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Clarifying multifactorial musculoskeletal disorder etiologies supports risk analysis and development of targeted prevention and treatment modalities. Deep learning enables comprehensive risk factor identification through systematic analysis of disease datasets but does not provide sufficient context for mechanistic understanding, limiting clinical applicability for etiological investigations. Conversely, multiscale biomechanical modeling can evaluate mechanistic etiology within the relevant biomechanical and physiological context. We propose a hybrid approach combining 3D explainable deep learning and multiscale biomechanical modeling; we applied this approach to investigate temporomandibular joint (TMJ) disorder etiology by systematically identifying risk factors and elucidating mechanistic relationships between risk factors and TMJ biomechanics and mechanobiology. Our 3D convolutional neural network recognized TMJ disorder patients through subject-specific morphological features in condylar, ramus, and chin. Driven by deep learning model outputs, biomechanical modeling revealed that small mandibular size and flat condylar shape were associated with increased TMJ disorder risk through increased joint force, decreased tissue nutrient availability and cell ATP production, and increased TMJ disc strain energy density. Combining explainable deep learning and multiscale biomechanical modeling addresses the "mechanism unknown" limitation undermining translational confidence in clinical applications of deep learning and increases methodological accessibility for smaller clinical datasets by providing the crucial biomechanical context.
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In current clinical trial development, historical information is receiving more attention as it provides utility beyond sample size calculation. Meta-analytic-predictive (MAP) priors and robust MAP priors have been proposed for prospectively borrowing historical data on a single endpoint. To simultaneously synthesize control information from multiple endpoints in confirmatory clinical trials, we propose to approximate posterior probabilities from a Bayesian hierarchical model and estimate critical values by deep learning to construct pre-specified strategies for hypothesis testing. This feature is important to ensure study integrity by establishing prospective decision functions before the trial conduct. Simulations are performed to show that our method properly controls family-wise error rate and preserves power as compared with a typical practice of choosing constant critical values given a subset of null space. Satisfactory performance under prior-data conflict is also demonstrated. We further illustrate our method using a case study in Immunology.
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Proyectos de Investigación , Teorema de Bayes , Simulación por Computador , Humanos , Probabilidad , Tamaño de la MuestraRESUMEN
Temporomandibular joint (TMJ) disorders disproportionally affect females, with female to male prevalence varying from 3:1 to 8:1. Sexual dimorphisms in masticatory muscle attachment morphometry and association with craniofacial size, critical for understanding sex-differences in TMJ function, have not been reported. The objective of this study was to determine sex-specific differences in three-dimensional (3D) TMJ muscle attachment morphometry and craniofacial sizes and their impact on TMJ mechanics. Human cadaveric TMJ muscle attachment morphometry and craniofacial anthropometry (10Males; 11Females) were determined by previously developed 3D digitization and imaging-based methods. Sex-differences in muscle attachment morphometry and craniofacial anthropometry, and their correlation were determined, respectively using multivariate general linear and linear regression statistical models. Subject-specific musculoskeletal models of the mandible were developed to determine effects of sexual dimorphisms in mandibular size and TMJ muscle attachment morphometry on joint loading during static biting. There were significant sex-differences in craniofacial size (p = 0.024) and TMJ muscle attachment morphometry (p < 0.001). TMJ muscle attachment morphometry was significantly correlated with craniofacial size. TMJ contact forces estimated from biomechanical models were significantly, 23% on average (p < 0.001), greater for females compared to those for males when generating the same bite forces. There were significant linear correlations between TMJ contact force and both 3D mandibular length (R2 = 0.48, p < 0.001) and muscle force moment arm ratio (R2 = 0.68, p < 0.001). Sexual dimorphisms in masticatory muscle morphology and craniofacial sizes play critical roles in subject-specific TMJ biomechanics. Sex-specific differences in the TMJ mechanical environment should be further investigated concerning mechanical fatigue of TMJ discs associated with TMJ disorders.
