High body mass index and night shift work are associated with COVID-19 in health care workers.

OBJECTIVE: To assess the magnitude of COVID-19 spread and the associated risk factors among health care workers (HCWs), we conducted an in-hospital survey in a central Italian COVID Hospital. METHODS: Participants underwent nasopharyngeal swab and/or serum collection for SARS-CoV-2 IgG examination. We divided participants according to working status, into rotating-night shift workers (r-NSW) and day-workers. RESULTS: We found 30 cases of COVID-19 infection in a total of 1180 HCWs (2.5%). Most COVID-19-positive hospital employees were r-NSWs with significantly higher BMI than that of individuals who tested negative. After adjustment for covariates, night work and BMI > 30 were associated with a markedly greater risk of COVID-19 diagnosis (OR 3.049 [95%CI 1.260-7.380] and OR 7.15 [95%CI 2.91-17.51], respectively). CONCLUSIONS: Our results describe a low prevalence of COVID-19 infection among HCWs at a central Italian COVID Hospital. COVID-19 infection risk appears to be associated with obesity and night shift work, thus supporting the need for careful health surveillance among frontline HCWs exposed to COVID-19.

Lipid composition modulates ATP hydrolysis and calcium phosphate mineral propagation by TNAP-harboring proteoliposomes.

Bone biomineralization is mediated by a special class of extracellular vesicles, named matrix vesicles (MVs), released by osteogenic cells. The MV membrane is enriched in sphingomyelin (SM), cholesterol (Chol) and tissue non-specific alkaline phosphatase (TNAP) compared with the parent cells' plasma membrane. TNAP is an ATP phosphohydrolase bound to cell and MV membranes via a glycosylphosphatidylinositol (GPI) anchor. Previous studies have shown that the lipid microenvironment influences the catalytic activity of enzymes incorporated into lipid bilayers. However, there is a lack of information about how the lipid microenvironment controls the ability of MV membrane-bound enzymes to induce mineral precipitation. Herein, we used TNAP-harboring proteoliposomes made of either pure dimyristoylphosphatidylcholine (DMPC) or DMPC mixed with either Chol, SM or both of them as MV biomimetic systems to evaluate how the composition modulates the lipid microenvironment and, in turn, TNAP incorporation into the lipid bilayer by means of calorimetry. These results were correlated with the proteoliposomes' catalytic activity and ability to induce the precipitation of amorphous calcium phosphate (ACP) in vitro. DMPC:SM proteoliposomes displayed the highest efficiency of mineral propagation, apparent affinity for ATP and substrate hydrolysis efficiency, which correlated with their highest degree of membrane organization (highest ΔH), among the tested proteoliposomes. Results obtained from turbidimetry and Fourier transformed infrared (FTIR) spectroscopy showed that the tested proteoliposomes induced ACP precipitation with the order DMPC:SM>DMPC:Chol:SM≈DMPC:Chol>DMPC which correlated with the lipid organization and the presence of SM in the proteoliposome membrane. Our study arises important insights regarding the physical properties and role of lipid organization in MV-mediated mineralization.

Monthly fluctuations in 25-hydroxy-vitamin D levels in day and rotating night shift hospital workers.

PURPOSE: Epidemiological studies have suggested that indoor hospital employees, either day or night shift workers, are at high risk of metabolic and cardiovascular diseases. Interestingly, previous reports have also described a higher prevalence of vitamin D (25OHD) deficiency among these workers. However, few studies have determined the monthly variations in 25OHD levels in indoor hospital employees. METHODS: To address this lack of knowledge, in 2018, during the periodic health surveillance checks at the Service of Occupational Medicine, we measured 25OHD levels in a group of indoor hospital workers (88 rotating night shift workers vs 200 day workers). Each participant received a single annual health surveillance check. RESULTS: The mean levels of 25OHD were consistently below the lower limit of the normal range in both groups throughout the year. Only in the summer, day workers but not rotating night shift workers (mean 25.9 ± 11.3 ng/ml vs 23.1 ± 9.1 ng/ml; p = 0.042) showed levels significantly higher than those in the other seasons. This difference remained statistically significant even after correction for study covariates [ß = -  1.649 (CI - 0.283/- 3.482), p = 0.039]. A cosinor analysis confirmed that the difference in the 25OHD levels between groups was present later in the year. CONCLUSIONS: We found that relatively young healthy hospital workers, especially those with rotating night shifts, in the absence of significant metabolic risk factors, have a high risk of 25OHD deficiency/insufficiency. Because 25OHD deficiency may lead to a progression to more severe conditions such as osteoporosis or bone fractures, our results should be verified in larger cohorts including different ancestries.

