Evaluation of a specific diagnostic marker for rheumatoid arthritis based on cyclic citrullinated peptide

AbstractA specific peptide marker for diagnosing rheumatoid arthritis (RA) was found based on cyclic citrullinated peptide (CCP) using the following three steps: (1) analysis of the binding epitope of autoimmune antibodies using ϵ-aminocaproic acid-modified peptides; (2) RA diagnosis using sequence-modified peptides; and (3) evaluation of the peptides’ diagnostic performance for RA diagnosis. Ninety-five serum samples were analyzed by ELISA and compared using MedCalc (version 15.2.1). Microplate binding ϵ-aminocaproic acid was added to the N- or C-terminal of the CCP sequence. The N-terminal anchoring peptide assay showed 15% higher specificity compared with the C-terminal anchoring peptide assay. Based on this result, the hydrophilic C-terminal sequence of CCP was substituted with a hydrophobic amino acid. Among the sequence-modified peptides, CCP11A (in which alanine was substituted for the 11th amino acid of CCP) assay showed the highest sensitivity (87%) and specificity (100%) for RA diagnosis. Thus, CCP11A was selected as a possible specific marker peptide for RA diagnosis and further analyzed. The results of this analysis indicated that CCP11A showed better specificity than the CCP assay in both healthy individuals (11% better) and OA cohort (20% better). From these results, CCP11A was evaluated as a specific marker for diagnosing RA with higher diagnostic performance

Isolation and characterization of the outer membrane of Escherichia coli with autodisplayed Z-domains

Abstract“Autodisplay technology” is an expression technique used to display the various recombinant proteins on the outer membrane (OM) of Escherichia coli. The resulting autodisplayed Z-domain has been used to improve the sensitivity of immunoassays. In this work, a facile isolation method of the OM fraction of E. coli with autodisplayed Z-domains was presented using (1) an enzyme reaction for the hydrolysis of the peptidoglycan layer and (2) short centrifugation steps. The purity of the isolated OM fraction was analyzed. For the estimation of contamination with bacterial proteins from other parts of E. coli, Western blots of marker proteins for the OM (OmpA), periplasm (β-lactamase), inner membrane (SecA), and cytoplasm (β-galactosidase) were performed. Additionally, assays of marker components or enzymes from each part of E. coli were carried out including the OM (KDO), inner membrane (NADH oxidase), periplasm (β-lactamase), and cytoplasm (β-galactosidase). The yield of OM isolation using this new method was determined to be 80% of the total OM amount, with less than 1% being contaminants from other parts of E. coli

Integration of amyloid-β oligomerization tendency as a plasma biomarker in Alzheimer's disease diagnosis

IntroductionThere has been significant development in blood-based biomarkers targeting amyloidopathy of Alzheimer's disease (AD). However, the guidelines for integrating such biomarkers into AD diagnosis are still inadequate. Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) as a plasma biomarker detecting oligomerization tendency is available in the clinical practice.Main textWe suggest how to interpret the results of plasma biomarker for amyloidopathy using MDS-OAβ with neuropsychological test, brain magnetic resonance imaging (MRI), and amyloid PET for AD diagnosis. Combination of each test result differentiates various stages of AD, other neurodegenerative diseases, or cognitive impairment due to the causes other than neurodegeneration.DiscussionA systematic interpretation strategy could support accurate diagnosis and staging of AD. Moreover, comprehensive use of biomarkers that target amyloidopathy such as amyloid PET on brain amyloid plaque and MDS-OAβ on amyloid-β oligomerization tendency can complement to gain advanced insights on amyloid-β dynamics in AD

Predictors of pre-operative cognitive impairment in meningioma patients over 60 years old

Abstract Background The aim of this study was to assess the cognitive function of patients over 60 years old with meningioma using a domain-specific neuropsychological test and to investigate the relevant factors affecting pre-operative cognitive decline in different subdomains. Methods We retrospectively investigated 46 intracranial meningioma patients between the ages of 60 and 85 years. All patients underwent brain MRI and neuropsychological test. Tumor size, location, peritumoral edema, and medial temporal atrophy (MTA) were examined to determine the association with cognitive impairment. We performed a logistic regression analysis to examine the odds ratios (ORs) for cognitive decline of four subdomains: verbal memory, language, visuospatial, and executive functions. Results Tumor size and age were associated with executive dysfunction (OR 1.083, 95% confidence interval (CI) 1.006–1.166, and OR 1.209, 95% CI 1.018–1.436, respectively). There was no statistically significant association in other cognitive domains (language, verbal memory, and visuospatial function) with variables in regression analysis. Conclusions We conclude that tumor size and age are positively related with executive function in pre-operative meningioma patients over 60 years old

Eosinophilic gastroenteritis in an 18-year-old male with prolonged nephrotic syndrome

