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This study enhances the molecular analysis of bitumen by transitioning from traditional chemical descriptors, such as SARA (Saturates, Aromatics, Resins, and Asphaltenes) fractions and elemental compositions, to specific force field atom types in Molecular Dynamics (MD) models. This shift improves the precision in predicting material properties critical for bituminous material characterization. Machine Learning Models (MLMs) were developed to use these atom types as input features, inherently reflecting fundamental chemical characteristics. Trained on data from over 1,770 LAMMPS simulations of diverse bitumen types and conditions, these MLMs enable the prediction of properties like density, heat capacity, solubility parameters, and thermal expansion coefficients without the need for additional MD simulations. The models utilize 30 chemical descriptors corresponding to specific atom types in the PCFF force field, which collectively account for over 95% of the influence on these properties. By accurately predicting fundamental, thermodynamic, and kinetic properties, the use of MLMs and force field atom types allows researchers to efficiently tweak the chemical nature of organic molecules and mixtures to achieve desired properties. With near-instantaneous prediction times, these MLMs offer valuable insights for advancing bitumen research in the construction and petroleum industries, reducing the need for more intensive simulation techniques.

This paper presents a United Atom (UA) force field for simulating hydrocarbon molecules in bituminous materials, integrating explicit hydrogens into beads with their parent atom. This method simplifies all-atom molecular models, significantly accelerating Molecular Dynamics (MD) simulations of bitumen by 10 to 100 times. Key advantages include halving the particle count, eliminating complex hydrogen interactions, and decreasing the degrees of freedom of the molecules. Developed by mapping forces from an all-atom model to the centers of mass of UA model beads, the force field ensures accurate replication of energies, forces, and molecular conformations, mirroring properties like pressure and density. It features 17 bead types and 287 interaction types, encompassing various hydrocarbon molecules. The UA force field's stability, surpassing all-atom models, is a notable achievement. This stability, stemming from smoother potential energy surfaces, leads to consistent property measurements and improved stress tensor accuracy. It enables the extension of MD simulations to larger spatiotemporal scales, crucial for understanding complex phenomena such as phase separation in bituminous materials. This foundational work sets the stage for future developments, including refining parameters and introducing new bead types, to enhance the modeling capabilities of the force field, thereby advancing the application and understanding of bituminous materials.

Conventional Molecular Dynamics (MD) models of bitumen are built by homogeneously mixing molecules in a volume without considering that the molecules in bitumen are known to exhibit phase behavior and form distinctive molecular arrangements. These are known to have a significant impact in the behavior of bitumen, and considering their existence is paramount in producing improved representations of bitumen using computational models. This study explores whether MD models of bitumen that are conventionally assumed to be in equilibrium can still undergo significant phase separation over considerably long simulation times. It also aims to establish a more formal pathway to build and study models with highly heterogeneous arrangements of their molecules. Moreover, it aims to evaluate whether the presence of distinct morphologies have a significant impact in numerous physical properties of bitumen. The study shows that conventional and widely used models of bitumen exhibit significant molecular rearrangements over long times (>360 ns). It also shows that building heterogeneous morphologies is possible and result in energetically favorable conformations. Moreover, it proves that studying properties regularly used to validate MD models of bitumen (e.g., density) are insufficient in assessing the impact of different morphologies; more thorough methods are required to evaluate them.

Legacy persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) are chemicals that undergo long-range transport to the Arctic. These chemicals possess endocrine disruptive properties raising concerns for development and reproduction. Here, we report the relationship between concentrations of testosterone (T) and persistent organic pollutant (POPs) in 40 East Greenland male polar bears (Ursus maritimus) sampled during January to September 1999–2001. The mean ± standard concentrations of blood T were 0.31 ± 0.49 (mean ± SD) ng/mL in juveniles/subadults (n = 22) and 3.58 ± 7.45 ng/mL in adults (n = 18). The ∑POP concentrations (mean ± SD) in adipose tissue were 8139 ± 2990 ng/g lipid weight (lw) in juveniles/subadults and 11,037 ± 3950 ng/g lw in adult males, respectively, of which Σpolychlorinated biphenyls (ΣPCBs) were found in highest concentrations. The variation in T concentrations explained by sampling date (season), biometrics and adipose tissue POP concentrations was explored using redundancy analysis (RDA). The results showed that age, body length, and adipose lipid content in adult males contributed (p = 0.02) to the variation in POP concentrations. However, although some significant relationships between individual organochlorine contaminants and T concentrations in both juveniles/subadults and adult polar bears were identified, no significant relationships (p = 0.32) between T and POP concentrations were identified by the RDAs. Our results suggest that confounders such as biometrics and reproductive status may mask the endocrine disruptive effects that POPs have on blood T levels in male polar bears, demonstrating why it can be difficult to detect effects on wildlife populations.

