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We have developed a flexible undergraduate curriculum that leverages the place-based research of environmental microbiomes to increase the number of Indigenous researchers in microbiology, data science and scientific computing. Monitoring Environmental Microbiomes (MEM) provides a curriculum and research framework designed to integrate an Indigenous approach when conducting authentic scientific research and to build interest and confidence at the undergraduate level. MEM has been successfully implemented as a short summer workshop to introduce computing practices in microbiome analysis. Based on self-assessed student knowledge of topics and skills, increased scientific confidence and interest in genomics careers were observed. We propose MEM be incorporated in a scalable course-based research experience for undergraduate institutions, including tribal colleges and universities, community colleges and other minority serving institutions. This coupled curricular and research framework explicitly considers cultural perspectives, access and equity to train a diverse future workforce that is more informed to engage in microbiome research and to translate microbiome science to benefit community and environmental health.
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Addressable quantum states well isolated from the environment are of considerable interest for quantum information science and technology. Carbon nanotubes are an appealing system, since a perfect crystal can be grown without any missing atoms and its cylindrical structure prevents ill-defined atomic arrangement at the surface. Here, we develop a reliable process to fabricate compact multielectrode circuits that can sustain the harsh conditions of the nanotube growth. Nanotubes are suspended over multiple gate electrodes, which are themselves structured over narrow dielectric ridges to reduce the effect of the charge fluctuators of the substrate. We measure high-quality double- and triple-quantum dot charge stability diagrams. Transport measurements through the triple-quantum dot indicate long-range tunneling of single electrons between the left and right quantum dots. This work paves the way to the realization of a new generation of condensed-matter devices in an ultraclean environment, including spin qubits, mechanical qubits, and quantum simulators.
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OBJECTIVE: The aims of this study are to quantify the adhesion strength differential between an oral bacterial biofilm and an osteoblast-like cell monolayer to a dental implant-simulant surface and develop a metric that quantifies the biocompatible effect of implant surfaces on bacterial and cell adhesion. METHODS: High-amplitude short-duration stress waves generated by laser pulse absorption are used to spall bacteria and cells from titanium substrates. By carefully controlling laser fluence and calibration of laser fluence with applied stress, the adhesion difference between Streptococcus mutans biofilms and MG 63 osteoblast-like cell monolayers on smooth and rough titanium substrates is obtained. The ratio of cell adhesion strength to biofilm adhesion strength (i.e., Adhesion Index) is determined as a nondimensionalized parameter for biocompatibility assessment. RESULTS: Adhesion strength of 143 MPa, with a 95% C.I. (114, 176), is measured for MG 63 cells on smooth titanium and 292 MPa, with a 95% C.I. (267, 306), on roughened titanium. Adhesion strength for S. mutans on smooth titanium is 320 MPa, with a 95% C.I. (304, 333), and remained relatively constant at 332 MPa, with a 95% C.I. (324, 343), on roughened titanium. The calculated Adhesion Index for smooth titanium is 0.451, with a 95% C.I. (0.267, 0.622), which increased to 0.876, with a 95% C.I. (0.780, 0.932), on roughened titanium. SIGNIFICANCE: The laser spallation technique provides a platform to examine the tradeoffs of adhesion modulators on both biofilm and cell adhesion. This tradeoff is characterized by the Adhesion Index, which is proposed to aid biocompatibility screening and could help improve implantation outcomes. The Adhesion Index is implemented to determine surface factors that promote favorable adhesion of cells greater than biofilms. Here, an Adhesion Index â« 1 suggests favorable biocompatibility.
