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Sergio Minelli,1 Pierluca Minelli,2 Maria Rosa Montinari3 1Department of Cardiology, Local Health Unit Lecce, Lecce, Italy; 2Faculty of Medicine and Surgery “A. Gemelli”, Catholic University of the Sacred Heart, Rome, Italy; 3Department of Biological and Environmental Science and Technology, University of Salento, Lecce, ItalyCorrespondence: Maria Rosa MontinariDepartment of Biological and Environmental Science and Technology, University of Salento, Complex Ecotekne, Way Monteroni, Lecce 73100, ItalyTel +39 083 229 8855Email mariarosa.montinari@unisalento.itAbstract: The clinical manifestations of atherosclerosis are nowadays the main cause of death in industrialized countries, but atherosclerotic disease was found in humans who lived thousands of years ago, before the spread of current risk factors. Atherosclerotic lesions were identified on a 5300-year-old mummy, as well as in Egyptian mummies and other ancient civilizations. For many decades of the twentieth century, atherosclerosis was considered a degenerative disease, mainly determined by a passive lipid storage, while the most recent theory of atherogenesis is based on endothelial dysfunction. The importance of inflammation and immunity in atherosclerosis’s pathophysiology was realized around the turn of the millennium, when in 1999 the famous pathologist Russell Ross published in the New England Journal of Medicine an article entitled “Atherosclerosis – an inflammatory disease”. In the following decades, inflammation has been a topic of intense basic research in atherosclerosis, albeit its importance has ancient scientific roots. In fact, in 1856 Rudolph Virchow was the first proponent of this hypothesis, but evidence of the key role of inflammation in atherogenesis occurred only in 2017. It seemed interesting to retrace the key steps of atherosclerosis in a historical context: from the teachings of the physicians of the Roman Empire to the response-to-injury hypothesis, up to the key role of inflammation and immunity at various stages of disease. Finally, we briefly discussed current knowledge and future trajectories of atherosclerosis research and its therapeutic implications.Keywords: atherosclerosis, history of medicine, cardiovascular disease, inflammation

Pierluca Minelli,1 Maria Rosa Montinari2 1Faculty of Medicine and Surgery “A. Gemelli”, Catholic University of the Sacred Heart, Rome, Italy; 2Department of Biological and Environmental Science and Technology, University of Salento, Lecce, ItalyCorrespondence: Maria Rosa MontinariDepartment of Biological and Environmental Science and Technology, Complex Ecotekne, way Monteroni, University of Salento, Lecce 73100, ItalyTel +39 83 229 8855Email mariarosa.montinari@unisalento.itAbstract: Ancient Greece was the cradle of the Mediterranean food tradition, characterized by the Mediterranean “eternal trinity” wheat - olive oil - wine, the very essence of the country’s traditional agricultural and dietary regime, enriched by a culture of sharing and commensality. This food model, subsequently adopted and spread by the Romans, was rediscovered at the end of the Second World War by two American researchers, Leland Allbaugh and Ancel Keys. With the famous Seven Countries Study, Keys demonstrated for the first time that populations practicing a Mediterranean diet - such as the Greeks and southern Italians - showed low mortality rates from ischemic heart disease compared to the peoples of Northern Europe and North America. Since then, numerous subsequent epidemiological studies and randomized clinical trials have confirmed the beneficial effects of the Mediterranean diet both in primary and secondary prevention of cardiovascular diseases. This review will focus on the origins of the Mediterranean diet from its roots and its relationship to cardiovascular disease, with a brief overview of the nutritional mechanisms that influence atherosclerosis.Keywords: mediterranean diet, cardiovascular disease, medical history

This study focuses on the ethical foundations of learning in virtual environments and identifies the ethical values perceived by university students and faculty in the learning process. We analyzed 235 participants, including students from different Spanish-speaking countries and virtual education teachers, and employed a design-based research methodology using quantitative tools for empirical data collection. The analysis showed that: (a) the learning experience in virtual environments is ethical; (b) responsibility, commitment, respect, solidarity, and tolerance can be considered typical of learning in virtual learning environments; and (c) students and teachers have shared ethical experiences regarding the values considered most relevant in virtual education.

