Antibiotic consumption is a major driver of antibiotic resistance in calves raised on Italian cow-calf beef farms.

Although its importance, little information is available on antibiotic-resistance in cow-calf beef farms. This study aimed to determine prevalence and risk factors for antibiotic-resistant organisms in this livestock system. Fifty-four farms from Central Italy were included to assess the presence of antibiotic-resistant indicator Escherichia coli and of ESBL and/or AmpC-producing E. coli (ESBL/AmpC-EC) in calves. Antimicrobial usage (AMU) was recorded, and farm-related variables were collected through questionnaires. Potential risk factors were tested using a mixed-effects logistic regression model. The presence of resistant-E. coli was recorded in 75.9% of farms (95% confidence interval [CI]: 62.4-86.5) with resistance to tetracyclines, sulfonamides, penicillins, and fluoroquinolones as the most frequent. The prevalence of farms positive for ESBL/AmpC-EC was 35.2% (95% CI: 22.7-49.4). AMU on the farms originating a resistant-E. coli was higher than that on the farms originating a susceptible-E. coli. The same difference was found for the consumption of beta-lactams (beta-DCD/year) and AMU via the parenteral route, which resulted also associated with the presence of ESBL/AmpC-EC. Farms with higher beta-DCD/year had an increased risk of being positive for resistant-E. coli, whereas farms with higher overall AMU had an increased risk for ESBL/AmpC-EC presence. Among farm-related factors, only farm size was associated with the presence of ESBL/AmpC-EC (odds ratio: 5.8, 95% CI: 1.3-26.3). Our findings highlight a reduction of the risk of ESBL/AmpC-EC in small cow-calf farms, and a strong association between AMU and antibiotic-resistance. Antibiotic stewardship programs are needed to improve the health status of cow-calf farms and ensure their long-term sustainability.

[Road map for health and safety management systems in healthcare facilities, according to the OHSAS 18001:2007 standard]. / ROAD MAP per i Sistemi di Gestione in Sanità, secondo lo Standard OHSAS 18001:2007.

The 81/2008 Act has defined a model of a health and safety management system that can contribute to prevent the occupational health and safety risks. We have developed the structure of a health and safety management system model and the necessary tools for its implementation in health care facilities. The realization of a model is structured in various phases: initial review, safety policy, planning, implementation, monitoring, management review and continuous improvement. Such a model, in continuous evolution, is based on the responsibilities of the different corporate characters and on an accurate analysis of risks and involved norms.

Implications of metal exposure and liver function in Parkinsonian patients resident in the vicinities of ferroalloy plants.

Valcamonica is an Italian valley where ferro-manganese industries have been active for a century and where an increased prevalence of parkinsonism was observed. A group of 93 patients (65 from Valcamonica, 28 from the reference area of Brescia city) and 76 controls (52 from Valcamonica, 24 from Brescia) were screened for serum Cu, Zn, Fe, Mn in blood (MnB) and urine (MnU), transferrin, peroxides, alanine (ALT) and aspartate (AST) transaminases and direct bilirubin. Test results were compared among groups according to the residential area and related to the disease severity. Valcamonica patients had a serum-increase of Cu, as well as of AST/ALT ratio, and a serum-decrease of Zn and Fe compared with other subgroups of cases and controls. Cases and controls from Valcamonica had higher MnB and MnU levels compared to cases and controls from Brescia. After controlling for the duration of illness, the Unified Parkinson's Disease Rating Scale III domain correlated with serum Cu and AST/ALT ratio. Our results suggest the possibility that, in this area, a lifetime exposure to neurotoxicants and to Mn in particular, when accompanied to a subclinical liver dysfunction, may pose an increased risk for neurodegenerative disorders via metal metabolism (Cu, Zn, Fe) abnormalities.

[Application of an integrated method for risk assessment of related work-stress in health care]. / Applicazione di un metodo integrato per la valutazione dei fattori di rischio stress-correlati nel settore sanitario.

