Effects of periodontal therapy on white blood cell count and levels of transforming growth factor beta in serum of subjects with severe periodontitis

This study aimed to investigate the effects of nonsurgical periodontal therapy on white blood cell (WBC) count and levels of transforming growth factor beta (TGF—β) in serum from subjects with severe periodontitis. Serum from 28 subjects with periodontitis (mean age: 34.36±6.24; 32% men) and 27 healthy controls (mean age: 33.18±6.42; 33% men) were collected prior to therapy. Blood samples were obtained from 23 subjects who completed therapy (9—12 months). A well—controlled periodontal treatment protocol was established in three stages: mechanical periodontal therapy (scaling and root planning), reinstrumentation of dental sites, and supportive periodontal therapy. Periodontal and systemic parameters such as the total number of WBCs and TGF—β levels, accessed by enzyme—linked immunosorbent assay (ELISA), were included. After therapy, all clinical periodontal parameters decreased (

Influence of Various Light Timber Retrofit Layouts on the Dynamic Response of Typical Duch Masonry Terraced Houses

A majority of the residential building stock in Groningen (The Netherlands), which has been lately exposed to low intensity ground motions due to gas extraction, consists of unreinforced masonry (URM) structures not originally designed to withstand earthquakes. Amongst them, the terraced house building typology proved to be particularly vulnerable towards horizontal actions. Experimental results from a recently performed shake-table test on a full-scale terraced house prototype, characterised by the presence of a timber retrofitting system, seem to indicate that the dynamic response of these structures might be consistently improved through the employment of such a cost-effective light retrofitting solution. In this work, an advanced discontinuum-based model, implemented in the framework of the Applied Element Method (AEM), is developed to extend experimental results and to numerically investigate the influence of a number of additional timber retrofit layouts, characterised by different geometrical configurations, on the building behaviour. Each timber component was explicitly represented in the AEM models to represent the possible interaction among URM walls and the retrofitting system. First, the proposed modelling strategy is validated against experimental tests on both non-retrofitted and retrofitted URM panels subjected to cyclic shear compression loading. Then, calibrated mechanical parameters were directly implemented in the full-scale building model. Given the good agreement between numerical and experimental outcomes in terms of both damage evolution and hysteretic response, a comprehensive parametric study was undertaken. Numerical evidence seems to suggest that the employment of different retrofit layouts may have a significant influence on the dynamic behaviour of the selected building typology

ATAC-clock: An aging clock based on chromatin accessibility.

The establishment of aging clocks highlighted the strong link between changes in DNA methylation and aging. Yet, it is not known if other epigenetic features could be used to predict age accurately. Furthermore, previous studies have observed a lack of effect of age-related changes in DNA methylation on gene expression, putting the interpretability of DNA methylation-based aging clocks into question. In this study, we explore the use of chromatin accessibility to construct aging clocks. We collected blood from 159 human donors and generated chromatin accessibility, transcriptomic, and cell composition data. We investigated how chromatin accessibility changes during aging and constructed a novel aging clock with a median absolute error of 5.27 years. The changes in chromatin accessibility used by the clock were strongly related to transcriptomic alterations, aiding clock interpretation. We additionally show that our chromatin accessibility clock performs significantly better than a transcriptomic clock trained on matched samples. In conclusion, we demonstrate that the clock relies on cell-intrinsic chromatin accessibility alterations rather than changes in cell composition. Further, we present a new approach to construct epigenetic aging clocks based on chromatin accessibility, which bear a direct link to age-related transcriptional alterations, but which allow for more accurate age predictions than transcriptomic clocks

Low drug levels and thrombotic complications in high-risk atrial fibrillation patients treated with direct oral anticoagulants

