush and tap water following meals and immersion of the denture in NitrAdineTM-based denture tablets (Medical InterporousTM). Each method was used for 21 days. Denture biofilm was disclosed by a 1% neutral red solution and quantified by means of digital photos taken from the internal surface before and after the use of the product. Microbiological assessment was conducted to quantify Candida sp. RESULTS: An independent t-test revealed a significant lower biofilm percentage for the experimental group (4.7, 95% CI 2.4 to 7.9) in comparison with the control group (mean 37.5, 95% CI 28.2 to 48.1) (t38=7.996, p<0.001). A significant reduction of yeast colony forming units could be found after treatment with Medical InterporousTM denture tablets as compared to the control group (Mann-Whitney test, Z=1.90; p<0.05). CONCLUSION: The present findings suggest that NitrAdineTM-based disinfecting cleaning tablets are efficient in removal of denture biofilm. In addition, a clear antimicrobial action was demonstrated. Therefore, they should be recommended as a routine denture maintenance method for the prevention of the development of microbial biofilm induced denture stomatitis

Bacterial, fungal and yeast contamination in six brands of irreversible hydrocolloid impression materials Contaminação por bactérias, fungos e leveduras em seis marcas comerciais de materiais de moldagem à base de hidrocolóide irreversível

This study assessed the level of contamination of six commercially available irreversible hydrocolloids (two containing chlorhexidine) and identified the contamination present in the materials. Petri dishes containing selective and enriched culture media were inoculated with alginate powder (0.06 g), in triplicate. After incubation (37&deg;C/7 days), the colony-forming units (CFU) were counted and Gram stained. Biochemical identification of the different morphotypes was also performed. The contamination levels for the materials were: Jeltrate - 389 CFU/g; Jeltrate Plus - 516 CFU/g; Jeltrate Chromatic - 135 CFU/g; Hydrogum - 1,455 CFU/g; Kromopan - 840 CFU/g; and Greengel - 59 CFU/g. Gram staining revealed the presence of Gram-positive bacillus and Gram-positive cocci. The bacteria Staphylococcus epidermidis, Bacillus subtilis, Bacillus sp., Bacillus coagulans, Bacillus licheniformis, Bacillus cereus, Micrococcus luteus, and Nocardia sp.; the filamentous fungi Aspergillus niger, Aspergillus flavus, Rhizopus sp., Neurospora sp.; and the yeast Candida sp. were isolated. The contamination detected in the impression materials points out the need for adopting measures to improve the microbiological quality of these materials. The use of contaminated materials in the oral cavity goes against the basic principles for controlling cross-contamination and may represent a risk for debilitated or immunocompromised patients.<br>Este estudo avaliou o nível de contaminação de seis marcas comerciais de alginato (duas contendo clorexidina) e identificou a contaminação presente nesses materiais. Alíquotas de alginato (0,06 g) foram semeadas em meios de cultura seletivos e enriquecidos, em triplicata. Após incubação (37&deg;C/7 dias), as unidades formadoras de colônia (UFC) foram contadas e foram realizadas as identificações morfotintorial (Gram) e bioquímica. Os níveis de contaminação dos materiais foram: Jeltrate - 389 UFC/g; Jeltrate Plus - 516 UFC/g; Jeltrate Chromatic - 135 UFC/g; Hydrogum - 1.455 UFC/g; Kromopan - 840 UFC/g; e Greengel - 59 UFC/g. A coloração de Gram revelou a presença de bacilos Gram-positivos e cocos Gram-positivos. As bactérias Staphylococcus epidermidis, Bacillus subtilis, Bacillus sp., Bacillus coagulans, Bacillus licheniformis, Bacillus cereus, Micrococcus luteus e Nocardia sp.; os fungos filamentosos Aspergillus niger, Aspergillus flavus, Rhizopus sp., Neurospora sp.; e a levedura Candida sp. foram isolados. A contaminação detectada nos materiais aponta a necessidade de adoção de medidas para melhorar seu controle de qualidade microbiológica. O uso de materiais contaminados na boca contradiz os princípios básicos de controle de infecção-cruzada e pode representar um risco para pacientes debilitados ou imunocomprometidos

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to &lt; 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of &amp; GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P &lt; 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes