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Brucella abortus is able to persist inside the host despite the development of potent CD8+ T-cell responses. We have recently reported the ability of B. abortus to inhibit the interferon-γ-induced major histocompatibility complex (MHC)-I cell surface expression on human monocytes. This phenomenon was due to the B. abortus-mediated retention of MHC-I molecules within the Golgi apparatus and was dependent on bacterial viability. However, the implications of bacterial virulence or replicative capacity and the signaling pathways remained unknown. Here we demonstrated that the B. abortus mutant strains RB51 and virB10− are able to inhibit MHC-I expression in the same manner as wild-type B. abortus, even though they are unable to persist inside human monocytes for a long period of time. Consistent with this, the phenomenon was triggered early in time and could be observed at 8 h postinfection. At 24 and 48 h, it was even stronger. Regarding the signaling pathway, targeting epidermal growth factor (EGF) receptor (EGFR), ErbB2 (HER2) or inhibition of tumor necrosis factor-α-converting enzyme, one of the enzymes which generates soluble EGF-like ligands, resulted in partial recovery of MHC-I surface expression. Moreover, recombinant EGF and transforming growth factor-α as well as the combination of both were also able to reproduce the B. abortus-induced MHC-I downmodulation. Finally, when infection was performed in the presence of an extracellular signal-regulated kinase 1/2 (Erk1/2) inhibitor, MHC-I surface expression was significantly recovered. Overall, these results describe how B. abortus evades CD8+ T-cell responses early during infection and exploits the EGFR-ERK signaling pathway to escape from the immune system and favor chronicity. [ABSTRACT FROM AUTHOR]

With an enormous potential in immunology and vaccinology, lipopolysaccharides (LPSs) are among the most extensively studied bacteria-derived molecules. LPS centered studies are countless, and their results reverberate in all areas of the life sciences, including chemistry, biology, genetics, biophysics, and medicine. Most of these research activities are focused on the LPS-induced immune response activation by means of Myeloid Differentiation protein-2/Toll Like Receptor 4 (MD-2/TLR4) complex, which currently is the most largely explored LPS sensing pathway. However, the enormous structural variability of LPS allows interactions with numerous other receptors involved in a wide range of equally important immunological scenarios. In this review, we explore these additional LPS recognition systems, which operate within interconnected signaling cascades, highlighting their role in maintaining physiological homeostasis and their involvement in the development of severe human diseases. Understanding these pathways, their interconnections, and the crosstalk between them and TLR4/MD-2 is essential for guiding the development of pharmacologically active molecules that could specifically modulate the inflammatory response, paving the way to new strategies for combating immune-mediated diseases and resistant infections., (© 2025 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

