Transition path theory from biased simulations.

Transition Path Theory (TPT) provides a rigorous framework to investigate the dynamics of rare thermally activated transitions. In this theory, a central role is played by the forward committor function q+(x), which provides the ideal reaction coordinate. Furthermore, the reactive dynamics and kinetics are fully characterized in terms of two time-independent scalar and vector distributions. In this work, we develop a scheme which enables all these ingredients of TPT to be efficiently computed using the short non-equilibrium trajectories generated by means of a specific combination of enhanced path sampling techniques. In particular, first we further extend the recently introduced self-consistent path sampling algorithm in order to compute the committor q+(x). Next, we show how this result can be exploited in order to define efficient algorithms which enable us to directly sample the transition path ensemble.

Intramolecular oxidative deselenization of acylselenoureas: a facile synthesis of benzoxazole amides and carbonic anhydrase inhibitors.

A mild, efficient and one pot procedure to access benzoxazoles using easily accessible acylselenoureas as starting materials has been discovered. Mechanistic studies revealed a pH dependent intramolecular oxidative deselenization, with ring closure due to an intramolecular nucleophilic attack of a phenoxide ion. All the benzoxazoles herein reported possessed a primary sulfonamide zinc binding group and showed effective inhibitory action on the enzymes, carbonic anhydrases.

Design, synthesis and preliminary evaluation of a series of histone deacetylase inhibitors carrying a benzodiazepine ring.

A series of new histone deacetylase inhibitors were designed and synthesized based on hybridization between SAHA or oxamflatin and 5-phenyl-1,4-benzodiazepines. The compounds were tested for their enzyme inhibitory activity on HeLa nuclear extracts, and on human recombinant HDAC1 and HDAC6. Antiproliferative activity was tested on different cancer cells types, while proapoptotic activity was primarily tested on NB4 cells. The compounds showed IC50 values similar to those of SAHA. Compound (S)-8 displayed interesting activity against hematological and solid malignancies.

Work stress and negative affectivity: a multi-method study.

BACKGROUND: In the literature negative affectivity (NA) is considered both a confounding variable as well as a predictive variable for work-related stress. However, a common limitation in this line of research relates to the use of self-report measures for determining NA, perceived stressors and psychophysical strain. AIMS: To test, using a multi-method study, a theoretical model that correlates NA, perceived interpersonal conflict (with co-workers and supervisors), psychophysical strain and medically certified sickness absences. METHODS: A multi-method prospective study was carried out on a sample of metalworkers. NA and interpersonal conflict were determined using self-report (Time 1), whereas psychophysical strain was determined by an occupational physician (Time 2). Data on medically certified sickness absences were collected from the company's database (Time 3). RESULTS: There were 326 participants. The results showed an association between NA and conflict with co-workers, as well as between NA and conflict with supervisors. Psychophysical strain could be predicted from NA and conflict with co-workers but not from conflict with supervisors. NA had a significant indirect effect on psychophysical strain through conflict with co-workers. Lastly, psychophysical strain predicted sickness absences from work. CONCLUSIONS: NA influenced psychophysical strain in the worker, both directly and indirectly, through perceived conflict with co-workers.

[Guides to chemical risk assessment in the construction industry]. / Percorsi di valutazione del rischio chimico in edilizia.

The presence of chemical agents in construction is certainly relevant in terms of quality, quantity and toxicity. Their manipulation can result in potential exposure as inhaled and/or through the skin. It is therefore possible and necessary to identify a list of substances to be considered relevant for the risk assessment and the possible environmental monitoring to verify the adequacy of the estimate made. The many variables inherent in construction make it extremely difficult to apply the usual methods of the industrial hygiene because it would not very significant conclusions in terms of space-time representation. SIMLII in one of its guidelines have proposed a "indexes" method that can provide useful information to the figures of prevention for the actions of their competence. The subsequent introduction of the REACH Regulation and exposure scenarios may help to further sharpening the assessment of chemical hazards in construction.

[Experiences of environmental and biological monitoring in the construction industry]. / Esperienze di monitoraggio ambientale e biologico in edilizia.

After emphasizing the characteristics of the sector and the difficulty of applying traditional industrial hygiene methods for assessing exposure to chemical agents in the construction industry, we have reviewed the major experiences of environmental and biological monitoring that can be derived from the literature. Although the determination of exposure through environmental measures should be considered the most appropriate instrument, it should be paid for the study of specific activities, while it is preferable in many situations the use of simplified tools (such as algorithms and databases) that allow the risk estimation and enable the adoption of safe work procedures and environmental and individual protection devices.

