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About 10% of Europe's surface area is prone to rapid flooding of rivers confined in valleys. The devastating potential of such floods is exacerbated by the deficits of existing gauging networks, including low station densities and recording frequencies, and lack of information beyond stage height. Here, we use seismic data of the July 2021 Ahrtal flood, Germany, to extract information to complement sparse hydrometric data, and to reconstruct the rapid evolution of this fatal event. We show that a seismic station can deliver essential flood metrics such as magnitude, propagation velocity and debris transport rate. These seismic products provide high resolution insight to the non‐linear flood behavior. We argue that an approach combining distributed low‐cost seismometers with existing seismic stations, can provide important real time data on future catastrophic floods and associated hazards in upland catchments, offering precious response time also in currently ungauged landscapes. Plain Language Summary: Rapidly evolving floods are a major hazard for 10% of European landscapes. They are hard to adequately detect and describe by the classic gauge station scheme, but seismic sensors provide a valuable alternative to this difficulty. A seismometer can sense a flood like the devastating one that hit the Ahr valley, Germany, in July 2021 up to 1.5 km away. The seismic footprint of the flood allows to provide information on flood magnitude, velocity and trajectory at sub‐minute resolution and at near real time. We show how this new approach can be utilized for future flood protection. Key Points: Seismic sensing of valley confined floods improves classic detection approachesNear‐real time information on flood magnitude, trajectory, and velocityGate keeper seismometer networks can improve flood risk management in Europe [ABSTRACT FROM AUTHOR]

This paper introduces a generative model for 3D surfaces based on a representation of shapes with mean curvature and metric, which are invariant under rigid transformation. Hence, compared with existing 3D machine learning frameworks, our model substantially reduces the influence of translation and rotation. In addition, the local structure of shapes will be more precisely captured, since the curvature is explicitly encoded in our model. Specifically, every surface is first conformally mapped to a canonical domain, such as a unit disk or a unit sphere. Then, it is represented by two functions: the mean curvature half‐density and the vertex density, over this canonical domain. Assuming that input shapes follow a certain distribution in a latent space, we use the variational autoencoder to learn the latent space representation. After the learning, we can generate variations of shapes by randomly sampling the distribution in the latent space. Surfaces with triangular meshes can be reconstructed from the generated data by applying isotropic remeshing and spin transformation, which is given by Dirac equation. We demonstrate the effectiveness of our model on datasets of man‐made and biological shapes and compare the results with other methods. [ABSTRACT FROM AUTHOR]

Hepatitis C virus ( HCV) is a human hepatotropic virus, but many hepatoma cell lines are not permissive to this virus. In a previous study, we observed that SNU-182, SNU-398 and SNU-449 hepatoma cell lines were nonpermissive to HCV. To understand the nonpermissivity, we evaluated the ability of each cell line to support the different steps of HCV life cycle (entry, replication and production of infectious particles). Using retroviral pseudoparticles pseudotyped with HCV envelope proteins and recombinant HCV produced in cell culture, we observed that low level or absence of claudin-1 (CLDN1) expression limited the viral entry process in SNU-182 and SNU-398 cells, respectively. Our results also showed that supplementation of the three cell lines with miR-122 partly restored the replication of a JFH1 HCV replicon. Finally, we observed that expression of apolipoprotein E (ApoE) was very low or undetectable in the three cell lines and that its ectopic expression permits the production of infectious viral particles in SNU-182 and SNU-398 cells but not in SNU-449 cells. Nevertheless, the supplementation of SNU-182, SNU-398 and SNU-449 cells with CLDN1, miR-122 and ApoE was not sufficient to render these cells as permissive as HuH-7 cells. Thus, these cell lines could serve as cell culture models for functional studies on the role of CLDN1, miR-122 and ApoE in HCV life cycle but also for the identification of new restriction and/or dependency host factors essential for HCV infection. [ABSTRACT FROM AUTHOR]

Intravascular imaging provides new insights into the condition of vessel walls. This is crucial for cerebrovascular diseases including stroke and cerebral aneurysms, where it may present an important factor for indication of therapy. In this work, we provide new information of cerebral artery walls by combining ex vivo optical coherence tomography (OCT) imaging with histology data sets. To overcome the obstacles of deflated and collapsed vessels due to the missing blood pressure, the lack of co-alignment as well as the geometrical shape deformations due to catheter probing, we developed the new image processing method virtual inflation. We locally sample the vessel wall thickness based on the (deflated) vessel lumen border instead of the vessel's centerline. Our method is embedded in a multi-view framework where correspondences between OCT and histology can be highlighted via brushing and linking yielding OCT signal characteristics of the cerebral artery wall and its pathologies. Finally, we enrich the data views with a hierarchical clustering representation which is linked via virtual inflation and further supports the deduction of vessel wall pathologies. [ABSTRACT FROM AUTHOR]