Summary: Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p

Objective: This study explored cancer caregivers' individual and communal coping through their use of personal and communal pronouns during naturally occurring conversations. Methods: Nurse-home hospice visits involving cancer patients and their partner caregivers were audio recorded and then transcribed. Pronoun use was analyzed using Linguistic Inquiry Word Count (LIWC) software and descriptive statistics compared patient and partner caregivers' pronoun use. Personal and communal pronoun use was examined within six identified topics of caregiver speech: patient medical care, daily life, emotion, criticism/disagreement, relationships with family/friends, and asserting needs. Results: Dyads (N = 76) had an average of 35.8 years in their relationship. Caregivers used proportionately more first-person singular (I-talk) than first-person plural (we-talk). However, they used significantly less I-talk than patients and less I-talk than LIWC measures in naturally occurring speech. Caregivers were most likely to discuss patient medical care (41.9%) and least likely to discuss their own needs (3.8%). Conclusion: Partner caregivers may find it easier to express emotions related to communal stressors, rather than their individual ability to cope with end-of-life caregiving. Innovation: Examining personal and communal pronoun use by partner caregivers during nurse-home hospice visits may provide a more objective measure of caregiver coping than standard self-report measures.

Objective: To compare general ophthalmologists, retina specialists, and the EyeArt Artificial Intelligence (AI) system to the clinical reference standard for detecting more than mild diabetic retinopathy (mtmDR). Design: Prospective, pivotal, multicenter trial conducted from April 2017 to May 2018. Participants: Participants were aged ≥ 18 years who had diabetes mellitus and underwent dilated ophthalmoscopy. A total of 521 of 893 participants met these criteria and completed the study protocol. Testing: Participants underwent 2-field fundus photography (macula centered, disc centered) for the EyeArt system, dilated ophthalmoscopy, and 4-widefield stereoscopic dilated fundus photography for reference standard grading. Main Outcome Measures: For mtmDR detection, sensitivity and specificity of EyeArt gradings of 2-field, fundus photographs and ophthalmoscopy grading versus a rigorous clinical reference standard comprising Reading Center grading of 4-widefield stereoscopic dilated fundus photographs using the ETDRS severity scale. The AI system provided automatic eye-level results regarding mtmDR. Results: Overall, 521 participants (999 eyes) at 10 centers underwent dilated ophthalmoscopy: 406 by nonretina and 115 by retina specialists. Reading Center graded 207 positive and 792 eyes negative for mtmDR. Of these 999 eyes, 26 eyes were ungradable by the EyeArt system, leaving 973 eyes with both EyeArt and Reading Center gradings. Retina specialists correctly identified 22 of 37 eyes as positive (sensitivity 59.5%) and 182 of 184 eyes as negative (specificity 98.9%) for mtmDR versus the EyeArt AI system that identified 36 of 37 as positive (sensitivity 97%) and 162 of 184 eyes as negative (specificity of 88%) for mtmDR. General ophthalmologists correctly identified 35 of 170 eyes as positive (sensitivity 20.6%) and 607 of 608 eyes as negative (specificity 99.8%) for mtmDR compared with the EyeArt AI system that identified 164 of 170 as positive (sensitivity 96.5%) and 525 of 608 eyes as negative (specificity 86%) for mtmDR. Conclusions: The AI system had a higher sensitivity for detecting mtmDR than either general ophthalmologists or retina specialists compared with the clinical reference standard. It can potentially serve as a low-cost point-of-care diabetic retinopathy detection tool and help address the diabetic eye screening burden.

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

Summary: Tissue homeostasis relies on the timely renewal of cells that have been damaged or have surpassed their biological age. Nonetheless, the underlying molecular mechanism coordinating tissue renewal is unknown. The planarian Schmidtea mediterranea harbors a large population of stem cells that continuously divide to support the restoration of tissues throughout the body. Here, we identify that TNF Receptor Associated Factors (TRAFs) play critical roles in cellular survival during tissue repair in S. mediterranea. Disruption with RNA-interference of TRAF signaling results in rapid morphological defects and lethality within 2 weeks. The TRAF phenotype is accompanied by an increased number of mitoses and cell death. Our results also reveal TRAF signaling is required for proper regeneration of the nervous system. Taken together, we find functional conservation of TRAF-like proteins in S. mediterranea as they act as crucial regulators of cellular survival during tissue homeostasis and regeneration.