Abstract Ubiquitination is a posttranslational modification in eukaryotes that plays a significant role in the infection of intracellular microbial pathogens, such as Legionella pneumophila. While the Legionella-containing vacuole (LCV) is coated with ubiquitin (Ub), it avoids recognition by autophagy adaptors. Here, we report that the Sdc and Sde families of effectors work together to build ubiquitinated species around the LCV. The Sdc effectors catalyze canonical polyubiquitination directly on host targets or on phosphoribosyl-Ub conjugated to host targets by Sde. Remarkably, Ub moieties within poly-Ub chains are either modified with a phosphoribosyl group by PDE domain-containing effectors or covalently attached to other host substrates via Sde-mediated phosphoribosyl-ubiquitination. Furthermore, these modifications prevent the recognition by Ub adaptors and therefore exclude host autophagy adaptors from the LCV. In this work, we shed light on the nature of the poly-ubiquitinated species present at the surface of the LCV and provide a molecular mechanism for the avoidance of autophagy adaptors by the Ub-decorated LCV.

Abstract Background Electroconvulsive therapy (ECT) benefits patients with treatment-resistant depression (TRD), but the underlying biological processes are unclear. We conducted an epigenome-wide association study in 32 TRD patients undergoing ECT to depict ECT-associated methylation changes. Illness severity and ECT outcomes were assessed with the Montgomery–Åsberg Depression Rating Scale at baseline (T0) and 1 month after its end (T1). Methylation was profiled at T0 and T1 with the Illumina Infinium Methylation EPIC BeadChip array. Results Longitudinal T0–T1 analyses showed 3 differentially methylated probes (DMPs) with nominal p values ≤ 10−5, with 2 annotated in the genes CYB5B and PVRL4. Including covariates, we found 4 DMPs for symptoms variation, annotated in FAM20C, EPB41, OTUB1 and ADARB1, and 3 DMPs for response status, with 2 annotated in IQCE and FAM20C. Regional analysis revealed 54 differentially methylated regions (DMRs) with nominal p value area ≤ 0.05, with 9 presenting adjusted p-value area ≤ 0.10, annotated in MCF2L, SLC25A24, RUNX3, MIR637, FOXK2, FAM180B, POU6F1, ALS2CL and CCRL2. Considering covariates, we found 21 DMRs for symptoms variation and 26 DMRs for response (nominal p value area ≤ 0.05), with 4 presenting adjusted p-value area ≤ 0.10 for response, annotated in SNORD34, NLRP6, GALNT2 and SFT2D3. None remained significant after false discovery rate correction. Notably, ADARB1 variants are associated with suicide attempt in patients with psychiatric disorders, and SLC25A24 relates to conduct disorder. Several DMPs and DMRs are annotated in genes associated with inflammatory/immune processes. Longitudinal analyses on females (n = 22) revealed statistically significant DMRs (adjusted p value area ≤ 0.05) and trend-significant DMRs (adjusted p value area ≤ 0.07) for symptoms variation and response status, annotated in genes related to psychiatric disorders (ZFP57, POLD4, TRIM10, GAS7, ADORA2A, TOLLIP), trauma exposure (RIPOR2) and inflammatory/immune responses (LAT, DLX4, POLD4, FAM30A, H19). Pathway analysis on females revealed enrichment for transcriptional activity, growth factors, DNA maintenance, and immune pathways including IRF7 and IRF2. Conclusion Although no significant results were found for the whole cohort, the study provides insights into ECT-associated methylation changes, highlighting DMPs and DMRs related to ECT outcomes. Analyses on females revealed significant DMRs and pathways related to psychiatric disorders and inflammatory/immune processes.

Congenital pseudarthrosis of the tibia (CPT) is a rare disorder affecting the skeletal system in pediatric population with an estimated incidence of 1:140,000 to 1:250,000 newborns. It is characterized by deformity of the tibia, including anterolateral bowing of the bone diaphysis and/or narrowing of the medullary canal, leading to instability or fracture. CPT can be either idiopathic or associated with underlying conditions such as type 1 neurofibromatosis (NF1), fibrous dysplasia, or Campanacci's osteofibrous dysplasia. Diagnosis is based on clinical and imaging findings, using conventional radiography and magnetic resonance imaging (MRI). The disorder is characterized by recurrent pathological fractures of the tibia or fibula during childhood, often beginning by the age of 2 years. Treatment options include surgical and nonsurgical management.