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Implantes Dentales , Adhesión Bacteriana , Biopelículas , Adhesión Celular , Propiedades de Superficie , TitanioRESUMEN
BACKGROUND: A core outcome set (COS) represents the agreed minimum set of domains and measurement instruments that should be measured and reported in any clinical trial for a given condition. In BMS randomized controlled trials (RCTs), the outcomes identified in the existing literature regarding the efficacy of therapeutic interventions are numerous and diverse. Although the standardized IMMPACT core outcome domains has been developed for measurement of outcomes in chronic pain RCTs, no BMS-specific COS have been adopted and validated. With the evolving landscape of BMS management end points and the development of new therapies, a consensus on a COS for use in future BMS trials is paramount to reduce heterogeneity in outcome reporting. The aim of this study was to reach a consensus for adopting the standardized Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) outcome domains, and their tools of assessment, for burning mouth syndrome (BMS) clinical trials and clinical practice. METHODS: A BMS-specific COS will be developed using the method recommended by the Core Outcome Measures in Effective Trials (COMET) initiative (Registration: http://www.comet-initiative.org/studies/details/1357 ). Selection of questionnaire outcome measures was informed by the IMMPACT consensus and previous systematic review of RCTs in BMS conducted by the consortium. An international group of clinicians and researchers will be invited to participate in several rounds of a Delphi survey. A consensus meeting will be held with the objective of ratifying the outcomes for inclusion in the COS. A finalized COS explanatory document will be drafted, including all outcomes and measurements as determined by the Delphi rounds and consensus meeting. DISCUSSION: A COS for the management of BMS will improve the quality of future RCTs, reduce outcome reporting heterogeneity, and facilitate more vigorous data synthesis of management interventions for systematic reviews and meta-analysis. This would ensure enhanced quality evidence for clinical management of the condition.
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Síndrome de Boca Ardiente , Proyectos de Investigación , Síndrome de Boca Ardiente/diagnóstico , Síndrome de Boca Ardiente/terapia , Técnica Delphi , Determinación de Punto Final , Humanos , Metaanálisis como Asunto , Evaluación de Resultado en la Atención de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto , Encuestas y Cuestionarios , Revisiones Sistemáticas como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: There is limited information regarding the daily shedding of JC virus (JCV) in urine and its correlation with serum JCV antibody levels. METHODS: The dynamic expression of JCV in urine and its correlation with JCV antibody status in patients receiving disease modifying therapy for multiple sclerosis were examined in a longitudinal case-control study. JCV antibody index levels were determined using a two-step ELISA (Stratify). JCV shedding in urine samples was determined by quantitative PCR during two 30-day study periods separated by intervals of at least 6 months. RESULTS: Of 42 study subjects (57% female; ages 22-56, average age 39.6 years), 27 (64.3%) were JCV antibody positive (index >0.40) at initial urine collection. Twelve seropositive subjects (44.4%) had detectable JCV in their urine with values ranging from 290 to 5.08 × 108 copies/mL. Daily viral shedding in these patients remained fairly constant throughout the study. Urinary JCV shedding was not detected in any JCV antibody index negative or indeterminate subject. In JCV urinary shedders, the average JCV antibody index was 2.69 (range 1.67-3.57). The average anti-JCV antibody index for the remaining JCV seropositive individuals without viral urinary shedding was 1.35 (range 0.46-3.91). CONCLUSION: MS patients displayed a consistent pattern of JCV shedding over days and months in which higher levels of viruria appeared to have driven higher levels of JCV antibody index. The findings provide additional insights into the dynamic expression of JCV and host response; however, studies in larger populations and of longer duration will be needed to determine their significance to the development of progressive multifocal leukoencephalopathy (PML).
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Anticuerpos Antivirales/sangre , Factores Inmunológicos/uso terapéutico , Virus JC , Esclerosis Múltiple , Infecciones por Polyomavirus , Esparcimiento de Virus , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Virus JC/inmunología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/orina , Infecciones por Polyomavirus/sangre , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/orina , Adulto JovenRESUMEN
OBJECTIVE: To examine the effects of direct oral anticoagulants (DOACs) on bleeding complications following dental surgeries. SUBJECTS AND METHODS: This 6-year retrospective study collected data from records of patients undergoing oral surgical procedures within a university setting. An electronic health record database was searched using current procedural terminology codes for oral surgical procedures. Information regarding patient, procedural factors, and postoperative complications were extracted. Data were analyzed by Fisher's exact test. RESULTS: Of patients who had a procedural code associated with oral surgery, only 0.11% (12/11,320) took a DOAC. Twelve patients (10 males, age ranging from 44 to 90 years) underwent 17 surgeries by nine different practitioners involving 98 extractions, 14 alveoloplasties, two tuberosity reductions, and two tori removals. In nine cases, the DOAC was discontinued a mean of 52.5 hrs prior to surgery (range 12-120 hrs). Bleeding complications were not reported for patients whose drug was discontinued or continued. Documentation of drug continuation/discontinuation was poor. CONCLUSIONS: Bleeding was not observed with direct oral anticoagulation use in this oral surgery cohort. Drug discontinuation/continuation was not a factor in bleeding outcomes, and direct oral anticoagulation interruption was variable and poorly documented.
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Anticoagulantes/administración & dosificación , Procedimientos Quirúrgicos Orales/efectos adversos , Hemorragia Posoperatoria/etiología , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Documentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Privación de TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: Periodontal diseases are a major public health concern leading to tooth loss and have also been shown to be associated with several chronic systemic diseases. Smoking is a major risk factor for the development of numerous systemic diseases, as well as periodontitis. While it is clear that smokers have a significantly enhanced risk for developing periodontitis leading to tooth loss, the population varies regarding susceptibility to disease associated with smoking. This investigation focused on identifying differences in four broad sets of variables, consisting of: (i) host-response molecules; (ii) periodontal clinical parameters; (iii) antibody responses to periodontal pathogens and oral commensal bacteria; and (iv) other variables of interest, in a population of smokers with (n = 171) and without (n = 117) periodontitis. MATERIAL AND METHODS: Bayesian network structured learning (BNSL) techniques were used to investigate potential associations and cross-talk between the four broad sets of variables. RESULTS: BNSL revealed two broad communities with markedly different topology between the populations of smokers, with and without periodontitis. Confidence of the edges in the resulting network also showed marked variations within and between the periodontitis and nonperiodontitis groups. CONCLUSION: The results presented validated known associations and discovered new ones with minimal precedence that may warrant further investigation and novel hypothesis generation. Cross-talk between the clinical variables and antibody profiles of bacteria were especially pronounced in the case of periodontitis and were mediated by the antibody response profile to Porphyromonas gingivalis.
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Periodontitis/etiología , Fumar/efectos adversos , Adulto , Anciano , Anticuerpos Antibacterianos/sangre , Teorema de Bayes , Estudios de Casos y Controles , Cotinina/análisis , Femenino , Gingivitis/etiología , Humanos , Masculino , Persona de Mediana Edad , Índice Periodontal , Periodontitis/sangre , Periodontitis/microbiología , Saliva/química , Fumar/sangre , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Adiponectin is produced by adipose cells and is considered an anti-inflammatory molecule. In contrast, C-reactive protein (CRP) has been identified as a hallmark of systemic inflammation and used as a risk marker of cardiovascular disease (CVD). Of interest was the relationship of these two biomarkers to oral health and CVD risk. MATERIAL AND METHODS: This investigation examined these two molecules in serum and unstimulated whole saliva of patients within 48 h of an acute myocardial infarction (AMI) compared to control subjects. We hypothesized a differential response in these biomolecules resulting from the heart attack that would be affected by both the body mass index and oral health characteristics of the individuals. RESULTS: Significantly lower adiponectin levels were observed in the serum of patients with AMI. Serum adiponectin in both groups and salivary adiponectin in patients with AMI decreased with increasing body mass index. Oral health was significantly worse in patients with AMI, and both serum and salivary adiponectin were elevated with better oral health in control subjects. Serum CRP levels were increased in patients with AMI regardless of their oral health, and both serum and salivary CRP were significantly elevated in S-T wave elevated patients with MI. CONCLUSIONS: These initial data provide evidence relating obesity and oral health to salivary and serum analyte levels that occur in association with cardiac events. Relationships have been described between CVD risk and periodontal disease. Additionally, various systemic inflammatory biomarkers appear to reflect both the CVD risk and the extent/severity of periodontitis. Our findings indicated that oral health and obesity contribute to altering levels of these salivary and serum analytes in association with cardiac events. The potential that serum and/or salivary biomarkers could aid in evaluating CVD risk requires knowledge regarding how the oral health of the individual would impact the effectiveness of these biological measures.
