Impact of Exposure to Vaccination and Infection on Cellular and Antibody Response to SARS-CoV-2 in CVID Patients Through COVID-19 Pandemic.

PURPOSE: The purpose of this study is to investigate the kinetics of response against SARS-CoV-2 elicited by vaccination and/or breakthrough infection (occurred after 3 doses of BNT162b2) in a cohort CVID patients. METHODS: We measured humoral and cellular immunity using quantitative anti-spike antibody (anti-S-IgG) and neutralization assay and specific interferon-gamma release assay (IGRA) before and after the third or fourth dose of BNT162b2 and/or after COVID-19. RESULTS: In CVID, 58.3% seroconverted after 2 doses that increased to 77.8% after 3 doses. Between the second and third dose, there was a decline in humoral compartment that led to titers below the cutoff of 1:10 (MNA90%) in CVID. This was paralleled by a significantly lower proportion (30%) and reduced magnitude of the residual cellular response among CVID. The third dose achieved a lower titer of anti-S and nAb against the Wuhan strain than HC and significantly decreased the rate of those showing solely a positive neutralizing activity and those with simultaneous negativity of IGRA and nAbs; the differences in IGRA were overall reduced with respect to HC. At further sampling after breakthrough SARS-COV-2 infection, mostly in the omicron era, or fourth dose, 6 months after the last event, the residual nAb titer to Wuhan strain was still significantly higher in HC, while there was no significant difference of nAbs to BA.1. The rate of IGRA responders was 65.5% in CVID and 90.5% in HC (p=0.04), while the magnitude of response was similar. None of CVID had double negativity to nAbs and IGRA at the last sampling. CONCLUSION: This data shows an increase of adaptive immunity in CVID after mRNA vaccination in parallel to boosters, accrual number of exposures and formation of hybrid immunity.

Continuous assessment of trunk posture in healthcare workers assigned to wards with different MAPO index.

Healthcare professionals generally experience an above-average incidence of low back disorders (LBDs) compared with workers of other professions, and its level of risk is commonly assessed using observational methods such as the MAPO method (Movement and Assistance of Hospital Patients). In this study, we continuously monitored the trunk posture of 30 healthcare workers using a single inertial sensor to: (1) understand whether the MAPO classification is effective in adequately discriminating the risk associated with the time spent in non-neutral trunk postures and (2) characterise the variability of biomechanical exposure among workers employed in wards with the same MAPO index. The results substantially confirm the validity of the MAPO approach in discriminating among wards characterised by different levels of biomechanical exposure associated with the risk of developing LBDs. However, they also highlight the need to assess workers' exposure on an individual basis due to the high intra-group variability.Practitioner summary: Employing a quantitative measurement setup to monitor trunk posture along with an observational method (ie MAPO) can identify the existence of criticalities or the poor application of ergonomic recommendations given during the training of healthcare workers even in hospital wards characterised by little or no risk of developing low back disorders.

Evaluation of humoral and cellular response to third dose of BNT162b2 mRNA COVID-19 vaccine in patients treated with B-cell depleting therapy.

OBJECTIVE: to investigate the responses to mRNA COVID-19 vaccines in a cohort of immunosuppressed patients affected by immune-mediated inflammatory diseases (IMID). METHODS: we have measured humoral and cellular immunity using quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG), neutralization assays and specific interferon-gamma (IFN-g) release assay (IGRA) before and after the third dose of BNT162b2. The response of those on anti-CD20 (n = 18) was then compared with healthy controls (HC, n = 18) and IMID naïve to anti-CD20 drugs (n = 13). RESULTS: a third BNT162b2 dose is highly immunogenic in IMID patients naïve to anti-CD20, as 100% of the subjects seroconverted compared to the 55% in anti-CD20. The rate of IGRA response was of 79% in anti-CD20, 50% in IMID naïve to anti-CD20, 100% in HC. Among those who have seroconverted, IMID patients had significantly reduced anti-S-IgG and neutralization titers compared to HC, whereas no significant difference was observed when comparing anti-CD20 and HC. Furthermore, 13% of anti-CD20 and 7.7% of IMID were simultaneously negative for both neutralizing antibodies and IGRA after three doses. CONCLUSION: these data draw attention to the immunogenicity of COVID-19 vaccination in treated IMID, taking specific groups into consideration for vaccination program.

