ABSTRACT
Medical management of caries is a distinct treatment philosophy that employs topical minimally invasive therapies that treat the disease and is not merely prevention. This strategy is justified as an alternative or supplement to traditional care by significant disease recurrence rates following comprehensive operative treatment under general anesthesia. Silver diamine fluoride (SDF) is one agent to enable effective noninvasive treatment. The announcement of breakthrough therapy designation by the Food and Drug Administration (FDA) suggests that SDF may become the first FDA-approved drug for treating caries. Since our systematic review performed in April 2015, 4 clinical trials have been completed, which inform an update to the application protocol and frequency regimen. Suggestions from these studies are to skip the rinsing step due to demonstration of safety in young children, start patients with high disease severity on an intensive regimen of multiple applications over the first few weeks, and continue with semiannual maintenance doses as previously suggested. Breakthroughs in elucidating the impact of SDF on the dental plaque microbiome inform potential opportunities for understanding caries arrest. SDF can be added to the set of evidence-based noninvasive methods to treat caries lesions in primary teeth, such as the Hall crown technique and sealing lesions with accessible margins.
Subject(s)
Cariostatic Agents/pharmacology , Dental Caries/prevention & control , Quaternary Ammonium Compounds/pharmacology , Silver Compounds/pharmacology , Cariostatic Agents/administration & dosage , Evidence-Based Dentistry , Fluorides, Topical/administration & dosage , Fluorides, Topical/pharmacology , Humans , Quaternary Ammonium Compounds/administration & dosage , Silver Compounds/administration & dosage , Tooth Remineralization/methods , United States , United States Food and Drug AdministrationABSTRACT
Dental caries is the most common disease to cause irreversible damage in humans. Several therapeutic agents are available to treat or prevent dental caries, but none besides fluoride has significantly influenced the disease burden globally. Etiologic mechanisms of the mutans group streptococci and specific Lactobacillus species have been characterized to various degrees of detail, from identification of physiologic processes to specific proteins. Here, we analyze the entire Streptococcus mutans proteome for potential drug targets by investigating their uniqueness with respect to non-cariogenic dental plaque bacteria, quality of protein structure models, and the likelihood of finding a drug for the active site. Our results suggest specific targets for rational drug discovery, including 15 known virulence factors, 16 proteins for which crystallographic structures are available, and 84 previously uncharacterized proteins, with various levels of similarity to homologs in dental plaque bacteria. This analysis provides a map to streamline the process of clinical development of effective multispecies pharmacologic interventions for dental caries.
Subject(s)
Dental Caries/prevention & control , Dental Plaque/microbiology , Drug Discovery/methods , Proteomics/methods , Streptococcus mutans/genetics , Databases, Protein , Dental Caries/drug therapy , Dental Caries/etiology , Humans , Models, Molecular , Streptococcus mutans/ultrastructure , Structural Homology, Protein , Virulence FactorsABSTRACT
Eight multiparous Holstein cows averaging 570 +/- 43 kg of body weight and 60 +/- 20 d in milk were used in a double Latin square design with four 21-d experimental periods to determine the effects of feeding ground or whole flaxseed with or without monensin supplementation (0.02% on a dry matter basis) on milk production and composition, feed intake, digestion, blood composition, and fatty acid profile of milk. Intake of dry matter was similar among treatments. Cows fed whole flaxseed had higher digestibility of acid detergent fiber but lower digestibilities of crude protein and ether extract than those fed ground flaxseed; monensin had no effect on digestibility. Milk production tended to be greater for cows fed ground flaxseed (22.8 kg/d) compared with those fed whole flaxseed (21.4 kg/d). Processing of flax-seed had no effect on 4% fat-corrected milk yield and milk protein and lactose concentrations. Monensin supplementation had no effect on milk production but decreased 4% fat-corrected milk yield as a result of a decrease in milk fat concentration. Feeding ground compared with whole flaxseed decreased concentrations of 16:0, 17:0, and cis6-20:4 and increased those of cis6-18:2, cis9, trans11-18:2, and cis3-18:3 in milk fat. As a result, there was a decrease in concentrations of medium-chain and saturated fatty acids and a trend for higher concentrations of long-chain fatty acids in milk fat when feeding ground compared with whole flaxseed. Monensin supplementation increased concentrations of cis9 and trans11-18:2 and decreased concentrations of saturated fatty acids in milk fat. There was an interaction between flaxseed processing and monensin supplementation, with higher milk fat concentration of trans11-18:1 for cows fed ground flaxseed with monensin than for those fed the other diets. Flaxseed processing and monensin supplementation successfully modified the fatty acid composition of milk fat that might favor nutritional value for consumers.