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Caracteres Sexuales , Articulación Temporomandibular , Fuerza de la Mordida , Femenino , Humanos , Masculino , Mandíbula , Músculos MasticadoresRESUMEN
Diffusion is an important mechanism of transport for nutrients and drugs throughout the avascular corneal stroma. The purpose of this study was to investigate the depth- and direction-dependent changes in stromal transport properties and their relationship to changes in collagen structure following ultraviolet A (UVA)-riboflavin induced corneal collagen cross-linking (CXL). After cross-linking in ex vivo porcine eyes, fluorescence recovery after photobleaching (FRAP) was performed to measure fluorescein diffusion in the nasal-temporal (NT) and anterior-posterior (AP) directions at corneal depths of 100, 200, and 300 µm. Second harmonic generation (SHG) imaging was also performed at these three corneal depths to quantify fiber alignment. For additional confirmation, an electrical conductivity method was employed to quantify ion permeability in the AP direction in corneal buttons and immunohistochemistry (IHC) was used to image collagen structure. Cross-linked corneas were compared to a control treatment that received the riboflavin solution without UVA light (SHAM). The results of FRAP revealed that fluorescein diffusivity decreased from 23.39 ± 11.60 µm2/s in the SHAM group to 19.87 ± 10.10 µm2/s in the CXL group. This change was dependent on depth and direction: the decrease was more pronounced in the 100 µm depth (P = 0.0005) and AP direction (P = 0.001) when compared to the effect in deeper locations and in the NT direction, respectively. Conductivity experiments confirmed a decrease in solute transport in the AP direction (P < 0.0001). FRAP also detected diffusional anisotropy in the porcine cornea: the fluorescein diffusivity in the NT direction was higher than the diffusivity in the AP direction. This anisotropy was increased following CXL treatment. Both SHG and IHC revealed a qualitative decrease in collagen crimping following CXL. Analysis of SHG images revealed an increase in coherency in the anterior 200 µm of CXL treated corneas when compared to SHAM treated corneas (P < 0.01). In conclusion, CXL results in a decrease in stromal solute transport, and this decrease is concentrated in the most anterior region and AP direction. Solute transport in the porcine cornea is anisotropic, and an increase in anisotropy with CXL may be explained by a decrease in collagen crimping.
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Sustancia Propia/efectos de los fármacos , Reactivos de Enlaces Cruzados , Fluoresceína/metabolismo , Fármacos Fotosensibilizantes/farmacología , Riboflavina/farmacología , Animales , Transporte Biológico Activo/fisiología , Colágeno Tipo I/metabolismo , Sustancia Propia/metabolismo , Conductividad Eléctrica , Inmunohistoquímica , Transporte Iónico/fisiología , Masculino , Fotoquimioterapia , Sus scrofa , Rayos UltravioletaRESUMEN
This study examined the interactive effects of acculturation (host culture acquisition) and enculturation (heritage culture retention) on Latina/o caregivers' beliefs about their child completing the human papillomavirus vaccine series. Participants were 161 caregiver-child dyads from Florida. Using multiple regression, caregiver knowledge and health beliefs (perceived threat, benefits, barriers, subjective norms, and self-efficacy) about series completion were predicted from caregivers' scores on acculturation, enculturation, and their interaction, controlling for sociodemographics. Acculturation and enculturation interacted to predict knowledge, benefits, barriers, and self-efficacy. Caregivers with high acculturation scores generally supported series completion, regardless of their enculturation score. However, when acculturation was low, caregivers who retained more (vs. less) of their heritage culture were more knowledgeable and held more favorable beliefs about series completion. Findings highlight the importance of independently assessing acculturation and enculturation in Latina/o immigrant populations. Overlooking enculturation may lead to incomplete conclusions about acculturation and health.
