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Simple Summary: Prostheses are highly beneficial as they reduce the need for formal healthcare and support services, but they are not without side effects. Despite advancements, issues such as implant rejection and perioperative complications persist, and new concerns have arisen, including the potential link between long-term prosthetic use and cancer, specifically lymphoma. While the overall risk of developing lymphoma from prosthetic implants remains low, it is essential to explore the factors contributing to this risk. This highlights the need for ongoing research into the safety and long-term effects of prosthetic devices. Based on this evidence, we conducted a descriptive analysis using individual patient data from primary studies to investigate the relationship between lymphomas and different types of prosthetic devices, excluding breast implants. Background: Medical devices used for functional or esthetic purposes improve health and quality of life; however, they are not risk-free. Anaplastic large-cell lymphoma (ALCL), associated with breast implants, is a well-known and recognized distinct lymphoma entity. More recently, additional lymphomas have been reported in relation to prosthesis other than breast implants, as these allow the pericyte to develop into a clone that undergoes a maturation process, progressing toward full malignancy. Methods: We performed a systematic review with a descriptive analysis of data extracted from primary studies following PRISMA guidelines, including the search string "(IMPLANT* OR PROSTHES*) AND LYMPHOM*" in the PubMed, Scopus, Embase, and Google-Scholar databases. Data such as patient sex, age, implant site, prosthesis material, and lymphoma type were analyzed. Statistical methods, including Student's t-test and Fisher's exact test, were employed to compare lymphoma characteristics, with significance set at a p-value < 0.05. Results: From a total of 5992 studies, we obtained 43 case reports and series on a total of 52 patients diagnosed with prosthesis-associated lymphomas. The majority of implant-related lymphoma cases (85%) were of the B-cell type, mostly fibrin-associated large B-cell lymphoma (LBCL). This lymphoma type was more associated with biological (non-human-derived biological tissue), metallic, and synthetic implants (synthesized from non-organic components) (p-value = 0.007). Patients with ALCL had equal frequencies of metal and silicone prostheses (37.5%, 3 cases each), followed by synthetic prostheses (25%, 2 cases). ALCL cases were most common at skeletal (50%) and muscular-cutaneous sites (25%), whereas B-cell lymphomas were predominantly found in cardiovascular implants (50%), followed by skeletal (27%) and muscular-cutaneous (21%) sites. Death attributed to lymphoma took place in 67% of the cases, mostly LBCL occurring in cardiovascular sites. Conclusions: Because the included studies were limited to case reports and series, a potential non-causal link might have been documented between different implant materials, implant sites and lymphoma types. This underscores the importance of further comprehensive research and monitoring of non-breast implants. [ABSTRACT FROM AUTHOR]

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Dietary changes expose consumers to risks from Anisakis larvae in seafood, leading to parasitic diseases and allergies. Anisakis is recognized by EFSA as a significant hazard, with potential oncogenic implications. Diagnostic advancements, like the Basophil Activation Test (BAT), enhance sensitivity and accuracy in identifying Anisakis sensitization, complementing traditional IgE tests. We conducted a cross-sectional study on patients with allergic symptoms from April 2021 to April 2023 at two outpatient clinics in western Sicily. Our goal was to assess the prevalence of Anisakis-related allergies and to identify risk profiles using specific Anisakis IgE and the BAT, especially in regions with high raw fish consumption. The study evaluated specific Anisakis IgE as a screening tool for Anisakis sensitization, using questionnaires, blood samples, and immuno-allergology analyses. Anisakis-specific IgE values were compared with the BAT results, with statistical analyses including Fisher's exact test and logistic regression. The results showed an 18.5% seroprevalence of Anisakis IgE, while the BAT as a second-level test showed 4.63%, indicating the BAT's superior specificity and accuracy. The study highlighted the importance of the BAT in diagnosing Anisakis sensitization, especially in cases of cross-reactivity with Ascaris and tropomyosin. The findings confirm the BAT's exceptional specificity in identifying Anisakis sensitization and support using Anisakis-specific IgE for population-based risk profiling. The BAT can effectively serve as a confirmatory test. [ABSTRACT FROM AUTHOR]

Background: Influenza represents a serious public health threat, especially for the management of severe cases and complications of the disease, requiring the implementation of control measures. We aimed to assess the acceptance and impact of qLAIV vaccination among a representative sample of family paediatricians (FPs) operating in Palermo Local Health Authority (LHA). To this end we evaluated vaccination coverage rates, comparing it with that observed in Sicilian context, while actively monitoring possible adverse reactions and their severity. Methods: An observational descriptive non-controlled study was conducted in two phases, from September 2022 to June 2023. The first phase involved a formative and educational intervention with a pre-intervention questionnaire to assess the knowledge and attitudes of FPs on paediatric influenza vaccination. The second phase consisted of an active surveillance on qLAIV safety and acceptance among the paediatric population assisted by the participating FPs, from October 2022 to April 2023. Frequencies, chi-squared tests, and comparisons statistics were performed using Stata/MP 14.1. Results: The overall coverage rate among the paediatric population involved in the intervention was 13.2%, with an I.M./qLAIV ratio of vaccine administered of 1/4.25. This coverage rate was significantly higher (p-value <0.001) when compared to the average values reported in the population under the Palermo Local Health Authority (LHA) (6.7%) and in the entire Sicily (5.9%). Adverse events in the qLAIV group were mild, with only 3.3% experiencing them, primarily presenting as a feverish rise (3.2%). No severe adverse reaction was reported. Conclusions: The educational intervention significantly raised paediatric influenza vaccination rates among the participating FPs, and in general improved influenza vaccination coverage rates in the Palermo's LHU. Minimal, non-serious adverse events underscored the vaccine's safety. Training sessions ensured paediatricians stayed informed, enabling them to provide comprehensive information to parents for secure and informed vaccination decisions in their practices. [ABSTRACT FROM AUTHOR]

