The challenge of ecological validity in temporomandibular disorders research.

OBJECTIVE: To review the ecological validity of outcomes from current research involving temporomandibular disorders (TMDs), with an emphasis on chronic myofascial pain and the precocious development of degenerative disease of the temporomandibular joint (TMJ). MATERIALS AND METHODS: Current approaches used to study TMDs in terms of neuromechanics, masticatory muscle behaviours, and the dynamics of the autonomic nervous system (ANS) were assessed for ecological validity in this review. In particular, the available literature was scrutinized regarding the effects of sampling, environmental and psychophysiological constraints and averaging data across biological rhythms. RESULTS: Validated computer-assisted numerical modelling of the neuromechanics used biological objective functions to accurately predict muscle activation patterns for jaw-loading tasks that were individual-specific. With respect to masticatory muscle behaviour, current findings refute the premise that sustained bruxing and clenching at high jaw-loading magnitudes were associated with painful TMDs such as myofascial pain. Concerning the role of the ANS in TMDs, there remains the need for personalized assessments based on biorhythms, and where the detection of dysregulated physiologic oscillators may inform interventions to relieve pain and restore normal function. CONCLUSIONS: Future human research which focuses on TMD myofascial pain or the precocious development and progression of TMJ degenerative joint disease requires experimental designs with ecological validity that capture objectively measured data which meaningfully reflect circadian and ultradian states.

Orthognathic surgery effects on temporomandibular joint compressive stresses.

INTRODUCTION: This study tested orthognathic surgery effects on temporomandibular joint (TMJ) compressive stresses. METHODS: Pre- (T1) and post-surgery (T2) cone-beam computed tomography images were collected from consenting subjects aged ≥15 years. Anatomical data were used to measure surgical changes in anteroposterior mandibular position and occlusal plane angle (FH-OP), estimate condylar loading areas (mm2 ) and calculate T1 and T2 TMJ and jaw muscle forces (N) during canine biting via numerical modelling. Analysis of covariance tested for sex and biting angle differences in T2 - T1 TMJ compressive stresses (TMJ force/loading area, MPa). Principal component analyses identified jaw muscle forces that accounted for changes in T2 - T1 TMJ loads. Regression analyses tested the correlations between surgical changes in mandibular position, FH-OP, TMJ loads and muscle forces. RESULTS: Of 148 cases screened, 28 females and 16 males provided complete records. Condylar loading areas were significantly smaller (P = .024) for females vs males (124 ± 5 vs 144 ± 7 mm2 ). T2 - T1 differences in TMJ compressive stresses varied by surgical change, biting angle and sex. Overall, the largest increases in TMJ compressive stresses post-surgery were for females with mandibular setbacks where FH-OP angle decreased. T2 - T1 changes in jaw muscle forces had moderate (ipsilateral, λ = 4.59; η2 = 0.071) to large (contralateral, λ = 1.49; η2 = 0.31) effects on TMJ loads. CONCLUSIONS: T2 - T1 differences in TMJ compressive stresses during canine biting were affected by surgical changes in mandibular position and occlusal plane angle, biting angle and sex. Surgical changes altered jaw muscle forces for the same biting conditions and, thus, affected TMJ loads and compressive stresses.

Null mutation of 5α-reductase type I gene alters ethanol consumption patterns in a sex-dependent manner.

The neuroactive steroid allopregnanolone (ALLO) is a positive modulator of GABAA receptors, and manipulation of neuroactive steroid levels via injection of ALLO or the 5α-reductase inhibitor finasteride alters ethanol self-administration patterns in male, but not female, mice. The Srd5a1 gene encodes the enzyme 5α-reductase-1, which is required for the synthesis of ALLO. The current studies investigated the influence of Srd5a1 deletion on voluntary ethanol consumption in male and female wildtype (WT) and knockout (KO) mice. Under a continuous access condition, 6 and 10 % ethanol intake was significantly greater in KO versus WT females, but significantly lower in KO versus WT males. In 2-h limited access sessions, Srd5a1 deletion retarded acquisition of 10 % ethanol intake in female mice, but facilitated it in males, versus respective WT mice. The present findings demonstrate that the Srd5a1 gene modulates ethanol consumption in a sex-dependent manner that is also contingent upon ethanol access condition and concentration.

Effects of mechanical stress and growth on the velocity of tooth movement.

INTRODUCTION: In this study, we investigated the effects of the magnitudes of applied stress and growth status on the speed of tooth movement. METHODS: Eighty-two maxillary canines in 41 subjects were retracted for 84 days by estimated stresses of 4, 13, 26, 52, or 78 kPa applied continuously via segmental mechanics. Dental impressions made at intervals of 1 to 14 days resulted in 9 or 10 dental casts per subject. Three-dimensional tooth movements were quantified using these casts, custom reference templates, and a measuring microscope. Serial height and cephalometric measurements determined growth status. RESULTS: Distal tooth movement was linear with no lag phase in 96% of the teeth. Speeds averaged 0.028, 0.040, 0.050, 0.054, and 0.061 mm per day (standard errors, ± 0.004) for 4, 13, 26, 52, and 78 kPa, respectively. The maximum difference in speed between teeth was 9:1. Teeth moved significantly faster (P <0.0001) in growing compared with nongrowing subjects, on average by 1.6-fold. Stress and speed of tooth movement were logarithmically related in growing (R(2) = 0.47) and nongrowing (R(2) = 0.34) subjects. Other tooth movements were relatively small, except for the distopalatal rotation of teeth moved by 78 kPa that averaged more than 19°. CONCLUSIONS: The speed of retraction was logarithmically related to the applied stress and was significantly faster in actively growing subjects compared with those who were not growing.

Outcome assessment of orthodontic clear aligner vs fixed appliance treatment in adolescents with moderate to severe malocclusions.

OBJECTIVE: To compare the efficacy and efficiency of treatment with clear aligners (CAT) vs fixed appliances (FAT) in adolescents with Class I and II moderate to severe malocclusions. MATERIALS AND METHODS: One operator's (Garfinkle) cases from 2014 to 2019, started at age 12-18 years, with pre- and posttreatment records were identified and used according to an institutional review board-approved protocol. Records were measured by two calibrated, blinded investigators, aided by software (OrthoCAD [Cadent, Fairview, N.J.], Dolphin Imaging & Management Solutions [Chatsworth, Calif]). Discrepancy index (DI) and cast radiograph evaluation (CRE) scores, treatment duration, number of scheduled and emergency visits, and reported appliance and interarch elastic wear compliance were compared between groups using Wilcoxon rank sum and Fisher's exact tests. Cephalometric superimpositions were completed to evaluate craniofacial growth and dental changes. RESULTS: Records from 72 cases met the criteria and were included. For the 47 CAT and 25 FAT cases, mean DI (21 ± 5 and 24 ± 8, respectively; P = .20) and CRE (35 ± 10 and 34 ± 9, respectively; P = .90) scores were not significantly different. Other case attributes and reported appliance and interarch elastic wear compliance were also not significantly different. CAT vs FAT cases had significantly smaller treatment durations (24 ± 6 vs 27 ± 5 months; P = .01) and visit numbers (16 ± 5 vs 24 ± 4; P < .01), but emergency visit numbers were not significantly different (2 ± 2 vs 3 ± 2; P = .08). CONCLUSIONS: In adolescents with Class I and II malocclusions and moderate to severe DI scores, on average, CAT vs FAT cases were completed 3 months faster with eight fewer visits, but treatment efficacy was not significantly different.

An augmented Lagrangian method for sliding contact of soft tissue.

Despite the importance of sliding contact in diarthrodial joints, only a limited number of studies have addressed this type of problem, with the result that the mechanical behavior of articular cartilage in daily life remains poorly understood. In this paper, a finite element formulation is developed for the sliding contact of biphasic soft tissues. The augmented Lagrangian method is used to enforce the continuity of contact traction and fluid pressure across the contact interface. The resulting method is implemented in the commercial software COMSOL Multiphysics. The accuracy of the new implementation is verified using an example problem of sliding contact between a rigid, impermeable indenter and a cartilage layer for which analytical solutions have been obtained. The new implementation's capability to handle a complex loading regime is verified by modeling plowing tests of the temporomandibular joint (TMJ) disc.

Archwire vibration and stick-slip behavior at the bracket-archwire interface.