Occupational exposure to glyphosate and risk of lymphoma:results of an Italian multicenter case-control study.

BACKGROUND: The International Agency for Research on Cancer (IARC) recently classified glyphosate, the most used herbicide worldwide, as a probable human carcinogen. We inquired into the association between occupational exposure to glyphosate and risk of lymphoma subtypes in a multicenter case-control study conducted in Italy. METHODS: The Italian Gene-Environment Interactions in Lymphoma Etiology (ItGxE) study took place in 2011-17 in six Italian centres. Overall, 867 incident lymphoma cases and 774 controls participated in the study. Based on detailed questionnaire information, occupational experts classified duration, confidence, frequency, and intensity of exposure to glyphosate for each study subject. Using unconditional regression analysis, we modelled risk of major lymphoma subtypes associated with exposure to glyphosate adjusted by age, gender, education, and study centre. RESULTS: Very few study subjects (2.2%) were classified as ever exposed to glyphosate. Risk of follicular lymphoma (FL) was elevated 7-fold in subjects classified as ever exposed to glyphosate with medium-high confidence, 4.5-fold in association with medium-high cumulative exposure level, 12-fold with medium-high exposure intensity, and 6-fold with exposure for 10 days or more per year. Significant upward trends were detected with all the exposure metrics, but duration. The overall p-value for an upward trend with four independent metrics was 1.88 × 10- 4. There was no association with risk of lymphoma (any subtype), Non Hodgkin Lymphoma, B-cell lymphoma, or the major lymphoma subtypes other than FL. CONCLUSIONS: Our findings provide limited support to the IARC decision to classify glyphosate as Group 2A human carcinogen.

Task-oriented exercises improve disability of working patients with surgically-treated proximal humeral fractures. A randomized controlled trial with one-year follow-up.

BACKGROUND: General physiotherapy is a common means of rehabilitation after surgery for proximal humeral fracture (PHF). Better-targeted exercises seem worthy of investigation and the aim of this study was to assess the efficacy of a rehabilitation program including task-oriented exercises in improving disability, pain, and quality of life in patients after a PHF. METHODS: By means of a randomized controlled trial with one-year follow-up, 70 working patients (mean age of 49 ± 11 years; 41 females), who were selected for open reduction and internal fixation with plates caused by PHF, were randomized to be included in an experimental (n = 35) or control group (n = 35). There was a permuted-block randomization plan, and a list of program codes was previously created; subsequently, an automatic assignment system was used to conceal the allocation. The first group underwent a supervised rehabilitation program of task-oriented exercises based on patients' specific job activities, and occupational therapy. The second group underwent general physiotherapy, including supervised mobility, strengthening and stretching exercises. Both groups individually followed programs of 60-min session three times per week for 12 weeks in the outpatient setting. The Disability Arm Shoulder Hand questionnaire (DASH; scores range from 0 to 100; primary outcome), a Pain intensity Numerical Rating Scale (scores range 0 to 10; secondary outcomes), and the Short-Form Health Survey (scores range from 0 to 100; secondary outcomes) assessed the interventions. Participants were evaluated before surgery, before and after rehabilitation (primary endpoint), and at the one-year follow-up (secondary endpoint). A linear mixed model analysis for repeated measures was carried out for each outcome measure (p < 0.05). RESULTS: Time, group and time by group showed significant effects for all outcome measures in favour of the experimental group. The DASH and the DASH work achieved clinically important between-group differences of 16.0 points (95% confidence interval [C.I.] 7.3 to 24.7) and 19.7 (95% C.I. 9.0 to 30.5) at follow-up, respectively. The NRS achieved a between-group difference of 2.9 (95% C.I. 1.0 to 3.9) at follow-up. As for SF-36, there were between-group differences ranging from 17.9 to 37.0 at follow-up. CONCLUSIONS: A rehabilitation program based on task-oriented exercises was useful in improving disability, pain, and quality of life in working patients after PHFs. Improvements lasted for at least 12 months. TRIAL REGISTRATION: On 16/12/2019, the trial was retrospectively registered in the ISRCTN registry with the ID number 17996552 .

Metals and Metal-Nanoparticles in Human Pathologies: From Exposure to Therapy.