Five Iron Age ceramic lamps from a tomb at the site of Sahab in the south-eastern part of central Jordan were analysed using gas chromatography - mass spectrometry (GC-MS). The results of this study provide data on the type of fuel used in three of these lamps. The study proposes that animal fat, possibly of ruminant origin, was used in three Early Iron Age II lamps. The material used in the other two Iron Age I lamps could not be determined due to the absence of diagnostic biomarkers. The data obtained from the lamps can be put in conjunction with the archaeological evidence on the availability of domestic animals and, most probably, use of their products at the site of Sahab during the Iron Age. [ABSTRACT FROM AUTHOR]

Background and Objective Matrix metalloproteinase-8 ( MMP-8) is involved in a wide range of pathologies including periodontitis and cardiovascular diseases ( CVD). The association between periodontitis and CVD has been repeatedly recognized. The aim of the study was to analyze to what extent circulating active MMP-8 ( aMMP-8) is associated with periodontal disease status and oral fluid aMMP-8 levels in otherwise healthy subjects. Material and Methods In a cross-sectional study, aMMP-8 was measured in serum of 59 volunteers, comprising 19 periodontally healthy subjects, 20 patients with gingivitis as well as 20 with periodontitis. All study subjects were characterized regarding aMMP-8 concentrations in different oral fluids as well as clinically and microbiologically with respect to periodontal disease. aMMP-8 levels in gingival crevicular fluid were measured using the enzyme-linked immunosorbent assay. Saliva enzyme levels as well as circulating aMMP-8 were determined by a time-resolved immunofluorometric assay. Both methods utilized the same monoclonal antibodies. Correlation and regression analyses were performed to study the potential association between serum aMMP-8 and oral parameters. Results Oral aMMP-8 levels were significantly higher in patients with periodontitis compared to periodontally healthy or gingivitis subjects. Highest serum aMMP-8 concentration was also found in the periodontitis group. The serum levels correlated significantly with oral aMMP-8 as well as with clinical parameters in a dose-dependent manner. These results were confirmed in a multivariate regression analysis. After adjusting for potential confounders, saliva aMMP-8 concentrations as well as periodontitis severity were significant predictors of serum aMMP-8. Conclusion The associations between circulating aMMP-8 and oral aMMP-8 as well as periodontal findings in a dose-dependent manner may contribute to linking periodontal disease with increased CVDsusceptibility. [ABSTRACT FROM AUTHOR]

Background and Objectives Severe periodontitis affects about 10% of the world population. In addition, associations between periodontitis and systemic diseases exist. Therefore, the diagnosis should be made quickly and at an early stage. Matrix metalloproteinase-8 (MMP-8) is the most prominent collagenase found in inflamed periodontal tissues. Its active form (aMMP-8) is increasingly used as a diagnostic biomarker. Aim of the present study is to evaluate the diagnostic accuracy of a novel aMMP-8 point-of-care (POC) test in comparison to the standard laboratory test to diagnose the disease rapidly and reliably. Material and Methods In a prospective, mono-center, double-blinded, case-control study, participants with healthy gums ( n = 35), gingivitis ( n = 60) and periodontitis ( n = 35) were investigated before and after therapy. Beside clinical variables for plaque and inflammation, aMMP-8 concentrations were determined in oral rinsing specimens by the enzyme-linked immunosorbent assay (ELISA) and by POC. Positive and negative percent agreements with their exact one-sided lower 95% confidence limits were calculated. Results Of 130 participants, 111 finished the study. Overall, positive percent agreements were 75.8% (57.7-88.9) before treatment and 73.7% (56.9-86.6) after treatment. Negative percent agreements were 92.8% (85.7-97.0) before and 93.3% (85.1-97.8) after treatment. Positive test results (POC and ELISA) ranged from 5.7% to 8.6% in healthy patients, 25.0-29.8% in patients with gingivitis and 40.0-48.1% in patients with periodontitis. Patients who had positive aMMP-8 test results (POC) showed higher scores for plaque and inflammation. Conclusions The novel POC test to detect aMMP-8 has proved to agree strongly with the standard method, ELISA. The test can be recommended to screen patients at risk for periodontitis in dental offices, at the general practitioner and at specialists for associated diseases. [ABSTRACT FROM AUTHOR]

