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The period between the beginning and the end of the COVID-19 pandemic emergency generated a general state of stress, affecting both the mental state and physical well-being of the general population. Stress is the body’s reaction to events or stimuli perceived as potentially harmful or distressing. Particularly when prolonged over time, it can promote the consumption of different psychotropic substances such as alcohol, and thus the genesis of various pathologies. Therefore, our research aimed to evaluate the differences in alcohol consumption in a cohort of 640 video workers who carried out activities in smart working, subjects particularly exposed to stressful situations due to the stringent rules of protection and prevention implemented during the pandemic. Furthermore, based on the results obtained from the administration of the AUDIT-C, we wanted to analyse the different modes of alcohol consumption (low, moderate, high, severe) to understand whether there is a difference in the amount of alcohol consumed that could predispose individuals to health problems. To this end, we administered the AUDIT-C questionnaire in two periods (T0 and T1), coinciding with annual occupational health specialist visits. The results of the present research showed an increase in the number of subjects consuming alcohol (p = 0.0005) and in their AUDIT-C scores (p < 0.0001) over the period considered. A significant decrease in subgroups who drink in a low-risk (p = 0.0049) mode and an increase in those with high (p = 0.00012) and severe risk (p = 0.0002) were also detected. In addition, comparing the male and female populations, it emerged that males have drinking patterns that lead to a higher (p = 0.0067) health risk of experiencing alcohol-related diseases than female drinking patterns. Although this study provides further evidence of the negative impact of the stress generated by the pandemic emergency on alcohol consumption, the influence of many other factors cannot be ruled out. Further research is needed to better understand the relationship between the pandemic and alcohol consumption, including the underlying factors and mechanisms driving changes in drinking behaviour, as well as potential interventions and support strategies to address alcohol-related harm during and after the pandemic.

Background: Insomnia is the perception of inadequate, insufficient or non-restorative sleep. Of all sleep-related disorders, insomnia is the most common. It is important to remember that the sleep–wake cycle also plays a central role in the genesis of anxiety and depression. The aim of our study is to evaluate the association between sleep disturbances and anxiety and depression in a group of workers of both sexes who perform night shift work. Methods: Information on sleep disorders was collected by administering the Insomnia Severity Index (ISI) questionnaire. Statistical analysis was conducted using the Chi-square test to assess whether there were any differences between sex for those who were healthy or who were diagnosed with psychiatric disorders. Results: The results showed that there was a good percentage of subjects with insomnia problems, impairing normal daily activities and promoting the onset of fatigue, daytime sleepiness, cognitive performance deficits and mood disorders. Conclusion: We highlighted how anxious and depressive anxiety disorders are more pronounced in people who suffer from altered sleep–wake rhythms. Further research in this direction could prove to be fundamental for understanding the genesis of the onset of other disorders as well.

Extracellular vesicles (EVs) are nanometric spherical structures, enclosed in a lipid bilayer membrane and secreted by multiple cell types under specific physiologic and pathologic conditions. Their complex cargo modulates immune cells within an inflammatory microenvironment. Milk is one of the most promising sources of EVs in terms of massive recovery, and milk extracellular vesicles (mEVs) have immunomodulatory and anti-inflammatory effects. The aim of this study was to characterize goat mEVs’ immunomodulating activities on Toll-like receptors (TLRs) and related immune genes, including cytokines, using a porcine intestinal epithelial cell line (IPEC-J2) after the establishment of a pro-inflammatory environment. IPEC-J2 was exposed for 2 h to pro-inflammatory stimuli as a model of inflammatory bowel disease (IBD), namely LPS for Crohn’s disease (CD) and H2O2 for ulcerative colitis (UC); then, cells were treated with goat mEVs for 48 h. RT-qPCR and ELISA data showed that cell exposure to LPS or H2O2 caused a pro-inflammatory response, with increased gene expression of CXCL8, TNFA, NOS2 and the release of pro-inflammatory cytokines. In the LPS model, the treatment with mEVs after LPS determined the down-regulation of NOS2, MMP9, TLR5, TGFB1, IFNB, IL18 and IL12A gene expressions, as well as lower release of IL-18 in culture supernatants. At the same time, we observed the increased expression of TLR1, TLR2, TLR8 and EBI3. On the contrary, the treatment with mEVs after H2O2 exposure, the model of UC, determined the increased expression of MMP9 alongside the decrease in TGFB1, TLR8 and DEFB1, with a lower release of IL-1Ra in culture supernatants. Overall, our data showed that a 48 h treatment with mEVs after a pro-inflammatory stimulus significantly modulated the expression of several TLRs and cytokines in swine intestinal cells, in association with a decreased inflammation. These results further highlight the immunomodulatory potential of these nanosized structures and suggest their potential application in vivo.