An increasing number of pathologies correlates with both toxic and essential metal ions dyshomeostasis. Next to known genetic disorders (e.g., Wilson's Disease and ß-Thalassemia) other pathological states such as neurodegeneration and diabetes are characterized by an imbalance of essential metal ions. Metal ions can enter the human body from the surrounding environment in the form of free metal ions or metal-nanoparticles, and successively translocate to different tissues, where they are accumulated and develop distinct pathologies. There are no characteristic symptoms of metal intoxication, and the exact diagnosis is still difficult. In this review, we present metal-related pathologies with the most common onsets, biomarkers of metal intoxication, and proper techniques of metal qualitative and quantitative analysis. We discuss the possible role of drugs with metal-chelating ability in metal dyshomeostasis, and present recent advances in therapies of metal-related diseases.

Metal Complex Formation and Anticancer Activity of Cu(I) and Cu(II) Complexes with Metformin.

Metformin has been used for decades in millions of type 2 diabetes mellitus patients. In this time, correlations between metformin use and the occurrence of other disorders have been noted, as well as unpredictable metformin side effects. Diabetes is a significant cancer risk factor, but unexpectedly, metformin-treated diabetic patients have lower cancer incidence. Here, we show that metformin forms stable complexes with copper (II) ions. Both copper(I)/metformin and copper(II)/metformin complexes form adducts with glutathione, the main intracellular antioxidative peptide, found at high levels in cancer cells. Metformin reduces cell number and viability in SW1222 and K562 cells, as well as in K562-200 multidrug-resistant cells. Notably, the antiproliferative effect of metformin is enhanced in the presence of copper ions.

Occupational exposure to ionizing radiation and risk of lymphoma subtypes: results of the Epilymph European case-control study.

BACKGROUND: Evidence linking risk of lymphoma and B-cell lymphoma subtypes to ionizing radiation is inconclusive, particularly at low exposure levels. METHODS: We investigated risk of lymphoma (all subtypes), B-cell lymphomas, and its major subtypes, associated with low-level occupational exposure to ionizing radiation, in 2346 lymphoma cases and 2463 controls, who participated in the multicenter EpiLymph case-control study. We developed a job-exposure matrix to estimate exposure to ionizing radiation, distinguishing between internal and external radiation, and we applied it to the lifetime occupational history of study subjects, We calculated the Odds Ratio (OR) and its 95% confidence interval (95% CI) for lymphoma (all subtypes combined), B-cell lymphoma, and its major subtypes using unconditional, polytomous logistic regression adjusting for age, gender, and education. RESULTS: We did not observe an association between exposure metrics of external and internal radiation and risk of lymphoma (all subtypes), nor with B-cell lymphoma, or its major subtypes, at the levels regularly experienced in occupational settings. An elevated risk of diffuse large B cell lymphoma was observed among the most likely exposed study subjects with relatively higher exposure intensity, which would be worth further investigation. CONCLUSIONS: Further investigation is warranted on risk of B cell lymphoma subtypes associated with low-level occupational exposure to external ionizing radiation, and to clarify whether lymphoma should be included among the cancer outcomes related to ionizing radiation.

Compassion fatigue, watching patients suffering and emotional display rules among hospice professionals: a daily diary study.

BACKGROUND: Hospice workers are required to regularly use emotional regulation strategies in an attempt to encourage and sustain terminally ill patients and families. Daily emotional regulation in reaction to constantly watching suffering patients may be intensified among those hospice professionals who have high levels of compassion fatigue. The main object of this study was to examine the relationship between daily exposition to seeing patient suffering and daily emotional work, and to assess whether compassion fatigue (secondary traumatic stress and burnout) buffers this relationship. METHODS: We used a diary research design for collecting daily fluctuations in seeing patients suffering and emotional work display. Participants filled in a general survey and daily survey over a period of eight consecutive workdays. A total of 39 hospice professionals from two Italian hospices participated in the study. RESULTS: Multilevel analyses demonstrated that daily fluctuations in seeing patients suffering was positively related to daily emotional work display after controlling for daily death of patients. Moreover, considering previous levels of compassion fatigue, a buffering effect of high burnout on seeing patients suffering - daily emotional work display relationship was found. CONCLUSIONS: A central finding of our study is that fluctuations in daily witness of patients suffering are positively related to daily use of positive emotional regulations. Further, our results show that burnout buffers this relationship such that hospice professionals with high burnout use more emotional display in days where they recurrently witness patients suffering.