Background: Injection of the noxious peptide Bv8 has previously been shown to induce a biphasic thermal hyperalgesia in rodents, the first peak presumably due to peripheral sensitization. This hypothesis has never been directly confirmed. We have assessed whether Bv8 can indeed sensitize peripheral nerve fibres in the mouse to heat.Methods: We used recordings from single cutaneous fibres, cutaneous calcitonin gene-related peptide (CGRP) release and immunostaining in nerves and plantar skin to evaluate the Bv8 effects on cutaneous nerves.Results: Application of Bv8 at nanomolar concentrations (30-310 nmol/L) to skin preparations significantly increased the heat-induced discharge, the heat-induced afterdischarge and reduced threshold temperature of single unmyelinated polymodal fibres. Furthermore, application of Bv8 to hind-paw skin flaps or trigeminal ganglia significantly elevated their heat-induced CGRP release. Capsaicin-induced and to a lesser extent also KCl-induced CGRP releases were also augmented after Bv8 treatment. Immunohistochemistry revealed co-localization of prokineticin 2 (Bv8 ortholog in rodents) and CGRP in both plantar skin and nerve tissues. These results confirm that Bv8 sensitizes cutaneous nerve endings to heat, partly, although not exclusively through TRPV1 activation.Conclusion: Our results thus support the hypothesis that the first hyperalgesic phase to follow Bv8 injection to hind paws of intact animals is due to peripheral sensitization of nociceptors. WHAT DOES THIS STUDY ADD?: Our data provide mechanistic insights into the effect Bv8 application exerts on afferent nerve endings and into the concomitant development of thermal hyperalgesia. [ABSTRACT FROM AUTHOR]

Background: Tooth extractions lead to morphological changes of the alveolar ridge. For oral rehabilitation sufficient bone volume of the alveolar ridge is required. This clinical study compared the ability of Bio-Oss® Collagen to autogenous bone to preserve bone volume after tooth extraction.Methods: A total of 17 patients with 20 extraction sites were examined. After extraction, 10 sockets were each filled with either autogenous bone or Bio-Oss® Collagen and covered with a resorbable membrane. The width of the alveolar ridge was measured postoperatively, and after 4 and 6 months respectively. Prior to implant insertion, a bone biopsy was taken from the grafted sites and evaluated histologically.Results: The width of the alveolar ridge in the Bio-Oss® Collagen group decreased about 5.33 ± 6.62% after 4 months and 9.45 ± 10.51% after 6 months. The reduction in the group augmented with autogenous bone was 14.31 ± 21.41% after 4 months and 19.17 ± 8.38% after 6 months. No statistically significant differences were observed. The histological examination showed comparable area fractions of total bone in both groups (Bio-Oss® Collagen: 59.99 ± 24.23%; autogenous bone: 61.55 ± 25.13%; p = 1.0).Conclusions: The present study demonstrated that autogenous bone and Bio-Oss® Collagen are suitable for ridge preservation. However, both techniques could not entirely prevent tissue volume loss. [ABSTRACT FROM AUTHOR]

Background: When a child is diagnosed with autism, parents are faced with the task of choosing from many different intervention options. To find information about the options available, parents turn to a number of different sources. This study explores parents' (n = 23) intervention decisionmaking processes and information preferences following the diagnosis of ASD for their child. Methods: Qualitative thematic analysis of verbatim transcripts from interviews and focus groups involving parents of children with an autism diagnosis was undertaken. Results: Analysis of the results revealed that there are concurrent emotional and pragmatic intervention 'journeys' undertaken by parents post diagnosis, which encompass the primary themes of: (1) information sources used, (2) parents' information preferences and (3) factors influencing intervention decision making. Parents described a journey from the point of diagnosis that involved seeking information on ASD interventions from multiple sources, with the Internet being the primary source. They were overwhelmed by the sheer volume of information available, and their preferences for information varied according to their stage in the journey post diagnosis. Parents had a 'trial and error' approach to choosing ASD interventions, with confidence increasing as they became more familiar with their child's condition, and had opportunities to explore numerous information sources about their child's diagnosis. While confidence increased over time, consideration of the effectiveness or evidence supporting interventions remained largely absent throughout the journey. Conclusion: This study highlights the need for parents of children with ASD to be supported to make informed intervention decisions, particularly with consideration for research evidence. [ABSTRACT FROM AUTHOR]

