Background: and Purpose: Amyloid-beta (Aβ) plaques are key in Alzheimer’s disease (AD), with Aβ positron emission tomography imaging enabling non-invasive quantification.To address regional Aβ deposition, we developed regional Centiloid scales (rdcCL) and commercialized them through the computed tomography (CT)-based BeauBrain Amylo platform, eliminating the need for three-dimensional T1 magnetic resonance imaging (MRI). Objective: We aimed to establish robust regional Aβ cutoffs using the commercialized BeauBrain Amylo platform and to explore the prevalence of subgroups defined by global, regional, and striatal Aβ cutoffs across cognitive stages. Methods: We included 2,428 individuals recruited from the Korea-Registries to Overcome Dementia and Accelerate Dementia Research project. We calculated regional Aβ cutoffs using Gaussian Mixture Modeling. Participants were classified into subgroups based on global, regional, and striatal Aβ positivity across cognitive stages (cognitively unimpaired [CU], mild cognitive impairment, and dementia of the Alzheimer’s type). Results: MRI-based and CT-based global Aβ cutoffs were highly comparable and consistent with previously reported Centiloid values. Regional cutoffs revealed both similarities and differences between MRI- and CT-based methods, reflecting modality-specific segmentation processes. Subgroups such as global(−)regional(+) were more frequent in non-dementia stages, while global(+)striatal(−) was primarily observed in CU individuals. Conclusions Our study established robust regional Aβ cutoffs using a CT-based rdcCL method and demonstrated its clinical utility in classifying amyloid subgroups across cognitive stages. These findings highlight the importance of regional Aβ quantification in understanding amyloid pathology and its implications for biomarker-guided diagnosis and treatment in AD.

Background: and Purpose: Amyloid-beta (Aβ) plaques are key in Alzheimer’s disease (AD), with Aβ positron emission tomography imaging enabling non-invasive quantification.To address regional Aβ deposition, we developed regional Centiloid scales (rdcCL) and commercialized them through the computed tomography (CT)-based BeauBrain Amylo platform, eliminating the need for three-dimensional T1 magnetic resonance imaging (MRI). Objective: We aimed to establish robust regional Aβ cutoffs using the commercialized BeauBrain Amylo platform and to explore the prevalence of subgroups defined by global, regional, and striatal Aβ cutoffs across cognitive stages. Methods: We included 2,428 individuals recruited from the Korea-Registries to Overcome Dementia and Accelerate Dementia Research project. We calculated regional Aβ cutoffs using Gaussian Mixture Modeling. Participants were classified into subgroups based on global, regional, and striatal Aβ positivity across cognitive stages (cognitively unimpaired [CU], mild cognitive impairment, and dementia of the Alzheimer’s type). Results: MRI-based and CT-based global Aβ cutoffs were highly comparable and consistent with previously reported Centiloid values. Regional cutoffs revealed both similarities and differences between MRI- and CT-based methods, reflecting modality-specific segmentation processes. Subgroups such as global(−)regional(+) were more frequent in non-dementia stages, while global(+)striatal(−) was primarily observed in CU individuals. Conclusions Our study established robust regional Aβ cutoffs using a CT-based rdcCL method and demonstrated its clinical utility in classifying amyloid subgroups across cognitive stages. These findings highlight the importance of regional Aβ quantification in understanding amyloid pathology and its implications for biomarker-guided diagnosis and treatment in AD.

Background: and Purpose: Amyloid-beta (Aβ) plaques are key in Alzheimer’s disease (AD), with Aβ positron emission tomography imaging enabling non-invasive quantification.To address regional Aβ deposition, we developed regional Centiloid scales (rdcCL) and commercialized them through the computed tomography (CT)-based BeauBrain Amylo platform, eliminating the need for three-dimensional T1 magnetic resonance imaging (MRI). Objective: We aimed to establish robust regional Aβ cutoffs using the commercialized BeauBrain Amylo platform and to explore the prevalence of subgroups defined by global, regional, and striatal Aβ cutoffs across cognitive stages. Methods: We included 2,428 individuals recruited from the Korea-Registries to Overcome Dementia and Accelerate Dementia Research project. We calculated regional Aβ cutoffs using Gaussian Mixture Modeling. Participants were classified into subgroups based on global, regional, and striatal Aβ positivity across cognitive stages (cognitively unimpaired [CU], mild cognitive impairment, and dementia of the Alzheimer’s type). Results: MRI-based and CT-based global Aβ cutoffs were highly comparable and consistent with previously reported Centiloid values. Regional cutoffs revealed both similarities and differences between MRI- and CT-based methods, reflecting modality-specific segmentation processes. Subgroups such as global(−)regional(+) were more frequent in non-dementia stages, while global(+)striatal(−) was primarily observed in CU individuals. Conclusions Our study established robust regional Aβ cutoffs using a CT-based rdcCL method and demonstrated its clinical utility in classifying amyloid subgroups across cognitive stages. These findings highlight the importance of regional Aβ quantification in understanding amyloid pathology and its implications for biomarker-guided diagnosis and treatment in AD.

