Development of a Sensitive Diagnostic Assay for Parkinson Disease Quantifying α-Synuclein-Containing Extracellular Vesicles

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011853
Author(s):  
Zhen Hong ◽  
Chen Tian ◽  
Tessandra Stewart ◽  
Patrick Aro ◽  
David Soltys ◽  
...  

ObjectiveTo develop a reliable and fast assay to quantify the α-synuclein (α-syn)-containing extracellular vesicles (EVs) in CSF and to assess their diagnostic potential for Parkinson disease (PD).MethodsA cross-sectional, multicenter study was designed, including 170 patients with PD and 131 healthy controls (HCs) with a similar distribution of age and sex recruited from existing center studies at the University of Washington and Oregon Health and Science University. CSF EVs carrying α-syn or aggregated α-syn were quantified using antibodies against total or aggregated α-syn, respectively, and highly specific, sensitive, and rapid assays based on the novel Apogee nanoscale flow cytometry technology.ResultsNo significant differences in the number and size distribution of total EVs between PD and HCs in CSF were observed. When examining the total α-syn-positive and aggregated α-syn-positive EV subpopulations, the proportions of both among all detected CSF EVs were significantly lower in PD compared to HCs (p < 0.0001). While each EV subpopulation showed better diagnostic sensitivity and specificity than total CSF α-syn measured directly with an immunoassay, a combination of the 2 EV subpopulations demonstrated a diagnostic accuracy that attained clinical relevance (area under curve = 0.819, sensitivity = 80%, specificity = 71%).ConclusionUsing newly established, sensitive nanoscale flow cytometry assays, we have demonstrated that total α-syn-positive and aggregated α-syn-positive EVs in CSF may serve as a helpful tool in PD diagnosis.Classification of evidenceThis study provides Class III evidence that total and aggregated α-syn-positive EVs in CSF identify patients with PD.

Neurology ◽  
2020 ◽  
Vol 95 (9) ◽  
pp. e1267-e1284 ◽  
Author(s):  
Lana M. Chahine ◽  
Thomas G. Beach ◽  
Michael C. Brumm ◽  
Charles H. Adler ◽  
Christopher S. Coffey ◽  
...  

ObjectiveThe Systemic Synuclein Sampling Study (S4) measured α-synuclein in multiple tissues and biofluids within the same patients with Parkinson disease (PD) vs healthy controls (HCs).MethodsS4 was a 6-site cross-sectional observational study of participants with early, moderate, or advanced PD and HCs. Motor and nonmotor measures and dopamine transporter SPECT were obtained. Biopsies of skin, colon, submandibular gland (SMG), CSF, saliva, and blood were collected. Tissue biopsy sections were stained with 5C12 monoclonal antibody against pathologic α-synuclein; digital images were interpreted by neuropathologists blinded to diagnosis. Biofluid total α-synuclein was quantified using ELISA.ResultsThe final cohort included 59 patients with PD and 21 HCs. CSF α-synuclein was lower in patients with PD vs HCs; sensitivity/specificity of CSF α-synuclein for PD diagnosis was 87.0%/63.2%, respectively. Sensitivity of α-synuclein immunoreactivity for PD diagnosis was 56.1% for SMG and 24.1% for skin; specificity was 92.9% and 100%, respectively. There were no significant relationships between different measures of α-synuclein within participants.ConclusionsS4 confirms lower total α-synuclein levels in CSF in patients with PD compared to HCs, but specificity is low. In contrast, α-synuclein immunoreactivity in skin and SMG is specific for PD but sensitivity is low. Relationships within participants across different tissues and biofluids could not be demonstrated. Measures of pathologic forms of α-synuclein with higher accuracy are critically needed.Classification of evidenceThis study provides Class III evidence that total CSF α-synuclein does not accurately distinguish patients with PD from HCs, and that monoclonal antibody staining for SMG and skin total α-synuclein is specific but not sensitive for PD diagnosis.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Tomislav Lauc ◽  
Enita Nakaš ◽  
Melina Latić-Dautović ◽  
Vildana Džemidžić ◽  
Alisa Tiro ◽  
...  