Urinary 1H NMR metabolomics profile of Italian citizens exposed to background levels of arsenic: a (pre)cautionary tale.

Objectives: Arsenic is a toxic metal ubiquitous in the environment and in daily life items. Long-term arsenic exposure is associated with severe adverse health effects involving various target organs. It would be useful to investigate the existence of metabolic alterations associated with lifestyle and/or with the environment. For this purpose, we studied the correlation between urinary arsenic levels and urinary proton nuclear magnetic resonance spectroscopy (1H NMR) metabolomics profiles in a non-occupationally nor environmentally arsenic exposed general population.Methods: Urine samples were collected from 86 healthy subjects. Total and non-alimentary urinary arsenic (U-naAs) levels, namely the sum of arsenite, arsenate, monomethylarsonate and dimethylarsinate, were measured and 1H NMR analysis was performed. Orthogonal Projection to Latent Structures was applied to explore the correlation between the metabolomics profiles and U-naAs levels.Results: Despite the extremely low U-naAs levels (mean value = 6.13 ± 3.17 µg/g creatinine) of our studied population a urinary metabolomics profile related to arsenic was identified.Conclusion: The identified profile could represent a fingerprint of early arsenic biological effect and could be used in further studies as an indicator of susceptibility, also in subjects exposed to a low arsenic dose, with implications in occupational health, toxicology, and public health.

The role of collective affective commitment in the relationship between work-family conflict and emotional exhaustion among nurses: a multilevel modeling approach.

BACKGROUND: Work-family conflict (WFC) is a crucial problem in nursing because of the demanding conditions of the job, such as strenuous shifts, physical and emotional workload, and intense patient involvement. Using a multilevel approach, this study investigated the moderating role of collective affective commitment as a protective resource in the relationship between WFC and emotional exhaustion. METHODS: The sample included 647 nurses from 66 working units in 4 Italian hospitals. A self-administrated questionnaire was administered to nurses. To analyze data, hierarchical linear modeling was used to examine cross-level relationships between variables. RESULTS: The results indicated that emotional exhaustion increased with augmenting of WFC and that this relationship was stronger when collective affective commitment was low and weaker when it was high. CONCLUSIONS: The study thus suggests that collective affective commitment may be considered a protective resource for nurses. Moreover, the results show that high work-family conflict should not represent a serious problem when nurses have high affective commitment. Interventions at both individual and group level are discussed in order to mitigate WFC, promoting collective affective commitment and thus reducing emotional exhaustion.

Indexes of cardiac autonomic profile detected with short term Holter ECG in health care shift workers: a cross sectional study.

BACKGROUND: The assessment of early effect of shift work-related circadian rhythms desynchronization and work-related stress in health care workers has gained a primary role among the duties of the occupational physician. OBJECTIVES: Aim of our study was to assess the cardiac autonomic modulation through quantification of sinus rhythm variability, as an index of the adaptability to shift work of the cardiovascular system in healthcare shift workers. METHODS: We measured Heart Rate Variability (HRV) by short-term (60 minutes) Holter Electrocardiography (ECG) during the regular duties in the respective department of 42 healthcare workers (31 nurses and 11 physicians) of an Italian Hospital (12 male and 30 females, aged 24-58 years), working on 3 shifts with a forward fast rotation with rest at the end of the night shift (7 am - 2 pm; 2 pm - 10 pm; 10 pm - 7 am) or in a fixed daytime shift (8 am - 2 pm). Measurements were all performed between 9 am and 12 am for fixed day workers and between 9 am and 12 pm or between 10 pm and 1 am for shift workers. The following HRV parameters were compared between the subgroups of shift workers and daytime workers: mean heart rate (HR), standard deviation of all normal RR (NN) intervals (SDNN), standard deviation of the averages of NN intervals in all 5-minute segments of a recording (SDaNN) and the triangular index (the integral of the density distribution divided by the maximum of the density distribution). We used parametric tests for independent series to compare HRV parameters by subgroups within the study subjects. We also tested correlation between the variables of interest and the association between HRV and shift work modality, along with other covariates, by means of a multiple linear regression analysis. RESULTS: We found significantly lower values of SDaNN in shift workers compared with workers engaged solely on day shifts (50.80 ms vs 66.71 ms; p=0,014). The mean heart rate did not show any significant difference between day workers and shift workers (85.78 bmp vs 85.53 bpm respectively). Multivariate analysis showed a significant association between SDNN and female gender and age, while no significant associations were found between HRV and shift work. DISCUSSION: The autonomic control of the heart rhythm could be disrupted by desynchronization of the biological rhythm secondary to the organization of shift work and night work. Shift work is an important factor of social and biological distress, influencing the adaptability of the cardiovascular system to stimuli and demands of work organization.