Background: Vulvar squamous cell carcinoma (VSCC) has been recently associated with Equus caballus papillomavirus type 2 (EcPV2) infection. Still, few reports concerning this disease are present in the literature. Objective: To describe a case of naturally occurring EcPV2‐induced VSCC, by investigating tumour ability in undergoing the epithelial‐to‐mesenchymal transition (EMT). Study design: Case report. Methods: A 13‐year‐old Haflinger mare was referred for a rapidly growing vulvar mass. After surgical excision, the mass was submitted to histopathology and molecular analysis. Histopathological diagnosis was consistent with a VSCC. Real‐time qPCR, real‐time reverse transcriptase (RT)‐qPCR and RNAscope were carried out to detect EcPV2 infection and to evaluate E6/E7 oncogenes expression. To highlight the EMT, immunohistochemistry (IHC) was performed. Expression of EMT‐related and innate immunity‐related genes was investigated through RT‐qPCR. Results: Real‐time qPCR, RT‐qPCR and RNAscope confirmed EcPV2 DNA presence and expression of EcPV2 oncoproteins (E6 and E7) within the neoplastic vulvar lesion. IHC highlighted a cadherin switch together with the expression of the EMT‐related transcription factor HIF1α. With RT‐qPCR, significantly increased gene expression of EBI3 (45.0 ± 1.62, p < 0.01), CDH2 (2445.3 ± 0.39, p < 0.001), CXCL8 (288.7 ± 0.40, p < 0.001) and decreased gene expression of CDH1 (0.3 ± 0.57, p < 0.05), IL12A (0.04 ± 1.06, p < 0.01) and IL17 (0.2 ± 0.64, p < 0.05) were detected. Main limitations: Lack of ability to generalise and danger of over‐interpretation. Conclusion: The results obtained were suggestive of an EMT event occurring within the neoplastic lesion. [ABSTRACT FROM AUTHOR]

Simple Summary: The epidemiology of primary liver cancer is changing according to effective primary prevention interventions, a strictly clinical follow up of chronic patients with hepatitis and successful drug treatments of virus-related liver diseases. A reduction in virus-related hepatocellular carcinomas cases was followed by an increase in the non-viral aetiology, including metabolic and cryptogenetic factors. We used cancer surveillance data to investigate determinants potentially associated with primary liver cancer survival in a southern Italian setting characterised by a high prevalence of hepatitis viral infections and overweight and obesity. Our study provided some new insights into the potential relationship between deprivation, geographic location, access to care and hepatocarcinoma survival. Comprehensive national and regional health plans should consider the evidence provided to ensure equitable access to prevention and care pathways. While entering the digital prevention era, interoperating cancer registries with other sources providing data on lifestyles and health determinants should be promoted. A retrospective observational study utilising cancer incidence data from a population-based registry investigated determinants affecting primary liver cancer survival in a southern Italian region with high hepatitis viral infection rates and obesity prevalence. Among 2687 patients diagnosed between 2006 and 2019 (65.3% male), a flexible hazard-based regression model revealed factors influencing 5-year survival rates. High deprivation levels [HR = 1.41 (95%CI = 1.15–1.76); p < 0.001], poor access to care [HR = 1.99 (95%IC = 1.70–2.35); p < 0.0001], age between 65 and 75 [HR = 1.48 (95%IC = 1.09–2.01); p < 0.05] or >75 [HR = 2.21 (95%CI = 1.62–3.01); p < 0.0001] and residing in non-urban areas [HR = 1.35 (95%CI = 1.08–1.69); p < 0.01] were associated with poorer survival estimates. While deprivation appeared to be a risk factor for primary liver cancer patients residing within the urban area, the geographic distance from specialised treatment centres emerged as a potential determinant of lower survival estimates for residents in the non-urban areas. After balancing the groups of easy and poor access to care using a propensity score approach, poor access to care and a lower socioeconomic status resulted in potentially having a negative impact on primary liver cancer survival, particularly among urban residents. We emphasise the need to interoperate cancer registries with other data sources and to deploy innovative digital solutions to improve cancer prevention. [ABSTRACT FROM AUTHOR]

