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Introduction: This in vitro study sought to compare the efficacy of a sonic irrigant activation device with ultrasonic activation and needle irrigation in removing hard tissue debris (HTD) from anatomic complexities of the root canal system., Methods: Twenty-seven mesial roots of extracted human mandibular molars with 2 canals connected by an isthmus were selected based on micro-computed tomography scans (12-μm voxel size). The mesial canals were mechanically prepared to ProTaper Next X3 (Dentsply Maillefer, Ballaigues, Switzerland) and anatomically distributed into 3 groups (n = 9) according to the final irrigation protocol: sonically activated irrigation (SAI) using the EDDY system (VDW GbmH, Munich, Germany) for 3 × 20 seconds, ultrasonically activated irrigation (UAI) using a size 20 Irrisafe tip (Satelec Acteon, Mérignac, France) for 3 × 20 seconds, and conventional irrigation using a 30-G needle adapted to a syringe. Micro-computed tomographic scans were taken after instrumentation and after supplementary activation of the irrigant. After reconstruction and coregistration, the volume filled with HTD before and after irrigant activation was calculated, and the mean percentage of HTD reduction after final irrigation was compared within and among groups using the paired sample t test and 1-way analysis of variance post hoc Tukey test, respectively (α = 5%)., Results: A significant reduction in the volume filled with HTD after irrigant activation was observed in all groups (P < .05). The percentage reduction of HTD in the UAI group (66.8%) was significantly higher than that in the SAI group (36.4%) (P < .05), whereas the conventional irrigation group result (43.7%) did not differ statistically from the UAI or SAI groups (P > .05)., Conclusions: All tested supplementary irrigation steps significantly reduced the amount of debris created during root canal preparation. Ultrasonic activation resulted in the highest mean debris reduction., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Analytical capabilities of Nanoscopic Secondary Ion Mass Spectrometry (nano-SIMS) and Synchrotron Radiation based X-ray Fluorescence (SR nano-XRF) techniques were compared for nanochemical imaging of polymorphonuclear human neutrophils (PMNs). PMNs were high pressure frozen (HPF), cryo-substituted, embedded in Spurr's resin and cut in thin sections (500 nm and 2 μm for both techniques resp.) Nano-SIMS enabled nanoscale mapping of isotopes of C, N, O, P and S, while SR based nano-XRF enabled trace level imaging of metals like Ca, Mn, Fe, Ni, Cu and Zn at a resolution of approx. 50 nm. The obtained elemental distributions were compared with those of whole, cryofrozen PMNs measured at the newly developed ID16A nano-imaging beamline at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Similarities were observed for elements more tightly bound to the cell structure such as phosphorus and sulphur, while differences for mobile ions such as chlorine and potassium were more pronounced. Due to the observed elemental redistribution of mobile ions such as potassium and chlorine, elemental analysis of high pressure frozen (HPF), cryo-substituted and imbedded cells should be interpreted critically. Although decreasing analytical sensitivity occurs due to the presence of ice, analysis of cryofrozen cells - close to their native state - remains the golden standard. In general, we found nanoscale secondary ion mass spectrometry (nano-SIMS) and synchrotron radiation based nanoscopic X-ray fluorescence (SR nano-XRF) to be two supplementary alternatives for nanochemical imaging of single cells at the nanoscale., Competing Interests: Declaration of competing interest The author(s) declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: The purpose of this study was to compare in vitro the canal and isthmus debridement of manual-dynamic, passive ultrasonic, and laser-activated irrigation with an Er:YAG laser in mesial roots of human mandibular molars., Methods: Fifty extracted mandibular molars with an isthmus were embedded in resin and sectioned axially 4 mm from the apex. The teeth were reassembled with guide pins and bolts, and the mesial canals were instrumented up to a ProTaper F2 rotary file (Dentsply Maillefer, Ballaigues, Switzerland). Teeth were randomly assigned to the following irrigant activation groups (n = 10): conventional needle irrigation (NI), manual-dynamic irrigation with a ProTaper F2 gutta-percha cone, ultrasonically activated irrigation using a size 20 Irrisafe (Satelec Acteon, Mérignac, France), and laser-activated irrigation (LAI) with an Er:YAG laser and a conical 400-μm fiber tip in the canal entrance or a 600-μm tip over the canal entrance. Root cross-sectional images were taken before and after final irrigation, and the area occupied by debris in the main canal and the isthmus was determined using image analysis software. Differences in debris before and after activation were statistically compared within and across groups., Results: Significant reductions in debris levels were observed in all groups, except for NI and manual-dynamic irrigation (canal only). None of the methods rendered the canal systems debris free. In the canal, LAI with an Er:YAG laser and a 600-μm tip over the canal entrance removed significantly more debris than NI. In the isthmus, LAI with an Er:YAG laser and a conical 400-μm fiber tip in the canal entrance removed significantly more debris than NI., Conclusions: Within the limitations of this in vitro study, canal and isthmus cleanliness significantly improved after irrigant activation., (Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