Eosinophilic gastroenteritis is a rare disease characterized by prominent eosinophilic tissue infiltration of the gastrointestinal tract. Here, we report a case of eosinophilic gastroenteritis in an 18-year-old patient with prolonged nephrotic syndrome who presented with abdominal pain and peripheral hypereosinophilia. During the previous 2 years, he had visited local Emergency Department several times because of epigastric pain and nausea. He had been treated with steroid-dependent nephrotic syndrome since 3 years of age. Tests ruled out allergic and parasitic disease etiologies. Gastroduodenoscopy with biopsy revealed marked eosinophilic infiltration in the duodenum. Renal biopsy findings indicated minimal change disease spectrum without eosinophilic infiltration. The oral deflazacort dosage was increased, and the patient was discharged after abdominal pain resolved. To our knowledge, this is the first report of eosinophilic gastroenteritis in a patient with minimal change disease

A pathogenic PSEN1 Trp165Cys mutation associated with early-onset Alzheimers disease

Background Presenilin-1 (PSEN1) is one of the causative genes for early onset Alzheimers disease (EOAD). Recently, emerging studies reported several novel PSEN1 mutations among Asian. We describe a male with EOAD had a pathogenic PSEN1 mutation. Case presentation A 53-year-old male presented with memory decline, followed by difficulty in finding ways. Patient had positive family history, since his mother and one of his brother was also affected with dementia. Brain magnetic resonance imaging (MRI) scan showed mild degree of atrophy of bilateral hippocampus and parietal lobe. 18F-Florbetaben-PET (FBB-PET) revealed increased amyloid deposition in bilateral frontal, parietal, temporal lobe and precuneus. Whole exome analysis revealed a heterozygous, probably pathogenic PSEN1 (c.695G > T, p.W165C) mutation. Interestingly, Trp165Cys mutation is located in trans membrane (TM)-III region, which is conserved between PSEN1/PSEN2. In vitro studies revealed that PSEN1 Trp165Cys could result in disturbances in amyloid metabolism. This prediction was confirmed by structure predictions and previous in vitro studies that the p.Trp165Cys could result in decreased Aβ42/Aβ40 ratios. Conclusion We report a case of EOAD having a pathogenic PSEN1 (Trp165Cys) confirmed with in silico and in vitro predictions.This work was supported by a National Research Foundation of Korea (NRF) Grants, awarded by the Korean government (MEST, No. 2017R1A2B4012636 & 2017R1C1B5017807). Dr. An SS receives the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST, No. 2017R1A2B4012636). Dr. Eva Bagyinszky receives the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST, No. 2017R1C1B5017807). Dr. Giau VV reports no disclosure. Dr. Pyun JM reports no disclosure. Dr. Suh J reports no disclosure. Dr. Kim SY reports no disclosure

A More Appropriate Cardiac Troponin T Level That Can Predict Outcomes in End-Stage Renal Disease Patients with Acute Coronary Syndrome

Purpose: Cardiac troponin T (cTnT), a useful marker for diagnosing acute myocardial infarction (AMI) in the general population, is significantly higher than the usual cut-off value in many end-stage renal disease (ESRD) patients without clinically apparent evidence of AMI. The aim of this study was to evaluate the clinical usefulness of cTnT in ESRD patients with acute coronary syndrome (ACS). Materials and methods: Two hundred eighty-four ESRD patients with ACS were enrolled between March 2002 and February 2008. These patients were followed until death or June 2009. Medical records were reviewed retrospectively. The cut-off value of cTnT for AMI was evaluated using a receiver operating characteristic (ROC) curve. We calculated Kaplan-Meier survival curves, and potential outcome predictors were determined by Cox proportional hazard analysis. Results: AMIs were diagnosed in 40 patients (14.1%). The area under the curve was 0.98 in the ROC curve (p<0.001; 95% CI, 0.95-1.00). The summation of sensitivity and specificity was highest at the initial cTnT value of 0.35 ng/mL (sensitivity, 0.95; specificity, 0.97). Survival analysis showed a statistically significant difference in all-cause and cardiovascular mortalities for the group with an initial cTnT ≥0.35 ng/mL compared to the other groups. Initial serum cTnT concentration was an independent predictor for mortality. Conclusion: Because ESRD patients with an initial cTnT concentration ≥0.35 ng/mL have a poor prognosis, it is suggested that urgent diagnosis and treatment be indicated in dialysis patients with ACS when the initial cTnT levels are ≥0.35 ng/mL.ope

Use of the Clock Drawing Test and the Rey–Osterrieth Complex Figure Test-copy with convolutional neural networks to predict cognitive impairment

