Elevated levels of autoantibodies against EXD2 and PHAX in the sera of patients with chronic thromboembolic pulmonary hypertension.

While circulating autoantibodies have been detected in patients with several cardiovascular diseases, such studies have not been performed for chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Here we investigated the production of certain auto-antibodies in CTEPH patients. Initial screening was performed in 5 CTEPH patients and 5 healthy donors (HDs) using a ProtoArray Human Protein Microarray v5.1 containing 9,375 human proteins, and we selected 34 antigens recognized by IgG antibodies more strongly in the sera of CTEPH patients than in the sera of HDs. In subsequent second/third analyses, we validated the auto-antibody level using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in 96 CTEPH patients and 96 HDs as follows: At the second screening, we used 63 crude peptides derived from those selected 34 antigens and found that the serum levels of autoantibodies for 4 peptides seemed higher in CTEPH patients than in HDs. In third analysis, we used the purified peptides of those selected in second screening and found that serum antibodies against peptides derived from exonuclease 3'-5' domain-containing 2 (EXD2) and phosphorylated adaptor for RNA export (PHAX) were significantly higher in CTEPH patients than in HDs. The serum antibody levels to these antigens were also elevated in PAH patients. The titers against EXD2 peptide decreased after surgical treatment in CTEPH patients. These autoantibodies may be useful as biomarkers of CTEPH and PAH, and further investigations may provide novel insight into the etiology

Relationship between person with dementia and adolescents: A preliminary survey of the Association Between Children and Dementia Elders (ABCDE) Project

Objectives: The aim of this study was to clarify the relationship and psychological reaction of person with dementia and their grandchildren by administering aquestionnaire to the primary caregiver.Methods: A total of 109 caregivers of people with dementia in outpatient enrolled in this study. Questionnaire collected information on age, gender, cognitive severity(Mini-Mental State Examination), clinical diagnosis, relationship of the caregiver, frequency of meeting with grandchildren, and reaction of person with dementia tospending time with their grandchildren and/or great-grandchildren, and vice versa.Results: Eighty-four people had at least one grandchild (77.1%) and a quarter lived with their grandchild and/or great-grandchild. Age of grandchildren increasedwith increasing age of person with dementia; frequency of seeing each other decreased with increasing age. While most people with dementia were reported to lookhappy when spending time with their grandchildren (94.5%), young people tended to be more non-reactive (26.0%). Non-reactive grandchildren were more prevalentin the older dementia age group (p < 0.001). Nevertheless, the majority of grandchildren (74.0%) enjoyed spending time together.Conclusions: People with dementia enjoy spending time with their grandchildren, although older grandchildren are less reactive in these situations

The Neuropsychological Correlates of Brain Perfusion and Gray Matter Volume in Alzheimer’s Disease

Background:Neuropsychological tests, structural neuroimaging, and functional neuroimaging are employed as diagnostic and monitoring biomarkers of patients with Alzheimer’s disease (AD) Objective:We aimed to elucidate the similarities and differences in neuropsychological tests and neuroimaging with the use of the Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog), structural magnetic resonance image (MRI), and perfusion single photon emission computed tomography (SPECT), and parametric image analyses to understand its role in AD. Methods:Clinically-diagnosed AD patients (n = 155) were scanned with three-dimensional T1-weighted MRI and N-isopropyl-p-[123I] iodoamphetamine SPECT. Statistical parametric mapping 12 was used for preprocessing images, statistical analyses, and voxel-based morphometry for gray matter volume analyses. Group comparison (AD versus healthy controls), multiple regression analyses with MMSE, ADAS-cog total score, and ADAS-cog subscores as variables, were performed. Results:The AD group showed bilateral hippocampal volume reduction and hypoperfusion in the bilateral temporo-parietal lobe and posterior midline structures. Worse MMSE and ADAS-cog total score were associated with bilateral temporo-parietal volume loss and hypoperfusion. MMSE, but not ADAS-cog, was associated with the posterior midline structures. The ADAS-cog subscores were associated with the temporal volume, while perfusion analyses were linked to the left temporo-parietal region with the language function and right analogous region with the constructional praxis subscore. Conclusion:MMSE and ADAS-cog are associated with temporo-parietal regions, both in volume and perfusion. The MMSE score is associated with posterior midline structures and linked to an abnormal diagnostic AD pattern. Perfusion image analyses better represents the cognitive function in AD patient