Background: The most known and commonly studied behavioral obstacle to dental care is dental anxiety. An obstacle that is less studied though no less problematic is excessive gag reflex, which can severely impede dental treatment. Another understudied and possibly related syndrome is emetophobia (a specific phobia of vomiting)., Objective: The aim of this study was to examine possible comorbidity amongst self-reported emetophobia, dental anxiety, and excessive gagging in the dental office., Methods: A cross-sectional online survey was conducted using the following self-report questionnaires: Dental Anxiety Scale, Gagging Problem Assessment, Gagging Assessment Scale (GAS), and Specific Phobia of Vomiting Inventory (SPOVI)., Results: In all, 164 participants fully completed the questionnaires (87.8% female; mean age, 34 ± 11.07 years). Positive correlations were found amongst all variables (P < .001). High gagging (GAS > 6) was associated with a 7.29 times (P < .000) greater risk of positive emetophobia (SPOVI ≥ 10). Linear regression analyses revealed that the intensity of the reflex and the experience of gagging upon encountering odours in the dental office as well as dental anxiety and vomiting phobia significantly predicted participants' gagging scores as evaluated by GAS (R 2 = 0.59; F = 21.16; P < .001)., Conclusions: The study shows that excessive gagging reflex in the dental office is closely related both to dental anxiety and to emetophobia., Competing Interests: Conflict of interest None disclosed., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Dorsal root ganglion stimulation (DRGS) is a newer form of neuromodulation that targets the dorsal root ganglion. DRGS has superior efficacy in complex regional pain syndrome compared to spinal cord stimulation (SCS) and may have efficacy in other forms of chronic pain. While decades of safety data are available for SCS, there is less available safety information for DRGS. The objectives of this systematic review and pooled analysis of incidence are to determine the overall incidence of DRGS infections, incidence at each stage (trial vs implant vs revision), infection characteristics, and outcomes., Materials and Methods: A comprehensive search of databases from January 1980 to January 2021 was conducted., Results: Ten studies met inclusion criteria. Eight studies reported patients with trial data (n = 291), ten studies reported patients with implant data (n = 250), and seven studies reported data with revisions (n = 26). The pooled incidence of trial infections was 1.03% (95% CI 0.35-2.99%), implant infections was 4.80% (95% CI 2.77-8.20%), revision infections was 3.85% (95% CI 0.20-21.59%), and overall infections was 2.82% (95% CI 1.62-4.54%). There was a statistically significant difference in infection rates between the trial, implant, and revision stages, X 2 (2, N = 567) = 8.9839, p = 0.01., Conclusions: This is the first systematic review and pooled analysis that followed PRISMA guidelines to report infectious complications of DRGS by stage (trial vs implant vs revision). DRGS trial appears to be low risk for infection but that risk is significantly increased with DRGS implant. Our findings highlight the need for further study of infectious complications, their risks, and optimal prophylaxis., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Objective: Being a member of the dental profession is often associated with stress and high levels of burnout. Stress coping strategies may significantly help mediate burnout. The present cross-sectional study sought to examine the role of stress coping strategies on burnout, secondary traumatic stress, and compassion satisfaction amongst Israeli dentists., Methods: The study was carried out amongst Israeli dentists with the use of the following questionnaires: (1) the Professional Quality of Life Scale 5 (ProQOL), referring to burnout, compassion satisfaction, and level of secondary traumatic stress; (2) the Coping Inventory for Stressful Situations-Situation Specific Coping Inventory (CISS-SSC), referring to coping strategies (task-focused, emotion-focused, or avoidance-focused coping); and (3) demographic and professional variables (eg, specialisation, workload). Participants included 243 Israeli dentists. Univariate analyses and linear regressions were conducted to evaluate the relationships amongst coping strategies and burnout, secondary traumatic stress, and compassion satisfaction., Results: Female dentists had higher emotion-focused and avoidance coping scores than male dentists. Burnout could be explained by higher emotion-focused coping scores and lower task-focused and avoidance-focused coping. Secondary traumatic stress could be explained by higher emotion-focused scores, having fewer years of professional experience, and younger ages. Compassion satisfaction could be explained by lower emotion-focused coping as well as by higher task-focused coping and workload scores, specialisation, and gender., Conclusions: The findings suggest that emotional coping may cause dentists to be vulnerable to burnout and to secondary traumatic stress., Competing Interests: Conflict of interest None disclosed., (Copyright © 2021. Published by Elsevier Inc.)

Aim: Dentistry is a stressful and exhausting profession with high levels of burnout. Sensory processing sensitivity (SPS) is a basic personality trait characterised by a gradient of sensitivity to both internal and external stimuli, including social and emotional cues. In this study, the influence of SPS on burnout and professional quality of life among Israeli dentists was analysed., Methods: Two-hundred and forty-three Israeli dentists responded to questionnaires that collected information on their SPS and professional quality of life (burnout, satisfaction at work and level of secondary traumatic stress), as well demographic variables, professional specialisation and workload., Results: Linear regression analyses showed that burnout can be predicted by the three aspects of SPS (ease of excitation, low sensory threshold and aesthetic sensitivity; 32% of the variance). Additionally, the same three aspects of SPS also predicted dentists' satisfaction at work (24% of the variance). Ease of excitation and low sensory threshold, but not aesthetic sensitivity, predicted dentists' reaction to their patients' stress and trauma (23% of the variance)., Conclusions: Sensory processing sensitivity can serve as a tool to identify dentists who are prone to develop burnout and whose professional quality of life can be adversely affected by their profession., (© 2019 FDI World Dental Federation.)