Pulmonary functionality among workers of a Central Italy waste-to-energy plant: a retrospective study.

BACKGROUND: We are observing a growing trend towards the use of waste incineration in waste-to-energy (WTE) plants in Italy. Various authors started to investigate their potential health effects, but without univocal outcomes. The aim of this study is to assess whether or not main pulmonary function indexes could be decreased in a group of workers employed in a municipal solid WTE plant located in Central Italy, and if there's a correlation between the levels of exposure to airborne pollutants and alterations in the pulmonary apparatus. METHODS: The study was conducted with a retrospective cohort approach. We reviewed data from clinical records of 58 waste-to-energy plant workers undergoing annual health surveillance in the period 2010-2015. We considered the exposure to airborne dust and the main parameters of respiratory function (FVC, FEV1, Tiffeneau Index and FEF 25-75%) at time zero and after a period of 5 years. We divided our study population into two groups: low (< 1 mg/m3) and high (> 1 mg/m3) exposure. We estimated odds ratios (OR) with 95% confidence interval (95% CI) adjusted for potential confounders. RESULTS: We observed a decrease in lung function parameters both in high and in low exposure group after a five-years exposure period. FEV1, FEV1/VC ratio and FEF 25-75% were worst in more exposed group, even if this difference resulted not significant at Wilcoxon test. CONCLUSIONS: Active employee in WTE plants is associated to a non-significant worsening in the main parameters of lung function after 5 years exposure. Clinical significant of these variations need to be assessed.

Diabetes and work: The need of a close collaboration between diabetologist and occupational physician.

AIM: The Italian Society of Occupational Medicine (SIML), the Italian Diabetes Society (SID) and the Association of Diabetologists (AMD) joined a working group that produced a consensus paper aimed to assess the available evidence regarding the interplay between specific working conditions, including shift- and night-time work, working activities at high risk of accidents and work at heights, working tasks requiring high-energy expenditure, working activities at extreme temperatures and diabetes. DATA SYNTHESIS: Diabetes is a group of metabolic disorders caused by defects in insulin secretion and/or action affecting millions of people worldwide, many of whom are or wish to be active members of the workforce. Although diabetes, generally, does not prevent a person from properly performing his/her working tasks, disease complications can significantly compromise a person's ability to work. Therefore, it appears evident the need to understand the relationship between occupational risk factors and diabetes. The working group included in the document some practical recommendations useful to ensure diabetic workers the possibility to safely and effectively undertake their jobs and to adequately manage and treat their disease, also in the workplace. In this perspective concerted action of all the workplace preventive figures, occupational physicians and diabetologists should be strongly encouraged. CONCLUSIONS: Further studies are necessary to define workplace-based interventions, which should be minimally invasive towards the work organization, allowing diabetic workers to fully realize their work skills while improving their wellbeing at work.

Is there a relationship between stature and age of onset of type 2 Diabetes?

AIMS: MSP1A and MSP1B polymorphic sites located in the GH genomic area have been found associated with GH response to insulin stimulation, with familiar short stature and with age at onset of Type 2 Diabetes (T2D). These observations prompted us to search for a possible relationship between stature and age at onset of the disease. METHODS: We have reexamined the data of 272 subjects with T2D mellitus. RESULTS: There is a highly significant negative correlation between stature and age at onset in non obese females (p < 0.001) but not in obese females and in males. In non obese females with stature within the first quartile the mean age at onset is 62 years while in those with a stature greater than the first quartlile the mean age at onset is 52 yesrs (p < 0.001). No difference is observed in obese females and males. CONCLUSIONS: These observations suggest the existence of different mechanisms underlying susceptibility to T2D. In addition to the well known increased risk due to obesity, endocrine dysfunctions related to genetic variability within the GH genomic area could represent another mechanism operating in non obese females. A cluster of non obese women characterized by short stature and late onset of diabetes seems to be separated by this mechanism from other women.

Managing the risk of bacterial meningitis among healthcare workers.