Background The Clock Drawing Test (CDT) and Rey–Osterrieth Complex Figure Test (RCFT) are widely used as a part of neuropsychological test batteries to assess cognitive function. Our objective was to confirm the prediction accuracies of the RCFT-copy and CDT for cognitive impairment (CI) using convolutional neural network algorithms as a screening tool. Methods The CDT and RCFT-copy data were obtained from patients aged 60–80 years who had more than 6 years of education. In total, 747 CDT and 980 RCFT-copy figures were utilized. Convolutional neural network algorithms using TensorFlow (ver. 2.3.0) on the Colab cloud platform ( www.colab.research.google.com ) were used for preprocessing and modeling. We measured the prediction accuracy of each drawing test 10 times using this dataset with the following classes: normal cognition (NC) vs. mildly impaired cognition (MI), NC vs. severely impaired cognition (SI), and NC vs. CI (MI + SI). Results The accuracy of the CDT was better for differentiating MI (CDT, 78.04 ± 2.75; RCFT-copy, not being trained) and SI from NC (CDT, 91.45 ± 0.83; RCFT-copy, 90.27 ± 1.52); however, the RCFT-copy was better at predicting CI (CDT, 77.37 ± 1.77; RCFT, 83.52 ± 1.41). The accuracy for a 3-way classification (NC vs. MI vs. SI) was approximately 71% for both tests; no significant difference was found between them. Conclusions The two drawing tests showed good performance for predicting severe impairment of cognition; however, a drawing test alone is not enough to predict overall CI. There are some limitations to our study: the sample size was small, all the participants did not perform both the CDT and RCFT-copy, and only the copy condition of the RCFT was used. Algorithms involving memory performance and longitudinal changes are worth future exploration. These results may contribute to improved home-based healthcare delivery.The costs for manuscript publication, design of the study, data management, and writing of the manuscript were supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2017S1A6A3A01078538)

Korean Brain Rehabilitation Registry for Rehabilitation of Persons with Brain Disorders: Annual Report in 2009

This first annual report provides a description of patients discharged from rehabilitation facilities in Korea based on secondary data analysis of Korean Brain Rehabilitation Registry V1.0 subscribed in 2009. The analysis included 1,697 records of patients with brain disorders including stroke, traumatic brain injury, brain tumor and other disorders from 24 rehabilitation facilities across Korea. The data comprised 1,380 cases of stroke, 104 cases of brain injury, 55 cases of brain tumor, and 58 cases of other brain diseases. The functional status of each patient was measured using the Korean version of the Modified Barthel Index (KMBI). The average change in the KMBI score was 15.9 for all patients in the inpatient rehabilitation facility. The average length of stay for inpatient rehabilitation was 36.9 days. The transfer rates to other hospitals were high, being 62.4% when all patients were considered. Patients with brain disorders of Korea in 2009 and measurable functional improvement was observed in patients. However, relatively high percentages of patients were not discharged to the community after inpatient rehabilitation. Based on the results of this study, consecutive reports of the status of rehabilitation need to be conducted in order to provide useful information to many practitioners

Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment

Background: The combinatorial effect of multiple genetic factors calculated as a polygenic risk score (PRS) has been studied to predict disease progression to Alzheimer's disease (AD) from mild cognitive impairment (MCI). Previous studies have investigated the performance of PRS in the prediction of disease progression to AD by including and excluding single nucleotide polymorphisms within the region surrounding the APOE gene. These studies may have missed the APOE genotype-specific predictability of PRS for disease progression to AD. Methods: We analyzed 732 MCI from the Alzheimer's Disease Neuroimaging Initiative cohort, including those who progressed to AD within 5 years post-baseline (n = 270) and remained stable as MCI (n = 462). The predictability of PRS including and excluding the APOE region (PRS+APOE and PRS-APOE) on the conversion to AD and its interaction with the APOE ε4 carrier status were assessed using Cox regression analyses. Results: PRS+APOE (hazard ratio [HR] 1.468, 95% CI 1.335-1.615) and PRS-APOE (HR 1.293, 95% CI 1.157-1.445) were both associated with a significantly increased risk of MCI progression to dementia. The interaction between PRS+APOE and APOE ε4 carrier status was significant with a P-value of 0.0378. The association of PRSs with the progression risk was stronger in APOE ε4 non-carriers (PRS+APOE: HR 1.710, 95% CI 1.244-2.351; PRS-APOE: HR 1.429, 95% CI 1.182-1.728) than in APOE ε4 carriers (PRS+APOE: HR 1.167, 95% CI 1.005-1.355; PRS-APOE: HR 1.172, 95% CI 1.020-1.346). Conclusions: PRS could predict the conversion of MCI to dementia with a stronger association in APOE ε4 non-carriers than APOE ε4 carriers. This indicates PRS as a potential genetic predictor particularly for MCI with no APOE ε4 alleles