During the last years, two new cardiovascular drug classes, namely inhibitors of DPP IV or neprilysin, have been developed. In both cases, there is clinical evidence for their potential to induce angioedema as known already from blockers of the renin-angiotensin-aldosterone system ( RAAS). The majority of angioedema induced by DPP IV inhibitors occurs during concomitant treatment with ACEi and is therefore likely mediated by overactivation of bradykinin type 2 receptors (B2). In striking contrast, the molecular pathways causing angioedema induced by neprilysin inhibitors, that is, sacubitril, are unclear, although a contribution of bradykinin appears likely. Nevertheless, there is no clinical evidence suggesting that inhibition of B2 might relieve the symptoms and/or prevent invasive treatment including coniotomy or tracheotomy in angioedema caused by these drugs. Therefore, the risk of angioedema should always be considered, especially in ambulatory care situations where patients have no rapid access to intensive care. [ABSTRACT FROM AUTHOR]

Aim Intact surface active agent (surfactant) composed of surfactant-associated proteins ( SPs) and lipids is necessary for respiration and prevents alveoli from collapsing. CD26, a transmembrane glycoprotein exerting dipeptidyl peptidase activity ( DPP4), highly expressed in lung parenchyma, is involved in inflammatory processes. A pharmacological inhibition of DPP4 influenced not only the inflammation but also elevated the SPs. Thus, DPP4 inhibitors may be a novel drug for treatment of diseases with surfactant deficiency. Therefore, we tested firstly the hypothesis that DPP4 inhibitors increase the expression of SPs in healthy rats. Methods SP mRNA and protein expression were determined different times after nebulization of aerosolized DPP4 inhibitors [L-isoleucine-thiazolidide (L-Ile-Thia), L-valine-pyrrolidide (L-Val-Pyrr)], budesonide, saline or stereoisomers. Results Compared with negative controls (1) L-Ile-Thia as well as budesonide led to a significant higher and L-Val-Pyrr had the tendency to a significant higher expression of SP-A mRNA 6 h after nebulization, (2) the expression of SP-D mRNA increased significantly 6 h after nebulization with L-Ile-Thia and 3 and 6 h after nebulization with Val-pyrr, (3) SP-B mRNA levels showed significantly higher values 3 and 6 h after nebulization with L-Val-Pyrr, (4) protein levels of SP-A, SP-B and SP-C were elevated significantly 6 h after nebulization with L-Val-Pyrr as well as with budesonide, and (5) phospholipids were also increased in response to DPP4 inhibition; the minimal surface tension was comparable. Conclusion DPP4 inhibition influence differently the expression of surfactant proteins in healthy rats and may be suitable to elevate surfactant synthesis in different diseases accompanied with surfactant deficiencies. [ABSTRACT FROM AUTHOR]

Background: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach., Objective: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach., Methods: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed., Results: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers., Conclusions: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Acute lymphoblastic leukemia (ALL) represents the most frequent malignancy in children, and relapse/refractory (r/r) disease is difficult to treat, both in children and adults. In search for novel treatment options against r/r ALL, we studied inhibitor of apoptosis proteins (IAP) and Smac mimetics (SM). SM-sensitized r/r ALL cells towards conventional chemotherapy, even upon resistance against SM alone. The combination of SM and chemotherapy-induced cell death via caspases and PARP, but independent from cIAP-1/2, RIPK1, TNFα or NF-κB. Instead, XIAP was identified to mediate SM effects. Molecular manipulation of XIAP in vivo using microRNA-30 flanked shRNA expression in cell lines and patient-derived xenograft (PDX) models of r/r ALL mimicked SM effects and intermediate XIAP knockdown-sensitized r/r ALL cells towards chemotherapy-induced apoptosis. Interestingly, upon strong XIAP knockdown, PDX r/r ALL cells were outcompeted in vivo, even in the absence of chemotherapy. Our results indicate a yet unknown essential function of XIAP in r/r ALL and reveal XIAP as a promising therapeutic target for r/r ALL., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Bacillus subtilis, in its natural habitat, is regularly exposed to rapid changes in the osmolarity of its surrounding. As its primary survival strategy, it accumulates large amounts of the compatible solute proline by activating the de novo proline biosynthesis pathway and exploiting the glutamate pools. This osmotically-induced biosynthesis requires activation of a SigA-type promoter that drives the expression of the proHJ operon. Population-wide studies have shown that the activity of the proHJ promoter correlates with the increased osmotic pressure of the environment. Therefore, the activation of the proHJ transcription should be an adequate measure of the adaptation to osmotic stress through proline synthesis in the absence of other osmoprotectants. In this study, we investigate the kinetics of the proHJ promoter activation and the early adaptation to mild osmotic upshift at the single-cell level. Under these conditions, we observed a switching point and heterogeneous proline biosynthesis gene expression, where the subpopulation of cells showing active proHJ transcription is able to continuously divide, and those unresponsive to osmotic stress remain dormant. Additionally, we demonstrate that bactericidal antibiotics significantly upregulate proHJ transcription in the absence of externally imposed osmotic pressure, suggesting that the osmotically-controlled proline biosynthesis pathway is also involved in the antibiotic-mediated stress response., (© 2022 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

