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Background: Micrometric and nanometric particles are increasingly used in different fields and may exhibit variable toxicity levels depending on their physicochemical characteristics. The aim of this study was to determine the impact of the size parameter on cellular uptake and biological activity, working with well-characterized fluorescent particles. We focused our attention on macrophages, the main target cells of the respiratory system responsible for the phagocytosis of the particles. Methods: FITC fluorescent silica particles of variable submicronic sizes (850, 500, 250 and 150 nm) but with similar surface coating (COOH) were tailored and physico-chemically characterized. These particles were then incubated with the RAW 264.7 macrophage cell line. After microscopic observations (SEM, TEM, confocal), a quantitative evaluation of the uptake was carried out. Fluorescence detected after a quenching with trypan blue allows us to distinguish and quantify entirely engulfed fluorescent particles from those just adhering to the cell membrane. Finally, these data were compared to the in vitro toxicity assessed in terms of cell damage, inflammation and oxidative stress (evaluated by LDH release, TNF-α and ROS production respectively). Results and conclusion: Particles were well characterized (fluorescence, size distribution, zeta potential, agglomeration and surface groups) and easily visualized after cellular uptake using confocal and electron microscopy. The number of internalized particles was precisely evaluated. Size was found to be an important parameter regarding particles uptake and in vitro toxicity but this latter strongly depends on the particles doses employed. [ABSTRACT FROM AUTHOR]

Background: The use of micro- or nanometric particles is in full expansion for the development of new technologies. These particles may exhibit variable toxicity levels depending on their physicochemical characteristics. We focused our attention on macrophages (MA), the main target cells of the respiratory system responsible for the phagocytosis of the particles. The quantification of the amount of phagocytosed particles seems to be a major element for a better knowledge of toxicity mechanisms. The aim of this study was to develop a quantitative evaluation of uptake using both flow cytometry (FCM) and confocal microscopy to distinguish entirely engulfed fluorescent microsized particles from those just adherent to the cell membrane and to compare these data to in vitro toxicity assessments. Methods: Fluorescent particles of variable and well-characterised sizes and surface coatings were incubated with MA (RAW 264.7 cell line). Analyses were performed using confocal microscopy and FCM. The biological toxicity of the particles was evaluated [lactate dehydrogenase (LDH) release, tumor necrosis factor (TNF)-α, and reactive oxygen species (ROS) production]. Results and conclusion: Confocal imaging allowed visualization of entirely engulfed beads. The amount of phagocytic cells was greater for carboxylate 2-µm beads (49 ± 11%) than for amine 1-µm beads (18 ± 5%). Similarly, side scatter geometric means, reflecting cellular complexity, were 446 ± 7 and 139 ± 12, respectively. These results confirm that the phagocytosis level highly depends on the size and surface chemical groups of the particles. Only TNF-α and global ROS production varied significantly after 24-h incubation. There was no effect on LDH and H2O2 production. [ABSTRACT FROM AUTHOR]

Abstract: An 80-year-old man had to be operated for cutaneous neoplasia. Local anaesthesia with sedation was required. Preoperative examination revealed a pronounced albeit asymptomatic bradycardia. Electrocardiogram showed a complete atrioventricular block. Use of a pacemaker was discussed. Finally, surgery was performed uneventfully after transient reversal of the anticholinesterasic effects of galantamine administered in Alzheimer''s disease control over several hours with atropine. [Copyright &y& Elsevier]

Abstract: Concentrations of Cd, Cu, Pb and Zn in sediments of Egypt Bay in Hancock County, Maine, are elevated above background levels. The source of the contamination is Cu mining that occurred in the uplands adjacent to Egypt Stream between 1877 and 1885. Egypt Stream is a tributary to Egypt Bay. Egypt Bay is part of the Taunton Bay estuary system. The Hagan Mine was one of the mines extracting metals from the sulfide deposits in Downeast Maine north of Penobscot Bay. Metal concentrations were determined using ICP-AES after sample digestion with nitric acid. Soil collected from the coarse textured mine tailings pile contained elevated concentrations of Cd, Cu, Pb and Zn, but the majority of the surface soils at the Hagan Mine site were not contaminated. Estuary sediments from the surface to 100cm depth were collected in four locations within Egypt Bay. Below 40cm, metal concentrations in sediments were similar to those in uncontaminated upland soils. Metal concentrations in the estuary sediments between the surface and 26cm were above background levels. According to 210Pb dating, the sediment at 26–34cm depth was likely to have been deposited at the time the historic mines were in operation. Concentrations of Cd, Cu, Pb, and Zn in sediment from the 32–34cm depth interval are similar to concentrations in the upland soil sample from the mine tailings pile. Elevated Pb concentrations in sediments from the surface to 24cm are from atmospheric Pb deposition from anthropogenic sources. Sediment in the top 10cm of the estuary has been mixed both by the polychaete worm Nereis virens and by those harvesting the worms for sale as fish bait. [Copyright &y& Elsevier]

