Serum neuronal exosomes predict and differentiate Parkinson's disease from atypical parkinsonism

ObjectiveParkinson's disease is characterised neuropathologically by α-synuclein aggregation. Currently, there is no blood test to predict the underlying pathology or distinguish Parkinson's from atypical parkinsonian syndromes. We assessed the clinical utility of serum neuronal exosomes as biomarkers across the spectrum of Parkinson's disease, multiple system atrophy and other proteinopathies.MethodsWe performed a cross-sectional study of 664 serum samples from the Oxford, Kiel and Brescia cohorts consisting of individuals with rapid eye movement sleep behavioural disorder, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, frontotemporal dementia, progressive supranuclear palsy, corticobasal syndrome and controls. Longitudinal samples were analysed from Parkinson's and control individuals. We developed poly(carboxybetaine-methacrylate) coated beads to isolate L1 cell adhesion molecule (L1CAM)-positive extracellular vesicles with characteristics of exosomes and used mass spectrometry or multiplexed electrochemiluminescence to measure exosomal proteins.ResultsMean neuron-derived exosomal α-synuclein was increased by twofold in prodromal and clinical Parkinson's disease when compared with multiple system atrophy, controls or other neurodegenerative diseases. With 314 subjects in the training group and 105 in the validation group, exosomal α-synuclein exhibited a consistent performance (AUC=0.86) in separating clinical Parkinson's disease from controls across populations. Exosomal clusterin was elevated in subjects with non-α-synuclein proteinopathies. Combined neuron-derived exosomal α-synuclein and clusterin measurement predicted Parkinson's disease from other proteinopathies with AUC=0.98 and from multiple system atrophy with AUC=0.94. Longitudinal sample analysis showed that exosomal α-synuclein remains stably elevated with Parkinson's disease progression.ConclusionsIncreased α-synuclein egress in serum neuronal exosomes precedes the diagnosis of Parkinson's disease, persists with disease progression and in combination with clusterin predicts and differentiates Parkinson's disease from atypical parkinsonism

Systematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinics

Data availability: The datasets supporting the current study have not been deposited in a public repository due to institutional ethics restrictions but are available from the corresponding author on request.This is the final version. Available from Springer via the DOI in this record. AIMS/HYPOTHESIS: Current clinical guidelines for childhood-onset monogenic diabetes outside infancy are mainly focused on identifying and testing for dominantly inherited, predominantly MODY genes. There are no systematic studies of the recessively inherited causes of monogenic diabetes that are likely to be more common in populations with high rates of consanguinity. We aimed to determine the contribution of recessive causes of monogenic diabetes in paediatric diabetes clinics and to identify clinical criteria by which to select individuals for recessive monogenic diabetes testing. METHODS: We conducted a cross-sectional study of 1093 children from seven paediatric diabetes clinics across Turkey (a population with high rates of consanguinity). We undertook genetic testing of 50 known dominant and recessive causes of monogenic diabetes for 236 children at low risk of type 1 diabetes. As a comparison, we used monogenic diabetes cases from UK paediatric diabetes clinics (a population with low rates of consanguinity). RESULTS: Thirty-four children in the Turkish cohort had monogenic diabetes, equating to a minimal prevalence of 3.1%, similar to that in the UK cohort (p = 0.40). Forty-one per cent (14/34) had autosomal recessive causes in contrast to 1.6% (2/122) in the UK monogenic diabetes cohort (p 10%) assisted the identification of the dominant (all p ≤ 0.0003) but not recessive cases (all p ≥ 0.2) in Turkey. The presence of certain non-autoimmune extra-pancreatic features greatly assisted the identification of recessive (p < 0.0001, OR 66.9) but not dominant cases. CONCLUSIONS/INTERPRETATION: Recessively inherited mutations are a common cause of monogenic diabetes in populations with high rates of consanguinity. Present MODY-focused genetic testing strategies do not identify affected individuals. To detect all cases of monogenic paediatric diabetes, it is crucial that recessive genes are included in genetic panels and that children are selected for testing if they have certain non-autoimmune extra-pancreatic features in addition to current criteria.Wellcome TrustRoyal SocietyNational Institute for Health Researc

Case report: maternal mosaicism resulting in inheritance of a novel GATA6 mutation causing pancreatic agenesis and neonatal diabetes mellitus.

Haploinsufficiency of the GATA6 transcription factor gene was recently found to be the most common cause of pancreatic agenesis, a rare cause of neonatal diabetes mellitus. Although most cases are de novo, we describe three siblings with inherited GATA6 haploinsufficiency and the rare finding of parental mosaicism.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

