Impact of aging on animal models of Parkinson's disease.

Aging is the biggest risk factor for developing Parkinson's disease (PD), the second most common neurodegenerative disorder. Several animal models have been developed to explore the pathophysiology underlying neurodegeneration and the initiation and spread of alpha-synuclein-related PD pathology, and to investigate biomarkers and therapeutic strategies. However, bench-to-bedside translation of preclinical findings remains suboptimal and successful disease-modifying treatments remain to be discovered. Despite aging being the main risk factor for developing idiopathic PD, most studies employ young animals in their experimental set-up, hereby ignoring age-related cellular and molecular mechanisms at play. Consequently, studies in young animals may not be an accurate reflection of human PD, limiting translational outcomes. Recently, it has been shown that aged animals in PD research demonstrate a higher susceptibility to developing pathology and neurodegeneration, and present with a more disseminated and accelerated disease course, compared to young animals. Here we review recent advances in the investigation of the role of aging in preclinical PD research, including challenges related to aged animal models that are limiting widespread use. Overall, current findings indicate that the use of aged animals may be required to account for age-related interactions in PD pathophysiology. Thus, although the use of older animals has disadvantages, a model that better represents clinical disease within the elderly would be more beneficial in the long run, as it will increase translational value and minimize the risk of therapies failing during clinical studies. Furthermore, we provide recommendations to manage the challenges related to aged animal models.

Passive Dosing of Petroleum and Essential Oil UVCBs-Whole Mixture Toxicity Testing at Controlled Exposure.

Petroleum products and essential oils are produced and used in large amounts and are categorized as "Substances of Unknown or Variable composition, Complex reaction products or Biological materials (UVCBs)." These UVCBs are notorious difficult-to-test substances, since they are complex mixtures of hydrophobic and volatile compounds. This study introduces two passive dosing (PD) approaches for whole UVCB toxicity testing: (1) headspace PD applies the UVCB and purified lipid oil as a donor to control exposure via the headspace and (2) silicone rod PD applies UVCB-loaded silicone rods to control exposure via an aqueous test medium and headspace. Headspace gas chromatography-mass spectrometry measurements were used to cross-validate the approaches at the saturation level and to confirm exposure and maintain mixture composition at varying donor concentration levels. Both approaches were applied to whole-mixture toxicity tests of petroleum and essential oil UVCBs with daphnia and algae. Finally, the observed toxicity was linked to concentrations in the donor and in lipid membranes at equilibrium with the donors. Dose-response curves were similar across the dosing approaches and tested species for petroleum products but differed by an order of magnitude between essential oils and PD systems. All observed toxic effects were consistent with baseline toxicity, and no excess mixture toxicity was observed.

Insufficient access to harm reduction measures in prisons in 5 countries (PRIDE Europe): a shared European public health concern.

BACKGROUND: Prisoners constitute a high-risk population, particularly for infectious diseases. The aim of this study was to estimate the level of infectious risk in the prisons of five different European countries by measuring to what extent the prison system adheres to WHO/UNODC recommendations. METHODS: Following the methodology used in a previous French survey, a postal/electronic questionnaire was sent to all prisons in Austria, Belgium, Denmark and Italy to collect data on the availability of several recommended HIV-HCV prevention interventions and HBV vaccination for prisoners. A score was built to compare adherence to WHO/UNODC recommendations (considered a proxy of environmental infectious risk) in those 4 countries. It ranged from 0 (no adherence) to 12 (full adherence). A second score (0 to 9) was built to include data from a previous French survey, thereby creating a 5-country comparison. RESULTS: A majority of prisons answered in Austria (100 %), France (66 %) and Denmark (58 %), half in Belgium (50 %) and few in Italy (17 %), representing 100, 74, 89, 47 and 23 % coverage of the prison populations, respectively. Availability of prevention measures was low, with median adherence scores ranging from 3.5 to 4.5 at the national level. These results were confirmed when using the second score which included France in the inter-country comparison. Overall, the adherence score was inversely associated with prison overpopulation rates (p = 0.08). CONCLUSIONS: Using a score of adherence to WHO/UNODC recommendations, the estimated environmental infectious risk remains extremely high in the prisons of the 5 European countries assessed. Public health strategies should be adjusted to comply with the principle of equivalence of care and prevention with the general community.