INTRODUCTION: It is unknown whether or not intraoral vibrations affect stick-slip behavior at orthodontic bracket-archwire interfaces. In this study, we evaluated bracket-archwire stick-slip behavior as a function of ligation method and archwire vibration. METHODS: In-vivo archwire vibrations were measured to obtain frequencies and amplitudes for ex-vivo testing. A piezoresistive accelerometer ligated to the maxillary right canines of 6 subjects transduced the intraoral vibrations. All subjects gave informed consent to participate. Amplitude and frequency of the vibrations were quantified and used in a bench-top friction testing apparatus. Active and passive ligation methods were compared for 9 vibration scenarios. The amount of time to move the bracket along a stainless steel wire was recorded in 90 trials. Analysis of variance and post-hoc tests were used for statistical analyses of the data. RESULTS: During carrot biting, orthodontic wire vibrations had a mean frequency of 98 Hz and a peak-to-peak mean amplitude of 151 mV. The bench-top stick-slip measurement trials containing medium (150 mV) and high (190 mV) amplitude vibrations had significantly less friction (ln, s), 4.81 ± 2.08 and 4.67 ± 2.00, respectively, than those subjected to low (110 mV) amplitudes, 5.80 ± 1.39 (P = 0.04). There were no significant differences between passive and active ligation methods. CONCLUSIONS: Amplitudes of archwire vibrations affect stick-slip behavior at the bracket-archwire interfaces.

A theoretical analysis of longitudinal temporomandibular joint compressive stresses and mandibular growth.

OBJECTIVES: To determine if temporomandibular joint (TMJ) compressive stresses during incisor biting (1) differed between growing children over time, and (2) were correlated with Frankfort Horizontal-mandibular plane angle (FHMPA, °) and ramus length (Condylion-Gonion (Co-Go), mm). MATERIALS AND METHODS: Three-dimensional anatomical geometries, FHMPA and Co-Go, were measured longitudinally from lateral and posteroanterior cephalographs1 of children aged 6 (T1), 12 (T2), and 18 (T3) years. Geometries were used in numerical models to estimate subject-specific TMJ eminence shape and forces for incisor bite-forces of 3, 5, and 8 Newtons at T1, T2, and T3, respectively. TMJ compressive stresses were estimated via two steps: First, TMJ force divided by age-dependent mandibular condylar dimensions, and second, modified by loading surfaces' congruency. Analysis of variance and Tukey honest significant difference post-hoc tests, plus repeated measures and mixed effects model analyses were used to evaluate differences in variables between facial groups. Regression analyses tested for correlation between age-dependent compressive stresses, FHMPA, and Co-Go. RESULTS: Sixty-five of 842 potential subjects had T1-T3 cephalographs and were grouped by FHMPA at T3. Dolichofacial (FHMPA ≥ 27°, n = 36) compared to meso-brachyfacial (FHMPA< 27°, n = 29) subjects had significantly larger FHMPA at T1-T3, shorter Co-Go at T2 and T3 (all P < .01), and larger increases in TMJ compressive stresses with age (P < .0001). Higher compressive stresses were correlated with larger FHMPA (all R2 ≥ 0.41) and shorter Co-Go (all R2 ≥ 0.49). CONCLUSIONS: Estimated TMJ compressive stress increases from ages 6 to 18 years were significantly larger in dolichofacial compared to meso-brachyfacial subjects and correlated to FHMPA and Co-Go.

Intrathoracic lipoma in a cat.

A 10 yr old female cat presented for an acute onset of back arching, regurgitation, and open mouth breathing. Radiographs indicated the presence of a large intrathoracic mass. Computed tomography confirmed the presence of a large mass of fatty density in the dorso-caudal mediastinum. The mass was removed via right intercostal thoracotomy, and histopathology confirmed the mass as a lipoma. The cat was continuing to recover well as of 21 mo after surgery. This is the first reported case of an intrathoracic lipoma in a cat.

Comparison between cone-beam computed tomography and intraoral digital radiography for assessment of tooth root lesions.

