Early wound healing score (EHS): an intra- and inter-examiner reliability study

The early wound healing score (EHS) was introduced to assess early wound healing of periodontal soft tissues after surgical incision. The purpose of this study is to evaluate the intra- and inter-examiner reliability of the EHS. Six examiners with different levels of training and clinical focus were enrolled. Each examiner was trained on the use of the EHS before starting the study. Thereafter, 63 photographs of three different types of surgical incisions taken at day 1, 3 or 7 post-operatively were independently evaluated according to the proposed assessment method. A two-way random intra-class correlation coefficient (ICC) and 95% confidence interval (CI) were used to analyze the intra- and inter-examiner reliability for the EHS. The inter-examiner reliability for the EHS was 0.828 (95% CI: 0.767-0.881). The intra-examiner reliability ranged between 0.826 (95% CI: 0.728-0.891) and 0.915 (95% CI: 0.856-0.950). The results therefore show an "almost perfect agreement" for intra- and inter-examiner reliability. The EHS provides a system for reproducible repeated ratings for the early healing assessment of incisions of periodontal soft tissues. Even when used by examiners with different clinical experience and specialty, it shows a high correlation coefficient

Reproducibility is Nothing without Correctness: The Importance of Testing Code in NLP

Despite its pivotal role in research experiments, code correctness is often presumed only on the basis of the perceived quality of the results. This comes with the risk of erroneous outcomes and potentially misleading findings. To address this issue, we posit that the current focus on result reproducibility should go hand in hand with the emphasis on coding best practices. We bolster our call to the NLP community by presenting a case study, in which we identify (and correct) three bugs in widely used open-source implementations of the state-of-the-art Conformer architecture. Through comparative experiments on automatic speech recognition and translation in various language settings, we demonstrate that the existence of bugs does not prevent the achievement of good and reproducible results and can lead to incorrect conclusions that potentially misguide future research. In response to this, this study is a call to action toward the adoption of coding best practices aimed at fostering correctness and improving the quality of the developed software

Beclomethasone/formoterol fixed combination for the management of asthma: patient considerations

Drugs for asthma and other chronic obstructive diseases of the lungs should be preferably delivered by the inhalation route to match therapeutic effects with low systemic exposure. Inhaled drugs are delivered to the lungs via different devices, mainly metered dose inhalers and dry powder inhalers, each characterized by specific inhaler technique and instructions for use. The patient–device interaction is part of the prescribed therapy and can have a relevant impact on adherence and clinical outcomes. The most suitable device should be considered for each patient to assure the correct drug intake and adherence to the prescribed therapy. The development of new drugs/devices in the past decades improved the compliance with inhaler and possibly drug delivery to the bronchi. The present review focuses on the recently developed beclomethasone/formoterol extrafine fixed combination and technical aspects of drug delivery to the lungs in patient’s perspective

Knowledge and attitude towards retrograde peri-implantitis among Italian implantologists: a cross-sectional survey

Abstract Background: Retrograde peri-implantitis (RPI) is a pathological entity with an unclear etiology (e.g., overheating during implant insertion, residual infection of the tooth replaced by the implant or the endodontic lesion of neighboring teeth) and an extremely low prevalence and has been scarcely investigated. Therefore, the aim of this cross-sectional survey was to evaluate the knowledge and attitude of Italian implantologists regarding RPI. Methods: An anonymous questionnaire was sent via email to implantologists randomly selected, including a section about demographic information and questions related to RPI origin, radiographic representation, symptoms and treatment options. All questions were multiple answer and close-ended. Binomial logistic regression was performed to investigate the relationship between correct answers and the following independent variables: age, years of experience and number of dental implants placed per year. Results: In total, 475 implantologists completed the questionnaire, with a response rate of 46.3%. Based on the results of the study, incorrect answers were associated with less experienced participants (<80 implants/year) for all questions evaluated, with the exception of treatment strategies. Furthermore, 26.7% of the survey takers did not recognize radiographic representation of RPI and 35.5% picked "implant removal" when asked about treatment modality. Conclusions: The majority of participants were able to recognize symptoms and indicated the probable causes of RPI; however, around 30% of them showed very limited knowledge of available management strategies

Iodothyronine deiodinases and reduced sensitivity to thyroid hormones.

