Gliadin induces neutrophil migration via engagement of the formyl peptide receptor, FPR1

Background Gliadin, the immunogenic component within gluten and trigger of celiac disease, is known to induce the production of Interleukin-8, a potent neutrophil-Activating and chemoattractant chemokine.We sought to study the involvement of neutrophils in the early immunological changes following gliadin exposure. Methods Utilizing immunofluorescence microscopy and flow cytometry, the redistribution of major tight junction protein, Zonula occludens (ZO)-1, and neutrophil recruitment were assessed in duodenal tissues of gliadin-gavaged C57BL/6 wild-Type and Lys-GFP reporter mice, respectively. Intravital microscopy with Lys-GFP mice allowed monitoring of neutrophil recruitment in response to luminal gliadin exposure in real time. In vitro chemotaxis assays were used to study murine and human neutrophil chemotaxis to gliadin, synthetic alpha-gliadin peptides and the neutrophil chemoattractant, fMet-Leu-Phe, in the presence or absence of a specific inhibitor of the fMet-Leu-Phe receptor-1 (FPR1), cyclosporine H. An irrelevant protein, zein, served as a control. Results Redistribution of ZO-1 and an influx of CD11b+Lys6G+ cells in the lamina propria of the small intestine were observed upon oral gavage of gliadin. In vivo intravital microscopy revealed a slowing down of GFP+ cells within the vessels and influx in the mucosal tissue within 2 hours after challenge. In vitro chemotaxis assays showed that gliadin strongly induced neutrophil migration, similar to fMet-Leu-Phe.We identified thirteen synthetic gliadin peptide motifs that induced cell migration. Blocking of FPR1 completely abrogated the fMet-Leu-Phe-, gliadin- and synthetic peptide-induced migration. Conclusions Gliadin possesses neutrophil chemoattractant properties similar to the classical neutrophil chemoattractant, fMet-Leu-Phe, and likewise uses FPR1 in the process. Copyright

Effects of lockdown on emergency room admissions for psychiatric evaluation: an observational study from the AUSL Romagna, Italy

Objectives: An observation of the admissions to the emergency room (ER) requiring psychiatric evaluation during the lockdown and investigation of the demographic and clinical variables. Methods: Retrospective longitudinal observational study of ER accesses for psychiatric evaluation was performed, comparing two periods (9 March–3 May 2020 vs. 9 March–3 May 2019). Data (number of admissions, key baseline demographic and clinical variables) were extracted from the ER databases of referral centres in a well-defined geographic area of North-Eastern Italy (Cesena, Ravenna, Forlì, and Rimini). Results: A 15% reduction of psychiatric referrals was observed, together with a 17% reduction in the total number of patients referring to the ER. This reduction was most evident in the first month of the lockdown period (almost 25% reduction of both referrals and patients). Female gender (OR: 1.52: 95%, CI: 1.12–2.06) and being a local resident (OR: 1.54: 95%CI: 1.02–2.34) were factors associated with the decrease. Conclusions: Lockdown changed dramatically health priorities in the local population, including people with mental health. We speculate that our observations do not only refer to the confinement due to the lockdown regime but also to fear of contagion and adoption of different coping strategies, especially in women.Key-points During lockdown 15% reduction of psychiatric visits and >17% reduction in the number of psychiatric patients referring to the ER was observed. in the first four weeks of the lockdown almost 25% reduction of both visits and patients was observed Female gender and being a local resident were factors associated with the decrease

Loan Officer Authority and Small Business Lending.Evidence from a survey.

A vast literature has emphasized that small banks are at a comparative advantage in small business lending. In this paper, we show that apart from size, which is negatively correlated with bank specialization in small business lending, organizational characteristics affect bank loan portfolio choices. By using a unique dataset based on a recent survey of Italian banks, we find that after having controlled for bank size, a branch loan officer’s authority has a key role in explaining bank specialization in small business lending. In particular, banks which delegate more decision-making power to their branch loan officers are more willing to lend to small firms than other banks. We approximate loan officers’ authority by controlling for several factors which shape their incentives: loan officer turnover, the amount of money up to which they are allowed to lend autonomously, their role in loan approval and in setting loan interest rates, the kind of information (soft versus hard information) used for screening and monitoring borrowers, and the structure of their compensation schemes

Loan Officer Authority and Small Business Lending.Evidence from a survey.

