Occupational risk of nano-biomaterials: Assessment of nano-enabled magnetite contrast agent using the BIORIMA Decision Support System.

The assessment of the safety of nano-biomedical products for patients is an essential prerequisite for their market authorization. However, it is also required to ensure the safety of the workers who may be unintentionally exposed to the nano-biomaterials (NBMs) in these medical applications during their synthesis, formulation into products and end-of-life processing and also of the medical professionals (e.g., nurses, doctors, dentists) using the products for treating patients. There is only a handful of workplace risk assessments focussing on NBMs used in medical applications. Our goal is to contribute to increasing the knowledge in this area by assessing the occupational risks of magnetite (Fe3O4) nanoparticles coated with PLGA-b-PEG-COOH used as contrast agent in magnetic resonance imaging (MRI) by applying the software-based Decision Support System (DSS) which was developed in the EU H2020 project BIORIMA. The occupational risk assessment was performed according to regulatory requirements and using state-of-the-art models for hazard and exposure assessment, which are part of the DSS. Exposure scenarios for each life cycle stage were developed using data from literature, inputs from partnering industries and results of a questionnaire distributed to healthcare professionals, i.e., physicians, nurses, technicians working with contrast agents for MRI. Exposure concentrations were obtained either from predictive exposure models or monitoring campaigns designed specifically for this study. Derived No-Effect Levels (DNELs) were calculated by means of the APROBA tool starting from in vivo hazard data from literature. The exposure estimates/measurements and the DNELs were used to perform probabilistic risk characterisation for the formulated exposure scenarios, including uncertainty analysis. The obtained results revealed negligible risks for workers along the life cycle of magnetite NBMs used as contrast agent for the diagnosis of tumour cells in all exposure scenarios except in one when risk is considered acceptable after the adoption of specific risk management measures. The study also demonstrated the added value of using the BIORIMA DSS for quantification and communication of occupational risks of nano-biomedical applications and the associated uncertainties.

Particle release from refit operations in shipyards: Exposure, toxicity and environmental implications.

European harbours are known to contribute to air quality degradation. While most of the literature focuses on emissions from stacks or logistics operations, ship refit and repair activities are also relevant aerosol sources in EU harbour areas. Main activities include abrasive removal of filler and spray painting with antifouling coatings/primers/topcoats. This work aimed to assess ultrafine particle (UFP) emissions from ship maintenance activities and their links with exposure, toxicity and health risks for humans and the aquatic environment. Aerosol emissions were monitored during mechanical abrasion of surface coatings under real-world operating conditions in two scenarios in the Mallorca harbour (Spain). Different types of UFPs were observed: (1) highly regular (triangular, hexagonal) engineered nanoparticles (Ti-, Zr-, Fe-based), embedded as nano-additives in the coatings, and (2) irregular, incidental particles emitted directly or formed during abrasion. Particle number concentrations monitored were in the range of industrial activities such as drilling or welding (up to 5 ∗ 105/cm3, mean diameters <30 nm). The chemical composition of PM4 aerosols was dominated by metallic tracers in the coatings (Ti, Al, Ba, Zn). In vitro toxicity of PM2 aerosols evidenced reduced cell viability and a moderate potential for cytotoxic effects. While best practices (exhaust ventilation, personal protective equipment, dust removal) were in place, it is unlikely that exposures and environmental release can be fully avoided at all times. Thus, it is advisable that health and safety protocols should be comprehensive to minimise exposures in all types of locations (near- and far-field) and periods (activity and non-activity). Potential release to coastal surface waters of metallic engineered and incidental nanomaterials, as well as fine and coarse particles (in the case of settled dust), should be assessed and avoided.

Effectiveness of ustekinumab in patients with psoriatic arthritis in a real-world, multicenter study.

OBJECTIVE: To assess the effectiveness and survival of ustekinumab (UST) among patients with psoriatic arthritis (PsA) treated under routine clinical care. METHODS: Multicenter study. Epidemiological and clinical data was collected through electronic medical records of all patients with PsA who started UST in 15 hospitals of Spain. RESULTS: Two hundred and one patients were included, 130 (64.7%) with 45 mg and 71 (35.3%) with 90 mg. One hundred and thirty one patients (65.2%) had previously received another biological therapy. The median baseline DAS 28 ESR was 3.99, and Psoriasis Area and Severity Index (PASI) was 3. Overall, there was a significant decrease in DAS66/68 CRP, swollen joint count (SJC), tender joint count (TJC), and PASI in the first month of treatment, with earlier improvement in skin (PASI) than joints outcomes. Survival was numerically lower in patients with UST 45 mg (58.1%) than 90 mg (76.1%), although significant differences were not found (p = 0.147). When comparing naïve and < 1 TNF blocker versus > 2 TNF blocker-experienced patients, a significantly earlier response was seen in the former group regarding SJC (p = 0.029) at 1 month. Fifty-one patients (25.3%) stopped UST due to joint inefficacy and 4 patients due to adverse events (1.9%). Drug survival was significantly better in patients with fewer lines of previous biological agents (p = 0.003 for < 1 TNF blocker versus > 2 TNF blocker users). CONCLUSIONS: UST was effective in PsA patients in a routine clinical care setting. Patients with UST 90 mg and fewer lines of previous biologics achieved better and faster responses. Key Points • Largest cohort of patients with PsA in treatment with UST with specific rheumatological indication. • First cohort of patients with PsA comparing effectiveness of UST according to 45/90 mg dose.

Compostability assessment of nano-reinforced poly(lactic acid) films.

