Objective Evaluation of Active Interactions between the Operator and Display Screen Equipment Using an Innovative Acquisition System.

The occupational risk of operators using display screen equipment (DSE) is usually evaluated according to the extent of time spent in active operator-DSE interactions. Risk assessment is based on activity data collected through questionnaires. We evaluated an original and innovative system that can objectively assess active operator-DSE interactions by collecting electrical impulses generated by the activation of mouse, keyboard and a camera that collects attentive eye-screen fixation. The main aim of this study was to evaluate the system's performance on an employee sample involved in the task of active reading and copying at a DSE workstation connected to the system. In the context of mandatory health surveillance at work, we enrolled 38 DSE operators with normal neuropsychological and eye assessments who were required to complete two predefined reading and writing tasks. The obtained results show that the system is able to collect activity data derived from operator-DSE interactions through screen fixation, keyboard tapping and mouse handling. In the copying task, the session duration as recorded by the system was highly related to the screen fixation time. In the copying task, mouse and keyboard activities were more strongly related to session duration than screen fixation. For the copying task, it was also possible to obtain individual profiles of operator-DSE interactions while performing the same standardized tasks. Collected data can allow an objective evaluation of active time spent by DSE operators at their workstations, thus allowing a more accurate occupational health risk assessment and management. Prospective analysis of individual operator-DSE interaction profiles can favor the setup of targeted preventive and organizational interventions from an of even wider worker wellbeing perspective.

A Twenty-Year Retrospective Analysis of Risk Assessment of Biomechanical Overload of the Upper Limbs in Multiple Occupational Settings: Comparison of Different Ergonomic Methods.

BACKGROUND: Several methods with which to assess the risk of biomechanical overload of the upper limb are described in the literature. METHODS: We retrospectively analysed the results of the risk assessment of the biomechanical overload of the upper limb in multiple settings by comparing the application of the Washington State Standard, the threshold limit values (TLV) proposed by the American Conference of Governmental Industrial Hygienists (ACGIH), based on hand-activity levels (HAL) and normalised peak force (PF), the Occupational Repetitive Actions (OCRA) checklist, the Rapid Upper-Limb Assessment (RULA), and the Strain Index and Outil de Repérage et d'Evaluation des Gestes of INRS (Institut National de Recherche et de Sécurité). RESULTS: Overall, 771 workstations were analysed for a total of 2509 risk assessments. The absence of risk demonstrated for the Washington CZCL, used as the screening method, was in good agreement with the other methods, with the sole exception of the OCRA CL, which showed at-risk conditions in a higher percentage of workstations. Differences in the assessment of the frequency of actions were observed among the methods, while their assessments of strength appeared to be more uniform. However, the greatest discrepancies were observed in the assessment of posture. CONCLUSIONS: The use of multiple assessment methods ensures a more adequate analysis of biomechanical risk, allowing researchers to investigate the factors and segments in which different methods show different specificities.

Importance of Work-Related Psychosocial Factors in Exertion Perception Using the Borg Scale Among Workers Subjected to Heavy Physical Work.

Objective: This study aimed to analyse the role of several environmental and time variables, as well as individual and psychosocial factors, on the perception of exertion, expressed by using the Borg scale, on logistics workers performing heavy manual tasks. Materials and Methods: We enrolled 56 subjects working in logistics sector that were interviewed on the perceived exertion required to execute a task of manual lifting of heavy loads, by using the Borg scale. The interviews were carried out during different shifts, at different times during the shifts and during several different months of the year. We also assessed the workers' anthropometric characteristics, length of service, any musculoskeletal diseases, and physical activity outside work. Workers were also interviewed using the structured OREGE questionnaire, in order to evaluate the main symptoms of stress and work-related psychosocial risk factors. Results: Overall, the subjective perception of the strength exerted by the workers exposed to a high risk of manual handling of loads was moderate. The rating attributed using the Borg scale showed no correlation with any of the investigated variables. 100% of the workers denied to suffer from symptoms of stress, whereas in terms of psychosocial factors, the workload was globally perceived as positive. Conclusion: The study results support the hypothesis that optimal work conditions-from a psychosocial point of view-reduce the subjective perception of exertion by workers even if exposed to a high risk of biomechanical overload.