Work-related stress in the banking sector: a study on an Italian aged population of over 2,000 workers.

INTRODUCTION: In the European Union, the employment rate for the population in the age group 55-64 years has greatly increased in the last two decades. Companies, especially in sectors such as banking, are looking for new strategies to improve the productivity of workers in this age group. OBJECTIVES: This study was conceived with the purpose of exploring the associations between job characteristics that could influence stress and certain organizational aspects in a large population of banking workers. METHODS: More than 2,000 workers over 50 years of age of an Italian banking group participated in the study. Work-related stress was measured with the Stress Questionnaire (SQ). Organizational aspects of work were measured with a dedicated scale included in the SQ. Demographic aspects were detected by specific questions. Structural equation modelling was used and correlation coefficients were calculated. RESULTS: The results from the structural equation modeling supported the theoretical model. Organizational policies are associated with both stress correlated factors (ß=0.468) and perceptions of supervisor support and social support (ß=0.710). The perception of both parameters is associated with stress outcomes (ß=0.365). The proposed model offered better results than a competitive model, on which a total mediation was tested, rather than a partial one (p<0.001). CONCLUSIONS: The results highlight the importance of an integrated assessment of the effects of organizational aspects of work and stress factors to implement the protection of physical and mental health. Further research will help to understand more thoroughly if the issues emerged are effectively related to age. This can be assessed through a case-control study that also includes younger workers.

Occupational exposure to airborne formaldehyde in hospital: setting an automatic sampling system, comparing different monitoring methods and applying them to assess exposure.

BACKGROUND: In recent years, under-vacuum sealing (UVS) and containers with formalin encapsulated in the lid have been proposed for the reduction of occupational exposure to airborne formaldehyde (FA) in healthcare environments. OBJECTIVES: We are presenting a study focused on the assessment of FA in hospitals: an automatic sampling system was set, different sampling devices were compared, and the concentration of FA was assessed, following its use in different scenarios. METHODS: Three different devices for sampling/measuring FA were compared. They are based on: 1. silica gel cartridges impregnated with 2,4-dinitrophenylhydrazine (2,4-DNPH); 2. SPME® fiber using O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine; 3. direct reading commercial instrumentation. Three typical scenarios using FA were investigated: operating theatres where small biopsies are soaked into closed-circuit system 4% FA containers, secretariat of pathology laboratories during the registration of biopsies and pathology laboratories during the filling procedure by UVS and the slicing of biopsies. RESULTS: The automatic sampling system allowed short-, long-, and in continuous-sampling time to measure airborne FA. Different sampling devices provided comparable results when tested to assess FA concentration ranging from 0.020-0.320 ppm in a test chamber, although  the devices based on 2,4-DNPH were  the best in terms of sensitivity and accuracy. The results of 246 samples showed that the FA concentration was less than 0.04 ppm in 91% of the measurements. CONCLUSIONS: The automatic methods efficiently allow sampling and measurement of FA in hospital settings. When using safe practices, the concentration of FA is well below occupational limit values.

High-Throughput Analysis of Selected Urinary Hydroxy Polycyclic Aromatic Hydrocarbons by an Innovative Automated Solid-Phase Microextraction.

