Multiple drug-susceptibility screening in Mycobacterium bovis: new nucleotide polymorphisms in the embB gene among ethambutol susceptible strains

Objectives: Pyrazinamide-resistant Mycobacterium bovis isolates of animal origin were assessed for drug susceptibility to five antituberculosis drugs by the agar based Middlebrook 7H11 method as gold standard as well as by a simplified, dichotomous resazurin microtitre assay (d-REMA). Methods: A total of 53 M. bovis isolates were typed and tested against isoniazid, rifampin, streptomycin, ethambutol, kanamycin and the control drug pyrazinamide. On the basis of the results obtained, pncA and embB genes were PCR-amplified and DNA-sequenced for all isolates. Results: All M. bovis isolates, classified into 21 spoligotype/MIRU-VNTR profiles, were resistant to pyrazinamide by both methods, as expected. The pncA gene sequencing confirmed the presence of the resistance-conferring H57D mutation. All strains were found to be susceptible to the other five drugs by the agar based gold standard method. The d-REMA was in agreement with these results for all five drugs, with the exception of 12 isolates, which showed ambiguous and therefore inconclusive results in ethambutol testing. Mutations in the embB gene were observed in all 53 isolates: four new single-nucleotide polymorphisms were identified. No association was found between embB genetic profiles and ethambutol resistance results by the gold standard. Conclusion: All M. bovis isolates were sensitive to the most common antituberculosis drugs used for treatment. There was a good agreement between the d-REMA assay and the agar based reference method. Among ethambutol susceptible isolates, four new embB mutations were found

The effects of low doses of pregabalin on morphine analgesia in advanced cancer patients

Abstract OBJECTIVES: The aim of this study was to evaluate the opioid response in patients receiving morphine and pregabalin, independently from the presumed pain mechanisms, in comparison with patients receiving morphine treatment only. METHODS: A multicenter prospective randomized controlled study was carried out in a sample of 70 advanced cancer patients with pain requiring strong opioids. Thirty-five patients (group MO) were randomized to receive sustained-release morphine using initial doses of 60 mg/day. Thirty-five patients (group MO-PR) were randomized to start the same morphine doses and pregabalin in increasing doses, starting with 25 mg/day up to 150 mg/day in one week. The following data were also recorded before starting the treatments (T0) and then at week intervals for four weeks (W1-4): age, gender, primary cancer and known metastases, pain causes and mechanisms, symptoms associated with opioid therapy, pain intensity, Brief Pain Inventory (BPI), morphine doses and escalation indexes (OEIs), and quality of life. RESULTS: Forty-eight patients completed the study, twenty-eight and sixteen patients in group MO and MO-PR, respectively. Twenty patients were females, the mean age was 65.5 (± 10.3), and the mean Karnofsky status was 66.0 (± 18.9). No differences between groups were found in age (P = 0.839), Karnofsky status (P = 0.741), opioid doses as well as escalation indexes (OEI mg, P = 0.260, and OEI%, P = 0.270). No differences between the two groups were found in quality of life and all BPI items. CONCLUSION: The use of low doses of pregabalin added to morphine therapy in advanced cancer patients does not seem to provide advantageous analgesic effects, despite limitations of the present study due to the number of drop-outs

An Italian Multicenter Study on the Epidemiology of Respiratory Syncytial Virus During SARS-CoV-2 Pandemic in Hospitalized Children

Since the beginning of 2020, a remarkably low incidence of respiratory virus hospitalizations has been reported worldwide. We prospectively evaluated 587 children, aged <12 years, admitted for respiratory tract infections from 1 September 2021 to 15 March 2022 in four Italian pediatric hospitals to assess the burden of respiratory viruses during the COVID-19 pandemic in Italy. At admission, a Clinical Respiratory Score was assigned and nasopharyngeal or nasal washing samples were collected and tested for respiratory viruses. Total admissions increased from the second half of October 2021 to the first half of December 2021 with a peak in early November 2021. The respiratory syncytial virus (RSV) incidence curve coincided with the total hospitalizations curve, occurred earlier than in the pre-pandemic years, and showed an opposite trend with respect to the incidence rate of SARS-CoV-2. Our results demonstrated an early peak in pediatric hospitalizations for RSV. SARS-CoV-2 may exhibit a competitive pressure on other respiratory viruses, most notably RSV

