Helminth-derived inhibitors of the IL-33 pathway

Allergic asthma is a chronic inflammatory disease of the airways characterised by type 2 immune responses in the lungs. Increased mucus production, airway hyperresponsiveness and eosinophilia are the main features of the asthmatic lung, and they are caused by an increased production of IL-5 and IL-13. A strong inducer of these cytokines is the alarmin IL-33 that it is released upon necrotic death of epithelial cells. IL-33 can be released in the lung due to damage caused by inhalation of proteolytic allergens, parasite migration or respiratory viral infection. IL-33 activates several immune cell populations such as mast cells, TH2 lymphocytes and type 2 Innate Lymphoid cells (ILC2s). Parasitic infection is associated with a decreased risk of developing allergic immune responses, and this prevention appears to be mediated by the release of immunomodulatory excretory/secretory products (ES). The aims of this project are to study ES products from the intestinal murine nematode Heligmosomoides polygyrus (HES), and in particular identifying and characterising single proteins that interfere with the IL-33 pathway. HES administration has been shown to suppress both IL-33 and ST2 (the IL-33 receptor) in a mouse model of asthma. Therefore parasites may suppress the development of allergic asthma via the secretion of soluble mediators. Firstly, before the beginning of this project, a single protein from HES was identified as suppressor of IL-33: the H. polygyrus Alarmin Release Inhibitor (HpARI). Through direct binding assay, HpARI was shown to bind directly to the active cytokine, blocking IL-33- ST2 interaction. In vitro HpARI suppressed the release of IL-5 and IL-13 in response to IL-33. In vivo, administration of HpARI in an asthma model using the fungal allergen Alternaria alternata reduces ILC2s activation and eosinophilic inflammation. Next, type 2 inflammation was analysed in a neonatal model of RSV infection. Respiratory viral infections during childhood have been associated with increased risk of asthma development later in life, especially in those infant hospitalised with severe RSV bronchiolitis. In a neonatal mouse model of RSV infection IL-33 play an important role for the development of type 2 immune responses. In our model, RSV infection in neonates induces activation of lung ILC2s 24h post-infection. When HpARI was co-administered with RSV, ILC2 activation was suppressed at primary RSV infection, and at RSV reinfection in later life. A trend for reduced viral titre was observed when HpARI was co-administered with RSV suggesting that HpARI might interfere with viral infectivity. Finally, the next focus of the project was identifying a novel single protein involved in the suppression of ST2. Fractionation of HES was used to identify a novel protein which in recombinant form suppresses ST2. We named this novel protein H. polygyrus Binds Alarmin Receptor and Inhibits (HpBARI). HpBARI is a CCP domain-containing protein that suppresses IL-33 responses in vitro and in vivo. Using ELISA, direct binding assay and surface plasmon resonance, I showed that HpBARI binds directly to ST2 and that this interaction prevents IL-33 from binding to its receptor, blocking initiation of type 2 immune responses. These two newly identified parasite proteins, HpARI and HpBARI, both interfere with the IL-33 pathway. HpARI and HpBARI are related proteins as they each consist of 3 or 2 CCP domains, respectively, and they give insight into how parasites can immune modulate the host immune system

The impact of innovative and emerging technologies on the surveying activities

Non peer reviewe

Circulating MicroRNAs in Elderly Type 2 Diabetic Patients

The circulating microRNAs (miRNAs) associated with type 2 diabetes (T2D) in elderly patients are still being defined. To identify novel miRNA biomarker candidates for monitoring responses to sitagliptin in such patients, we prospectively studied 40 T2D patients (age > 65) with HbA1c levels of 7.5–9.0% on metformin. After collection of baseline blood samples (t0), the dipeptidyl peptidase-IV (DPP-IV) inhibitor (DPP-IVi) sitagliptin was added to the metformin regimen, and patients were followed for 15 months. Patients with HbA1c0.5% after 3 and 15 months of therapy were classified as “responders” (group R, n = 34); all others were classified as “nonresponders” (group NR, n = 6). Circulating miRNA profiling was performed on plasma collected in each group before and after 15 months of therapy (t0 and t15). Intra- and intergroup comparison of miRNA profiles pinpointed three miRNAs that correlated with responses to sitagliptin: miR-378, which is a candidate biomarker of resistance to this DPP-IVi, and miR-126-3p and miR-223, which are associated with positive responses to the drug. The translational implications are as immediate as evident, with the possibility to develop noninvasive diagnostic tools to predict drug response and development of chronic complications