Vulvo-vaginal epithelial tumors are uncommon in mares, and data on the epithelial-to-mesenchymal transition (EMT) and the tumor-immune microenvironment (TIME) are still lacking. This is a study investigating the equus caballus papillomavirus type 2 (EcPV2) infection state as well as the EMT process and the tumor microenvironment in vulvo-vaginal preneoplastic/ benign (8/22) or malignant (14/22) epithelial lesions in mares. To do this, histopathological, immunohistochemical, transcriptomic, in situ hybridization, and correlation analyses were carried out. Immunohistochemistry quantification showed that cytoplasmic E-cadherin and β-catenin expression as well as nuclear β-catenin expression were features of malignant lesions, while benign/preneoplastic lesions were mainly characterized by membranous E-cadherin and β-catenin expression. Despite this, there were no differences between benign and malignant equine vulvo-vaginal lesions in the expression of downstream genes involved in the canonical and noncanonical wnt/β-catenin pathways. In addition, malignant lesions were characterized by a lower number of cells with cytoplasmic cytokeratin expression as well as a slightly higher cytoplasmic vimentin immunolabeling. The TIME of malignant lesions was characterized by more numerous CD204+ M2-polarized macrophages. Altogether, our results support the hypothesis that some actors in TIME such as CD204+ M2-polarized macrophages may favor the EMT process in equine vulvo-vaginal malignant lesions providing new insights for future investigations in the field of equine EcPV2-induced genital neoplastic lesions. [ABSTRACT FROM AUTHOR]

Simple Summary: Olive mill waste-water (OMWW) is a liquid waste produced by the olive oil industry that has been recently regarded as a good source of polyphenols. Phenolic molecules are among the most active secondary molecules in the gut for their antioxidant, anti-inflammatory and antimicrobial effects. They may also contribute to positively changing the distribution of gut microbial species, but their effects have not been widely explored in pigs. The intestinal porcine epithelial cell line IPEC-J2 represents a good model for the study of innate immunity and inflammatory response in animal intestinal diseases and has already been used to investigate the effect of phytogenic feed additives on swine intestinal epithelium. This study aimed to evaluate the in vitro effects of an OMWW extract enriched in polyphenols on Salmonella typhimurium (S. typhimurium) infection in IPEC-J2 cells. Polyphenols extracted from OMWW showed the ability to regulate the host–pathogen interaction by decreasing S. typhimurium invasiveness and modulating the expression of many innate immune genes. The dietary supplementation of olive oil by-products, including olive mill waste-water (OMWW) in animal diets, is a novel application that allows for their re-utilization and recycling and could potentially decrease the use of antibiotics, antimicrobial resistance risk in livestock species, and the occurrence of intestinal diseases. Salmonella serovar typhimurium is one of the most widespread intestinal pathogens in the world, causing enterocolitis in pigs. The aim of this study was to investigate the effect of an OMWW extract enriched in polyphenols (hydroxytyrosol and tyrosol) in the immune response of an intestinal porcine epithelial cell line (IPEC-J2) following S. typhimurium infection. Cells were pre-treated with OMWW-extract polyphenols (OMWW-EP, 0.35 and 1.4 µg) for 24 h and then infected with S. typhimurium for 1 h. We evaluated bacterial invasiveness and assayed IPEC-J2 gene expression with RT-qPCR and cytokine release with an ELISA test. The obtained results showed that OMWW-EP (1.4 µg) significantly reduced S. typhimurium invasiveness; 0.35 µg decreased the IPEC-J2 gene expression of IL1B, MYD88, DEFB1 and DEFB4A, while 1.4 µg down-regulated IL1B and DEFB4A and increased TGFB1. The cytokine content was unchanged in infected cells. This is the first study demonstrating the in vitro immunomodulatory and antimicrobial activity of OMWW extracts enriched in polyphenols, suggesting a protective role of OMWW polyphenols on the pig intestine and their potential application as feed supplements in farm animals such as pigs. [ABSTRACT FROM AUTHOR]

The European healthcare sector faces a significant shortage of healthcare workers. Assessing the prevalence of this issue and understanding its direct and indirect determinants are essential for formulating effective recruitment programs and enhancing job retention strategies for physicians and nurses. A multicentric cross-sectional study was conducted, involving 381 physicians and 1351 nurses recruited from eight European hospitals in Belgium, the Netherlands, Italy, and Poland. The study focused on assessing turnover intentions among healthcare workers based on the Job Demands-Resources model, using an online questionnaire. Structural equation models were employed to test the data collection questionnaires' construct validity and internal consistency. The turnover intention was assessed by agreement with the intention to leave either the hospital or the profession. Among physicians, 17% expressed an intention to leave the hospital, while 9% intended to leave the profession. For nurses, the figures were 8.9% and 13.6%, respectively. The internal consistency of the questionnaires exceeded 0.90 for both categories of health workers. Depersonalization and job dissatisfaction were identified as direct determinants of turnover intention, with work engagement being particularly relevant for nurses. We found a higher intention to leave the hospital among physicians, while nurses were more prone to leave their profession. To mitigate turnover intentions, it is recommended to focus on improving job satisfaction, work engagement and fostering a positive working climate, thereby addressing depersonalisation and promoting job retention. [ABSTRACT FROM AUTHOR]

