Publications by authors named "Andrea Magrini"

110 Publications

Seroprevalence for vaccine-preventable diseases among Italian healthcare workers.

Hum Vaccin Immunother 2020 Oct 5:1-5. Epub 2020 Oct 5.

Department of Systems Medicine, University of Rome Tor Vergata , Rome, Italy.

Healthcare workers (HCWs) have an increased risk to be exposed to infectious diseases compared to the general population. For this reason, according to the National Immunization and Prevention Plan, all HCWs should have demonstrable evidence of immunity to measles, mumps, rubella, varicella and Hepatitis B. Earlier studies have already shown that a large percentage of Italian operators lacked immune protection for one or more of those pathogens. The aim of this study was to evaluate the immunization status for vaccine-preventable diseases of HCWs in a large Italian teaching hospital. We retrospectively evaluated clinical records and serological data of HCWs who followed the occupational health surveillance program between January 1 and December 31 2019. We reviewed the clinical records of 1,017 HCWs: 393 males and 624 females with a median age of 35.69 y (range: 19-67). Protective IgG antibody values were documented in the 88.0%, 75.7%, 90.3%, 87.4% and 85.7% of the HCWs screened, respectively, against measles, mumps, rubella, varicella and Hepatitis B. Age was significantly related to serological protection against measles, mumps and varicella but was not significantly related to protective IgG levels for rubella and HBV. Female gender was significantly related to a higher protection rate against Hepatitis B (87.8 vs 82.4%; < .01) whereas males were significantly more protected against varicella (92-4 vs 84.1%; < .01). Our study shows suboptimal levels of protection among Italian HCWs and a consequent increased risk of infection for them and their patients. Public health policies should be focused on improving preventive strategies, including serological screening and workplace vaccination of nonimmune individuals.
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http://dx.doi.org/10.1080/21645515.2020.1818523DOI Listing
October 2020

Depressive and anxiety symptoms in patients with SARS-CoV2 infection.

J Affect Disord 2021 01 14;278:339-340. Epub 2020 Sep 14.

Neurology Unit, University Hospital "Tor Vergata", Rome, Italy; Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy.

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http://dx.doi.org/10.1016/j.jad.2020.09.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489218PMC
January 2021

Carotid intimal medial thickness in rotating night shift is related to IL1β/IL6 axis.

Nutr Metab Cardiovasc Dis 2020 09 7;30(10):1826-1832. Epub 2020 Jun 7.

Department of Systems Medicine, University of Rome Tor Vergata, Italy.

Background And Aims: Sleep disturbances may promote glucose abnormalities and inflammatory burden among shift workers. Therefore, precocious subclinical atherosclerotic process might develop in healthy shift workers even without known metabolic and cardiovascular risk factors.

Methods And Results: We measured anthropometric parameters, glucose, lipids, inflammation and common carotid Intimal Medial Thickness (cIMT) in rotating-night shift workers (r-NSW, n = 88, age = 40.3 ± 7.8 y) in comparison with former-night shift workers (f-NSW, n = 35, age = 44.2 ± 6.4 y) and with day-only workers (DW, n = 64, age = 44.1 ± 8.9 y). R-NSW and f-NSW showed significantly higher cIMT and high sensitivity C-Reactive Protein (hs-CRP) respect to DW (p = 0.043 and p = 0.025, respectively). IL-1β levels were higher in r-NSW than in DW and f-NSW (p = 0.043) and significantly correlated with IL6 (r = 0.365, p < 0.001). In addition, r-NSW and f-NSW had higher HbA1c levels in comparison with DW (p = 0.047). Carotid-IMT was significantly related to night shift work (p = 0.023), with age (p < 0.001), with HOMA IR (p = 0.009), with insulin (p = 0.006) with HbA1c (p = 0.002), with LDL cholesterol (p < 0.001), with diastolic BP (p < 0.001), with WBC (p = 0.002) and with IL6 (p = 0.004). After performing a multivariate analysis night shift work remained statistically related to cIMT (B = 2.633, 95%CI = 0.489-4.776, p = 0.016).

Conclusions: Our result described a possible link bridging night shift work, inflammation and carotid Intimal Medial Thickness. Future studies are warranted to understand if carotid atherosclerosis process should be mainly driven by the IL1β/IL6 citokine axis connected to sleep disturbances.
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http://dx.doi.org/10.1016/j.numecd.2020.05.028DOI Listing
September 2020

Relationship between the night shift work and thyroid disorders: A systematic review and meta-analysis.

Endocr Regul 2020 Jan;54(1):64-70

Italian study group on the metabolic and immunological effects of night shift workDepartment of Occupational Medicine, University of Rome Tor Vergata, Rome, Italy.

Objectives: The night shift workers were reported to have health consequences, ranging from mild, as cluster headache, to severe, as heart attacks and hormonal irregularities. This study is aimed to perform a systematic review and meta-analyze of the association between the night shift work and the thyroid disorders.

Methods: We comprehensively searched eight databases, including PubMed and Google Scholar for the relevant articles. This systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement.

Results: We finally included six papers involving 4074 participants. Four papers were eligible for meta-analysis involving 1864 night shift workers and 2017 day shift workers. We against found that thyroid stimulating hormone (TSH) is significantly higher in the night shift group compared to the day shift group.

Conclusions: The higher TSH among the night shift workers is attributed to disruption of the circadian rhythm and sleep/wake cycle, with subsequent eating disorders. We proposed that more attention should be paid to the working pattern and the related health consequences.
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http://dx.doi.org/10.2478/enr-2020-0008DOI Listing
January 2020

Subjective neurological symptoms frequently occur in patients with SARS-CoV2 infection.

Brain Behav Immun 2020 08 19;88:11-16. Epub 2020 May 19.