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Adiponectina/sangre , Proteína C-Reactiva/análisis , Infarto del Miocardio/metabolismo , Enfermedades Periodontales/complicaciones , Saliva/química , Adiponectina/análisis , Biomarcadores/análisis , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/complicaciones , Obesidad/sangre , Obesidad/metabolismo , Salud Bucal/estadística & datos numéricos , Enfermedades Periodontales/sangre , Enfermedades Periodontales/metabolismo , Periodontitis/sangre , Periodontitis/complicaciones , Periodontitis/metabolismoRESUMEN
OBJECTIVE: The objective of this study was to determine the efficacy of a novel point-of-care immunoflow device (POCID) for detecting matrix metalloproteinase (MMP)-8 concentrations in oral fluids in comparison with a gold standard laboratory-based immunoassay. METHODS: Oral rinse fluid and whole expectorated saliva samples were collected from 41 participants clinically classified as periodontally healthy or diseased. Samples were analyzed for MMP-8 by Luminex immunoassay and POCID. Photographed POCID results were assessed by optical scan and visually by two examiners. Data were analyzed by Pearson's correlation and receiver-operating characteristics. RESULTS: MMP-8 was readily detected by the POCID, and concentrations correlated well with Luminex for both saliva and rinse fluids (r = 0.57-0.93). Thresholds that distinguished periodontitis from health were delineated from both the optical scans and visual reads of the POCID (sensitivity: 0.7-0.9, specificity: 0.5-0.7; P < 0.05). CONCLUSIONS: Performance of this POCID for detecting MMP-8 in oral rinse fluid or saliva was excellent. These findings help demonstrate the utility of salivary biomarkers for distinguishing periodontal disease from health using a rapid point-of-care approach.
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Metaloproteinasa 8 de la Matriz/análisis , Enfermedades Periodontales/enzimología , Saliva/enzimología , Adulto , Biomarcadores/análisis , Femenino , Humanos , Inmunoensayo/métodos , Masculino , Periodontitis/enzimología , Sistemas de Atención de PuntoRESUMEN
This study used conventional digital radiography to estimate the rate of tooth wear (TW) of maxillary and mandibular central incisors based on a cross-sectional study design. The crown length of 1239 permanent maxillary and mandibular central incisors from 346 persons (age groups: 10, 25, 40, 55 and 70 years ± 3) were measured by three calibrated dentists. Study teeth were intact incisally, had clearly visible incisal edges and cementoenamel junctions and had natural tooth antagonists. Measures were based on digital radiographic images (N = 666) archived in MiPACS within the electronic health record (axiUm(®)) from the College of Dentistry patient database. Incisor crown length decreased at a linear rate in both arches over the 60 years represented by the age groups. The average crown length for maxillary incisors in the youngest age group was 11.94 mm, which decreased by an average of 1.01 mm by median age 70. For mandibular incisors, the average crown length in the youngest age group was 9.58 mm, which decreased by an average of 1.46 mm in the oldest age group. Males and females showed similar rates of TW. Regardless of age, females demonstrated smaller mean crown height for maxillary incisors than males (P < 0.0001). Measures by the examiners demonstrated good agreement, with an interclass correlation coefficient of 0.869 and an average intra-examiner correlation of 99.5%, based on repeated measurements (n = 100). TW was estimated to average 1.01 mm for maxillary central incisors and 1.46 mm for mandibular central incisors by age 70 years.
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Incisivo/diagnóstico por imagen , Mandíbula/diagnóstico por imagen , Maxilar/diagnóstico por imagen , Desgaste de los Dientes/diagnóstico por imagen , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Estudios Transversales , Femenino , Humanos , Incisivo/anatomía & histología , Masculino , Persona de Mediana Edad , Radiografía Dental Digital , Adulto JovenRESUMEN
Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model.