Introduction: Breast implant-associated anaplastic large-cell lymphoma (BIAALCL) 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 investigated the main characteristics of the disease and the factors predicting BIA-ALCL onset in patients with and without an implant replacement. Methods: A quantitative analysis was performed by two independent researchers on cases extracted from 52 primary studies (case report, case series, and systematic review) published until April 2022 and searched in PubMed, Scopus, and Google-Scholar databases using "Breast-Implant" AND/OR "Associated" AND/OR "Anaplastic-Large-Cell-Lymphoma". The statistical significance was verified by Student's t-test for continuous variables, while Fisher's exact test was applied for qualitative variables. Cox model with time-dependent covariates was used to estimate BIA-ALCL's onset time. The Kaplan-Meier model allowed the estimation of the probability of survival after therapy according to breast implant exposure time. Results: Overall, 232 patients with BIA-ALCL were extracted. The mean age at diagnosis was 55 years old, with a mean time to disease onset from the first implant of 10.3 years. The hazard of developing BIA-ALCL in a shorter time resulted significantly higher for patients not having an implant replacement (hazard ratio = 0.03; 95%CI: 0.005-0.19; p-value < 0.01). Patients with implant replacement were significantly older than patients without previous replacement at diagnosis, having a median time to diagnosis since the first implant of 13 years (7 years in patients without replacement); anyway, the median time to BIA-ALCL occurrence since the last implantation was equal to 5 years. Discussion: Our findings suggest that, in BIA-ALCL patients, the implant substitution and/or capsulectomy may delay the disease's onset. However, the risk of reoccurrence in an earlier time should be considered in these patients. Moreover, the time to BIA-ALCL onset slightly increased with age. Selection bias, lack of awareness, misdiagnosis, and limited data availability could be identified as limits of our study. An implant replacement should be considered according to a risk stratification approach to delay the BIA-ALCL occurrence in asymptomatic patients, although a stricter follow-up after the implant substitution should be recommended. [ABSTRACT FROM AUTHOR]

Papillomas are benign epithelial lesions protruding on the epithelial surfaces as finger-like or warty projections. These lesions are often caused by papillomavirus (PV) infection. Congenital papillomas have been reported in foals. However, to date, no evidence of PV infection has been provided. In the present paper, we describe the main clinical–pathological features of a congenital papilloma observed in a foal. In addition, biomolecular tests demonstrated BPV1 infection in the case under study. Such data stimulate further investigations, even on archived samples, aiming to clarifying the etiology of equine congenital papilloma and the clinical relevance, if any, of BPV1 vertical transmission in horses. [ABSTRACT FROM AUTHOR]

Introduction: Extracellular vesicles (EVs) are nanometric-membrane-bound subcellular structures, which can be recovered from milk. Milk EVs have drawn increasing interest due to their potential biomedical applications, therefore it is important to investigate their impact on key immune cells, such as macrophages. Methods: In this work, the immunomodulatory effects of goat milk EVs on untreated (moMΦ) and classically activated (moM1) porcine monocyte-derived macrophages were investigated using flow cytometry, ELISA, and gene expression assays. Results: These particles were efficiently internalized by macrophages and high doses (60 mg protein weight) triggered the upregulation of MHC I and MHC II DR on moMΦ, but not on moM1. In moMΦ, exposure to low doses (0.6 mg) of mEVs enhanced the gene expression of IL10, EBI3, and IFNB, whereas high doses up-regulated several pro-inflammatory cytokines. These nanosized structures slightly modulated cytokine gene expression on moM1. Accordingly, the cytokine (protein) contents in culture supernatants of moMO were mildly affected by exposure to low doses of mEVs, whereas high doses promoted the increased release of TNF, IL-8, IL-1a, IL-1b, IL-1Ra, IL-6, IL-10, and IL-12. The cytokines content in moM1 supernatants was not critically affected. Discussion: Overall, our data support a clinical application of these molecules: they polarized macrophages toward an M1-like phenotype, but this activation seemed to be controlled, to prevent potentially pathological over-reaction to stressors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The rising popularity of undercooked or raw seafood containing larvae of the Anisakis parasite has led to issues of public health concern due to allergic manifestations. We conducted an observational study on the use of an innovative Anisakis allergy diagnostic algorithm in a convenience sample of 53 allergic outpatients recruited in Western Sicily, between April 2021 and March 2022. We included individuals with an anamnesis suggestive of IgE sensitization to Anisakis reporting clinical manifestation in the last month due to allergic reactions after eating fresh fish, or in subjects at high exposure risk with sea products while abstaining from fish ingestion, excluding those with documented fish sensitization. Outpatients were tested via Skin Prick Test, IgE-specific dosage and Basophil Activation Test (BAT). Twenty-six outpatients were diagnosed with Anisakis, while 27 with Chronic Urticaria (CU). We found a seven-fold excess risk for Anisakis (p4) positivity in the Anisakis allergic outpatients, as compared to the CU ones. BAT showed the best diagnostic accuracy (92.45%) and specificity (100%), while specific IgE to Ascaris (p1) documented the best sensitivity (92.31%) but a very low specificity (37.04%). In conclusion, our findings may represent a potentially useful contribution to the future development of updated clinical guidelines. [ABSTRACT FROM AUTHOR]