The nitrogen-fixing rhizobia-legume symbiosis relies on a complex interchange of molecular signals between the two partners during the whole interaction. On the bacterial side, different surface polysaccharides, such as lipopolysaccharide (LPS) and exopolysaccharide (EPS), might play important roles for the success of the interaction. In a previous work we studied two Sinorhizobium fredii HH103 mutants affected in the rkpK and lpsL genes, which are responsible for the production of glucuronic acid and galacturonic acid, respectively. Both mutants produced an altered LPS, and the rkpK mutant, in addition, lacked EPS. These mutants were differently affected in symbiosis with Glycine max and Vigna unguiculata, with the lpsL mutant showing a stronger impairment than the rkpK mutant. In the present work we have further investigated the LPS structure and the symbiotic abilities of the HH103 lpsL and rkpK mutants. We demonstrate that both strains produce the same LPS, with a truncated core oligosaccharide devoid of uronic acids. We show that the symbiotic performance of the lpsL mutant with Macroptilium atropurpureum and Glycyrrhiza uralensis is worse than that of the rkpK mutant. Introduction of an exoA mutation (which avoids EPS production) in HH103 lpsL improved its symbiotic performance with G. max, M. atropurpureum, and G. uralensis to the level exhibited by HH103 rkpK, suggesting that the presence of EPS might hide the truncated LPS produced by the former mutant., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background: Alzheimer's and other neurodegenerative forms of dementia affect 8 million Europeans. Assistive technologies are suggested to reduce the burden of care and improve the quality of life of person living with dementia. Nonetheless, the acceptance and attitudes toward technological interventions pose challenges not only for people living with dementia and caregivers but also for healthcare workers. This review specifically aims to investigate how these key groups perceive and accept technology in European dementia care settings., Methods: This systematic review was conducted to identify studies, published between 2013 and 2023, that examined the acceptance and attitude of assistive technologies in Alzheimer's and other dementia European settings, following the PRISMA guidelines. Rayyan AI was used for data extraction, and bias was assessed using the Mixed Methods Appraisal Tool., Results: Among the 1,202 identified articles, 13 met the inclusion criteria, revealing a prevailing positivity toward technological interventions in dementia care. Nonetheless, several barriers to adoption, including technological unfamiliarity, and specific dementia-related symptoms that complicate usage were identified. They also unveiled varying attitudes, influenced by factors such as familiarity with technologies, perceived usefulness, and the broader context of the COVID-19 pandemic which accelerated telemedicine and digital solution acceptance during restricted mobility and social distancing., Conclusion: Understanding attitudes toward technology in dementia care is crucial as it influences the adoption and utilization of tech-based interventions, impacting symptom management and quality of life. Addressing these attitudes through tailored interventions and education can enhance well-being and quality of life for people living with dementia, caregivers, and healthcare professionals., Competing Interests: MMo has received financial support by the MUR PNRR Extended Partnership (MNESYS no. PE00000006, and DHEAL-COM no. PNC-E3-2022-23683267); research grants from the ECTRIMS-MAGNIMS, the UK MS Society, and Merck; and honoraria from Biogen, BMS Celgene, Ipsen, Jansenn, Merck, Novartis, Roche, and Sanofi-Genzyme; and serves as editorial board member in Neurology and Multiple Sclerosis Journal. RP has received support from the UK MS Society (Award 146) and has taken part in advisory boards/consultancy for MSD, Sanofi, and BMS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sorrentino, Fiorilla, Mercogliano, Esposito, Stilo, Affinito, Moccia, Lavorgna, Salvatore, Maida, Barbi, Triassi and Palladino.)