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Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Aculturación , Cuidadores , Niño , Femenino , Florida , Hispánicos o Latinos , Humanos , Masculino , VacunaciónRESUMEN
OBJECTIVE: Diabetes is a major health problem that is closely linked with cardiovascular disease (CVD), the leading cause of death in the United States. The purpose of this analysis was to determine the effect of a culturally relevant diabetes health promotion program on diabetes knowledge and self-reported self-care behaviors. DESIGN: A cluster randomized controlled trial was conducted in 12 rural church settings. Seven churches were randomized to the intervention group and five to the control group. SAMPLE: The sample included 146 African American participants diagnosed with diabetes and prediabetes. INTERVENTION: The intervention group participants (n = 75) received the diabetes health program, and those in the control group (n = 71) group received a publicly available diabetes health brochure. MEASURES: Data were collected about diabetes knowledge, self-care activities, fatalism, and social support. RESULTS: Linear mixed model was the statistical test used to analyze group differences. Compared with the control group, the intervention group showed significant changes from pretest to posttest for diabetes knowledge and behaviors associated with diet and blood glucose testing. CONCLUSION: Health promotion programs implemented by public health nurses among rural groups at increased risk for developing CVD can facilitate understanding about strategies to reduce disease risk.
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Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus/epidemiología , Promoción de la Salud/métodos , Estado Prediabético/epidemiología , Población Rural/estadística & datos numéricos , Adulto , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Anciano , Análisis por Conglomerados , Dieta , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Autocuidado , Apoyo Social , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: Approximately 2 to 4% of the US population have been estimated to seek treatment for temporomandibular symptoms, predominately women. The study purpose was to determine whether sex-specific differences in temporomandibular morphometry result from scaling with sex differences in skull size and shape or intrinsic sex-specific differences. MATERIALS AND METHODS: A total of 22 (11 male [aged 74.5 ± 9.1 years]; 11 female [aged 73.6 ± 12.8 years]) human cadaveric heads with no history of temporomandibular disc derangement underwent cone beam computed tomography and high-resolution magnetic resonance imaging scanning to determine 3-dimensional cephalometric parameters and temporomandibular morphometric outcomes. Regression models between morphometric outcomes and cephalometric parameters were developed, and intrinsic sex-specific differences in temporomandibular morphometry normalized by cephalometric parameters were determined. Subject-specific finite element (FE) models of the extreme male and extreme female conditions were developed to predict variations in articular disc stress-strain under the same joint loading. RESULTS: In some cases, sex differences in temporomandibular morphometric parameters could be explained by linear scaling with skull size and shape; however, scaling alone could not fully account for some differences between sexes, indicating intrinsic sex-specific differences. The intrinsic sex-specific differences in temporomandibular morphometry included an increased condylar medial length and mediolateral disc lengths in men and a longer anteroposterior disc length in women. Considering the extreme male and female temporomandibular morphometry observed in the present study, subject-specific FE models resulted in sex differences, with the extreme male joint having a broadly distributed stress field and peak stress of 5.28 MPa. The extreme female joint had a concentrated stress field and peak stress of 7.37 MPa. CONCLUSIONS: Intrinsic sex-specific differences independent of scaling with donor skull size were identified in temporomandibular morphometry. Understanding intrinsic sex-specific morphometric differences is critical to determining the temporomandibular biomechanics given the effect of anatomy on joint contact mechanics and stress-strain distributions and requires further study as one potential factor for the increased predisposition of women to temporomandibular disc derangement.