Los valores en la docencia son un tema de gran interés debido a su relevancia y trascendencia en la formación del alumnado. Este trabajo pretende recopilar las investigaciones que abordan dicha temática con el fin de sistematizar y analizar el cuerpo de evidencias generadas. La revisión incluyó 32 artículos extraídos de las bases de datos SCOPUS, ERIC y Dialnet. Se encontró que las investigaciones analizadas muestran coincidencias en la metodología, técnica de recolección de datos y resultados. El corpus de estudios analizados destaca la importancia de los valores en la práctica docente, siendo los valores más mencionados la responsabilidad, el respeto y el compromiso. Se encontraron también otros aspectos como las estrategias que se utilizan en el aula, algunas dificultades para la enseñanza de valores y otras variables que pueden intervenir en este proceso. A partir de los resultados se recomienda realizar investigaciones que estudien y traten de comprender de forma más profunda el tema utilizando diversas técnicas de recogida más complejas que permitan realizar una triangulación de la información y determinar el impacto que tienen los valores en la formación y el aprendizaje de los estudiantes, al igual que implementar en las instituciones estrategias como la evaluación docente de forma sistemática, la creación de códigos de ética, la capacitación al docente y la inclusión formal de estos temas en los planes de estudio.

Learning in virtual environments is an ethical experience. This research aimed to understand the ethical experience of a virtual learning environment from the perspective of university students and their teachers. The participants were 205 higher education students from different Spanish-speaking countries (Colombia, Argentina, Mexico, Ecuador, and Spain) and 30 teachers who acted as tutors in virtual education. The study used a design-based research method and quantitative instruments for the collection of empirical data. The data analysis showed that students and teachers perceive responsibility, commitment, and respect as values inherent to virtual education, and may have a moderately different ethical experience based on these values. With this research, we intend to contribute to a better understanding of the coexistence of human beings in virtual learning environments. We argue that it is necessary to question or rethink the pedagogical paradigms that guide virtual education, endowing them with humanity, and recognizing their ethical dimension as funda-mental.

Viral vectors are agents enabling gene transfer and genome editing and have widespread utility across the healthcare and biotechnology sectors. In January 2023, the International Bureau for Weights and Measures’ Consultative Committee for Amount of Substance (CCQM) held a workshop on Metrology for Viral systems as molecular tools. The workshop brought together international leaders from across regulatory, industry, government science, and metrology sectors to better understand key challenges for the community: Exploring current limitations in the measurement of virus-derived, virus-based, and virus-like systems in terms of quantification and characterisation; surveying the state-of-the-art in analytical methods and reference material provision for these entities; and initiating a dialog for the strategic development and implementation of suitable standardisation approaches for this sector. This article presents the workshop background and rationale, presentation summaries, conclusions, and recommendations.

RSV infection causes severe respiratory illness and mortality in the elderly, especially in the presence of comorbidities. Early identification of infection would result in appropriate clinical-therapeutic management, avoiding hospitalizations, the risk of healthcare-associated infections, and inappropriate antibiotic prescriptions, thus reducing healthcare costs and fighting antimicrobial resistance. The aim of this study was to assess RSV hospitalizations in subjects >64 years hospitalized in a large tertiary care hospital in Southern Italy, in order to assess their usefulness as a proxy for targeting a potential vaccination strategy. Fifty-two RSV-positive patients were identified from the 2014–2015 to the 2022–2023 seasons. RSV type B was found in 71.2% of cases. The median age was 78 years (IQR: 72–84) and 40.4% of the subjects had at least one comorbidity; 5.8% needed intensive care. The use of combined rapid tests for SARS-CoV-2/influenza/RSV identification in primary care settings may contribute to an improved definition of the burden of RSV in the elderly. The implementation of an anti-RSV vaccination strategy in the elderly population would reduce direct and indirect infection costs. More robust epidemiological data in Italy are needed for targeted preventive strategies.

Abstract Background Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018. Methods The Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20–84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater. Results During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107–109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer. Conclusions For the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.

