Voxel-based specific regional analysis system for Alzheimer's disease utility as a screening tool for unrecognized cognitive dysfunction of elderly patients in diabetes outpatient clinics: Multicenter retrospective exploratory study.

AIMS/INTRODUCTION: An efficient screening strategy for identification of cognitive dysfunction remains a clinical issue in the management of elderly adults with diabetes. A magnetic resonance imaging voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) has been developed as an automated brain morphometry system that includes the hippocampus. We carried out a multicenter retrospective study to evaluate the utility of VSRAD for screening cognitive dysfunction in diabetes outpatient clinics. MATERIALS AND METHODS: We enrolled patients with diabetes aged >65 years who underwent brain magnetic resonance imaging scans for the purpose of a medical checkup between November 2018 and May 2019. Patients who were already suspected or diagnosed with mild cognitive impairment and/or dementia as well as those with a history of cerebrovascular disease were excluded. RESULTS: A total of 67 patients were enrolled. Five patients were diagnosed with mild cognitive impairment or dementia (clinical cognitive dysfunction). Patients with clinical cognitive dysfunction showed a significantly higher z-score in VSRAD analysis (2.57 ± 0.47 vs 1.15 ± 0.55, P < 0.01). The sensitivities and specificities for diagnosis of clinical cognitive dysfunction were 80 and 48% for the Mini-Mental State Examination, 100 and 89% for the z-score, and 100 and 90% for the combination of the Mini-Mental State Examination score and z-score, respectively. CONCLUSIONS: VSRAD analysis can distinguish patients with clinical cognitive dysfunction in the elderly with diabetes, and also shows reasonable sensitivity and specificity compared with the Mini-Mental State Examination alone. Thus, VSRAD analysis can be useful for early identification of clinical cognitive dysfunction in the elderly with diabetes.

Cyclopolymerization of Cleavable Acrylate-Vinyl Ether Divinyl Monomer via Nitroxide-Mediated Radical Polymerization: Copolymer beyond Reactivity Ratio.

Cyclopolymerization of a divinyl monomer, where two different vinyl groups, that is, acrylate and vinyl ether, are connected via an ester bond, was performed under diluted condition with nitroxide-meditated radical polymerization (NMP). Both vinyl groups were consumed at almost same rate under suitable condition, although the inherent cross-propagation ability between the two vinyl groups are pretty low in radical copolymerization. Furthermore, the polymerization was controlled to some extent to give polymers of unimodal molecular weight distributions. The results obviously differed from copolymerization and homopolymerization with vinyl monomers that constitutes the divinyl monomer, 2-methoxyethyl acrylate and 2-acetoxyethyl vinyl ether. Structural analyses indicated formation of the cyclopolymer but the cyclo-efficiency was imperfect indicating that some units of olefinic dangling were incorporated. Eventually, the ester bonds of the cyclo units were cleaved to convert into the copolymer consisting of acrylic acid and 2-hydroxy ethyl vinyl ether and the composition ratio (DPacryl/DPVE) was 55:45. The copolymer showed higher glass transition temperature than that estimated from the composition ratio and Tg values of the homopolymers, which is likely due to the formation of quasi-cyclopolymer between carboxylic acid and hydroxy groups aligned in alternating fashion.

Mff functions with Pex11pß and DLP1 in peroxisomal fission.

PEROXISOMAL DIVISION COMPRISES THREE STEPS: elongation, constriction, and fission. Translocation of dynamin-like protein 1 (DLP1), a member of the large GTPase family, from the cytosol to peroxisomes is a prerequisite for membrane fission; however, the molecular machinery for peroxisomal targeting of DLP1 remains unclear. This study investigated whether mitochondrial fission factor (Mff), which targets DLP1 to mitochondria, may also recruit DLP1 to peroxisomes. Results show that endogenous Mff is localized to peroxisomes, especially at the membrane-constricted regions of elongated peroxisomes, in addition to mitochondria. Knockdown of MFF abrogates the fission stage of peroxisomal division and is associated with failure to recruit DLP1 to peroxisomes, while ectopic expression of MFF increases the peroxisomal targeting of DLP1. Co-expression of MFF and PEX11ß, the latter being a key player in peroxisomal elongation, increases peroxisome abundance. Overexpression of MFF also increases the interaction between DLP1 and Pex11pß, which knockdown of MFF, but not Fis1, abolishes. Moreover, results show that Pex11pß interacts with Mff in a DLP1-dependent manner. In conclusion, Mff contributes to the peroxisomal targeting of DLP1 and plays a key role in the fission of the peroxisomal membrane by acting in concert with Pex11pß and DLP1.