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Luxaciones Articulares , Disco de la Articulación Temporomandibular , Articulación Temporomandibular , Anciano , Anciano de 80 o más Años , Cadáver , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Cóndilo Mandibular/anatomía & histología , Persona de Mediana Edad , Caracteres Sexuales , Cráneo , Articulación Temporomandibular/anatomía & histología , Disco de la Articulación Temporomandibular/anatomía & histologíaRESUMEN
PURPOSE: The purpose of this longitudinal study was to identify individual and interpersonal factors associated with human papillomavirus (HPV) vaccine series completion in a sample of low-income Latina/o adolescent girls and boys. METHODS: Caregiver-adolescent dyads (N = 161) were recruited from a rural Federally Qualified Health Center in southwest Florida when the adolescent (aged 11-17 years) received the first dose of HPV vaccine. Dyads completed a baseline assessment that measured demographic and cultural characteristics, past medical history, provider-patient communication, HPV knowledge, health beliefs about completing the series, and the adolescent's experience receiving the first dose. Using multivariable logistic regression, we identified caregiver- and adolescent-related factors associated with series completion (receipt of three doses of HPV vaccine within 1 year of initiation) as indicated in the adolescent's medical record and state immunization registry. RESULTS: Within 1 year of initiation, 57% (n = 92) completed the three-dose series. Missed opportunities for completion were observed for 20% of the sample who returned to the clinic. Caregiver-related predictors of completion included education, self-efficacy to complete the series, and knowledge of the required number of doses. Adolescent-related predictors included age, influenza vaccination within the past 2 years, having a chronic medical condition, reason for the baseline visit, and receipt of written information about HPV vaccination from a health care provider. CONCLUSIONS: Findings highlight important opportunities for improving completion of the HPV vaccine series among Latina/o adolescents. Intervention efforts should involve health care providers and parent-adolescent dyads and prioritize evidence-based strategies for reducing missed opportunities for series completion.
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Comunicación , Conocimientos, Actitudes y Práctica en Salud , Hispánicos o Latinos/estadística & datos numéricos , Esquemas de Inmunización , Vacunas contra Papillomavirus/administración & dosificación , Aceptación de la Atención de Salud , Adolescente , Cuidadores , Niño , Femenino , Florida , Humanos , Estudios Longitudinales , Masculino , Infecciones por Papillomavirus/prevención & control , Pobreza/etnología , Proveedores de Redes de Seguridad , Adulto JovenRESUMEN
Cardiovascular disease (CVD) is a major cause of death among people living in the United States. Populations, especially minorities, living in the rural South are disproportionately affected by CVD and have greater CVD risk, morbidity and mortality. Culturally relevant cardiovascular health programs implemented in rural community settings can potentially reduce CVD risk and facilitate health behavior modification. The purpose of this study was to examine the effects of a cardiovascular health promotion intervention on the health habits of a group of rural African American adults. The study had a cluster randomized controlled trial design involving 12 rural churches that served as statistical clusters. From the churches (n = 6) randomized to the intervention group, 115 participants were enrolled, received the 6-week health program and completed pretest-posttest measures. The 114 participants from the control group churches (n = 6) did not receive the health program and completed the same pretest-posttest measures. The linear mixed model was used to compare group differences from pretest to posttest. The educational health intervention positively influenced select dietary and confidence factors that may contribute toward CVD risk reduction.
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Negro o Afroamericano , Enfermedades Cardiovasculares/etnología , Organizaciones Religiosas/organización & administración , Conductas Relacionadas con la Salud , Promoción de la Salud/organización & administración , Adulto , Anciano , Terapia Conductista/métodos , Enfermedades Cardiovasculares/prevención & control , Dieta , Femenino , Humanos , Masculino , Persona de Mediana Edad , Población Rural , Estados UnidosRESUMEN
Cardiovascular disease (CVD) is a major cause of death and disability, especially among people living in the rural, southern United States. Rural African Americans are often diagnosed with CVD earlier in life, and they bear a disproportionate burden of CVD risk factors, morbidity, and mortality. Health equity among historically underserved, rural populations can potentially be attained through culturally relevant interventions that teach people skills to stay well and avoid CVD-related risk and diagnoses. The purpose of this secondary analysis was to determine the effect of an evidence-based intervention on cardiovascular health knowledge and the stages of change toward the action and maintenance phases. The pre-test-post-test data were obtained during a cluster randomized trial involving twelve rural churches that were randomized to intervention (n = 6) and control (n = 6) groups. Participants (n = 115) in the intervention group received a cardiovascular health intervention, and those (n = 114) in the control group could receive the intervention following the study’s completion. The data were analyzed using a linear mixed model to compare group differences from pre-test to post-test. The cardiovascular health promotion intervention significantly improved cardiovascular health knowledge and was associated with advancements in the stages of change toward the action and maintenance phases.
