Jichi Medical University (自治医科大学, Jichi ika daigaku) is a private university in Shimotsuke, Tochigi, Japan, established in 1972. In 2008 the Gates Foundation awarded $100,000 to Hiroyuki Matsuoka, a medical researcher at the university, to do research on flying syringes.
Abstract CEP152 is essential for centriole function and neurodevelopment, and pathogenic recessive variants in CEP152 cause primary microcephaly. We identified new compound heterozygous CEP152 variants, c.314 G > A,p.(W105*) and c.2689 A > T,p.(K897*), in a microcephalic patient and analyzed them alongside a homozygous variant c.95 A > C,p.(Q32P) associated with severe microcephaly with marked gyral simplification. In vitro assays revealed distinct effects: p.K897* prevented centrosomal localization, p.W105* led to protein degradation, and p.Q32P retained centrosomal targeting but disrupted binding to Polo-like kinase 4, a key centriole biogenesis kinase and CEP152 partner. In vivo, both Cep152W105*/K897* and Cep152Q32P/Q32P knock-in mice displayed microcephaly; notably, Cep152Q32P/Q32P mice also exhibited severe cortical defects during brain development. Cellular analyses revealed centrosome dysfunction, mitotic errors, and increased apoptosis, which were exacerbated in Cep152Q32P/Q32P brains. Morphological examination, including electron microscopy, further demonstrated structural abnormalities of the centrosomes and centrioles in Cep152Q32P/Q32P brains. Electrophysiological and gene expression analyses confirmed variant-specific neuronal impairments, which correlate with clinical severity. Collectively, these findings demonstrate that distinct CEP152 variants disrupt neurodevelopment through different mechanisms, thereby explaining the spectrum of microcephaly severity and associated phenotypes.
Percutaneous coronary intervention (PCI) for ostial right coronary artery (RCA) lesions remains challenging and is associated with higher rates of restenosis and target lesion revascularization, even in the contemporary drug-eluting stent era. These unfavorable outcomes are largely attributable to the unique anatomical and histological characteristics of the aorto-ostial junction, including severe calcification, limited vessel compliance, and hinge motion. Intravascular ultrasound (IVUS) studies have identified distinct morphological patterns of ostial RCA lesions, including isolated ostial lesions, diffuse atherosclerotic disease without calcified nodules, and lesions characterized by calcified nodules, which are associated with poorer clinical outcomes. Optimal management of ostial RCA lesions requires careful lesion assessment and tailored therapeutic strategies. For de novo lesions, adequate lesion preparation using high-pressure/scoring balloon dilation, rotational atherectomy (RA), or intravascular lithotripsy is essential to achieve optimal stent expansion. Precise ostial stent placement and intravascular imaging–guided optimization are critical procedural components, and drug-coated balloon (DCB) therapy may be considered in selected cases with a high risk of restenosis. In-stent restenosis (ISR) of the ostial RCA is frequently driven by mechanical factors such as stent underexpansion or fracture. DCBs are the preferred first-line treatment for ISR, while additional lesion modification using high-pressure balloons, RA may be required in cases with significant mechanical constraints. This review summarizes current evidence on the morphology, mechanisms, and contemporary treatment strategies for ostial RCA lesions, with a particular focus on intravascular imaging–guided intervention and practical considerations in clinical practice.
Abstract Human serum amyloid A (SAA) is an apolipoprotein that predominantly associates with high-density lipoprotein (HDL) in the blood and participates in lipid metabolism. In addition, SAA serves as a precursor of amyloid fibrils that contribute to the development of AA amyloidosis. Chemical modifications of amyloidogenic proteins can influence the formation of amyloid fibrils. Recently, various modified SAA molecular species have been discovered in patients with AA amyloidosis. In the present study, we examined how carbamoylation and oxidation affect the structural stability, lipid binding, and amyloid fibril formation of SAA. Thermal denaturation experiments showed that these modifications reduced the thermal stability of the SAA molecule at low temperatures, although SAA itself is unstructured at physiological temperature. Upon binding to phospholipid vesicles, α-helical structure was induced. Carbamoylation exerted minimal effects on the lipid binding, whereas oxidation markedly reduced it. Chemical modifications affected not only the kinetics of amyloid fibril formation but also their fibril morphologies. Overall, these findings suggest that chemical modifications of SAA can alter its structural stability, lipid-binding ability, and amyloidogenic properties, thereby potentially contributing to the onset of AA amyloidosis.
Coronary artery disease (CAD) is a major risk factor for the development of heart failure (HF) with preserved ejection fraction (HFpEF) and is associated with increased mortality. However, an optimal strategy to screen for HFpEF among patients with CAD has not yet been established. The HFpEF-ABA score was introduced to estimate the pretest probability of HFpEF and was shown to predict adverse HF events. This retrospective multicenter cohort study included patients registered in the Clinical Deep Data Accumulation System database who underwent percutaneous coronary intervention from April 2013 to March 2019. Patients with a left ventricular (LV) ejection fraction ≥ 50
Background Superficialization of the brachial artery is an alternative vascular access strategy for selected hemodialysis patients for whom conventional access options are limited. Dissection of a superficialized brachial artery (SBA) used for dialysis access has rarely been described, and its management is not well established. Case presentation A 76-year-old man with end-stage kidney disease due to diabetic nephropathy underwent right brachial artery superficialization and maintenance hemodialysis via the superficialized artery. During routine cannulation, bedside duplex ultrasonography incidentally suggested a localized arterial dissection, despite the absence of local symptoms. Contrast-enhanced computed tomography revealed a focal dilatation of the SBA with an intraluminal thrombus. Hemodialysis was temporarily performed using a right internal jugular venous catheter to avoid cannulation of the suspected lesion. Duplex ultrasound showed preserved distal perfusion, and a flap-like structure with a mural thrombus and caliber irregularity near the antecubital fossa; the presumed entry site was approximately 2 cm proximal to the antecubital fossa. After confirming the feasibility of proximal cannulation under ultrasound guidance, the catheter was removed, and hemodialysis was continued using an adjusted puncture site approach. Conclusions This case suggests that bedside duplex ultrasound can be used in the early detection of arterial wall pathology in SBA access; and in selected patients with preserved distal perfusion and non-flow-limiting localized lesions, an ultrasound-guided conservative approach with repeat ultrasound assessment during hospitalization may allow the safe continuation of hemodialysis.
