Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination

Introduction: Disease-modifying therapies (DMTs) have been shown to improve disease outcomes in multiple sclerosis (MS) patients. They may also impair the immune response to vaccines, including the SARS-CoV-2 vaccine. However, available data on both the intrinsic immune effects of DMTs and their influence on cellular response to the SARS-CoV-2 vaccine are still incomplete. Methods: Here, we evaluated the immune cell effects of 3 DMTs on the response to mRNA SARS-CoV-2 vaccination by comparing MS patients treated with one specific therapy (fingolimod, dimethyl fumarate, or natalizumab) with both healthy controls and untreated patients. We profiled 23 B-cell traits, 57 T-cell traits, and 10 cytokines, both at basal level and after stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS patients, treated with DMTs or untreated, and 32 healthy controls. Measurements were made before vaccination and at three time points after immunization. Results and discussion: MS patients treated with fingolimod showed the strongest immune cell dysregulation characterized by a reduction in all measured lymphocyte cell classes; the patients also had increased immune cell activation at baseline, accompanied by reduced specific immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike specific B cells progressively increased over the three time points after vaccination, even when antibodies measured from the same samples instead showed a decline. Our findings demonstrate that repeated booster vaccinations in MS patients are crucial to overcoming the immune cell impairment caused by DMTs and achieving an immune response to the SARS-CoV-2 vaccine comparable to that of healthy controls

Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian multiple sclerosis patients, a follow-up study

Monitoring immune responses to SARS-CoV-2 vaccination and its clinical efficacy over time in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) help to establish the optimal strategies to ensure adequate COVID-19 protection without compromising disease control offered by DMTs. Following our previous observations on the humoral response one month after two doses of BNT162b2 vaccine (T1) in MS patients differently treated, here we present a cross-sectional and longitudinal follow-up analysis six months following vaccination (T2, n=662) and one month following the first booster (T3, n=185). Consistent with results at T1, humoral responses were decreased in MS patients treated with fingolimod and anti-CD20 therapies compared with untreated patients also at the time points considered here (T2 and T3). Interestingly, a strong upregulation one month after the booster was observed in patients under every DMTs analyzed, including those treated with fingolimod and anti-CD20 therapies. Although patients taking these latter therapies had a higher rate of COVID-19 infection five months after the first booster, only mild symptoms that did not require hospitalization were reported for all the DMTs analyzed here. Based on these findings we anticipate that additional vaccine booster shots will likely further improve immune responses and COVID-19 protection in MS patients treated with any DMT

Degree correlations in directed scale-free networks

Scale-free networks, in which the distribution of the degrees obeys a power-law, are ubiquitous in the study of complex systems. One basic network property that relates to the structure of the links found is the degree assortativity, which is a measure of the correlation between the degrees of the nodes at the end of the links. Degree correlations are known to affect both the structure of a network and the dynamics of the processes supported thereon, including the resilience to damage, the spread of information and epidemics, and the efficiency of defence mechanisms. Nonetheless, while many studies focus on undirected scale-free networks, the interactions in real-world systems often have a directionality. Here, we investigate the dependence of the degree correlations on the power-law exponents in directed scale-free networks. To perform our study, we consider the problem of building directed networks with a prescribed degree distribution, providing a method for proper generation of power-law-distributed directed degree sequences. Applying this new method, we perform extensive numerical simulations, generating ensembles of directed scale-free networks with exponents between~2 and~3, and measuring ensemble averages of the Pearson correlation coefficients. Our results show that scale-free networks are on average uncorrelated across directed links for three of the four possible degree-degree correlations, namely in-degree to in-degree, in-degree to out-degree, and out-degree to out-degree. However, they exhibit anticorrelation between the number of outgoing connections and the number of incoming ones. The findings are consistent with an entropic origin for the observed disassortativity in biological and technological networks.Comment: 10 pages, 5 figure

What is an emerging technology?