BACKGROUND: Meningococcal disease is generally caused by A, B, C, W and Y subgroups of Neisseria meningitidis. In 2015, the Italian mass media focused on this disease due to the death of two nurses. This generated alarm in the general population, especially in healthcare workers (HCWs). The Occupational Medicine department of the Foundation PTV Polyclinic Tor Vergata (PTV) offered free MenACWY vaccine to HCWs and to students of the University of Rome Tor Vergata. AIMS: To analyse the prevalence of N. meningitidis in PTV, a large teaching hospital, and to evaluate preventive measures offered to individuals at risk (i.e. HCWs and students). METHODS: The Hospital Informatic Service provided data about patients admitted to PTV from January 2012 to December 2016. Hospital Discharge Registers were analysed and all cases of meningitis were selected. MenACWY vaccine administered to HCWs and students of PTV in 2017 was analysed. RESULTS: There was just one case of meningococcal disease in 2016. Of the 117 MenACWY vaccines administered, 42% were given to students, 32% to doctors, 8% to nurses, 2% to clerks and 16% to other healthcare professionals. CONCLUSIONS: International guidelines recommend MenACWY vaccine for microbiologists exposed to N. meningitidis isolates. The Italian Legislative Decree 81/2008, however, states that occupational physicians can adopt special protective measures such as vaccination programmes for HCWs. The response rate highlights how perceived risk may influence behaviour even in populations with a higher background knowledge than the general population.

Measles immunity in an Italian teaching hospital.

BACKGROUND: Healthcare workers (HCWs) have an increased exposure risk to measles, which can put them, their patients and their relatives at risk of infection. In Italy, 4617 cases of measles were reported in 2017; 302 involving HCWs. According to the Italian National Immunization and Prevention Plan, all HCWs should have demonstrable evidence of immunity to measles. AIMS: To evaluate measles immunization status in HCWs at a large Italian teaching hospital. METHODS: We analysed clinical records and measles-specific IgG antibody titres of HCWs undergoing occupational health surveillance between 1 January and 31 August 2017. RESULTS: Among the 1532 HCWs (mean age 32.7 ± 10.4 years) included in the study, 87% (1328) had protective antibody titres. The proportion of protective titres was highest in those born before 1982. No significant gender differences in mean measles-specific IgG antibody titres were detected. CONCLUSIONS: Our study shows non-protective measles IgG antibody titres in a substantial percentage of HCWs, especially those born in the 1980s and 1990s. Due to the increased risk of measles transmission in the hospital environment, increased prevention strategies are required, including rigorous screening and prompt vaccination of non-immune workers.

Smoking and hypertension: Effect of adenosine deaminase polymorphism.

Adenosine modulates cardiovascular functions reducing blood pressure and heart rate. Adenosine deaminase (ADA) by the irreversible deamination of adenosine to inosine contributes to the regulation of adenosine concentration in body fluids. We have studied the interaction between smoking and ADA genetic variability concerning their effects on blood pressure. We have studied 344 subjects admitted to the hospital for cardiovascular diseases. The genotypes of two polymorphic loci within the ADA gene were determined: ADA1 and ADA2. Both loci show two alleles: ADA1*1 and ADA1*2 in ADA1 locus and ADA2*1 and ADA2*2 in ADA2 locus. In the absence of smoking, the proportion of subjects with hypertension tends to be lower in carriers of the ADA1*2 allele. In smoking subjects, the pattern is reversed and the proportion of those with hypertension tends to be higher in carriers of the ADA1*2 allele. A similar pattern is observed for ADA2 locus. Smoking increases the proportion of subjects showing hypertension: such effect is more marked in those carrying the ADA1*2 allele as compared to subjects with ADA1*1/*1 genotype. The same pattern of association is observed for ADA2 locus. The two loci show an additive effect. The odds ratio for hypertension in smokers vs nonsmokers is 1.450 in subjects carrying ADA1*1/*1 and ADA2*1/*1 genotypes, while it is 11.200 in subjects carrying the *2 alleles in both loci. From a practical point, a view of our results suggest that smokers carrying both ADA1*2 and ADA2*2 alleles have a higher risk of hypertension.

Nasal cytology as a screening tool in formaldehyde-exposed workers.

Background: Workers in pathology and anatomy laboratories may be exposed to formaldehyde. An evaluation of the early effects of this substance is, therefore, paramount. This preliminary study was conducted to evaluate if nasal cytology could be used as a tool to detect changes in nasal mucosa in workers exposed to formaldehyde. Aims: To assess whether nasal cytology was able to reveal any alteration of nasal mucosa in workers exposed to formaldehyde compared to unexposed subjects, and to ascertain whether a specific pattern of alterations correlated with years of exposure in order to evaluate long-term occupational exposure effects. Methods: The study included a group of workers exposed to formaldehyde and a group of non-exposed workers. All subjects underwent clinical examination, followed by nasal cytology. Pathological indices from each rhinocytograms were compared between the two groups. Results: Nasal cytology revealed a chronic inflammatory non-allergic condition in the exposed group. Qualitative analysis of data distribution of neutrophils and mucous-secreting/ciliated cells ratio showed data clustering with a cut-off set at 15 years of exposure. The mean formaldehyde concentrations ranged from <0.04 to 0.15 parts per million (ppm). The maximum levels of formaldehyde concentrations ranged from 0.2 to 0.67 ppm. Conclusions: Our data indicate that nasal cytology may be a promising tool for the health surveillance of workers exposed to formaldehyde and may also represent a useful research tool for the study of the health effects of other chemicals irritants for the upper airways.

