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Intestinal microbiota is composed by symbiotic innocuous bacteria and potential pathogens also called pathobionts. Even if the mechanism of action of intestinal bacteria remain still unknown, specific microbial species seem to have important role in the maintenance of immunological equilibrium in the gut through the direct interaction with immune cells. Some studies have found a dysregulated interaction between the intestinal bacteria, the gut barrier, and the intestinal associated immune system in Inflammatory Bowel Disease (IBD) patients and in the pathogenesis of these pathologies. In IBD patients some Butyrate producing bacteria, as Faecalibacterium Prausnitzii, are under represented and this could be related with their chronic inflammatory state.

Twenty-nine of 54 uremic patients had low levels of protein C measured as anticoagulant activity, contrasting with normal levels measured as amidolytic activity or antigenic concentration. We demonstrate that this discrepancy is due to the presence of a soluble plasma inhibitor that interferes specifically with the anticoagulant activity of activated protein C. The inhibitor does not interfere with other coagulation assays. It is resistant to diisopropylfluorophosphate, high temperatures and repeated freezing and thawing. It can be dissociated from protein C by anti-protein C antibodies or by dialysis in vitro and in vivo. It binds to positively charged resins and can be eluted with high salt concentrations without losing its inhibitory capacity. The inhibitory effect is correlated with plasma creatinine levels and fluctuates with time.

Some reports correlate the administration of all forms of interferon with the development or exacerbation of autoimmune phenomena and diseases, including sarcoidosis, because of the strong and complex immune action of interferons. We report on a case of sarcoidosis following beta-interferon treatment for multiple myeloma. Differently from what had been observed in all the 8 previously reported cases of associated multiple myeloma and sarcoidosis, where the plasmacellular malignancy followed the onset of the respiratory disease, in the case of our patient, sarcoidosis arose after multiple myeloma was first diagnosed.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that commonly presents during early childhood. In the last decades the prevalence of AD has increased, especially in western societies. This frequently relapsing inflammatory condition has a strong impact on the quality of life of patients and families. The recent advances in the understanding of this disease have paved the way for the development of new strategies for the prevention and treatment of AD. Among the new therapeutic options, there is increasing interest in the potential benefit of probiotic supplementation. It has been widely demonstrated that the human microbiota plays a fundamental role not only in the maintenance of intestinal homeostasis through the interaction between microorganisms and the innate immune system, but also in the microbiota-mediated development of adaptive immunity. In addition, several studies have demonstrated that probiotics are able to influence the composition of gut microbiota and may exert immunomodulatory effects. According to these promising results, the possible application of probiotics in the therapeutic management of allergic diseases has been investigated in many studies. In particular, a considerable body of literature has been published analyzing the effects of probiotics on patients with AD. In order to shed light on frequently conflicting results, we reviewed the data regarding the application of probiotics in AD, with the aim to provide a state-of-the-art assessment of the most important studies exploring the role of probiotics both in the prevention and treatment of AD.

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

Mass spectrometry (MS) is widely used for the identification of chemical compounds by matching the experimentally acquired mass spectrum against a database of reference spectra. However, this approach suffers from a limited coverage of the existing databases causing a failure in the identification of a compound not present in the database. Among the computational approaches for mining metabolite structures based on MS data, one option is to predict molecular fingerprints from the mass spectra by means of chemometric strategies and then use them to screen compound libraries. This can be carried out by calibrating multi-task artificial neural networks from large datasets of mass spectra, used as inputs, and molecular fingerprints as outputs. In this study, we prepared a large LC-MS/MS dataset from an on-line open repository. These data were used to train and evaluate deep-learning-based approaches to predict molecular fingerprints and retrieve the structure of unknown compounds from their LC-MS/MS spectra. Effects of data sparseness and the impact of different strategies of data curing and dimensionality reduction on the output accuracy have been evaluated. Moreover, extensive diagnostics have been carried out to evaluate modelling advantages and drawbacks as a function of the explored chemical space.

In the recent years, ecotoxicological hazard potential of biocidal products has been receiving increasing attention in the industries and regulatory agencies. Biocides/pesticides are currently one of the most studied groups of compounds, and their registration cannot be done without the empirical toxicity information. In view of limited experimental data available for these compounds, we have developed Quantitative Structure-Activity Relationship (QSAR) models for the toxicity of biocides to fish and Daphnia magna following principles of QSAR modeling recommended by the OECD (Organization for Economic Cooperation and Development). The models were developed using simple and interpretable 2D descriptors and validated using stringent tests. Both models showed encouraging statistical quality in terms of determination coefficient R2 (0.800 and 0.648), cross-validated leave-one-out Q2 (0.760 and 0.602) and predictive R2pred or Q2ext (0.875 and 0.817) for fish (nTraining = 66, nTest = 22) and Daphnia magna (nTraining = 100, nTest = 33) toxicity datasets, respectively. These models should be applicable for data gap filling in case of new or untested biocidal compounds falling within the applicability domain of the models. In general, the models indicate that the toxicity increases with lipophilicity and decreases with polarity, branching and unsaturation. We have also developed interspecies toxicity models for biocides using the daphnia and fish toxicity data and used the models for data gap filling.