Purpose. – Multiple endocrine neoplasias (MEN) are autosomal dominant inherited syndromes characterized by the association of different glandular lesions in several members of the same kindred. The main clinical features of MEN 1 include primary hyperparathyroidism, pancreatic islet cell tumors and pituitary adenomas; less common features are adrenal adenomas, thymic and bronchial carcinoid tumors, lipomas and various cutaneous lesions. The MEN 2 syndromes (MEN 2A, MEN 2B and familial medullary thyroid carcinomas) are characterized by high penetrance of medullary thyroid carcinoma and differ in their variable expression of pheochromocytoma, hyperparathyroidism and other clinical features.Current knowledge and key points. – MEN 1 tumor suppressor gene encodes a nuclear protein, menin, which interacts with different regulation transcription factors. The MEN 2 syndromes are caused by germ-line mutations of the RET proto-oncogene, which encodes a transmembrane tyrosine kinase. Genetic testing for mutations in these 2 genes allows identification of individuals predisposed to the disease, early diagnosis, and clinical and therapeutic management.Future prospects and projects. – Fondamental approach will allow a best comprehension of physiopathogenic mechanisms of these disorders and the improvement of therapeutic management. [Copyright &y& Elsevier]

Objective The RET (rearranged during transfection) proto-oncogene G691S variant is over-represented in the germline of patients with sporadic medullary thyroid carcinoma (sMTC) vs. normal controls but so far is not associated with any medical or pathological features of the tumour. The aim of our study was to assess the influence of this variant on the age of onset, clinical, biological and pathological features of sMTC. Design and patients One hundred patients with histologically proven MTC, for whom the germline genetic analysis of RET was negative and medical records were available, were included in the study. Results Patients with the heterozygous GS variant or the homozygous SS variant ( n = 36) were on average 8·0 years younger than patients with the wild-type GG variant ( n = 64, mean age 43·9 vs. 51·9 years, P < 0·01). The former group did not differ from the wild-type group in terms of MTC size, prevalence of C-cell hyperplasia (CCH) or papillary thyroid carcinoma (PTC). However, the prevalence of an increased preoperative basal calcitonin (bCT) level (> 1000 pg/ml) was 2·75-fold higher in the patients with the GS or SS variant than in those with the wild-type variant ( P < 0·001). The proportion of patients with lymph node metastases was also higher in the former group ( P < 0·05). Multivariate analysis confirmed that the presence of the RET variant is independently associated with higher preoperative bCT values ( P = 0·011). Conclusions Our data demonstrate that the RET G691S variant could modulate the age of onset of sMTC as demonstrated previously for familial tumours. Moreover, this variant is an independent predictor of a higher basal calcitonin synthesis rate in patients with sMTC. [ABSTRACT FROM AUTHOR]

Pathogens can impact host survival, fecundity, and population dynamics even when no obvious disease is observed. Few baseline data on pathogen prevalence and diversity of caribou are available, which hampers our ability to track changes over time and evaluate impacts on caribou health. Archived blood samples collected from ten migratory caribou herds in Canada and two in Greenland were used to test for exposure to pathogens that have the potential to effect population productivity, are zoonotic or are emerging. Relationships between seroprevalence and individual, population, and other health parameters were also examined. For adult caribou, the highest overall seroprevalence was for alphaherpesvirus (49%, n = 722), pestivirus (49%, n = 572) and Neospora caninum (27%, n = 452). Lower seroprevalence was found for parainfluenza virus type 3 (9%, n = 708), Brucella suis (2%, n = 758), and Toxoplasma gondii (2%, n = 706). No animal tested positive for antibodies against West Nile virus (n = 418) or bovine respiratory syncytial virus (n = 417). This extensive multi-pathogen survey of migratory caribou herds provides evidence that caribou are exposed to pathogens that may have impacts on herd health and revealed potential interactions between pathogens as well as geographical differences in pathogen exposure that could be linked to the bio-geographical history of caribou. Caribou are a keystone species and the socio-economic cornerstone of many indigenous cultures across the North. The results from this study highlight the urgent need for a better understanding of pathogen diversity and the impact of pathogens on caribou health. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Toxicological risk is linked to the physico-chemical parameters that can be modified during incineration process. • The incineration can lead to chemical transformation of pristine nanofillers (i.e. transformation of boehmite into alumina). • in vitro cytotoxicity responses show that safe boehmite nanoparticles become toxic after incineration process. Abstract The number of products containing nanomaterials is increasing this last ten years. Information and literature about the end-of-life of nanocomposites often remains partial and does not address the overall fate and transformations of nanoparticles that may affect biological responses. This paper underlines that the physico-chemical features of nanoparticles can be modified by the incineration process and the available toxicological data on pristine nanofillers might not be relevant to assess the modified nanoparticles included in soot. Combustion tests have been performed at lab-scale using a cone calorimeter modified to collect fumes (particulate matter and gas phase) and have been characterized using various techniques. Nanocomposites selected were poly(ethylene vinyl acetate) containing Al-based nanoparticles, i.e. boehmites or alumina. Evaluations of in vitro cytotoxicity responses on pristine nanofillers, soot and residual ash, show that safe boehmite nanoparticles, become toxic due to a chemical modification after incineration process. [ABSTRACT FROM AUTHOR]

