Intra-household agreement of urinary elemental concentrations in Tanzania and Kenya: potential surrogates in case–control studies

Element deficiencies and excesses play important roles in non-communicable disease aetiology. When investigating their roles in epidemiologic studies without prospective designs, reverse-causality limits the utility of transient biomarkers in cases. This study aimed to investigate whether surrogate participants may provide viable proxies by assessing concentration correlations within households. We obtained spot urine samples from 245 Tanzanian and Kenyan adults (including 101 household pairs) to investigate intra-household correlations of urinary elements (As, Ba, Ca, Cd, Co, Cs, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, S, Se, Sr, Tl, V and Zn) and concentrations (also available for: Bi, Ce, Sb, Sn and U) relative to external population-levels and health-based values. Moderate-strong correlations were observed for As (r = 0.65), Cs (r = 0.67), Li (r = 0.56), Mo (r = 0.57), Se (r = 0.68) and Tl (r = 0.67). Remaining correlations were <0.41. Median Se concentrations in Tanzania (29 µg/L) and Kenya (24 µg/L) were low relative to 5738 Canadians (59 µg/L). Exceedances (of reference 95th percentiles) were observed for: Co, Mn, Mo, Ni and U. Compared to health-based values, exceedances were present for As, Co, Mo and Se but deficiencies were also present for Mo and Se. For well correlated elements, household members in East African settings provide feasible surrogate cases to investigate element deficiencies/excesses in relation to non-communicable diseases

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Dependence of gold nanoparticle radiosensitization on functionalizing layer thickness

Gold nanoparticles functionalized with polyethylene glycol of different chain lengths are used to determine the influence of the capping layer thickness on the radiosensitizing effect of the particles. The size variations in organic coating, built up with polyethylene glycol polymers of molecular weight 1-20 kDa, allow an evaluation of the decrease in dose enhancement percentages caused by the gold nanoparticles at different radial distances from their surface. With localized eradication of malignant cells as a primary focus, radiosensitization is most effective after internalization in the nucleus. For this reason, we performed controlled radiation experiments, with doses up to 20 Gy and particle diameters in a range of 5-30 nm, and studied the relaxation pattern of supercoiled DNA. Subsequent gel electrophoresis of the suspensions was performed to evaluate the molecular damage and consecutively quantify the gold nanoparticle sensitization. In conclusion, on average up to 58.4% of the radiosensitizing efficiency was lost when the radial dimensions of the functionalizing layer were increased from 4.1 to 15.3 nm. These results serve as an experimental supplement for biophysical simulations and demonstrate the influence of an important parameter in the development of nanomaterials for targeted therapies in cancer radiotherapy

Growth of functional cranial components in rats submitted to intergenerational undernutrition

The aim of the present study was to discover how intergenerational undernutrition affects the growth of major and minor functional cranial components in two generations of rats. Control animals constituted the parental generation (P). The undernourished generations (F1 and F2) were fed 75% of the control diet. Animals were X-rayed every 10 days from 20 to 100 days of age. The length, width and height of the major (neurocranium and splanchnocranium) and minor (anterior-neural, middle-neural, posterior-neural, otic, respiratory, masticatory and alveolar) cranial components were measured on each radiograph. Volumetric indices were calculated to estimate size variations of these components. Data were processed using the Kruskal–Wallis and Kolmogorov–Smirnov tests for two samples. Impairment in splanchnocranial and neurocranial growth was found, the latter being more affected than the former in F1. Comparison between F2 and F1 animals showed cumulative effects of undernutrition in both major and minor components (anterior-neural, respiratory, masticatory and alveolar in males, and middle-neural and respiratory in females). Such differential effects on minor components may reflect a residual mechanical strain resulting from the linkage between components. This phenomenon was clearly observed in the neurocranium and could be understood as an adaptive response to the demands of the associated functional matrices

Occupational and consumer risk estimates for nanoparticles emitted by laser printers

Several studies have reported laser printers as significant sources of nanosized particles (&lt;0.1 &mu;m). Laser printers are used occupationally in office environments and by consumers in their homes. The current work combines existing epidemiological and toxicological evidence on particle-related health effects, measuring doses as mass, particle number and surface area, to estimate and compare the potential risks in occupational and consumer exposure scenarios related to the use of laser printers. The daily uptake of laser printer particles was estimated based on measured particle size distributions and lung deposition modelling. The obtained daily uptakes (particle mass 0.15&ndash;0.44 &mu;g d&minus;1; particle number 1.1&ndash;3.1 &times; 109 d&minus;1) were estimated to correspond to 4&ndash;13 (mass) or 12&ndash;34 (number) deaths per million persons exposed on the basis of epidemiological risk estimates for ambient particles. These risks are higher than the generally used definition of acceptable risk of 1 &times; 10&minus;6, but substantially lower than the estimated risks due to ambient particles. Toxicological studies on ambient particles revealed consistent values for lowest observed effect levels (LOELs) which were converted into equivalent daily uptakes using allometric scaling. These LOEL uptakes were by a factor of about 330&ndash;1,000 (mass) and 1,000&ndash;2,500 (particle surface area) higher than estimated uptakes from printers. This toxicological assessment would indicate no significant health risks due to printer particles. Finally, our study suggests that particle number (not mass) and mass (not surface area) are the most conservative risk metrics for the epidemiological and toxicological risks presented here, respectively