Bortezomib (BTZ) is a first-in-class proteasome inhibitor approved for the therapy of multiple myeloma that also displays unique regulatory activities on immune cells. The enzyme indoleamine ...2,3-dioxygenase 1 (IDO1) is a tryptophan metabolizing enzyme exerting potent immunoregulatory effects when expressed in dendritic cells (DCs), the most potent antigen-presenting cells capable of promoting either immunity or tolerance. We previously demonstrated that, in inflammatory conditions, IDO1 is subjected to proteasomal degradation in DCs, turning these cells from immunoregulatory to immunostimulatory. In non-obese diabetic (NOD) mice, an experimental model of autoimmune diabetes, we also identified an IDO1 defect such that the DCs do not develop tolerance toward pancreatic islet autoantigens. We found that BTZ rescues IDO1 protein expression
in a particular subset of DCs, i.e., plasmacytoid DCs (pDCs) from NOD mice. When administered
to prediabetic mice, the drug prevented diabetes onset through IDO1- and pDC-dependent mechanisms. Although the drug showed no therapeutic activity when administered alone to overtly diabetic mice, its combination with otherwise suboptimal dosages of autoimmune-preventive anti-CD3 antibody resulted in disease reversal in 70% diabetic mice, a therapeutic effect similar to that afforded by full-dosage anti-CD3. Thus, our data indicate a potential for BTZ in the immunotherapy of autoimmune diabetes and further underline the importance of IDO1-mediated immune regulation in such disease.
We describe the behavior of a beam balance used for the measurement of small forces, in macroscopic samples, in tens of mHz frequency band. The balance, which works at room temperature, is the ...prototype of the cryogenic balance of the Archimedes experiment, aimed at measuring the interaction between electromagnetic vacuum fluctuations and the gravitational field. The balance described has a 50-cm aluminum arm and suspends an aluminum sample of 0.2 Kg and a lead counterweight. The read-out is interferometric, and the balance works in closed loop. It is installed in the low seismic noise laboratory of SAR-GRAV (Sardinia—Italy). Thanks to the low sensing and actuation noise and finally thanks to the low environmental noise, the sensitivity in torque
τ
n
~
is about
τ
n
~
≈
2
∗
10
-
12
Nm
/
Hz
at 10 mHz and reaches a minimum of about
τ
n
~
≈
7
∗
10
-
13
Nm
/
Hz
at tens of mHz, corresponding to the force sensitivity
F
n
~
of
F
n
~
≈
3
∗
10
-
12
N/
Hz
. The achievement of this sensitivity, which turns out to be compatible with thermal noise estimation, on the one hand, demonstrates the correctness of the optical and mechanical design and on the other paves the way to the completion of the final balance. Furthermore, since the balance is equipped with weight and counterweight made of different materials, it is sensitive to the interaction with dark B-L photons. A first very short run made to evaluate constraints on B-L dark photon coupling shows encouraging results that will be discussed in view of next future scientific runs.
Abstract
Background
Involvement in research activities is complex in pediatric nursing and allied health professionals (AHPs). It is important to understand which individual factors are associated ...with it to inform policy makers in promoting research.
Methods
A cross-sectional observational study was conducted to describe the level of participation in research activities over the last ten years of nurses and AHPs working in a tertiary pediatric hospital. A large sample of nurses and AHPs working in an Italian academic tertiary pediatric hospital completed an online self-report questionnaire between June and December 2018. Three multivariate logistic regression analyses were performed to predict participation in research projects, speaking at conferences, and writing scientific articles.
Results
Overall, data from 921 health professionals were analyzed (response rate = 66%), of which about 21% (
n
= 196) reported participating in a research project, while 33% (
n
= 297) had attended a scientific conference as a speaker, and 11% (
n
= 94) had written at least one scientific paper. Having a Master or a Regional Advanced Course, working as an AHP or a ward manager, as well as regularly reading scientific journals and participation in an internal hospital research group or attendance in a specific course about research in the hospital, significantly predicted participation in research projects, speaking at conferences and writing scientific papers. It is important to foster research interest and competencies among health professionals to improve participation in research projects, speaking at conferences, and writing scientific papers.