Biological monitoring of exposure to perchloroethylene in dry cleaning workers.

BACKGROUND: Perchloroethylene (PCE) is the most widely used solvent in dry cleaning. OBJECTIVES: The aim was to evaluate PCE pollution and to identify the most reliable biological indicators for the assessment of workers' exposure. METHODS: The study was performed in 40 dry cleaning shops covering a total of 71 subjects. Environmental monitoring was carried out with personal diffusive samplers (Radiello) for the entire work shift; biological monitoring was performed by measuring PCE in urine and blood and trichloroacetic acid (TCA) in urine on Thursday evening at end-of shift and on Friday morning pre-shift. RESULTS: The mean concentration of PCE in air was 52.32 mg/m3, about 30% of the TLV-TWA and the mean value of the PCE inpre-shift blood samples was 0.304 mg/l, slightly more than 50% of the BEI. In dry cleaning shops employing less than 3 persons PCE in air exceeded the TLV-TWA in 7.8% of cases; the size of the shops was inversely related to pollution. Statistically significant correlations were found between PCE exposure and PCE in blood end-of-shift (r = 0.67) and pre-shift (r = 0.70), and PCE in urine end-of-shift (r = 0.68); no correlation was found between exposure and PCE in urine pre-shift and urinary TCA. CONCLUSIONS: Dry cleaning shops still register conditions of exposure and pollution by PCE, although to a lesser extent than in the past. The most reliable indicators for biological monitoring are CE in end-of-shift urine and PCE in blood both at end-of-shift and pre-shift at the end of the workweek.

[A new scale for measuring the psycho-physical effects of work-related stress in a perspective of methods integration]. / Una nuova scala di misura degli effetti psico-fisici dello stress lavoro-correlato in una prospettiva d'integrazione di metodi.

BACKGROUND: This study fits into a perspective of integrated work-related stress assessment, in response to the need to limit the common method variance and the role played by individual variables in subjective measures. OBJECTIVES: The goal of this study was to check the metric properties of a new scale of mental and physical strain developed for the evaluation of stress symptoms by the physician and to detect the antecedents of psycho-physical symptoms, in terms of both individual and work characteristics, through an integrated approach. METHOD: The study was conducted on 409 workers involved in health surveillance activities, to whom the new scale and a subjective assessment tool were administered. RESULTS: Confirmatory factor analysis showed that the scale is a reliable tool for hetero-evaluation of psycho-physical symptoms attributable to stress at work. Moreover, specific individual characteristics, such as the presence of prior health disorders and the female gender, and organizational features, such as the pathological work/life conflict and the workload, were found to be risk factors in relation to psychological and physical strain. Age, consumption of alcoholic beverages between meals, relationships with colleagues, and the characteristics of the workplace were instead found to be important protective factors. DISCUSSION: The adoption of an integrated approach made it possible to improve and study in depth the ways of work-related stress assessment, highlighting the pivotal role of the occupational health physician making the evaluation.

Occupational diseases due to allergic and toxic chemicals in health care workers: fitness for work.

The purpose of this review is to suggest job fitness criteria for health care workers exposed to sensitizing or chemical agents. These recommendations are derived from a comparison between previous documents on prevention and management of allergic and chemical risks in health care settings and updated evidence; the job fitness criteria and the main documents on these topics are summarized in tables. Glove allergy, in particular latex allergy, is still a significant problem but we should remember that a wide choice of alternative materials is now easily available; many different alternative health products are also currently available when an allergy to disinfectants or detergents is diagnosed. Hence the prevention of allergic diseases is mostly based on an appropriate choice and use of the gloves and health products according to the specific tasks and possible individual susceptibility; this meets the requirements of the "good health care organization", which translates into lower costs, if possible, as well as the best protection of worker's health. Concerning chemical risk, it should be remembered that during the last 20 years the improvements made in work environments have profoundly changed the mode and the levels of exposure to chemical substances and the current recommendations concerning the management of workers exposed to anesthetic gases, antineoplastic agents and sterilizers/disinfectants significantly differ from those of early 1990s. However, the past prudential guidelines are still valid for formaldehyde.

[Drugs use assessment in a group of bus drivers]. / Valutazione dell'assunzione di sostanze stupefacenti in un gruppo di conducenti di autobus.