Gender perspective in occupational medicine and workplace risk assessment: state of the art and research agenda.

The aim of this study was to investigate the current situation and the research agenda in the field of gender differences, both generically in the occupational settings and in the specific activity of risk assessment. Gender is a key determinant of health; the evaluation of documents and scientific literature shows increasing attention to a gender oriented approach, as demonstrated by the development of Gender Medicine, actually cross-oriented in all medical specialties, the publication of books dedicated to this topic and the birth of "ad hoc" new scientific societies and journals. Even today, however, the gender differences are not considered as they should in the context of health disciplines, including occupational medicine. In this respect, in fact, the critical issues to be overcome are numerous, such as the phenomena of "segregation", the exposure to risk factors and their effects, related also to non-professional, socio-cultural features that differentiate male and female workers. All these factors can lead to situations of inequality in health. In fact, the European directives on safety at work repeatedly highlight the attention to gender differences in prevention, assessment and management of risks. In this regard, the European Agency for Safety and Health at Work advocates an approach "more sensitive" to gender in all the processes of assessment and risk management, from the research of all potential sources of risk to the decision-making processes, in order to address the prevention of risks in a holistic manner.

Forecasting nanoparticle toxicity using nonlinear predictive regressor learning systems.

Nanoparticle (NP) toxicity is determined by a vast number of topological, sterical, physico-chemical as well as biological properties, rendering a priori evaluation of the effect of NP on biological tissue as arduous as it is necessary and urgent. We aimed at mining the HORIZON 2020 MODENA COST NP cytotoxicity database through nonlinear predictive regressor learning systems in order to assess the power of available NP descriptors and assay characteristics in predicting NP toxicity. Specifically, we assessed the results of cytotoxicity assays performed on 57 NP and trained two different nonlinear regressors (Support Vector Regressors [SVR] with polynomical kernels and Radial Basis Function [RBF] regressors) within a nested-cross validation scheme for parameter optimization to predict toxicity as quantified by EC25, EC50 and slope while using the regressional ReliefF algorithm (RReliefF) for feature selection. Available NP attributes were material, coating, cell type, dispersion protocol, shape, 1st and 2nd dimension, aspect ratio, surface area, zeta potential and size in situ. In most regressor learning systems, after feature selection with the RReliefF algorithm, the correlation between real and estimated toxicity endpoint values increased monotonically with the number of included features, reaching values above 0.90. The best performance was obtained with RBF regressors, and the most informative features in predicting toxicity endpoints were related to nanoparticle structure. These trends did not change significantly between toxicity endpoints. In conclusion, EC25, EC50 and slope can be predicted with high correlation using purely data-driven, machine learning methods in Adenosine triphosphate (ATP)-based NP cytotoxicity assays.

[Alcohol and work. Consensus Document of the La.R.A. (Workers representing a risk for others) group]. / Alcol e Lavoro. Documento di consenso del gruppo La.R.A.

AIM: Current Italian legislation obliges employers to prevent workers who are occupationally at risk or who perform jobs that may be hazardous for the safety or health of third parties from consuming alcohol. The LaRA Group undertook to assess whether the law fully safeguards the health and safety of both workers and third parties, without impinging upon the civil rights of workers. METHOD: A written document expressing agreement was produced following discussions between doctors, lawyers, bioethicists and social partners. RESULTS: There are gaps and inconsistencies in current laws; the differences in local and regional provisions prevent authorities from applying a single strategy at national level. There should be a change in existing rules under which the employer's obligation to enforce the ban on consumption alcohol in the workplace is enacted solely by the "competent" physician whose institutional role is to safeguard and promote health. Some occupational categories that are subject to a ban on alcohol consumption do not currently under-go health surveillance. For example, if road transport drivers are not exposed to a specific occupational risk foreseen under another law, they can be placed under health surveillance only in those regions where the local laws contemplate this type of control. In other cases, the practice of assessing the risk to third parties and providing for compulsory health surveillance in the Risk Assessment Document, is considered by some jurists to be a "consuetudo praeter legem" and therefore acceptable in a field not yet covered by a specific law, but to be "contra legem" or unlawful by other jurists. Moreover, the competent physician who uses a breathanalyser or tests for alcohol addiction faces an ethical dilemma, since by communicating the results to an employer or authorities responsible for the issuing of licenses, he may be violating his professional oath of secrecy. Furthermore, the emphasis placed on testing has induced companies and inspectors to overlook educational and rehabilitation aspects. It is essential to involve general practitioners, educators and specialist services in addressing the problems of alcohol abuse so as to inform/train, recover and rehabilitate. The few studies available indicate that the rules are poorly enforced and that non-compliance may go unobserved. CONCLUSIONS: The Group urges all employers to assess the risk for third parties caused by alcohol abuse and to devise a policy on alcohol. Controlling alcohol-related risks in the workplace calls for a better definition of the roles of Vigilance Bod-ies and Company Physicians together with a shift from a reactive to a proactive attitude of all the parties involved.