Subject(s)
Cattle/physiology , Fatty Acids/analysis , Flax , Ionophores/administration & dosage , Milk/chemistry , Monensin/administration & dosage , Animal Feed , Animal Nutritional Physiological Phenomena , Animals , Cattle/growth & development , Detergents , Dietary Fiber/metabolism , Digestion , Eating , Female , Food Handling/methods , Lactation , Milk/metabolism , Milk Proteins/analysis , Nutritive Value , Particle Size , Random Allocation , SeedsABSTRACT
The shape of the clasps on removable partial dentures often has to be adjusted by bending. Occasionally they fracture during the small plastic deformation that takes place during the adjustment. The tendency to brittle failure of three Co-Cr-Mo alloys for prosthetic use with different carbon and chromium contents was investigated by tensile testing. The total elongation which can be used as a measure of the ductility was observed to vary from 4-17% for the investigated alloys. The reasons for these differences have been sought by studying the structures of the alloys and analysing the fracture mechanisms. The fractures are basically brittle and seem to be initiated during straining by cracking of particles. Microprobe analyses showed that many of the particles were agglomerations of constituents which in all cases were substantially enriched in C, Cr and Mo. Each of these constituents may contain phases too small to be resolved by SEM and by the electron beam in the microprobe. TEM investigations showed that many of the constituents were eutectic with alternating lamellae of Co-rich FCC structure and M23C6. The crack propagates rapidly either by following the interface between the matrix and the particles or by running inside the particles. Cleavage along stacking faults in FCC Co-rich grains in the matrix takes place when the distance between neighbouring particles increases. The ductility of the alloys is clearly improved by decreasing amounts of particles and thus by a reduction of the C content.
Subject(s)
Chromium Alloys , Dental Casting Investment , Cobalt , Denture, Partial, Removable , Elasticity , Microscopy, Electron, Scanning , Tensile StrengthABSTRACT
Amelogenesis Imperfecta (AI) is a clinical diagnosis that encompasses a group of genetic mutations, each affecting processes involved in tooth enamel formation and thus, result in various enamel defects. The hypomaturation enamel phenotype has been described for mutations involved in the later stage of enamel formation, including Klk4, Mmp20, C4orf26, and Wdr72. Using a candidate gene approach we discovered a novel Wdr72 human mutation in association with AI to be a 5-base pair deletion (c.806_810delGGCAG; p.G255VfsX294). To gain insight into the function of WDR72, we used computer modeling of the full-length human WDR72 protein structure and found that the predicted N-terminal sequence forms two beta-propeller folds with an alpha-solenoid tail at the C-terminus. This domain iteration is characteristic of vesicle coat proteins, such as beta'-COP, suggesting a role for WDR72 in the formation of membrane deformation complexes to regulate intracellular trafficking. Our Wdr72 knockout mouse model (Wdr72(-/-)), containing a LacZ reporter knock-in, exhibited hypomineralized enamel similar to the AI phenotype observed in humans with Wdr72 mutations. MicroCT scans of Wdr72(-/-) mandibles affirmed the hypomineralized enamel phenotype occurring at the onset of the maturation stage. H&E staining revealed a shortened height phenotype in the Wdr72(-/-) ameloblasts with retained proteins in the enamel matrix during maturation stage. H(+)/Cl(-) exchange transporter 5 (CLC5), an early endosome acidifier, was co-localized with WDR72 in maturation-stage ameloblasts and decreased in Wdr72(-/-) maturation-stage ameloblasts. There were no obvious differences in RAB4A and LAMP1 immunostaining of Wdr72(-/-) mice as compared to wildtype controls. Moreover, Wdr72(-/-) ameloblasts had reduced amelogenin immunoreactivity, suggesting defects in amelogenin fragment resorption from the matrix. These data demonstrate that WDR72 has a major role in enamel mineralization, most notably during the maturation stage, and suggest a function involving endocytic vesicle trafficking, possibly in the removal of amelogenin proteins.
