Limitations and consequences of public health models centred on hospitals and lacking connections with territorial and home-based social and health services.

BACKGROUND: Delayed discharge from hospital to home or other care institutions is a significant problem and has been investigated in the international scientific literature for many years. Behind this condition is a health care system based on a hospital-centered concept characterized by a lack of territorial health and social welfare services. This phenomenon causes two different problems: an excessive length of hospital stay, resulting in slow turnover of bed utilization; and overcrowding in emergency rooms (ERs). The phenomenon of frequent users assumes particular importance in this context. These patients repeatedly visit the emergency department (ED) in the same year because care needs are not met by primary care services. The authors in this study tried to describe the Frequent users (FUs) population and the variables associated with this condition. MATERIALS AND METHODS: A retrospective "single-arm" descriptive study was conducted by analysing all accesses made to the ED of Policlinico Tor Vergata (PTV) from January 1, 2022, to December 31, 2022. FUs were defined as patients who had 4 or more accesses to PTV ER during the year. RESULTS: A total of 37,800 accesses occurred during the study period. A total of 31,691 users accessed the PS, with a mean age of 55.8 ± 22.2 years. There were 359 FU patients (approximately 1%) who had a total of 1984 accesses, corresponding to 5.2% of the total accesses. The triage codes for the FU patients were red, 2%; orange, 21%; blue, 45%; green, 26%; white, 5%; and not performed, 1%. Considering the 1984 FU accesses, the most frequently attributed "main problems" in the ED were "other symptoms or disorders" (54%), "psychomotor agitation" (12%), "trauma or burn" (8%), "abdominal pain" (6%), "chest pain" (4%), "dyspnea" (4%) and "urological symptoms or disorders" (4%). Multivariate analysis revealed that the main determinants of FUs were psychomotor agitation (HR = 7,23; CL95%:6,194-8,443), urological disorders (HR = 2,16; CL95%:1,68-2,76) and poor socioeconomic status (HR = 2,40; CL95%:2,213-2,663). CONCLUSIONS: The FUs phenomenon expresses an area of health and social distress where poverty and lack of territorial services oblige people to refer to the ED. Primary care interventions integrated with social support are crucial for managing access to the ED.

Low-Dose Occupational Exposure to Ionizing Radiation and Cardiovascular Effects: A Narrative Review.

Historically, non-cancer diseases have not been considered a health risk following low-dose exposure to ionizing radiation. However, it is now well known that high-dose ionizing radiation causes cardiovascular disease, and emerging epidemiological evidence suggests an excess risk of non-cancer diseases even following exposure to lower doses of ionizing radiation than previously thought. In fact, the evidence is strongest for cardiovascular disease (CVD). The aim of this review was to report the most representative studies and data on the risk of CVD from low-dose radiation in people with occupational exposure. We reported the results of 27 articles selected from a database search of 1151 studies. The results show a complex evidence landscape on the relationship between radiation exposure and cardiovascular disease. In general, published papers show a positive association between ionizing radiation exposure and dermal microcirculation damage, ischemic heart disease, and cerebrovascular disease. Overall, they highlight the need for comprehensive and detailed research to clarify this relationship. Due to limited statistical power, the dose-risk relationship below 0.5 Gy is inconclusive, but if this relationship is found to have no threshold, it could have a significant impact on current estimates of health risks at low doses.

Pulmonary function assessment after COVID-19 in vaccinated healthcare workers.

COVID-19 typically presents with flu-like symptoms due to the viral infection itself. The most severe cases are characterised by lung damage, an important factor in fatal outcome due to alveolar damage. In some cases, patients develop a long COVID with persistent symptoms of chest pain and fatigue. Causes, including organ damage or inflammation, are being investigated. Clinical outcomes are variable and permanent lung damage is not fully understood, while vaccination is effective against severe infection but its effect on respiratory function in mild cases remains uncertain. This retrospective study aims to analyse changes in lung function in HCWs who had COVID-19 between 2020 and 2022, comparing their spirometric test results before and after the pandemic and taking into account their vaccination status. 321 HCWs were included in the study. The study examined spirometric parameters both before and after the pandemic, and all measured outcomes except the FEV1/FVC ratio showed a significant decrease during the study period. We then assessed the association between SARS-CoV-2 infection and changes in lung function parameters, analysing infections in 2020, 2021 and 2022 separately. We found a statistically significant difference in Forced vital capacity (FVC) between infected and non-infected subjects in 2020 and 2021, but not in 2022. To evaluate the protective effect of SARS-CoV-2 vaccination on respiratory function, a linear regression analysis was performed using changes in FVC, Forced expiratory volume in 1 s (FEV1), FVC/FEV1 ratio and Peak expiratory flow (PEF) as dependent variables. The analysis showed that the decline in FVC was significantly lower in subjects who had been vaccinated prior to infection. The study concludes that subclinical SARS-CoV-2 infections in 2020 and 2021 worsened respiratory parameters (FVC and FEV1), but vaccination protected against these effects. Even healthy individuals with previous infections showed respiratory changes, with vaccination providing protection, especially for FVC decline. This highlights the importance of vaccinating healthcare workers against COVID-19.