INTRODUCTION: Cone-beam computed tomography (CBCT) might be more accurate in identifying radicular surface lesions compared with digital periapical radiography. In this study, we compared these techniques in detecting simulated root resorption lesions. METHODS: A porcine mandible was used to support 10 human maxillary central incisors. CBCT and digital periapical radiographic images were generated before and after the introduction of standardized and sequentially larger root defects on either the mesial or the lingual root surfaces. The images were randomly labeled and evaluated by 3 examiners. Each image was classified according to defect size (0, none; 1, mild; 2, moderate; 3, severe). RESULTS: Interrater reliability was acceptable (0.856 ≤ P ≤ 0.981). The location of the root defect (mesial vs lingual) had no significant effect on the evaluation of defect size. Both periapical radiographs and CBCT were slightly better at detecting lingual defects than mesial defects (75% vs 65% and 65% vs 60%, respectively), but these effects were not statistically significant (P = 0.49 and P = 0.74, respectively). The mean percentages of correctly diagnosed defect sizes were 65% for CBCT and 75% for periapical radiographs. Examiners using CBCT images tended to overestimate defect sizes (κ = 0.481) and correctly categorized teeth with no, mild-moderate, and severe defects 80%, 45%, and 90% of the time, respectively. Examiners using periapical radiographs tended to underestimate defect sizes (κ = 0.636) and categorized teeth with no, mild-moderate, and severe defects 100%, 50%, and 100% of the time, respectively. CONCLUSIONS: There was no difference in accuracy of identifying defects between periapical radiographs and CBCT images.

Expert consensus on Didactic Clinical Skills Development for orthodontic curricula.

PURPOSE/OBJECTIVE: Competence is expected of each beginning dentist and orthodontist. However, the broad definition of competence presents a challenge to academic programs in identifying the level of cognition for students to achieve competence. This study aimed to determine the Didactic Clinical Skills Development curriculum content and competency in predoctoral and advanced education orthodontic programs. METHOD: A modified Delphi method with a consensus threshold of 70% was employed using an expert panel of academic orthodontists. RESULTS: Round One (n = 26) identified that all topics proposed by a focus group were necessary, except for predoctoral Appliances, which was at 65%. Round Two (n = 23) included subtopics of Appliances to confirm the lack of consensus, plus subtopics of all the other topics and the level of cognition required for each subtopic. The expert panel reached a consensus that all 24 subtopics, hence all topics, were necessary. In Round Three, subtopic responses in Round Two were assigned a value between 1 (remember) and 6 (create) to generate a hierarchical level-of-learning scale. Mean values were calculated for each subtopic response. For all subtopics, the mean level of cognition for predoctoral education was at understand; for advanced education, it was at evaluate. CONCLUSION: This consensus suggests that, to be deemed competent, beginning dentists must learn these topics and subtopics in the cognitive domain of understand, and beginning orthodontists in the cognitive domain of evaluate. This study showed an expert consensus on Didactic Clinical Skills Development orthodontic curriculum content and a panorama of educational objectives that could be used as a template for curriculum design.

Mechanobehavior and mandibular ramus length in different facial phenotypes.

OBJECTIVES: To test the hypotheses that mechanobehavior scores (MBS) were correlated with mandibular ramus lengths (Co-Go) and differed between facial phenotypes. MATERIALS AND METHODS: Subjects gave informed consent to participate. Co-Go (mm), mandibular plane angles (SN-GoGn, °), and three-dimensional anatomy were derived from cephalometric radiography or cone beam computed tomography. Temporomandibular joint (TMJ) energy densities (ED) (mJ/mm3) were measured using dynamic stereometry and duty factors (DF) (%) were measured from electromyography, to calculate MBS (= ED2 × DF,) for each TMJ. Polynomial regressions, K-means cluster analysis, and analysis of variance (ANOVA) with Tukey post-hoc tests were employed. RESULTS: Fifty females and 23 males produced replete data. Polynomial regressions showed MBS were correlated with Co-Go (females, R2 = 0.57; males, R2 = 0.81). Cluster analysis identified three groups (P < .001). Dolichofacial subjects, with shorter normalized Co-Go, clustered into two subgroups with low and high MBS compared to brachyfacial subjects with longer Co-Go. SN-GoGn was significantly larger (P < .03) in the dolichofacial subgroups combined (33.0 ± 5.9°) compared to the brachyfacial group (29.8 ± 5.5°). CONCLUSIONS: MBS correlated with Co-Go within sexes and differed significantly between brachyfacial and dolichofacial subjects.