Objective. To evaluate the difference between chronological and dental age, calculated by Willems and Cameriere methods, in various skeletal patterns according to Steiner’s ANB Classification.Methods. This retrospective cross-sectional study comprised the sample of 776 participants aged between 7 and 15 years (368 males and 408 females). For each participant, panoramic images (OPT) and laterolateral cephalograms (LC) were collected from the medical database. On LC ANB angle was measured; on OPT dental age (DA) was calculated while chronological age (CA) and sex were recorded. The sample was divided into three subgroups (Class I, Class II, and Class III) with similar distribution based on the chronological age and ANB angle. CA was calculated as the difference between the date of OPT imaging and the date of birth, while DA was evaluated using Willems and Cameriere methods. ANB angle was measured on LC by two independent investigators using the cephalometric software. Differences between sexes and the difference between dental and chronological age were tested by independent and paired samplest-test, respectively; one-way ANOVA was used to test differences among ANB classes with Tukey post hoc test to compare specific pairs of ANB classes.Results. The significant difference was found between Class III and other two skeletal classes in males using both dental age estimation methods. In Class III males dental age was ahead averagely by 0.41 years when using Willems method, while Cameriere method overestimated CA for 0.22 years.Conclusion. In males with Class III skeletal pattern, dental development is faster than in Classes I and II skeletal pattern. This faster development is not present in females.


2014 ◽  
Vol 1 (1) ◽  
pp. 193-198
Author(s):  
Heiko Haase ◽  
Arndt Lautenschläger

AbstractThe paper aims at exploring determinants of the university students' intentions to stay within their university region. At this, we presume that students' career choice motivations are related to their professional intentions, which again, along with demographic characteristics, affect their migration decision. Our analysis is based on a cross-sectional study of 2,353 students from three different higher education institutions, two of them located in Germany and one in Namibia. Results indicate that in Germany migration matters because a considerable proportion of students intend to leave the university region after graduation. At this, we found that the students' geographical provenance exerts the most significant effect on the intention to stay. Moreover, certain professional intentions were directly and some career choice motivations were indirectly linked with the intention to remain at the university location. We present several conclusions and implications.


Author(s):  
Nham Phong Tuan ◽  
Nguyen Ngoc Quy ◽  
Nguyen Thi Thanh Huyen ◽  
Hong Tra My ◽  
Tran Nhu Phu

The objective of this study is to investigate the impact of seven factors causing academic stress on students of University of Economics and Business - Vietnam National University: Lack of leisure time, Academic performance, Fear of failure, Academic overload, Finances, Competition between students, Relationships with university faculty. Based on the results of a practical survey of 185 students who are attending any courses at the University of Economics and Business - Vietnam National University, the study assesses the impact of stress factors on students. The thesis focuses on clarifying the concept of "stress" and the stress level of students, while pointing out its negative effects on students. This study includes two cross-sectional questionnaire surveys. The first survey uses a set of 16 questions to assess students’ perceptions and attitudes based on an instrument to measure academic stress - Educational Stress Scale for Adolescents (ESSA). The second survey aims to test internal consistency, the robustness of the previously established 7-factor structure. Henceforth, the model was brought back and used qualitatively, combined with Cronbach’s Alpha measurement test and EFA discovery factor analysis. This study was conducted from October 2019 to December 2019. From these practical analyzes, several proposals were made for the society, the school and the students themselves.


2018 ◽  
Vol 20 (1) ◽  
Author(s):  
Ada C. Nwaneri ◽  
Okwudili Callistus Ezike ◽  
Agnes N. Anarado ◽  
Ifeoma Ndubisi ◽  
Jane-Lovena Onyia-Pat

 A national sentinel survey of 2006 shows that Enugu State in south-eastern Nigeria is the worst hit by HIV infections. Despite numerous control strategies having been implemented, the state was still reported by another national HIV sentinel survey in 2010 as the worst hit by HIV/AIDS within the zone, and that youths are the most affected. The researchers conducted a cross-sectional descriptive survey to assess the HIV/AIDS knowledge and risk-taking behaviours of youths at a federal university in Enugu, south-eastern Nigeria. They adopted a multistage sampling method to recruit 460 unmarried, consenting students between 15 and 30 years of age, from three faculties of the university. Almost 90 per cent of the university youths had a sound knowledge of key concepts related to HIV/AIDS; despite this, a subset (7.39%) still engaged in risk-taking behaviours. The major risky behaviours identified include having premarital sex, having multiple sexual partners, the sharing of shaving or razor blades, the use of public clippers and tribal marking. Although an analysis of variance demonstrated no significant relationship (t = −0.036) between university youths’ knowledge of HIV/AIDS and their related risk-taking behaviour, risky behaviours were found to be more (13%) among respondents who had insufficient or incorrect knowledge of the disease. An analysis of covariance, however, showed that gender and socio-economic backgrounds were not determinants of the HIV/AIDS risk-taking behaviours of these youths. Therefore, factors such as attitude or culture are areas that should be focused on, and should then, along with educational awareness campaigns, help to reduce the spread and prevalence of the disease.


