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Background: Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. Methods: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. Findings: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33–52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25–43]; p

The interest in multitask and deep learning strategies has been increasing in the last few years, in application to large and complex dataset for quantitative structure-activity relationship (QSAR) analysis. Multitask approaches allow the simultaneous prediction of molecular properties that are related, through information sharing, whereas deep learning strategies increase the potential of capturing nonlinear relationships. In this work, we compare the binary classification capability of multitask deep and shallow neural networks to single-task strategies used as benchmark (i.e., as k-nearest neighbours, N-nearest neighbours, random forest and Naïve Bayes), as well as multitask supervised self-organizing maps. Comparison was carried out with an extended QSAR dataset containing annotations of molecular binding, agonism and antagonism activity on 11 nuclear receptors, for a total of 14,963 molecules, divided into training and test sets and labelled for their bioactivity on at least one of 30 binary tasks. Additional 304 chemicals were used as external evaluation set to further validate models. Although no approach systematically overperformed the others, task-specific differences were found, suggesting the benefit of multitask learning for tasks that are less represented. On average, some of the single-task approaches and multitask deep learning strategies had similar performances. However, the latter can have advantages, such as a simpler management of predictions and applicability domain assessment for future samples. On the other hand, the parameter tuning required by neural networks are generally time expensive suggesting that the modelling strategy should be evaluated case by case.

During the COVID-19 pandemic, a shortage of mechanical ventilators was reported and ventilator sharing between patients was proposed as an ultimate solution. Two lung simulators were ventilated by one anesthesia machine connected through two respiratory circuits and T-pieces. Five different combinations of compliances (30–50 mL × cmH2O−1) and resistances (5–20 cmH2O × L−1 × s−1) were tested. The ventilation setting was: pressure-controlled ventilation, positive end-expiratory pressure 15 cmH2O, inspiratory pressure 10 cmH2O, respiratory rate 20 bpm. Pressures and flows from all the circuit sections have been recorded and analyzed. Simulated patients with equal compliance and resistance received similar ventilation. Compliance reduction from 50 to 30 mL × cmH2O−1 decreased the tidal volume (VT) by 32% (418 ± 49 vs. 285 ± 17 mL). The resistance increase from 5 to 20 cmH2O × L−1 × s−1 decreased VT by 22% (425 ± 69 vs. 331 ± 51 mL). The maximal alveolar pressure was lower at higher compliance and resistance values and decreased linearly with the time constant (r² = 0.80, p &lt, 0.001). The minimum alveolar pressure ranged from 15.5 ± 0.04 to 16.57 ± 0.04 cmH2O. Cross-flows between the simulated patients have been recorded in all the tested combinations, during both the inspiratory and expiratory phases. The simultaneous ventilation of two patients with one ventilator may be unable to match individual patient’s needs and has a high risk of cross-interference.

Introduction: Gastroesophageal reflux disease (GERD) as well as its treatment with acid-suppressive medications have been considered possible risk factors for the development of asthma, but few studies have disentangled the role of GERD with that of its treatment. The present study aimed at estimating the association of treated and untreated GERD in the first year of life with the risk of asthma. Methods: Retrospective cohort study including all children born between 2004 and 2015 registered in Pedianet, an Italian primary care database. We analyzed the association of children exposed to GERD (both treated and untreated) in the first year of life with the risk of developing clinically assessed asthma (clinical asthma) after 3 years. Secondary outcomes included asthma identified by anti-asthmatic medications (treated asthma) and wheezing after 3 years. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated comparing children with and without GERD, stratifying by treatment with acid-suppressive medications. Results: Out of 86,381 children, 1652 (1.9%) were affected by GERD in the first year of life, of which 871 (53%) were treated with acid-suppressive medications. Compared with controls, children with GERD were at increased risk of clinical asthma (HR: 1.40, 95% CI 1.15–1.70). Risks were similar between treated and untreated GERD (p = 0.41). Comparable results were found for treated asthma, but no risk increase was seen for wheezing. Discussion: Early-life GERD was associated with subsequent childhood asthma. Similar risks among children with treated and untreated GERD suggest that acid-suppressive medications are unlikely to play a major role in the development asthma.

Nuclear receptors (NRs) are involved in fundamental human health processes and are a relevant target for toxicological risk assessment. To help prioritize chemicals that can mimic natural hormones and be endocrine disruptors, computational models can be a useful tool.1,2 In this work we i) created an exhaustive collection of NR modulators and ii) applied machine learning methods to fill the data-gap and prioritize NRs modulators by building predictive models.

Neural networks are rapidly gaining popularity in chemical modeling and Quantitative Structure–Activity Relationship (QSAR) thanks to their ability to handle multitask problems. However, outcomes of neural networks depend on the tuning of several hyperparameters, whose small variations can often strongly affect their performance. Hence, optimization is a fundamental step in training neural networks although, in many cases, it can be very expensive from a computational point of view. In this study, we compared four of the most widely used approaches for tuning hyperparameters, namely, grid search, random search, tree-structured Parzen estimator, and genetic algorithms on three multitask QSAR datasets. We mainly focused on parsimonious optimization and thus not only on the performance of neural networks, but also the computational time that was taken into account. Furthermore, since the optimization approaches do not directly provide information about the influence of hyperparameters, we applied experimental design strategies to determine their effects on the neural network performance. We found that genetic algorithms, tree-structured Parzen estimator, and random search require on average 0.08% of the hours required by grid search; in addition, tree-structured Parzen estimator and genetic algorithms provide better results than random search.