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STUDY DESIGN: Regional measurements of fixed charge densities (FCDs) of healthy human cartilage endplate (CEP) using a two-point electrical conductivity approach. OBJECTIVE: The aim of this study was to determine the FCDs at four different regions (central, lateral, anterior, and posterior) of human CEP, and correlate the FCDs with tissue biochemical composition. SUMMARY OF BACKGROUND DATA: The CEP, a thin layer of hyaline cartilage on the cranial and caudal surfaces of the intervertebral disc, plays an irreplaceable role in maintaining the unique physiological mechano-electrochemical environment inside the disc. FCD, arising from the carboxyl and sulfate groups of the glycosaminoglycans (GAG) in the extracellular matrix of the disc, is a key regulator of the disc ionic and osmotic environment through physicochemical and electrokinetic effects. Although FCDs in the annulus fibrosus (AF) and nucleus pulposus (NP) have been reported, quantitative baseline FCD in healthy human CEP has not been reported. METHODS: CEP specimens were regionally isolated from human lumbar spines. FCD and ion diffusivity were concurrently investigated using a two-point electrical conductivity method. Biochemical assays were used to quantify regional GAG and water content. RESULTS: FCD in healthy human CEP was region-dependent, with FCD lowest in the lateral region (Pâ=â0.044). Cross-region FCD was 30% to 60% smaller than FCD in NP, but similar to the AF and articular cartilage (AC). CEP FCD (average: 0.12â±â0.03âmEq/g wet tissue) was correlated with GAG content (average: 31.24â±â5.06âµg/mg wet tissue) (Pâ=â0.005). In addition, the cross-region ion diffusivity in healthy CEP (2.97â±â1.00â×â10âcm/s) was much smaller than the AF and NP. CONCLUSION: Healthy human CEP acts as a biomechanical interface, distributing loads between the bony vertebral body and soft disc tissues and as a gateway impeding rapid solute diffusion through the disc. LEVEL OF EVIDENCE: N/A.
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Conductividad Eléctrica , Cartílago Hialino , Disco Intervertebral , Fenómenos Electrofisiológicos , Humanos , Cartílago Hialino/química , Cartílago Hialino/fisiología , Disco Intervertebral/química , Disco Intervertebral/fisiologíaRESUMEN
Approximately 30% of temporomandibular joint (TMJ) disorders include degenerative changes to the articular disc, with sex-specific differences in prevalence and severity. Limited tensile biomechanical properties of human TMJ discs have been reported. Stress relaxation tests were conducted on TMJ disc specimens harvested bilaterally from six males and six females (68.9±7.9 years), with step-strain increments of 5%, 10%, 15%, 20% and 30%, at 1% strain-per-second. Stress versus strain plots were constructed, and Young׳s Modulus, Instantaneous Modulus and Relaxed Modulus were determined. The effects of direction, region, and sex were examined. Regional effects were significant (p<0.01) for Young׳s Modulus and Instantaneous Modulus. Anteroposteriorly, the central region was significantly stiffer than medial and lateral regions. Mediolaterally, the posterior region was significantly stiffer than central and anterior regions. In the central region, anteroposteriorly directed specimens were significantly stiffer compared to mediolateral specimens (p<0.04). TMJ disc stiffness, indicated by Young׳s Modulus and Instantaneous Modulus, was higher in directions corresponding to high fiber alignment. Additionally, human TMJ discs were stiffer for females compared to males, with higher Young׳s Modulus and Instantaneous Modulus, and female TMJ discs relaxed less. However, sex effects were not statistically significant. Using second-harmonic generation microscopy, regional collagen fiber organization was identified as a potentially significant factor in determining the biomechanical properties for any combination of direction and region. These findings establish structure-function relationships between collagen fiber direction and organization with biomechanical response to tensile loading, and may provide insights into the prevalence of TMJ disorders among women.