Author(s):  
Sarwat Memon

Background: The palatal rugae are special constructions that are inalterable in their position and pattern during the lifestyles of an individual. This imparts them an exceptional role in the forensic dentistry and may play potential role in malocclusion identification. This study was aimed to see association of rugae pattern with sagittal skeletal malocclusion in orthodontic patients visiting tertiary care hospital. Methods: This cross-sectional examination was completed on pretreatment records (lateral Cephalometric radiographs and maxillary dental casts) of 384 subjects at the orthodontic department of Ziauddin Dental Hospital, Karachi. The study duration was from January to July 2019. The samples were sub-divided into three sagittal skeletal groups based on ANB angle proposed by Steiner’s on lateral Cephalometric radiographs (Class I with ANB angle between 0° to 4°; Class II: ANB angle greater than 5°; Class III: ANB angle less than 0°). The shapes of three most-anterior primary rugae were then evaluated bilaterally using Kapali et al., Classification. Chi Square test was applied to find association of rugae pattern among sagittal skeletal malocclusions groups. Results: Circular and curved rugae shapes were the most prevalent in all skeletal malocclusions. The primary palatal rugae pattern was seen to be significantly different among three skeletal malocclusion groups (p<0.05). The right and left sided palatal rugae pattern showed significant difference in all three skeletal malocclusion groups (p<0.05). Conclusion: The present study showed no specific palatal rugae pattern associated with sagittal skeletal malocclusion. Further studies on larger sample and use of modern 3D technologies to scan the maxillary casts are required for results that are more precise.


2017 ◽  
Vol 68 (1) ◽  
pp. 108-110
Author(s):  
Gina Botnariu ◽  
Norina Forna ◽  
Alina Popa ◽  
Raluca Popescu ◽  
Alina Onofriescu ◽  
...  

To assess the correlation between main parameters of glycemic control and cardiovascular risk scores in non-diabetic persons. Risk scores were calculated by using the University of Edinburgh Risk Calculator. Risk scores are used to estimate the probability of cardiovascular disease in individuals who have not already developed major atherosclerotic disease. We correlated the results of these scores with the parameters that describes the glycaemic profile: preprandial glicaemia, HbA1c and 1 hour and 2 h post-prandial glycaemia, determined during Oral Glucose Tolerance Test (OGTT).Both fasting glycaemia and HbA1c significantly correlated with cardiovascular risk scores calculated for a period of 10 years. The recorded post-prandial glycaemic values at 1h and 2h after glucose loading didn�t significantly correlate with calculated scores, in the study group. The observed correlations underline the importance of glycaemia in the pathogenesis of cardiovascular diseases.


Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1264
Author(s):  
Joanne Karam ◽  
Maria del Mar Bibiloni ◽  
Mireille Serhan ◽  
Josep A. Tur

Scarce studies described eating habits and diet quality among university students in Lebanon. The aim of this study is to assess the rate of adherence to the Mediterranean diet (MedDiet) among Lebanese university students. A cross-sectional nutritional survey was carried out on 525 students (53% men, 18–25 years old) from the University of Balamand, Lebanon. Adherence to the MedDiet was assessed using a validated 14-item MedDiet adherence score. Mean adherence to the MedDiet was 7.96 (standard deviation 2.2), and it was adequate in 59% of participants. Adherence to the MedDiet was higher in older students and nonsmokers. Legumes, vegetables, fruits, and nuts were consumed according to the MedDiet standards among a minimum of 48.4% and a maximum of 69.5% of participants. Chicken, turkey, or rabbit was preferred by 66.9% of participants instead of beef, pork, hamburgers, or sausages; however, just 56.2% of participants showed adequate intake of red meat, hamburger, or meat products. Only 28.8% of them referred to an adequate intake of fish or shellfish. Most of the participants (86.3%) used olive oil as the main added fat, and 67.2% reported a low intake of butter and derivatives. Sofrito was also very usual among participants (79.6%). Only half of the studied sample reported an adequate intake of sweet or carbonated beverages and commercial sweets or pastries. Among the assessed sample, half the participants showed adequate adherence to the MedDiet; however, the mean of adherence among the sample is low.


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