This retrospective cohort study evaluated the effectiveness of maternal vaccination against COVID-19 in reducing the risk of SARS-CoV-2 infection in infants younger than 12 months. The study, conducted at the “Policlinico” University Hospital of Bari, included 3346 newborns and their mothers. The study explored the degree of protection offered by maternal vaccination depending on the timing, type, and trimester of vaccination, also taking into account the mother’s history of infection. We compared the incidence rate of infection between children of vaccinated and unvaccinated mothers; the values were 10.2% and 18.1%, respectively, and the difference was statistically significant. The overall effectiveness of the vaccine against the infection was 45%. Further analysis revealed increasing efficacy as the doses of vaccine administered to the mother increased and in case of a previous history of maternal infection. Dual immune stimulation (vaccination and natural infection) was 83% effective in preventing infection among newborns. The multivariable models confirmed the protective effect of vaccination with all types of vaccines used. The analysis of infection’s incidence in newborns revealed an interesting temporal trend, with increasing incidence with time, suggesting a possible correlation with the persistence of maternal antibodies or with the gradual weaning. The results on the protective capacity of vaccines are in line with the global literature. Strengths of study include sample size, robust methodology, and multivariate analyses. Institutions could intensify awareness campaigns to encourage both pregnant women and all those who would like to become pregnant to receive SARS-CoV-2 vaccination.

ABSTRACTBackground: Stressful events increase the risk for treatment-resistant depression (TRD), and trauma-focused psychotherapy can be useful for TRD patients exposed to early life stress (ELS). Epigenetic processes are known to be related to depression and ELS, but there is no evidence of the effects of trauma-focused psychotherapy on methylation alterations.Objective: We performed the first epigenome-wide association study to investigate methylation changes related to trauma-focused psychotherapies effects in TRD patients.Method: Thirty TRD patients assessed for ELS underwent trauma-focused psychotherapy, of those, 12 received trauma-focused cognitive behavioural therapy, and 18 Eye Movement Desensitization and Reprocessing (EMDR). DNA methylation was profiled with Illumina Infinium EPIC array at T0 (baseline), after 8 weeks (T8, end of psychotherapy) and after 12 weeks (T12 – follow-up). We examined differentially methylated CpG sites and regions, as well as pathways analysis in association with the treatment.Results: Main results obtained have shown 110 differentially methylated regions (DMRs) with a significant adjusted p-value area associated with the effects of trauma-focused psychotherapies in the entire cohort. Several annotated genes are related to inflammatory processes and psychiatric disorders, such as LTA, GFI1, ARID5B, TNFSF13, and LST1. Gene enrichment analyses revealed statistically significant processes related to tumour necrosis factor (TNF) receptor and TNF signalling pathway. Stratified analyses by type of trauma-focused psychotherapy showed statistically significant adjusted p-value area in 141 DMRs only for the group of patients receiving EMDR, with annotated genes related to inflammation and psychiatric disorders, including LTA, GFI1, and S100A8. Gene set enrichment analyses in the EMDR group indicated biological processes related to inflammatory response, particularly the TNF signalling pathway.Conclusion: We provide preliminary valuable insights into global DNA methylation changes associated with trauma-focused psychotherapies effects, in particular with EMDR treatment.

Addressing the thermal loss from building envelopes is a crucial challenge and requires the exploration of various mitigation strategies. This study employs comprehensive 3D computational fluid dynamics simulations to investigate the incorporation of various bio-based Phase Change Materials (PCMs) including CrodaTherm (CT) 19, CT21, and CT24W, within inter-floor void formers between the roof-floor boundary in multi-story office buildings to optimize energy management during inactive periods in one of the adjacent units. Aside from the PCM type, the void former shape, its placement, and the combinations of PCMs and insulating layers are examined through heat flux and solid fraction plots as well as liquid fraction contours. Results highlight the exceptional performance of CT24W-integrated void formers, achieving a remarkable 36.74 % reduction in the 48-h average heat flux in comparison with the case without void formers, and offering lower heat flux values than the scenario with insulating layers for 89.38 h (endurance time). Based on the findings, with identical PCM volumes, the semi-ellipsoid PCM-integrated void former provides 11.07 % lower heat flux and 27.56 % longer endurance time compared to the one with a spherical shape. The results underscore PCM integration as a superior strategy over standalone insulation for managing thermal loss between apartment floors.