There is considerable and growing interest in the emergence of novel technologies, especially from the policy-making perspective. Yet as an area of study, emerging technologies lacks key foundational elements, namely a consensus on what classifies a technology as ’emergent’ and strong research designs that operationalize central theoretical concepts. The present paper aims to fill this gap by developing a definition of ’emerging technologies’ and linking this conceptual effort with the development of a framework for the operationalisation of technological emergence. The definition is developed by combining a basic understanding of the term and in particular the concept of ’emergence’ with a review of key innovation studies dealing with definitional issues of technological emergence. The resulting definition identifies five attributes that feature in the emergence of novel technologies. These are: (i) radical novelty, (ii) relatively fast growth, (iii) coherence, (iv) prominent impact, and (v) uncertainty and ambiguity. The framework for operationalising emerging technologies is then elaborated on the basis of the proposed attributes. To do so, we identify and review major empirical approaches (mainly in, although not limited to, the scientometric domain) for the detection and study of emerging technologies (these include indicators and trend analysis, citation analysis, co-word analysis, overlay mapping, and combinations thereof) and elaborate on how these can be used to operationalise the different attributes of emergence

Are Italian Newly Licensed Nurses Ready? A Study on Self-Perceived Clinical Autonomy in Critical Care Scenarios

The experience and self-confidence of healthcare professionals play critical roles in reducing anxiety levels during emergencies. It is important to recognize the potential impact of anxiety on performance. To enhance preparedness and confidence in managing emergencies, healthcare professionals benefit from regular training and simulations. Additionally, repeated exposure to emergency scenarios can help modulate physiological responses. Managing anxiety effectively is key, as heightened sympathetic stimulation associated with anxiety can adversely affect performance. This study aimed to investigate nurses’ self-assessed ability to manage emergency guidelines and their self-confidence in performing tasks in critical care settings. A questionnaire was provided to 1097 nurses. We compared the self-confidence of experienced nurses (ENs) and newly licensed nurses (NLNs) in managing emergency department shifts or critical patients, and found that ENs are more confident in these scenarios. This phenomenon was also observed in subjects who had taken simulation courses, although they were still a low percentage. Most NLNs feel sufficiently ready to work in medium-intensity wards. Attending advanced training courses enhances nurses’ self-confidence and may improve patient safety management., improving patient recovery, and minimizing errors. Attending courses improves the perception of autonomy of nurses in different scenarios

“This Is Public Health in Italy”. An ASPPH-ASPHER campaign to raise awareness on health prevention and Health in All Policies

Introduction In many European countries, Public Health (PH) and Preventive Medicine are not perceived as important tools 1 2.The general population, especially those working in non-healthcare related fields, underestimates the crucial role of PH policies as food & veterinary safety, energy efficiency, transport regulation, healthcare design and city planning 3-8. The Health in All Policies (HiAP) approach is instrumental in tackling this information gap 9 10. Originally conceived in the EU, HiAP is now included in WHO’s Sustainable Development Goals. In the US, in 2018, the Association of Schools & Programs of Public Health (ASPPH) launched an international campaign called “This is Public Health” (TIPH), whose aim was “to brand public health and raise awareness of how [it] affects individuals, families, communities, and populations” 11. The Association of Schools of Public Health in the European Region (ASPHER) responded by creating a European campaign to reproduce the American one. An open challenge was set, in which PH Schools – students and staff – were requested to formulate country-specific proposals. The Accademia Lombarda di Sanità Pubblica, coordinating the Schools and Programs of PH of Vita-Salute “San Raffaele” University, Milan, University of Parma, University of Pavia and Politecnico of Milan set up a proposal to increase PH awareness both in the general population and in healthcare workers. Materials and methods The preliminary phase was dedicated to the Project setup and was conducted by the ten new Residents of the Vita-Salute “San Raffaele” University, with the coordination and supervision of the PI and the Schools’ Directors. The working group extensively discussed the need for an appropriate translation of the catchphrase and a new graphic rendering of the TIPH logo. An agreement was finally reached to adapt all the elements of the Campaign, re-elaborating them according to the Italian context. The word “health” has a double meaning in Italian (“salute” and “sanità”). Furthermore, people with limited English proficiency are a large part of the target population. Therefore, the Group opted for a non-literal translation (“Per la salute di tutti”). To further boost the Campaign online, the group created “TIPH – Italy” accounts and pages on the main social media (i.e. Facebook, Twitter, Instagram). Subsequently, the PI assigned tasks to each of the team’s members from the various PH Schools involved. The operational phase is currently underway, and a series of activities are already in schedule. All laws and resolutions enacted by local governments (Lombardy Region and, in a future phase, Emilia Romagna Region) are being thoroughly analysed, to assess their direct or indirect PH impact. Spreading the project will be a key for its success. In the next months, multiple promotional events will be organised, addressing both operators and the public at large. Surveys will be administered before and after the events, both to assess baseline knowledge and attitudes towards PH initiatives, and to verify the interventions’ effectiveness in raising awareness. Running a social media photo contest will be a useful option for targeting younger age groups, following in the steps of the US campaign. Side events will be organised, such as congress, meeting, press conferences, with the purpose of giving the latest updates about the Campaign. Conclusions Italy is a challenging country. A fairly strong National Health Service, with plenty of positive health indicators, coexist with impressive inequalities and contradictions, both in the North-South and in the rich-poor axis. In light of this scenario, stronger recognition of the role and the importance of PH is essential. PH awareness is ultimately directed at informing policymaking and improving community health 12. While the potential impact of TIPH in Italy is still to be fully explored, the basis for its potential success can only lie in the delivery of a culturally appropriate message. TIPH Italy is a wonderful opportunity of making PH accessible to the general population in an effective, yet entertaining way