Background: The use of venous duplex ultrasonography (VDU) for confirmation of deep venous thrombosis in neurosurgical patients is costly and requires experienced personnel. We evaluated a protocol using D-dimer levels to screen for venous thromboembolism (VTE), defined as deep venous thrombosis and asymptomatic pulmonary embolism., Methods: We used a retrospective bioinformatics analysis to identify neurosurgical inpatients who had undergone a protocol assessing the serum D-dimer levels and had undergone a VDU study to evaluate for the presence of VTE from March 2008 through July 2017. The clinical risk factors and D-dimer levels were evaluated for the prediction of VTE., Results: In the 1918 patient encounters identified, the overall VTE detection rate was 28.7%. Using a receiver operating characteristic curve, an area under the curve of 0.58 was identified for all D-dimer values (P = 0.0001). A D-dimer level of ≥2.5 μg/mL on admission conferred a 30% greater relative risk of VTE (sensitivity, 0.43; specificity, 0.67; positive predictive value, 0.27; negative predictive value, 0.8). A D-dimer value of ≥3.5 μg/mL during hospitalization yielded a 28% greater relative risk of VTE (sensitivity, 0.73; specificity, 0.32; positive predictive value, 0.24; negative predictive value, 0.81). Multivariable logistic regression showed that age, male sex, length of stay, tumor or other neurological disease diagnosis, and D-dimer level ≥3.5 μg/mL during hospitalization were independent predictors of VTE., Conclusions: The D-dimer protocol was beneficial in identifying VTE in a heterogeneous group of neurosurgical patients by prompting VDU evaluation for patients with a D-dimer values of ≥3.5 μg/mL during hospitalization. Refinement of this screening model is necessary to improve the identification of VTE in a practical and cost-effective manner., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: In health care, empathy is associated with compassion, thoughtfulness, attentiveness and caring. While empathy is perceived as desirable and positive, it can potentially be associated with negative aspects, such as secondary traumatic stress or vicarious trauma (VT). VT addresses the secondary vicarious influences of patients' pain and discomfort on clinicians. Dentists are routinely exposed to patients' anxiety, pain and discomfort. These may lead to VT, which in turn can affect empathy. The objectives of the present study were to examine the existence of VT among dentists and its association with their empathic approach., Materials and Methods: Two-hundred and fifty dentists were approached personally and by mail, and asked to complete: (i) the Jefferson Scale of Physician Empathy - Health Professionals; (ii) the Vicarious Trauma Scale; and (iii) demographic, personal and professional data, including age, definition of professional speciality, number of working hours per week and number of sleeping hours per night., Results: A total of 200 dentists responded (80% response rate). No differences were found between genders regarding empathy or VT. Dentists who have been accredited as a specialist in one of the dental fields (dental specialists) presented higher empathy scores than general practitioners. VT correlated positively with number of working hours per week and negatively with empathy. The best predictor of empathy was number of sleeping hours per night, followed by VT and age., Conclusions: Empathy in the clinical setting is closely associated with secondary VT among dentists. Decreasing dentists' VT may benefit dentists' empathy and through this lead to better clinical outcomes., (© 2019 FDI World Dental Federation.)