Rubella Vaccine Uptake among Women of Childbearing Age in Healthcare Settings.

BACKGROUND: Rubella is a contagious viral infection that occurs most often in children and young adults. Rubella is the leading vaccine-preventable cause of birth defects. Rubella infection in pregnant women may cause fetal death or congenital defects known as congenital rubella syndrome. There is no specific treatment for rubella, but the disease is preventable by vaccination with an efficacy of over 95%. Vaccination coverage is still below the recommended levels and many cases have occurred worldwide. The COVID-19 pandemic has had a negative impact on the immunization programs and the quality of disease surveillance worldwide. Operators of the healthcare setting are at increased risk of infection due to their work duties and should receive preventive vaccination or serologic protection to work in a healthcare setting. AIMS: To evaluate the serological evidence of rubella IgG antibodies in female healthcare operators of childbearing age, to assess the risk of a breakthrough infection and the need for an additional dose of vaccine. METHODS: We collected age and antibody titers from 449 young female operators aged <50 years who underwent the periodic surveillance at the Occupational Medicine Unit of the Policlinico Tor Vergata, Rome, from January to July 2022. Subjects were considered immune if the anti-rubella IgG titer was >11.00 IU/mL. RESULTS: The rate of serologically unprotected subjects was 9.13% (41/449). The mean age of protected subjects was 26.93 years, while the mean age of unprotected subjects was 28.24 years. Age did not correlate with mean titer on statistical analysis (p = 0.10). The acceptance rate among unprotected operators was 31.7%. A positive attitude towards vaccination was found in 11/28 (39.3%) of the unvaccinated subjects, while a negative tendency was found in 2/28 (7.1%) of these subjects; most of the unvaccinated operators 15/28 (53.6%) prefer to postpone the administration of the vaccine. When compared with a similar population from the pre-pandemic period, the actual proportion of immune female subjects was not significantly different from that found in 2019 (90.87% vs. 90.3%). CONCLUSIONS: Protection against rubella was suboptimal among female healthcare workers of childbearing age. Acceptance of the rubella vaccine among these operators was low. Most of those who were hesitant intended to postpone the vaccination, while a minority had negative attitudes toward vaccination. A policy of mandatory vaccination policy should overcome the reluctance of operators.

Protective Anti-HBs Antibodies and Response to a Booster Dose in Medical Students Vaccinated at Childhood.

The immune system in humans is regulated by the circadian rhythm. Published studies have reported that the time of vaccination is associated with the immune response to vaccine for some pathogens. Our study aimed to evaluate the association between time of dose administration of challenge HBV vaccine and seroconversion for anti-HBs in medical students vaccinated at birth who were found to be unprotected at pre-training screening. Humoral protection for HBV was assessed in 885 medical students vaccinated during childhood. In total, 359 (41.0%) of them showed anti-HBs titer < 10 UI/mL and received a challenge dose of HBV vaccine followed by post-vaccination screening 30-60 days later. The challenge dose elicited a protective immune response (anti-HBs IgG titer > 10 UI/mL) in 295 (83.8%) individuals. Seroconversion was significantly associated with female gender and time of vaccination after controlling for age group and nationality at logistic regression analysis. Students who received the booster dose in the morning had a higher response rate than those who received the vaccine in the afternoon (OR 1.93; 95% C.I. 1.047-3.56: p < 0.05). This finding suggests that morning administration of the HBV booster may result in a better immune response in susceptible individuals.