Quality assurance for automatically generated contours with additional deep learning

Objective: Deploying an automatic segmentation model in practice should require rigorous quality assurance (QA) and continuous monitoring of the model’s use and performance, particularly in high-stakes scenarios such as healthcare. Currently, however, tools to assist with QA for such models are not available to AI researchers. In this work, we build a deep learning model that estimates the quality of automatically generated contours. Methods: The model was trained to predict the segmentation quality by outputting an estimate of the Dice similarity coefficient given an image contour pair as input. Our dataset contained 60 axial T2-weighted MRI images of prostates with ground truth segmentations along with 80 automatically generated segmentation masks. The model we used was a 3D version of the EfficientDet architecture with a custom regression head. For validation, we used a fivefold cross-validation. To counteract the limitation of the small dataset, we used an extensive data augmentation scheme capable of producing virtually infinite training samples from a single ground truth label mask. In addition, we compared the results against a baseline model that only uses clinical variables for its predictions. Results: Our model achieved a mean absolute error of 0.020 ± 0.026 (2.2% mean percentage error) in estimating the Dice score, with a rank correlation of 0.42. Furthermore, the model managed to correctly identify incorrect segmentations (defined in terms of acceptable/unacceptable) 99.6% of the time. Conclusion: We believe that the trained model can be used alongside automatic segmentation tools to ensure quality and thus allow intervention to prevent undesired segmentation behavior

[Bicuspid aortic valve and its complications: from molecules to surgery]

: Bicuspid aortic valve is a relevant condition to the epidemiology of degenerative (stenosis, regurgitation) and infective (endocarditis) aortic valve disease. This review will address the topics of treatment of those valvular complications, focusing on the peculiar aspects distinguishing them from tricuspid aortic valve diseases, in particular transcatheter treatment of stenosis, valve repair/sparing surgery for regurgitation, prevention of endocarditis. Bicuspid aortopathy represents a clinical entity with remarkable prognostic, and likely also pathogenetic, heterogeneity. A deeper understanding of the tissue and molecular factors as well as flow-related and biomechanical aspects of its development and progression could help guiding better risk stratification (identification of more severe forms, prevention of acute aortic dissection), allowing for a personalized therapeutic approach. The present review will also summarize the state of the art about bicuspid aortopathy pathogenesis, moreover forwarding new hypotheses for the interpretation of the many sparse pieces of evidence currently available

Latest Advances in the Treatment of Bicuspid Aortic Valve

: Bicuspid aortic valve (BAV) is the most frequent congenital cardiac defect, and affects 0.5-2% of live births. Almost half of BAV subjects develop different degrees of valvular dysfunction during their lifetime. In both echocardiographic cohorts and surgical series, pure aortic regurgitation is significantly less common than stenosis. BAV also carries a higher risk of aortic aneurysm, aortic dissection or aortic valve endocarditis compared to the general population. Once aortic insufficiency reaches threshold criteria for surgical treatment, the valve has to be replaced (conventional aortic valve replacement, the outcomes of which are well established) or repaired. Repair techniques for regurgitant BAVs and valve-sparing surgery for BAV-related aneurysms have evolved remarkably over the past several decades. Improvements in our understanding of the mechanisms of normal and pathological BAV function and the development of criteria and techniques to address all the pathologic components of valve and root have supported better repair results. The more frequent stenotic BAV is treated by prosthetic valve replacement or, in recent years, by trans-catheter prosthetic replacement (TAVR), the application of which in the BAV setting is increasing, as with tricuspid aortic valve (TAV) stenosis, especially since indications are extended to medium-risk patients. It has been reported that the risk of paravalvular leak and/or prosthesis malposition is higher in BAV than in TAV stenosis, due to the more elliptical annulus and the calcified raphe of the bicuspid valve. New-generation balloon-expandable devices seem to be capable of lowering the rates of these complications. As research in this field keeps filling in the gaps in current knowledge about bicuspid malformation and its common complications, further advancements in their treatment are awaited

Update on biomarkers of bicuspid aortic disease: still a long road to run?