Circular no. 40 of 2021 of the Italian Customs Agency is important, as it addresses a significant problem for non-established economic operators who must carry out import operations into a Member State of the European Union, as it emphasizes the need to have a VAT (Value Added Tax) number and a tax representative who fulfils the formalities connected with the payment of the duties; from the customs point of view, this person is regarded as the importer and therefore able to provide all the information required for the procedure of release for free circulation and will be identified through the EORI (acronym for Economic Operator Registration and Identification) code that will be assigned to them by the customs authority at the time of the first relevant transaction. However, operators not established in the Union territory will be required, in order to be able to submit a customs declaration (in the specific case, of release for free circulation), to assign a mandate without representation to an established subject, in order for the latter to carry out this fulfilment, remaining jointly and severally obliged with its principal for the obligation deriving from the presentation of the declaration for the release for free circulation regime. Importer, non-established, mandate, representation, declaration, person, territory, obligations, duties

Population-based cancer registries (PBCRs) are advanced public health systems providing ongoing surveillance through systematic collection, analysis, interpretation, and dissemination of high-quality data on cancer incident cases registered in a defined population residing in a specific geographical area (1, 2). Basically, PBCRs are well equipped for strengthening cancer surveillance, playing a strategic role in making geographic and temporal variation comparisons to highlight cancer epidemics, while assessing the effectiveness of preventive interventions and oncological care (3). Furthermore, many PBCRs provide cancer risk communication to local communities and authorities by using valuable tools to spread epidemiological data on cancer in intelligible ways to better address preventive intervention and changes in lifestyles (4). To these ends, PBCRs link records and merge data from different administrative, demographic and health sources, following international standards, recommendations, and guidelines (5– 7). Standards in cancer surveillance have been defined in Europe and several cancer research domains are continuously alimented by the cancer registries networks in support of public health and clinical research, with specific regard to aetiologic research, mass screening evaluation, quality of care, translational prognostics, and survivorship (3). More recently, progress has been documented regarding the PBCRs’ capability to estimate the effectiveness of immunisation programmes against vaccine preventable viral infections associated to cancer as well as of cancer screening programmes to decrease late-stage incidence and mortality (8–10). Much more fruits can be harvested from “RegisTrees” having strong roots (11), including the ones allowing the deterministic linkage between cancer registries and clinical registries to generate real-world evidence on treatments, particularly on elderly patients as well, a target population that is usually not included in clinical trials (12, 13). However, the latest revision of the European Union (EU) data protection framework and of the General Data Protection Regulation (GDPR), while suggesting a harmonization of health registries requirements for confidentiality and individual consent to data processing, made it raise concerns from researchers and epidemiologists experiencing some excessive restrictions that may hamper data linkages between cancer registries and other sources (14–16). As documented by a survey on how GDPR could have impacted the running of the daily activities of the cancer registries in different EU countries, conducted in 2018 by the European network of cancer registries (ENCR), some critical points related to the implementation and interpretation of the GDPR emerged from PBCRs (17, 18). Of interest, in 2017 the European Commission adopted a strategy to implement an interoperability framework, in order to improve “the ability of organizations to interact towards mutually beneficial goals, involving the sharing of information and knowledge by means of the exchange of data between the respective ICT systems” (19). As the digital interoperability was conceived to maximize the use of huge amounts of data, by contrast an unnecessarily strict interpretation of EU data protection regulation may lead to missed data linkages in cancer registration and other epidemiological activities (20). Therefore, the nature and the use of data from cancer registries in public health and research purposes, and their potentialities in the age of health digital interoperability, are herein discussed (16).

On 9 September 2021, Regulation (EU) no. 821/2021, of the European Parliament and of the Council, of 20 May 2021, relating to the control of exports, brokering, technical assistance, transit and transfer of dual-use items, i.e., all those products, including software and technologies, which can be used for both civil and military purposes, came into effect. The new Regulation has as its main objective (see in particular ‘Whereas (5)’ in the preamble to the Regulation) that of making the common system for the control of exports of dual-use items even more effective, to ensure compliance with the commitments and responsibilities of the Member States and of the Union, particularly in the fields of non-proliferation, regional peace, security and stability and respect for human rights and international humanitarian law. For these purposes, the definitions of ‘dual-use products’ and ‘exporter’ have been expanded and, moreover, a specific Article (8) is dedicated to the issue of technical assistance, which in the previous Regulation (428/2009) was covered exclusively in certain explanatory notes in the Annexes. The changes in this Regulation also concern the authorizations for the export from the European Union of ‘dual-use’ goods: a whole new ‘large project authorization’ (Article 2 (14) of the Regulation) has been created, which consists of an individual export authorization or a global export authorization granted to one specific exporter for a type or category of dual-use items, which may be valid for exports to one or more specific end-users in one or more specified third countries for the purpose of a specified large-scale project. This permission can relate to intra-group technology transfers and cryptography. Also with regard to the procedures for the export of dual-use items, the European Union decided to make use of the ‘Internal Compliance Programmes’, already present in other legislative sectors of the Union. Dual use export controls, authorizations, civil, military, technologies, compliance, exportation, controls, Regulation