Introduction & Objective: Recently we developed and internally-validated the Soroka Acute Myocardial Infarction (SAMI) Score for prediction of all-cause long-term mortality (c-statistic 0.83-0.94) among hospital-survivors of AMI. We aimed to perform an external-validation of the SAMI score for long-term risk-stratification of STEMI patients undergoing PCI., Methods & Settings: A prospective registry of 1273 STEMI patients treated using primary PCI and discharged alive from Rabin Medical Center in Israel between 2004 and 2014 (age 60.8 ± 12.5 years, 83% males) was utilized for the validation. Chi-square test and logistic regression were used for calibration, and c-statistic (ROC procedure) for discrimination assessment of the SAMI score., Results: All-cause mortality following one- and 5-years post-discharge was 3.8% and 8.1%, respectively. SAMI score values ranged between (-5) and (+15) points (median 2-points). In a univariate analysis the SAMI score variables were significantly associated with 1- and 5-years mortality. Higher SAMI score was associated with increased risk for dying: a one-point increase was associated with OR of 1.33 (95%CI: 1.24-1.42, p < 0.001) and 1.37 (95%CI: 1.29-1.44, p < 0.001) for 1- and 5-years mortality respectively. No statistically significant difference was found in the currently observed mortality rates by groups of SAMI score and the expected mortality rates as per the SAMI score index. The c-statistics were 0.82 and 0.83 for 1- and 5-year mortality, respectively., Conclusions: The SAMI score is a simple, robust and now also externally-validated prognostic tool for prediction of long-term all-cause mortality in hospital survivors of STEMI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The tuberculum sellae is a relatively common location for meningiomas. We assessed our experience with the use of transcranial resection, which, although criticized for its more invasive nature compared with endonasal approaches, may be the ideal approach in selected patients with tuberculum sellae meningiomas (TSMs)., Methods: We retrospectively reviewed the charts of patients with TSMs treated by frontotemporal or bifrontal open cranial resection. Clinical, radiographic, and surgical variables were analyzed., Results: Forty-nine patients with a TSM treated by frontotemporal or bifrontal open cranial resection were identified. The mean patient age was 53.2 ± 14.0 years, and the mean duration of follow-up was 42.3 ± 45.4 months. The mean tumor volume was 12.4 ± 18.0 cm 3 . Optic canal invasion was seen in 46.9% of the patients, and 91.8% presented with visual deficits. Gross total resection (GTR) was achieved in 42 patients (85.7%), and near-total resection was performed in 7 patients (14.3%). Postoperatively, visual outcomes improved in 17 patients (34.7%), remained stable in 22 (44.9%), were intact in 6 (12.2%), and worsened in 1 (2.0%). Good outcome (Glasgow Outcome Scale [GOS] ≥4) was achieved by 46 of 49 patients (93%) at discharge and by 39 of 41 patients (95.1%) at 6 months. A total of 16 manageable and self-limiting complications occurred in 16 patients., Conclusions: In most patients undergoing a frontotemporal approach, a GTR/Simpson grade I resection with manageable and self-limiting surgical complications, a good 6-month GOS in most patients, and improved to stable vision were seen at follow-up. Various treatment approaches can be considered for TSM resection, but the ability to decompress the optic canal and achieve a GTR makes the frontotemporal approach attractive in many cases., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: A retrospective cohort study of patients with tuberculum sellae meningioma (TSM)-associated sphenoidal pneumosinus dilatans (PSD) over a recent epoch was evaluated using a propensity-matched morphometric analysis., Methods: A total of 38 patients with TSM and sphenoidal PSD were identified and matched by age and sex to 32 patients without tumors (controls)., Results: Overall, no significant difference between test and control groups was noted in sphenoid sinus size or other parameters; however, significantly greater mean distances from the posterior margin of the planum sphenoidale to the diaphragma sella (0.76 ± 0.23 vs. 1.03 ± 0.27, respectively; P = 0.0001) and angle between the planum sphenoidale to anterior face of sella turcica (113.41 ± 10.58 vs. 123.21 ± 12.55, respectively; P = 0.001) were seen in patients with TSM and PSD, suggestive of a selective expansion of the tuberculum sellae region. TSM/sphenoid sinus morphologies were divided into 3 types (A, B, and C) based on the extent of tumor and sinus morphology. There was progressive increase in tumor volume and anteroposterior sinus diameter from sphenoidal PSD types A-C, which influenced selection of surgical approach., Conclusions: This study suggests that TSM-associated sphenoidal PSD leads to more selective splaying of the tuberculum sellae region rather than cumulative increase in sinus volume. This may lead to operative corridor expansion for endonasal access to TSM associated with sphenoidal PSD. A radiologic classification scheme for sphenoidal PSD associated with TSM is suggested that may aid surgical decision-making., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Treatment with clopidogrel is subject to wide variability in response, and high on-treatment platelet reactivity (HTPR) is associated with increased risk of ischemic events. Ticagrelor has been shown to have antiplatelet effects superior to those of clopidogrel, with subsequent reduced clinical ischemic events. However, the efficacy of ticagrelor in high-risk patients with coronary disease who have high on-treatment platelet reactivity (HTPR) with clopidogrel has not been examined., Methods: We recruited 201 patients (mean age, 64 ± 10 years; 20% women) with stable/unstable angina who were receiving clopidogrel treatment and in whom coronary catheterization was planned. Platelet reactivity was tested using VerifyNow P2Y12 assay (Accumetrics, San Diego, CA) (HTPR defined as P2Y12 reaction units [PRU] ≥ 208). Patients with HTPR were randomized to receive either additional clopidogrel 300 mg or ticagrelor 180 mg before coronary angiography, and persisted with the respective treatment after percutaneous coronary intervention (PCI). The primary end point was the rate of troponin elevation after PCI, and the secondary end point was the change in platelet reactivity 24 hours after PCI. In addition, clinical outcomes at 30 days were evaluated., Results: Eighty-four (42%) patients had HTPR (mean PRU, 270.8 ± 46.5) and were randomly assigned to clopidogrel or ticagrelor treatment. Subsequently, 49 patients underwent percutaneous coronary intervention (PCI) (26 receiving ticagrelor and 23 receiving clopidogrel). After PCI, the mean PRU in the ticagrelor group declined significantly (ticagrelor, 59.3 ± 49 vs clopidogrel, 202.4 ± 60.4; P < 0.0001). The rate of cardiac troponin elevation and clinical ischemic events were similar between the groups., Conclusions: In high-risk patients with coronary disease and HTPR on clopidogrel, ticagrelor was highly effective in platelet inhibition and overcoming HTPR compared with continued clopidogrel treatment but had no apparent effect on troponin release or short-term clinical outcomes., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objective: Aneurysmal subarachnoid hemorrhage management is hampered by our incomplete understanding of what variables promote aneurysm formation, growth, and rupture. Because hypovitaminosis D has been identified as a risk factor for other vascular diseases, we examined its association with cerebral aneurysms requiring treatment., Methods: We retrospectively reviewed charts of patients with cerebral aneurysms with recorded 25-hydroxy vitamin D levels undergoing treatment at our institution from May 2010 to May 2015. We compared these patients with a group of patients without aneurysms. We used multivariable Poisson regression and backward elimination to identify factors associated with cerebral aneurysms, with a threshold P < 0.20. A propensity-matching algorithm was used, incorporating all factors with P < 0.10 in our regression model., Results: Patients in the aneurysm group were older than those in the control group (P = 0.001) and more likely to be female (P = 0.004), to be tobacco users (P < 0.001), and to have a diagnosis of hypertension (P = 0.001), but ethnicity, body mass index, and diabetes rates did not differ. Vitamin D levels in the aneurysm group were lower than in the control group (23.3 ± 12.3 vs. 28.7 ± 14.1 ng/mL, P = 0.001), and the patients were more likely to be vitamin D deficient (P = 0.028). Multivariable Poisson regression demonstrated that vitamin D level, tobacco use, age, and sex were significantly associated with aneurysms requiring treatment (P < 0.05). The propensity-matching algorithm confirmed a significant difference in vitamin D levels between the aneurysm and control groups (P = 0.01)., Conclusions: Patients with cerebral aneurysms requiring treatment have a significantly higher incidence of hypovitaminosis D compared with patients in a control group., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Helicobacter pylori is a Gram-negative bacterium that colonizes the human stomach and contributes to peptic ulceration and gastric adenocarcinoma. H. pylori secretes a pore-forming exotoxin known as vacuolating toxin (VacA). VacA contains two distinct domains, designated p33 and p55, and assembles into large "snowflake"-shaped oligomers. Thus far, no structural data are available for the p33 domain, which is essential for membrane channel formation. Using single-particle electron microscopy and the random conical tilt approach, we have determined the three-dimensional structures of six VacA oligomeric conformations at ~15-Å resolution. The p55 domain, composed primarily of β-helical structures, localizes to the peripheral arms, while the p33 domain consists of two globular densities that localize within the center of the complexes. By fitting the VacA p55 crystal structure into the electron microscopy densities, we have mapped inter-VacA interactions that support oligomerization. In addition, we have examined VacA variants/mutants that differ from wild-type (WT) VacA in toxin activity and/or oligomeric structural features. Oligomers formed by VacA∆6-27, a mutant that fails to form membrane channels, lack an organized p33 central core. Mixed oligomers containing both WT and VacA∆6-27 subunits also lack an organized core. Oligomers formed by a VacA s2m1 chimera (which lacks cell-vacuolating activity) and VacAΔ301-328 (which retains vacuolating activity) each contain p33 central cores similar to those of WT oligomers. By providing the most detailed view of the VacA structure to date, these data offer new insights into the toxin's channel-forming component and the intermolecular interactions that underlie oligomeric assembly., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Emerging evidence demonstrates that proangiogenic cells (PACs) originate from the BM and are capable of being recruited to sites of ischemic injury where they contribute to neovascularization. We previously determined that among hematopoietic progenitor stem cells, common myeloid progenitors (CMPs) and granulocyte-macrophage progenitor cells (GMPs) differentiate into PACs and possess robust angiogenic activity under ischemic conditions. Herein, we report that a TGF-β1-responsive Krüppel- like factor, KLF10, is strongly expressed in PACs derived from CMPs and GMPs, ∼ 60-fold higher than in progenitors lacking PAC markers. KLF10(-/-) mice present with marked defects in PAC differentiation, function, TGF-β responsiveness, and impaired blood flow recovery after hindlimb ischemia, an effect rescued by wild-type PACs, but not KLF10(-/-) PACs. Overexpression studies revealed that KLF10 could rescue PAC formation from TGF-β1(+/-) CMPs and GMPs. Mechanistically, KLF10 targets the VEGFR2 promoter in PACs which may underlie the observed effects. These findings may be clinically relevant because KLF10 expression was also found to be significantly reduced in PACs from patients with peripheral artery disease. Collectively, these observations identify TGF-β1 signaling and KLF10 as key regulators of functional PACs derived from CMPs and GMPs and may provide a therapeutic target during cardiovascular ischemic states.