Determinants of SARS-CoV-2 infection in Italian healthcare workers: a multicenter study.

Healthcare workers (HCWs) are at increased risk of being infected with SARS-CoV-2, yet limited information is available on risk factors of infection. We pooled data on occupational surveillance of 10,654 HCW who were tested for SARS-CoV-2 infection in six Italian centers. Information was available on demographics, job title, department of employment, source of exposure, use of personal protective equipment (PPEs), and COVID-19-related symptoms. We fitted multivariable logistic regression models to calculate odds ratios and 95% confidence intervals of infection. The prevalence of infection ranged from 3.0 to 22.0%, and was correlated with that of the respective areas. Women were at lower risk of infection compared to men. Fever, cough, dyspnea and malaise were the symptoms most strongly associated with infection, together with anosmia and ageusia. No differences in the risk of infection were detected according to job title, or working in a COVID-19 designated department. Reported contact with a patient inside or outside the workplace was a risk factor. Use of a mask was strongly protective against risk of infection as was use of gloves. The use of a mask by the source of exposure (patient or colleague) had an independent effect in reducing infection risk.

Health effects of living near an incinerator: A systematic review of epidemiological studies, with focus on last generation plants.

Huge reductions in incinerators' emissions occurred over time, and results of older studies cannot be directly generalized to modern plants. We conducted a systematic review of the epidemiologic evidence of the health effects of incinerators, classifying plants in three generations, according to emission limits. A systematic search identified 63 epidemiologic studies, published in English, investigating health effects of incinerators on humans. We focused on cancer, cardio-cerebrovascular diseases (CVD) and respiratory diseases, pregnancy outcomes and congenital anomalies. Only six studies in the general population were on third generation incinerators providing data on pregnancy outcomes and congenital anomalies. Given the heterogeneity of methods, the abundance of ecological/semi-ecological studies and the lack of reliable quantitative measures of exposure in several studies we did not perform any meta-analysis. No excesses emerged concerning all cancers and lung cancer. An excess of non-Hodgkin lymphoma was reported in some earlier studies, but not for second generation plants. Possible excesses of soft tissue sarcomas were confined to earlier incinerators and the areas closer to the plants. No clear association emerged for CVD and diseases of the respiratory system. Several different pregnancy outcomes were considered, and no consistent association emerged, in spite of a few positive results. Studies were negative for congenital anomalies as a whole. Sporadic excesses were reported in a few studies for specific types of anomalies, but no consistent pattern emerged. Evaluation of the evidence was hindered by heterogeneity in reporting and classification of outcomes across studies. Direct evidence from third generation plants is scarce. Methodological issues in study design (mainly related to exposure assessment, confounding and ecological design) and analysis make interpretation of results complex. In spite of this, the overall evidence suggests that, if there were any excesses at all for older incinerators, they were modest at most. Additional monitoring of third generation plants needs to overcome methodological weaknesses.

Selenium supplementation in patients with subclinical hypothyroidism affected by autoimmune thyroiditis: Results of the SETI study / Suplementos de selenio en pacientes con hipotiroidismo subclínico afectados por tiroiditis autoinmune: resultados del estudio SETI

Objective: The purpose of this prospective study was to assess the effects of selenium supplementation on TSH and interferon-γ inducible chemokines (CXCL9, CXCL10 and CXCL11) levels in patients with subclinical hypothyroidism due to Hashimoto's thyroiditis. Patients and methods: Patients with subclinical hypothyroidism due to Hashimoto thyroiditis were prospectively enrolled in the SETI study. They received 83mcg of selenomethionine/day orally in a soft gel capsule for 4 months with water after a meal. No further treatment was given. All patients were measured thyroid hormone, TPOAb, CXCL9, CXCL10, CXCL11, iodine, and selenium levels at baseline and at study end. Results: 50 patients (43/7 female/male, median age 43.9 ± 11.8 years) were enrolled, of which five withdrew from the study. At the end of the study, euthyroidism was restored in 22/45 (48.9%) participants (responders), while 23 patients remained hypothyroid (non-responders). There were no significant changes in TPOAb, CXCL9, CXCL10, CXCL11, and iodine levels from baseline to the end of the study in both responders and non-responders. TSH levels were re-tested six months after selenomethionine withdrawal: 83.3% of responding patients remained euthyroid, while only 14.2% of non-responders became euthyroid. Conclusions: The SETI study shows that short-course supplementation with selenomethionine is associated to a normalization of serum TSH levels which is maintained 6 months after selenium withdrawal in 50% of patients with subclinical hypothyroidism due to chronic autoimmune thyroiditis. This TSH-lowering effect of selenium supplementation is unlikely to be related to changes in humoral markers of autoimmunity and/or circulating CXCL9