In aqueous environment amphiphilic molecules organize themselves into supramolecular structures deeply affecting the chemo-physical properties. Supramolecular assemby is also crucial in the pharmaceutical development of bioactive lipophilic molecules whose attitude to self-aggregate is a recognized factor affecting the in vivo pharmacokinetic, but can also play a crucial role in the interaction with the biological targets in in vitro tests. In aqueous solution, amphiphilic drugs exist in a complex equilibrium involving free monomers, oligomers and larger supramolecular aggregates held together by noncovalent bonds. In this review we focus our attention on the dual effect of drugs self-assembly, which can both reduce the availability of active compounds and create multivalent scaffolds, potentially improving binding affinity and avidity to cellular targets. We examine the effect of aggregation on different classes of amphiphatic molecules with significant biological activities, such as immunomodulatory, anti-tumor, antiviral, and antibiotic. Our purpose is to provide a comprehensive overview of how supramolecular chemistry influences the pharmacological and biological responses of amphiphilic molecules, emphasizing the need to consider these effects in early-stage drug development and in vitro testing. By elucidating these phenomena, this review aims to offer insights into optimizing drug design and formulation to overcome challenges posed by self-aggregation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cold environments are predominant over the Earth and are inhabited by bacteria able to cope with a series of simultaneous environmental pressures. Gram-negative species of the Pseudomonas genus are the predominant ones isolated from cold habitats, making them an excellent model for studying the mechanisms of bacterial adaptation to the most extreme habitats on our planet. Here we focused on the lipopolysaccharide (LPS) structure and the outer membrane dynamics of Pseudomonas sp. EW#7, a strain isolated from Enigma Lake in Antarctica where, among other extreme characteristics, water temperature can reach 0.4 °C. We show that near-zero growth temperature mostly affects the LPS lipid A component. An uncommon tendency of decreasing lipid A secondary hydroxylation while increasing its phosphorylation degree was observed. This resulted in a faster lateral diffusion of lipid chains in the membrane and therefore in an enhancement of its fluctuations that guarantee membrane integrity and flexibility., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Violence against healthcare workers is an escalating public health concern, affecting the quality of care, and causing significant psychological and physical effects on healthcare professionals. This study analysed the trend in aggressions in healthcare settings in the pre-pandemic, pandemic, and post-pandemic periods., Methods: An observational descriptive study was conducted to analyse reports of violence against healthcare workers from January 2018 to June 2023 at a Local Health Authority "ASL3" in the Liguria region of Italy. The study considered variables such as the severity of aggression, professional category involved, and location of incident. Episodes of violence were classified according to severity by means of a colour-coded system. We used multinomial logistic regression to examine any associations between the pandemic phase and the various factors, while controlling for relevant variables., Results: The number of reported aggressions rose from 48 in 2018 to 90 in 2022, with a partial count of 35 in the first half of 2023. The pandemic phase saw a rise in incidents classified as Green codes, which accounted for 58.3%, and a significant involvement of District Services. The post-pandemic phase showed a reversion to pre-pandemic levels but with an increase in Yellow codes (5.6%). Nurses were the most frequent victims, with figures ranging from 50.8% to 95.6% over the years. The Emergency Department and Psychiatric Services emerged as the most critical settings of aggressions, with incidents recorded in these areas constituting over half of the total number. However, an increase in violence was also recorded in district healthcare settings during the post-pandemic phase., Conclusions: There is an urgent need for comprehensive strategies for the prevention of violence in healthcare settings. The increasing trend in violence, especially during the pandemic, necessitates integrated approaches that encompass training, psychological support, security policies, and a strong organizational culture to promote safety and respect. Protecting healthcare workers is crucial to their wellbeing and the quality of healthcare delivery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©2024 Pacini Editore SRL, Pisa, Italy.)

Background: The Herpes Zoster (HZ) poses a significant public health threat, leading to morbidity and occasional mortality in unvaccinated adults aged 50 and older. With over 95 % of individuals in this age group globally having prior exposure to Varicella-Zoster Virus, a substantial portion of the world's population is susceptible to developing HZ. Without vaccination, individuals reaching 85 years face a 50 % lifetime risk of HZ. Organizational and logistical barriers further hinder vaccination efforts, involving complexities in cost management, demanding vaccine storage requirements, supply limitations, distribution challenges, absence of a streamlined status collection system, and healthcare system deficiencies., Methods: A systematic review was conducted on the studies that examined the logistical and organizational barriers to HZ vaccination among frail and older adults, aligning with the PRISMA guidelines. Eligibility criteria focus on English studies in Europe, excluding pediatric or irrelevant populations. Rayyan AI was used for data extraction, and bias was assessed using the AXIS tool., Results: After excluding 841 based on titles and abstracts, 22 publications were selected. A thorough analysis identified 4 studies meeting inclusion criteria, conducted between 2009 and 2022, unveiling several barriers on HZ vaccination: challenges with healthcare professionals, obstacles related to patients' perceptions and knowledge, difficulties in accessibility, structural issues, social dynamics., Conclusions: The study represents a comprehensive examination, emphasizing the need for targeted interventions to overcome these barriers. The findings underscore the urgency of addressing these challenges to enhance vaccination rates and mitigate the public health burden associated with HZ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Medical residents constitute a vulnerable population susceptible to mental health disorders. In Italy, this was evident during the COVID-19 pandemic, when medical residents served on the front line and provided significant support to healthcare services. Therefore, the working group on "Public Mental Health" of the Medical Residents' Council of the Italian Society of Hygiene, Preventive Medicine, and Public Health (S.It.I.) designed the "Residents' mental health investigation, a dynamic longitudinal study in Italy" (ReMInDIt). This longitudinal study aims to assess the mental status of medical residents and to explore potential cause-effect relationships between risk/protective factors (identified among sociodemographic, residency program, and lifestyle characteristics) and mental health outcomes (anxiety and depressive symptoms). Data will be collected from a study population of 3615 residents enrolled in Italian residency programs in public health, occupational medicine, and forensic medicine through an online questionnaire that includes validated tools, requires 10 min for completion, and is disseminated by the residents' Councils. It will be followed by a follow-up administration after 12 months. The ReMInDIt study will play a significant role in generating evidence crucial for enhancing mental health services and promoting protective factors for the mental well-being of this important segment of healthcare professionals.