On the choice of entropy variables in multifield inflation

We discuss the usefulness and theoretical consistency of different entropy variables used in the literature to describe isocurvature perturbations in multifield inflationary models with a generic curved field space. We clarify which is the proper entropy variable to be used to match the evolution of isocurvature modes during inflation to the one after the reheating epoch in order to compare with observational constraints. In particular, we find that commonly used variables, as the relative entropy perturbation or the one associated to the decomposition in tangent and normal perturbations with respect to the inflationary trajectory, even if more useful to perform numerical studies, can lead to results which are wrong by several orders of magnitude, or even to apparent destabilisation effects which are unphysical for cases with light kinetically coupled spectator fields.Comment: 20 pages + appendices, 3 figure

THE EFFECT OF THE PANDEMIC ON THE CARE OF PATIENTS WITH MENTAL DISORDERS: MEASURE OF "COMPASSION FATIGUE" AND "BURN-OUT" IN THE OPERATOR

Background: The Covid-19 Pandemic has had a significant impact on psychophysical well-being and the ability to work productively in contexts concerning people\u27s physical and mental care. The helping professions involved have seen an increase in stress levels, a sense of helplessness, fear, pain and social isolation. They are anchored to the hope of being able to return to their normality. Method: In this study, 87 mental health operators were evaluated, divided into nurses, psychiatric rehabilitation technicians, educators, social workers, psychologists and doctors, working in two psychiatric care rehabilitation communities in Puglia and Campania in southern Italy. Results: The results obtained with the administration of the scales ProQOL, BHS, Save-9, BDI-II, BEES reported a remarkable impact in nursing and medical professions due to the pandemic. A 11%. burn-out was reported by nurses. Conclusions: The collected data are comparable to the previous work (Franza et al. 2015, 2020); however, there is no evidence of a high level of burnout in the helping professions involved in this study

MENTAL ILLNESS AND PREJUDICES IN PSYCHIATRIC PROFESSIONALS Data from the social stigma questionnaire for psychiatric professionals: a multicentre study

The prejudices about mental illness and the related social stigma are still present in the population. People suffer from both the disease and the marginalization behaviors implemented by the "so-called healthy" towards them and their relatives. Even psychiatric professionals can get sick and suffer for the same reason. The authors of this multicentric study have focused their attention on the presence or absence of groups of psychiatric pathologies among the "insiders". The most frequent pathologies encountered were the mood and anxiety disorders, in a percentage similar to that of the general population. To continue the research on the stigma begun in a previous study, the authors asked themselves if there could be prejudices and/or stigma among psychiatric professionals towards sick colleagues, how they relate in the workplace and how they react to the behavior of colleagues. The stigma questionnaire has been used on psychiatric professionals, and 130 Italian colleagues were tested in the provinces of Avellino, Brindisi and Trento. The data were compared with those of the research on the stigma "Thinking of Psychiatric Disorders as" Normal "Illness" (Tavormina et al. 2016) and it emerged that among the attending professionals there are no statistically significant behaviors of marginalization, exclusion or stigma against sick colleagues, even if there is a certain discomfort in working together. Above all, it emerged that 80% of the interviewees, who have had work experience with sick colleagues, have replied that the latter can treat those who are also sick of their own disease, thus showing esteem and confidence in their work, in analogy with the Jungian thesis of the "wounded Healer" in the myth of the centaur Chiron