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Trastornos de Ansiedad/etiología , Dolor Facial/complicaciones , Dolor Facial/etiología , Traumatismos del Nervio Trigémino/complicaciones , Adaptación Ocular , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Conducta Exploratoria , Lateralidad Funcional , Hiperalgesia/fisiopatología , Masculino , Aprendizaje por Laberinto , Ratones , Ratones Endogámicos C57BL , Dimensión del Dolor , Umbral del Dolor , Reflejo de SobresaltoRESUMEN
The comparative utility of serum and saliva as diagnostic fluids for identifying biomarkers of acute myocardial infarction (AMI) was investigated. The goal was to determine if salivary biomarkers could facilitate a screening diagnosis of AMI, especially in cases of non-ST elevation MI (NSTEMI), since these cases are not readily identified by electrocardiogram (ECG). Serum and unstimulated whole saliva (UWS) collected from 92 AMI patients within 48 hours of chest pain onset and 105 asymptomatic healthy control individuals were assayed for 13 proteins relevant to cardiovascular disease, by Beadlyte technology (Luminex(®)) and enzyme immunoassays. Data were analyzed with concentration cut-points, ECG findings, logistic regression (LR) (adjusted for matching for age, gender, race, smoking, number of teeth, and oral health status), and classification and regression tree (CART) analysis. A sensitivity analysis was conducted by repetition of the CART analysis in 58 cases and 58 controls, each matched by age and gender. Serum biomarkers demonstrated AMI sensitivity and specificity superior to that of saliva, as determined by LR and CART. The predominant discriminators in serum by LR were troponin I (TnI), B-type natriuretic peptide (BNP), and creatine kinase-MB (CK-MB), and TnI and BNP by CART. In saliva, LR identified C-reactive protein (CRP) as the biomarker most predictive of AMI. A combination of smoking tobacco, UWS CRP, CK-MB, sCD40 ligand, gender, and number of teeth identified AMI in the CART decision trees. When ECG findings, salivary biomarkers, and confounders were included, AMI was predicted with 80.0% sensitivity and 100% specificity. These analyses support the potential utility of salivary biomarker measurements used with ECG for the identification of AMI. Thus, saliva-based tests may provide additional diagnostic screening information in the clinical course for patients suspected of having an AMI.
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Biomarcadores/análisis , Infarto del Miocardio/diagnóstico , Saliva/química , Adulto , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Ligando de CD40/análisis , Estudios de Casos y Controles , Estudios de Cohortes , Forma MB de la Creatina-Quinasa/sangre , Estudios Transversales , Árboles de Decisión , Dentición , Diagnóstico Precoz , Electrocardiografía/métodos , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Péptido Natriurético Encefálico/sangre , Salud Bucal , Proteínas y Péptidos Salivales/análisis , Sensibilidad y Especificidad , Factores Sexuales , Fumar , Troponina I/sangreRESUMEN
BACKGROUND AND OBJECTIVE: Antimicrobial agents provide valuable adjunctive therapy for the prevention and the control of oral diseases. Limitations in their prolonged use have stimulated the search for new, naturally occurring agents with more specific activity and fewer adverse effects. Here we sought to determine the antibacterial properties of blackberry extract (BBE) in vitro against oral bacterial commensals and periodontopathogens. MATERIAL AND METHODS: The effects of whole and fractionated BBE on the metabolism of 10 different oral bacteria were evaluated using the colorimetric water-soluble tetrazolium-1 assay. The bactericidal effects of whole BBE against Fusobacterium nucleatum were determined by quantitating the numbers of colony-forming units (CFUs). Cytotoxicity was determined in oral epithelial (OKF6) cells. RESULTS: BBE at 350-1400 µg/mL reduced the metabolic activity of Porphyromonas gingivalis, F. nucleatum and Streptococcus mutans. The reduced metabolic activity observed for F. nucleatum corresponded to a reduction in the numbers of CFUs following exposure to BBE for as little as 1 h, indicative of its bactericidal properties. An anthocyanin-enriched fraction of BBE reduced the metabolic activity of F. nucleatum, but not of P. gingivalis or S. mutans, suggesting the contribution of species-specific agents in the whole BBE. Oral epithelial cell viability was not reduced following exposure to whole BBE (2.24-1400 µg/mL) for ≤ 6 h. CONCLUSION: BBE alters the metabolic activity of oral periodontopathogens while demonstrating a minimal effect on commensals. The specific antibacterial properties of BBE shown in this study, along with its previously demonstrated anti-inflammatory and antiviral properties, make this natural extract a promising target as an adjunct for prevention and/or complementary therapy of periodontal infections.