Background: and Purpose: Amyloid-beta (Aβ) plaques are key in Alzheimer’s disease (AD), with Aβ positron emission tomography imaging enabling non-invasive quantification.To address regional Aβ deposition, we developed regional Centiloid scales (rdcCL) and commercialized them through the computed tomography (CT)-based BeauBrain Amylo platform, eliminating the need for three-dimensional T1 magnetic resonance imaging (MRI). Objective: We aimed to establish robust regional Aβ cutoffs using the commercialized BeauBrain Amylo platform and to explore the prevalence of subgroups defined by global, regional, and striatal Aβ cutoffs across cognitive stages. Methods: We included 2,428 individuals recruited from the Korea-Registries to Overcome Dementia and Accelerate Dementia Research project. We calculated regional Aβ cutoffs using Gaussian Mixture Modeling. Participants were classified into subgroups based on global, regional, and striatal Aβ positivity across cognitive stages (cognitively unimpaired [CU], mild cognitive impairment, and dementia of the Alzheimer’s type). Results: MRI-based and CT-based global Aβ cutoffs were highly comparable and consistent with previously reported Centiloid values. Regional cutoffs revealed both similarities and differences between MRI- and CT-based methods, reflecting modality-specific segmentation processes. Subgroups such as global(−)regional(+) were more frequent in non-dementia stages, while global(+)striatal(−) was primarily observed in CU individuals. Conclusions Our study established robust regional Aβ cutoffs using a CT-based rdcCL method and demonstrated its clinical utility in classifying amyloid subgroups across cognitive stages. These findings highlight the importance of regional Aβ quantification in understanding amyloid pathology and its implications for biomarker-guided diagnosis and treatment in AD.

BACKGROUND: Intramedullary (IM) nailing is widely performed in elderly patients with trochanteric fractures. Thus, it is important to identify causative factors associated with fixation failure. We investigated fixation failures after IM nailing in elderly patients with trochanteric fractures and compared the failure group with nonfailure group to identify risk factors of fixation failure. METHODS: A total of 396 patients aged 65 years or older underwent IM nailing for trochanteric fractures between January 2012 and August 2016 at our institution. Of those, 194 patients who were followed up for more than 12 months were enrolled in this study; 202 patients were excluded due to death during follow-up, bedridden status before injury, and loss to follow-up. All patients underwent plain radiography and preoperative computed tomography (CT). RESULTS: Fixation failure occurred in 11 patients (5.7%). Seven patients had stable fractures (AO/OTA); eight patients had basicervical fractures (confirmed by CT). Five patients had comminution in the greater trochanter (confirmed by CT). Regarding fracture reduction, eight patients showed discontinuity in the anterior cortex. The position of the lag screw on the lateral view was in the center in six patients and in a posterior area in the other five patients. On the basis of comparison with the 183 patients without fixation failure, risk factors of fixation failure were higher body mass index (BMI; p = 0.003), basicervical type of fracture (p = 0.037), posterior placement of the lag screw on the lateral view (p < 0.001), and inaccurate reduction of the anterior cortex (p = 0.011). CONCLUSIONS Among the risk factors of fixation failure after IM nailing in elderly patients with trochanteric fractures, discontinuity of the anterior cortex and posterior position of the lag screw are modifiable surgeon factors, whereas higher BMI and basicervical type of fracture are nonmodifiable patient factors. Therefore, care should be taken to avoid fixation failure in IM nailing for patients with a basicervical type of fracture or higher BMI or both.

