Immunization status against measles of health-care workers operating at three sicilian university hospitals: An observational study

Measles is a highly contagious vaccine-preventable disease (VPD) that also commonly affects health-care workers (HCWs). Measles immunization of HCWs was strongly recommended by international health authorities, in order to limit the spreading of the illness to susceptible patients and colleagues. An observational study, evaluating the immunization and vaccination status against measles of HCWs working at three Sicilian university hospitals, was conducted. All subjects not completely immune (vaccinated with only one dose in their lifetime), not immune (not vaccinated or not naturally immunized), and with an unknown immunization status were considered not immunized. Among HCWs operating in the three Sicilian university hospitals, 54.6% were not immune against measles. The average age of not immune HCWs was 51.3 (SD ± 9.8), ranging between 25 and 71 years old. In particular, 46.9% of HCWs not immunized worked in “at-risk” hospital units, based on medical conditions of patients which increases the probability of contracting an infection. Vaccination coverage rates observed against measles are considerably lower than other European countries and inadequate. It is therefore crucial to tackle vaccine hesitancy among HCWs, promoting strategies targeted to evaluate immunization status against VPDs and to significantly increase vaccine coverages, such as tailored training and vaccination offer or compulsory vaccination program

Molecular Epidemiology and Genetic Diversity of Human Respiratory Syncytial Virus in Sicily during Pre- and Post-COVID-19 Surveillance Seasons

Human respiratory syncytial virus (hRSV) is an important pathogen of acute respiratory tract infection of global significance. In this study, we investigated the molecular epidemiology and the genetic variability of hRSV over seven surveillance seasons between 2015 and 2023 in Sicily, Italy. hRSV subgroups co-circulated through every season, although hRSV-B mostly prevailed. After the considerable reduction in the circulation of hRSV due to the widespread implementation of non- pharmaceutical preventive measures during the COVID-19 pandemic, hRSV rapidly re-emerged at a high intensity in 2022–2023. The G gene was sequenced for genotyping and analysis of deduced amino acids. A total of 128 hRSV-A and 179 hRSV-B G gene sequences were obtained. The phylogenetic analysis revealed that the GA2.3.5a (ON1) and GB5.0.5a (BA9) genotypes were responsible for the hRSV epidemics in Sicily.; only one strain belonged to the genotype GB5.0.4a. No differences were observed in the circulating genotypes during pre- and post-pandemic years. Amino acid sequence alignment revealed the continuous evolution of the G gene, with a combination of amino acid changes specifically appearing in 2022–2023. The predicted N-glycosylation sites were relatively conserved in ON1 and BA9 genotype strains. Our findings augment the understanding and prediction of the seasonal evolution of hRSV at the local level and its implication in the monitoring of novel variants worth considering in better design of candidate vaccines

Proposal for an Alliance Between Healthcare and Legal Area Professionals for Shared Public Health and Preventive Strategies in Italy and Europe.

Following the implementation of the new Italian legislation on responsibility of healthcare workers, a multi-professional framework, involving representatives of the Italian public health professionals and legal professionals expert in the field, drafted a proposal of the actionable recommendations to be implemented in the management of civil and penal disputes arising from the practice of public health interventions. In order to prevent legal disputes concerning some public health fields such as vaccinations, cancer screening, environmental health surveillance, and hospital management, it should be primary taken into account to update guidelines in supporting decision-making processes, in accordance with the “best scientific evidence available.” Furthermore, a multidisciplinary alliance between public health and legal area professionals should be encouraged and should be promoted both at national and European level

Respiratory Syncytial Virus: New Challenges for Molecular Epidemiology Surveillance and Vaccination Strategy in Patients with ILI/SARI.

Abstract: Several respiratory pathogens are responsible for influenza-like illness (ILI) and severe respiratory infections (SARI), among which human respiratory syncytial virus (hRSV) represents one of the most common aetiologies. We analysed the hRSV prevalence among subjects with ILI or SARI during the five influenza seasons before the emergence of SARS-CoV-2 epidemic in Sicily (Italy). Respiratory specimens from ILI outpatients and SARI inpatients were collected in the framework of the Italian Network for the Influenza Surveillance and molecularly tested for hRSV-A and hRSV-B. Overall, 8.1% of patients resulted positive for hRSV. Prevalence peaked in the age-groups <5 years old (range: 17.6–19.1%) and ≥50 years old (range: 4.8–5.1%). While the two subgroups co-circulated throughout the study period, hRSV-B was slightly predominant over hRSV-A, except for the season 2019–2020 when hRSV-A strongly prevailed (82.9%). In the community setting, the distribution of hRSV subgroups was balanced (47.8% vs. 49.7% for hRSV-A and hRSV-B, respectively), while most infections identified in the hospital setting were caused by hRSV-B (69.5%); also, this latter one was more represented among hRSV cases with underlying diseases, as well as among those who developed a respiratory complication. The molecular surveillance of hRSV infections may provide a valuable insight into the epidemiological features of ILI/SARI. Our findings add new evidence to the existing knowledge on viral aetiology of ILI and SARI in support of public health strategies and may help to define high-risk categories that could benefit from currently available and future vaccines

Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes

Human CD4[superscript +] T cells process and present functional class II MHC-peptide complexes, but the endogenous peptide repertoire of these non-classical antigen presenting cells remains unknown. We eluted and sequenced HLA-DR-bound self-peptides presented by CD4[superscript +] T cells in order to compare the T cell-derived peptide repertoire to sequences derived from genetically identical B cells. We identified several novel epitopes derived from the T cell-specific proteome, including fragments of CD4 and IL-2. While these data confirm that T cells can present peptides derived from the T-cell specific proteome, the vast majority of peptides sequenced after elution from MHC were derived from the common proteome. From this pool, we identified several identical peptide epitopes in the T and B cell repertoire derived from common endogenous proteins as well as novel endogenous epitopes with promiscuous binding. These findings indicate that the endogenous HLA-DR-bound peptide repertoire, regardless of APC type and across MHC isotype, is largely derived from the same pool of self-protein.National Institutes of Health (U.S.) (grant P01AI039671)National Institutes of Health (U.S.) (P01AI045757

Frontal Bone Remodeling for Gender Reassignment of the Male Forehead: A Gender-Reassignment Surgery

Gender-reassignment therapy, especially for reshaping of the forehead, can be an effective treatment to improve self-esteem. Contouring of the cranial vault, especially of the forehead, still is a rarely performed surgical procedure for gender reassignment. In addition to surgical bone remodeling, several materials have been used for remodeling and refinement of the frontal bone. But due to shortcomings of autogenous bone material and the disadvantages of polyethylene or methylmethacrylate, hydroxyapatite cement (HAC) composed of tetracalcium phosphate and dicalcium phosphate seems to be an alternative. This study aimed to analyze the clinical outcome after frontal bone remodeling with HAC for gender male-to-female reassignment. The 21 patients in the study were treated for gender reassignment of the male frontal bone using HAC. The average age of these patients was 33.4 years (range, 21–42 years). The average volume of HAC used per patient was 3.83 g. The authors’ clinical series demonstrated a satisfactory result. The surgery was easy to perform, and HAC was easy to apply and shape to suit individual needs. Overall satisfaction was very high. Therefore, HAC is a welcome alternative to the traditional use of autogenous bone graft for correction of cranial vault irregularities

pp32 (ANP32A) Expression Inhibits Pancreatic Cancer Cell Growth and Induces Gemcitabine Resistance by Disrupting HuR Binding to mRNAs

The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, including gemcitabine. pp32 overexpression reduced the association of HuR with the mRNA encoding the gemcitabine-metabolizing enzyme deoxycytidine kinase (dCK), causing a significant reduction in dCK protein levels. Similarly, ectopic pp32 expression caused a reduction in HuR binding of mRNAs encoding tumor-promoting proteins (e.g., VEGF and HuR), while silencing pp32 dramatically enhanced the binding of these mRNA targets. Low pp32 nuclear expression correlated with high-grade tumors and the presence of lymph node metastasis, as compared to patients' tumors with high nuclear pp32 expression. Although pp32 expression levels did not enhance the predictive power of cytoplasmic HuR status, nuclear pp32 levels and cytoplasmic HuR levels associated significantly in patient samples. Thus, we provide novel evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt HuR binding to target mRNAs encoding key proteins for cancer cell survival and drug efficacy

Vitamin D Status Is Positively Correlated with Regulatory T Cell Function in Patients with Multiple Sclerosis

In several autoimmune diseases, including multiple sclerosis (MS), a compromised regulatory T cell (Treg) function is believed to be critically involved in the disease process. In vitro, the biologically active metabolite of vitamin D has been shown to promote Treg development. A poor vitamin D status has been linked with MS incidence and MS disease activity. In the present study, we assess a potential in vivo correlation between vitamin D status and Treg function in relapsing remitting MS (RRMS) patients.Serum levels of 25-hydroxyvitamin D (25(OH)D) were measured in 29 RRMS patients. The number of circulating Tregs was assessed by flow-cytometry, and their functionality was tested in vitro in a CFSE-based proliferation suppression assay. Additionally, the intracellular cytokine profile of T helper cells was determined directly ex-vivo by flow-cytometry. Serum levels of 25(OH)D correlated positively with the ability of Tregs to suppress T cell proliferation (R = 0.590, P = 0.002). No correlation between 25(OH)D levels and the number of Tregs was found. The IFN-gamma/IL-4 ratio (Th1/Th2-balance) was more directed towards IL-4 in patients with favourable 25(OH)D levels (R = -0.435, P = 0.023).These results show an association of high 25(OH)D levels with an improved Treg function, and with skewing of the Th1/Th2 balance towards Th2. These findings suggest that vitamin D is an important promoter of T cell regulation in vivo in MS patients. It is tempting to speculate that our results may not only hold for MS, but also for other autoimmune diseases. Future intervention studies will show whether modulation of vitamin D status results in modulation of the T cell response and subsequent amelioration of disease activity