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Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Enfermedades Periodontales/microbiología , Extractos Vegetales/farmacología , Rosaceae , Actinomyces/efectos de los fármacos , Aggregatibacter actinomycetemcomitans/efectos de los fármacos , Antocianinas/farmacología , Antiinfecciosos Locales/farmacología , Carga Bacteriana/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Clorhexidina/análogos & derivados , Clorhexidina/farmacología , Colorimetría/métodos , Células Epiteliales/efectos de los fármacos , Fusobacterium nucleatum/efectos de los fármacos , Humanos , Indicadores y Reactivos , Queratinocitos/efectos de los fármacos , Ensayo de Materiales , Mucosa Bucal/citología , Mucosa Bucal/efectos de los fármacos , Porphyromonas gingivalis/efectos de los fármacos , Prevotella intermedia/efectos de los fármacos , Streptococcus gordonii/efectos de los fármacos , Streptococcus mutans/efectos de los fármacos , Streptococcus oralis/efectos de los fármacos , Sales de Tetrazolio , Factores de Tiempo , Veillonella/efectos de los fármacosRESUMEN
Data on the strength of the utero-placental interface (UPI) would help improve understanding of the mechanisms of placental abruption (premature separation of the placenta from the uterus) during motor-vehicle crashes involving pregnant occupants. An ovine model was selected for study because like the human, its placenta has a villous attachment structure. Uteri with intact placentas were obtained from three sheep as by-products of another research study. The samples were harvested between 102 and 119 days of the 145-day gestational period. Rectangular specimens with areas measuring 15 mm × 5 mm were cut through the thickness of the placenta and uterus. Each subject provided eight samples, of which four were tested at a nominal strain rate of 0.10 strains/sec and the remainder was tested at a nominal strain rate of 1.0 strains/sec. Sutures were used to secure the uterine side of the specimens to the test fixture, while mechanical clamps were used to attach the placenta side. A FARO arm scanner recorded the initial geometry of the tissue, and a random dot pattern applied to the placenta and uterus tissue allowed visualization of displacement. For the structure of the UPI, mean tensile failure strain and standard deviations are 0.37 (0.11) and 0.37 (0.18) for the 0.10 and 1.0 strain rates, respectively (p-value = 0.970) while the associated failure stresses are 6.5 (1.37) and 15.0 (5.08) kPa, (p-value = 0.064). The results from sheep UPI testing provide the first estimate of the human UPI structural failure tolerance.