Objetivo: El objetivo de este estudio prospectivo es evaluar los efectos de los suplementos de selenio sobre las concentraciones de TSH y de quimiocinas inducibles por interferón γ (CXCL9, CXCL10 y CXCL11) en pacientes con hipotiroidismo subclínico, debido a tiroiditis de Hashimoto. Pacientes y métodos: Se incluyó prospectivamente en el estudio SETI a pacientes con hipotiroidismo subclínico, debido a tiroiditis de Hashimoto. Recibieron 83μg de selenometionina al día por vía oral en una cápsula de gel blanda durante 4 meses con agua después de una comida. No se administró más tratamiento. Se sometió a todos los pacientes a evaluaciones del perfil hormonal tiroideo, anticuerpos anti-TPO, CXCL9, CXCL10, CXCL11, yodo y selenio en el momento del reclutamiento y al final del estudio. Resultados: Se reclutó a 50 pacientes (43/7 mujeres/varones, mediana de edad de 43,9 ± 11,8 años); 5 se retiraron del ensayo. Al final del estudio, 22/45 (48,9%) participantes recuperaron el eutiroidismo (respondedores) y 23 se mantuvieron hipotiroideos (no respondedores). No se observaron diferencias significativas en los valores de anticuerpos anti-TPO, CXCL9, CXCL10 y CXCL11 y yodo entre el momento basal y el final del estudio en los pacientes con y sin respuesta. La TSH se volvió a analizar 6 meses después de la retirada de la selenometionina: el 83,3% de los sujetos con respuesta seguían siendo eutiroideos, mientras que solo el 14,2% de los que no habían respondido se convirtieron en eutiroideos. Conclusión: El estudio SETI muestra que la suplementación de corta duración con selenometionina se asocia con una normalización de las concentraciones séricas de TSH que se mantiene 6 meses después de la retirada del selenio en el 50% de los pacientes con hipotiroidismo subclínico debido a tiroiditis autoinmunitaria crónica. Es improbable que esta acción reductora de la TSH de los suplementos de selenio esté relacionada con cambios de los marcadores humorales de autoinmunidad o del CXCL9 circulante

Selenium supplementation in patients with subclinical hypothyroidism affected by autoimmune thyroiditis: Results of the SETI study.

OBJECTIVE: The purpose of this prospective study was to assess the effects of selenium supplementation on TSH and interferon-γ inducible chemokines (CXCL9, CXCL10 and CXCL11) levels in patients with subclinical hypothyroidism due to Hashimoto's thyroiditis. PATIENTS AND METHODS: Patients with subclinical hypothyroidism due to Hashimoto thyroiditis were prospectively enrolled in the SETI study. They received 83mcg of selenomethionine/day orally in a soft gel capsule for 4 months with water after a meal. No further treatment was given. All patients were measured thyroid hormone, TPOAb, CXCL9, CXCL10, CXCL11, iodine, and selenium levels at baseline and at study end. RESULTS: 50 patients (43/7 female/male, median age 43.9±11.8 years) were enrolled, of which five withdrew from the study. At the end of the study, euthyroidism was restored in 22/45 (48.9%) participants (responders), while 23 patients remained hypothyroid (non-responders). There were no significant changes in TPOAb, CXCL9, CXCL10, CXCL11, and iodine levels from baseline to the end of the study in both responders and non-responders. TSH levels were re-tested six months after selenomethionine withdrawal: 83.3% of responding patients remained euthyroid, while only 14.2% of non-responders became euthyroid. CONCLUSIONS: The SETI study shows that short-course supplementation with selenomethionine is associated to a normalization of serum TSH levels which is maintained 6 months after selenium withdrawal in 50% of patients with subclinical hypothyroidism due to chronic autoimmune thyroiditis. This TSH-lowering effect of selenium supplementation is unlikely to be related to changes in humoral markers of autoimmunity and/or circulating CXCL9.