Nanomaterials can provide plastics with great advantages on mechanical and active properties (i.e. release and capture of specific substances). Therefore, packaging is expected to become one of the leading applications for these substances by 2020. There are some applications already in the market. Nevertheless, there is still some areas under development. A key issue to be analyzed is the end-of-life of these materials once they become waste, and specifically when nanomaterials are used in biodegradable products. The present study evaluated the disintegration, biodegradability, and ecotoxicity of poly(lactic acid) films reinforced with the three following nanomaterials: (1) montmorillonite modified with an ammonium quaternary salt, (2) calcium carbonate and (3) silicon dioxide. Results on disintegration showed that films completely disintegrated into visually indistinguishable residues after 6-7weeks of incubation in composting environment. Moreover, no differences were observed in the evolution of the bioresidue with respect to color, aspect, and odor in comparison with the control. It was also observed that nanomaterials did not significantly reduce the level of biodegradability of PLA (p>0.05). In fact, biodegradation was higher, without finding significant differences (p>0.05), in all the nano-reinforced samples with respect to PLA after 130days in composting (9.4% in PLA+Nano-SiO2; 34.0% in PLA+Clay1; 48.0% in PLA+Nano-CaCO3). Finally, no significant differences (p>0.05) in ecotoxicity in plants were observed as a result of the incorporation of nanoparticles in the PLA matrix.

Correlación entre la densiometría ósea (DEXA) de cadera y columna lumbar con la de falange (ACCUDEXA). Valoración de la densitometría de falange como herramienta diagnóstica o de cribado / Correlation between bone densiometry (DEXA) of the lumbar spine and femoral neck with phalangeal density (ACCUDEXA®). Evaluation of phalangeal densitometry as a diagnostic and screening tool

Objetivos: 1. Evaluar la correlación entre la densitometría de cadera y columna lumbar, medida con densitómetro dexa, con la de falange, medida con densitómetro Accudexa®. 2. Analizar la utilidad del densitómetro de falange Accudexa®, como herramienta diagnóstica o de cribado. Métodos: Realizamos densitometría de falange a 207 pacientes a quienes se había hecho densitometría de cadera y columna lumbar en los 3 meses previos. Resultados: La correlación entre la densidad mineral ósea (DMO) (g/cm2) de falange y cuello femoral es de 0,568 y entre falange y columna lumbar, de 0,531. Esta correlación no es inferior a la hallada entre la columna lumbar y la cadera. La sensibilidad y especificidad de la densitometría de falange con una t-score inferior a -2,5 en falange, es de 25,9 y 94,8, respectivamente. El mejor corte como herramienta diagnóstica lo proporciona una t-score en falange de -1 desviación estándar (DE), con la que se obtiene una sensibilidad de 70,4 y una especificidad de 73,2. Con distintos cortes de la t-score en falange hallamos que el intervalo -0,5 a -1,9 se puede usar como herramienta de cribado: por debajo de -1,9 la especificidad es del 90,7 por ciento, y por debajo de -0,5 la sensibilidad es del 89,8 por ciento. Realizando densitometría de cadera y columna sólo cuando los valores de t de falange están comprendidos en este intervalo, en nuestra serie habríamos ahorrado el 55 por ciento de las densitometrías axiales. Conclusiones: 1. La correlación entre la DMO de cadera y columna lumbar con la de falange es moderada. 2. Como uso diagnóstico, el mejor corte de la t-score de la densitometría de falange es -1 DE. 3. Como herramienta de cribado, el intervalo de los valores de t de falange comprendidos entre Correlación entre la densitometría ósea (DEXA) de cadera y columna lumbar con la de falange (ACCUDEXA). (AU)

Circulating CD8+ T cells in polymyalgia rheumatica and giant cell arteritis: a review.

BACKGROUND AND OBJECTIVE: During the last few years, there have been several studies on T cell subsets in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), with conflicting results. Whereas some authors have found normal values of circulating CD8+ T cells, others have found a decreased number. Furthermore, in some studies, the level of CD8+ cells was found to be related to disease activity, and it has been proposed that a decrease of CD8+ T cells be used as a diagnostic criterion for PMR. The purpose of our study was to determine the value of assessing T cell subsets in PMR and GCA. METHODS: T lymphocyte subsets were determined by flow cytometry using a whole blood lysis technique in the following groups: 28 PMR and 6 GCA patients before corticosteroid treatment, 20 PMR and 12 GCA patients in clinical remission with steroid treatment, 55 PMR patients in remission without steroid treatment, 17 rheumatoid arthritis (RA) patients before treatment, and 18 age-matched controls with noninflammatory conditions. Total white cell, lymphocyte, and platelet counts, hemoglobin, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured by routine techniques. Comparisons were made by the Student's t-test and the Mann-Whitney test. A MEDLINE database search for studies published between 1983 and 1997 was performed. RESULTS: Compared with noninflammatory controls, CD8+ T cells were not reduced before steroid treatment in patients with active PMR/GCA in proportion (P =.7) or absolute numbers (P =.1). Patients with active disease had significantly lower hemoglobin levels and higher platelet counts, CRP, and ESR than noninflammatory controls (P <.05). When compared with active RA, CD8+ T cells were not reduced in patients with active PMR in proportion (P =.5) or absolute numbers (P =.2). Between these two groups, RA patients were significantly younger (P =.003) and had lower ESR values (P =.003). We did not find significant differences between patients with active PMR/GCA and those in remission with steroid therapy, except for the lower hemoglobin levels and higher platelet count, CRP, and ESR in the active disease group (P <.05). The same results were found when patients with active disease were compared with PMR in remission and no longer on steroid therapy, the only significant differences were those parameters reflecting the acute phase response (hemoglobin levels, platelet count, CRP and ESR). CONCLUSIONS: This study does not confirm the previous findings that the proportion or number of circulating CD8+ T cells are reduced in patients with active PMR/GCA. The utility of the determination of CD8+ T cells for diagnostic and prognostic purpose should be evaluated in a large multicenter study.