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Desprendimiento Prematuro de la Placenta/prevención & control , Placenta/fisiología , Estrés Mecánico , Resistencia a la Tracción , Útero/fisiología , Animales , Femenino , Embarazo , Oveja DomésticaRESUMEN
BACKGROUND AND OBJECTIVE: The field of salivary diagnostics lacks an accepted and validated biomarker of alveolar bone remodeling. To address this, we examined levels of salivary biomolecules specifically associated with biological aspects of bone remodeling in subjects with chronic periodontitis in a case-control study. MATERIAL AND METHODS: Levels of macrophage inflammatory protein-1α (MIP-1α), osteoprotegerin, C-telopeptide pyridinoline cross-links of type I collagen and ß-C-terminal type I collagen telopeptide in unstimulated whole saliva of 80 subjects (40 subjects with moderate to severe chronic periodontitis and 40 sex- and age-matched healthy control subjects) were measured using enzyme immunosorbent assays. Saliva was collected before clinical examination, which included probing depth, clinical attachment loss and bleeding on probing. RESULTS: The mean level of MIP-1α in subjects with periodontitis was 18-fold higher than in healthy subjects (p < 0.0001). Clinical periodontal indices correlated significantly with MIP-1α levels (p < 0.0001). Of the biomolecules examined, MIP-1α demonstrated the greatest ability to discriminate between periodontal disease and health as determined by the area under the curve (0.94) and classification and regression tree analysis (sensitivity 94% and specificity 92.7%). Osteoprotegerin levels were elevated 1.6-fold (p = 0.055), whereas C-telopeptide pyridinoline cross-links of type I collagen and ß-C-terminal type I collagen telopeptide levels were below the level of detection in the majority of subjects. CONCLUSION: These findings suggest that the chemokine MIP-1α may aid in identifying periodontitis. Future longitudinal studies are warranted to determine whether this biomarker can help in ascertaining the progression of bone loss in subjects with periodontal disease.
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Remodelación Ósea/fisiología , Quimiocina CCL3/análisis , Periodontitis Crónica/metabolismo , Periodoncio/metabolismo , Proteínas y Péptidos Salivales/análisis , Adulto , Área Bajo la Curva , Biomarcadores/análisis , Estudios de Casos y Controles , Colágeno Tipo I/análisis , Estudios Transversales , Femenino , Hemorragia Gingival/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Osteoprotegerina/análisis , Péptidos/análisis , Pérdida de la Inserción Periodontal/metabolismo , Índice Periodontal , Bolsa Periodontal/metabolismo , Sensibilidad y Especificidad , Adulto JovenRESUMEN
The protonation state of ionizable residues is an important contributor to protein stability and function. Histidine is of particular importance because its side chain pK(a) is near physiological pH. The sensitivity of carbon deuterium (C-D) vibrational frequencies to the protonation state of histidine dipeptide (Hdp) was investigated in the gas-phase using density functional theory (DFT) calculations, and in aqueous solution using two-layered integrated molecular orbital and molecular mechanics (ONIOM) calculations. All three C-D vibrational probes on the side chain (C(beta)-D(2), C(delta)-D, and C(epsilon)-D) independently exhibited a striking sensitivity to the gas-phase histidine protonation state, with calculated shifts of up to 40 cm(-1) upon deprotonation of the histidine residue. Simultaneously including all three C-D vibrational probes on the Hdp side chain produced significant shifts of 28 to 43 cm(-1) between the neutral and charged states. The calculated intensities also dropped precipitously upon deprotonation, which is an important factor for the interpretation of experiments employing C-D vibrational probes to investigate side chain protonation. Solvating the labeled Hdp molecule produces an overall blue-shift in the average C-D vibrational frequencies relative to the gas-phase. The C(beta)-D(2), C(delta)-D, and C(epsilon)-D vibrational probes all showed sensitivity to the histidine protonation state, with shifts of up to 40 cm(-1) in the mean frequencies after deprotonation, which bodes well for studies employing C-D probes to study histidine protonation state in peptides and proteins.
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Carbono/química , Deuterio/química , Gases/química , Histidina/química , Protones , Agua/química , Dipéptidos/química , VibraciónRESUMEN
OBJECTIVE: The aim of this study was to determine the presence and quantity of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA in the saliva of patients with periodontitis, and investigate the correlation between these factors. METHODS: Presence and amounts of viral DNA in saliva and subgingival plaque samples, from healthy and disease sites, of 65 adults diagnosed with chronic periodontitis were determined using quantitative real-time polymerase chain reaction. RESULTS: Epstein-Barr virus DNA was detected in saliva of 81.5% (53/65) of patients at a median concentration of 4325 copies ml(-1). CMV DNA was detected in saliva of one individual (1.5%) at low copy number. Patients who had EBV in saliva were 10 times more likely to have EBV in subgingival plaque than patients lacking EBV in saliva (odds ratio = 10.1, 95% confidence interval = 2.6-39.5; P = 0.0009). EBV DNA burden in saliva positively correlated with the amounts detected in plaque and with amounts detected in increasing number of affected sites (P < 0.0001). EBV DNA presence and quantity in saliva did not correlate with increasing severity of disease as measured by periodontal indices. CONCLUSIONS: Epstein-Barr virus DNA presence and burden in saliva are associated with its presence and burden in subgingival plaque, but presence and burden in saliva does not correlate with periodontal disease severity.