To assess the risk from exposure to occupational stress and burnout in health care workers (HCW), a cross-sectional study was planned to compare objective data that can represent potential job stressors in hospital wards and subjective symptoms reported by the workers. Medical doctors, nurses and ancillary workers of the Internal Medicine Wards of a large public hospital in Northern Italy were enrolled in the study. Three subjective questionnaires were administered: the Job Content Questionnaire, the State-Trait Anxiety Inventory, the Maslach Burnout Inventory. In addition, seven objective parameters were collected as average on the 3 months period prior to the study: a) working understaffed; b) number of patients/HCW on service; c) number of HCW on sick leave/on service; d) number of skipped days off after night shifts; e) number of sick leaves; f) number of deceased patients; g) number of accidents at work. A total group of 230 HCW were examined, employed in six different sub-units of the Medical wards. The female workers were 67.8% and the male workers 32.2%, the mean age was 37.4 years (SD 9.3) in the total group, 35.1 years (SD 7.9) in females and 42.3 years (SD 10.3) in males. The average scores of subjective and objective parameters resulted significantly higher in the same sub-units. The correlation analysis showed that the subjective questionnaires were highly inter-related. The multivariate analysis showed that the number of sick leave days was significantly related to the subjective questionnaires, and the subjective subscales of emotional exhaustion, job demand, decision latitude and STAIt were significantly related to some of the objective parameters. Therefore, the best approach to measure occupational stress is an integrated one, which involves the use of multiple subjective and objective assessment modalities.

Identification of a 2-propanol analogue modulating the non-enzymatic function of indoleamine 2,3-dioxygenase 1.

Indoleamine 2,3 dioxygenase 1 (IDO1) is a metabolic enzyme that catalyzes the conversion of the essential amino acid tryptophan (Trp) into a series of immunoactive catabolites, collectively known as kynurenines. Through the depletion of Trp and the generation of kynurenines, IDO1 represents a key regulator of the immune responses involved in physiologic homeostasis as well as in neoplastic and autoimmune pathologies. The IDO1 enzyme has been described as an important immune checkpoint to be targeted by catalytic inhibitors in the treatment of cancer. In contrast, a defective expression/activity of the enzyme has been demonstrated in autoimmune diseases. Beside its catalytic activity, the IDO1 protein is endowed with an additional function associated with the presence of two immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which, once phosphorylated, bind SHP phosphatases and mediate a long-term immunoregulatory activity of IDO1. Herein, we report the screening of a focused library of molecules bearing a propanol core by a protocol combining microscale thermophoresis (MST) analysis and a cellular assay. As a result, the combined screening identified a 2-propanolol analogue, VIS351, as the first potent activator of the ITIM-mediated function of the IDO1 enzyme. VIS351 displayed a good dissociation constant (Kd = 1.90 µM) for IDO1 and a moderate cellular inhibitor activity (IC50 = 11.463 µM), although it did not show any catalytic inhibition of the recombinant IDO1 enzyme. Because we previously demonstrated that the enzymatic and non-enzymatic (i.e., ITIM-mediated) functions of IDO1 reside in different conformations of the protein, we hypothesized that in the cellular system VIS351 may shift the dynamic conformational balance towards the ITIM-favoring folding of IDO1, resulting in the activation of the signaling rather than catalytic activity of IDO1. We demonstrated that VIS351 activated the ITIM-mediated signaling of IDO1 also in mouse plasmacytoid dendritic cells, conferring those cells an immunosuppressive phenotype detectable in vivo. Thus the manuscript describes for the first time a small molecule as a positive modulator of IDO1 signaling function, paving the basis for an innovative approach to develop first-in-class drugs acting on the IDO1 target.

[A method for the measurement of workplace violence in health care workers]. / Misurazione degli episodi di violenza nei lavoratori della sanità: un metodo di indagine.