Conclusions
Overall, we found a good level of attendance at conferences as speakers (33%), a moderate level of participation in research (21%), and low levels for writing scientific papers (11%). Our study highlighted the need to support participation in research activities among nurses and AHPs. Policymakers should identify strategies to promote research among nurses and AHPs, such as protected rewarded time for research, specific education, strengthened collaboration with academics, and financial support. Moreover, hospital managers should promote the development of research culture among health professionals, to improve their research competencies and evidence-based practice.
Benign lipomatous lesion of the heart includes an heterogeneous group of entities including neoplastic, congenital and reparative phenomena. Among these lipomas and lipomatous hypertrophy of the ...atrial septum ( LHIS) represent the most common lesion. Patients suffering from LHIS are often asymptomatic, however atrial fibrillation, congestive heart failure and supraventricular tachycardia are typical findings. Here we present a rare case of LHIS symptomatic for asthenia and dyspnea. (
www.actabiomedica.it
)
The area surrounding the dismissed mine of Sos Enattos (Sardinia, Italy) is the Italian candidate site for hosting Einstein Telescope (ET), the third-generation gravitational wave (GW) observatory. ...One of the goals of ET is to extend the sensitivity down to frequencies well below those currently achieved by GW detectors, i.e. down to 2 Hz. In the bandwidth 1,10 Hz, the seismic noise of anthropogenic origin is expected to represent the major perturbation to the operation of the infrastructure, and the site that will host the future detector must fulfill stringent requirements on seismic disturbances. In this paper we describe the operation of a temporary, 15-element, seismic array deployed in close proximity to the mine. Signals of anthropogenic origin have a transient nature, and their spectra are characterized by a wide spectral lobe spanning the 3,20 Hz frequency interval. Superimposed to this wide lobe are narrow spectral peaks within the 3,8 Hz frequency range. Results from slowness analyses suggest that the origin of these peaks is related to vehicle traffic along the main road running east of the mine. Exploiting the correlation properties of seismic noise, we derive a dispersion curve for Rayleigh waves, which is then inverted for a shallow velocity structure down to depths of
≈
150 m. This data, which is consistent with that derived from analysis of a quarry blast, provide a first assessment of the elastic properties of the rock materials at the site candidate to hosting ET.
Objective:
Neurological sequelae of SARS-CoV-2 infection have already been reported, but there is insufficient data about the impact of the pandemic on the management of the patients with chronic ...neurological diseases. We aim to analyze the effect of COVID-19 pandemic and social restriction rules on these fragile patients.
Methods:
Patients with chronic neurologic diseases routinely followed at the outpatient clinic of Gemelli University Hospital, Rome, were assessed for symptoms suggestive of SARS-CoV-2 infection in the pandemic period, consequences of social restrictions, and neurological disease features, concomitant medical conditions, current medical and disease-specific treatments. Data source: a dedicated telephone survey designed to encompass questions on COVID-19 symptoms and on pandemic effects in chronic neurologic conditions.
Results:
Overall, 2,167 individuals were analyzed: 63 patients reported contact with COVID-19 positive cases, 41 performed the swab, and 2 symptomatic patients tested positive for COVID-19 (0.09%). One hundred fifty-eight individuals (7%) needed urgent neurological care, deferred due to the pandemic; 641 patients (30%) suspended hospital treatments, physiotherapy or other support interventions; 405 individuals (19%) reported a subjective worsening of neurological symptoms.
Conclusions:
In our population, the presence of neurological chronic diseases did not increase the prevalence of COVID-19 infection. Nevertheless, the burden of neurological disorders has been worsened by the lockdown.