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Periodontitis Crónica/virología , Citomegalovirus/aislamiento & purificación , ADN Viral/aislamiento & purificación , Herpesvirus Humano 4/aislamiento & purificación , Saliva/virología , Adulto , Anciano , Periodontitis Crónica/patología , Citomegalovirus/genética , Placa Dental/patología , Placa Dental/virología , Femenino , Líquido del Surco Gingival/virología , Herpesvirus Humano 4/genética , Humanos , Masculino , Persona de Mediana Edad , Índice Periodontal , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Índice de Severidad de la Enfermedad , Curetaje Subgingival , Carga ViralRESUMEN
The protonation state of titratable amino acid residues has profound effects on protein stability and function. Therefore, correctly determining the acid dissociation constant, pK(a), of charged residues under physiological conditions is an important challenge. The general utility of site-specific carbon-deuterium (C-D) vibrational probes as reporters of the protonation state of arginine, aspartic acid, glutamic acid, and lysine amino acid side chains was examined using density functional theory (DFT) calculations. Substantial shifts were observed in the anharmonic vibrational frequencies of a C-D(2) probe placed immediately adjacent to the titratable group. Lysine exhibited the largest C-D(2) frequency shifts upon protonation, 44.9 cm(-1) (symmetric stretch) and 69.5 cm(-1) (asymmetric stretch). Furthermore, the predicted harmonic intensities of the C-D(2) probe vibrations were extraordinarily sensitive to the protonation state of the nearby acidic or basic group. Accounting for this dramatic change in intensity is essential to the interpretation of an infrared (IR) absorption spectrum that contains the signature of both the neutral and charged states.
Asunto(s)
Aminoácidos/química , Carbono/química , Deuterio/química , Sondas Moleculares/química , Protones , Simulación por Computador , Leucina/química , Modelos Químicos , Proteínas/química , VibraciónRESUMEN
The utility of alpha-carbon deuterium-labeled bonds (C(alpha)-D) as infrared reporters of local peptide conformation was investigated for two model dipeptide compounds: C(alpha)-D labeled alanine dipeptide (Adp-d(1)) and C(alpha)-D(2) labeled glycine dipeptide (Gdp-d(2)). These model compounds adopt structures that are analogous to the motifs found in larger peptides and proteins. For both Adp-d(1) and Gdp-d(2), we systematically mapped the entire conformational landscape in the gas phase by optimizing the geometry of the molecule with the values of phi and psi, the two dihedral angles that are typically used to characterize the backbone structure of peptides and proteins, held fixed on a uniform grid with 7.5 degrees spacing. Since the conformations were not generally stationary states in the gas phase, we then calculated anharmonic C(alpha)-D and C(alpha)-D(2) stretch transition frequencies for each structure. For Adp-d(1) the C(alpha)-D stretch frequency exhibited a maximum variability of 39.4 cm(-1) between the six stable structures identified in the gas phase. The C(alpha)-D(2) frequencies of Gdp-d(2) show an even more substantial difference between its three stable conformations: there is a 40.7 cm(-1) maximum difference in the symmetric C(alpha)-D(2) stretch frequencies and an 81.3 cm(-1) maximum difference in the asymmetric C(alpha)-D(2) stretch frequencies. Moreover, the splitting between the symmetric and asymmetric C(alpha)-D(2) stretch frequencies of Gdp-d(2) is remarkably sensitive to its conformation.