Aiming to register workplace violence in health care workers, we adopted two evaluation methods: direct and indirect. The direct method is represented by the Violent Incident Form (VIF), a 16 items checklist, which resumes the key aspects of violence events, identifying spatial and temporal circumstances, aggressor, type of violence and consequences. Indirect method is constituted by the observation of injury reports, through three sources: the Prevention and Protection Service (SPP), the Public Relation Office and the Police Position of the First Aid Unit. Although the instruments adopted, thus not comparable each other, pointed out a rather high number of violence events suffered by health care workers (direct method: 34 reports in the period 2002-2006; indirect method: 25 subjects, 8.5% of total); in most cases, the events were perpetrated by a patient, and directed against female of nurses. The most reported types of violence were: kicking, beating, hitting (indirect method) and verbal assault/threats (direct method). The study pointed out that workplace violence is an important risk factor, and therefore it is necessary to consider it for preventive intervention.

[Occupational exposure to manganese in ferroalloy industry: neurobehavioral effects in a workers' cohort]. / Esposizione professionale a manganese nell'industria delle ferroleghe: effetti neurocomportamentali in una coorte di lavoratori.

Our Institute has been following for 20 years a group of workers of a ferroalloy industry in order to evaluate neurobehavioral effects due to manganese exposure. Five years after the last study we have planned another one, to evaluate differences in neuromotor e cognitive functions between exposed and controls and to perform a longitudinal evaluation of the results. Environmental and biological sampling were collected, liver and kidney functionality, haemochrome, iron metabolism and sieric prolactine were evaluated. Several tests were administered: postural evaluation, tremor, four tests of the SPES battery, Pursuing Aiming, five tests of the Luria Nebraska Motor Battery, Raven Progressive Matrices, Trail Making Test, Mood Scale, Brief Symptoms Inventory, neuropsychological symptoms questionnaire. Personal habits and working, living and clinical histories were collected. We evaluated 43 exposed workers and 40 controls. Exposure indicators resulted all significantly higher in exposed workers. Neuropsychological examination showed differences in Raven Progressive Matrices and Pursuit Aiming, higher tremor values and differences in postural evaluation between exposed and controls.

[A follow-up study to assess stress and burnout in healthcare workers. Preliminary data]. / Studio di follow-up per la valutazione di stress e di burnout negli operatori sanitari. Dati preliminari.

To compare data obtained in a pilot study (2002) which evaluated the risk from exposure to stress and burnout in health care workers, the same three subjective questionnaires were administered: the Job Content Questionnaire (JCQ), the State-Trait Anxiety Inventory (STAI), the Maslach Burnout Inventory (MBI). The evaluation considered 294 workers employed in eight units: two of the six previous units were reorganized in four subunits. Preliminary data showed that questionnaires' scores have a concordant trend in the different units, as observed in 2002, confirming the validity of the instruments adopted. Results indicated a decreased level of the perceived stress in all the units, especially in the Third Division. We can hypothesize that the new organization, workers' turnover during the 5 years and the effect due to individual variables could have contribute to the observed variation. No significant associations, compared to 2002, between questionnaires' scores and task were found. Further evaluations, including measurement of objective parameters, will be carried out to complete the follow-up study and to determine which variables could have a role in the variation of the levels of stress and burnout's subjective perception.

[Metals and oxidative stress in Parkinson's disease from industrial areas with exposition to environmental toxins or metal pollution]. / Dismetabolismo dei metalli e stress ossidativo in pazienti con in Parkinson's disease di un'area industriale esposta ad inquinamento da metalli.