Subject(s)
Amelogenesis Imperfecta/genetics , Dental Enamel/chemistry , Models, Molecular , Proteins/genetics , Tooth Demineralization/genetics , Ameloblasts/metabolism , Animals , Base Sequence , Humans , Mice , Mice, Knockout , Molecular Sequence Data , Mutation/genetics , Pedigree , Protein Conformation , Protein Folding , Proteins/chemistryABSTRACT
Estimaram-se correlações genéticas entre algumas características de tipo e intervalo de partos (IP) em vacas da raça Holandesa no Estado do Paraná. Foram analisados registros de conformação de 23.014 vacas, classificadas no período de 2000 a 2010, oriundas de 248 rebanhos, filhas de 797 touros. Os componentes de variância necessários para obtenção das estimativas das herdabilidades e das correlações genéticas foram obtidos pelo método da Máxima Verossimilhança Restrita (REML), utilizando-se o procedimento MIXED do pacote estatístico SAS. As estimativas de herdabilidade para as características de tipo variaram de 0,09 a 0,24 e para IP foi 0,05. As estimativas de correlação genética entre as características de tipo foram, em geral, de pequena magnitude, sendo o maior valor observado entre largura de peito e profundidade corporal (0,52). As estimativas de correlação genética entre as características de tipo e IP foram, em sua maioria, de pequena magnitude. A baixa correlação genética entre ângulo de garupa e IP (0,02) sugere que a seleção para ângulo de garupa pode não ser efetiva em determinar ganho genético para fertilidade.
Genetic correlations between type traits and calving interval (CI) in Holstein cows in Parana State - Brazil were estimated. The data comprised linear classification of 23,014 cows, from 248 herds, classified from 2000 to 2010, daughters of 797 sires. Variance components for heritability and genetic correlation were estimated with Restricted Maximum Likelihood method (REML), using the MIXED procedure of statistics package SAS. Heritability estimates for type traits ranged from 0.09 to 0.24 and for CI it was 0.05. Genetic correlation estimations among type traits were, in general, of low magnitude, with the higher value between chest width and body depth (0.52). Estimates of genetic correlations between type traits and CI were mostly small. The low genetic correlation between rump angle and CI (0.02) suggests that the selection for rump angle may not be effective in determining genetic gain for fertility.
Subject(s)
Animals , Female , Cattle , Cattle/embryology , Cattle/genetics , Parturition/geneticsABSTRACT
A doença de Alzheimer (DA) é caracterizada por distúrbios que podem comprometer a nutrição do paciente e causar perda de peso e deficiências nutricionais durante a doença. O objetivo deste estudo foi avaliar o estado nutricional e o consumo alimentar de pacientes brasileiros com doença de Alzheimer em diferentes estágios da doença. A amostra foi composta por 30 indivíduos, com idade média de 77 anos, de ambos os sexos, com provável DA. Os indivíduos foram avaliados através de dados antropométricos, Mini Avaliação Nutricional (MAN), albumina sérica, Mini Exame do Estado Mental, e recordatório de 24 horas. Embora tenha sido encontrada uma diminuição no peso médio entre os estágios da doença (CDR1: 70,8±15,9 kg; CDR2: 61,4±15,7 kg; CDR3: 56,1± 8,4kg) conforme a progressão da doença, a diferença não foi significativa. Os parâmetros MAN e albumina sérica mostraram uma diminuição entre os estágios da doença (p = 0,042,p = 0,047, respectivamente), sendo que no estágio grave metade dos pacientes estava desnutrida e a outra metade em risco de desnutrição. De acordo com o índice de massa corporal, 23,3% dos pacientes estavam com sobrepeso. O valor nutricional da ingestão alimentar foi similar nos estágios de DA. Em conclusão, a maioria dos pacientes brasileiros com DA neste estudo apresentaram desnutrição, apesar de o consumo alimentar ter sido similar entre os estágios da doença, uma vez que não apresentou associação direta com a progressão da DA...
Alzheimer's disease (AD) is characterized by disorders that can impair the nutrition of the patient and lead to weight loss and nutritional deficits during the course of the disease. The aim of this study was to assess the nutritional status and food intake of Brazilian patients with Alzheimer's disease at 3 different stages of the disease. The sample consisted of 30 subjects of both genders, mean age 77 years, with probable AD. Subjects were assessed by collecting anthropometric data, the Mini Nutritional Assessment (MNA), serum albumin content, Mini Mental State Examination and 24-hour records of food and drink. Although a steady decrease in average weight was observed as the disease progressed (CDR1: 70.8±15.9 kg; CDR2: 61.4±15.7 kg; CDR3: 56.1± 8.4 kg), the differences were not significant. MNA and serum albumin both fell during the progression of the disease (p = 0.042; p = 0.047, respectively) and, at the severe stage, half the patients were found to be undernourished and the other half at risk of undernutrition. According to their body mass index, 23.3% of patients were overweight. The nutritional value of the food consumed was similar across the stages of AD. In conclusion, the majority of Brazilian patients with AD in this study exhibited cognitive decline and malnutrition. However, food intake was similar among the stages of the disease, thus having no direct association with the progression of AD...