Accumulation of α-synuclein in the bowel of patients in the pre-clinical phase of Parkinson's disease.

Parkinson's disease primarily affects the central nervous system, but autopsy and small patient studies have revealed autonomic nervous system pathology in most cases. We looked for α-synuclein pathology in routinely acquired biopsies from patients and matched controls. Immunocytochemistry was performed and assessed blind to the clinical diagnoses. One hundred and seventeen gastrointestinal tissue samples from 62 patients, and 161 samples from 161 controls, were examined. Twelve biopsies from seven patients showed accumulation of α-synuclein within mucosal and submucosal nerve fibres, and ganglia, which was more extensive with an antibody to phosphorylated, than with an antibody to non-phosphorylated, α-synuclein. These included gastric, duodenal and colonic biopsies, and were taken up to 8 years prior to the onset of motor symptoms. All patients with positive biopsies had early autonomic symptoms and all controls were negative. This large scale study demonstrates that accumulation of α-synuclein in the gastrointestinal tract is a highly specific finding that could be used to confirm a clinical diagnosis of Parkinson's disease. We have shown that α-synuclein accumulation occurs prior to the onset of motor symptoms in the upper, as well as the lower gastrointestinal tract, remains present in serial biopsies until the onset of motor symptoms and is predominantly composed of phosphorylated α-synuclein. Accumulation of α-synuclein in the bowel therefore offers an accessible biomarker which allows further study of the early stages of the disease and could be of value in the assessment of disease modifying treatments.

Therapeutic delivery systems for rheumatoid arthritis based on hydrogel carriers.

Rheumatoid arthritis (RA) is an autoimmune disease suffered by millions of people worldwide. It can significantly affect the patient's quality of life by damaging not only the joints but also organs such as the lungs and the heart. RA is normally treated using nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease-modifying antirheumatic drugs (DMARDs), and biologics. These active agents often cause side effects and offer low efficacy due to their lack of specificity and limited retention time. In an attempt to improve RA treatments, hydrogel-based systems have been proposed as drug delivery carriers. Due to their exceptional adaptability and biocompatibility, hydrogels have the potential of enhancing the delivery of RA therapy through different administration routes in an efficient and effective manner. In this review, we explore the application of hydrogel systems as potential carriers in RA treatment. Additionally, we discuss recent work in the field and highlight the required hydrogel properties, depending on the administration route. The outstanding potential of hydrogel systems as carriers for RA was demonstrated; however, there is extensive research yet to be done to improve available treatments for RA.

Assessing the quality of footwear marks recovered from simulated graves.

Footwear marks are one of the most frequently encountered evidence types recovered from a crime scene and can provide valuable scene intelligence regarding potential suspects. It has been acknowledged that impressions of footwear and tools can be recovered from graves, but previous studies have only focused on tool mark recovery. This has led to a lack of published information regarding footwear mark recovery from graves. It is therefore important to demonstrate whether the recovery of footwear marks is feasible and, if so, under what conditions this can be achieved. To address recovery, this study, placed 60 three dimensional (3D) impressions of footwear marks within 60 simulated graves. This was done to assess time (1, 2, 4 months) and at known depths (20, 30, 40 cm). The footwear marks within the graves were covered with clothing or left uncovered. The shoe's design patterns were grouped and counted in a photographic comparison between the 3D footwear impressions, placed within the test-pits, and any recovered impressions. A grading system was adapted by the authors to score the quality of footwear impressions observed during recovery. The results demonstrate that the preservation and recovery of footwear impressions from graves is feasible. The simulated graves covered with clothing showed better preservation of footwear impressions, but there was no clear evidence that time or depth had an effect. The authors note that careful consideration and vigilant excavation skills are needed when excavating graves which may bear potential footwear marks, as their recovery will lead to an increased amount of intelligence that can link suspects to homicide scenes.