Type 1 diabetes mellitus. Comparison between the association with PTPN22 genotype and the association with ACP1-ADA1 joint genotype.

AIMS: T1D has been found associated with PTPN22 and with ACP1-ADA1 joint genotype. In the present note we have collected further data to evaluate the relative importance of the two systems and to search for possible interaction of PTPN22 with ACP1-ADA1 joint genotype. METHODS: We have studied 314 children with T1D and 770 controls from the White population of Central Italy. ACP1, ADA1 and PTPN22 genotypes were determined by DNA analysis. Chi square test of independence was performed by SPSS program and three way contingency analysis by a log-linear model. RESULTS: Both carriers of *T allele of PTPN22 and subjects with ACP1 *A/*A and *A/*B genotypes carrying ADA1 *2 allele show an increase of susceptibility to T1D. There is evidence of additive effect (p=0.0002) but not of epistatic interaction. The association of T1D with ACP1-ADA1 joint genotype is stronger (OR=2.494, 95% C.I. 1.509-4.122) as compared to that with PTPN22 (OR=1.825, 95% C.I. 1.951-2.859). CONCLUSIONS: It has been suggested that the *T variant of PTPN22 inhibits T cell receptor signaling leading to failure to delete autoreactive T cells during intrathymic selection resulting in increased susceptibility to autoimmune disorders. The joint genotype ACP1 *A/*A and *A/*B carrying the ADA1 *2 allele shows a decreased activity of ACP1 resulting in a lowering of Zap70 activity that may decrease T cell receptor signaling with an additive effects to the inhibition due to the *T variant of PTPN22.

Engineered nanoparticles at the workplace: current knowledge about workers' risk.

BACKGROUND: The novel physicochemical properties of engineered nanoparticles (ENPs) make them very attractive for industrial and biomedical purposes, but concerns have been raised regarding unpredictable adverse health effects in humans. Current evidence for the risk posed by ENPs to exposed workers is the subject of this review. AIMS: To perform an in-depth review of the state of art of nanoparticle exposure at work. METHODS: Original articles and reviews in Pubmed and in principal databases of medical literature up to 2013 were included in the analysis. In addition, grey literature released by qualified regulatory agencies and by governmental and non-governmental organizations was also taken into consideration. RESULTS: There are significant knowledge and technical gaps to be filled for a reliable evaluation of the risk posed for workers by ENPs. Evidence for potential workplace release of ENPs however seems substantial, and the amount of exposure may exceed the proposed occupational exposure limits (OELs). The rational use of conventional engineering measures and of protective personal equipment seems to mitigate the risk. CONCLUSIONS: A precautionary approach is recommended for workplace exposure to ENPs, until health-based OELs are developed and released by official regulatory agencies.

The association of PTPN22 polymorphism with endometriosis: effect of genetic and clinical factors.

OBJECTIVE: To investigate the possible effect of clinical and genetic variables on the association between PTPN22 and endometriosis. METHODS: PTPN22, ACP1 and p53 codon 72 genetic polymorphisms and duration of previous pharmacological treatment were studied. The study sample consisted of 132 women hospitalized for endometriosis diagnosed by laparoscopic intervention and histologically confirmed: 359 healthy blood donors were studied as controls. PTPN22, ACP1 and p53 codon 72 genotypes were determined by DNA analysis. Discriminant statistical analysis, logistic regression analysis, chi square of independence, power test and linear correlation were performed using SPSS programs. RESULTS: A significant increase of PTPN22 *T allele in endometriosis is observed in women carrying ACP1*C allele, in women carrying p53 codon 72 *Pro allele and in women with prolonged pharmacological treatment. CONCLUSIONS: PTPN22 may not be a primary factor in the etiology of endometriosis but may cooperate with clinical and genetic factors influencing susceptibility and clinical course of disease. These new observations point to a multifactorial origin of endometriosis and help to explain the reported differences between human populations concerning the association between PTPN22 and endometriosis.