PURPOSE: The transversely oriented fracture lines are very difficult to reduce during operations, even after clear exposure of the fracture site, in acetabular fractures. The purpose of this study is to verify the quality of reduction between the different subtypes (transtectal, juxtatectal, and infratectal) of transverse fractures. This study also determined the proper type of clamps to use and the proper zone for achieving accurate reductions in Sawbones models. MATERIALS AND METHODS: Six fractures in 3 different subtypes of transverse fractures were artificially created. Ten different reduction clamps were applied for reduction of the fractures. Twelve holes around the fracture were drilled for the maintenance of the clamps. The fracture displacements were measured at the extra-articular area and the intra-articular joint portion. The pictures of the intra-articular fracture displacements were taken by a camera and these were uploaded and analyzed by the TraumaCad® computer program (Brainlab). RESULTS: The reduction quality was poor in order of transtectal, juxtatectal and infratectal. The intraarticular opening was more prominent in the transtectal subtype. The safe zone, when giving consideration of the neurovascular bundles, was a quadrilateral surface of the ilium. Drill holes are useful for maintenance of the reduction clamps. Reduction clamps with points (Weber clamp) were the best for maintenance and accurate reduction. Regarding the concerns of placement of clamps, the middle to posterior combination was the best. The upper hole among the posterior holes in the ilium was the most likely to well reduce the intra-articular opening. CONCLUSION: Transtectal was the more complicated subtype in the aspect of reduction quality. The Weber type reduction clamp was the best for reduction by centrally located holes in the quadrilateral surface and posteriorly located iliac holes in transverse acetabular fractures. The upper hole, among the posterior holes in the ilium, was the best for reduction of the fracture displacements in the intraarticular portion of acetabulum.
Acetabulum ; Ilium ; Intra-Articular Fractures ; Joints

Invasive fungal infections caused by Cyberlindnera fabianii have recently increased. However, biochemical kits such as API 20 C AUX and Vitek-2C have misidentified this species as other Candida spp. such as C. pelliculosa or C. utilis due to no information of Cy. fabianii in yeast database. During our 2016–2017 surveys, eleven isolates of Cy. fabianii were obtained in International St. Mary's Hospital in Korea. Here, we describe its morphological and molecular characteristics and tested its antifungal susceptibility against nine antifungal agents. The sequences of the ITS region and the D1/D2 region of LSU revealed 100% identity with the sequences of Cy. fabianii. In comparison with the results from MALDI-TOF mass spectrometry, we found that Cy. fabianii can be distinguished from other species. In antifungal susceptibility test, voriconazole and echinocandins exhibited good antifungal activities against the majority of Cy. fabianii isolates despite the absence of standard criteria.

Excessive extracellular matrix (ECM) accumulation is the main feature of chronic renal disease including diabetic nephropathy. Plasminogen activator inhibitor (PAI)-1 is known to play an important role in renal ECM accumulation in part through suppression of plasmin generation and matrix metalloproteinase (MMP) activation. The present study examined the effect of PAI-1 antisense oligodeoxynucleotide (ODN) on fibronectin upregulation and plasmin/MMP suppression in primary mesangial cells cultured under high glucose (HG) or transforming growth factor (TGF)-beta1, major mediators of diabetic renal ECM accumulation. Growth arrested and synchronized rat primary mesangial cells were transfected with 1 microM phosphorothioate-modified antisense or control mis-match ODN for 24 hours with cationic liposome and then stimulated with 30 mM D-glucose or 2 ng/ml TGF-beta1. PAI-1 or fibronectin protein was measured by Western blot analysis. Plasmin activity was determined using a synthetic fluorometric plasmin substrate and MMP-2 activity analyzed using zymography. HG and TGF-beta1 significantly increased PAI-1 and fibronectin protein expression as well as decreased plasmin and MMP-2 activity. Transient transfection of mesangial cells with PAI-1 antisense ODN, but not mis-match ODN, effectively reversed basal as well as HG- and TGF-beta1-induced suppression of plasmin and MMP-2 activity. Both basal and upregulated fibronectin secretion were also inhibited by PAI-1 antisense ODN. These data confirm that PAI-1 plays an important role in ECM accumulation in diabetic mesangium through suppression of protease activity and suggest that PAI-1 antisense ODN would be an effective therapeutic strategy for prevention of renal fibrosis including diabetic nephropathy.
Animals ; Blotting, Western ; Diabetic Nephropathies ; Extracellular Matrix ; Fibrinolysin ; Fibronectins ; Fibrosis ; Glucose ; Liposomes ; Mesangial Cells ; Oligodeoxyribonucleotides ; Plasminogen ; Plasminogen Activator Inhibitor 1 ; Plasminogen Activators ; Rats ; Renal Insufficiency, Chronic ; Transfection ; Transforming Growth Factor beta1 ; Transforming Growth Factors ; Up-Regulation