Pitavastatin reduces elevated IL-18 levels in Japanese subjects with hypercholesterolemia: sub-analysis of Kansai investigation of statin for hyperlipidemic intervention in metabolism and endocrinology (KISHIMEN).

AIM: Pitavastatin significantly improved lipid profiles and reduced serum high-sensitivity C-reactive protein (hs-CRP) levels in a multi-center and prospective study. The aim of this study was to explore the effect of pitavastatin on serum levels of another inflammatory biomarker, interleukin-18 (IL-18), in a sub-analysis of the previous multi-center prospective study. METHODS: The subjects were 83 patients derived from the KISHIMEN study. Pitavastatin (1-2 mg/day) was administered for 12 months. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), remnant-like particle cholesterol (RLP-C), triglycerides (TG), IL-18, and high sensitivity C-reactive protein (hs-CRP) levels were measured. RESULTS: TC, LDL-C, and RLP-C levels were significantly reduced by 18.3%, 30.1%, and 21.0% (mean values) at 12 months after pitavastatin administration. TG levels were decreased by 9.8% in subjects whose basal TG levels were above 150 mg/dL. HDL-C levels were significantly increased at 6 months (11.9%). Pitavastatin did not significantly alter IL-18 levels in overall subjects, but reduced IL-18 levels in the highest quartile by 24.5% (median value) at 12 months. Pitavastatin significantly reduced hs-CRP levels by 28.6% in overall subjects and by 62.4% in the highest quartile at 12 months. There was a significant correlation between IL-18 and hs-CRP at baseline after both values were transformed into logarithms (Pearson's correlation coefficient, r = 0.259, p = 0.0181); however, percent changes in these levels were not significantly correlated. CONCLUSION: Pitavastatin significantly improves lipid profiles, and reduces enhanced inflammation monitored by IL-18, as well as by hs-CRP, in hypercholesterolemic subjects.

Effects of pitavastatin on lipid profiles and high-sensitivity CRP in Japanese subjects with hypercholesterolemia: Kansai Investigation of Statin for Hyperlipidemic Intervention in Metabolism and Endocrinology (KISHIMEN) investigatars.

AIM: The effect of pitavastatin on high-sensitivity C-reactive protein (hs-CRP) has not been reported, yet, in humans. We, therefore, investigated the effects of pitavastatin on lipid profiles and hs-CRP in Japanese subjects with hypercholesterolemia. METHODS: The subjects were 178 Japanese with hypercholesterolemia, including 103 (58%) with type 2 diabetes. Pitavastatin (12 mg/day) was administered for 12 months. Serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), remnant-like particle cholesterol (RLP-C), triglycerides (TG) and hs-CRP levels were measured for 12 months. RESULTS: Serum LDL-C and RLP-C levels were significantly decreased by 30.3% and 22.8%, respectively. Serum TG levels were decreased by 15.9% in subjects with basal TG levels above 150 mg/dl. Serum HDL-C levels were significantly increased. The administration of pitavastatin reduced serum hs-CRP levels by 34.8%. No serious adverse events were observed, including changes in glycosylated hemoglobin levels of diabetic patients. CONCLUSION: These results suggest that pitavastatin significantly improves lipid profiles and reduces proinflammatory responses, without adverse effects, in Japanese subjects with hypercholesterolemia, including those with diabetes mellitus.