In most patients with chronic myeloid leukemia (CML) clonal cells can be kept under control by BCR::ABL1 tyrosine kinase inhibitors (TKI). However, overt resistance or intolerance against these TKI may occur. We identified the epigenetic reader BRD4 and its downstream-effector MYC as growth regulators and therapeutic targets in CML cells. BRD4 and MYC were found to be expressed in primary CML cells, CD34 + /CD38 - leukemic stem cells (LSC), and in the CML cell lines KU812, K562, KCL22, and KCL22 T315I . The BRD4-targeting drug JQ1 was found to suppress proliferation in KU812 cells and primary leukemic cells in the majority of patients with chronic phase CML. In the blast phase of CML, JQ1 was less effective. However, the BRD4 degrader dBET6 was found to block proliferation and/or survival of primary CML cells in all patients tested, including blast phase CML and CML cells exhibiting the T315I variant of BCR::ABL1. Moreover, dBET6 was found to block MYC expression and to synergize with BCR::ABL1 TKI in inhibiting the proliferation in the JQ1-resistant cell line K562. Furthermore, BRD4 degradation was found to overcome osteoblast-induced TKI resistance of CML LSC in a co-culture system and to block interferon-gamma-induced upregulation of the checkpoint antigen PD-L1 in LSC. Finally, dBET6 was found to suppress the in vitro survival of CML LSC and their engraftment in NSG mice. Together, targeting of BRD4 and MYC through BET degradation sensitizes CML cells against BCR::ABL1 TKI and is a potent approach to overcome multiple forms of drug resistance in CML LSC., (© 2022 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Background: Despite successful resuscitation with return of spontaneous circulation (ROSC), the prediction of survival in patients suffering out-of-hospital cardiac arrest (OHCA) remains difficult. Several studies have shown alterations in sublingual microcirculation in the critical ill. We hypothesized that early alterations in sublingual microcirculation may predict short-term survival after OHCA., Methods: We prospectively included all adults admitted to our university hospital between April and September 2019 with ROSC following OHCA. Sidestream dark-field microscopy to obtain sublingual microcirculation was performed at admission and after 6, 12 and 24 hours. Primary outcome was survival until discharge., Results: Twenty-five patients were included. Six hours after ROSC, the proportion of perfused small vessels (PPV small ) was lower in non-survivors than in survivors (85 ± 7.9 vs. 75 ± 6.6%; p = .01). PPV small did not correlate with serum lactate. Stratification for survival with cutoff values >78.4% for PPV small 6 h post-admission and <5.15 mmol/l for initial serum lactate as suggested by ROC-Analyses results in a positive predictive value of 100% and a negative one of 67% for our study population., Conclusion: Estimating short-term prognosis of OHCA patients with ROSC may be supported by measuring the PPV small at the sublingual microcirculation 6 hours after admission., (© 2021 The Authors. Microcirculation published by John Wiley & Sons Ltd.)

Background Long QT has been associated with ventricular dysrhythmias, cardiovascular disease (CVD) mortality, and sudden cardiac death. However, no studies to date have investigated the dynamics of within-person QT change over time in relation to risk of incident CVD and all-cause mortality in a real-world setting. Methods and Results A cohort study among members of an integrated health care delivery system in Northern California including 61 455 people (mean age, 62 years; 60% women, 42% non-White) with 3 or more ECGs (baseline in 2005-2009; mean±SD follow-up time, 7.6±2.6 years). In fully adjusted models, tertile 3 versus tertile 1 of average QT corrected (using the Fridericia correction) was associated with cardiac arrest (hazard ratio [HR], 1.66), heart failure (HR, 1.62), ventricular dysrhythmias (HR, 1.56), all CVD (HR, 1.31), ischemic heart disease (HR, 1.28), total stroke (HR, 1.18), and all-cause mortality (HR, 1.24). Tertile 3 versus tertile 2 of the QT corrected linear slope was associated with cardiac arrest (HR, 1.22), ventricular dysrhythmias (HR, 1.12), and all-cause mortality (HR, 1.09). Tertile 3 versus tertile 1 of the QT corrected root mean squared error was associated with ventricular dysrhythmias (HR, 1.34), heart failure (HR, 1.28), all-cause mortality (HR, 1.20), all CVD (HR, 1.14), total stroke (HR, 1.08), and ischemic heart disease (HR, 1.07). Conclusions Our results demonstrate improved predictive ability for CVD outcomes using longitudinal information from serial ECGs. Long-term average QT corrected was more strongly associated with CVD outcomes than the linear slope or the root mean squared error. This new evidence is clinically relevant because ECGs are frequently used, noninvasive, and inexpensive.

Aim: The aim was to identify benefit thresholds for clinical variables. We hypothesize, if variables fall below or exceed these threshold levels, systemic amoxicillin/metronidazole may contribute to reducing progression of periodontitis., Material & Methods: This is an explorative per-protocol collective analysis (n = 345) conducted on the placebo-controlled, multi-centre ABPARO trial (ClinicalTrials.gov NCT00707369). Patients received debridement with systemic amoxicillin 500 mg/metronidazole 400 mg (3×/day, 7 days, n = 170) or placebo (n = 175) and maintenance therapy every three months. To identify thresholds, each of the following baseline characteristics was classified into two groups (≥threshold value/ 5 mm (5.2%) at baseline compared to the placebo (9.0%, 11.6%, and 12.5%, respectively; p < 0.005)., Conclusions: The clinical benefits of systemic amoxicillin/metronidazole may depend on periodontitis severity and patients' age., (© 2019 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Objective: With more teeth retained for longer in an ageing population, population-wide periodontal treatment needs may increase. We assessed and projected periodontal treatment needs from 1997 to 2030 in Germany., Methods: Partial-mouth probing-pocket depths (PPDs) from repeated waves (1997, 2005, 2014) of the nationally representative German Oral Health Studies were transformed into full-mouth PPDs via decision-tree-based ensemble-modelling. In line with German healthcare-regulations, teeth with PPD ≥ 4 mm were regarded as needing periodontal treatment. Weighted means were interpolated cross-sectionally by fitting spline-curves and then regressed longitudinally 1997-2030., Results: In 1997, younger adults (35-44 years old) had a mean of 7.4 teeth needing treatment (overall 93.8 million teeth); this decreased to 4.8 teeth (47.3 million teeth) in 2014. For 2030, we project 3.2 teeth (33.7 million teeth). In seniors, an increase was recorded (1997: 4.5 teeth, 33.5 million teeth; 2014: 7.5 teeth, 63.4 million teeth); this is expected to continue until 2030 (to 12.2 teeth, 140.8 million teeth). The cumulative number of teeth needing treatment increased from 2000 (355 million) to 2015 (365 million), and will increase further to 2030 (464 million)., Conclusions: Population-wide periodontal treatment needs may increase until 2030, mainly in the elderly. Concepts for addressing, these growing needs are required., (© 2018 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.)

Context: Complete reporting of intervention details in trials of evidence-based practice (EBP) educational interventions is essential to enable clinical educators to translate research evidence about interventions that have been shown to be effective into practice. In turn, this will improve the quality of EBP education., Objectives: This study was designed to examine the completeness of reporting of EBP educational interventions in published studies and to assess whether missing details of educational interventions could be retrieved by searching additional sources and contacting study authors., Methods: A systematic review of controlled trials that had evaluated EBP educational interventions was conducted using a citation analysis technique. Forward and backward citations of the index articles were tracked until March 2016. The TIDieR (template for intervention description and replication) checklist was used to assess the completeness of intervention reporting. Missing details were sought from: (i) the original publication; (ii) additional publicly available sources, and (iii) the study authors., Results: Eighty-three articles were included; 45 (54%) were randomised controlled trials (RCTs) and 38 (46%) were non-RCTs. The majority of trials (n = 62, 75%) involved medical professionals. None of the studies completely reported all of the main items of the educational intervention within the original publication or in additional sources. However, details became complete for 17 (20%) interventions after contact with the respective authors. The item most frequently missing was 'intervention materials', which was missing in 80 (96%) of the original publications, in additional sources for 77 (93%) interventions, and in 59 (71%) studies after contact with the authors. Authors of 69 studies were contacted; 33 provided the details requested., Conclusions: The reporting of EBP educational interventions is incomplete and remained so for the majority of studies, even after study authors had been contacted for missing information. Collaborative efforts involving authors and editors are required to improve the completeness of reporting of EBP educational interventions., (© 2017 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