BACKGROUND: Parkinson's disease (PD) is characterized by a progressive degeneration of the nigrostriatal dopaminergic pathway resulting in movement disorders. PD is a complex disease, in which and environmental factors, as exposure to toxins or metals coul be involved. OBJECTIVE: To assess if serum metals (Cu, Fe, Zn), biological variables of their metabolism, total peroxides and antioxidants were abnormal in PD, in relation to environmental exposure. METHODS: We compared levels of serum copper, iron, zinc, ceruloplasmin and transferrin, peroxides, antioxidants (TRAP) in 65 PD patients coming from an Industrial zone highly exposed to metal pollution (Valcamonica) with measures from 28 PD patients from no metal pollution areas of the province of Brescia and 52 healthy controls coming from Valcamonica and 24 from the province of Brescia. RESULTS: PD patients had higher serum concentration of zinc than controls. Only in PD patients coming from Valcamonica levels of Cu were higher than in subjects coming from the province of Brescia. Moreover, In patients with PD levels of sieric Cu significantly correlated with score of the Unified Parkinson's Disease Rating Scale (UDPRS). CONCLUSIONS: Zinc seems to be higher in PD independently from the exposition to metal pollution. Perturbation of copper metabolism in PD seems to be related to exposition to environmental toxins or metal pollution and coul be involved in the progression of the disease itself.

Neurological and neuropsychological features in Parkinsonian patients exposed to neurotoxic metals.

BACKGROUND: Environmental exposure to heavy metals and especially manganese (Mn) took place in Valcamonica, Italy, where a high prevalence of Parkinsonism was observed (age and sex standardized 407/100,000; 95% CI: 393.87-420.12), and the Standardized Morbidity Ratios was associated with environmental Mn levels. METHODS: A cross sectional study compared Parkinsonian patients residents in Valcamonica with patients from Brescia, Italy. Age- and sex-matched healthy individuals were recruited as controls. The protocol included information on clinical, occupational, residential history and life habits, neuro-psychological testing, and assessment of genetic polymorphism. RESULTS: The target group included 65 patients and 52 controls from Valcamonica, 28 patients and 14 controls from Brescia. Age at onset of the disease was lower in women from both areas. After adjusting for age and age at onset, patients from Valcamonica showed more severe motor impairment at the UPDRS scale, higher damage of cognitive and motor functions at MMSE, Token and Trial Making tests. Genetic variables showed a different allelic distribution of DRD4 gene between cases and controls, outside Valcamonica, where a less frequent familiarity for parkinsonism was reported. CONCLUSIONS: Parkinsonian patients with previous exposure to metals showed a more severe neuropsychological phenotype, without detectable contribution from genetic factors.

[Work-related musculoskeletal disorders of the upper extremity in spinning: lack of risk or of adequate methods for assessing risk?]. / Patologie muscoloscheletriche dell'arto superiore in addetti alla filatura: assenza di rischio o carenza di metodi per valutare in modo adeguato il rischio?

The existence of a risk of musculoskeletal disorders work-related of the upper extremity (UEWMSDs) in the textile industry, specifically in particular working phases as spinning, appears today controversial. The upper limb disorders, sometimes described, have not a location ever plausible with the level of the biomechanical overload, as when carpal tunnel syndromes are signalled during activities in which the shoulder is the only segment eventually interested. Moreover these findings are shown in workers appointed at tasks or actions not clearly identified at risk. For example the spinning activity, that requires the movement of shuttles of modest weight, sometimes on levels above the shoulder line, is organized with cyclical cadences sometimes as repetitive tasks concentrated in a short period, sometimes in longer during the entire shift. Distribution and number of the actions, would however allow a sufficient biomechanical recovery. The identification of the single technical action may result difficult, due to interindividual variability of actions, of their speed and complexity. Furthermore the other possible activities, alternate with specific spinning activities, can require strength or not correct posture even if they may have short duration. In this paper we present and discuss the results of the ergonomic survey for risk assessment of musculoskeletal disorders work-related of the upper limb. These analysis have been carried out in two textile plants, in which some cases of disorders of the upper limb in workers employed in spinning activities have been described by occupational health physicians. In addition to assessment of possible risk for UEWMSDs in spinning activities, we founded the capability of usual methods for ergonomic analysis to adequately examine work situations like spinning, in which the hazardous actions are diluted over the entire shift or concentrate in a short period and in which there is a specific biomechanically overloaded segment i.e. the shoulder. Finally attention was paid to evaluate psychosocial factors which appear to be important when biomechanical factors are low-lying.