MENTAL ILLNESS AND PREJUDICES IN PSYCHIATRIC PROFESSIONALS Data from the social stigma questionnaire for psychiatric professionals: a multicentre study

The prejudices about mental illness and the related social stigma are still present in the population. People suffer from both the disease and the marginalization behaviors implemented by the "so-called healthy" towards them and their relatives. Even psychiatric professionals can get sick and suffer for the same reason. The authors of this multicentric study have focused their attention on the presence or absence of groups of psychiatric pathologies among the "insiders". The most frequent pathologies encountered were the mood and anxiety disorders, in a percentage similar to that of the general population. To continue the research on the stigma begun in a previous study, the authors asked themselves if there could be prejudices and/or stigma among psychiatric professionals towards sick colleagues, how they relate in the workplace and how they react to the behavior of colleagues. The stigma questionnaire has been used on psychiatric professionals, and 130 Italian colleagues were tested in the provinces of Avellino, Brindisi and Trento. The data were compared with those of the research on the stigma "Thinking of Psychiatric Disorders as" Normal "Illness" (Tavormina et al. 2016) and it emerged that among the attending professionals there are no statistically significant behaviors of marginalization, exclusion or stigma against sick colleagues, even if there is a certain discomfort in working together. Above all, it emerged that 80% of the interviewees, who have had work experience with sick colleagues, have replied that the latter can treat those who are also sick of their own disease, thus showing esteem and confidence in their work, in analogy with the Jungian thesis of the "wounded Healer" in the myth of the centaur Chiron

THE EFFECT OF THE PANDEMIC ON THE CARE OF PATIENTS WITH MENTAL DISORDERS: MEASURE OF "COMPASSION FATIGUE" AND "BURN-OUT" IN THE OPERATOR

Background: The Covid-19 Pandemic has had a significant impact on psychophysical well-being and the ability to work productively in contexts concerning people\u27s physical and mental care. The helping professions involved have seen an increase in stress levels, a sense of helplessness, fear, pain and social isolation. They are anchored to the hope of being able to return to their normality. Method: In this study, 87 mental health operators were evaluated, divided into nurses, psychiatric rehabilitation technicians, educators, social workers, psychologists and doctors, working in two psychiatric care rehabilitation communities in Puglia and Campania in southern Italy. Results: The results obtained with the administration of the scales ProQOL, BHS, Save-9, BDI-II, BEES reported a remarkable impact in nursing and medical professions due to the pandemic. A 11%. burn-out was reported by nurses. Conclusions: The collected data are comparable to the previous work (Franza et al. 2015, 2020); however, there is no evidence of a high level of burnout in the helping professions involved in this study

Severe pertussis infection in infants less than 6 months of age: clinical manifestations and molecular characterization

We conducted a study to determine the main traits of pertussis among unimmunized infants less than 6 months of age. From August 2012 to March 2015, 141 nasopharyngeal aspirates (NPAs) were collected from infants with respiratory symptoms attending 2 major hospitals in Rome. Clinical data were recorded and analyzed. Lab-confirmation was performed by culture and realtime PCR. B. pertussis virulence-associated genes (ptxP, ptxA and prn), together with multilocus variable-number tandem repeat analysis (MLVA), were also investigated by the sequence-based analysis on the DNAs extracted from positive samples. Antibiotic susceptibility with Etest was defined on 18 viable B. pertussis isolates. Samples from 73 infants resulted positives for B. pertussis. The median age of the patients was 45 d (range 7–165); 21 infants were treated with macrolides before hospital admission. Cough was reported for a median of 10 d before admission and 18 d after hospital discharge among infected infants, 84% of whom showed paroxysmal cough. No resistance to macrolides was detected. Molecular analysis identified MT27 as the predominant MLVA profile, combined with ptxP3-ptxA1-prn2 associated virulence genes. Although our data may not be generalized to the whole country, they provide evidence of disease severity among infants not vaccinated against pertussis. Moreover, genetically related B. pertussis strains, comprising allelic variants of virulence associated genes, were identified