Neurology Unit, University Hospital "Tor Vergata", Rome, Italy; Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy; IRCCS Santa Lucia Foundation, Rome, Italy.

Objective: Coronavirus disease 2019 (COVID-19) represents a novel pneumonia leading to severe acute respiratory syndrome (SARS). Recent studies documented that SARS-Coronavirus2 (SARS-CoV2), responsible for COVID-19, can affect the nervous system. The aim of the present observational study was to prospectively assess subjective neurological symptoms (sNS) in patients with SARS-CoV2 infection.

Methods: We included patients hospitalized at the University Hospital of Rome "Tor Vergata", medical center dedicated to the treatment of patients with COVID-19 diagnosis, who underwent an anamnestic interview about sNS consisting of 13 items, each related to a specific symptom, requiring a dichotomized answer.

Results: We included 103 patients with SARS-CoV2 infection. Ninety-four patients (91.3%) reported at least one sNS. Sleep impairment was the most frequent symptom, followed by dysgeusia, headache, hyposmia, and depression. Women more frequently complained hyposmia, dysgeusia, dizziness, numbeness/paresthesias, daytime sleepiness, and muscle ache. Moreover, muscle ache and daytime sleepiness were more frequent in the first 2 days after admission. Conversely, sleep impairment was more frequent in patients with more than 7 days of hospitalization. In these patients we also documented higher white blood cells and lower C-reactive protein levels. These laboratory findings correlated with the occurrence of hyposmia, dysgeusia, headache, daytime sleepiness, and depression.

Conclusions: Patients with SARS-CoV2 infection frequently present with sNS. These symptoms are present from the early phases of the disease. The possibly intrinsic neurotropic properties of SARS-CoV2 may justify the very high frequency of sNS. Further studies targeted at investigating the consequences of SARS-CoV2 infection on the CNS should be planned.
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http://dx.doi.org/10.1016/j.bbi.2020.05.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235586PMC
August 2020

Prevalence and Risk Factors for Latent Tuberculosis Infection among Healthcare Workers in a Low Incidence Country.

Open Respir Med J 2019 30;13:1-4. Epub 2019 Apr 30.

Occupational Medicine Department, University of Rome "Tor Vergata", Viale Oxford 81, 00133 Roma, Italy.

Background: Tuberculosis prevention is a major goal in the hospital setting. Because of the possible progression or reactivation of latent disease, the screening of healthcare workers is an important issue in the TB control program. The aim of the study was to assess the prevalence of LTBI (latent tuberculosis infection) and to evaluate the main risk factors related to this condition in a teaching hospital in Italy.

Methods: We reviewed the data of a tuberculosis screening conducted on 3622 healthcare professionals in a teaching hospital in Rome. All subjects were evaluated by QuantiFERON test which if positive, was followed by appropriate clinical and diagnostic procedures.

Results: Latent Tuberculosis Infection LTBI condition was detected in 2.1% of the cases, most commonly in men. Male gender, higher age class, country of birth and nurse job were statistically related with the positivity to QuantiFERON test.

Conclusion: LTBI was relatively uncommon in our population, however, given the potential risk of reactivation and progression to overt disease, the screening of healthcare workers and students is recommended in the hospital of low-incidence countries.
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http://dx.doi.org/10.2174/1874306401913010001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918539PMC
April 2019

Night Shift Working Is Associated With an Increased Risk of Thyroid Nodules.

J Occup Environ Med 2020 01;62(1):1-3

Department of Systems Medicine (Dr Rizza, Dr Federici); Department of Biomedicine and Prevention (Dr Neri, Dr Capanna, Dr Grecuccio, Dr Pietroiusti, Dr Magrini, Dr Coppeta), University of Rome Tor Vergata, Rome, Italy.

Objectives: To study thyroid alterations in health care workers according to their working status.

Methods: We performed a retrospective study including 299 hospital employers who underwent in 2016 a periodic health surveillance checks in the Service of Occupational Medicine. According to the working status (rotating night-shift working [no. 160] vs day-working [no. 139]), we divided participant's clinical, anthropometric, and thyroid echographic characteristics.

Results: Respect to day workers, rotating night-shift workers were slightly older and more frequently male whereas had similar thyroid stimulating hormone, Ft3, Ft4 levels, and autoimmunity (anti-TPO levels more than 30). Univariate and multivariate regression analysis revealed that rotating night shift work is associated to a significantly increased number of thyroid nodules.

Conclusions: This retrospective report suggests that the alteration in the molecular clocks typical of rotating night-shift workers harbors a higher risk of thyroid nodule development compared with diurnal workers. This novel result deserves replication in larger cohorts since thyroid nodules not rarely can represent thyroid cancers.
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http://dx.doi.org/10.1097/JOM.0000000000001711DOI Listing
January 2020

Cost-effectiveness of workplace vaccination against measles.

Hum Vaccin Immunother 2019 24;15(12):2847-2850. Epub 2019 Jul 24.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Measles is one of the most contagious infectious diseases. Measles vaccine, which has been introduced in Italy in 1979, is highly effective in preventing the disease (two-dose vaccine effectiveness is 99%). In 2017, Italy was the second country of EU for number of cases of measles. A study conducted in the same year showed that 22.3% of measles infection happened in hospital settings and 6.6% of cases occurred in HCWs. This risk group showed low rates of adhesion to the vaccination campaign. For this reason, we hypothesized that workplace vaccination could lead to better vaccination rates in HCWs. Moreover, we focused the vaccination campaign on a specific target group composed of HCWs not serologically immune and previously not vaccinated. We analyzed the clinical records of measles-specific IgG antibodies of 2,940 HCWs, that underwent occupational health surveillance between 1 January 2017 and 31 December 2017. 15.3% (450) was seronegative for measles, especially in the age group under 35 years. We compared the costs related to strategies with and without serological screening. Our study confirmed that immunization strategy with pre-vaccination screening was cost-effective compared to the vaccination without screening. In our sample, in fact, administration of two dose vaccine only susceptible HCWs determine a saving of 146,262 €. The vaccination of HCWs remains a topical issue in preventing the transmission of infectious disease in the hospital setting. Due to the cost-effectiveness evaluation, we recommend extending the pre-vaccination screening to identify the real susceptible workers.
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http://dx.doi.org/10.1080/21645515.2019.1616505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930095PMC
May 2020

Persistence of Immunity for Hepatitis B Virus among Heathcare Workers and Italian Medical Students 20 Years after Vaccination.