Position Paper on Asbestos of the Italian Society of Occupational Medicine.

The Position Paper (PP) on asbestos of the Italian Society of Occupational Medicine (SIML) aims at providing a tool to the occupational physician to address current diagnostic criteria and results of epidemiological studies, and their consequences in terms of preventive and evaluation actions for insurance, compensation and litigation. The PP was based on an extensive review of the scientific literature and was compiled by a Working Group comprising researchers who have contributed to the international literature on asbestos-related diseases, as well as occupational physicians with extensive experience in the evaluation of risks and the medical surveillance of workers currently and formerly exposed to asbestos. The PP was drafted and reviewed between 2017 and 2018; its final version was prepared according to the guidelines of AGREE Reporting Checklist. All the members of the Working Group subscribed to the document, which was eventually approved by SIML's Executive Committee. The first section addresses industrial hygiene issues, such as methods for environmental monitoring, advantages and limitations of different microscopy techniques, the potential role of microfibers and approaches for retrospective assessment of exposure, in particular in epidemiological studies. The second section reviews the biological effects of asbestos with particular attention to the diagnostic aspects of asbestosis, pleural changes, mesothelioma and lung cancer. In the following section the criteria of causal attribution are discussed, together with different hypotheses on the form of the risk functions, with a comparison of the opinions prevalent in the literature. In particular, the models of the risk function for mesothelioma were examined, in the light of the hypothesis of an acceleration or anticipation of the events in relation to the dose. The last section discusses topics of immediate relevance for the occupational physician, such as health surveillance of former exposed and of workers currently exposed in remediation activities.

Occupational exposure to formaldehyde and risk of non hodgkin lymphoma: a meta-analysis.

BACKGROUND: Formaldehyde, a widely used chemical, is considered a human carcinogen. We report the results of a meta-analyses of studies on the relationship between occupational exposure to formaldehyde and risk of non-Hodgkin lymphoma (NHL). METHODS: We performed a systematic review and meta-analysis according to international guidelines and we identified 12 reports of occupational populations exposed to formaldehyde. We evaluated inter-study heterogeneity and we applied a random effects model. We conducted a cumulative meta-analysis and a meta-analysis according to estimated average exposure of each study population. RESULTS: The meta-analysis resulted in a summary relative risk (RR) for NHL of 0.93 (95% confidence interval 0.83-1.04). The cumulative meta-analysis suggests that higher RRs were detected in studies published before 1986, while studies available after 1986 did not show an association. No differences were found between different levels of occupational exposure. Conclusions Notwithstanding some limitations, the results of this meta-analysis do not support the hypothesis of an association between occupational exposure to formaldehyde and risk of NHL.

Serum levels of polychlorinated biphenyls and risk of non-Hodgkin lymphoma: A hospital-based case-control study.

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma and limited evidence for non-Hodgkin lymphoma (NHL). However present findings on the association of PCB exposure and NHL are still controversial. This study examined the relationship between PCB serum levels and risk of NHL in a Northern Italy area (Brescia province), where a chemical factory produced PCBs from 1938 to 1984, causing human contamination. A case-control study of 215 NHL patients and 215 control subjects was conducted. Cases and controls were assayed for serum levels of 33 PCB congeners. No associations were found between risk of NHL and serum levels of total PCBs (OR = 0.51; 95% CI: 0.25-1.04 for highest vs lowest quartile) or specific PCB congeners. The study confirmed a strong association of NHL with HCV infection (OR = 3.60; 95% CI: 1.30-10.02). This case-control study does not support the hypothesis of an association between current serum levels of PCBs and NHL development in the general population.

Is age more than manual material handling associated with lumbar vertebral body and disc changes? A cross-sectional multicentre MRI study.