Objective: To examine the potential yield of three-dimensional (3D) reconstruction of left main coronary lesions., Methods: A novel, previously validated, system for 3D reconstruction of the coronary vessels was used to evaluate 302 angiographic images, before and after stenting, from 62 consecutive patients (age 73.5 ± 11.3 years) with unprotected left main lesions., Results: Three-dimensional reconstructions significantly improved morphological analysis, especially for ostial and bifurcation lesions. In cases of bifurcation involvement, lesion length was significantly longer in the 3D reconstructions than in the 2D images (12.3 ± 4.1 vs. 10.6 ± 4.9 mm, P=.003). The 3D analysis showed that procedures performed in distal left main were associated with a decrease in the bifurcation angle after intervention (from 82 ± 27° to 72 ± 28°, P=.01). The mortality rate was 18% at 6 months. Elective intervention was associated with significantly lower mortality (5% vs. 39% at 6 months)., Conclusions: Three-dimensional reconstruction adds insights on the morphology and lesion length of unprotected left main artery lesions, especially those involving the bifurcation, which may make it an important tool in planning interventional procedures and evaluating their results., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: The risk of stent thrombosis (ST) following drug-eluting stent (DES) implantation may extend beyond the initial period after successful implantation., Methods: We evaluated the incidence, timing, and clinical outcomes of patients who presented with DES-related early (30 days) angiographic ST. Between 1/2004 and 9/2006, a total of 1339 patients underwent DES implantation (90% using Cypher stents) at our institution. Dual antiplatelet therapy was recommended for 3 to 12 months. Clinical follow-up was obtained and adjudicated at 1 and 6 months following any ST event., Results: We identified eight patients (0.6% of the total patients treated with DES) with definite ST. Their mean age was 67+/-13 years. Six patients (75%) were male and 37.5% (3/8) had diabetes. Acute myocardial infarction (AMI) was the clinical presentation in 87.5% of patients. Time to ST was 4 days in two (25%) of eight patients. The other six patients (75%) had late ST (>30 days). The median time to late ST was 480 days (range: 90-1080 days). Two patients had recurrent events of late ST. All cases of late ST, except one, occurred after clopidogrel treatment was discontinued. Median time from clopidogrel withdrawal to late ST was 18 months (range: 0.5-35 months). At 6 months' follow-up from the time of ST, the subsequent major adverse cardiac event (MACE) rate (including death, re-infarction, recurrent ST or need for emergent CABG) was 62.5% and overall and/or cardiac mortality rate was 12.5%., Conclusion: We found that ST occurred infrequently (0.6%) and the majority (75%) of patients developed ST late (>30 days) and beyond the period recommended for dual anti-platelet pharmacotherapy. Major adverse cardiac events following ST are substantial at 6 months and thus deserve careful clinical attention.