Introduction: Vaccines are the most cost-effective and straightforward intervention against severe infectious diseases. However, in Europe and in Italy, paediatric vaccination coverage for certain vaccines remains suboptimal, with considerable regional differences in Italy. Vaccine coverage varies significantly due to socio-economic and organisational factors. Aim of this study was to assess the influence of the Deprivation Index, the density of General Practitioners and General Paediatricians per inhabitants on the coverage of both mandatory and non-mandatory paediatric vaccinations across local health authorities and health districts in the Campania Region for birth cohorts from 2001 to 2015., Materials and Methods: Population-based, ecological time series analysis focusing on the Campania Region, most populous region in the south of Italy. Vaccination coverage data were extracted from the regional immunization database, whilst information on the Deprivation Index and number of primary care doctors and primary care paediatricians per local health district were extracted from public health records. Univariate descriptive statistics were employed to describe study characteristics, as appropriate, whilst and mixed-effect linear regression models were employed to assess the associations between variables of interest and vaccination coverage., Results: Overall vaccination coverage has generally increased, except for the MMR vaccine, which showed coverage fluctuations. An increase in the Deprivation Index, indicative of less favourable socio-economic conditions, was associated with decreased vaccination coverage in the 24-month age group for some mandatory vaccines (DTaP: Coef -0.97, 95% CI -1.77 | -0.17; Poliomyelitis: Coef -0.98, 95% CI -1.78 | -0.17; Hepatitis B: Coef -0.90, 95% CI -1.71 | -0.10). Moreover, areas with a greater density of General Paediatricians per inhabitants saw increased coverage for Haemophilus influenzae type b in the 6-year age group (Coef 9.78, 95% CI 1.00 | 18.56)., Conclusions: It is necessary to target public health policies to address vaccination inequalities. These efforts should include expanding vaccination campaigns, enhancing catch-up programs, and increase resource allocation in primary care settings to facilitate the role of General Practitioners and Paediatricians in fostering awareness and adherence., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Recently, we described synthetic sulfolipids named Sulfavants as a novel class of molecular adjuvants based on the sulfoquinovosyl-diacylglycerol skeleton. The members of this family, Sulfavant A ( 1 ), Sulfavant R ( 2 ), and Sulfavant S ( 3 ), showed important effects on triggering receptor expressed on myeloid cells 2 (TREM2)-induced differentiation and maturation of human dendritic cells (hDC), through a novel cell mechanism underlying the regulation of the immune response. As these molecules are involved in biological TREM2-mediated processes crucial for cell survival, here, we report the synthesis and application of a fluorescent analogue of Sulfavant A bearing the 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza- s -indacene moiety (Me 4 -BODIPY). The fluorescent derivative, named PB-SULF A ( 4 ), preserving the biological activity of Sulfavants, opens the way to chemical biology and cell biology experiments to better understand the interactions with cellular and in vivo organ targets and to improve our comprehension of complex molecular mechanisms underlying the not fully understood ligand-induced TREM2 activity.