The aim of the present study is to evaluate the effects of 60-day artichoke leaf extract (ALE) supplementation (250mg, twice daily) on cytokines levels, natural killer cell (NK) response, and lipo-metabolic profile (HDL, LDL, and total-cholesterol, triglycerides (TG), ApoB, ApoA, lipid accumulation product (LAP), glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR)) in twenty adults (9/11 males/females, age=49.10 ± 13.74 years, and BMI=33.12 ± 5.14 kg/m2) with low HDL-C and mild hypercholesterolemia. Hierarchical generalized linear model, adjusted for sex, BMI, and age, has been used to evaluate pre-post treatment changes. A significant increase for HDL-C (β=0.14, p=0.0008) and MCP-1 (β=144.77, p=0.004) and a significant decrease for ApoB/ApoA (β=-0.07, p=0.03), total-C/HDL-C ratio (β=-0.58, pβ=0.43, p=0.04), medium (β=0.40, pβ=0.42, p=0.001) have been found. These results support the benefits of ALE supplementation on metabolic profile.

Background: Evidence suggests a role of intestinal microbiota-host interactions in the pathophysiology and symptoms of irritable bowel syndrome (IBS). Objective: The objective of this article is to assess the effects of Lactobacillus paracasei CNCM I-1572 on clinical and gut microbiota-related factors in IBS. Methods: We conducted a multicenter, randomized, double-blind, cross-over, 18-week, placebo-controlled, pilot trial assessing the effect of Lactobacillus paracasei CNCM I-1572 on symptoms, gut microbiota composition, fecal short chain fatty acid (SCFA), immunoglobulin A, and cytokines in IBS. The intestinal microbial ecosystem was characterized by 16S rRNA gene profiling. Results: Forty IBS patients were enrolled from five Italian centers. Lactobacillus paracasei CNCM I-1572 did not significantly improve IBS symptoms, including primary efficacy variables worst abdominal pain/discomfort and IBS degree of relief. Interestingly, Lactobacillus paracasei CNCM I-1572 induced a significant reduction in genus Ruminococcus, dominated by taxa related to Ruminococcus bromii and Ruminococcus callidus, a significant increase in the SCFAs acetate and butyrate, and a significant reduction in the pro-inflammatory cytokine interleukin-15. Conclusions: This pilot study shows that Lactobacillus paracasei CNCM I-1572 is able to modulate gut microbiota structure/function and reduce immune activation in IBS. As no statistically significant effect on IBS-symptoms was found, further studies are necessary to determine the role of this probiotic in IBS. The study was registered at ClinicalTrials.gov registry under identifier NCT02371499.

Objective To define whether there is any relation between the iron status of patients with hepatitis C virus (HCV) chronic liver disease and their response to interferon therapy. Design To evaluate the long-term response to 1 year of interferon therapy with addition of phlebotomies after 3 months of treatment if at that time alanine aminotransferase (ALT) had not normalized in a group of patients with HCV-positive chronic liver disease whose iron status had been characterized. Setting A northern Italian hospital. Participants Fifty-eight anti-HCV-positive patients (four HCV-RNA negative) with biopsy proven chronic hepatitis and no evidence of iron overload as indicated by normal transferrin saturation at the time of enrollment in the study. Intervention Three times a week intramuscular injection of alpha interferon 3 MU for 1 year with addition of phlebotomies (350 ml/week) till iron depletion if after 3 months of interferon therapy ALT had not normalized. Results A long-term response was observed in 19 of the 52 patients who completed the treatment, four HCV-RNA negative and 15 positive. The four RNA-negative and seven of the 15 RNA-positive long-term responders had been treated with interferon alone, and the other eight also with phlebotomies. At univariate analysis only HCV genotype, gamma-glutamyltranspeptidase and liver iron concentration were significantly associated with response whereas sinusoidal iron deposition was of borderline significance. No association was found with sex, age, duration of disease, histology, Knodell score, transferrin saturation %, serum ferritin, hepatocytic iron score, and portal iron score. HCV-RNA serum levels, measured in 29 patients, did not correlate with response. At multivariate analysis liver iron concentration was still significant and one unit reduction of liver iron concentration (natural logarithm transformed) was associated with 2.95 odds ratio of response. Conclusion These results indicate that iron in the liver is more closely related to response to interferon than the other variables considered, including HCV characteristics.

The exact prevalence of food allergy in the general population is unknown, but almost 12% of pediatric population refers a suspicion of food allergy. IgE mediated reactions to food are actually the best-characterized types of allergy, and they might be particularly harmful especially in children. According to the “hygiene hypothesis” low or no exposure to exogenous antigens in early life may increase the risk of allergic diseases by both delaying the development of the immune tolerance and limiting the Th2/Th1 switch. The critical role of intestinal microbiota in the development of immune tolerance improved recently the interest on probiotics, prebiotics, antioxidants, polyunsaturated fatty acid, folate and vitamins, which seem to have positive effects on the immune functions. Probiotics consist in bacteria or yeast, able to re-colonize and restore microflora symbiosis in intestinal tract. One of the most important characteristics of probiotics is their safety for human health. Thanks to their ability to adhere to intestinal epithelial cells and to modulate and stabilize the composition of gut microflora, probiotics bacteria may play an important role in the regulation of intestinal and systemic immunity. They actually seem capable of restoring the intestinal microbic equilibrium and modulating the activation of immune cells. Several studies have been recently conducted on the role of probiotics in preventing and/or treating allergic disorders, but the results are often quite contradictory, probably because of the heterogeneity of strains, the duration of therapy and the doses administered to patients. Therefore, new studies are needed in order to clarify the functions and the utility of probiotics in food allergies and ion other types of allergic disorders.