Papillomaviruses (PVs) are small, non-enveloped viruses, ubiquitous across the animal kingdom. PVs induce diverse forms of infection, such as cutaneous papillomas, genital papillomatosis, and carcinomas. During a survey on the fertility status of a mare, a novel Equus caballus PV (EcPV) has been identified using Next Generation Sequencing, and it was further confirmed with genome-walking PCR and Sanger sequencing. The complete circular genome 7607 bp long shares 67% average percentage of identity with EcPV9, EcPV2, EcPV1, and EcPV6, justifying a new classification as Equus caballus PV 10 (EcPV10). All EcPV genes are conserved in EcPV10, and phylogenetic analysis indicates that EcPV10 is closely related to EcPV9 and EcPV2, genus Dyoiota 1. A preliminary EcPV10 genoprevalence study, carried out on 216 horses using Real Time PCRs, suggested a low incidence of this isolate (3.7%) compared to EcPVs of the same genus such as EcPV2 and EcPV9 in the same horse population. We hypothesize a transmission mechanism different from the one observed in the closely related EcPV9 and EcPV2 that particularly infect Thoroughbreds. This horse breed is usually submitted to natural mating, thus indicating a possible sexual diffusion. No differences were detected for breeds in terms of susceptibility to EcPV10. Further studies are needed to investigate the molecular mechanisms behind the host and EcPV10 infection to explain the reduced viral spread. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article focuses on the concerns of the authorities as shown in the provisions on witchcraft and magic contained in the Romano-Germanic laws enacted from the sixth century (leges). !ese provisions shed light on what was prohibited and what was designated as magic; however, the attitude of the authorities towards magic and witchcraft was not univocal, mainly because of the religious and ethnic bipolarism underlying early European legislation on magic. Early medieval laws allow observing the formal expression of areas through which public concerns over the practice of magic operated. In most leges the use of magic was not punished as a religious offence, but rather for its destabilizing aspect regarding the social order. Moreover, the Church's attitude towards magic was not monolithic: the official Church coexisted with local magical customs. The early medieval leges confirm that magic is a category dependent on the perceiver, encompassing practices and beliefs that border on other features of human experience, such as religion and law itself. [ABSTRACT FROM AUTHOR]

Shift work, including the early start of work, compressed working weeks with 12-hour shifts and night work, especially if prolonged over many years, alters the normal sleep-wake pattern, causing short sleep with reduced quality, daytime dysfunction, and sleepiness. Recently, the effects of shift work on sleep have been investigated more consistently and many studies have supported the existence of an association between shift work and insufficient sleep and many chronic diseases, such as coronary artery disease, stroke, obesity, type 2 diabetes, breast, prostate, and colorectal cancer. In addition, occupational injuries have also been associated with the negative effects of shift work on sleep. However, future studies are still needed to definitively identify shift work as a causal factor of chronic health dysfunctions, which, inevitably, have repercussions on the work activity as a risk factor in the performance of the same. Considering the small number of studies, it is recommended that future research focus on reducing this knowledge gap. [ABSTRACT FROM AUTHOR]

Extracellular Vesicles (EVs) are nano-sized double-lipid-membrane-bound structures, acting mainly as signalling mediators between distant cells and, in particular, modulating the immune response and inflammation of targeted cells. Milk and colostrum contain high amounts of EVs that could be exploited as alternative natural systems in antimicrobial fighting. The aim of this study is to evaluate cow colostrum-derived EVs (colosEVs) for their antimicrobial, anti-inflammatory and immunomodulating effects in vitro to assess their suitability as natural antimicrobial agents as a strategy to cope with the drug resistance problem. ColosEVs were evaluated on a model of neonatal calf diarrhoea caused by Escherichia coli infection, a livestock disease where antibiotic therapy often has poor results. Colostrum from Piedmontese cows was collected within 24 h of calving and colosEVs were immediately isolated. IPEC-J2 cell line was pre-treated with colosEVs for 48 h and then infected with EPEC/NTEC field strains for 2 h. Bacterial adherence and IPEC-J2 gene expression analysis (RT-qPCR) of CXCL8, DEFB1, DEFB4A, TLR4, TLR5, NFKB1, MYD88, CGAS, RIGI and STING were evaluated. The colosEVs pre-treatment significantly reduced the ability of EPEC/NTEC strains to adhere to cell surfaces (p = 0.006), suggesting a role of ColosEVs in modulating host–pathogen interactions. Moreover, our results showed a significant decrease in TLR5 (p < 0.05), CGAS (p < 0.05) and STING (p < 0.01) gene expression in cells that were pre-treated with ColosEVs and then infected, thus highlighting a potential antimicrobial activity of ColosEVs. This is the first preliminarily study investigating ColosEV immunomodulatory and anti-inflammatory effects on an in vitro model of neonatal calf diarrhoea, showing its potential as a therapeutic and prophylactic tool. [ABSTRACT FROM AUTHOR]