Despite the existing body of evidence, there is still limited knowledge about the impact of SARS-CoV-2 positivity on delivery outcomes. We aimed to assess the impact of SARS-CoV-2 infection in women who gave birth at the University Hospital "Federico II" of Naples, Italy, between 2020 and 2021. We conducted a retrospective single-center population-based observational study to assess the differences in the caesarean section and preterm labor rates and the length of stay between women who tested positive for SARS-CoV-2 and those who tested negative at the time of labor. We further stratified the analyses considering the time period, dividing them into three-month intervals, and changes in SARS-CoV-2 as the most prevalent variant. The study included 5236 women with 353 positive cases. After vaccination availability, only 4% had undergone a complete vaccination cycle. The Obstetric Comorbidity Index was higher than 0 in 41% of the sample. When compared with negative women, positive ones had 80% increased odds of caesarean section, and it was confirmed by adjusting for the SARS-CoV-2 variant. No significant differences were found in preterm birth risks. The length of stay was 11% higher in positive cases but was not significant after adjusting for the SARS-CoV-2 variant. When considering only positive women in the seventh study period (July-September 2021), they had a 61% decrease in the odds of receiving a caesarean section compared to the fourth (October-December 2020). Guidelines should be implemented to improve the safety and efficiency of the delivery process, considering the transition of SARS-CoV-2 from pandemic to endemic. Furthermore, these guidelines should aim to improve the management of airborne infections in pregnant women.

Introduction: Despite proven efficacy, HPV vaccination coverage is still suboptimal. Factors influencing vaccination uptake are education attainment, socio-economic position, and knowledge about HPV. This study aimed to assess HPV vaccination uptake and its correlates among medical students and identify logistic-organizational barriers, knowledge, and attitudes with regard towards HPV vaccination to improve current public health vaccination strategies. Medical students, with their acquired biological knowledge, were selected as a low-risk groups for HPV vaccination uptake. This cross-sectional study was conducted using a validated questionnaire., Methods: Students in their the first 3 years of study students were preferentially invited. Eventually, the invitation was extended to every medical student. Logistic multivariable regression was used to assess determinants of HPV vaccination uptake. Additional analysis explored determinants of knowledge of and attitude toward HPV vaccination. Finally, a sensitive analysis was conducted to further assess the effect of knowledge and attitude on the HPV vaccination rate., Results: A total of 882 medical students participated, with 74.5% enrolled in the first 3 years of their training. HPV vaccination uptake was 55.5%, ranging from 78.5% for females to 16.5% for males. Male sex and increasing age were consistently associated with a lower vaccination uptake (males sex: OR 0.03, CI 0.02-0.05; age: OR 0.77, CI 0.68-0.88), whereasilst progress in their academic career was associated with a to higher likelihood of being vaccinated (6th year: OR 3.45, CI 1.24-9.57). These associations were confirmed when considering the knowledge of and attitude towards HPV. Additionally also, an active outreach from healthcare institutions was associated with a higher likelihood of receiving HPV vaccination (OR 1.70, CI 1.09-2.65., Conclusion: HPV vaccination in medical students was higher than in the general population; however, it was still suboptimal. An active and up-to-date call strategy and extending the free-of-charge offer are essential measures for to improvinge vaccination uptake. The findings support the need to improve public health strategies and increase awareness and knowledge ofregarding HPV vaccination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sorrentino, Mercogliano, Esposito, Lamberti, Buonocore, Riganti, Triassi and Palladino.)

Diverse natural and synthetic furan derivatives have shown biological activity. Here, we describe the preparation of benzyl and arylethyl β-furanamides with OH or OMe aryl substituents by an adapted sustainable method from a furoic acid using methyl chloroformate. Symmetric and asymmetric β,β'-furanamides have instead been prepared using azabenzotriazole based catalyst (HATU). The products have been evaluated for their antimicrobial properties on Gram positive and Gram negative bacteria. Just a minimal not-significant activity has been observed in some derivatives.