High-throughput screening of samples is the strategy of choice to detect occupational exposure biomarkers, yet it requires a user-friendly apparatus that gives relatively prompt results while ensuring high degrees of selectivity, precision, accuracy and automation, particularly in the preparation process. Miniaturization has attracted much attention in analytical chemistry and has driven solvent and sample savings as easier automation, the latter thanks to the introduction on the market of the three axis autosampler. In light of the above, this contribution describes a novel user-friendly solid-phase microextraction (SPME) off- and on-line platform coupled with gas chromatography and triple quadrupole-mass spectrometry to determine urinary metabolites of polycyclic aromatic hydrocarbons 1- and 2-hydroxy-naphthalene, 9-hydroxy-phenanthrene, 1-hydroxy-pyrene, 3- and 9-hydroxy-benzoantracene, and 3-hydroxy-benzo[a]pyrene. In this new procedure, chromatography's sensitivity is combined with the user-friendliness of N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide on-fiber SPME derivatization using direct immersion sampling; moreover, specific isotope-labelled internal standards provide quantitative accuracy. The detection limits for the seven OH-PAHs ranged from 0.25 to 4.52 ng/L. Intra-(from 2.5 to 3.0%) and inter-session (from 2.4 to 3.9%) repeatability was also evaluated. This method serves to identify suitable risk-control strategies for occupational hygiene conservation programs.

Healthcare-associated respiratory infections in intensive care unit can be reduced by a hand hygiene program: A multicenter study.

PURPOSE: Healthcare-associated respiratory tract infections are common and markedly affect the quality of life and mortality, as well as increasing costs for health systems due to prolonged hospitalisation. This study aimed to assess the change in both level and trend of respiratory tract infections after a specific hand hygiene program for intensive care unit (ICU) staff. MATERIALS AND METHODS: The infection data collection was carried out from January 2013 to August 2014. The hand hygiene program started in December 2013. To analyse the change in level and trend of infections after the intervention, the Interrupted Time Series method was used. Chi-square test was used to compare the incidence of respiratory tract infections before and after the intervention. RESULTS: A total of 825 patients were hospitalised in three Italian ICUs. The infection level was significantly decreased by 36.3 infections per 1000 device-days after the intervention. The infection trend was also decreased of about 1 infection per month. CONCLUSIONS: After the hand hygiene program a decreased level of infection was found. Continuous performance feedback should be provided to promote a long-term adherence to the guidelines. Organisational and individual risk factors must be individuated and correctly managed to increase quality of practice.

[Accurate compiling of the hospital discharge records according to clinicians' perception: critical issues and perspectives]. / L'accurata compilazione delle schede di dimissione ospedaliera secondo la percezione dei medici: criticità e prospettive.

OBJECTIVES: to explore clinicians vision on hospital discharge records in order to identify useful elements to foster a more accurate compiling. DESIGN: qualitative research with phenomenological approach. SETTING AND PARTICIPANTS: participants were selected through purposive sampling among clinicians of two hospitals located in Sardinia; the sample included 76 people (32 medical directors and 44 doctors in training). MAIN OUTCOME MEASURES: identified codes for themes under investigation: vision of accurate compiling, difficulties, and proposals. RESULTS: collected data highlighted two prevailing visions, respectively focused on the importance of an accurate compiling and on the burden of such activity. The accurate compiling is hindered by the lack of motivation and training, by the limits of the registration system and the information technology, by the distortions induced by the prominent role of the hospital discharge records in the evaluation processes. Training, timely updating of the information system accompanied by a proper cross-cultural validation process, improvement of the computer system, and activation of support services could promote more accurate compiling. CONCLUSIONS: the implementation of services, unconnected with evaluation and control processes, dedicated to training and support in the compiling of the hospital discharge records and in the conduction of related epidemiological studies would facilitate the compliance to the compilation. Such services will make tangible the benefits obtainable from this registration system, increasing skills, motivation, ownership, and facilitating greater accuracy in compiling.

Study of congenital malformations among the progeny of the personnel of an interforce military shooting range in Sardinia, Italy. / Studio sulla comparsa di malformazioni congenite nella progenie del personale del Poligono Interforze del Salto di Quirra (Sardegna).