Objective: Melatonin improves hepatic perfusion after hemorrhagic shock and may reduce stress-induced gastric lesions. This study was designed to investigate whether pretreatment with melatonin may influence gastric mucosal microcirculatory perfusion (μflow), oxygenation (μHbO 2 ), or intestinal barrier function during physiological and hemorrhagic conditions in dogs., Methods: In a randomized crossover study, five anesthetized foxhounds received melatonin 100 μg kg -1 or vehicle (ethanol 5%) intravenously in the absence or presence of hemorrhagic shock (60 minutes, -20% blood volume). Systemic hemodynamic variables, gastric mucosal perfusion, and oxygenation were recorded continuously; intestinal barrier function was assessed intermittently via xylose absorption., Results: During hemorrhagic shock, melatonin significantly attenuated the decrease in μflow, compared with vehicle (-19±9 vs -43±10 aU, P<.05), without influence on μHbO 2 . A significant increase in xylose absorption was detected during hemorrhage in vehicle-treated dogs, compared with sham-operated animals (13±2 vs 8±1 relative amounts, P<.05); this was absent in melatonin-treated animals (6±1 relative amounts). Melatonin did not influence macrocirculation., Conclusions: Melatonin improves regional blood flow suggesting improved oxygen delivery in gastric mucosa during hemorrhagic shock. This could provide a mechanism for the observed protection of intestinal barrier function in dogs., (© 2017 John Wiley & Sons Ltd.)