BACKGROUND: Toll like receptor (TLR), an element of innate immunity, is upregulated by Ischemia/reperfusion (IR) injury and may be involved in adaptive immune response. Immunosuppressive agents may increase or attenuate IR injury and TLR expression. To explore the involvement of TLRs in hypoxic tubular injury and modification by mycophenolic acid (MPA) rapamycin (RAP), this study examined TLR expression in hypoxia-induced human renal proximal tubular epithelial cells (HK-2). METHODS: HK-2 cells were cultured in keratinocyte-SFM media supplemented with epidermal growth factor and bovine pituitary extract. The Induction of hypoxia was achieved using GasPak pouch system. TLR 2, 3, and 4 mRNA expression was analyzed by real time RT-PCR using SYBR green and TLR 4 protein expression was evaluated by Western blot analysis. MPA at concentration of 100 nM and 1uM and RAP at concentration of 20, 50, and 100 nM were added to culture medium. RESULTS: TLR4 but noTLR2 or TLR3 mRNA expressions increased in hypoxic HK-2 cells at 24 and 48 hrs. TLR4 protein expression also increased in hypoxic HK-2 cells at 24 and 48 hrs. MPA (100 nM and 1uM) and RAP (20, 50, and 100 nM) decreased hypoxia-induced TLR4 mRNA expression in HK-2 cells compared to normoxia at 24 hrs. However, TLR4 protein expression was decreased only by RAP at 20 and 50 nM. CONCLUSIONS: The results suggest that RAP may modify hypoxic renal tubular damage by decreasing TLR4-mediated inflammatory and immune reactions.
Adaptive Immunity ; Anoxia ; Blotting, Western ; Epidermal Growth Factor ; Epithelial Cells ; Humans ; Immunity, Innate ; Immunosuppressive Agents ; Mycophenolic Acid ; RNA, Messenger ; Sirolimus ; Toll-Like Receptors

PURPOSE: Mesangial cell extracellular matrix (ECM) synthesis plays an important role in various renal diseases. Mycophenolic acid (MPA), which is an inhibitor of inosine monophosphate dehydrogenase (IMPDH), inhibits mesangial cell proliferation and ECM synthesis. However, the exact mechanism of MPA has not been clearly elucidated in mesangial cells. To examine the relative importance of IMPDH on the inhibitory action of MPA, we compared the effects of MPA or IMPDH2 siRNA on platelet-derived growth factor (PDGF)-induced fibronectin secretion and cellular reactive oxygen species (ROS) in mouse mesangial cells (MMC). METHODS: MMC were stimulated with PDGF 10 ng/ml with or without MPA 0.1~10micrometer, IMPDH2 siRNA 10~50 nM, or N-acetylcystein (NAC). IMPDH2 siRNA was transiently transfected by lipofectamine for 24 hours. MPA 0.1~10micrometer, ribavirin 10~100micrometer, and NAC 5 mM were administered 1 hour before the stimulation. Cell viability was measured by methylthiazoletetrazolium (MTT) assay, fibronectin secretion by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS by flow cytometry. RESULTS: PDGF 10 ng/ml effectively increased fibronectin secretion and cellular ROS in MMC. MPA and NAC at concentration without affecting basal level of fibronectin and cellular ROS ameliorated PDGF-induced fibronectin secretion and cellular ROS. However, IMPDH2 siRNA only partially reduced PDGF- induced fibronectin secretion and cellular ROS in MMC. CONCLUSION: These results suggest that MPA may inhibit PDGF-induced fibronectin secretion partly through IMPDH2 or cellular ROS in MMC, and there may be other mechanisms on the inhibitory action of MPA in mesenchymal cells.
Animals ; Blotting, Western ; Cell Survival ; Extracellular Matrix ; Fibronectins* ; Flow Cytometry ; Inosine Monophosphate* ; Inosine* ; Mesangial Cells* ; Mice* ; Mycophenolic Acid ; Oxidoreductases* ; Platelet-Derived Growth Factor ; Reactive Oxygen Species* ; Ribavirin ; RNA, Small Interfering