Bus driver is one of those tasks inherent transport activity, which involves special risks to safety and health of others and for which it is necessary, according to art. 41 of Decree No. 81/08, to check the consumption of psychoactive substances during the health surveillance. This assumption was investigated in a group of 461 bus drivers of a large trucking company. In medical history, one subject reported a previous history of opiate addiction and another, in the past, occasional taking of cannabis, and at the time of the visit, in no cases the objectivity has shown intoxication or abstinence signs, or signs of parenteral injection. Laboratory tests were found positive in one case of screening texts, not confirmed by subsequent laboratory analysis and a case of positive analysis for confirmation. The worker, temporarily suspended from driving and taken over by the Service for Drug Addiction of competence, was then reinstated in his job, having held that the absence of drug addiction.

[Lesser validity of urinary benzene than S-phenylmercapturic acid for measuring occupational and environmental exposure to very low concentrations of benzene]. / Minore validità del benzene urinario rispetto all'acido S-fenilmercapturico nel rilevare l'esposizione occupazionale ed ambientale a concentrazioni molto basse di benzene.

AIM: To study the validity of urinary benzene as a biomarker of low and very low exposure to this toxicant, as compared with t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (SPMA), also taking into account the influence of cigarette smoking and co-exposure to toluene on the urinary excretion of benzene. MATERIALS AND METHODS: The results obtained in two different studies were compared: in the first, workers occupationally exposed to low concentrations of benzene (18 fuel tanker drivers and 23 filling station attendants) were compared with 31 controls and in the second, workers exposed to very low concentrations of benzene (the same 23 filling station attendants) were compared with the 31 controls. Exposure to airborne benzene and toluene was monitored with passive personal samplers (Radiello). Then the urine collected at the end of the work shift was analyzed for t,t-MA, SPMA and urinary benzene. All participants also filled out a questionnaire about their lifestyle habits. RESULTS: There were no differences among the three groups in terms of age and smoking habit. Occupational exposure to benzene and toluene and the urinary concentrations of t,t-MA, SPMA and urinary benzene were higher in the fuel tanker drivers than the filling station attendants and higher in the latter than in the controls. Cigarette smoking was found to be associated with urinary excretion of t,t-MA, SPMA and urinary benzene at both low and very low exposure to benzene. The biomarkers t,t-MA, SPMA and urinary benzene were almost always correlated, for both low and very low exposure to benzene. Notably, for low exposure to benzene a dependency relation was found with the levels of t,t-MA, SPMA and urinary benzene on both cigarette smoking and airborne benzene, whereas for very low exposure to benzene there was a dependency relation of SPMA on cigarette smoking and airborne benzene, of urinary benzene only on cigarette smoking and of t,t-MA on none of the variables considered. CONCLUSIONS: For occupational exposure to low concentrations of benzene, urinary benzene and SPMA showed a comparable validity, while for exposure to very low concentrations of this toxicant the validity of SPMA was confirmed while urinary benzene was found to be less useful. Cigarette smoking was the main factor conditioning the excretion of all the biomarkers of benzene in conditions of both low and very low exposure to the toxicant, so for the analysis of occupational exposure to benzene it is best to recommend abstention from smoking at least in the hours immediately before urine collection.

Personal exposure to particulate matter is associated with worse health perception in adult asthma.

BACKGROUND: Epidemiological studies have shown positive associations between particulate matter (PM) air pollution and short-term mortality and morbidity for asthma. The hypothesis that lung inflammation is responsible for these effects has been tested in panel and controlled exposure studies in asthmatic adults, with inconsistent results. OBJECTIVES: We investigated whether personal exposure to PM10 and PM2.5 were related to changes in the clinical course of asthma and to lung inflammatory responses in adult asthmatics. METHODS: A cohort of 32 asthmatic patients was followed for 2 years. Asthma control test (ACT) and St George's Respiratory Questionnaire (SGRQ) scores, forced expired volume in the first second (FEV1), exhaled nitric oxide (Fe(NO)), and pH of exhaled breath condensate (EBC) were determined on 6 occasions during different seasons. Personal exposure to PM was measured for 24 hours prior to clinical assessments. RESULTS: A 10 microg/m3 increase in PM10 personal exposure was associated with an increase in SGRQ scores (regression coefficient beta = 0.22; 95% confidence interval [CI], -0.005 to 4.451; P =.055) and with a decrease in ACT scores (beta = -0.022; 95% CI, -0.045 to 0.001; P = .060), whereas no associations were found between PM10 and FEV1, Fe(NO), or EBC pH. A positive association was detected between Fe(NO) and outdoor O3 (P = .042) and SO2 (P = .042) concentrations in the subgroup of nonsmoking asthmatics. CONCLUSIONS: We concluded that increments in personal exposure to PM10 are associated with a decrease in asthma control and health-related quality of life. However, this study does not provide evidence that 24-hour exposures to PM are associated with short-term changes in lung function or inflammatory responses of the lung.