Background: We aim to evaluate whether fertility, pregnancy, delivery and breastfeeding have been actually improving in women with multiple sclerosis (MS), compared with general population, and in relation to treatment features., Methods: We included 2018-2020 population-level healthcare data on women with MS living in the Campania region (Italy). Fertility, pregnancy and delivery outcomes were obtained from Certificate of Delivery Assistance; breastfeeding was collected up to 6 months after delivery by trained personnel., Results: Out of 2748 women with MS in childbearing age, 151 women delivered 156 babies. Fertility rate was 0.58 live births per woman with MS, compared with 1.29 in Campania region and 1.25 in Italy. Disease-modifying treatment (DMT) continuation during pregnancy was associated with lower birth weight (coeff -107.09; 95% CI -207.91 to -6.26; p=0.03). Exposure to DMTs with unknown/negative effects on pregnancy was associated with birth defects (OR 8.88; 95% CI 1.35 to 58.41; p=0.02). Birth defects occurred in pregnancies exposed to dimethyl fumarate (2/21 exposed pregnancies), fingolimod (1/11 exposed pregnancies) and natalizumab (2/30 exposed pregnancies). After delivery, 18.8% of women with MS were escalated of DMT efficacy, while 50.7% started on same/similar-efficacy DMTs, and 30.5% did not receive DMT. The probability of breastfeeding was higher in women who were treated with breastfeeding-safe DMTs (OR 5.57; 95% CI 1.09 to 28.55; p=0.03)., Conclusions: Fertility rate in women with MS remains below the general population. Family planning and subsequent DMT decisions should aim to achieve successful pregnancy, delivery and breastfeeding outcomes, while controlling disease activity., Competing Interests: Competing interests: MaM has received research grants from the ECTRIMS-MAGNIMS, the UK MS Society and Merck; honoraria from Biogen, Ipsen, Merck, Roche and Sanofi-Genzyme. AC has received research grants from Almirall, research grants from ECTRIMS-MAGNIMS and honoraria from Almirall, Biogen, Roche Sanofi-Genzyme and Novartis. MP has received research grants from Italian MS Foundation and Baroni Foundation, honoraria from HEALTH&LIFE S.r.l. and Biogen and sponsorship for travel/meeting expenses from Novartis, Roche and Merck. RL has received honoraria from Biogen, Merck, Novartis, Roche and Teva. VBM has received research grants from the Italian MS Society, and Roche, and honoraria from Bayer, Biogen, Merck, Mylan, Novartis, Roche, Sanofi-Genzyme and Teva., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In Europe, there is still suboptimal tetanus, diphtheria, and acellular pertussis (Tdap) booster coverage. This study aimed to assess coverage status, knowledge, and attitude on Tdap vaccination in healthcare workers (HcWs) of the University Hospital "Federico II" in Naples, Southern Italy, in 2022, to improve current vaccination strategies., Methods: A cross-sectional study was conducted using a validated anonymous questionnaire. Knowledge and attitude were measured as scores. Multivariable logistic and linear regression models were employed to identify correlates of Tdap booster and knowledge and attitude toward the vaccination, as appropriate. Models were controlled for age, sex, profession, department, and job seniority., Results: A total of 206 questionnaires were administered among HcWs, and 143 (69.4%) were medical doctors. In total, 71 (34.47%) HcWs received the Tdap booster. Those who have worked 5-9 years at the hospital had a 78% lower likelihood of being vaccinated with the Tdap booster (5-9 years-OR: 0.22, CI: 0.06 | 0.85) as compared with newly hired HcWs. No differences in the average knowledge score were found. Other healthcare workers had a lower attitude as compared to medical doctors (Other-Coef. -2.15; CI: -4.14 | -0.15) and, as compared with those who worked in a clinical department, those who worked in a diagnostic-therapeutic department or medical management had 3.1 and 2.0 lower attitude scores, on average, respectively (diagnostic-therapeutic-Coef. -3.12, CI: -5.13 | -1.12; public health-Coef. -1.98, CI: -3.41 | -0.56)., Discussion: The study findings support the necessity to implement public health strategies and improve knowledge and attitude toward vaccinations and specifically highlight the importance of Tdap booster every 10 years as a prevention tool to protect high-risk populations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mercogliano, Fiorilla, Esposito, Sorrentino, Mirizzi, Parisi, Tajani, Buonocore, Triassi and Palladino.)