Measles vaccine uptake among Italian medical students compared to the pre-COVID-19 era.

The COVID-19 pandemic has severely affected health systems worldwide and raised the issue of vaccine hesitancy. In 2022, the World Health Organization reported an outbreak of measles infection among people over 20 years of age in the European Region. Previous studies found low rates of measles immunization among Italian healthcare workers (HCWs) and medical students. Vaccine hesitancy is a relevant cause of low immunization rate among HCWs and the general population. We aim to evaluate the measles vaccine uptake among medical students of a large teaching hospital, compared to the pre-pandemic period. This is a retrospective observational study, that evaluated the immune status and the vaccine acceptance rate for measles in medical students at the University of Tor Vergata, Rome, who underwent occupational health surveillance from 1 January to 1 December 2022. We also compared the data with the results of a pre-pandemic survey conducted in 2018. Vaccine uptake among unprotected medical students was 59.5%. The data showed no significant difference in vaccine uptake compared with the pre-COVID-19 period. Conversely, the rate of serologically immune subjects to measles increased from 89.66% in 2018 to 97.45% in 2022 as a result of the recent mandatory vaccination policy. Despite efforts to tackle vaccine hesitancy during the COVID-19 pandemic, measles vaccine uptake is still low among young adults starting their medical training, and their compliance with free workplace vaccination offers is suboptimal. Occupational health services should raise awareness among workers and work together to implement strategies to achieve comprehensive measles vaccination coverage among occupational health workers.

Serological Evaluation for Measles among Italian and Foreign Medical Students in a University Hospital in Rome.

BACKGROUND: Measles infection in the hospital setting is a major issue. Despite the availability of an effective vaccine, measles outbreaks continue to occur in some European countries. We aimed to evaluate the immunological status of medical students attending the Tor Vergata Polyclinic (PTV). METHODS: Measles antibodies titers were assessed by venipuncture on a sample of 2717 medical students who underwent annual health surveillance visits from January 2021 to March 2023. Subjects showing serum IgG values above 1.0 S/CO were considered serologically protected. Personal data, country of origin, and main demographic characteristic were also collected. RESULTS: 66.7% (1467 Italian and 346 foreign) of medical students showed protective IgG antibodies levels. Female students were serologically immune more frequently than males (68.6% vs. 63.3%; p < 0.01 at Chi2). The mean antibody titer was 1.72 S/CO, significantly higher in females than males (1.67 vs. 1.75, respectively; p < 0.05), and significantly related to age (p < 0.01). Albanian students, who were the largest foreign population in our study, showed a low serological protection rate (40/90: 44.4%). CONCLUSIONS: The proportion of serologically non-immune students is high, raising concerns about the possible risk of hospital transmission. Substantial differences in the rate of immunity have been found between subjects coming from different parts of Europe and the world. Pre-training assessment of all medical students and vaccination of susceptible individuals is highly recommended, particularly for those from low immunization rate countries.

A New Algorithm for Estimating a Noiseless, Evenly Sampled, Heart Rate Modulating Signal.

Heart rate variability (HRV) is commonly intended as the variation in the heart rate (HR), and it is evaluated in the time and frequency domains with various well-known methods. In the present paper, the heart rate is considered as a time domain signal, at first as an abstract model in which the HR is the instantaneous frequency of an otherwise periodic signal, such as with an electrocardiogram (ECG). In this model, the ECG is assumed to be a frequency modulated signal, or carrier signal, where HRV or HRV(t) is the time-domain signal which is frequency modulating the carrier ECG signal around its average frequency. Hence, an algorithm able to frequency demodulate the ECG signal to extract the signal HRV(t) is described, with possibly enough time resolution to analyse fast time-domain variations in the instantaneous HR. After exhaustive testing of the method on simulated frequency modulated sinusoidal signals, the new procedure is eventually applied on actual ECG tracings for preliminary nonclinical testing. The purpose of the work is to use this algorithm as a tool and a more reliable method for the assessment of heart rate before any further clinical or physiological analysis.

A novel, integrated approach for understanding and investigating Healthcare Associated Infections: A risk factors constellation analysis.