Risk factors of Parkinson\u2019s disease: simultaneous assessment, interactions and etiological subtypes

Objective: To perform a simultaneous evaluation of potential risk/protective factors of Parkinson's disease (PD) in order to identify independent risk/protective factors, assess interaction among factors and determine whether identified risk factors predict etiological subtypes of PD. Methods: We designed a large case-control study assessing 31 protective/risk factors of PD, including environmental and lifestyle factors, comorbidities, and drugs. The study enrolled 694 PD patients and 640 healthy controls from six neurological centers. Data were analyzed by logistic regression models, additive interaction models, and cluster analysis. Results: The simultaneous assessment of 31 putative risk/protective factors of PD showed that only coffee consumption (odds ratio [OR]: 0.6; 95% confidence interval [CI]: 0.4-0.9), smoking (OR: 0.7; 95% CI: 0.6-0.9), physical activity (OR: 0.8; 95% CI: 0.7-0.9), family history of PD (OR: 3.2; 95% CI: 2.2- 4.8), dyspepsia (OR: 1.8; 95% CI:1.3-2.4), exposure to pesticides (OR: 2.3; 95% CI:1.3- 4.2), oils (OR: 5.6; 95% CI: 2.3-13.7), metals (OR: 2.8; 95% CI: 1.5-5.4), and general anesthesia (OR: 6.1; 95% CI: 2.9-12.7) were independently associated with PD. There was no evidence of interaction among risk/protective factors, but cluster analysis identified four subtypes with different risk factor profiles. In Group 1, all patients had a family history of PD, while dyspepsia or exposure to toxic agents were present in 30% of patients. In Group 2 and 3, a family history of PD was lacking, while exposure to toxic agents (Group 2) and dyspepsia (Group 3) played major roles. Group 4 consisted of patients with no risk factors. Conclusions: This study demonstrated that nine factors independently modify PD risk by coexisting in the same patient rather than interacting with others. Our study suggests the need for future preventive strategies aimed at reducing the coexistence of different risk factors within the same subject

The campaign "This Is Public Health" in Italy, set up by a team of Public Health Schools in Northern Italy

Despite the great effort to raise awareness among health promotion, nowadays Public Health policies are not often recognized as important tools. For this reason, the Health in All Policies (HiAP) approach is instrumental in tackling this information gap. In 2018, the US Association of Schools and Programs of Public Health (ASPPH) launched an international campaign called "This is Public Health" (TIPH), whose aim was "to brand public health and raise awareness of how it affects individuals, communities and populations". The Association of Schools of Public Health in the European Region (ASPHER), in coordination with ASPPH, decided to create a European campaign to support and to reproduce the American one, by opening a challenge among the European Public Health Schools. The Schools and Programs of PH of Vita-Salute "San Raffaele" University, Milan, University of Parma, University of Pavia and Politecnico of Milan won this bid. In this "briefing on" we present a report on the Italian project for raising awareness of Public Health among general population and health care personell