Essentials Direct oral anticoagulants (DOACs) do not require laboratory monitoring currently. DOAC specific measurements were performed at trough in patients with atrial fibrillation. Patients who developed thromboembolic events showed lower DOAC plasma levels. This study supports the concept of measuring DOAC levels at steady state. Summary: Background Direct oral anticoagulants (DOACs) are administered at fixed doses without the need for dose adjustment according to laboratory testing. High interindividual variability in drug blood levels has been shown with all DOACs. To evaluate a possible relationship between DOAC C-trough anticoagulant levels and thromboembolic events, 565 consecutive naive patients with atrial fibrillation (AF) were enrolled in this study performed within the START Laboratory Registry. Methods DOAC-specific measurements (diluted thrombin time or anti-activated factor II calibrated for dabigatran; anti-activated FX calibrated for rivaroxaban or apixaban) at C-trough were performed locally at steady state within 15–25 days after the start of treatment. For each DOAC, the interval of C-trough levels, from the limit of quantification to the highest value, was subdivided into four equal classes, and results were attributed to these classes; the median values of results were also calculated. Thromboembolic complications occurring during 1 year of follow-up were recorded. Results Thromboembolic events (1.8%) occurred in 10 patients who had baseline C-trough levels in the lowest class of drug levels. The incidence of thromboembolic events among patients with DOAC C-trough levels in the lowest level class was 2.4%, and that in the remaining groups was 0%. The patients with thrombotic complications also had a higher mean CHA2DS2-VASc score than that of the total patient population: 5.3 (95% confidence interval [CI] 4.3–6.3 versus 3.0 (95% CI 2.9–3.1). Conclusion In this study cohort, thrombotic complications occurred only in DOAC-treated AF patients who had very low C-trough levels, with a relatively high CHA2DS2-VASc score. Larger studies are warranted to confirm these preliminary observations. © 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis

Acute tryptophan depletion Moja-De: a method to study central nervous serotonin function in children and adolescents

Serotonin (5-HT) is widely implicated as a key neurotransmitter relevant to a range of psychiatric disorders and psychological processes. The role of central nervous 5-HT function underlying these processes can be examined through serotonergic challenge methodologies. Acute tryptophan depletion (ATD) is a key challenge method whereby a diminished dietary intake of tryptophan—the amino acid precursor to brain 5-HT synthesis—results in temporary diminished central nervous 5-HT synthesis. While this particular methodology has been used in adult populations, it was only recently that modifications were made to enable the use of ATD in child and adolescent populations. Additionally, the Moja-De modification of the ATD challenge methodology has demonstrated benefits over other ATD techniques used previously. The aim of this protocol paper is to describe the ATD Moja-De methodology in detail, its benefits, as well as studies that have been conducted to validate the procedure in child and adolescent samples. The ATD Moja-De protocol provides a potential methodology for investigating the role of central nervous 5-HT via manipulation of brain tryptophan availability in human psychopathology from a developmental viewpoint

Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study

Objectives: Canakinumab is an IL-1? antibody that neutralises the activity of IL-1?. This study examined the efficacy and safety of canakinumab in patients with moderate COVID-19-related pneumonia. Design: This study aimed to evaluate the reduction in duration of hospitalisation with adequate oxygen status. Forty-eight patients with moderate COVID-19-related pneumonia were asked to participate in the prospective case-control study: 33 patients (cases) signed informed consent and received canakinumab (Cohort 1) and 15 patients (Controls) refused to receive the experimental drug and received institutional standard of care (Cohort 2). Results: Hospital discharge within 21 days was seen in 63% of patients in Cohort 1 vs. 0% in Cohort 2 (median 14 vs. 26 days, respectively; p < 0.001). There was significant clinical improvement in ventilation regimes following administration of canakinumab compared with Cohort 2 (Stuart-Maxwell test for paired data, p < 0.001). Patients treated with canakinumab experienced a significant increase in PaO2: FiO2 (p < 0.001) and reduction in lung damage by CT (p = 0.01), along with significant decreases in immune/inflammation markers that were not observed in Cohort 2. Only mild side-effects were seen in patients treated with canakinumab; survival at 60 days was 90.0% (95% CI 71.9?96.7) in patients treated with canakinumab and 73.3% (95% CI 43.6?89.1) for Cohort 2. Conclusions: Treatment with canakinumab in patients with COVID-19-related pneumonia rapidly restored normal oxygen status, decreased the need for invasive mechanical ventilation, and was associated with earlier hospital discharge and favourable prognosis versus standard of care. ? 2021 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-n