INTRODUCTION: Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) are major public health threats in upper- and lower-middle-income countries. Electronic health records (EHRs) are an invaluable source of data for achieving different goals, including the early detection of HAIs and AMR clusters within healthcare settings; evaluation of attributable incidence, mortality, and disability-adjusted life years (DALYs); and implementation of governance policies. In Italy, the burden of HAIs is estimated to be 702.53 DALYs per 100,000 population, which has the same magnitude as the burden of ischemic heart disease. However, data in EHRs are usually not homogeneous, not properly linked and engineered, or not easily compared with other data. Moreover, without a proper epidemiological approach, the relevant information may not be detected. In this retrospective observational study, we established and engineered a new management system on the basis of the integration of microbiology laboratory data from the university hospital "Policlinico Tor Vergata" (PTV) in Italy with hospital discharge forms (HDFs) and clinical record data. All data are currently available in separate EHRs. We propose an original approach for monitoring alert microorganisms and for consequently estimating HAIs for the entire period of 2018. METHODS: Data extraction was performed by analyzing HDFs in the databases of the Hospital Information System. Data were compiled using the AREAS-ADT information system and ICD-9-CM codes. Quantitative and qualitative variables and diagnostic-related groups were produced by processing the resulting integrated databases. The results of research requests for HAI microorganisms and AMR profiles sent by the departments of PTV from 01/01/2018 to 31/12/2018 and the date of collection were extracted from the database of the Complex Operational Unit of Microbiology and then integrated. RESULTS: We were able to provide a complete and richly detailed profile of the estimated HAIs and to correlate them with the information contained in the HDFs and those available from the microbiology laboratory. We also identified the infection profile of the investigated hospital and estimated the distribution of coinfections by two or more microorganisms of concern. Our data were consistent with those in the literature, particularly the increase in mortality, length of stay, and risk of death associated with infections with Staphylococcus spp, Pseudomonas aeruginosa, Klebsiella pneumoniae, Clostridioides difficile, Candida spp., and Acinetobacter baumannii. Even though less than 10% of the detected HAIs showed at least one infection caused by an antimicrobial resistant bacterium, the contribution of AMR to the overall risk of increased mortality was extremely high. CONCLUSIONS: The increasing availability of health data stored in EHRs represents a unique opportunity for the accurate identification of any factor that contributes to the diffusion of HAIs and AMR and for the prompt implementation of effective corrective measures. That said, artificial intelligence might be the future of health data analysis because it may allow for the early identification of patients who are more exposed to the risk of HAIs and for a more efficient monitoring of HAI sources and outbreaks. However, challenges concerning codification, integration, and standardization of health data recording and analysis still need to be addressed.

The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma.

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.

Correction: Guerrieri et al. Nasal and Salivary Mucosal Humoral Immune Response Elicited by mRNA BNT162b2 COVID-19 Vaccine Compared to SARS-CoV-2 Natural Infection. Vaccines 2021, 9, 1499.

The authors wish to make the following corrections to this paper [...].

Evaluation of the accuracy in the mucosal detection of anti-SARS-CoV-2 antibodies in nasal secretions and saliva.

COVID-19 vaccination with mRNA vaccines induces immune responses capable of neutralizing SARS-CoV-2. Commercially available serological anti-SARS-CoV-2 quantitative and neutralizing assays are essential for the determination of immune responses to vaccines. Nevertheless, at present there is a lack of validated tests to assess the mucosal response to COVID-19 vaccination and standardized analytic and pre-analytic methods have not yet been defined. The aim of our study was to evaluate the accuracy of two diagnostic immunoassays for COVID-19 (ELISA for IgA-S1 and chemiluminescent assay for IgG-RBD) on serum, saliva, and nasal secretions, by the enrollment of three study populations (healthy controls, vaccinated subjects, and subjects recovered from COVID-19 infection). In order to obtain an appropriate cut-off value for the biological matrices studied, ROC curve analyses were performed. Data demonstrate that the analytical and pre-analytical method we have developed can provide accurate and reliable results for the detection of anti-SARS-CoV-2 mucosal specific antibodies (IgA-S1 and IgG-RBD) on saliva and, as a novelty, on nasal secretions, either after COVID-19 infection or in vaccinated subjects.

Hypocalcemia is associated with adverse outcomes in patients hospitalized with COVID-19.