In humans, receptor-interacting protein kinase 4 (RIPK4) mutations can lead to the autosomal recessive Bartsocas-Papas and popliteal pterygium syndromes, which are characterized by severe skin defects, pterygia, as well as clefting. We show here that the epithelial fusions observed in RIPK4 full knockout (KO) mice are E-cadherin dependent, as keratinocyte-specific deletion of E-cadherin in RIPK4 full KO mice rescued the tail-to-body fusion and fusion of oral epithelia. To elucidate RIPK4 function in epidermal differentiation and development, we generated epidermis-specific RIPK4 KO mice (RIPK4 EKO ). In contrast to RIPK4 full KO epidermis, RIPK4 EKO epidermis was normally stratified and the outside-in skin barrier in RIPK4 EKO mice was largely intact at the trunk, in contrast to the skin covering the head and the outer end of the extremities. However, RIPK4 EKO mice die shortly after birth due to excessive water loss because of loss of tight junction protein claudin-1 localization at the cell membrane, which results in tight junction leakiness. In contrast, mice with keratinocyte-specific RIPK4 deletion during adult life remain viable. Furthermore, our data indicate that epidermis-specific deletion of RIPK4 results in delayed keratinization and stratum corneum maturation and altered lipid organization and is thus indispensable during embryonic development for the formation of a functional inside-out epidermal barrier., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The T axis was postulated to be a general marker of repolarisation abnormality, indicative of subclinical myocardial damage. The aim of this investigation was to assess the prognostic importance of the T axis for fatal and non-fatal cardiac events, in a prospective cohort study of men and women aged 55 years and older., Methods: 2352 men and 3429 women from the population-based Rotterdam Study took part in the study. Electrocardiograms were done, and T axes were categorised as normal, borderline, or abnormal. Data were analysed with Cox's proportional-hazards models; adjustment for age and sex was done where appropriate., Findings: During 3-6 (mean 4) years of follow-up of the 5781 participants, 165 (2.9%) fatal and 192 (3.3%) non-fatal cardiac events occurred. Participants with an abnormal T axis (n=609) had an increased risk of cardiac death (hazard ratio 3.9 [95% CI 2.8-5.6]), sudden cardiac death (4.4 [2.6-7.4]), non-fatal cardiac events (2.7 [1.9-3.9]), and combined fatal or non-fatal cardiac events (3.2 [2.5-4.1]); p<0.001 for each. Additional adjustment for established cardiovascular risk factors resulted in lower, but still significant risk for all endpoints. The risk associated with an abnormal T axis was higher than those for any other cardiovascular risk factor. Additional subgroup analyses indicated that the risk of cardiac death was not substantially modified by age, sex, or history of myocardial infarction., Interpretation: The T axis is a strong and independent risk indicator of fatal and non-fatal cardiac events in the elderly.

We assessed the performance of diagnostic electrocardiogram (ECG) interpretation by the computer program MEANS and by research physicians, compared to cardiologists, in a physician-based study. To establish a strategy for ECG interpretation in health surveys, we also studied the diagnostic capacity of three scenarios: use of the computer program alone (A), computer program and cardiologist (B), and computer program, research physician, and cardiologist (C). A stratified random sample of 381 ECGs was drawn from ECGs collected in the Rotterdam Study (n = 3057), which were interpreted both by a trained research physician using a form for structured clinical evaluation and by MEANS. All ECGs were interpreted independently by two cardiologists; if they disagreed (n = 175) the ECG was judged by a third cardiologist. Five ECG diagnoses were considered: anterior and inferior myocardial infarction (MI), left and right bundle branch block (LBBB and RBBB), and left ventricular hypertrophy (LVH). Overall, sensitivities and specificities of MEANS and the research physicians were high. The sensitivity of MEANS ranged from 73.8% to 92.9% and of the research physician ranged from 71.8% to 96.9%. The specificity of MEANS ranged from 97.5% to 99.8% and of the research physician from 96.3% to 99.6%. To diagnose LVH, LBBB, and RBBB, use of the computer program alone gives satisfactory results. Preferably, all positive findings of anterior and inferior MI by the program should be verified by a cardiologist. We conclude that diagnostic ECG interpretation by computer can be very helpful in population-based research, being at least as good as ECG interpretation by a trained research physician, but much more efficient and therefore less expensive.