3D Slicer Craniomaxillofacial Modules Support Patient-Specific Decision-Making for Personalized Healthcare in Dental Research.

The biggest challenge to improve the diagnosis and therapies of Craniomaxillofacial conditions is to translate algorithms and software developments towards the creation of holistic patient models. A complete picture of the individual patient for treatment planning and personalized healthcare requires a compilation of clinician-friendly algorithms to provide minimally invasive diagnostic techniques with multimodal image integration and analysis. We describe here the implementation of the open-source Craniomaxillofacial module of the 3D Slicer software, as well as its clinical applications. This paper proposes data management approaches for multisource data extraction, registration, visualization, and quantification. These applications integrate medical images with clinical and biological data analytics, user studies, and other heterogeneous data.

Ethanol intake patterns in female mice: influence of allopregnanolone and the inhibition of its synthesis.

The neurosteroid allopregnanolone (ALLO) is a positive modulator of GABA(A) receptors that exhibits a psychopharmacological profile similar to ethanol (i.e., anxiolytic, sedative-hypnotic). Based on research suggesting that manipulation of ALLO levels altered ethanol self-administration in male rodents, the current studies determined whether exogenous ALLO administration or the inhibition of its synthesis in vivo modulated ethanol intake patterns in female C57BL/6J mice. Lickometer circuits collected temporal lick records of ethanol (10%, v/v) and water consumption during daily 2h limited access sessions. Following the establishment of stable ethanol intake, studies examined the effect of an acute ALLO challenge (3.2-24.0 mg/kg) or a 7-day blockade of ALLO production with finasteride (FIN; 50 or 100 mg/kg) on ethanol intake in a within-subjects design. In contrast to results in male mice, ethanol dose (g/kg), ethanol preference and most of the bout parameters were unaltered by ALLO pretreatment in female mice. Ethanol intake in females also was recalcitrant to 7-day treatment with 50 mg/kg FIN, whereas 100 mg/kg FIN significantly reduced the ethanol dose consumed by 35%. The FIN-attenuated ethanol intake was attributable to a significant decrease in bout frequency (up to 45%), with lick patterns indicating reduced maintenance of consumption throughout the 2-h session. FIN also produced a dose-dependent decrease in brain ALLO levels. In conjunction with data in male mice, the present findings indicate that there are sex differences in the physiological regulation of ethanol intake patterns by GABAergic neurosteroids.

Psychosocial Scores and Jaw Muscle Activity in Women.

AIMS: To test whether women with temporomandibular disorder (TMD)-related pain showed higher psychosocial scores and higher awake- and sleep-time jaw muscle activities (characterized by duty factors) compared to pain-free controls and whether psychosocial scores and the jaw muscle duty factors were associated. METHODS: Subjects gave informed consent to participate. The Diagnostic Criteria for TMD (DC/TMD) were used for diagnosis of TMD pain, and 31 and 36 women were included in the TMD-related pain and control groups, respectively. DC/TMD Axis II instruments were used to determine psychosocial scores. Subjects self-recorded masseter and anterior temporalis electromyography (EMG) over 3 days and 3 nights. The duty factor (time of muscle activity/total recording time [%]) was quantified using subject-specific EMG/bite-force calibration via data recorded in the laboratory. Group differences (α = .05) were assessed for psychosocial scores and duty factors using chi-square and two-sample t tests. Linear regression assessed whether psychosocial scores were associated with duty factors. RESULTS: Average duty factors were ≤ 2.4% for awake and sleep times in both muscles, and between-group comparisons showed no significant differences. For physical symptom scores, there were significantly fewer TMD-related pain subjects in the normal category and significantly more in the moderate-severe category (all P < .01) compared to controls. Subjects with elevated compared to normal psychosocial scores showed significantly higher jaw muscle duty factors by ≥ 1.5-fold. CONCLUSION: A significantly larger proportion of TMD-related pain subjects compared to control subjects had moderate-severe physical symptom scores. Awake- and sleep-time jaw muscle duty factors were not different between groups and were generally low among all subjects. Additionally, higher than normal psychosocial scores were associated with significantly more low-magnitude jaw muscle activity.

Gender differences in the association of periodontitis and type 2 diabetes.