Benchmark data and model independent event classification for the large hadron collider

We describe the outcome of a data challenge conducted as part of the Dark Machines (https://www.darkmachines.org) initiative and the Les Houches 2019 workshop on Physics at TeV colliders. The challenged aims to detect signals of new physics at the Large Hadron Collider (LHC) using unsupervised machine learning algorithms. First, we propose how an anomaly score could be implemented to define model-independent signal regions in LHC searches. We define and describe a large benchmark dataset, consisting of > 1 billion simulated LHC events corresponding to 10 fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV. We then review a wide range of anomaly detection and density estimation algorithms, developed in the context of the data challenge, and we measure their performance in a set of realistic analysis environments. We draw a number of useful conclusions that will aid the development of unsupervised new physics searches during the third run of the LHC, and provide our benchmark dataset for future studies at https://www.phenoMLdata.org. Code to reproduce the analysis is provided at https://github.com/bostdiek/DarkMachines-UnsupervisedChallenge

Inter-society consensus for the use of inhaled corticosteroids in infants, children and adolescents with airway diseases

Background: In 2019, a multidisciplinary panel of experts from eight Italian scientific paediatric societies developed a consensus document for the use of inhaled corticosteroids in the management and prevention of the most common paediatric airways disorders. The aim is to provide healthcare providers with a multidisciplinary document including indications useful in the clinical practice. The consensus document was intended to be addressed to paediatricians who work in the Paediatric Divisions, the Primary Care Services and the Emergency Departments, as well as to Residents or PhD students, paediatric nurses and specialists or consultants in paediatric pulmonology, allergy, infectious diseases, and ear, nose, and throat medicine. Methods: Clinical questions identifying Population, Intervention(s), Comparison and Outcome(s) were addressed by methodologists and a general agreement on the topics and the strength of the recommendations (according to the GRADE system) was obtained following the Delphi method. The literature selection included secondary sources such as evidence-based guidelines and systematic reviews and was integrated with primary studies subsequently published. Results: The expert panel provided a number of recommendations on the use of inhaled corticosteroids in preschool wheezing, bronchial asthma, allergic and non-allergic rhinitis, acute and chronic rhinosinusitis, adenoid hypertrophy, laryngitis and laryngospasm. Conclusions: We provided a multidisciplinary update on the current recommendations for the management and prevention of the most common paediatric airways disorders requiring inhaled corticosteroids, in order to share useful indications, identify gaps in knowledge and drive future research

Proposta di una “checklist” per il prelievo di sangue venoso

The collection of venous blood is central in clinical laboratory activity. Although there is widespread perception that this practice is simple and free of complications and side effects, it is undeniable that the vast majority of laboratory errors arises from ignorance, incompetence or negligence during venipuncture. It has hence become advisable to prepare a document in simplified form of checklist, consisting of a concise but comprehensive list of activities to be completed or verified in order to prevent errors during venous blood collection. In the intention of authors, this synthetic checklist is a modular tool, adaptable to different local contexts, it can be easily and gradually implemented, it is supported by scientific evidence and consensus of experts and created with the support of different healthcare professionals and it is adherent to the best practices and requires minimal resources for implementation. It is reasonable to assume that this checklist may be able to withstand system and individual changes, strengthening the standards for safety of both operators and patients, limiting potential failure patterns. We hope that the checklist may be implemented in all healthcare facilities where routine venous blood collection is performed, after adaptation to suit characteristics of local organization