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Disco de la Articulación Temporomandibular/fisiología , Anciano , Colágeno/fisiología , Módulo de Elasticidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Estrés Mecánico , Trastornos de la Articulación Temporomandibular/fisiopatología , Resistencia a la TracciónRESUMEN
The cartilage endplate (CEP) is implicated as the main pathway of nutrient supply to the healthy human intervertebral disc (IVD). In this study, the diffusivities of nutrient/metabolite solutes in healthy CEP were assessed, and further correlated with tissue biochemical composition and structure. The CEPs from non-degenerated human IVD were divided into four regions: central, lateral, anterior, and posterior. The diffusivities of glucose and lactate were measured with a custom diffusion cell apparatus under 0%, 10%, and 20% compressive strains. Biochemical assays were conducted to quantify the water and glycosaminoglycan (GAG) contents. The Safranin-O and Ehrlich׳s hematoxylin and eosin staining and scanning electron microscopy (SEM) were performed to reveal the tissue structure of the CEP. Average diffusivities of glucose and lactate in healthy CEP were 2.68±0.93×10-7cm2/s and 4.52±1.47×10-7cm2/s, respectively. Solute diffusivities were region-dependent (p<0.0001) with the highest values in the central region, and mechanical strains impeded solute diffusion in the CEP (p<0.0001). The solute diffusivities were significantly correlated with the tissue porosities (glucose: p<0.0001, r=0.581; lactate: p<0.0001, r=0.534). Histological and SEM studies further revealed that the collagen fibers in healthy CEP are more compacted than those in the nucleus pulposus (NP) and annulus fibrosus (AF) and show no clear orientation. Compared to human AF and NP, much smaller solute diffusivities in human CEP suggested that it acts as a gateway for solute diffusion through the disc, maintaining the balance of nutritional environment in healthy human disc under mechanical loading and preventing the progression of disc degeneration.
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Cartílago/metabolismo , Glucosa/metabolismo , Disco Intervertebral/metabolismo , Ácido Láctico/metabolismo , Estrés Mecánico , Difusión , Femenino , Glicosaminoglicanos/metabolismo , Humanos , Disco Intervertebral/fisiología , Degeneración del Disco Intervertebral/metabolismo , Masculino , Persona de Mediana Edad , Agua/metabolismoRESUMEN
Much of what is known about bottle nose dolphin (Tursiops truncatus) anatomy and physiology is based on necropsies from stranding events. Measurements of total body length, total body mass, and age are used to estimate growth. It is more feasible to retrieve and transport smaller animals for total body mass measurement than larger animals, introducing a systematic bias in sampling. Adverse weather events, volunteer availability, and other unforeseen circumstances also contribute to incomplete measurement. We have developed a Bayesian mixture model to describe growth in detected stranded animals using data from both those that are fully measured and those not fully measured. Our approach uses a shared random effect to link the missingness mechanism (i.e. full/partial measurement) to distinct growth curves in the fully and partially measured populations, thereby enabling drawing of strength for estimation. We use simulation to compare our model to complete case analysis and two common multiple imputation methods according to model mean square error. Results indicate that our mixture model provides better fit both when the two populations are present and when they are not. The feasibility and utility of our new method is demonstrated by application to South Carolina strandings data.
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Regional biomechanical and biochemical properties of bovine cartilaginous endplate (CEP) and its role in disc mechanics and nutrition were determined. The equilibrium aggregate modulus and hydraulic permeability between the central and lateral regions were examined by confined compression testing. Biochemical assays were conducted to quantify the amount of water, collagen, and glycosaminoglycan (GAG). The equilibrium aggregate modulus of the CEP in the central region (0.23 ± 0.15 MPa) was significantly lower than for the lateral region (0.83 ± 0. 26 MPa). No significant regional difference was found for the permeability of the CEP (central region: 0.13 ± 0.07×10(-15)m(4)/Ns and lateral region: 0.09 ± 0.03 × 10(-15)m(4)/Ns). CEPs were an average of 75.6% water by wet weight, 41.1% collagen, and 20.4% GAG by dry weight in the central region, as well as an average of 70.2% water by wet weight, 73.8% collagen, and 11.7% GAG by dry weight in the lateral region. Regional differences observed for the equilibrium aggregate modulus were likely due to the regional variation in biochemical composition. The lateral bovine endplate is much stiffer and may share a greater portion of the load. Compared with the nucleus pulposus (NP) and annulus fibrosus (AF), a smaller hydraulic permeability was found for the CEP in both the central and lateral regions, which could be due to its lower water content and higher collagen content. Our results suggest that the CEP may block rapid fluid exchange and solute convection, allow pressurization of the interstitial fluid, and play a significant role in nutrient supply in response to loading.