Applicability of urinary benzene to biological monitoring of occupational and environmental exposure to very low benzene concentrations.

OBJECTIVE: To verify whether urinary benzene is an applicable biomarker of occupational exposure to very low concentrations of benzene, considering the influence of cigarette smoke and benzene-toluene co-exposure. MATERIALS AND METHODS: 23 filling station attendants with occupational exposure to benzene and 31 controls were analyzed. Occupational and environmental exposure was monitored and t,t-muconic acid (t,t-MA), S-phenylmercapturic acid (SPMA), urinary benzene and creatinine in the urine samples were tested. RESULTS: Occupational exposure to benzene and toluene was significantly higher in the filling station attendants than in the controls, whereas t,t-MA, SPMA and urinary benzene were not different in the two groups. Instead, the smoker group showed significantly higher values for the above biomarkers than the non-smoker group, each of which included both exposed workers and controls. SPMA was dependent on airborne benzene and cigarette smoking, and urinary benzene only on cigarette smoking, while t,t-MA was not dependent on either of these variables. CONCLUSIONS: At very low concentrations of occupational exposure to benzene, urinary benzene is less valid than SPMA as a biomarker, even if both are strongly influenced by smoking habit. Abstention from smoking should therefore be recommended for at least two hours before urine collection.

[Manual material handling risk assessment and ergonomic improvement in foodstuff retailing company]. / Valutazione del rischio nella movimentazione manuale di carichi e interventi ergonomici correttivi in un'azienda di distribuzione di generi alimentari.

The aim of this study is to assess and reduce the risk due to manual material handling in a company involved in the foodstuff retailing. The risk assessment was performed by NIOSH Variable Lifing Index in 13 different occupational conditions. As result the risk was present in any case, with VLI values ranging from 2.12 to 2.81. A good risk reduction has been accomplished correcting properly the most important multiplier involved in the computation of the revised NIOSH Lifting equation (lifting frequency and weight of heavier products). Even if the performed risk reduction has been significant, the residual risk is still higher than the level of acceptability.

[Work-related stress: comparing two assessment methods]. / Stress lavoro-correlato: due metodi di valutazione a confronto.

Aim of the study is to compare and evaluate the possible integration of two methods of work-related stress risk assessment: the "subjective/perceptive" ISPESL-HSE and the "objective/intersubjective" VIS. Four different types of companies were examined: public education, social services, forestry work, agricultural machinery industry. Both VIS and HSE showed a different level of risk among the companies, with a good overlap of the results obtained with the two different methods of investigation. They also integrate each other in eliciting a better and more articulated study of work-related stress risk.

[Occupational exposure to ionizing radiation in hospital. Analysis of individual risk by area and occupational category]. / Valutazione dell'esposizione a radiazioni ionizzanti in ospedale. Analisi del rischio individuale per reparto e per mansione.

An analysis of occupational radiation exposure from 1988-2008 of 43 medical, 41 nurses and 4 nuclear medicine technicians of interventional cardiology, nuclear medicine, radiology-neuroradiology, urology and orthopedics has been performed. The mean annual effective dose to the whole body of all monitored workers are decreasing; one vascular surgeon, has exceeded 20 mSv/year. The doses received by physicians in the hands were up in radiology, urology and cardiology. Currently, interventional cardiology-hemodynamic is the most department-average exposure. Nurses are overall less exposed, the great exposure is in nuclear medicine, where the technicians are included.

[Environmental and biological limit values and reference values]. / I valori limite ambientali e biologici e i valori di riferimento.

The application of air quality guidelines and limits for occupational exposure in the workplace are the main tools for risk reduction and prevention of the effects of pollutants on health of the general population and workers respectively. The Biological Reference Values (BRVs), determined in situations of non-occupational exposure, and the Biological Limit Values (BLVs) contribute to the interpretation of biological monitoring data. In the occupational field the comparison with the BRVs should be informative about the existence of exposures greater than the general population and are particularly important for substances without VLBs or whose effects include chronic diseases.

[The role of scientific associations in the definition of occupational limit values]. / Il ruolo delle Società Scientifiche nella definizione dei valori limite.

The definition and compliance with occupational limit values for pollutants in the workplace are the main tool for risk reduction and prevention of possible adverse health effects. There is no doubt that the decisions on the limit values are now closely linked to what produced in the European Community, if not at the international level. However, we believe that Scientific Associations should play a role in proposing and updating the limit values adopted by law in Italy. Become prominent interlocutors of lawmakers and institutional bodies is equally important.