Simple Summary: Canine mammary cancer is very common and has many similarities with human breast cancer. Risk factors, physiological and pathological behaviors, and the clinical course in dogs are very similar to humans. Several molecular similarities have also been reported, such as overexpression of EGF, proliferation markers, metalloproteinase and cyclooxygenase, TP53 mutations, and CXCR4/SDF1 axis activation. These common characteristics make these breast tumors resistant to conventional therapies. It is therefore necessary to study therapeutic alternatives. Cell lines could be helpful to test in vitro immunomodulant anti-cancer therapies, allowing a reduction of laboratory animals' involvement in the preliminary tests and achieving results in a shorter time. Although the canine mammary carcinoma cell line CF33 has been widely used in many studies on dog mammary cancer, characterization of its gene expression profile and of the influence of infective stressors of this cell line is poor. Our study shows the interaction of CF33 and Salmonella Typhimurium (ST) as an infective stressor, indicating that these cells may represent an in vitro model for assessing novel therapeutic approaches using bacteria. Spontaneous mammary tumors are the most frequent neoplasms in bitches and show similarities with human breast cancer in risk factors, clinical course, and histopathology. The poor prognosis of some cancer subtypes, both in human and dog, demands more effective therapeutic approaches. A possible strategy is the new anticancer therapy based on immune response modulation through bacteria or their derivatives on canine mammary carcinoma cell lines. The aim of the present study was to analyze the CF33 cell line in terms of basal expression of immune innate genes, CXCR4 expression, and interaction with infectious stressors. Our results highlight that CF33 maintains gene expression parameters typical of mammary cancer, and provides the basal gene expression of CF33, which is characterized by overexpression of CXCR4, CD44, RAD51, LY96, and a non-continuous expression of TP53 and PTEN. No mutations appeared in the CXCR4 gene until the 58th passage; this may represent important information for studying the CXCR4 pathway as a therapeutic target. Moreover, the CF33 cell line was shown to be able to interact with Salmonella Typhimurium (ST) (an infective stressor), indicating that these cells could be used as an in vitro model for developing innovative therapeutic approaches involving bacteria. [ABSTRACT FROM AUTHOR]

Human-induced pluripotent stem cells (hiPSCs) represent one of the main and powerful tools for the in vitro modeling of neurological diseases. Standard hiPSC-based protocols make use of animal-derived feeder systems to better support the neuronal differentiation process. Despite their efficiency, such protocols may not be appropriate to dissect neuronal specific properties or to avoid interspecies contaminations, hindering their future translation into clinical and drug discovery approaches. In this work, we focused on the optimization of a reproducible protocol in feeder-free conditions able to generate functional glutamatergic neurons. This protocol is based on a generation of neuroprecursor cells differentiated into human neurons with the administration in the culture medium of specific neurotrophins in a Geltrex-coated substrate. We confirmed the efficiency of this protocol through molecular analysis (upregulation of neuronal markers and neurotransmitter receptors assessed by gene expression profiling and expression of the neuronal markers at the protein level), morphological analysis, and immunfluorescence detection of pre-synaptic and post-synaptic markers at synaptic boutons. The hiPSC-derived neurons acquired Ca2+-dependent glutamate release properties as a hallmark of neuronal maturation. In conclusion, our study describes a new methodological approach to achieve feeder-free neuronal differentiation from hiPSC and adds a new tool for functional characterization of hiPSC-derived neurons. [ABSTRACT FROM AUTHOR]

Papillomavirus (PV) infections may be related to anogenital lesions and cancer development in humans and several other animal species. To date, 11 different PVs have been reported in horses. Among them, a newly described PV named Equus caballus Papillomavirus Type9 (EcPV9) was thus far only reported in the semen of a stallion with penile lesions in Australia. This study reports for the first time the presence of EcPV9 in asymptomatic Italian horses. From July 2020 to January 2022, genital brush samples were collected from 209 horses with no apparent signs of neoplastic disease and no PV-associated lesions, clinically examined at the Didactic Veterinary University Hospital (OVUD) of Perugia and at the Veterinary University Hospital (OVU) of Turin. Brushes were submitted to real-time PCR targeting the EcPV9-L1 region. The first amplification targeted a region of ~116 bp, followed by the amplification and sequencing of ~533 bp of the positive samples. EcPV9-L1 DNA was found in eleven horses (5.3%), all female and mainly English Thoroughbred. Co-infection with EcPV2-L1 was found in 7 out of the 11 EcPV9-L1 positive horses (63.6%). This study contributes to the description of the prevalence of exposure or infection of EcPVs in the horse population in Italy, for which data are still limited. In this regard, here we provide a phylogenetic analysis and the completely reconstructed viral genomes of two Italian EcPV type 9 isolates, as well as four EcPV type 2 obtained from co-infected animals. [ABSTRACT FROM AUTHOR]