Brain magnetic resonance imaging and manganese exposure.

Due to its paramagnetic properties, manganese (Mn) can be effectively visualized by MRI. Mn accumulates selectively in the globus pallidus of basal ganglia, where it can produce high signals at brain magnetic resonance. These hyperintensities are bilateral, symmetrical, and visible in T1-weighted magnetic resonance imaging of different manganese overload conditions. A review of the literature shows identical findings in manganese exposed workers, hepatopatic patients, and patients undergoing total parenteral nutrition with excessive amount of manganese. Two indicators of exposure and hyperintensity were considered, represented respectively by the concentration of Mn in total blood (MnB), and the pallidal index (PI). These two indicators show a positive association, which indicates a possible continuum from normality to clinical stages both in workers occupationally exposed to Mn and in patients suffering from chronic liver disease. Since both MnB and PI show a high degree of variability, further research should be focused on the identification of more accurate indicators.

Assessment of neurobehavioral performance as a function of current and cumulative occupational lead exposure.

A cross sectional field study was planned to assess neurotoxic effects caused by low-level occupational lead exposure. Two groups of 66 workers and 86 controls were examined with a battery including a questionnaire on neurotoxic symptoms, the measure of performance at neurobehavioral testing, the detection of visual contrast sensitivity, and the dosage of serum prolactin. Both current and cumulative exposure to lead were defined. The average PbB was 27.50 +/- 28 microg/dl (median 28, range 6-61) in the exposed and 8.11 +/- 4.47 microg/dl (median 7, range 2-21). The test results were controlled for possible confounders including age, schooling, alcohol and coffee intake. Significant differences were observed between exposed and controls regarding neurotoxic symptoms reporting, the exposed reporting more frequently mood changes and abnormal fatigue. The exposed subjects showed a decreased visual contrast sensitivity, and a marked increase of prolactin secretion. No changes emerged regarding neurobehavioral testing. The alterations observed resulted associated to the current lead exposure and not to the cumulative indices. A safe exposure level was calculated on the basis of dose-response relationship with prolactin alteration, yielding a PbB value of 10 microg/dl.

Long-term exposure to "low levels" of manganese oxides and neurofunctional changes in ferroalloy workers.

Occupational exposure to manganese can cause early neurobehavioral effects in low- or a-symptomatic workers. A battery of neuropsychological tests was administered to a group of 61 ferroalloy male workers and 87 controls. The average (geometric mean) manganese concentrations in total dust at the plant have changed from 1981 to 1997 respectively from 1597.03 micrograms/m3 to 239 micrograms/m3 at the furnace area; from 151.53 to 255.76 micrograms/m3 at the casting area; from 167 to 54.7 micrograms/m3 at the maintenance (welding operations), yielding a current overall value of 54.25 micrograms/m3. A cumulative exposure index was calculated for each alloy worker and the average value (geometric mean) resulted to be 1204.87 micrograms/m3 x years, which divided by the average length of exposure (15.17 years), showed the concentration of 70.83 micrograms/m3 of manganese in total dust. Blood and urinary manganese geometric means resulted significantly higher in the exposed workers (9.18 micrograms/l and 1.53 micrograms/g creatinine, respectively) than in controls (5.74 micrograms/l and 0.40 microgram/g creatinine, respectively). A positive correlation was observed between the airborne manganese concentrations in total dust and blood manganese (n = 55; R = 0.36; R2 = 0.13; p = 0.0068), whereas no association resulted between cumulative exposure index and both blood manganese and urinary manganese. Higher prevalence of symptoms reporting was observed in the alloy workers concerning irritability, loss of equilibrium and rigidity. Tremor parameters including the central frequency and its dispersion, resulted to be statistically different in the exposed workers compared to the controls. Motor functions exploring the coordination of rapid and alternating movements and memory functions resulted to be impaired in the manganese workers. Dose-effect relationships were observed between the cumulative exposure index and some of the test results, whereas no relationship was found with the airborne manganese concentrations and the biological indicators of exposure. These findings are consistent with the existing knowledge of a cumulative mechanism of action of manganese, which must be carefully considered when setting safe exposure levels. In order to be protective for the entire working life, the average annual exposure level should be lower than 100 micrograms/m3.