IntroductionSARS-CoV-2 infection has been associated with the onset or persistence of symptoms in the long-term after the acute infection is resolved. This condition known as Post-COVID, might be particularly severe and potentially life-threatening. However, little is known on the impact of post-COVID condition on mortality. Aim of the present study is to assess and quantify Post-COVID deaths in Italy in years 2020 and 2021, based on an analysis of death certificates.MethodsData from the Italian National Cause of Death Register were analyzed. ICD-10 code U09.9, released by the World Health Organization in September 2020, was used to identify the ‘Post-COVID’ condition. Numbers of post-COVID deaths from October 2020 to December 2021 were analyzed. Rates of post-COVID deaths were calculated for the year 2021.ResultsBetween October 2020 and December 2021, 4,752 death certificates reporting post-COVID condition were identified. Of these, 14.9% (n = 706) occurred between October and December 2020 and 85.1% (n = 4,046) in 2021. In 46.0% of post-COVID-related deaths, the underlying cause of death was COVID-19. Other frequent underlying causes were heart disease (14.3% of cases), neoplasms (9.2%), cerebrovascular diseases (6.3%) and Alzheimer’s disease and other dementias (5.5%). The mortality rate related to post-COVID conditions in year 2021 was 5.1 deaths per 100 thousand inhabitants and it increased with increasing age. Men showed a higher mortality rate than women (4.3 deaths per 100 thousand in women and 6.0 deaths per 100 thousand in men).DiscussionPost-COVID conditions contributed to a substantial number of deaths in Italy. Strategies to identify the population at risk of severe long-term consequences of SARS-CoV-2 infection and interventions aimed at reducing this risk must be developed.

Abstract Background Actinomyces turicensis is rarely responsible of clinically relevant infections in human. Infection is often misdiagnosed as malignancy, tuberculosis, or nocardiosis, therefore delaying the correct identification and treatment. Here we report a case of a 55-year-old immunocompetent adult with brain abscess caused by A. turicensis. A systematic review of A. turicensis infections was performed. Methods A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases MEDLINE, Embase, Web of Science, CINAHL, Clinicaltrials.gov and Canadian Agency for Drugs and Technology in Health (CADTH) were searched for all relevant literature. Results Search identified 47 eligible records, for a total of 67 patients. A. turicensis infection was most frequently reported in the anogenital area (n = 21), causing acute bacterial skin and skin structure infections (ABSSSI) including Fournier’s gangrene (n = 12), pulmonary infections (n = 8), gynecological infections (n = 6), cervicofacial district infections (n = 5), intrabdominal or breast infections (n = 8), urinary tract infections (n = 3), vertebral column infections (n = 2) central nervous system infections (n = 2), endocarditis (n = 1). Infections were mostly presenting as abscesses (n = 36), with or without concomitant bacteremia (n = 7). Fever and local signs of inflammation were present in over 60% of the cases. Treatment usually involved surgical drainage followed by antibiotic therapy (n = 51). Antimicrobial treatments most frequently included amoxicillin (+clavulanate), ampicillin/sulbactam, metronidazole or cephalosporins. Eighty-nine percent of the patients underwent a full recovery. Two fatal cases were reported. Conclusions To the best of our knowledge, we hereby present the first case of a brain abscess caused by A. turicensis and P. mirabilis. Brain involvement by A. turicensis is rare and may result from hematogenous spread or by dissemination of a contiguous infection. The infection might be difficult to diagnose and therefore treatment may be delayed. Nevertheless, the pathogen is often readily treatable. Diagnosis of actinomycosis is challenging and requires prompt microbiological identification. Surgical excision and drainage and antibiotic treatment usually allow for full recovery.

Inferior vena cava leiomyosarcoma is a rare malignant mesenchymal tumor that originates from the smooth muscle cells of the venous media and is more frequent in females in the V-VI decade of life. Due to scarce and specific symptoms, diagnosis is not simple, and often metastases to the liver, lungs, and/or lymph nodes are already present. A 44-year-old male patient arrives at our institution presenting diffuse abdominal pain and a sense of weight associated with lumbar pain. He showed nothing relevant except for a moderate consumption of alcohol. Ultrasound examination of the abdomen revealed liver enlargement with hyperechoic nodularity and clear margins. Furthermore, the presence of a voluminous solid nodular formation was found, with an inhomogeneous echostructure and moderate vascularization on Doppler. Inferior vena cava leiomyosarcoma is a rare malignancy. The diagnosis is usually established after surgery, however, recurrences are common and the role of chemoradiation therapy remains to be defined. The only potential treatment is surgical resection with possible vessel reconstruction and en bloc removal of adjacent structures with 5 and 10-year survival rates of 49% and 29%, respectively.