Iodothyronine deiodinases are selenoproteins that regulate thyroid hormone metabolism. Of the three types of deiodinases, type 2 is the major regulator of intracellular triiodothyronine concentration in both the hypothalamus and pituitary, and therefore the major regulator of thyrotropin secretion. A defect in iodothyronine deiodinase activity can lead to a reduced sensitivity to thyroid hormones action and the most recent literature includes these defects in the so-called "syndromes of reduced sensitivity to thyroid hormones". To date, the pathogenic variants of the selenocysteine insertion sequence-binding protein 2 (SECISBP2) gene are the first and only inherited disorder of iodothyronine metabolism described. Moreover, there is a growing interest in understanding the possible role of polymorphisms of DIO1 and DIO2 genes in some pathological conditions and in determining the requirement of levothyroxine replacement and the role of combined levothyroxine-liothyronine therapy in carrying subjects affected by hypothyroidism and who need replacement therapy. Results on this topic are still conflicting and more studies are needed to assess the efficacy of combined levothyroxine-liothyronine replacement therapy in this subset of patients

Breast Cancer Following Hodgkin's Disease

The advent of effective chemo-radiotherapy has made Hodgkin Disease (HD) a highly curable malignancy, but the great improvement in survival rates allowed the observation in long-term survivors of several treatment complications. Secondary malignancies are the most serious complications and breast cancer (BC) represents the most common solid tumor among female survivors. The aim of our analysis is to describe the clinico-pathological characteristics and management of BC occurred after HD treatment. Between 1960 and 2003, 2,039 patients were treated for HD at the Department of Radiotherapy-Oncology of the Florence University. In this study we considered 1,538 patients on whom a minimum follow up of 6 months had been obtained. Of these, 725 were women. The most represented histological subtype was nodular sclerosis (50.6%). Supradiaphragmatic alone or with subdiaphragmatic complementary extended field radiotherapy was delivered to 83.1% of patients while supradiaphragmatic involved field radiotherapy was delivered to 10.7% of patients. Concerning the characteristics and incidence of BC, we focused our analysis exclusively on the female group. We found that BC occurred in 39, with an overall incidence of 5.4%. The mean interval after Hodgkin treatment was 19.5 years (SD +/- 9.0). The median age of BC diagnosis was 50.8 years (SD +/- 13.3) while the median age of Hodgkin diagnosis was 31.2 years (SD +/- 14.5). Thirty-seven women received mediastinal irradiation. We observed a decreasing trend of the secondary BC incidence with increasing age of Hodgkin treatment with the maximum incidence registered in women treated at age 20 or younger. In Our Institute we perform a whole life follow up and recommend that annual mammography begins 10 years after HD treatment or, in any case, not later than age 40

Phenomenology of COPD: interpreting phenotypes with the ECLIPSE study

The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study was a large 3-year observational multicentre international study aimed at defining COPD phenotypes and identifying biomarkers and/or genetic parameters that help to predict disease progression. The study has contributed to a better understanding of COPD heterogeneity, with the characterization of clinically important subtypes/phenotypes of patients, such as the frequent exacerbators or patient with persistent systemic inflammation, who may have different prognosis or treatment requirements. Because of the big amount of information that is starting to be produced from metabolomic, proteomic and genomic approaches, one of the biggest challenges is the integration of data in a biological prospective such as clinical prognosis and response to medicinal products. In this article we highlight some of the progress in phenotyping the heterogeneity of the disease that have been made thanks to the analyses of this longitudinal study

A Peptide Nucleic Acid (PNA) Masking the miR-145-5p Binding Site of the 3'UTR of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mRNA Enhances CFTR Expression in Calu-3 Cells