OBJECTIVE: Conflicting evidence exists to what extent manual material handling (MMH) causes lumbar disc disease, lack of evidence exist that this effect takes place especially at L5-S1 level, where the greatest moment occurs. The aim was to assess if lumbar vertebral body and disc changes are more common in people whose job involves significant MMH and, if so, to evaluate if lumbar vertebral body and disc changes are more prevalent in the lower part of the lumbar spine (L4-L5 and L5-S1). DESIGN: Observational, cross-sectional, with quasi-random recruitment. SETTING: Outpatient radiology units of three large hospitals in northern (Bologna and Brescia) and southern (Bari) Italy. PARTICIPANTS: 183 consecutive adult subjects (89 males, 94 females) aged 20-70 years referred by the general practitioner or a specialist for MRI of the lumbar spine. PRIMARY AND SECONDARY OUTCOME MEASURES: Neuroradiologists (blind to clinical assessment) evaluated the prevalence of intervertebral disc and vertebral body changes in standardised MRI examinations. History of personal and family musculoskeletal diseases and injuries, current and previous MMH at work and during leisure time were assessed by interview and self-administered questionnaire. RESULTS: Participants were classified according their occupational exposure to MMH. No association was found between MMH and vertebral body and intervertebral disc changes, whereas age over 45 years was consistently associated with more disc extension beyond the interspace changes, Pfirrmann changes, osteophytes and Modic changes: the association was statistically significant at the conventional 5% level. CONCLUSIONS: Age, and not MMH, seems to primarily affect the presence of intervertebral disc changes; prospective studies are needed to better explore the relationship between MMH and the possible presence (and level) of lumbar vertebral body and/or disc changes.

Occupational and environmental exposure to polychlorinated biphenyls and risk of non-Hodgkin lymphoma: a systematic review and meta-analysis of epidemiology studies.

We carryied out a meta-analysis of studies on exposure to polychlorinated biphenyls (PCBs) and risk of non-Hodgkin lymphoma (NHL). Through a systematic search of the literature, we identified relative risks (RRs) for PCB exposure and NHL risk in 30 populations (10 occupational exposure, seven high environmental exposure, 13 without special exposure). We performed random effects meta-analyses for exposure to all PCBs, specific PCB congeners and risk of all NHL and NHL subtypes. The meta-RR for studies of occupational exposure, high environmental exposure, and no special exposure were 0.94 [95% confidence interval (CI): 0.84-1.03], 1.05 (95% CI: 0.94-1.16), and 1.03 (95% CI: 0.72-1.34), respectively, and the cumulative meta-RR was 0.96 (95% CI: 0.85-1.07). No positive associations were found for exposure to specific congeners, nor for NHL subtypes. The meta-RR for an increase of 100 ppb serum or fat PCB level was 1.02 (95% CI: 1.00-1.04). There was weak indication of publication bias. Our meta-analysis found no association between PCB exposure and NHL risk, in particular in studies of occupational exposures. We detected a weak dose-response relation; the possibility of residual confounding and other sources of bias cannot be ruled out. PCBs are not likely to cause NHL in humans.

Biological monitoring of exposure to polycyclic aromatic hydrocarbons and to metallic elements in Italian Navy workers operating near the industrial area in Taranto (South Italy).