The war in Ukraine has taken its toll on the stability of the Balkans by reshuffling regional geopolitics and reviving diplomatic competition between the West and Russia. Since the summer of 2022, growing tensions between Kosovo and Serbia have raised concerns about a possible Russian involvement and pushed the European Union to react promptly. By brokering a new normalisation agreement, the West seeks to prevent new hotbeds in Europe and push Russia one step back from the Balkans. Meanwhile, the Russian invasion of Ukraine has given new momentum to the integration process of candidate states, making EU membership a tangible goal rather than an unattainable dream. Will the EU be able to stabilise the Balkans? Will Russia continue to exert its influence in the region? Are Belgrade and Pristina on the eve of a new phase in the normalisation process?

first_page settings Order Article Reprints Open AccessArticle Heterogeneity of Phenotypic and Functional Changes to Porcine Monocyte-Derived Macrophages Triggered by Diverse Polarizing Factors In Vitro by Giulia Franzoni 1,*, Lorena Mura 1,2, Elisabetta Razzuoli 3, Chiara Grazia De Ciucis 3, Floriana Fruscione 3, Filippo Dell’Anno 3, Susanna Zinellu 1, Tania Carta 1,4, Antonio G. Anfossi 4, Silvia Dei Giudici 1, Simon P. Graham 5and Annalisa Oggiano 1 1 Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna, 07100 Sassari, Italy 2 Department of Biomedical Sciences, School of Medicine, University of Sassari, 07100 Sassari, Italy 3 National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, 16129 Genova, Italy 4 Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy 5 The Pirbright Institute, Ash Road, Pirbright, Woking GU24 ONF, UK * Author to whom correspondence should be addressed. Int. J. Mol. Sci.2023,24(5), 4671;https://doi.org/10.3390/ijms24054671 Received: 27 January 2023/Revised: 23 February 2023/Accepted: 25 February 2023/Published: 28 February 2023 (This article belongs to the Special IssueMacrophage Polarization: Learning to Manage It 2.0) Download Browse Figures ReviewReportsVersionsNotes Abstract Swine are attracting increasing attention as a biomedical model, due to many immunological similarities with humans. However, porcine macrophage polarization has not been extensively analyzed. Therefore, we investigated porcine monocyte-derived macrophages (moMΦ) triggered by either IFN-γ + LPS (classical activation) or by diverse “M2-related” polarizing factors: IL-4, IL-10, TGF-β, and dexamethasone. IFN-γ and LPS polarized moMΦ toward a proinflammatory phenotype, although a significant IL-1Ra response was observed. Exposure to IL-4, IL-10, TGF-β, and dexamethasone gave rise to four distinct phenotypes, all antithetic to IFN-γ and LPS. Some peculiarities were observed: IL-4 and IL-10 both enhanced expression of IL-18, and none of the “M2-related” stimuli induced IL-10 expression. Exposures to TGF-β and dexamethasone were characterized by enhanced levels of TGF-β2, whereas stimulation with dexamethasone, but not TGF-β2, triggered CD163 upregulation and induction of CCL23. Macrophages stimulated with IL-10, TGF-β, or dexamethasone presented decreased abilities to release proinflammatory cytokines in response to TLR2 or TLR3 ligands: IL-10 showed a powerful inhibitory activity for CXCL8 and TNF release, whereas TGF-β provided a strong inhibitory signal for IL-6 production. While our results emphasized porcine macrophage plasticity broadly comparable to human and murine macrophages, they also highlighted some peculiarities in this species.

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare form of non-Hodgkin T-cell lymphoma associated with breast reconstruction post-mastectomy or cosmetic-additive mammoplasty. The increasing use of implants for cosmetic purposes is expected to lead to an increase in BIA-ALCL cases. This study will investigate the main characteristics of the disease and factors predicting BIA-ALCL onset in patients with and without an implant replacement.