Int J Environ Res Public Health 2019 04 29;16(9). Epub 2019 Apr 29.

Department of Occupational Medicine, University of Rome Tor Vergata, Viale Oxford 81, 00188 Roma, Italy.

Immunization of healthcare workers (HCWs) and medical students for the hepatitis B virus (HBV) is a crucial part of the hospital infection control programs. The aim of our study was to evaluate the persistence of anti-HBV specific antibodies in HCWs vaccinated during infancy or adolescence. Medical records of 734 consecutive subjects born after 1980 (481 females, 65.5% and 253 males, 34.5%) who underwent serological testing for anti-hepatitis B surface antibodies (anti-HBs) were evaluated. A non-protective titer (<10 mUI) was found in 88/734 (12.0%) subjects; 84 (47.8%) of them received a booster dose of anti-hepatitis B vaccine and the anti-HBs titer of 58 subjects was measured 1 month after administration. A protective titer (anti-HBs >10 mIU/mL) was observed in almost 90% of subjects receiving the booster dose. A substantial percentage of HCWs had a non-protective anti-HBs titer at the time of the first employment, especially those vaccinated at birth age. However, the response to the booster dose showed that in these subjects, an anti-HBs titer <10 mIU/mL was due to the physiological decline of antibodies over the years. Therefore, primary immunization in childhood is highly effective and provides lasting immunity against HBV infection.
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http://dx.doi.org/10.3390/ijerph16091515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539932PMC
April 2019

[Influenza prevention in health-care workers: enhancement of the influenza vaccination campaign at Policlinico Tor Vergata in Rome (Italy) during the 2017/2018 epidemic season].

Ig Sanita Pubbl 2018 Nov-Dec;74(6):589-600

Dipartimento di Biomedicina e Prevenzione, Università degli Studi di Roma "Tor Vergata", Roma, Italia.

Given the very low influenza vaccination coverage averaging 4% among health-care workers at Policlinico Tor Vergata during the previous epidemic seasons, it was decided to implement a series of interventions to promote influenza vaccination compliance in the current (2017/2018) season. The total number of vaccinated health-care workers at the end of the current season was 364, resulting in a vaccination coverage of approximately 12%. The increase took place in all professional groups, with a coverage of 25% among permanent MDs, 9% among Medical Residents, 3% among nurses and 8% among technicians. The influenza vaccination coverage of 12%, although very low compared to the minimum target of 75%, is broadly in line with the values reported by other hospitals in Italy.
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October 2019

Quantitative atomic force microscopy provides new insight into matrix vesicle mineralization.

Arch Biochem Biophys 2019 05 16;667:14-21. Epub 2019 Apr 16.

Nanoscience & Nanotechnology & Innovative Instrumentation (NAST) Centre, University of Rome Tor Vergata, Rome, Italy; Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA. Electronic address:

Matrix vesicles (MVs) are a class of extracellular vesicles that initiate mineralization in cartilage, bone, and other vertebrate tissues by accumulating calcium ions (Ca) and inorganic phosphate (P) within their lumen and forming a nucleation core (NC). After further sequestration of Ca and P, the NC transforms into crystalline complexes. Direct evidence of the existence of the NC and its maturation have been provided solely by analyses of dried samples. We isolated MVs from chicken embryo cartilage and used atomic force microscopy peak force quantitative nanomechanical property mapping (AFM-PFQNM) to measure the nanomechanical and morphological properties of individual MVs under both mineralizing (+Ca) and non-mineralizing (-Ca) fluid conditions. The elastic modulus of MVs significantly increased by 4-fold after incubation in mineralization buffer. From AFM mapping data, we inferred the morphological changes of MVs as mineralization progresses: prior to mineralization, a punctate feature, the NC, is present within MVs and this feature grows and stiffens during mineralization until it occupies most of the MV lumen. Dynamic light scattering showed a significant increase in hydrodynamic diameter and no change in the zeta potential of hydrated MVs after incubation with Ca. This validates that crystalline complexes, which are strongly negative relative to MVs, were forming within the lumen of MVs. These data were substantiated by transmission electron microscopy energy dispersive X-ray and Fourier transform infrared spectroscopic analyses of dried MVs, which provide evidence that the complexes increased in size, crystallinity, and Ca/P ratio within MVs during the mineralization process.
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http://dx.doi.org/10.1016/j.abb.2019.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104627PMC
May 2019

Severe facial reaction to thiurams in surgeons

Med Pr 2019 Mar;70(1):121-124

University of Rome “Tor Vergata,” Rome, Italy (Department of Occupational Medicine)

Contact dermatitis is a major problem in the healthcare environment and in other sectors. Healthcare professionals may be exposed to a large number of chemical agents, including the accelerators for rubber vulcanization process. The prevalence of allergic contact dermatitis among operators in the sector ranges 13–30%. This paper describes the case of a 46-year-old male cardiac surgeon affected by a severe skin reaction localized on the face in the absence of hand dermatitis, presumably resulting from the use of a surgical patch applied to the face. Patch tests were performed and the result was negative for latex and positive (+++) for thiuram mix. A thiuram-free tape was prescribed and the operator’s dermatitis improved significantly. Thus, it would be very important to pay attention to skin disorders in health workers and thiuram as an occupational allergen. Med Pr. 2019;70(1):121–4
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http://dx.doi.org/10.13075/mp.5893.00738DOI Listing
March 2019

Pre-vaccination IgG screening for mumps is the most cost-effectiveness immunization strategy among Health Care Workers.

Hum Vaccin Immunother 2019 27;15(5):1135-1138. Epub 2019 Mar 27.

a Department of Biomedicine and Prevention , University of Rome Tor Vergata , Rome , Italy.

Health Care Workers (HCWs) have an increased risk of contracting contagious disease, including mumps. In January 2017 the Italian National Vaccine Prevention Plan 2017-2019, recommended the administration of a dose of MMR vaccine (Measles-Mumps-Rubella) to the Health Care Workers (HCWs) that, working in a risky environment, did not carry out the complete vaccination cycle of MMR or that are seronegative for at least one of the three vaccine viruses. In October of the same year, the Advisory Committee on Immunization Practices (ACIP) recommended a third dose of a vaccine containing Mumps Virus for people previously vaccinated with 2 doses, belonging to a group or to a population at increased risk of acquire mumps in the event of an epidemic. We analyzed the clinical records and values of mumps-specific IgG antibodies of 3032 HCWs (mean age 32.80 ± 10.75 years), that underwent occupational health surveillance between January 1st 2017 and March 31th 2018. The HCWs were also screened for measles, rubella, mumps using serological methods. 13% (405) was seronegative for mumps, especially among HCWs between 18 and 36 years. We calculated the cost-effectiveness of two-doses and three-doses MMR vaccination. The cost of vaccination without screening was significantly more expensive (cost difference: 99 712 € and 184 996 €) both in case of two-dose and three-dose MMR vaccination respectively. Our study suggests that, in HCWs, the assessment of the mumps antibody titer before vaccination may be a useful complement to vaccination itself, because it is more accurate and cost-effective than direct immunization of unvaccinated subjects.
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http://dx.doi.org/10.1080/21645515.2018.1564442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605818PMC
February 2020

Risk of radiation-induced lens opacities among surgeons and interventional medical staff.

Radiol Phys Technol 2019 Mar 26;12(1):26-29. Epub 2018 Nov 26.

Department of Occupational Medicine, University of Rome "Tor Vergata", Viale Oxford 81, 00133, Rome, Italy.

The main effect of ionizing radiation on the eyes is the onset of posterior cortical and subcapsular cataracts. Recent studies have raised questions about the mechanism of ocular damage and the threshold dose for the onset of such effects. Currently, operators may be exposed to ionizing radiation during surgical procedures. It has been estimated that urologists can be exposed to an annual dose close to or above 20 mSv/year. The aim of our study was to evaluate the frequency of cataracts in a group of professional radiological operators to verify their possible association with the radiation dose to the crystalline lens and the tasks performed. The records of 73 health workers exposed to ionizing radiation were reviewed. The average annual dose to the crystalline lens, the number of years of exposure, and the presence of radiation-compatible opacities were assessed for all operators. Lenticular opacities were observed in 16.4% of subjects. The presence of alterations was associated with exposure doses below 10 mSv and > 10 years' experience in fluoroscopically guided procedures. Based on our results, protection of the crystalline lens against exposure to ionizing radiation by means of goggles is recommended. In addition, examination of the lens via slit lamp examination is recommended for all operators involved in interventional procedures with the current levels of radiation exposure.
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http://dx.doi.org/10.1007/s12194-018-0487-9DOI Listing
March 2019

Cancer Patients in the Emergency Department: A "Nightmare" that Might Become a Virtuous Clinical Pathway.

Anticancer Res 2018 Nov;38(11):6387-6391

Medical Oncology Unit, Tor Vergata University Hospital, Rome, Italy.

Background/aim: Emergency departments (EDs) often face overcrowding issues while simultaneously confronting with the increasing clinical needs of patients, such as cancer patients, with both acute and chronic illnesses. In order to guarantee a prompt and specialized treatment of ED-attending cancer patients and reduce inappropriate inpatient admissions, a dedicated ED cancer pathway (EDCP) consisting of ED-bound Medical Oncology (MO) resident doctor and direct admission for candidate patients exclusively to the MO division was established at the Tor Vergata University Hospital in April 2015.

Patients And Methods: Consecutive cancer patients attending the ED in two reference three-month periods were enrolled: pre-EDCP period, from 1st October 2014 to 31st December 2014, and post-EDCP period, from 1st October 2014 to 31st December 2015. Inpatient admission rate, mortality rate and both ED and inpatient length of stay were compared between the two analyzed periods, pre- and post-EDCP.

Results: In the pre- and post-EDCP periods 127 and 123 cancer patients, respectively, were included. Most of the analyzed indicators were improved by EDCP implementation: Inpatient admission rate from 70% to 41% (p<0.0001), ED mortality rate from 10-4% (p=0.04), mean ED length of stay, from 58 to 42 h (p=0.03), mean inpatient length of stay, from 15.5 to 6.5 days (p<0.0001), in the pre- and post-EDCp period, respectively.

Conclusion: EDCP implementation led to a significant improvement of health care delivery to cancer patients attending the Emergency Department.
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http://dx.doi.org/10.21873/anticanres.12998DOI Listing
November 2018

Are Shiftwork and Indoor Work Related to D3 Vitamin Deficiency? A Systematic Review of Current Evidences.

J Environ Public Health 2018 10;2018:8468742. Epub 2018 Sep 10.

Department of Occupational Medicine, University of Rome "Tor Vergata", Rome, Italy.

Background: Reported cases of vitamin D3 deficiency have been increasing in incidence worldwide. Although there is a lack of consensus relating to optimal levels of vitamin D, generally serum 25-(OH)D concentrations lower than 50 nmol/L (20 ng/mL) are at least considered to be detrimental to bone health.

Aim: Aim of this systematic review is to investigate if occupations, and specifically shiftworking and indoor working, may be considered as possible contributors to the increased incidence of vitamin D3 deficiency in industrialized nations.

Materials And Methods: Systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement using PubMed, Scopus, and ISI Web of Knowledge databases.

Results: Overall 90 papers were found, 23 articles through PubMed, 30 through Scopus, and 37 through ISI Web of Knowledge. Successively, 46 duplicates and 34 articles that did not respect the inclusion criteria were excluded. Finally 10 articles were selected: 9 cross-sectional studies and 1 systematic review. Results of the studies included revealed that certain occupations are either suffering from, or have a predilection to suffer from, a deficiency of this vitamin. Shiftworkers and indoor workers are consistently reported as being the occupational group most likely to suffer from a deficiency of vitamin D3. It would appear prudent to investigate the potential of providing nutritional education to workers in addition to including preventative measures in the workplace.
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http://dx.doi.org/10.1155/2018/8468742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151365PMC
January 2019

Fluorinated Oligoethylenimine Nanoassemblies for Efficient siRNA-Mediated Gene Silencing in Serum-Containing Media by Effective Endosomal Escape.

Nano Lett 2018 10 27;18(10):6301-6311. Epub 2018 Sep 27.

Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology of China , Beijing 100190 , P. R. China.

Efficient small interfering RNA (siRNA) delivery in the presence of serum is of crucial importance for effective gene therapy. Fluorinated vectors are considered to be attractive candidates for siRNA-mediated gene therapy because of their delivery efficacy in serum-containing media. However, the mechanisms driving the superior gene transfection behavior of fluorinated vectors are still not well-understood, and comprehensive investigations are warranted. Herein, we fabricated a library of perfluorooctanoyl fluoride-fluorinated (PFF-fluorinated) oligoethylenimines (f OEIs, x is the PFF:OEI feeding ratio), which can readily form nanoassemblies (f OEI NAs) capable of efficient siRNA delivery in cells cultured in medium both devoid of and supplemented with fetal bovine serum (FBS). The gene silencing test in serum-containing medium revealed that the fOEI/siRNA NAs achieved a luciferase silencing of ∼88.4% in Luc-HeLa cells cultured in FBS-containing medium, which was almost 2-fold greater than the silencing efficacy of siRNA delivered by the commercially available vector Lipo 2000 (∼48.8%). High levels of apolipoprotein B silencing were also achieved by fOEI/siRNA NAs in vivo. For an assessment of the underlying mechanisms of the efficacy of gene silencing of fluorinated vectors, two alkylated OEIs, aOEI-C8 and aOEI-C12, were fabricated as controls with similar molecular structure and hydrophobicity to that of fOEI, respectively. In vitro investigations showed that the superior gene delivery exhibited by fOEI NAs derived from the potent endosomal disruption capability of fluorinated vectors in the presence of serum, which was essentially attributed to the serum protein adsorption resistance of the fOEI NAs. Therefore, this work provides an innovative approach to siRNA delivery as well as insights into fluorine-associated serum resistance.
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http://dx.doi.org/10.1021/acs.nanolett.8b02553DOI Listing
October 2018

Significant relationship of combined ACP/PTPN22 genotype variants with the growth of uterine leiomyomas.

Taiwan J Obstet Gynecol 2018 Aug;57(4):567-569

Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133, Rome, Italy.

Objective: To analyze the interaction between ACP and PTPN22 concerning their effects on the growth of the tumor. In previous paper we have shown (i) that ACP*B/*B genotype of ACP is negatively associated with the growth of leiomyomas and (ii) that there is a negative association of *C/*C genotype of PTPN22 with tumor growth.

Materials And Methods: Two hundred and three White women from the population of Rome with symptomatic leiomyomas were recruited in the University of Rome Tor Vergata. All subjects gave consent for the participation in the study that was approved by the Council of Department. ACP and PTPN22 genotypes were determined by DNA analysis.

Results: The proportion of women with small leiomyomas decreases with the decrease of the number of protective factors and it is 37.2% in women carrying the joint genotype ACP*B/*B-PTPN22 *C/*C (two protective factors) and 0% in women carrying no protective factors. Three way contingency table analysis by a log linear model has shown no evidence of epistatic interaction between the two genetic systems but a highly significant cooperative effect on the dimension of leiomyomas. There is a highly significant negative correlation between the number of protective factors and the dimension of leiomyomas with a minimum (cm 4.74) in women carrying the joint genotype ACP*B/B-PTPN22 *C/*C and a maximum (cm 7.25) in women carrying no protective factors.

Conclusion: The present study suggests a cooperative interaction between ACP and PTPN22 concerning their effects on the growth of uterine leiomyomas. The determination of the genotype of the two systems may help to evaluate the risk of clinical manifestations of this common benign tumor.
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http://dx.doi.org/10.1016/j.tjog.2018.06.017DOI Listing
August 2018

Relevance to investigate different stages of pregnancy to highlight toxic effects of nanoparticles: The example of silica.

Toxicol Appl Pharmacol 2018 03 31;342:60-68. Epub 2018 Jan 31.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, Rome 00133, Italy. Electronic address:

Amorphous silica nanoparticles (SiONPs) have been recognized as safe nanomaterial, hence their use in biomedical applications has been explored. Data, however, suggest potential toxicity of SiO NPs in pregnant individuals. However, no studies relating nanoparticle biokinetic/toxicity to the different gestational stages are currently available. In this respect, we have investigated the possible embryotoxic effects of three-size and two-surface functionalization SiONPs in mice. After intravenous administration of different concentrations at different stages of pregnancy, clinical and histopathological evaluations, performed close to parturition, did not show signs of maternal toxicity, nor effects on placental/fetal development, except for amino-functionalized 25 nm NPs. Biodistribution was studied by ICP-AES 24 h after administration, and demonstrates that all particles distributed to placenta and conceptuses/fetuses, although size, surface charge and gestational stage influenced biodistribution. Our data suggest the need of comprehensive toxicological studies, covering the entire gestation to reliably assess the safety of nanoparticle exposure during pregnancy.
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http://dx.doi.org/10.1016/j.taap.2018.01.026DOI Listing
March 2018

Nitric Oxide Dependent Degradation of Polyethylene Glycol-Modified Single-Walled Carbon Nanotubes: Implications for Intra-Articular Delivery.

Adv Healthc Mater 2018 03 15;7(6):e1700916. Epub 2018 Jan 15.

Nanosafety & Nanomedicine Laboratory-NNL, Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, 171 77, Stockholm, Sweden.

Polyethylene glycol (PEG)-modified carbon nanotubes have been successfully employed for intra-articular delivery in mice without systemic or local toxicity. However, the fate of the delivery system itself remains to be understood. In this study 2 kDa PEG-modified single-walled carbon nanotubes (PNTs) are synthesized, and trafficking and degradation following intra-articular injection into the knee-joint of healthy mice are studied. Using confocal Raman microspectroscopy, PNTs can be imaged in the knee-joint and are found to either egress from the synovial cavity or undergo biodegradation over a period of 3 weeks. Raman analysis discloses that PNTs are oxidatively degraded mainly in the chondrocyte-rich cartilage and meniscus regions while PNTs can also be detected in the synovial membrane regions, where macrophages can be found. Furthermore, using murine chondrocyte (ATDC-5) and macrophage (RAW264.7) cell lines, biodegradation of PNTs in activated, nitric oxide (NO)-producing chondrocytes, which is blocked upon pharmacological inhibition of inducible nitric oxide synthase (iNOS), can be shown. Biodegradation of PNTs in macrophages is also noted, but after a longer period of incubation. Finally, cell-free degradation of PNTs upon incubation with the peroxynitrite-generating compound, SIN-1 is demonstrated. The present study paves the way for the use of PNTs as delivery systems in the treatment of diseases of the joint.
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http://dx.doi.org/10.1002/adhm.201700916DOI Listing
March 2018

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

Part Fibre Toxicol 2017 11 25;14(1):47. Epub 2017 Nov 25.

Department of Public Health, University of Naples Federico II, Naples, Italy.

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.
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http://dx.doi.org/10.1186/s12989-017-0226-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702111PMC
November 2017

Silver nanoparticles inhaled during pregnancy reach and affect the placenta and the foetus.

Nanotoxicology 2017 Jun 7;11(5):687-698. Epub 2017 Jul 7.

a Department of Biomedicine and Prevention , University of Rome Tor Vergata , Rome , Italy.

Recently, interest for the potential impact of consumer-relevant engineered nanoparticles on pregnancy has dramatically increased. This study investigates whether inhaled silver nanoparticles (AgNPs) reach and cross mouse placental barrier and induce adverse effects. Apart from their relevance for the growing use in consumer products and biomedical applications, AgNPs are selected since they can be unequivocally identified in tissues. Pregnant mouse females are exposed during the first 15 days of gestation by nose-only inhalation to a freshly produced aerosol of 18-20 nm AgNPs for either 1 or 4 h, at a particle number concentration of 3.80 × 107 part./cm and at a mass concentration of 640 μg/m³. AgNPs are identified and quantitated in maternal tissues, placentas and foetuses by transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy and single-particle inductively coupled plasma mass spectrometry. Inhalation of AgNPs results in increased number of resorbed foetuses associated with reduced oestrogen plasma levels, in the 4 h/day exposed mothers. Increased expression of pregnancy-relevant inflammatory cytokines is also detected in the placentas of both groups. These results prove that NPs are able to reach and cross the mouse placenta and suggest that precaution should be taken with respect to acute exposure to nanoparticles during pregnancy.
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http://dx.doi.org/10.1080/17435390.2017.1343875DOI Listing
June 2017

Exposure to ultrafine particles in different transport modes in the city of Rome.

Environ Pollut 2017 Sep 22;228:201-210. Epub 2017 May 22.

Department of Biomedicine and Prevention, University of Rome "Tor Vergata" - Via Montpellier 1, 00133 Rome, Italy.

There is evidence of adverse health impacts from human exposure to particulate air pollution, including increased rates of respiratory and cardiovascular illness, hospitalizations, and pre-mature mortality. Most recent hypotheses assign an important role to ultrafine particles (UFP) (<0.1 μm) and to associated transition metals (in particular Fe). In a large city like Rome, where many active people spend more than one hour per day in private or public transportation, it may be important to evaluate the level of exposure to harmful pollutants which occurs during urban travelling. In this context, the aim of this work was to examine the relative contribution of different transport modes to total daily exposure. We performed experimental measurements during both morning and evening traffic peak hours throughout the winter season (December 2013-March 2014), for a total of 98 trips. Our results suggest that the lowest UFP exposures are experienced by underground train commuters, with an average number concentration of 14 134 cm, and are largely a reflection of the routes being at greater distance from vehicular traffic. Motorcyclists experienced significantly higher average concentrations (73 168 cm) than all other exposure classes, and this is most likely a result of the presence of high-concentration and short-duration peaks which do not occur when the same routes are traveled by car. UFP concentrations in subway train environments were found to be comparable to urban background levels. Still, in underground trains we found the highest values of PM mass concentration with a maximum value of 422 μg/m. PM concentration in trains was found to be four and two times higher than what was measured in car and motorbike trips, respectively. Transport mode contribution to total integrated UFP daily exposure was found to be 16.3%-20.9% while travelling by car, 28.7% for motorbike trips, and 8.7% for subway trips. Due to lower exposure times, commuting by car and motorbike is comparable to other daily activities in terms of exposure. Our data can provide relevant information for transport decision-making and increase environmental awareness in the hope that the information about inhaled pollutants can translate into a more rational approach to urban travelling.
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http://dx.doi.org/10.1016/j.envpol.2017.05.032DOI Listing
September 2017

Delphi consensus on the monitoring tools of main individual risk factors for chronic diseases by the company doctor.

Med Lav 2017 02 15;108(1):24-32. Epub 2017 Feb 15.

Agenzia di Tutela della Salute di Bergamo.

Background: Data on individual risk factors for chronic diseases (smoking, physical activity, body mass) are collected by company physicians in heterogeneous ways. This makes comparisons, researches and evaluations difficult.

Objectives: The aim of the study was to find a consensus on evaluation tools for chronic diseases risk factors and for health promotion programs in workplaces that could be performed by company physicians during their clinical activity.

Methods: A first set of tools, proposed by a working group of occupational physicians in Bergamo, was submitted through the Delphi technique to a national expert panel of 22 persons including recognized national experts in specific fields and occupational physicians skilled in health promotion.

Results: In three Delphi rounds, the panel selected a set of tools to monitor the main individual risk factors for chronic diseases (smoking, alcohol, physical activity, nutrition, stress and mental health) as well as general data related to the worker and his job.

Conclusions: The use of these specific tools, collected in a homogeneous format, should be recommended to all Italian company physicians, in particular those who work in WHP-programs, in order to allow analysis, comparison and evaluation of health promotion programs effectiveness at a national level.
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http://dx.doi.org/10.23749/mdl.v108i1.5476DOI Listing
February 2017

Correlation between birth weight and placental weight in healthy and diabetic puerperae.

Taiwan J Obstet Gynecol 2016 Oct;55(5):697-699

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Objective: The birth weight/placental weight ratio has an important predictive value for perinatal mortality and morbidity and for cardiovascular diseases in adult life. In this study, we compared the birth weight/placental weight (BW/PW) ratio and the correlation between the two parameters in diabetic women with that observed in healthy women.

Materials And Methods: A total of 347 consecutive newborn infants from healthy puerperae, 164 newborns from puerperae with gestational diabetes, 148 newborns from puerperae with preexisting type 1 diabetes, and 40 newborns from puerperae with preexisting type 2 diabetes have been studied from the White population of Rome. The research project was approved by the Institutional Review Board and informed written consent was obtained from the participating mothers.

Results: The BW/PW ratio is higher, and the correlation between the two parameters is lower in all classes of diabetes as compared to healthy puerperae. A remarkably low correlation is observed in preexisting diabetes pointing to a dissociation of fetal growth from placental growth.

Discussion: In diabetic pregnancy the BW/PW ratio is higher, and the correlation between birth weight and placental weight is lower in all classes of diabetic as compared to healthy puerperae pointing to a relative dissociation between the two parameters. It has been suggested that the increase of glycemic levels in diabetic pregnancy predisposes to important diseases in adult life. The dissociation of BW from PW in infants of diabetic pregnancy could be a predictor of the risk for such diseases of adult life.
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http://dx.doi.org/10.1016/j.tjog.2015.03.013DOI Listing
October 2016

[Risk of tuberculosis in healthcare workers: risk assessment and medical surveillance].

Ig Sanita Pubbl 2016 Mar-Apr;72(2):137-43

Dipartimento di Biomedicina e Prevenzione, Università degli Studi di Roma Tor Vergata, Italia.

Tuberculosis screening is recommended for all health care workers. We evaluated the prevalence of latent tuberculosis infection among 939 hospital workers of Tor Vergata University teaching hospital in Rome, Italy, in the period 2007-2013, by using the QuantiFERON Gold In-Tube (QFT) test. The mean age of subjects tested was 31 years. The prevalence of positive subjects (cut-off 0.35 UI/ml) was 5.5% (46/939) and the mean age of those who tested positive was 39 years. The low rate of positivity may be partly related to the higher reliability of QFT in comparison to tuberculin skin testing.
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February 2017

Multi-walled carbon nanotubes directly induce epithelial-mesenchymal transition in human bronchial epithelial cells via the TGF-β-mediated Akt/GSK-3β/SNAIL-1 signalling pathway.

Part Fibre Toxicol 2016 06 1;13(1):27. Epub 2016 Jun 1.

Department of Oncology, University of Turin, via Santena 5/bis, 10126, Turin, Italy.

Background: Multi-walled carbon nanotubes (MWCNT) are currently under intense toxicological investigation due to concern on their potential health effects. Current in vitro and in vivo data indicate that MWCNT exposure is strongly associated with lung toxicity (inflammation, fibrosis, granuloma, cancer and airway injury) and their effects might be comparable to asbestos-induced carcinogenesis. Although fibrosis is a multi-origin disease, epithelial-mesenchymal transition (EMT) is recently recognized as an important pathway in cell transformation. It is known that MWCNT exposure induces EMT through the activation of the TGF-β/Smad signalling pathway thus promoting pulmonary fibrosis, but the molecular mechanisms involved are not fully understood. In the present work we propose a new mechanism involving a TGF-β-mediated signalling pathway.

Methods: Human bronchial epithelial cells were incubated with two different MWCNT samples at various concentrations for up to 96 h and several markers of EMT were investigated. Quantitative real time PCR, western blot, immunofluorescent staining and gelatin zymographies were performed to detect the marker protein alterations. ELISA was performed to evaluate TGF-β production. Experiments with neutralizing anti-TGF-β antibody, specific inhibitors of GSK-3β and Akt and siRNA were carried out in order to confirm their involvement in MWCNT-induced EMT. In vivo experiments of pharyngeal aspiration in C57BL/6 mice were also performed. Data were analyzed by a one-way ANOVA with Tukey's post-hoc test.

Results: Fully characterized MWCNT (mean length < 5 μm) are able to induce EMT in an in vitro human model (BEAS-2B cells) after long-term incubation at sub-cytotoxic concentrations. MWCNT stimulate TGF-β secretion, Akt activation and GSK-3β inhibition, which induces nuclear accumulation of SNAIL-1 and its transcriptional activity, thus contributing to switch on the EMT program. Moreover, a significant increment of nuclear β-catenin - due to E-cadherin repression and following translocation to nucleus - likely reinforces signalling for EMT promotion. In vivo results supported the occurrence of pulmonary fibrosis following MWCNT exposure.

Conclusions: We demonstrate a new molecular mechanism of MWCNT-mediated EMT, which is Smad-independent and involves TGF-β and its intracellular effectors Akt/GSK-3β that activate the SNAIL-1 signalling pathway. This finding suggests potential novel targets in the development of therapeutic and preventive approaches.
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http://dx.doi.org/10.1186/s12989-016-0138-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890337PMC
June 2016

Allergy and Uterine Leiomyomas: Cooperative Interaction with ACP1 Genetic Polymorphism.

J Reprod Infertil 2015 Oct-Dec;16(4):199-202

Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.

Background: The possible association between allergy and neoplastic disorders has been the subject of many investigations but no general relationship has been determined. Little attention, however, has been paid to the possible role of allergy in the clinical manifestations of these diseases. In this study, the role of allergy in the susceptibility to uterine leiomyomas and in their growth was investigated. Interaction with ACP1 , a genetic polymorphism associated with the growth of leiomyomas, has been also considered.

Methods: Two hundred and three White woman from the population of Rome hospitalized for symptomatic leiomyomas requiring surgical intervention have been studied. One hundred thirty eight healthy women have been considered as controls. Allergy has been evaluated by prick test. T-test for equality of means, analysis of variance and linear correlation analysis has been performed. The level of statistical significance was set at 0.05.

Results: The frequency of allergic manifestations in women with leiomyomas does not differ from healthy women. The dimension of leiomyomas is lower in allergic than in non allergic women (p=0.004). The ACP1 *B/*B genotype and allergy cooperate in lowering the dimension of leiomyomas; the proportion of woman with small leiomyomas (<10 percentile) is much higher in allergic women carrying the *B/*B genotype as compared to other women (p<0.001). About 8% of variance of leiomyomas dimension is attributable to the joint effect of ACP1 and allergy.

Conclusion: Allergic women with high concentration of ACP1 f isoform (*B/*B genotype) are protected from excessive leyomioma growth. If confirmed in other clinical settings, our observation may have practical importance in identifying women at risk of more severe clinical manifestations.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4819208PMC
April 2016

Genetic variability within Adenosine Deaminase gene and uterine leiomyomas.

Eur J Obstet Gynecol Reprod Biol 2016 Apr 17;199:108-9. Epub 2016 Feb 17.

Department of Biomedicine and Prevention, University of Rome, Tor Vergata, Rome, Italy.

Objective: The recent observation of an association of colon cancer with two polymorphic sites within the Adenosine Deaminase (ADA) gene suggests an involvement of these polymorphisms in the development of solid tumors. This prompted us to search for a similar association in uterine leiomyomas.

Study Design: We have studied 181 women admitted to the hospital for leiomyomas requiring surgical intervention and 248 women of comparable age without clinical signs of leiomyomas. All women were from the White population of Rome and gave verbal consent to participate in the study. The genotypes of three polymorphic sites (ADA1, ADA2, ADA6) of ADA gene were determined by DNA analysis.

Results: A higher proportion of ADA2*1/*1 genotype and of carriers of the ADA6*1 allele was observed in women with leiomyomas as compared to controls. This parallels the association found in colon cancer.

Conclusions: This pattern is identical to that previously observed in colon cancer making the possibility of mere sample chance artifact unlikely and supporting the hypothesis that genetic polymorphisms within the ADA gene could be involved in the susceptibility to solid tumors. Genetic variability within the ADA gene may influence adenosine concentration and in turn the immune response by lymphocytes in solid tumors. On the other hand ADA molecules acting as ecto-enzyme may be involved in the transduction of signals in the cell surface with important effects on tumor development.
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http://dx.doi.org/10.1016/j.ejogrb.2016.02.002DOI Listing
April 2016

[Ultrafine particle emissions from laser printers].

G Ital Med Lav Ergon 2015 Jul-Sep;37(3):135-43

In recent years there has been growing attention to the importance of indoor air quality on which scientist and experts have no doubts since in modern society we tend to spend most of the time in various types of indoor environments (office, private homes, etc.). Laser printers, in particular, release an aerosol into the environment including solid and liquid particles and gaseous compounds. The measurement of all these components is not practically feasible. Therefore, it is necessary to identify a marker which, when measured, shows accurately the frequency, duration and magnitude of the exposure. The measure with an optical particle counter (OPC) and a condensation particle counter (CPC) is an indicator with high sensitivity and representativeness. The major advantage of using these tools is the ability to detect the presence of ultrafine particles and also detect the particles in the liquid phase. The continuous recording of submicron particulate matter emitted during the printing activity allows to measure the exposure of personnel, while the ratio between the peak values and the values without printing activity can be used to classify the printers according to their emissivity. The particulate generated during the processes of printing has size less than 0.3 micron and therefore extends in the size range of nanoparticles (ultrafine particles less than 100 nm). These activities lead to high concentrations of ultrafine particles with a variability related to factors such as type of printer, toner, paper type, frequency of maintenance and air exchange. The concentrations of ultrafine particles in office environments can be reduced by proper choice of the printers, with the use of appropriate filtration techniques and placing the equipment away from workstations.
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March 2016