OBJECTIVES: To assess, by means of biological monitoring, exposure to polycyclic aromatic hydrocarbons (PAHs) and to metallic elements in Italian Navy workers operating near the industrial area in Taranto, and thereby estimate the health risk. METHODS: A total of 450 workers in the Italian Navy were examined; they had office type jobs, and 150 of them worked near the industrial area in Taranto (exposed group), 150 in Taranto but far from this area (internal control group) and 150 in Brindisi (external control group). The recruited workers were administered a questionnaire inquiring about current and previous working activities, personal medical history, lifestyle and dietary habits, and their residence location. Then they collected a urine sample for the determination of 1-hydroxypyrene, 2-naphthol, cotinine and the metallic elements As, Cd, Co, Cr, Mn, Ni, Pb, Cu, Zn and Hg. The latter were measured in 110 workers in each group. In addition, in some of the work sites of the three groups, environmental samplings were carried out to determine PAHs and the 10 metallic elements, also taking into account the wind direction. RESULTS: Airborne benzo(a)pyrene concentrations at the different sampling sites ranged from 0.02 to 0.06 ng/m3 and naphthalene between <25 and 65.3 ng/m3, regardless of the wind direction. Among the metallic elements, As, Cd, Co, Cr, Hg, Pb, Cu and Zn were present at concentrations below or just above the limit of detection (LOD). Mn and Ni were slightly higher in the work sites of the exposed group. The urinary concentrations of 1-hydroxypyrene, 2-naphthol and the single metallic elements were not higher in the exposed workers group than in the other 2 groups. Smokers had significantly higher urinary 1-hydroxypyrene and 2-naphthol concentrations, whereas cigarette smoking did not condition a higher urinary elimination of metallic elements in the three groups with the exception of Cd and Pb. Moreover, residence location conditioned Mn, Hg and As urinary excretion, consumption of shellfish and/or crustaceans in the 72 hours before urine collection conditioned As elimination, and consumption of legumes in the 72 hours before urine collection conditioned Ni elimination. CONCLUSIONS: This research did not find a higher urinary excretion of 1-hydroxypyrene, 2-naphthol and As, Cd, Co, Cr, Mn, Ni, Pb, Cu, Zn and Hg in the exposed workers group as compared to the internal control group working far from the industrial area of Taranto, nor in the group working in another city far away from Taranto, Brindisi. Therefore, it indicated that workers in the Italian Navy operating near the industrial area in Taranto were not exposed to a greater risk attributable to exposure to PAHs and metallic elements than the two control groups.

Urinary levels of metal elements in the non-smoking general population in Italy: SIVR study 2012-2015.

The purpose of this study of the Italian Society of Reference Values (SIVR) was to provide the reference values for metals in the urine of the Italian general population. Thirteen sampling centres situated in the north, centre and south of Italy took part in this project. Each sampling centre selected 20 adult subjects. The sample was made up of 120 male and 140 female non-smokers or smokers who had abandoned the habit at least 5 years previously, aged between 18 and 60 years. Urine samples were obtained from the same subjects in June and again in November of the same year. During collection of these two samples, we administered an ad hoc questionnaire designed to assess factors that might influence exposure and the results of the study such as personal characteristics, occupational or extra-occupational activities, dietary habits, the presence of dental fillings containing amalgam, the frequency and mode of exposure to passive smoking and exhaust gases of motor vehicles (traffic). Therefore, the urinary levels of thirteen trace elements (Be, Cd, Co, Cr, Cu, In, Mn, Ni, Pb, Pt, Sb, Tl and V) were determined by Inductively Coupled Plasma Mass Spectrometry. The concentrations obtained (95th percentile) are in µg/L: 0.034, 0.900, 2.24, 0.600, 24.0, 0.013, 1.53, 4.44, 2.64, 0.022, 0.095, 0.759 and 0.855 for Be, Cd, Co, Cr, Cu, In, Mn, Ni, Pb, Pt, Sb, Tl and V, respectively. Further studies with a larger number of subjects are needed in order to continue the biomonitoring of the Italian general population and to monitor the modified levels over time.

Plasma levels of polychlorinated biphenyls and risk of cutaneous malignant melanoma: A hospital-based case-control study.

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma (CMM), however few studies have been done in the general population. This study examined the relationship between PCB plasma levels and risk of CMM adjusting for sun sensitivity and sun exposure in a province of Northern Italy (Brescia), where a chemical factory produced PCBs from 1938 to 1984 causing human contamination. A case-control study of 205 CMM patients and 205 control subjects was conducted. Cases and controls were assayed for plasma levels of 33 PCB congeners. No associations was found between risk of CMM and plasma levels of total PCB (OR = 0.81; 95% CI: 0.34-1.96 for highest vs lowest quartile) or specific congeners. The study confirmed the association with light skin colour (OR = 3.00; 95% CI: 1.91-4.73), cumulative lifetime UV exposure (OR = 2.56; 95% CI: 1.35-4.85) and high level of education (OR = 1.45; 95% CI: 1.03-2.05). This case-control study does not support the hypothesis of an association between current plasma levels of PCBs and CMM development in the general population.

Serum Non-Ceruloplasmin Non-Albumin Copper Elevation in Mild Cognitive Impairment and Dementia due to Alzheimer's Disease: A Case Control Study.

