Multi-platform quantitation of alpha-synuclein human brain proteoforms suggests disease-specific biochemical profiles of synucleinopathies.

Based on immunostainings and biochemical analyses, certain post-translationally modified alpha-synuclein (aSyn) variants, including C-terminally truncated (CTT) and Serine-129 phosphorylated (pSer129) aSyn, are proposed to be involved in the pathogenesis of synucleinopathies such as Parkinson's disease with (PDD) and without dementia (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). However, quantitative information about aSyn proteoforms in the human brain in physiological and different pathological conditions is still limited. To address this, we generated sequential biochemical extracts of the substantia nigra, putamen and hippocampus from 28 donors diagnosed and neuropathologically-confirmed with different synucleinopathies (PD/PDD/DLB/MSA), as well as Alzheimer's disease, progressive supranuclear palsy, and aged normal subjects.

The subcellular arrangement of alpha-synuclein proteoforms in the Parkinson's disease brain as revealed by multicolor STED microscopy.

Various post-translationally modified (PTM) proteoforms of alpha-synuclein (aSyn)-including C-terminally truncated (CTT) and Serine 129 phosphorylated (Ser129-p) aSyn-accumulate in Lewy bodies (LBs) in different regions of the Parkinson's disease (PD) brain. Insight into the distribution of these proteoforms within LBs and subcellular compartments may aid in understanding the orchestration of Lewy pathology in PD. We applied epitope-specific antibodies against CTT and Ser129-p aSyn proteoforms and different aSyn domains in immunohistochemical multiple labelings on post-mortem brain tissue from PD patients and non-neurological, aged controls, which were scanned using high-resolution 3D multicolor confocal and stimulated emission depletion (STED) microscopy.

Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy.

Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson's disease (PD). Previously, we reported the structure of alpha-synuclein fibrils (residues 1-121), composed of two protofibrils that are connected via a densely-packed interface formed by residues 50-57 (Guerrero-Ferreira, eLife 218;7:e36402). We here report two new polymorphic atomic structures of alpha-synuclein fibrils termed polymorphs 2a and 2b, at 3.

Cryo-EM structure of alpha-synuclein fibrils.

Parkinson's disease is a progressive neuropathological disorder that belongs to the class of synucleinopathies, in which the protein alpha-synuclein is found at abnormally high concentrations in affected neurons. Its hallmark are intracellular inclusions called Lewy bodies and Lewy neurites. We here report the structure of cytotoxic alpha-synuclein fibrils (residues 1-121), determined by cryo-electron microscopy at a resolution of 3.

Oxidative stress-elevated high gamma glutamyl transferase levels, and aging, intake of tropical food plants, migration and visual disability in Central Africans.

Aim: To investigate the independent pathogenic role of high serum gamma-glutamyl transferase (GGT) levels, sociodemographic data, dietary and environmental risk factors for visual disability (VD).

Methods: This was a case-control study, run in 200 black Congolese patients managed in Saint Joseph Hospital Ophthalmology Division from Kinshasa town. Logistic regression model was used to identify determinants of VD (n=58) among sex, age, cigarette smoking, alcohol abuse, rural-urban migration, education levels, aging ≥60 years, intake of red Beans, Safou fruit and Taro leaves, lipid profile, residence, socioeconomic status, and GGT.

Effects of biomarkers of oxidative stress damage on prevalence and severity of visual disability among black Central Africans.

Background: Because of the demographic transition, lifestyle changes, urbanization, and nutrition transition, Central Africans are at higher risk of ocular diseases associated with oxidative stress and visual disability. This study aimed to estimate the normal values of oxidant status defined by oxidized low-density lipoprotein (Ox-LDL), 8-Isoprostane and 8-hydroxy-deoxyguanosine (8-OHdG) and to determine their pathogenic role in the prevalence and the severity of visual disability among these black Africans.

Methods: This was a cross-sectional study, run in a case-control study randomly selected from Kinshasa province, DR Congo.

[Return to sports following concussion].

The diagnosis of concussion during sports activity is since years one of the most challenging endeavours for all sports physician working on the field. In the last years, more then 20 management guidelines regarding return to play issues have been published. Current research has prompted a revaluation and revision of prior guidelines with the aim to create an "unité de doctrine" in concussion management strategies.

[Test for the determination of endurance fitness and training style in young ice hockey players].

A test similar to the Conconi test was developed by the authors, to be used specifically with ice hockey players. The aim was to measure the aerobic performance capacity of these athletes. The results give us on one hand informations on the actual performance potential of these sportsmen.

[The jejunal tube: a possibility for early postoperative enteral feeding].

Interest in enteral nutrition has recently been increasing. Enteral feeding is more physiological than parenteral nourishment; it is more effective, there are fewer complications, and it has the advantage of being cheaper. Enteral feeding is performed via nasogastric, nasoduodenal or transcutaneous catheter.

[Colonic complications after renal transplantation (author's transl)].

From December 1964 to June 1980, 569 kidney allotransplants were performed in 524 patients at the University Hospital in Zurich. Necrokidneys were used exclusively. Twelve of these patients exhibited severe colonic complications: four perforations (1 perforated diverticulitis of the sigmoid, 1 perforation of the cecum during cytomegalovirus infection, 2 cases of ischemic colitis), 5 cases of ischemic colitis without perforation, and 3 patients with erosive colitis.

Transplantation of the small intestine. An experimental study in young minipigs.

An experimental study on small intestinal transplantation on 82 young minipigs is reported. The selected experimental model allows for early recognition of complications in the graft. A monitoring system, based on multiple sequential mucosal suction biopsies is presented, Transplanted segments up to 120 cm were rejected in similar way as are other organs.