Studies have shown that the pandemic has led to an increase in sick leave periods among healthcare workers (HCWs); however, this might have changed over time considering increase in vaccination coverage and change in COVID-19 variant predominance. Therefore, we conducted an observational study to evaluate whether the type of symptoms and the duration of sick leave period for healthcare workers working in a large university hospital in the South of Italy changed between January 2021 and January 2022; 398 cases of COVID-19 were identified for a total of 382 subjects involved. A total of 191 subjects answered the questionnaire about symptoms; of these, 79 had COVID-19 during the period from March 2020 until February 2022. The results showed a decrease of about 1.2 days in sick leave period for each quarter without finding significant differences in the perception of symptoms. It is possible to hypothesize a contribution from the Omicron variant to the decrease in sick leave period in the last quarter, from vaccination coverage, from optimization of COVID-19 management, and from change in the regulations for the assessment of positivity.

The occurrence of analogues of bisphenol A (BPA), including bisphenol F(BPF) in milk is still not well known. BPF may enter the milk chain at the farm and during milk processing at the dairy company. This study identified the main BPF contamination pathways using a monitoring model based on the identification of the hazard at three stages along the dairy chain: raw milk from the storage tank, pasteurized milk from the storage tank, and cardboard packaged milk. Quantitative analysis was performed by high-performance liquid chromatography with fluorometric detection (HPLC/FD) system. BPF was detected in all analysed stages (from

Introduction: The role of the progesterone receptor (PR) in breast cancer remains a major clinical challenge. Although PR induces mammary tumor growth, its presence in breast tumors is a marker of good prognosis. We investigated coordinated PR rapid and nonclassical transcriptional effects governing breast cancer growth and endocrine therapy resistance., Methods: We used breast cancer cell lines expressing wild-type and mutant PRs, cells sensitive and resistant to endocrine therapy, a variety of molecular and cellular biology approaches, in vitro proliferation studies and preclinical models to explore PR regulation of cyclin D1 expression, tumor growth, and response to endocrine therapy. We investigated the clinical significance of activator protein 1 (AP-1) and PR interaction in a cohort of 99 PR-positive breast tumors by an immunofluorescence protocol we developed. The prognostic value of AP-1/PR nuclear colocalization in overall survival (OS) was evaluated using Kaplan-Meier method, and Cox model was used to explore said colocalization as an independent prognostic factor for OS., Results: We demonstrated that at the cyclin D1 promoter and through coordinated rapid and transcriptional effects, progestin induces the assembly of a transcriptional complex among AP-1, Stat3, PR, and ErbB-2 which functions as an enhanceosome to drive breast cancer growth. Our studies in a cohort of human breast tumors identified PR and AP-1 nuclear interaction as a marker of good prognosis and better OS in patients treated with tamoxifen (Tam), an anti-estrogen receptor therapy. Rationale for this finding was provided by our demonstration that Tam inhibits rapid and genomic PR effects, rendering breast cancer cells sensitive to its antiproliferative effects., Conclusions: We here provided novel insight into the paradox of PR action as well as new tools to identify the subgroup of ER+/PR + patients unlikely to respond to ER-targeted therapies.

A 66-year-old man presented with widespread annular and bullous subacute cutaneous lupus erythematosus (SCLE), developed after starting treatment for hypertension with the calcium channel blocker nitrendipine. A few days after withdrawal of the drug, while cutaneous manifestations were improving, left hemiparesis occurred. Laboratory investigations showed, in addition to anti-Ro, anti-La and anti-histone antibodies, the presence of lupus anticoagulant, anticardiolipin antibodies, prolonged APTT and thrombocytopenia. On the basis of the spontaneous regression of the patient's skin lesions after discontinuation of the drug, a possible relationship between nitrendipine intake, the clinical events and the biological findings is discussed.