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Disco Intervertebral/fisiología , Animales , Fenómenos Biomecánicos , Bovinos , Colágeno/química , Módulo de Elasticidad , Glicosaminoglicanos/química , Disco Intervertebral/anatomía & histología , Masculino , Permeabilidad , Viscosidad , Agua/químicaRESUMEN
In medicine, it is often useful to stratify patients according to disease risk, severity, or response to therapy. Since many diseases arise from complex gene-gene and gene-environment interactions, patient strata may be defined by combinations of genetic and environmental factors. Traditional statistical methods require specifying interactions a priori making it difficult to identify high order interactions. Alternatively, machine learning methods can model complex interactions, however these models are often difficult to interpret in a clinical setting. Logic regression (LR) enables modeling a binary outcome using logical combinations of binary predictors yielding easily interpretable models. However LR, as currently available, cannot model ordinal responses. This paper extends LR to model an ordinal response and the resulting method is called Ordinal Logic Regression (OLR). Several simulations comparing OLR and Classification and Regression Trees (CART) demonstrate that OLR is superior to CART for identifying variable interactions associated with an ordinal response. OLR is applied to data from a study to determine associations between genetic and health factors with severity of adult periodontitis.
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AIM: Following toll-like receptor (TLR) engagement, lipopolysaccharide (LPS) can stimulate the expression of pro-inflammatory cytokines thus activating the innate immune response. The production of inflammatory cytokines results, in part, from the activation of kinase-induced signalling cascades and transcriptional factors. Of the four distinct classes of mitogen-activated protein kinases (MAPK) described in mammals, p38, c-Jun N-terminal activated kinases (JNK1-3) and extracellular activated kinases (ERK1,2) are the best studied. Previous data have established that p38 MAPK signalling is required for inflammation and bone loss in periodontal disease pre-clinical animal models. MATERIALS & METHODS: In this study, we obtained healthy and diseased periodontal tissues along with clinical parameters and microbiological parameters. Excised fixed tissues were immunostained with total and phospho-specific antibodies against p38, JNK and ERK kinases. RESULTS: Intensity scoring from immunostained tissues was correlated with clinical periodontal parameters. Rank correlations with clinical indices were statistically significantly positive (p-value < 0.05) for total p38 (correlations ranging 0.49-0.68), phospho-p38 (range 0.44-0.56), and total ERK (range 0.52-0.59) levels, and correlations with JNK levels also supported association (range 0.42-0.59). Phospho-JNK and phospho-ERK showed no significant positive correlation with clinical parameters of disease. CONCLUSION: These data strongly implicate p38 MAPK as a major MAPK involved in human periodontal inflammation and severity.