AIMS: THE OBJECTIVE WAS TO INVESTIGATE IF GENDER DIFFERENCES EXIST IN THE ASSOCIATIONS BETWEEN PERIODONTITIS AND TYPE 2 DIABETES. DISPROPORTIONATE DISPARITIES BY GENDER WERE FOUND TO EXIST IN RATES OF BOTH PERIODONTITIS AND DIABETES WITH RESPECT TO DEMOGRAPHICS AND BEHAVIOURAL PREDICTORS THAT CANNOT BE EXPLAINED SOLELY BY THE WELL-ESTABLISHED ASSOCIATION BETWEEN THESE TWO DISEASES. MATERIALS AND METHODS: MULTIPLE DATASETS WERE EXTRACTED FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY (NHANES) 2009-2014, WHICH USED A STRATIFIED MULTISTAGE PROBABILITY SAMPLING TO OBTAIN SAMPLES FROM ALL CIVILIAN NON-INSTITUTIONALISED PEOPLE IN THE USA. BIVARIATE RELATIONSHIPS BETWEEN EACH EXPLANATORY VARIABLE AND PERIODONTITIS LEVEL WERE ASSESSED WITH ODDS RATIOS (OR) AND THEIR 95% CONFIDENCE INTERVALS (CI). A SET OF WEIGHTED LOGISTIC REGRESSION MODELS WAS USED TO INVESTIGATE THE ASSOCIATION DIFFERENTIATIONS BETWEEN PERIODONTITIS AND DIABETES BY GENDER. C-STATISTICS MEASURED THE GOODNESS-OF-FIT OF WEIGHTED LOGISTIC REGRESSION MODELS. RESULTS: THE PREVALENCE OF MODERATE-SEVERE PERIODONTITIS WAS 36.39% AND 22.71% AMONG PARTICIPANTS WITH TYPE 2 DIABETES AND WITHOUT DIABETES, RESPECTIVELY. TYPE 2 DIABETES WAS SIGNIFICANTLY ASSOCIATED WITH MODERATE-SEVERE PERIODONTITIS OR (OR = 1.47, 95% CI: 1.18-1.82) AMONG MALES EVEN AFTER ADJUSTING FOR DEMOGRAPHICS, SOCIOECONOMIC STATUS AND ORAL HEALTH BEHAVIOURS. THE AFOREMENTIONED RELATIONSHIP WAS NOT FOUND IN FEMALES. FURTHERMORE, DIFFERENT RELATIONSHIPS OF MODERATE-SEVERE PERIODONTITIS WITH BODY MASS INDEX AND THE USE OF MOUTHWASH WERE FOUND BETWEEN THE MALES AND FEMALES. CONCLUSIONS: THE CURRENT FINDINGS SUGGEST THAT IMPORTANT IMPROVEMENTS IN THE DEVELOPMENT OF GENDER-SPECIFIC STRATEGIES IN PREVENTION, SUCH AS ORAL HOME-CARE, TO REDUCE THE HIGH PREVALENCE OF PERIODONTAL DISEASE AND MAINTAIN GOOD ORAL HEALTH ARE VITAL, AND ARE ESPECIALLY IMPORTANT FOR MALE DIABETIC PATIENTS AND THOSE WHO ARE AT HIGH RISK OF DEVELOPING DIABETES, SUCH AS THOSE WHO ARE OBESE.

Allopregnanolone influences the consummatory processes that govern ethanol drinking in C57BL/6J mice.

Although systemic allopregnanolone (ALLO; a positive modulator of GABA(A) receptors) has been shown to enhance ethanol-reinforced responding and to modulate drinking patterns in rodents, the effects of centrally administered ALLO on ethanol intake are not known. The current work examined the effects of intracranial ALLO on operant ethanol self-administration in food- and water-satiated mice, with a procedure designed to estimate ALLO's influence on appetitive versus consummatory processes. Male C57BL/6J (B6) mice were trained to press an ethanol-appropriate lever by being reinforced with 30-min of continuous access to a 10% ethanol solution. Following surgical implantation of a guide cannula aimed at the lateral ventricle and subsequent habituation to vehicle infusions, ALLO (50-400 ng; ICV) was delivered immediately prior to session start. ALLO doses of 100 and 400 ng were further evaluated for their effects on locomotor behavior within activity chambers. ALLO selectively modulated ethanol intake patterns associated with the onset and maintenance of self-administration, while leaving appetitive (i.e., ethanol seeking) measures unaltered. The effects of ALLO on drinking patterns were dissociable from changes in locomotor behavior, as evidenced by the absence of ALLO's influence on response frequency and horizontal distance traveled. These findings support the premise that manipulations in brain ALLO levels may influence the regulatory processes governing ethanol consumption.