Mechanism of neurobehavioral alteration.

Behavioral toxicology is an emerging field which is becoming increasingly important in risk assessment of exposure to neurotoxic substances, due to the high sensitivity of behavior towards neurotoxic action and the integration in behavioral functions of several underlying processes and neurofunctions, such as motor, sensory, attention, motivational. Whenever it is difficult to isolate the relative contribution of sensory, motor, arousal, or cognitive factors that contribute to an observed behavioral change, possible mechanism of behavioral alteration may rely on the involvement of neurotransmitters, such as the dopaminergic system and catecholamines metabolism. Examples are given of different behavioral types of changes induced in humans by organic solvents (styrene), metals (manganese) and anaesthetic gases, based on a possible common underlying mechanism of toxicity.

Synthesis and antibacterial properties of 7-[2-(3-substituted-5-isoxazolyl)-2-methoxyiminoacetamido]cep halospora nic acid derivatives.

The synthesis of new 2-(3-substituted-5-isoxazolyl)-2-methoxyiminoacetic acids and their condensation derivatives with a suitable cephalosporanic nucleus, is reported. Their antibacterial properties were tested in vivo and in vitro also against beta-lactamase producer microorganisms; particularly the oral bioavailability of some of these new derivatives was studied.

In-vitro susceptibility of quinolone-resistant clinical isolates of Escherichia coli to fosfomycin trometamol.

Escherichia coli (E. coli) is the most commonly isolated microorganism in uncomplicated lower urinary tract infections (UTI). Due to the increased isolation of E. coli strains resistant to quinolones, it is important to have available alternative drugs to this class of antibiotics as therapy for UTIs caused by this pathogen. Among the large number of currently available antimicrobial agents, fosfomycin trometamol is a useful alternative due to its peculiar microbiological and pharmacokinetic properties. Therefore, we tested the in vitro susceptibility of 79 quinolone-resistant clinical urinary isolates of E. coli to fosfomycin trometamol in comparison with amoxicillin, chloramphenicol, cotrimoxazole, netilmicin, nitrofurantoin and tetracycline. Fosfomycin trometamol showed high activity with a MIC90 of 4 mg/l. While no strains were resistant to fosfomycin trometamol, 83.5%, 63.3%, 58.2%, and 48.1% of the isolates were resistant to tetracycline, amoxicillin, chloramphenicol and cotrimoxazole, respectively. Nitrofurantoin and netilmicin resistance was present only in 12.7% and 6.3% of the strains, respectively. In conclusion, fosfomycin trometamol has retained its activity against quinolone-resistant strains of E. coli and cross-resistance with other classes of antimicrobial agents is not presently a problem. The strains tested did present high levels of resistance to other classes of antibiotics.

Synthesis and in vitro antibacterial properties of 2-(3-bromo-5-isoxazolylideneamino-oxy)acetamido-beta-lactam derivatives.

The synthesis of new 2-(3-bromo-5-isoxazolylideneamino-oxy)acetic acids and their condensation derivatives with suitable beta-lactam nuclei is reported. Their antibacterial properties have been tested in vitro. An interesting activity against Gram-positive bacteria including beta-lactamase-producing microorganisms was found among the cephalosporanic acid derivatives.

Synthesis and antifungal properties of 3-bromo-4,5,6,7-tetrahydro-1,2-benzoisoxazole derivatives.

The synthesis of 3-bromo-4,5,6,7-tetrahydro-1,2-benzoisoxazole derivatives and their activity against human pathogen fungi are reported. In particular, compound 3,5-dibromo-6,7-dihydro-1,2-benzoisoxazol-4-(5H)-one showed a broad antifungal spectrum and good fungicidal activity against Trichophyton mentagrophytes.