PURPOSE: Calcium ions are involved in the regulation of several cellular processes and may also influence viral replication. Hypocalcemia has been frequently reported during infectious diseases and in critically ill patients, including also COVID-19 patients, significantly related with the pro-inflammatory state and mortality. The aim of this study is to investigate the prevalence of hypocalcemia at admission in patients hospitalized for COVID-19 (Coronavirus disease 2019) and to evaluate association of hypocalcemia with in-hospital COVID-19 outcomes. METHODS: Retrospective analysis on 118 consecutive patients, hospitalized for COVID-19 between March and May 2020. Clinical characteristics, inflammation markers, biochemical routine and mineral metabolism parameters at admission were collected. Hypocalcemia was defined as total serum calcium <2.2 mmol/L. Population was stratified by tertiles of total serum calcium. Primary outcome was the composite of in-hospital death or admission to intensive care unit (ICU). Secondary outcomes included in-hospital death, admission to ICU and need for non-invasive ventilation as separate events. Associations were tested by logistic regression and Cox-regression analysis with survival curves. RESULTS: Overall prevalence of hypocalcemia was 76.6%, with just 6.7% of patients reporting levels of 25-(OH)-vitamin D > 30 ng/ml. Total serum calcium was inversely related with selected inflammatory biomarkers (p < 0.05) and poorer outcome of COVID-19 during hospitalization. Lower tertile of total calcium (≤2.02 mmol/L) had increased risk of in-hospital mortality (HR 2.77; 1.28-6.03, p = 0.01) compared with other groups. CONCLUSION: Total serum calcium detected on admission is inversely related with proinflammatory biomarkers of severe COVID-19 and is useful to better define risk stratification for adverse in-hospital outcome.

Do Media Extracellular Vesicles and Extracellular Vesicles Bound to the Extracellular Matrix Represent Distinct Types of Vesicles?

Mineralization-competent cells, including hypertrophic chondrocytes, mature osteoblasts, and osteogenic-differentiated smooth muscle cells secrete media extracellular vesicles (media vesicles) and extracellular vesicles bound to the extracellular matrix (matrix vesicles). Media vesicles are purified directly from the extracellular medium. On the other hand, matrix vesicles are purified after discarding the extracellular medium and subjecting the cells embedded in the extracellular matrix or bone or cartilage tissues to an enzymatic treatment. Several pieces of experimental evidence indicated that matrix vesicles and media vesicles isolated from the same types of mineralizing cells have distinct lipid and protein composition as well as functions. These findings support the view that matrix vesicles and media vesicles released by mineralizing cells have different functions in mineralized tissues due to their location, which is anchored to the extracellular matrix versus free-floating.

Shedding Light on the Role of Na,K-ATPase as a Phosphatase during Matrix-Vesicle-Mediated Mineralization.

Matrix vesicles (MVs) contain the whole machinery necessary to initiate apatite formation in their lumen. We suspected that, in addition to tissue-nonspecific alkaline phosphatase (TNAP), Na,K,-ATPase (NKA) could be involved in supplying phopshate (Pi) in the early stages of MV-mediated mineralization. MVs were extracted from the growth plate cartilage of chicken embryos. Their average mean diameters were determined by Dynamic Light Scattering (DLS) (212 ± 19 nm) and by Atomic Force Microcopy (AFM) (180 ± 85 nm). The MVs had a specific activity for TNAP of 9.2 ± 4.6 U·mg-1 confirming that the MVs were mineralization competent. The ability to hydrolyze ATP was assayed by a colorimetric method and by 31P NMR with and without Levamisole and SBI-425 (two TNAP inhibitors), ouabain (an NKA inhibitor), and ARL-67156 (an NTPDase1, NTPDase3 and Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) competitive inhibitor). The mineralization profile served to monitor the formation of precipitated calcium phosphate complexes, while IR spectroscopy allowed the identification of apatite. Proteoliposomes containing NKA with either dipalmitoylphosphatidylcholine (DPPC) or a mixture of 1:1 of DPPC and dipalmitoylphosphatidylethanolamine (DPPE) served to verify if the proteoliposomes were able to initiate mineral formation. Around 69-72% of the total ATP hydrolysis by MVs was inhibited by 5 mM Levamisole, which indicated that TNAP was the main enzyme hydrolyzing ATP. The addition of 0.1 mM of ARL-67156 inhibited 8-13.7% of the total ATP hydrolysis in MVs, suggesting that NTPDase1, NTPDase3, and/or NPP1 could also participate in ATP hydrolysis. Ouabain (3 mM) inhibited 3-8% of the total ATP hydrolysis by MVs, suggesting that NKA contributed only a small percentage of the total ATP hydrolysis. MVs induced mineralization via ATP hydrolysis that was significantly inhibited by Levamisole and also by cleaving TNAP from MVs, confirming that TNAP is the main enzyme hydrolyzing this substrate, while the addition of either ARL-6715 or ouabain had a lesser effect on mineralization. DPPC:DPPE (1:1)-NKA liposome in the presence of a nucleator (PS-CPLX) was more efficient in mineralizing compared with a DPPC-NKA liposome due to a better orientation of the NKA active site. Both types of proteoliposomes were able to induce apatite formation, as evidenced by the presence of the 1040 cm-1 band. Taken together, the findings indicated that the hydrolysis of ATP was dominated by TNAP and other phosphatases present in MVs, while only 3-8% of the total hydrolysis of ATP could be attributed to NKA. It was hypothesized that the loss of Na/K asymmetry in MVs could be caused by a complete depletion of ATP inside MVs, impairing the maintenance of symmetry by NKA. Our study carried out on NKA-liposomes confirmed that NKA could contribute to mineral formation inside MVs, which might complement the known action of PHOSPHO1 in the MV lumen.