Objectives/hypothesis: To evaluate the application of the Flex Robotic System in transoral robotic surgery (TORS)., Study Design: Multicenter, prospective, open-label, single-armed clinical study., Methods: A prospective clinical follow-up multicenter study was performed from July 2014 to October 2015 assessing the safety and efficacy of the Medrobotics Flex Robotic System for access and visualization of the oropharynx, hypopharynx, and larynx as well as for resection of benign and malignant lesions. A total of 80 patients were enrolled. Access and visualization of five anatomic subsites (base of tongue, palatine tonsil area, epiglottis, posterior pharyngeal wall, and false vocal cords) were individually graded by the surgeon. Setup times, access and visualization times, surgical results, and adverse events were documented., Results: The relevant anatomic structures could be exposed and visualized properly in 75 patients, who went on to have a surgical procedure performed with the Flex Robotic System. Access and visualization of the palatine tonsil area, posterior pharyngeal wall, epiglottis, and posterior pharyngeal wall were excellent. However, false vocal cords and vocal cords were more difficult to expose. Seventy-two patients were treated successfully with the Flex Robotic System. There were no serious or unanticipated device-related adverse events caused by the Flex Robotic System., Conclusions: Lesions in the oropharynx, hypopharynx, and larynx could be successfully resected with the Flex Robotic System, specifically developed for TORS. Our study provides evidence that the Flex Robotic System is a safe and effective tool in TORS. Laryngoscope, 2016 127:391-395, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Evaluation of the clinical effect of systemic amoxicillin and metronidazole adjunctively to mechanical debridement at furcation sites., Material and Methods: This is an exploratory per-protocol collective subanalysis from a prospective, randomized, double-blind, multi-centre trial (ClinicalTrials.gov NCT00707369) on the effect of adjunctive systemic amoxicillin 500 mg plus metronidazole 400 mg (3×/day, 7 days) use on furcation involvement in moderate to severe periodontitis. Outcome was the change in frequency of classes of furcation involvement after 27.5 months. Therapy comprised mechanical debridement in conjunction with antibiotic or placebo administration, and maintenance therapy at three months intervals., Results: Three hundred and forty-five patients (175 placebo, 170 antibiotics) with 6576 furcation sites (class 0 2956; class I 2370; class II 886; class III 364) were examined (3472 placebo, 3104 antibiotics). Pocket reduction/attachment gain at the furcation sites was noticeably better after antibiotics (1.2/0.6 mm) than after placebo (0.7/0.2 mm) 27.5 months after therapy. However, most furcation degrees were unchanged (placebo 61.5%/antibiotics 62.2%), more sites improved than deteriorated (20.3%/18.2%, 22.1%/15.7% respectively) and no differences in the change of furcation degrees between treatments could be detected., Conclusion: Compared to placebo, prescription of adjunctive systemic antibiotics failed to show clinically relevant benefit with regard to furcation class involvement., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The aim of this study was to investigate the effect of mandibular third-molar (M3) removal on periodontal health of adjacent second molars (M2). Probing pocket depths (PPD) and probing attachment levels (PAL) have been described for primary outcome. As cofactors involved, gender, complications, two suture materials and two types of impaction were chosen as secondary outcomes., Materials and Methods: Seventy-eight patients (49 female; mean age: 16.0 ± 2.0 years) with 78 asymptomatic impacted mandibular M3 were included in this study. Plaque and gingival indices, PPD and PAL were recorded prior and 6 months after surgery. Impacted teeth were classified as either fully impacted (completely within in the bone) or submucosal (fully covered by oral mucosa)., Results: Average baseline PPD was reduced from 3.3 mm to 2.6 mm after 6 months (p < 0.05). Average PAL was reduced from 3.0 to 2.5 mm (p < 0.05). Preoperative PPD ≥ 4 mm at the distolingual and distobuccal sites was positively correlated with clinical improvement (PPD: p < 0.05; PAL: p < 0.05). The impaction class was also identified as positive cofactor for PPD (p = 0.039), but not for PAL., Conclusions: Young patients may benefit from an early removal of mandibular M3, especially in the presence of certain cofactors., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: We investigated the long-term impact of adjunctive systemic antibiotics on periodontal disease progression. Periodontal therapy is frequently supplemented by systemic antibiotics, although its impact on the course of disease is still unclear., Material & Methods: This prospective, randomized, double-blind, placebo-controlled multi-centre trial comprising patients suffering from moderate to severe periodontitis evaluated the impact of rational adjunctive use of systemic amoxicillin 500 mg plus metronidazole 400 mg (3x/day, 7 days) on attachment loss. The primary outcome was the percentage of sites showing further attachment loss (PSAL) ≥1.3 mm after the 27.5 months observation period. Standardized therapy comprised mechanical debridement in conjunction with antibiotics or placebo administration, and maintenance therapy at 3 months intervals., Results: From 506 participating patients, 406 were included in the intention to treat analysis. Median PSAL observed in placebo group was 7.8% compared to 5.3% in antibiotics group (Q25 4.7%/Q75 14.1%; Q25 3.1%/Q75 9.9%; p < 0.001 respectively)., Conclusions: Both treatments were effective in preventing disease progression. Compared to placebo, the prescription of empiric adjunctive systemic antibiotics showed a small absolute, although statistically significant, additional reduction in further attachment loss. Therapists should consider the patient's overall risk for periodontal disease when deciding for or against adjunctive antibiotics prescription., (© 2015 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.)

Aim: We aimed to assess changes of periodontal status in Germany., Materials & Methods: The Studies of Health in Pomerania (SHIP) are two cross-sectional population-based studies conducted during 1997-2001 (SHIP-0, 20-81 years, n = 3736) and 2008-2012 (SHIP-Trend, 20-84 years, n = 3622) in northeast Germany. The German Oral Health Studies (DMS, 35-44 and 65-74 years) are national cross-sectional population-based surveys conducted in 1997 (DMS III, n = 1454) and 2005 (DMS IV, n = 1668), whose results were separately reported for West and East Germany. Prevalences, percentages and numbers of teeth affected were defined., Results: In SHIP, prevalence of attachment loss (AL) ≥ 3 mm decreased from 89.7% (95% confidence interval (CI): 88.6-90.8) to 85.1% (95%CI: 83.9-86.3) (p < 0.05) and the mean extent reduced from 62.8% (95%CI: 61.7-63.8) to 55.9% (95%CI: 54.9-56.9) (p < 0.05). Probing depth (PD) ≥ 4 mm and the respective extent remained unchanged. In West Germany, AL ≥ 3 mm decreased for 35-44-year-olds and increased for 65-74-year-olds (p < 0.05). In SHIP and DMS, the number of teeth in dentates increased significantly in all age groups., Conclusions: Prevalences and extents of AL improved almost in all age categories in SHIP and West German adults, whereas PDs remained unchanged. Nonetheless, the improvement of periodontal conditions implies an increase of treatment needs regarding moderately diseased teeth because of simultaneous increases of the number of present teeth., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)