A system study on the processed glass division of Republic Asahi Glass

Executive Summary. This study is concerned with the production department of Processed Glass Division (PGD) of Republic-Asahi Glass Corporation. The problem of the study is: The cutting section incurred an average of 28.51% reject rate, which is 3.51% higher than the desired value of 25%. The problem is both urgent and serious because an additional cost of Php 3,834,132 from June 2000-June 2001 was incurred. Both the management and the proponents of the study believe that sufficient time and resources are available to solve the problem. The problem has the following specifications: WHAT: The average reject rate of glass from June 2000-June 2001 coming from the cutting section exceeded the allowable reject rate by 3.51%. Specifically, scratches and breakage made up 90% of the rejects of the raw glass that was cut in the cutting section. WHERE: the rejects occur in the cutting section of the production area of PGD. WHEN: The excessive reject rate was evident from June 2000-June 2001 base from the data gathered, but it was also happening before this period. HOW MUCH: From June 2000-June 2001, a total of 119,048.55 square meters out of the 417,622.53 square meters of glass fed into the cutting machine turned out to be rejects. The main causes for the scratches and breakages are: 1. PERSON: Carelessness of workers 2. EQUIPMENT: Culler chips accumulated in cutting table and caster wheels 3. EQUIPMENT: Poor condition of bottom support of pallets The following solutions are recommended to partly solve the problem: 1. Use an Industrial vacuum cleaner to clean the cutting table once every 10 loads of glass. 2. Check and clean caster wheels before feeding new load of glass. 3. Support the bottom of the pallet with rubber and tie the glass using nylon strips. The proposed solution is expected to bring about the following: 1. The initial cost of implementation amounting to Php 82,350 and yearly cost of Php 12,825. 2. Net Benefits of Php 5,309,728.70 at the end of the 5th year 3. Qualitative Benefits include good house keeping, proper maintenance of machines and worker involvement. A five-day implementation plan was tested to validate if the proposed system will be effective or not. A decrease of 1.97% in the excess reject rate was achieved after implementation. Full implementation is feasible with in two weeks

Low Omentin-1 Levels Are Related with Clinical and Metabolic Parameters in Obese Children

Objective: This is the first clinical study evaluating the relation of serum omentin 1 levels with anthropometric and metabolic parameters in obese children with a particular interest to identify the possible role of omentin 1 in childhood obesity and related metabolic disturbances

The effects of free choice feeding based on whole triticale on growth, meat quality, carcass characteristics and gastrointestinal traits in broilers

Effets des grains de triticale offerts en libre service sur la croissance,la qualité de la viande, les caractéristiques des carcasses et les paramètresgastro-intestinaux chez le pouletLes effets sur la croissance, la qualité de la viande, les caractéristiques descarcasses et les fonctions digestives des grains de triticale offerts en libre serviceont été explorés chez le poulet. Au total, 800 poussins Ross 308 de 1jour ont été aléatoirement répartis en 5 groupes égaux en fonction du régimealimentaire institué : les oiseaux du groupe témoin ont été nourris avec desrégimes standards (maïs et tourteau de soja) alors qu’en plus, dans les autresgroupes le triticale en libre service a été proposé dès l’âge de 1 jour (groupes2 et 3) ou à l’âge de 21 jours (groupes 4 et 5) et a éventuellement été associéà l’ajout dans la ration de xylanase (1g/kg) (groupes 3 et 5). Les poids vifs etles gains de poids les plus élevés, l’ingéré alimentaire le plus faible et la meilleurconversion alimentaire ont été obtenus chez les témoins. En outre, lescaractéristiques des carcasses, la qualité de la viande et les fonctions digestivesn’ont été négativement altérées ni par le triticale offert en libre serviceni par l’inclusion dans la ration de l’enzyme. Ces résultats montrent que lespoussins de 1 jour n’ont pas de préférence pour le triticale en libre service etque la xylanase dans la ration retarde la croissance, plus particulièrement durantla phase de démarrage (du 1er au 21ème jour) et suggèrent que les pouletsne consomment pas spontanément les aliments même en libre service defaçon optimale pour une croissance maximale.The effects of free choice feeding (FCF) based on whole triticale on growth,meat quality, carcass characteristics, and digestive functions were investigated.Eight hundred 1 day old Ross 308 broiler chickens were randomly dividedinto 5 equal groups according to the dietary regimens: birds from thecontrol group were fed with standard diets based on maize and soybean mealwhereas in the other groups, free choice of triticale feeding starting since the1st day (groups 2 and 3) or from the 21st day of age (groups 4 and 5) eventuallycoupled to dietary xylanase (1 g/kg of food) addition (groups 3 and 5) wasalso established. The highest body weight and weight gains, the lowest feedconsumption and the best food efficiency were observed in the control group.Furthermore, carcass traits, meat quality and digestive functions were not negativelyaltered by free choice feeding with triticale and/or dietary enzymeinclusion. The results showed that broilers starting FCF at 1 day of age didn’tprefer to eat whole cereal, and that xylanase supplementation had negativeeffect on growth especially in the starter period (from day 1 to day 21) andsuggest that broilers do not select feed to maximize growth when offered freechoice

Soda-lime scrap glass and lime for the manufacturing of new ceramics

Starting from a mix of clay and 40wt% of soda-lime scrap glass, different amounts, 5, 10 and 15wt%, of lime (calcium hydroxide), were added and different samples were prepared and sintered, allowing to reach a near 0.0wt% in water absorption. Scanning electron microscopy observation and X-ray diffraction analysis allowed to detect devitrification phenomena of the glass, in terms of devitrite and cristobalite, and the presence of newly wollastonite crystals, when lime was added. The results of mechanical characterization in terms of flexural strength, were explained taking into account the presence of the widespread formation of elongated wollastonite crystals. The present work is promising since it evidences the possibility to prepare ceramic materials, by using great amounts of soda-lime scrap glass, coupled to lime, which could represent by itself a form of waste (in the case lime from fume abatement systems)

Serum nesfatin-1 and leptin levels in non-obese girls with premature thelarche.

Aim We aimed to investigate serum nesfatin-1 level in girls with premature thelarche (PT) and its relationship with anthropometric parameters and leptin, which are involved in the initiation of pubertal process