In the analysis of complex and multivariate systems, set priorities and rank all the available objects is not a trivial task. In this framework, several multi-criteria decision-making (MCDM) techniques have been proposed, with successful applications in different research fields. However, it would be desirable to customize the ranking by weighting differently the criteria and to quantitatively assess the influence of each criterion on the final ranking. In this study, we applied a recently proposed ranking approach, called Deep Ranking Analysis by Power Eigenvectors (DRAPE) to study the sustainability of 154 countries expressed by 21 human, environmental and economic wellbeing criteria. The application of two systems for weighting the criteria and a retrospective analysis of the contribution of each criterion to the final ranking allowed the great potential of the considered approach to be expressed.

Multi-criteria decision making processes comprehend several ranking methods able to handle multiple and often conflicting criteria and sorting objects according to a definition of the optimality direction for each criterion. In the field of polypharmacology it can be useful for virtual screening or prioritization purposes to rank molecules distinguishing the most multi-target ones, i.e. molecules able to interact with different targets, from the selective or inactive ones. In this work, the Deep Ranking Analysis by Power Eigenvectors approach is applied to a small set of molecules characterized by their half maximal binding concentrations for seven different nuclear receptors. The existence of a correspondence between the DRAPE ranking and a manually grouping of molecules based on their multi-target behaviour was verified. Moreover, a comparison between DRAPE rankings and those obtained from five traditional methods was carried out in order to highlight the main similarities and the differences of the approaches.

The father’s right to kill his adulterous daughter that had been introduced by Roman law aroused some interesting discussions among law scholars even in the modern age. They accepted the idea that the father could kill his daughter and her lover with impunity in the case of flagrant adultery. This right could be deemed as connected to paternal authority. It was a relic of the ancient ius vitae ac necis which, meanwhile, had developed into a milder right to chastise a disobedient child. Some law scholars dealing with father’s powers between the 16th and the 17th centuries dedicated entire chapters of their works to this considerably interesting topic. The father would be granted impunity only if he had killed his adulterous daughter on certain conditions required by Roman law. The legacy of Roman law on this matter was very clear indeed, but the law scholars of the late ius commune had to update those conditions and to clarify them. Furthermore, law scholars discussed some aspects of the father’s right to kill his adulterous daughter that were still disputed and had not re-ceived a definitive solution, such as the father’s possibility to ask someone for help or to kill his daughter despite the fact that she was pregnant. Other im-portant subjects were also dealt with, e.g. presumptions and circumstantial ev-idences in adultery, which was a hard-to-prove crime. The father’s right to kill his adulterous daughter also caused moral problems because, although it was lawful, it did not prevent the father from committing a mortal sin: in this way, the relationship between internal forum and external forum was often dealt with as a pivotal topic.

Proteomics methodologies hold great promise in basic renal research and clinical nephrology. The classical approach for proteomic analysis couples two-dimensional gel electrophoresis (2-DE) with protein identification by mass spectrometry, to produce more global information regarding normal protein expression and alterations in different physiological and pathological states. In this report we have expanded the identification of proteins in the renal cortex, improving the previously published map to facilitate the study of different diseases affecting the human kidney. About 250 spots were analyzed by peptide mass fingerprinting, 89 proteins and 74 isoforms for some of them were identified and implemented in the normal human renal cortex 2-DE reference map. This more comprehensive view of the proteome of the human renal cortex could be of invaluable help to the differential proteomic display of urological diseases.

Heat shock protein 27 (HSP27, Swiss-Prot accession number P04792) is a component of the large and heterogeneous group of chaperone proteins, and its main functions are inhibition of apoptosis and prevention of aggregation of actin intermediate filament. Modified expression of HSP27 has been described in several cancers including testis, breast, and ovaric cancer. In the present work, 18 renal cell carcinoma (RCC) tissues and homologous normal kidney tissues have been investigated for HSP27 expression by combination of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) separation and Western blotting immunodetection. The results showed significant differences either in expression and in HSP27 isoform numbers in RCC compared to normal kidney. The average number of isoforms was 21 in RCC and 15 in normal tissues with 4.5-5.9 pI range and 18-29 kDa M(r) range. The overexpression was also observed by immunohistochemistry on tissue sections. Only two of RCC samples showed less isoforms than homologous normal samples. Two isoforms were not detected using anti-Ser82 phosphorylated HSP27 antibody, neither in normal nor in RCC samples. Five of all the immunodetected isoforms were confirmed by mass spectrometry as HSP27, but no evidence of post-translational modifications was pointed out. The numerous isoforms observed in RCC are not consistent with data reported in the literature so far, and they might be due to different post-translational modifications such as phosphorylation and S-thiolation. Since activation of HSP27 seems to be involved in tumor proliferation and drug resistance, it would be crucial to correlate the severity of disease with the different isoforms from RCC samples to generate diagnostic and prognostic markers.

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.