BACKGROUND: Claims of an excess of congenital malformations in a village nearby the military shooting range of Salto di Quirra (PISQ), Sardinia have attracted media attention. OBJECTIVE: To verify such reports with a retrospective study of the reproductive history of the PISQ personnel. METHODS: In 2011, we interviewed 390 soldiers employed at the PISQ shooting range (86.7% of the total workforce) about their reproductive history, including age at first conception, number of live births and spontaneous abortions, and cases of malformations among their progeny, as well as work history and lifestyle habits. We used a job-exposure matrix to assess occupational exposure to radiofrequency, extremely low frequency electromagnetic fields, solvents and nanoparticles, and whether holding an operative job in the shooting range areas. RESULTS: The rate of congenital malformations among the progeny of the study subjects was close to the expectation (20.2x10^-3 live births, 95% CI 6.3-34.0; 8 cases observed versus 8.6 expected based on the 2005 rate of the Emilia Romagna region), it was lower in the years subsequent to the onset of service at PISQ (11.0x10^-3, 95% CI 0.0-26.1; two cases observed versus 3.9 expected), and it did not vary by residence in the surrounding villages or elsewhere. None of the exposures we assessed was associated with an increase in the rate of congenital malformations. CONCLUSIONS: The limited statistical power of our study allows to exclude that a strong excess of congenital malformations occurred among the progeny of the PISQ shooting range personnel.

The unrecognized occupational relevance of the interaction between engineered nanomaterials and the gastro-intestinal tract: a consensus paper from a multidisciplinary working group.

BACKGROUND: There is a fundamental gap of knowledge on the health effects caused by the interaction of engineered nanomaterials (ENM) with the gastro-intestinal tract (GIT). This is partly due to the incomplete knowledge of the complex physical and chemical transformations that ENM undergo in the GIT, and partly to the widespread belief that GIT health effects of ENM are much less relevant than pulmonary effects. However, recent experimental findings, considering the role of new players in gut physiology (e.g. the microbiota), shed light on several outcomes of the interaction ENM/GIT. Along with this new information, there is growing direct and indirect evidence that not only ingested ENM, but also inhaled ENM may impact on the GIT. This fact, which may have relevant implications in occupational setting, has never been taken into consideration. This review paper summarizes the opinions and findings of a multidisciplinary team of experts, focusing on two main aspects of the issue: 1) ENM interactions within the GIT and their possible consequences, and 2) relevance of gastro-intestinal effects of inhaled ENMs. Under point 1, we analyzed how luminal gut-constituents, including mucus, may influence the adherence of ENM to cell surfaces in a size-dependent manner, and how intestinal permeability may be affected by different physico-chemical characteristics of ENM. Cytotoxic, oxidative, genotoxic and inflammatory effects on different GIT cells, as well as effects on microbiota, are also discussed. Concerning point 2, recent studies highlight the relevance of gastro-intestinal handling of inhaled ENM, showing significant excretion with feces of inhaled ENM and supporting the hypothesis that GIT should be considered an important target of extrapulmonary effects of inhaled ENM. CONCLUSIONS: In spite of recent insights on the relevance of the GIT as a target for toxic effects of nanoparticles, there is still a major gap in knowledge regarding the impact of the direct versus indirect oral exposure. This fact probably applies also to larger particles and dictates careful consideration in workers, who carry the highest risk of exposure to particulate matter.

Surgical and pharmacological reassignment: influence on transsexual cardiovascular risk profile.

BACKGROUND/AIM: To evaluate and stratify early cardiovascular risk of transsexuals who underwent pharmacological and/or surgical gender reassignment. METHODS: Fifty-six transsexuals were divided into two groups: group 1 - underwent gonadectomy (orchiectomy for transwomen and hystero-annessiectomy for transmen); group 2 - hormone replacement therapy alone. All participants underwent carotid artery intima-media thickness (C-IMT) and flow-mediated vasodilation (FMD) of brachial artery evaluations. RESULTS: FMD was lower in patients who had undergone gonadectomy compared with non-surgically treated patients (Group 1: 5.711 vs Group 2: 7.339, P < 0.0001). Mean C-IMT was higher in group 1 than group 2 (group 1: 0.733 vs group 2: 0.582). The duration of hormone therapy correlates positively with mean C-IMT (B = 0.001) and negatively with FMD (%) (B = - 0.007). CONCLUSIONS: Cardiovascular risk, which is expressed in terms of endothelial (FMD) and morphological (C-IMT) dysfunction, increases in subjects undergoing gonadectomy compared with those receiving cross-sex reassignment therapy alone.