We present a systematic study of the metallicity variations within the collisional ring galaxy NGC 922 based on long-slit optical spectroscopic observations. We find a metallicity difference between star-forming regions in the bulge and the ring, with metallicities ranging from almost solar to significantly sub-solar (⁠|$\rm {[12+\log (O/H)]\sim 8.2}$|⁠). We detect |$\rm{He\,{\small I}}$| emission in all the studied regions of the bulge and the ring, indicating ionization from massive stars associated with recent (<10 Myr) star formation, in agreement with the presence of very young star clusters. We find an anticorrelation between the X-ray luminosity and metallicity of the sub-galactic regions of NGC 922. The different regions have similar stellar population ages, leaving metallicity as the main driver of the anticorrelation. The dependence of the X-ray emission of the different regions in NGC 922 on metallicity is in agreement with similar studies of the integrated X-ray output of galaxies and predictions from X-ray binary population models. [ABSTRACT FROM AUTHOR]

Three Kentish laws (Æthelberht 9, Hloþære and Eadric 8 and 9) written in the 7th century mention the places where the men drink (þær mæn drincen).It has already been observed that drinking is not only a feature of a male warrior society, but represents a quasi-juridical institution which enjoys special protection (Renato Gendre 1992). However, the offences committed during these gatherings and the high fines duly paid can only partly be attributed to a general violation of the king's and house protection.Behind these laws there is an echo of more specific rituals. The legal character in drinking together, as it emerges in the symbolic offences described and fined in Hloþære and Eadric 8 and 9, has never been explored in the light of the recent works on ritual. The meaning of drinking (and toasting) as a binding moment inside some legal proceedings as well as its specific relation to consent are subject of the following investigation. As the most recent works on ritual show, the binding aspect and the creation of consent are among the major features of ritual. Only inside this discourse can thus be explained the meaning in the act of taking a cup from another where men are drinking (with no fault of the man from whom the cup was taken) and of drawing a weapon without doing any harm. These are two actions in which a boasting character is only an aspect, a superficial feature of a warrior society. The deep legal symbolism of both acts deserves further exploration, in which they prevent the participation of the concerned in a legal ceremony and disturb the building of the consensus. [ABSTRACT FROM AUTHOR]

Using the data products of the Chandra Galaxy Atlas (Kim et al.), we have investigated the radial profiles of the hot gas temperature in 60 early-type galaxies (ETGs). Considering the characteristic temperature and radius of the peak, dip, and break (when scaled by the gas temperature and virial radius of each galaxy), we propose a universal temperature profile of the hot halo in ETGs. In this scheme, the hot gas temperature peaks at R MAX = 35 ± 25 kpc (or ∼0.04 R VIR) and declines both inward and outward. The temperature dips (or breaks) at R MIN (or R BREAK) = 3–5 kpc (or ∼0.006 R VIR). The mean slope between R MIN (R BREAK) and R MAX is 0.3 ± 0.1. Allowing for selection effects and observational limits, we find that the universal temperature profile can describe the temperature profiles of 72 per cent (possibly up to 82 per cent) of our ETG sample. The remaining ETGs (18 per cent) with irregular or monotonically declining profiles do not fit the universal profile and require another explanation. The temperature gradient inside R MIN (R BREAK) varies widely, indicating different degrees of additional heating at small radii. Investigating the nature of the hot core (HC with a negative gradient inside R MIN), we find that HC is most clearly visible in small galaxies. Searching for potential clues associated with stellar, active galactic nucleus (AGN) feedback, and gravitational heating, we find that HC may be related to recent star formation. But we see no clear evidence that AGN feedback and gravitational heating play any significant role for HC. [ABSTRACT FROM AUTHOR]

Background: Measurement of saliva microbes is promoted as a way to detect oral and systemic disease, yet there is a multitude of factors that affect the oral microbiome. The salivary microbiome is influenced by oral biofilm of shedding (epithelial) and non‐shedding (tooth) surfaces. Methods: To gauge the ability of salivary microbial analytics to distinguish between edentulous and dentate oral conditions, we looked for differences in the saliva microbiome of subjects with and without teeth. Fifty‐two dentate and 49 edentulous subjects provided stimulated saliva samples. 16S rRNA gene sequencing, QIIME‐based data processing, and statistical analysis were done using several different analytical approaches to detect differences in the salivary microbiome between the two groups. Results: Bacteria diversity was lower in the edentulous group. Remarkably, all 31 of the most significant differences in taxa were deficits that occur in the edentulous group. As one might expect many of these taxa are attributed to dental plaque and gingival sulcus associated bacteria. Conclusion: In sum, the measurement of 16S rRNA genes in the bacteria of the saliva can be used to reproducibly measure differences in the oral microbiome that occur with edentulism, mainly the lack of tooth and tooth‐related structures. [ABSTRACT FROM AUTHOR]