A vast literature has emphasized that small banks are at a comparative advantage in small business lending. In this paper, we show that apart from size, which is negatively correlated with bank specialization in small business lending, organizational characteristics affect bank loan portfolio choices. By using a unique dataset based on a recent survey of Italian banks, we find that after having controlled for bank size, a branch loan officer’s authority has a key role in explaining bank specialization in small business lending. In particular, banks which delegate more decision-making power to their branch loan officers are more willing to lend to small firms than other banks. We approximate loan officers’ authority by controlling for several factors which shape their incentives: loan officer turnover, the amount of money up to which they are allowed to lend autonomously, their role in loan approval and in setting loan interest rates, the kind of information (soft versus hard information) used for screening and monitoring borrowers, and the structure of their compensation schemes

Mid-term psychiatric consequences of the COVID-19 pandemic: a 4 months observational study on emergency room admissions for psychiatric evaluation after the (first) lockdown period in Italy

Purpose: The aim of our study is to evaluate the number and the features of admissions to the emergency room (ER) requiring psychiatric consultation, in the period between May 4th and August 31st 2020. Methods: We carried out a retrospective longitudinal observational study examining the 4 months following the initial lockdown imposed during the COVID-19 outbreak (May 4th and August 31st 2020). More specifically, the ER admissions leading to psychiatric referral were reviewed at all seven public hospitals of AUSL Romagna (Emilia Romagna region, Italy). Socio-demographic variables, history of medical comorbidities or psychiatric disorders, reason for ER admission, psychiatric diagnosis at discharge, and actions taken by the psychiatrist were collected. Results: An 11.3% (p = 0.007) increase in psychiatric assessments was observed when compared with the same period of the previous year (2019). A positive personal history of psychiatric disorders (OR:0.68, CI: 0.53–0.87) and assessments leading to no indication for follow-up (OR: 0.22, CI: 0.13–0.39) were significantly less frequent, while there was a significant increase of cases featuring organic comorbidities (OR: 1.24, CI: 1.00–1.52) and suicidal ideation/self-harm/suicide attempt (OR: 1,71, CI: 1.19–2.45) or psychomotor agitation (OR: 1.46, CI: 1.02–2.07) as reason for admission. Conclusions: Our results showed an increase in ER psychiatric consultations compared to the previous year, underlying the increased psychological distress caused by the lockdown

Half-life measurement of 44Sc and 44mSc.

The half-lives of 44Sc and 44mSc were measured by following their decay rate using several measurement systems: two ionization chambers and three γ-spectrometry detectors with digital and/or analogue electronics. For 44Sc, the result was the combination of seven half-life values giving a result of 4.042(7) h, which agrees with the last reported value of 4.042(3) h and confirms the near to 2% deviation from the recommended half-life of 3.97(4) h. Scandium-44 is present as an impurity in the production of 44Sc by cyclotron proton irradiation. Its half-life was determined by measurements performed a few days after End of Bomardment (EoB), so that the 44Sc decayed down to a negligible level. Seven measurements were combined to obtain an average of 58.7(3) h, which is in agreement with the recommended value of 58.6(1) h

A facility for radiation hardness studies based on a medical cyclotron

The development of instrumentation for operation in high-radiation environments represents a challenge in various research fields, particularly in particle physics experiments and space missions, and drives an ever-increasing demand for irradiation facilities dedicated to radiation hardness studies. Depending on the application, different needs arise in terms of particle type, energy and dose rate. In this article, we present a versatile installation based on a medical cyclotron located at the Bern University Hospital (Inselspital), which is used as a controlled 18-MeV proton source. This accelerator is used for daily production of medical radioisotopes, as well as for multidisciplinary research, thanks to a 6.5-meter long beam transfer line that terminates in an independent bunker, dedicated only to scientific activities. The facility offers a wide range of proton fluxes, due to an adjustable beam current from approximately 10 pA to the micro-ampere range, together with a series of steering and focusing magnets along the beamline that allow for the beam spot to be focused down to a few mm^2. The beamline can be instrumented with a variety of beam monitoring detectors, collimators, and beam current measurement devices to precisely control the irradiation conditions. The facility also hosts a well equipped laboratory dedicated to the characterisation of samples after irradiation. An experimental validation of the irradiation setup, with proton fluxes ranging from 5×10^9 cm^-2s^-1 to 4×10^11 cm^-2s^-1, is reported

Consumer credit in comparative perspective

We review the literature in sociology and related fields on the fast global growth of consumer credit and debt and the possible explanations for this expansion. We describe the ways people interact with the strongly segmented consumer credit system around the world—more specifically, the way they access credit and the way they are held accountable for their debt. We then report on research on two areas in which consumer credit is consequential: its effects on social relations and on physical and mental health. Throughout the article, we point out national variations and discuss explanations for these differences. We conclude with a brief discussion of the future tasks and challenges of comparative research on consumer credit.Accepted manuscrip

The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML