Enhancing the role of occupational health services in the battle against Corona Virus Disease 2019.

Abstract: Occupational risk assessment is the core of any practice in occupational health and safety at the workplace. In Italy, the implementation of the preventive measures required by law (DPCM of April 26, 2020 and subsequent modifications and integrations) can exempt the employers from legal disputes in case of COVID-19 infection among employees. However, these laws have made meaningless the risk assessment process, which is the ideal setting where the preven-tive and protective measures must be identified and enhanced by individual employers, in collaboration with health and safety managers and occupational physicians, in the true exposure conditions. In this commentary, the authors stressed the role of workplace risk assessment and occupational health services for the valuable contribution that they may give to the battle against COVID-19, in terms of prevention, contact-tracing activity and COVID-19 rates of vaccinal coverage.

Crash sign: new first-trimester sonographic marker of spina bifida.

OBJECTIVES: To describe a new first-trimester sonographic sign, the 'crash sign', associated with fetal open spina bifida, and to evaluate its clinical usefulness in the first-trimester diagnosis of spina bifida. METHODS: This was a retrospective review of patients referred to three fetal medicine centers in the first trimester (11 + 0 to 13 + 6 weeks) with suspected spina bifida. Spina bifida was confirmed by direct visualization of the spinal defect on ultrasound by two experts and, when possible, by fetal postmortem examination. Ultrasound images were reviewed for the presence of the crash sign, which is the posterior displacement of the mesencephalon and deformation against the occipital bone in the axial view. The first-trimester ultrasound images of a mixed group of 10 cases and 40 control fetuses without spina bifida were assessed for the presence of the crash sign by two assessors blinded to the diagnosis. RESULTS: The crash sign was present in 48 out of 53 confirmed cases of spina bifida. Of these, 27 had isolated spina bifida and 21 had an associated anomaly. Of the five cases without the crash sign, one had isolated spina bifida and four had an associated anomaly. The crash sign was not reported in any of the control fetuses. CONCLUSIONS: We have described a new first-trimester sonographic marker for the diagnosis of spina bifida. Our results suggest that the crash sign may be a useful tool in the first-trimester detection of spina bifida. Prospective evaluation of the crash sign would be beneficial, ideally in a routine clinical screening ultrasound setting. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

RAS testing of liquid biopsy correlates with the outcome of metastatic colorectal cancer patients treated with first-line FOLFIRI plus cetuximab in the CAPRI-GOIM trial.

Background: Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in patients treated with first-line anti-EGFR monoclonal antibody-based therapy. Patients and methods: In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI. Tumor samples were retrospectively assessed by next generation sequencing (NGS). Baseline plasma samples were analyzed for KRAS and NRAS mutations using beads, emulsion, amplification, and magnetics digital PCR (BEAMing). Discordant cases were solved by droplet digital PCR (ddPCR) or deep-sequencing. Results: A subgroup of 92 patients with available both NGS data on tumor samples and baseline plasma samples were included in this study. Both NGS analysis of tumor tissue and plasma testing with BEAMing identified RAS mutations in 33/92 patients (35.9%). However, 10 cases were RAS tissue mutant and plasma wild-type, and additional 10 cases were tissue wild-type and plasma mutant, resulting in a concordance rate of 78.3%. Analysis of plasma samples with ddPCR detected RAS mutations in 2/10 tissue mutant, plasma wild-type patients. In contrast, in all tissue wild-type and plasma mutant cases, ddPCR or deep-sequencing analysis of tumor tissue confirmed the presence of RAS mutations at allelic frequencies ranging between 0.15% and 1.15%. The median progression-free survival of RAS mutant and wild-type patients according to tissue (7.9 versus 12.6 months; P = 0.004) and liquid biopsy testing (7.8 versus 13.8 moths; P < 0.001) were comparable. Similar findings were observed for the median overall survival of RAS mutant and wild-type patients based on tissue (22.1 versus 35.8 months; P = 0.016) and plasma (19.9 versus 35.8 months; P = 0.013) analysis. Conclusion: This study indicates that RAS testing of liquid biopsy results in a similar outcome when compared with tissue testing in mCRC patients receiving first-line anti-EGFR monoclonal antibodies.

Thermal evolution of MnxOy nanofibres as catalysts for the oxygen reduction reaction.

Manganese oxides (MnxOy) are considered as a promising catalyst alternative to platinum in fuel cell applications. In fact, a proper catalyst is needed in order to facilitate the oxygen reduction reaction (ORR) at the cathode, and platinum is considered the best material due to its low overpotential for this reaction. Contrary to platinum, MnxOy is inexpensive, environmentally friendly and can be shaped into several nanostructures; furthermore, most of them show significant electro-catalytic performance. Several strategies have been carried out in order to increase their efficiency, by preparing light and high-surface area materials. In this framework, nanofibres are among the most promising nanostructures that can be used for this purpose. In this work, a study of the thermal, morphological and catalytic behavior of MnxOy nanofibres obtained through the electrospinning technique is proposed. Emphasis is given to the thermal evolution of the precursors, proposing a possible crystallization mechanism of the different manganese oxides obtained. It turns out that manganese oxide nanofibres exhibit good catalytic performance for the ORR, comparable to those obtained by using Pt-based catalysts.

[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.

Bone marrow microenvironment in multiple myeloma progression.

Substantial advances have been made in understanding the biology of multiple myeloma (MM) through the study of the bone marrow (BM) microenvironment. Indeed, the BM niche appears to play an important role in differentiation, migration, proliferation, survival, and drug resistance of the malignant plasma cells. The BM niche is composed of a cellular compartment (stromal cells, osteoblasts, osteoclasts, endothelial cells, and immune cells) and a noncellular compartment including the extracellular matrix (ECM) and the liquid milieu (cytokines, growth factors, and chemokines). In this paper we discuss how the interaction between the malignant plasma cell and the BM microenvironment allowed myeloma progression through cell homing and the new concept of premetastatic niche.

[Working parents and welfare in Italy]. / Tutela della maternità e della paternità nei luoghi di lavoro. Percorso storico.

This paper considers parents empoyment laws in Italy, starting with the very first one in 1902. The legislative development is comparised with Italian history in twentieth and twenty-first centuries, with a particular attention to the Mussolinian age (1922-1943), the Constitution and 1975 Family Law. Social environment is also analyzed in this complex situation.

Withdrawal of active treatments in terminally ill heart failure patients.

INTRODUCTION: Heart failure (HF) constitutes a growing public health problem in aging societies: when pharmacological therapies fail, HF can be sustained intensively if patients are eligible for either orthotopic heart transplantation (OHT) or mechanical ventricular assistance, otherwise additional treatments could be inappropriate. In December 2017 Italian Legislator brought in the provisions regarding the end-of-life choices, including indications for withdrawing and withholding life-sustaining therapies. The aim of our study was to provide an overview of the daily practice of our center with regard to terminally ill HF patients. METHODS AND RESULTS: In April 2019 the 7 intensivist cardiologists and 21 nurses of a tertiary ICCU were asked in, to complete a questionnaire relating to a hypothetical terminally ill HF patient for whom the decision to withdraw active treatment had been made. To assess current practice, we also identified patients who died in the previous 12 months. Out of 29 deceased patients, 18 were identified as terminally ill HF, with no indications for therapy upgrading. We observed a striking disparity between belief and practice. CONCLUSIONS: Our survey showed that the care of terminally ill HF patients in our ICCU was characterized by aggressive use of medical therapy and invasive technology. The wide disparity between belief and practice could be in part a consequence of lack of professional training, with regard to law, ethics and communication techniques.

Metal removal processes in a pilot hybrid constructed wetland for the treatment of semi-synthetic stormwater.

This study investigates the reliability of a pilot hybrid constructed wetland (H-CW), located in Eastern Sicily (Italy). To address the uncertainty associated with implementing representative monitoring during highly variable storm events, unique to Mediterranean conditions, a recipe for semi-synthetic stormwater was used to evaluate the removal efficiency of the system. This was characterised by metals (Cd, Cr, Fe, Pb, Cu, Zn) and relative concentrations typically found in urban stormwater runoff (SR). Approximately one month of intensive monitoring activities were carried out and quality analyses were conducted on three matrices comprising the pilot H-CW: water, biomass (Canna indica, Typha latifolia), and volcanic gravel substrate. Metal retention in early clogging matter (SS) was also examined. The results showed a significantly high H-CW efficiency for the removal of all metals (70-98%) already at the horizontal flow unit outflow, confirming its strategic role. A metal mass balance analysis was also conducted to describe the retention capacity and influence of each system component on the overall efficiency (ranging from 87.8% for Cr to 99.2% for Pb). Metal removal was mostly related to sediment and substrate processes, while plants exhibited root bioaccumulation and phytostabilisation capacity even with a limited impact on overall system retention. The pilot H-CW exhibits characteristics suitable for the treatment of metal-enriched stormwater runoff and validates the useful application of decentralised natural systems for water resource management.

Impact of alcohol consumption on winter sports-related injuries.

INTRODUCTION: This study was carried out to evaluate data about trauma-related winter sports, including risk factors such as high speed, gender, age, alcohol consumption, details about the accident and snow conditions. METHODS: A retrospective review was conducted to determine the injury patterns and crash circumstances in holiday skiers and snowboarders. The data recorded were obtained from the database of the Pre-Hospital Emergency Registry of six skiing areas in the Dolomite mountains during the winter seasons November 2004-May 2009, injury data for major traumas from Ski Patrol Injury reports (helicopter, ambulance or ski slopes' patrol reports), and intrahospital Emergency Department data. Alcohol concentration in blood was detected in 200 individuals suffering from major trauma. RESULTS: A total of 4550 injured patients, predominantly male (69%), mean age 22 years (range 16-72), were included in the observational analysis. Knee, wrist and shoulder injuries were frequently associated with major thoracic, abdominal or head traumas (64% of cases). Suboptimal technical level, high speed, low concentration, snow or weather conditions, faulty equipment and protective devices were among the various causes of accidents. The analysis revealed that high alcohol blood concentration was present in 43% of 200 patients. CONCLUSIONS: Even though the major causes of accidents were excessive speed, excessive fatigue, technical errors and bad weather conditions, alcohol abuse was often discovered. Random sampling and a non-systematic detection of alcohol blood levels likely led to an underestimation of alcohol consumption-related injuries. It is recommended that investigations into alcoholic intoxication in injured skiers should be carried out on a large scale.

[Radon in workplaces, a review]. / Radon nei luoghi di lavoro, una panoramica.

Radon is a chemical radioactive element. It occurs naturally as the decay product of radium; it's responsible for the majority of the mean public exposure to ionizing radiation. It is often the single largest contributor to an individual's background radiation dose, and is the most variable from location to location. Radon gas from natural sources can accumulate in buildings, especially in confined areas such as attics, and basements. Breathing in radon is a cause of lung cancer. In Italy, high levels of radon should be found in underground spaces such as wineries, historical buildings, hot springs or mushrooms farms, and it's a hazard all this workplaces. To ensure the health and safety of employees and others who have access to their work environment, the occupational physician can program inexpensive surveys (with dosemeters) and develop an information plan.

Environmental electroactive consortia as reusable biosensing element for freshwater toxicity monitoring.

The development of tools to monitor water quality is mandatory in a scenario where clean water resources are decreasing. Here, the biosensing capability of an electroactive river sediment consortium was tested towards three model contaminants (glutaraldehyde, nickel(II) and chromium(III)). The proposed biosensor is a small membrane-less single chamber Microbial Fuel Cell (MFC), fabricated by 3D printing. Its semi-continuous mode of operation resulted in long-term current profile stability and reproducibility. A linear trend of response was obtained for glutaraldehyde in a concentration range of 5-1000 ppm. After the recovery of the electroactive consortium activity, the MFC-based biosensors were shown to be sensitive towards Ni(II) and Cr(III), at concentrations above 2 mg L-1. To effectively analyze biosensor response, a novel algorithm was proposed, offering advantages for the realization of energy-saving protocols for MFC-biosensor data transmission. Implementation of the device and method, from laboratory test to real environment, can offer a low cost in situ system for detection of water contaminants.

The novel HBx mutation F30V correlates with hepatocellular carcinoma in vivo, reduces hepatitis B virus replicative efficiency and enhances anti-apoptotic activity of HBx N terminus in vitro.

OBJECTIVE: We aimed to investigate HBx genetic elements correlated with hepatitis B virus (HBV) -related hepatocellular carcinoma (HCC) and their impact on (a) HBV replicative efficiency, (b) HBx binding to circular covalently closed DNA (cccDNA), (c) apoptosis and cell-cycle progression, and (d) HBx structural stability. METHODS: This study included 123 individuals chronically infected with HBV: 27 with HCC (77.9% (21/27) genotype D; 22.1% (6/27) genotype A) and 96 without HCC (75% (72/96) genotype D; 25.0% (24/96) genotype A). HepG2 cells were transfected by wild-type or mutated linear HBV genome to assess pre-genomic RNA (pgRNA) and core-associated HBV-DNA levels, HBx-binding onto cccDNA by chromatin immunoprecipitation-based quantitative assay, and rate of apoptosis and cell-cycle progression by cytofluorimetry. RESULTS: F30V was the only HBx mutation correlated with HCC (18.5% (5/27) in HCC patients versus 1.0% (1/96) in non-HCC patients, p 0.002); a result confirmed by multivariate analysis. In vitro, F30V determined a 40% and 60% reduction in pgRNA and core-associated HBV-DNA compared with wild-type (p <0.05), in parallel with a significant decrease of HBx binding to cccDNA and decreased HBx stability. F30V also decreased the percentage of apoptotic cells compared with wild-type (14.8 ± 6.8% versus 19.1 ± 10.1%, p <0.01, without affecting cell-cycle progression) and increased the probability of HBx-Ser-31 being phosphorylated by PI3K-Akt kinase (known to promote anti-apoptotic activity). CONCLUSIONS: F30V was closely correlated with HBV-induced HCC in vivo, reduced HBV replicative efficiency by affecting HBx-binding to cccDNA and increased anti-apoptotic HBx activity in vitro. This suggests that F30V (although hampering HBV's replicative capacity) may promote hepatocyte survival, so potentially allowing persistent production of viral progeny and initiating HBV-driven hepatocarcinogenesis. Investigation of viral genetic markers associated with HCC is crucial to identify those patients at higher risk of HCC, who hence deserve intensive liver monitoring and/or early anti-HBV therapy.

Early hemispherectomy in catastrophic epilepsy: a neuro-cognitive and epileptic long-term follow-up.

The authors report their experience about a neuro-cognitive and epileptic long-term follow-up of children with catastrophic epilepsy treated with hemispherectomy in the first 5 years of life. Nineteen children with resistant epilepsy that significantly interfered with their neuro-cognitive development underwent hemispherectomy within 5 years of life (mean: 2 years, 3 months; range: 5 months to 5 years). All patients were assessed before surgery and after, at least at the end of the follow-up (mean: 6 years and 6 months; range: 2-11 years and 2 months) with a full clinical examination including motor ability and functional status evaluation as well as behaviour observation, neuroimaging and an ictal/interictal prolonged scalp video-EEG. A seizure-free outcome was obtained in 73.7% of patients. Gross motility generally improved and cognitive competence did not worsen, with an evident progress in two cases. Consistently with previous reports, evolution was worse in cortical dysplasia than in progressive or acquired vascular cerebropathies. The excellent epileptic outcome and the lack of developmental deterioration in comparison with other more aged series seem to suggest a possible better evolution in earlier surgery treatment. To confirm this suggestion, however, further experience with larger series is needed.

[Workers with alcohol and drug addiction problems. Consensus Document of the Study Group on Hazardous Workers]. / Lavoratori con problemi di alcol e dipendenze. Documento di Consenso del gruppo La.R.A. (Lavoratori Rischiosi per gli Altri).

BACKGROUND: Italian Law 81/08 (so-called "Unified Text of Laws on Health and Safety at Work"), came into force on 15 May 2008 and incorporates provisions related to medical surveillance of drug and alcohol dependency at the workplace. OBJECTIVES: Occupational health traditionally addresses the issue of protection of worker from occupational hazards. The issue of protection of third parties from behaviour of workers resulting from drug and alcohol dependency implies an original methodological approach, involving full cooperation of employer, employees, and health and safety consultants. METHODS: A consensus development meeting was organized under the leadership of the Italian Study Group on Hazardous Workers (La.R.A. group). The meeting brought together physicians of different specialties, legal experts and bioethicists, labour and management policy-makers, to discuss the issue and define the research data available, the standards that were appropriate, and which policies were fair. RESULTS: The efficacy of medical surveillance, including workplace drug-testing, relies on a comprehensive policy, including written and verbal information on the use of alcohol and drugs on the job, training for supervisors and management, employee education, and employee assistance structures. Sample collection and testing should be carried out in accordance with standardized and tested procedures. Small businesses will need assistance, including development of model policies, setting up consortia for testing services and if necessary request for National Insurance benefits to reduce costs. CONCLUSIONS: The recently introduced Italian legislation on occupational safety and health closely resembles Finnish law since it consists of a "double channel" for workplace drug testing. At recruitment, the employer is entitled to ask a job applicant for a certificate of "Job fitness", including drug tests, that can be issued only by a public health institution, where the job applicant works on a well-defined set of tasks which require accuracy, trustworthiness, independent judgement or a very good reaction capacity. The employer may also refer the employee to the public health institution to obtain a certificate in the course of an employment contract when there is a legitimate suspicion that the employee is working while under the effects of drugs or alcohol or that the employee is a drug addict. After recruitment, the physician responsible for medical surveillance of workers (the so-called "Competent Physician") is entitled to perform drug tests on employees. The need for a test is decided by the health care professional, not by the employer, and only a general report on the health of the employee ("fit", fit with restrictions" or "unfit") may be given to the employer. Workers positive for drug tests will be referred to a public health institution for re-testing and treatment.

Reconstitution of cyclin D1-associated kinase activity drives terminally differentiated cells into the cell cycle.

Terminal cell differentiation entails definitive withdrawal from the cell cycle. Although most of the cells of an adult mammal are terminally differentiated, the molecular mechanisms preserving the postmitotic state are insufficiently understood. Terminally differentiated skeletal muscle cells, or myotubes, are a prototypic terminally differentiated system. We previously identified a mid-G(1) block preventing myotubes from progressing beyond this point in the cell cycle. In this work, we set out to define the molecular basis of such a block. It is shown here that overexpression of highly active cyclin E and cdk2 in myotubes induces phosphorylation of pRb but cannot reactivate DNA synthesis, underscoring the tightness of cell cycle control in postmitotic cells. In contrast, forced expression of cyclin D1 and wild-type or dominant-negative cdk4 in myotubes restores physiological levels of cdk4 kinase activity, allowing progression through the cell cycle. Such reactivation occurs in myotubes derived from primary, as well as established, C2C12 myoblasts and is accompanied by impairment of muscle-specific gene expression. Other terminally differentiated systems as diverse as adipocytes and nerve cells are similarly reactivated. Thus, the present results indicate that the suppression of cyclin D1-associated kinase activity is of crucial importance for the maintenance of the postmitotic state in widely divergent terminally differentiated cell types.