See Lerche (doi:10.1093/brain/awy073) for a scientific commentary on this article.Proline-rich transmembrane protein 2 (PRRT2) is the causative gene for a heterogeneous group of familial paroxysmal neurological disorders that include seizures with onset in the first year of life (benign familial infantile seizures), paroxysmal kinesigenic dyskinesia or a combination of both. Most of the PRRT2 mutations are loss-of-function leading to haploinsufficiency and 80% of the patients carry the same frameshift mutation (c.649dupC; p.Arg217Profs*8), which leads to a premature stop codon. To model the disease and dissect the physiological role of PRRT2, we studied the phenotype of neurons differentiated from induced pluripotent stem cells from previously described heterozygous and homozygous siblings carrying the c.649dupC mutation. Single-cell patch-clamp experiments on induced pluripotent stem cell-derived neurons from homozygous patients showed increased Na+ currents that were fully rescued by expression of wild-type PRRT2. Closely similar electrophysiological features were observed in primary neurons obtained from the recently characterized PRRT2 knockout mouse. This phenotype was associated with an increased length of the axon initial segment and with markedly augmented spontaneous and evoked firing and bursting activities evaluated, at the network level, by multi-electrode array electrophysiology. Using HEK-293 cells stably expressing Nav channel subtypes, we demonstrated that the expression of PRRT2 decreases the membrane exposure and Na+ current of Nav1.2/Nav1.6, but not Nav1.1, channels. Moreover, PRRT2 directly interacted with Nav1.2/Nav1.6 channels and induced a negative shift in the voltage-dependence of inactivation and a slow-down in the recovery from inactivation. In addition, by co-immunoprecipitation assays, we showed that the PRRT2-Nav interaction also occurs in brain tissue. The study demonstrates that the lack of PRRT2 leads to a hyperactivity of voltage-dependent Na+ channels in homozygous PRRT2 knockout human and mouse neurons and that, in addition to the reported synaptic functions, PRRT2 is an important negative modulator of Nav1.2 and Nav1.6 channels. Given the predominant paroxysmal character of PRRT2-linked diseases, the disturbance in cellular excitability by lack of negative modulation of Na+ channels appears as the key pathogenetic mechanism. [ABSTRACT FROM AUTHOR]

TBC1D24-related disorders include a wide phenotypic ranging from mild to lethal seizure disorders, non-syndromic deafness, and composite syndromes such as DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures). The TBC1D24 gene has a role in cerebral cortex development and in presynaptic neurotransmission. Here, we present a familial case of a lethal early-onset epileptic encephalopathy, associated with two novel compound heterozygous missense variants on the TBC1D24 gene, which were detected by exome sequencing. The detailed clinical data of the three siblings is summarized in order to support the variability of the phenotype, severity, and progression of this disorder among these family members. Functional studies demonstrated that the identified novel missense mutations result in a loss of expression of the protein, suggesting a correlation between residual expression, and the disease severity. This indicates that protein expression analysis is important for interpreting genetic results when novel variants are found, as well as for complementing clinical assessment by predicting the functional impact. Further analysis is necessary to delineate the clinical presentation of individuals with TBC1D24 pathogenic variants, as well as to develop markers for diagnosis, prognosis, and potential targeted treatments. [ABSTRACT FROM AUTHOR]

Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis is an extremely rare condition, so far reported in a single family of Algerian origin presenting an unusual, severe form of progressive myoclonus epilepsy characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment, with probable autosomal recessive inheritance. Disease onset was between 6 and 16 years of age. Genetic study allowed to identify a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18-ceramides. The mutation decreased C18-ceramide levels. In addition, downregulation of CerS1 in neuroblastoma cell line showed activation of ER stress response and induction of proapoptotic pathways. This observation demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A literary criticism of several works on American novelists F. Scott Fitzgerald and Ernest Hemingway such as books "Gatsby: The Cultural History of the Great American Novel" by Bob Batchelor and "Ernest Hemingway in Context" by Debra Moddelmog and Suzanne del Gizzo. Topics discussed include a collection of essays covering several aspects such as work and life, identifying and portraying means to success for young men and technology enslavement throwing imagery and facts at persons.

Objective Alterations of sphingolipid metabolism are implicated in the pathogenesis of many neurodegenerative disorders. Methods We identified a homozygous nonsynonymous mutation in CERS1, the gene encoding ceramide synthase 1, in 4 siblings affected by a progressive disorder with myoclonic epilepsy and dementia. CerS1, a transmembrane protein of the endoplasmic reticulum (ER), catalyzes the biosynthesis of C18-ceramides. Results We demonstrated that the mutation decreases C18-ceramide levels. In addition, we showed that downregulation of CerS1 in a neuroblastoma cell line triggers ER stress response and induces proapoptotic pathways. Interpretation This study demonstrates that impairment of ceramide biosynthesis underlies neurodegeneration in humans. Ann Neurol 2014;76:206-212 [ABSTRACT FROM AUTHOR]

The article discusses the literary works that made significant contributions to the scholarship devoted to the works of U.S. writers F. Scott Fitzgerald and Ernest Hemingway in 2014. Topics covered include the tendency of Fitzgerald's novels to dominate critical attention, Fitzgerald's developing knowledge of self and the arts, and the relationship of competition and psychological influence between Hemingway and Fitzgerald.