Objectives: To investigate the prevalence of bruxism and signs of temporomandibular disorders (TMDs) among psychiatric patients compared with a healthy population and to assess the effect of psychiatric medications on the parameters studied., Study Design: Subjects included 77 psychiatric patients under treatment at 2 psychiatric hospitals in Israel and 50 healthy individuals (control). One experienced calibrated examiner performed the clinical examination (presence of bruxism and signs of TMD)., Results: Abnormal attrition was evident in 46.8% of the psychiatric patients compared with 20% in the controls (P < .005). Significant differences between groups were apparent for mean muscle sensitivity to palpation, joint sensitivity to palpation, and range of mouth opening. There were no differences between groups in the prevalence of joint clicks and no association between time of receiving treatment with dopamine antagonists (or any other psychotropic drugs) and TMD signs and symptoms., Conclusion: The higher prevalence of bruxism and signs of TMD in psychiatric patients is a major clinical comorbidity. Whether it is a manifestation of the abnormal central nervous system of psychiatric patients or neuroleptic-induced phenomenon deserves further attention. The exact factors that affect the pain experience in these patients should be evaluated as well.

Objective: To explore and describe international oral health attitudes/ behaviours among final year dental students., Methods: Validated translated versions of the Hiroshima University-Dental Behavioural Inventory (HU-DBI) questionnaire were administered to 1,096 final-year dental students in 17 countries. Hierarchical cluster analysis was conducted within the data to detect patterns and groupings., Results: The overall response rate was 72%. The cluster analysis identified two main groups among the countries. Group 1 consisted of twelve countries: one Oceanic (Australia), one Middle-Eastern (Israel), seven European (Northern Ireland, England, Finland, Greece, Germany, Italy, and France) and three Asian (Korea, Thailand and Malaysia) countries. Group 2 consisted of five countries: one South American (Brazil), one European (Belgium) and three Asian (China, Indonesia and Japan) countries. The percentages of 'agree' responses in three HU-DBI questionnaire items were significantly higher in Group 2 than in Group 1. They include: "I worry about the colour of my teeth."; "I have noticed some white sticky deposits on my teeth."; and "I am bothered by the colour of my gums.", Conclusion: Grouping the countries into international clusters yielded useful information for dentistry and dental education.

Background: Pain measures associated with computerized delivery of intrasulcular anesthestic have not been reported. The authors evaluated a computerized delivery system for intrasulcular (CDS-IS) anesthesia in primary molars. METHODS; The study population consisted of children aged 2 to 13 years who received CDS-IS injections, 159 in mandibular molars and 48 in maxillary molars. Children were treated by one of three modes of behavioral management: behavior modification (BM) only, inhalation of nitrous oxide (N2O) in addition to BM or intrarectal sedation. Variables evaluated included the subjective perception of the child's well-being before and after administration of the anesthetic, the child's pain behavior during anesthetic administration, effectiveness of the anesthetic during dental treatment, incidence of reported postoperative dental pain (PDP) and analgesic use after the CDS-IS injections., Results: The effectiveness of CDS-IS anesthesia in mandibular molars was 97 percent, 92 percent, 63 percent and 71 percent for restorations, preformed stainless steel crowns, extractions and pulpal therapies, respectively (mean effectiveness, 89 percent). The effectiveness of CDS-IS anesthesia in maxillary molars was 96 percent, 50 percent, 92 percent and 78 percent, respectively (mean effectiveness, 90 percent). CDS-IS was less effective in children aged 2 to 4 years who received sedation than it was in older children. The authors found no differences between children's subjective self-reports of well-being before and after anesthetic administration, between the sexes and/or between modes of behavioral management (that is, BM or N2O). Most children exhibited low pain-related behavior during anesthetic administration, with no differences between boys and girls. The overall incidence of PDP was 31.4 percent; 64.9 percent of these patients received pain-relieving medications as a result, with no correlation to age, tooth treated, effectiveness of anesthesia or type of treatment., Conclusions: CDS-IS is effective for anesthetizing primary molars, mainly for amalgam, resin-based composite and stainless steel crown restorations.

Objective: To identify similarities and differences in oral health attitudes, behaviour and values among freshman dental students., Design: Cross-cultural survey of dental students., Setting: 18 cultural areas., Participants and Methods: 904 first-year dental students completed the Hiroshima University-Dental Behavioural Inventory (HU-DBI) translated into their own languages. Individual areas were clustered by similarity in responses to the questions., Results: The first group displayed an 'occidental-culture orientation' with the exception of Brazil (Cluster 1 comprised: Australia, United Kingdom, Ireland, Belgium and Brazil, Cluster 2: Germany, Italy, Finland and France). The second group displayed an 'oriental-cultural orientation' with the exception of Greece and Israel (Cluster 3 comprised: China and Indonesia, and Cluster 4: Japan, Korea, Israel, Hong Kong, Malaysia, Thailand and Greece). Australia and United Kingdom were the countries that were most alike. Ireland was the 'neighbour' to these countries. Greece and Malaysia had similar patterns of oral health behaviour although geographic conditions are very different. Although it was considered that in Hong Kong, occidental nations have affected the development of education, it remained in the oriental-culture group. Comparison with the data from the occidentals indicates that a higher percentage of the orientals put off going to the dentist until they have toothache (p < 0.001). Only a small proportion of the occidentals (8%) reported a perception of inevitability in having false teeth, whereas 33% of the orientals held this fatalistic belief (p = 0.001)., Conclusions: Grouping the countries into key cultural orientations and international clusters yielded plausible results, using the HU-DBI.