Peptide nucleic acids (PNAs) have been demonstrated to be very useful tools for gene regulation at different levels and with different mechanisms of action. In the last few years the use of PNAs for targeting microRNAs (anti-miRNA PNAs) has provided impressive advancements. In particular, targeting of microRNAs involved in the repression of the expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is defective in cystic fibrosis (CF), is a key step in the development of new types of treatment protocols. In addition to the anti-miRNA therapeutic strategy, inhibition of miRNA functions can be reached by masking the miRNA binding sites present within the 3'UTR region of the target mRNAs. The objective of this study was to design a PNA masking the binding site of the microRNA miR-145-5p present within the 3'UTR of the CFTR mRNA and to determine its activity in inhibiting miR-145-5p function, with particular focus on the expression of both CFTR mRNA and CFTR protein in Calu-3 cells. The results obtained support the concept that the PNA masking the miR-145-5p binding site of the CFTR mRNA is able to interfere with miR-145-5p biological functions, leading to both an increase of CFTR mRNA and CFTR protein content

The shed P2X7 receptor is an index of adverse clinical outcome in COVID-19 patients

Introduction: The pathophysiology of the Corona Virus Disease 2019 (COVID-19) is incompletely known. A robust inflammatory response caused by viral replication is a main cause of the acute lung and multiorgan injury observed in critical patients. Inflammasomes are likely players in COVID-19 pathogenesis. The P2X7 receptor (P2X7R), a plasma membrane ATP-gated ion channel, is a main activator of the NLRP3 inflammasome, of the ensuing release of inflammatory cytokines and of cell death by pyroptosis. The P2X7R has been implicated in COVID-19-dependent hyperinflammation and in the associated multiorgan damage. Shed P2X7R (sP2X7R) and shed NLRP3 (sNLRP3) have been detected in plasma and other body fluids, especially during infection and inflammation. Methods: Blood samples from 96 patients with confirmed SARS-CoV-2 infection with various degrees of disease severity were tested at the time of diagnosis at hospital admission. Standard haematological parameters and IL-6, IL-10, IL-1β, sP2X7R and sNLRP3 levels were measured, compared to reference values, statistically validated, and correlated to clinical outcome. Results: Most COVID-19 patients included in this study had lymphopenia, eosinopenia, neutrophilia, increased inflammatory and coagulation indexes, and augmented sNLRP3, IL-6 and IL-10 levels. Blood concentration of sP2X7R was also increased, and significantly positively correlated with lymphopenia, procalcitonin (PCT), IL-10, and alanine transaminase (ALT). Patients with increased sP2X7R levels at diagnosis also showed fever and respiratory symptoms, were more often transferred to Pneumology division, required mechanical ventilation, and had a higher likelihood to die during hospitalization. Conclusion: Blood sP2X7R was elevated in the early phases of COVID-19 and predicted an adverse clinical outcome. It is suggested that sP2X7R might be a useful marker of disease progression

Reliability assessment of the 2018 classification case definitions of peri-implant health, peri-implant mucositis, and peri-implantitis

Background: The purpose of this study was to evaluate the reliability and accuracy in the assignment of the case definitions of peri-implant health and diseases according to the 2018 Classification of Periodontal and Peri-implant Diseases and Conditions. MethodsTen undergraduate students, 10 general dentists, and 10 experts in implant dentistry participated in this study. All examiners were provided with clinical and radiographic documentation of 25 dental implants. Eleven out the 25 cases were also accompanied by baseline readings. Examiners were asked to define all cases using the 2018 classification case definitions. Reliability among examiners was evaluated using the Fleiss kappa statistic. Accuracy was estimated using percentage of complete agreement and quadratic weighted kappa for pairwise comparisons between each rater and a gold standard diagnosis. ResultsThe Fleiss kappa was 0.50 (95% CI: 0.48 to 0.51) and the mean quadratic weighted kappa value was 0.544. Complete agreement with the gold standard diagnosis was achieved in 59.8% of the cases. Expertise in implantology affected accuracy positively (p < 0.001) while the absence of baseline readings affected it negatively (p < 0.001). ConclusionBoth reliability and accuracy in assigning case definitions to dental implants according to the 2018 classification were mostly moderate. Some difficulties arose in the presence of specific challenging scenarios