Background: Occupational hazards believed to cause musculoskeletal disorders in rope workers are traditionally associated with maintaining incongruous postures for prolonged periods of time. Design and methods: A cross-sectional survey was conducted on 132 technical operators in the wind energy and acrobatic construction sectors, who work on ropes, analysing the ergonomic characteristics of the environments, the way in which tasks are carried out, the strain perceived by individual workers, and assessing the presence of any musculoskeletal disorders (MSDs) by means of an objective examination focused on the anatomical districts that were the object of our study. Results: Analysis of the data obtained showed that there were differences in the perception of the level of physical intensity and perceived exertion between the groups of workers. Statistical analysis also revealed a significant association between the frequency of MSDs analysed and perceived exertion. Discussion: The most significant finding to emerge from this study is the high prevalence of MSDs of the cervical spine (52.94%), the upper limbs (29.41%), and the dorso-lumbar spine (17.65%). These values differ from those classically found in those exposed to the risk of conventional manual handling of loads. Conclusions: The high prevalence of disorders of the cervical spine, the scapulo-humeral girdle and the upper limbs, indicates the need to consider the forced position to be assumed for a large part of the work activity, staticity, and the inability to move the lower limbs for long periods as the predominant risk in rope work.

Gut represents a major immunological defense barrier with mucosal immune system and intestinal epithelial cells (IECs). In all intestinal diseases, in particular inflammatory bowel disease (IBD), both the absorption and the local immune system are compromised and alternative effective therapies are sought after. Extracellular Vesicles (EVs) have the capability to regulate immune cells within the inflammatory microenvironment, by dampening inflammation and restoring intestinal barrier integrity. Recently, the immune-modulatory role of EVs has also been confirmed for milk EVs (mEVs), notable for their easy production, high sample volumes, cost-effective scalable production and non-toxic and non-immunogenic behavior. In this context, the aim of this study was to evaluate goat mEV anti-inflammatory and immuno-modulating effects on an in vitro model (IPEC-J2) of intestinal inflammation through gene expression evaluation with RT-qPCR and cytokine release dosage with ELISA test. After the establishment of a pro-inflammatory environment due to LPS stimuli, IL6, CXCL8, IL12p35, IL12p40, IFNB, IL18, TLR7 and NOS2 resulted significantly up-regulated in stimulated IPEC-J2 cells compared to those of the basal culture. After 48 h of mEV treatment in inflamed IPEC-J2 a partial restoration of initial conditions was detected, with the IL18 and IL12p40 significant down-regulation, and IL12p35, EBI3, TLR7, BD1 and BD3 up-regulation. IL-18 reduced protein production was also detected in supernatants. Moreover, a decrease of MMP9 and NOS2 together with a strong up-regulation of MUC2 indicated a recovery of cellular homeostasis and, therefore, potential beneficial effects on the intestinal mucosa. Nevertheless, 48 h post-treatment, an increased gene expression and protein release of IL-8 was observed. This paper is one of the firsts to assess the effect of goat mEVs and the first one, in particular, of doing this on an in vitro model of gut inflammation. The obtained results show a potential capability of goat mEVs to modulate inflammation and to play beneficial effects on the intestinal mucosa.

EuroMediterranean Biomedical Journal (EMBJ) can be considered both a scientific journal and a learning tool for “researchers-in-training” coming from Euro-Mediterranean Countries and other areas of the globe. We announce the launch of an international call for grants from Istituto Superiore di Sanità (ISS, the Italian National Institute Health), reserved to young Italian and foreign researchers. We strongly encourage the junior researchers that have authored manuscripts published in EMBJ to consider the application to this extraordinary opportunity.

On 15 March 2021, a new import control system for the European Union was launched, called Import Control System 2 (or ICS2): it will guarantee a more efficient and effective import control activity and facilitate communications between economic operators and customs administrations of Member States. However, a gradual adaptation of the information systems will be necessary and, further, different procedures, especially for postal operators and express carriers, who are the first to deal with the new system, will be needed. There are three versions of the new system, the first just entered into effect and the others to be implemented by 2024: Release 1 requires postal operators and express carriers to submit a subset of their Entry Summary Declaration data, for goods transported by air only; Release 2 will require all air carriers, for all goods transported by air, to integrate the subset of data with the other information required for the complete Entry Summary Declaration; Release 3 requires specific functions to submit the complete Entry Summary Declaration for all goods carried by means of transport other than air, and therefore will concern maritime, rail and road operators as well as certain importers and recipients of the goods in the European Union. Declaration, Control, Summary, Transport, Goods, Carriers, Air, Postal, Import

The European Union and the United Kingdom have reached a last-minute broad agreement on their future relations. In the field of trade and customs operations, rules have been defined to facilitate trade in goods, with the provision of total exemption from import duties for goods originating in one of the two Parties on the basis of rules which, for their characteristics, appear to favour products entirely manufactured in the territory of the Union or of the United Kingdom, albeit with some tolerances. Both for the purposes of proving the requirement of preferential origin and in carrying out customs operations, the Agreement follows a very clear line, simplifying obligations for the economic operators, with the aim of keeping the volume of commercial traffic unchanged, as developed over forty-seven years of union under the European flag. Agreement, United Kingdom, Preferential, REX, Protection, Exports, Origin, Duties, Authorized Economic Operator