Self-reported health and behavioral factors are associated with metabolic syndrome in Americans aged 40 and over.

To determine whether behavioral factors differ among metabolic conditions and self-reported health, and to determine whether self-reported health is a valid predictor of metabolic syndrome (MetS). A total of 2997 individuals (≥ 40 years old) were selected from four biennial U.S. National Health and Nutrition Examination Surveys (2007-2014). A set of weighted logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs)Individuals with light physical activity are more likely to have MetS and report poor health than those with vigorous physical activity with OR = 3.22 (95% CI: 2.23, 4.66) and 4.52 (95% CI: 2.78, 7.33), respectively. Individuals eating poor diet have greater odds of developing MetS and reporting poor health with OR = 1.32 (95% CI: 1.05, 1.66) and 3.13 (95% CI: 2.46, 3.98). The aforementioned relationships remained significant after adjustment for demographic and socio-economic status. A potential intervention strategy will be needed to encourage individuals to aggressively improve their lifestyle to reduce MetS and improve quality of life. Despite the significant association between self-reported health with MetS, a low sensitivity indicated that better screening tools for MetS, diabetes and cardiovascular disease are essential.

Disposable aptamer-sensor aided by magnetic nanoparticle enrichment for detection of salivary cortisol variations in obstructive sleep apnea patients.

We report a disposable point-of-care sensing platform specific to salivary cortisol detection. The sensor is inkjet printed on a paper substrate with a metalloporphyrin based macrocyclic catalyst ink that can electrochemically reduce cortisol, captured by aptamer functionalized magnetic nanoparticles. The sensor consists of a thin magnet disc, aligned at the back of the electrode, in order to populate the magnetic nanoparticle bound cortisol at the sensing electrode area. Proof of concept studies were performed to detect salivary cortisol levels in human subjects with high and low risks for obstructive sleep apnea (OSA). High selectivity was observed to salivary cortisol against a background of closely related steroids.

Novel anti-denatured collagen humanized antibody D93 inhibits angiogenesis and tumor growth: An extracellular matrix-based therapeutic approach.

Matrix metalloproteases (MMPs) secreted by both tumor and endothelial cells proteolytically degrade collagen during tumor growth and neo-vascularization. This exposes cryptic binding sites on collagen with functional relevance for angiogenesis. In this report, we characterized a novel humanized monoclonal IgG1 antibody, D93. After humanization, the antibody retained the binding specificity of the parental murine IgM antibody for denatured (dn) collagen. D93 recognized dn-collagen but not native (nat) collagen of different species, including mouse, chicken, and human, indicating that its cryptic binding site(s) is conserved across species. In immunohistochemistry (IHC) studies, D93 stained the basement membrane of blood vessels in several xenograft human tumors or in surgically removed tumor tissues from patients with different types of malignancies. D93 staining was rarely or not present in normal blood vessels of healthy tissues. In in vivo experiments, D93 significantly inhibited basic fibroblast growth factor (bFGF)-induced angiogenesis in chick embryo chorioallantoic membrane (CAM) and the tumor growth of pre-established orthotopic human breast (MDA-MB-435) tumors in mice. D93 i.v. administered in mice was subsequently detected in the subendothelial basement membrane of tumor blood vessels but not blood vessels of normal tissues. Inhibition of growth of pre-established orthotopic human breast MDA-MB-435 tumors was more effective when D93 was combined with Taxol, than either treatment alone. In addition, tumors from animals treated with D93 and/or Taxol showed significantly reduced levels of the endothelial cell-marker CD31. Our data suggest that blockade of cryptic epitopes exposed on collagen IV during angiogenesis and tumor growth by a monoclonal antibody may provide a novel therapeutic modality for treatment of cancer and pathogenic neo-vascularization.