The Personalized Parkinson Project: examining disease progression through broad biomarkers in early Parkinson's disease.

BACKGROUND: Our understanding of the etiology, pathophysiology, phenotypic diversity, and progression of Parkinson's disease has stagnated. Consequently, patients do not receive the best care, leading to unnecessary disability, and to mounting costs for society. The Personalized Parkinson Project (PPP) proposes an unbiased approach to biomarker development with multiple biomarkers measured longitudinally. Our main aims are: (a) to perform a set of hypothesis-driven analyses on the comprehensive dataset, correlating established and novel biomarkers to the rate of disease progression and to treatment response; and (b) to create a widely accessible dataset for discovery of novel biomarkers and new targets for therapeutic interventions in Parkinson's disease. METHODS/DESIGN: This is a prospective, longitudinal, single-center cohort study. The cohort will comprise 650 persons with Parkinson's disease. The inclusion criteria are purposely broad: age ≥ 18 years; and disease duration ≤5 years. Participants are followed for 2 years, with three annual assessments at the study center. Outcomes include a clinical assessment (including motor and neuro-psychological tests), collection of biospecimens (stool, whole blood, and cerebrospinal fluid), magnetic resonance imaging (both structural and functional), and ECG recordings (both 12-lead and Holter). Additionally, collection of physiological and environmental data in daily life over 2 years will be enabled through the Verily Study Watch. All data are stored with polymorphic encryptions and pseudonyms, to guarantee the participants' privacy on the one hand, and to enable data sharing on the other. The data and biospecimens will become available for scientists to address Parkinson's disease-related research questions. DISCUSSION: The PPP has several distinguishing elements: all assessments are done in a single center; inclusion of "real life" subjects; deep and repeated multi-dimensional phenotyping; and continuous monitoring with a wearable device for 2 years. Also, the PPP is powered by privacy and security by design, allowing for data sharing with scientists worldwide respecting participants' privacy. The data are expected to open the way for important new insights, including identification of biomarkers to predict differences in prognosis and treatment response between patients. Our long-term aim is to improve existing treatments, develop new therapeutic approaches, and offer Parkinson's disease patients a more personalized disease management approach. TRIAL REGISTRATION: Clinical Trials NCT03364894 . Registered December 6, 2017 (retrospectively registered).

Skin and liver diseases induced in flounder (Platichthys flesus) after long-term exposure to contaminated sediments in large-scale mesocosms.

Disease development in flounder (Platichthys flesus) was studied over a period of 3 years in three large mesocosms (40 m x 40 m x 3 m). Two of the mesocosms contained clean sand and the third, sharing a common water circulation with one of the clean-sand mesocosms, was stocked with contaminated dredged spoil. In this way, one of the clean-sand mesocosms was indirectly polluted via the water phase, and analysis of contaminant concentrations in sediments and flounder tissues showed that it had a status intermediate between the other two. Random samples of the flounder populations from the indirectly polluted and reference mesocosms were examined every 2 months for epidermal diseases (lymphocystis, skin ulcers, fin rot) and then released. In addition, every 6 months, random samples of fish from all three mesocosms were sacrificed for histological and chemical investigation. With regard to the development of epidermal disease, the results showed little difference between the reference mesocosm and the indirectly polluted mesocosm, with the exception that lymphocystis was significantly elevated in the indirectly polluted mesocosm. Although pollution may be a risk factor in the etiology of this disease, such a relationship would probably be obscured under field conditions due to variation arising from other factors. Histopathological analysis of the livers revealed in total four cases of hepatocellular adenoma (1.5% of sampled population) in fish from the polluted mesocosms, the first occurring after 2.5 years of exposure in fish from the indirectly polluted mesocosm. Furthermore, several other liver lesions, including foci of cellular alteration and hydropic vacuolated lesions, developed during the course of the experiment before tumor formation was apparent. Prevalences of these conditions were very much lower in the reference mesocosm than in the two polluted mesocosms. Densities of melanomacrophage centers in the liver showed a similar trend. The findings clearly indicate that long-term exposure to chemically contaminated dredged spoil can induce liver neoplasia and other liver lesions in flounder at contaminant levels comparable to those found in the natural environment.