Background: Hypnorelaxation has a potentially beneficial effect in the treatment of masticatory myofascial pain disorders (MPD). However, there are no data regarding the efficacy of hypnorelaxation in the treatment of MPD compared with other accepted modes of treatment (such as occlusal appliance) or with the mere effect of time., Objective and Subjects: The purpose of the present study was to evaluate the effectiveness of hypnorelaxation in the treatment of MPD compared with the use of occlusal appliance and/or to minimal treatment. The study population consisted of 40 female patients with myofascial pain who were allocated to 1 of 3 possible treatment groups: (1) hypnorelaxation (n = 15), (2) occlusal appliance (n = 15), and (3) minimal treatment group (n = 10)., Results: Both active treatment modes (hypnorelaxation and occlusal appliance) were more effective than minimal treatment regarding alleviating muscular sensitivity to palpation. However, only hypnorelaxation (but not occlusal appliance) was significantly more effective than minimal treatment with regard to the patient's subjective report of pain on the Visual Analog Scale., Conclusion: Hypnorelaxation is an effective mode of treatment in MPD, especially with regard to some of the subjective pain parameters.

Background: Bad breath, also known as halitosis, is a common concern for millions of people. Yet there is almost no reliable way for people to properly assess their breath odor. While many develop faulty perceptions about having bad breath that affect their entire lives, others who have halitosis are unaware of their condition., Overview: The authors discuss the issues affecting self-perception of breath odor in patients who complain of halitosis, as well as in a more general, "noncomplaining" population. The article presents self-perception of breath odor as a multifactorial, psychophysiological issue that is related closely to one's body image and psychopathological profile., Conclusions: Based on their data, the authors suggest that every patient has a breath odor self-image. This self-image ranges from little or no distortion to severe psychopathology. Because treating patients with a specific complaint of oral malodor primarily is the responsibility of the dental practitioner, several treatment approaches are outlined: collecting odor samples from the mouth to increase objectivity, involving a confidant in diagnosis and follow-up, corroborating odor judges' scores with objective measurements, increasing the patient's sense of control over the problem and obtaining guidance from mental health professionals, when necessary., Clinical Implications: Dentists increasingly are being called on to help patients with complaints of bad breath. In diagnosing and treating such cases, dentists should consider psychological and physiological factors.

Fear and anxiety are common emotional concomitants of acute pain that increase the perception of noxious events as painful. In the present study, 92 patients who were about to undergo various dental treatments (calculus removal, filling, root canal treatment, and extraction) were evaluated comparing the level of their dental anxiety and pain expectation from the intended treatment to their reaction to electric pulp stimulation. The data indicate that patients differ significantly in their dental anxiety levels and in their expectation to experience pain according to the following hierarchy (in descending order): extraction, root canal treatment, filling, and calculus removal. Anxiety and amount of pain expected from treatment correlated significantly with each other, but no simple correlations were found between anxiety and actual pain measures recorded after pulp stimulation.

Objective: Bitewing radiographs are the main tool for approximal caries detection. However, interpretation of findings is affected by numerous factors, such as beam angulation, exposure conditions, morphologic variations, etc. The objective of the present study was to compare the ability to detect virtually identical, artificial lesions in different tooth surfaces., Methods: The in vitro model included preparation and radiologic evaluation of approximal artificial lesions in premolars and molars in depths ranging from 0.00 mm to 1.50 mm., Results: Significant differences were found in the prospect of a lesion detection between the different lesion depths (p < 0.0000) and between the different surfaces examined (p < 0.05). The interaction between lesion depth and tooth surface was significant at the 0.0001 level (ANOVA with repeated measures)., Conclusions: The results indicate that initial approximal lesions of uniform size are more readily detected in premolars than in molars and that the chance of an incipient lesion to remain undetected is twice as high in molars than in premolars.

Objective: The decision to treat initial approximal carious lesions is based mainly on interpretation of bitewing radiographs. In a previous report, it was shown that artificial approximal lesions of uniform size are more readily detected on radiographs in premolars than in molars. The objective of the present study was to compare the ability to evaluate the depth of similar size artificial lesions on radiographs and reach decisions concerning treatment, in premolars and molars., Method: Clinicians were asked to evaluate on radiographs, the size of in vitro prepared artificial lesions, and decide at which point they would perform a restoration., Results: Significant differences were found in the evaluation of lesion depth between different tooth surfaces. The interaction between lesion depth and tooth surface originated from the examiners' trend to score same size lesions as penetrating deeper into the tooth in premolars than in molars. The probability of the examiners to decide on restorative treatment in shallow lesions (0.25 mm, 0.50 mm) was higher in premolars than in molars., Conclusions: The findings suggest that clinicians evaluate initial lesions as being deeper and more prone to treatment in premolars than in molars.

The use of spray-producing instruments in the dental clinic continuously creates a potentially harmful contamination of the room environment. In the present study a 13.5-kV corona discharge ionizing generator was used in order to investigate the effect of ions on the microbial air pollution of the dental clinic. Samples of microbial air population were collected in 9-cm-diameter plates containing either Bacto-Brain Heart Infusion Agar or Bacto-Mitis Salivarius Agar and exposed to different time periods in various locations of an active dental clinic. Microbial air levels in the dental clinic were significantly reduced with the generator (by 40-50%). The data suggest that the ionizing generator can be used to reduce the microbial air pollution within the dental clinic, thus reducing the environmental hazard of infections to the staff.