Results of a preliminary study using hypofractionated involved-field radiation therapy and concurrent carboplatin/paclitaxel in the treatment of locally advanced non-small-cell lung cancer

We aimed to evaluate the feasibility and efficacy of hypofractionated involved-field radiation therapy (IFRT) omitting elective nodal irradiation (ENI) with concurrent chemotherapy for locally advanced non-small-cell lung cancer (NSCLC). Between July 2004 and July 2006, ten patients with locally advanced NSCLC were included in this study. One had stage IIIA and 9 had stage IIIB disease. The treatment consisted of IFRT in fractions of 2.5 Gy and weekly carboplatin (CBDCA)/paclitaxel (PTX). Hypofractionated IFRT with a median total dose of 65 Gy with median percent total lung volume exceeding 20 Gy (V20) of 20.2%, and a median of five courses of chemotherapy with weekly CBDCA (area under the curve, 1.5-2.0)/PTX (30-35 mg/m(2)) were given to all patients. The median survival time and the 1-, 2-, and 3-year overall survival rates were 29.5 months and 90.0%, 58.3%, and 43.8%, respectively. No elective nodal failure was encountered during the median follow up of 18.2 months. No acute or late toxicities of grade 3 or worse were observed. No in-field recurrence occurred in the group with a total dose of 67.5 Gy or more, but there was such recurrence in 83.3% of those in the group with less than 67.5 Gy. Hypofractionated IFRT with weekly CBDCA/PTX was a feasible treatment regimen. Hypofractionated IFRT with a total dose of 67.5 Gy or more could be a promising modality to improve the treatment results in patients with locally advanced NSCLC

Effects of tumor necrosis factor inhibitors and tocilizumab on the glycosylated hemoglobin levels in patients with rheumatoid arthritis; an observational study

<div><p>Rheumatoid arthritis (RA) and diabetes mellitus (DM) are associated with inflammation. We tried to investigate the influence of tumor necrosis factor inhibitors (TNFi) and tocilizumab (TCZ) on the glucose metabolism of RA patients. RA patients in whom treatment with TNFi or TCZ was initiated from 2008 to 2015 were studied based on their medical records. We analyzed patients whose glycosylated hemoglobin (HbA1c) levels were measured both before and 3 months after the initiation of these biologic agents. The association between HbA1c reduction and the treatment was evaluated. From 971 cases treated with these biologic agents, 221 cases whose medical records of HbA1c were available, were included (TNFi, n = 154; TCZ, n = 67). Both the TNFi and TCZ groups had significantly lower HbA1c values at 1 month and 3 months after the initiation of treatment (TNFi, p<0.001; TCZ, p<0.001). Although the pretreatment HbA1c values did not differ (TNFi, 6.2%; TCZ, 6.2%; p = 0.532), the 3-month treatment HbA1c values were lower (TNFi, 6.1%; TCZ, 5.8%; p = 0.010) and the changes in HbA1c (ΔHbA1c) were greater (TNFi, 0.1%; TCZ, 0.4%; p<0.001) in the TCZ group. The reduction of HbA1c—defined by the achievement of a ΔHbA1c of ≥0.5%—was associated with baseline diagnosis of diabetes mellitus, baseline diabetes treatment, hospitalization, medical change during the observation period, and TCZ. In the multivariate logistic regression analysis, TCZ was associated with the reduction of HbA1c in comparison to TNFi (adjusted OR = 5.59, 95% CI = 2.56–12.2; p<0.001). The HbA1c levels in RA patients were significantly lower after the initiation of TNFi or TCZ. Our study suggests that TCZ decreases the HbA1c levels in RA patients to a greater extent than TNFi.</p></div

Effects of TNF inhibitors (TNFi) and tocilizumab (TCZ) on glycosylated hemoglobin (HbA1c) in 1 month and 3 months after initiation of biologic agents.

<p>Boxes indicate interquartile range and horizontal bars represent median values. Whiskers indicate most extreme points. Changes in HbA1c were evaluated by the Friedman test, which were significant in all the six groups (p<0.001). Subsequently, each HbA1c values were compared by the Wilcoxon signed rank test. The significance level was adjusted as 0.017 by Bonferroni method. *Number of missing value is 25. ** Number of missing value is 13. # Number of missing value is 13. ## Number of missing value is 7. ^ Number of missing value is 12. ^^ Number of missing value is 6.</p

The baseline characteristics of all the study subjects, overall and according to biologic agents.

<p>The baseline characteristics of all the study subjects, overall and according to biologic agents.</p