Global Policy to Reduce the Incidence of Infection Spreading in Non-Vaccinated Healthcare Workers: A Literature Review.

Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection because of their occupational exposure. Moreover, they can be a vehicle for the virus transmission among patients. The vaccination of healthcare personnel against COVID-19 is crucial in fighting the spread of SARS-CoV-2 infection, together with strict sanitary procedures that aim to limit the risk of contagion. Unfortunately, even if COVID-19 vaccination has been proved one of the most effective tools for protecting against COVID-19, many healthcare professionals are not yet vaccinated. The aim of the current review is to contribute to identifying an effective strategy for COVID-19 prevention especially among non-vaccinated HCWs. In this review, we collected the most recent and relevant findings from literature on the protection of unvaccinated HCWs, identifying three types of measures as principal actions to protect those operators: addressing vaccine hesitancy, improving non-pharmaceutical interventions and promoting actions at personal level (respiratory hygiene, hand hygiene and use of PPE). All these interventions are very effective in preventing contagion, if well respected and conducted; nevertheless, it is essential to promote vaccination, as it is the most effective measure.

Main Predictors of COVID-19 Vaccination Uptake among Italian Healthcare Workers in Relation to Variable Degrees of Hesitancy: Result from a Cross-Sectional Online Survey.

Background: Hesitancy remains one of the major hurdles to vaccination, regardless of the fact that vaccines are indisputable preventive measures against many infectious diseases. Nevertheless, vaccine hesitancy or refusal is a growing phenomenon in the general population as well as among healthcare workers (HCWs). Many different factors can contribute to hesitancy to COVID-19 vaccination in the HCWs population, including socio-demographic characteristics (female gender, low socio-economical status, lower age), individual beliefs regarding vaccine efficacy and safety, as well as other factors (occupation, knowledge about COVID-19, etc.). Understanding the determinants of accepting or refusing the COVID-19 vaccination is crucial to plan specific interventions in order to increase the rate of vaccine coverage among health care workers. Methods: We conducted a cross-sectional online survey on HCWs in seventeen Italian regions, between 30 June and 4 July 2021, in order to collect information about potential factors related to vaccine acceptance and hesitancy. Results: We found an overall vaccine uptake rate of 96.4% in our sample. Acceptance was significantly related to job task, with physicians showing the highest rate of uptake compared to other occupations. At univariate analysis, the HCWs population's vaccine hesitancy was significantly positively associated with fear of vaccination side effects (p < 0.01), and negatively related to confidence in the safety and efficacy of the vaccine (p < 0.01). Through multivariate analysis, we found that only the fear of possible vaccination side effects (OR: 4.631, p < 0.01) and the confidence in vaccine safety and effectiveness (OR: 0.35 p < 0.05) remained significantly associated with hesitancy. Conclusion: Action to improve operator confidence in the efficacy and safety of the vaccine should improve the acceptance rate among operators.

Impact of light therapy on rotating night shift workers: the EuRhythDia study.