Management criteria of patients with aortopathy are based mainly on dimensional parameters, namely aortic diameter and growth rate (1), with the rationale that elective treatment is aimed at preventing acute aortic events (AAEs), i.e., aortic dissection or rupture, and that the risk of AAEs is predicted by the aortic diameter. However, this principle has been questioned by some evidence: the majority of acute aortic dissections occur at diameters well below the threshold for prophylactic surgery, and their number may be even underestimated since an acute increase in aortic diameter occurs as the aorta dissects (2)

Work-family organizational support as a predictor of work-family conflict, enrichment, and balance: crossover and spillover effects in dual-income couples

Dual-income families are challenged by several issues in terms of conciliation between the working environment, the family context and the management of children. This paper, consistently with spillover and crossover hypotheses, aimed at examining the intermediate role of work-family balance, linking on work-family organizational support, work-to-family enrichment and conflict as predictors, and on family-life satisfaction of dual-income families’ both partners as final outcomes. It was expected that work-family organizational support would be related to lower work-to-family conflict and higher enrichment and, through them, with higher work-family balance; moreover, a positive association between work-family balance and family-life satisfaction of both partners was assumed. 390 double-income heterosexual couples participated in our study; 76.2% of the couples were parents. Structural equation modelling results showed that work-family balance was negatively predicted by work-to-family conflict and positively predicted by work-to-family enrichment. Furthermore, work-family organizational support positively predicted work-to-family enrichment, which also mediated its effect on work-family balance. Crossover and spillover effects were also confirmed, given that positive associations between work-family balance and family-life satisfaction of both partners were found. Implications for future research and organizational interventions aimed at both improving work-family balance and promoting greater satisfaction in family life are discussed

A Crossover Study From a Gender Perspective: The Relationship Between Job Insecurity, Job Satisfaction, and Partners’ Family Life Satisfaction

Background: In the last years, many changes have involved the labor context: new ways of working, more flexibility and uncertainty, new and more insecure job contracts. In this framework, perceived job insecurity, worker’s perception about potential involuntary job loss, has received renewed interest, also for those workers with a permanent contract in Italy. Consequences of job insecurity on work-related outcomes such as job satisfaction have been demonstrated; nevertheless, its possible effects outside the workplace seem to be underestimated so far. Moreover, literature highlighted the importance to consider gender as a possible moderator in the relationship between one partner’s stressors and the other partner’s strain. Aim: According to spillover and crossover theories, this study aim was to investigate the relationship between job insecurity and family life satisfaction of both partners, through the mediation of job satisfaction. The model has been simultaneously tested in two groups, women and men, in a sample of permanent workers. Method: The research involved a convenience sample of 344 employees with permanent contract (53% female) from different occupational sectors. Participants (focal persons) and their partners filled out a self-report questionnaire. Results: The multi-group SEM indicated a full mediation of job satisfaction in the relationship between job insecurity on the one side, and both individual’s and his/her partner’s family life satisfaction on the other side in both groups. Conclusion: These study findings highlighted how job insecurity may be indirectly and negatively related to both members’ family life satisfaction, through the mediation of job satisfaction. As regards gender, similar spillover and crossover patterns emerged, contributing to that literature that highlights a greater similarity in the models of interaction between work and family among women and men. Interventions should be aimed at reducing perception of job insecurity among workers, including those with permanent contract. Employers should improve communication and flow of information about future organizational changes. Moreover, interventions useful to monitor and reinforce employees’ job satisfaction should be planned. Finally, career practitioners may provide counseling and coaching projects aimed at strengthening employees’ employability and their ability to deal with changes