Abstract: Mackerel oil is prone to autooxidation because it has a high content of polyunsaturated fatty acids. Antioxidants therefore have to be added to the oil to control oxidation during processing. The effect of 50, 100, 250 and 500 parts per million (ppm) concentrations of α-tocopherol on the oxidation of unrefined mackerel oil samples (recovered by solvent extraction), was investigated at 30, 4 and −40°C over a period of 66 days by monitoring changes in peroxide values, conjugated diene content as well as levels of thiobarbituric acid reactive substances. There were significant differences (P <0.05) between treated and control samples at all the temperatures investigated for all the α-tocopherol concentrations over the storage period. Higher concentrations of α-tocopherol, i.e., 250 and 500ppm were less effective in controlling oxidation in the oils than lower α-tocopherol levels (50 and 100ppm). Oxidation was minimal at low temperatures as inferred from the methods used to assess autooxidation. Treatment of mackerel oil with 50 or 100ppm α-tocopherol at −40°C produced the lowest oxidation over the 66-day period and was considered as adequate levels of incorporation in crude mackerel oil to minimize oxidation. There was no significant difference (P >0.05) between the effects of 50 and 100ppm of α-tocopherol after 66 days. Fifty ppm of α-tocopherol is therefore regarded as the preferred concentration for controlling oxidation of mackerel oil on the basis of cost and efficacy. [Copyright &y& Elsevier]

Autism is a developmental disorder characterized by impairments in social interaction and communication associated with repetitive patterns of interest or behavior. Autism is highly influenced by genetic factors. Genome-wide linkage and candidate gene association approaches have been used to try and identify autism genes. A few loci have repeatedly been reported linked to autism. Several groups reported evidence for linkage to a region on chromosome 16p. We have applied a direct physical identity-by-descent (IBD) mapping approach to perform a high-density (0.85 megabases) genome-wide linkage scan in 116 families from the AGRE collection. Our results confirm linkage to a region on chromosome 16p with autism. High-resolution single-nucleotide polymorphism (SNP) genotyping and analysis of this region show that haplotypes in the protein kinase c-beta gene are strongly associated with autism. An independent replication of the association in a second set of 167 trio families with autism confirmed our initial findings. Overall, our data provide evidence that the PRKCB1 gene on chromosome 16p may be involved in the etiology of autism.Molecular Psychiatry (2005) 10, 950–960. doi:10.1038/sj.mp.4001704; published online 19 July 2005 [ABSTRACT FROM AUTHOR]

The melting temperature of water is depressed under pressure from 0 °C at atmospheric pressure down to −22 °C at 220 MPa. This property can be used for rapid thawing of foods and maintaining better quality in the thawed product. High pressure thawing of two selected sea foods was evaluated in comparison to thawing in water at atmospheric pressure: aiguillat (Spiny dogfish or Squalus acanthias) and scallops (Pecten irradians). Drip volume from thawing and drip volume from subsequent cooking were measured for this purpose. The influence of the high pressure residence time was also studied. Results showed that for both products, the thawing drip was significantly reduced when thawed under high pressure. Optimal results were obtained at 150 MPa. Total drip including thawing and cooking was higher for scallops and smaller for aiguillat with high pressure thawing in comparison to atmospheric thawing. Increasing the duration of the pressure had a significant effect on reducing the drip volume. These results showed that mass transfer might occur under high pressure between drip and product after thawing was completed. [Copyright &y& Elsevier]