AIMS: Disturbances in circadian rhythms may promote cardiometabolic disorders in rotating night shift workers (r-NSWs). We hypothesized that timed light therapy might reverse disrupted circadian rhythms and glucose intolerance observed among r-NSWs). METHODS: R-NSWs were randomly assigned to a protocol that included 12 weeks on followed by 12 weeks off light therapy (n = 13; 6 men; mean age, 39.5 ± 7.3 years) or a no-treatment control group (n = 9; 3 men; mean age 41.7 ± 6.3 years). Experimental and control participants underwent identical metabolic evaluations that included anthropometric, metabolic (including oral glucose tolerance tests), lipid, and inflammation-associated parameters together with an assessment of sleep quality and expression of circadian transcription factors REV-ERBα and BMAL1 in peripheral blood mononuclear cells (PBMCs) at baseline, 12 weeks, and 24 weeks of the protocol. RESULTS: Twelve weeks of warm white-light exposure (10,000 lx at 35 cm for 30 min per day) had no impact on sleep, metabolic, or inflammation-associated parameters among r-NSWs in the experimental group. However, our findings revealed significant decreases in REV-ERBα gene expression (p = 0.048) and increases in the REV-ERBα/BMAL1 ratio (p = 0.040) compared to baseline in PBMCs isolated from this cohort. Diminished expression of REV-ERBα persisted, although the REV-ERBα/BMAL1 ratio returned to baseline levels after the subsequent 12-day wash-out period. CONCLUSIONS: Our results revealed that intermittent light therapy had no impact on inflammatory parameters or glucose tolerance in a defined cohort of r-NSWs. However, significant changes in the expression of circadian clock genes were detected in PBMCs of these subjects undergoing light therapy.

Night Shift Work Is Associated with Reduced Rate of Humoral Response Following Vaccination for HBV.

Night shift work has been associated with cardiovascular and metabolic disease, endocrine and immunological disorders. Published studies have reported that a reduced total sleep time with sleep-wake cycle alterations were associated with a reduced rate of humoral response following vaccination. Our study aimed to evaluate the association between night shift work and serological status for HBV among workers employed in a university hospital in Rome. We evaluated medical records of 986 HCWs working at Tor Vergata Policlinic of Rome. We screened all study subjects for anti-HBs IgG, anti-HBc IgG and HBsAg. Serological protection for HBV was evaluated in relation to sex, age group, job task, risk setting and night shift work status. Protective titer was found in 856 (86.8%) study participants and the mean titer was significantly high in females, in subjects aged less than 40 years, in night shift workers and in high-risk setting workers. After adjustment for study covariates, night shift work was no longer associated with an HBV-protective titer. This finding suggests that a vaccination strategy for dampening HBV transmission should be carefully addressed in health care workers (HCWs) doing night shift.

An improved in vitro model simulating the feto-maternal interface to study developmental effects of potentially toxic compounds: The example of titanium dioxide nanoparticles.

The study of developmental effect of xenobiotics in humans is limited and often relies on epidemiological data. Whether and to which extent potentially toxic compounds may cross the placental barrier, and whether adverse effects on embryo development are the consequence of direct or indirect placental-mediated action is debated. The availability of in vitro models simulating the feto-maternal interface could contribute to elucidate this issue. Here, we report the development of a novel in vitro model using murine blastocyst derived trophoblast stem cells (TSC) to mimic the placental barrier and mouse embryoid bodies (EBs) to represent the embryonic tissues. We demonstrate that this model can be used for translocation studies, as well as embryotoxicity assessment of titanium dioxide nanoparticles (TiO2NPs). By evaluating trans-epithelial electrical resistance, translocation of fluorescein isothiocyanate-dextran beads and expression of junctional complex proteins, we show that TSCs cultured on transwell inserts under differentiating condition form syncytia. We also show that TiO2NPs administered in the upper transwell compartment are able to reach the lower compartment and interfere with EB differentiation when no TSC are cultured on the insert. On the contrary, when TSC are present, NPs translocate to a lesser extent and do not affect EB development. These results indicate that the proposed in vitro model is suitable to study the correlation between translocation and toxicity of TiO2NPs and suggest a direct effect of the particles on EB development. We propose that this model could be exploited to study developmental effect of other xenobiotics.