Several studies showed high serum copper levels in Alzheimer's disease (AD). The present study applied a newly developed method to detect serum copper free from proteins (free-Cu). Forty-four patients affected by dementia due to AD, thirty-six patients affected by mild cognitive impairment (MCI) due to AD, and twenty-eight healthy controls underwent clinical, cognitive, and MRI assessment. The new method showed higher free-Cu concentrations in MCI and dementia due to AD compared to controls (p < 0.0001). No correlation between copper levels, cognitive or MRI measures were found.

Ceruloplasmin replacement therapy ameliorates neurological symptoms in a preclinical model of aceruloplasminemia.

Aceruloplasminemia is a monogenic disease caused by mutations in the ceruloplasmin gene that result in loss of protein ferroxidase activity. Ceruloplasmin plays a role in iron homeostasis, and its activity impairment leads to iron accumulation in liver, pancreas, and brain. Iron deposition promotes diabetes, retinal degeneration, and progressive neurodegeneration. Current therapies mainly based on iron chelation, partially control systemic iron deposition but are ineffective on neurodegeneration. We investigated the potential of ceruloplasmin replacement therapy in reducing the neurological pathology in the ceruloplasmin-knockout (CpKO) mouse model of aceruloplasminemia. CpKO mice were intraperitoneal administered for 2 months with human ceruloplasmin that was able to enter the brain inducing replacement of the protein levels and rescue of ferroxidase activity. Ceruloplasmin-treated mice showed amelioration of motor incoordination that was associated with diminished loss of Purkinje neurons and reduced brain iron deposition, in particular in the choroid plexus. Computational analysis showed that ceruloplasmin-treated CpKO mice share a similar pattern with wild-type animals, highlighting the efficacy of the therapy. These data suggest that enzyme replacement therapy may be a promising strategy for the treatment of aceruloplasminemia.

Free copper in serum: An analytical challenge and its possible applications.

Copper (Cu), as an essential metal, plays a crucial role in biochemical reactions and in physiological regulations. Cu in plasma is mostly bound to proteins; about 65-90% of Cu is tightly binds with caeruloplasmin and the rest of Cu is loosely binds with albumin and transcuprein. A small but significant relatively "free" fraction, probably complexed with amino acids, is present at around 5% of the total concentration. We developed and validated a new method for direct measurement of free Cu in serum by ultrafiltration with AMICON®Ultra 100K device and determination with AAS. Also, we checked that there is no trace of albumin in the ultrafiltrates and we demonstrated the ultrafiltration of a known concentration of Cu added in artificial serum without albumin and, on the contrary, the retention of the Cu in artificial serum with albumin. The ultrafiltration procedure and the instrumental determination showed a good repeatability and a very low limit of detection (1µg/L). The method was applied to 30 healthy subjects, the mean value of the total Cu (994.8µg/L) is included in the normal range for healthy people and the values of free Cu (23.6µg/L) corresponding to 2.37% of the Cu total. The determination of free Cu by this simple and cheap method may be useful to measure the most bioavailable Cu fraction possibly implicated in neuro-degenerative and oxidative-stress related diseases.

Occupational exposure to polychlorinated biphenyls and risk of cutaneous melanoma: a meta-analysis.

The aim of this study was to carry out a meta-analysis of studies on exposure to polychlorinated biphenyls (PCBs) and the risk of malignant melanoma (MM). We searched Scopus, PubMed, and reference lists; among 807 potentially relevant articles, we selected those based on 12 populations. Data were extracted according to a standardized form; the Newcastle-Ottawa Scale was used to assess study quality. Meta-analyses were carried out according to fixed-effect and random-effects models. The fixed-effect summary relative risk (RR) for MM was 0.91 [95% confidence interval (CI): 0.82-1.00]; the random-effects summary RR was 1.05 (95% CI: 0.78-1.32). The random-effects summary RR from eight occupational cohorts was 1.13 (95% CI: 0.91-1.35) and that from four community-based studies was 0.84 (95% CI: 0.36-1.31). The quality of the studies and the methods for PCB exposure assessment did not influence the RR. These results do not support the hypothesis of an association between PCB exposure and the risk of MM.