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Periodontitis Crónica/enzimología , Proteínas Quinasas Activadas por Mitógenos/análisis , Bacteroides/aislamiento & purificación , Periodontitis Crónica/inmunología , Periodontitis Crónica/microbiología , Índice de Placa Dental , Femenino , Hemorragia Gingival/enzimología , Hemorragia Gingival/inmunología , Hemorragia Gingival/microbiología , Recesión Gingival/enzimología , Recesión Gingival/inmunología , Recesión Gingival/microbiología , Humanos , Linfocitos/inmunología , Macrófagos/inmunología , Masculino , Proteína Quinasa 1 Activada por Mitógenos/análisis , Proteína Quinasa 10 Activada por Mitógenos/análisis , Proteína Quinasa 3 Activada por Mitógenos/análisis , Proteína Quinasa 8 Activada por Mitógenos/análisis , Proteína Quinasa 9 Activada por Mitógenos/análisis , Pérdida de la Inserción Periodontal/enzimología , Pérdida de la Inserción Periodontal/inmunología , Pérdida de la Inserción Periodontal/microbiología , Índice Periodontal , Bolsa Periodontal/enzimología , Bolsa Periodontal/inmunología , Bolsa Periodontal/microbiología , Periodoncio/enzimología , Células Plasmáticas/inmunología , Porphyromonas gingivalis/aislamiento & purificación , Treponema denticola/aislamiento & purificación , Proteínas Quinasas p38 Activadas por Mitógenos/análisisRESUMEN
This study investigated the effect of mechanical strain on solute diffusion in human TMJ discs (mean cadaver age 77.8) using the electrical conductivity method. The electrical conductivity, as well as small ion diffusivity, of male and female TMJ discs was determined under three compressive strains. In the male group, the average disc electrical conductivity (mean ± SD) at 0% strain was 5.14 ± 0.97 mS/cm, decreased to 4.50 ± 0.91 mS/cm (-12.3%) at 10% strain, and 3.93 ± 0.81 mS/cm (-23.5%) at 20% compressive strain. Correspondingly, the average disc relative ion diffusivity at 0% strain was 0.44 ± 0.08, decreased to 0.40 ± 0.08 (-8.9%) at 10% strain, and 0.36 ± 0.08 (-16.7%) at 20% compressive strain. In the female group, the average disc electrical conductivity at 0% strain was 5.84 ± 0.59 mS/cm, decreased to 5.01 ± 0.50 mS/cm (-14.2%) at 10% strain, and 4.33 ± 0.46 mS/cm (-25.8%) at 20% compressive strain. Correspondingly, the average disc relative ion diffusivity at 0% strain was 0.49 ± 0.05, decreased to 0.43 ± 0.04 (-11.3%) at 10% strain, and 0.39 ± 0.04 (-19.9%) at 20% compressive strain. The results indicated that mechanical strain significantly impeded solute diffusion through the disc. This mechanical strain effect was larger in the female than in the male human TMJ disc. This study may provide new insights into TMJ pathophysiology.
Asunto(s)
Fuerza Compresiva , Modelos Biológicos , Caracteres Sexuales , Disco de la Articulación Temporomandibular/metabolismo , Trastornos de la Articulación Temporomandibular/metabolismo , Anciano , Anciano de 80 o más Años , Transporte Biológico , Impedancia Eléctrica , Femenino , Humanos , Iones/metabolismo , Masculino , Disco de la Articulación Temporomandibular/patología , Disco de la Articulación Temporomandibular/fisiopatología , Trastornos de la Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/fisiopatologíaRESUMEN
AIM: To assess associations of metabolic syndrome, and its individual components, with extent of severe periodontitis among patients with type 2 diabetes mellitus (T2DM). MATERIALS & METHODS: We performed a secondary data analysis (N = 283) using a cross-sectional study population of Gullah African Americans with T2DM. Extent of severe periodontitis was assessed as total diseased tooth-sites/person [evaluated as separate outcomes: 6+mm clinical attachment level (CAL), 5+mm periodontal probing depth (PPD)] using negative binomial regression techniques. Primary independent variables assessed in separate models included metabolic syndrome (yes/no), each metabolic syndrome component (low HDL, hypertension, high triglycerides, large waist circumference) and glycemic control (poor/good). RESULTS: Multivariable CAL-model results showed a significant association for metabolic syndrome status with extent of severe periodontitis (RR = 2.77, p = 0.03). The separate multivariable CAL-model including each metabolic syndrome component showed marginally increased rates among those with large waist circumference (RR = 2.33, p = 0.09) and those with HbA1c ≥ 7% (RR = 1.73, p = 0.06). Multivariable PPD-models showed marginally increased rates among those with metabolic syndrome (RR = 2.18, p = 0.06). CONCLUSION: Metabolic syndrome is associated with the extent of severe periodontitis in this Gullah population with T2DM.