Molecular cloning and expression of a novel human cDNA related to the diazepam binding inhibitor

AbstractIn order to isolate the unidentified autoantigens in autoimmune diabetes, a human pancreatic islet cDNA library was constructed and screened with the sera from the diabetic patients. From the library screening, one clone (DRS-1) that strongly reacted with the sera was isolated. Subsequent sequence analysis revealed that the clone was a novel cDNA related to the diazepam binding inhibitor. DRS-1 was expressed in most tissues including liver, lung, tonsil, and thymus, in addition to pancreatic islets. DRS-1 was in vitro translated and the recombinant DRS-1 protein was expressed in Escherichia coli and purified. The size of the in vitro translated or bacterially expressed DRS-1 protein was in agreement with the conceptually translated polypeptide of DRS-1 cDNA. Further studies are required to test whether or not DRS-1 is a new autoantigen in autoimmune diabetes

Artificial intelligence for the detection of sacroiliitis on magnetic resonance imaging in patients with axial spondyloarthritis

BackgroundMagnetic resonance imaging (MRI) is important for the early detection of axial spondyloarthritis (axSpA). We developed an artificial intelligence (AI) model for detecting sacroiliitis in patients with axSpA using MRI.MethodsThis study included MRI examinations of patients who underwent semi-coronal MRI scans of the sacroiliac joints owing to chronic back pain with short tau inversion recovery (STIR) sequences between January 2010 and December 2021. Sacroiliitis was defined as a positive MRI finding according to the ASAS classification criteria for axSpA. We developed a two-stage framework. First, the Faster R-CNN network extracted regions of interest (ROIs) to localize the sacroiliac joints. Maximum intensity projection (MIP) of three consecutive slices was used to mimic the reading of two adjacent slices. Second, the VGG-19 network determined the presence of sacroiliitis in localized ROIs. We augmented the positive dataset six-fold. The sacroiliitis classification performance was measured using the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). The prediction models were evaluated using three-round three-fold cross-validation.ResultsA total of 296 participants with 4,746 MRI slices were included in the study. Sacroiliitis was identified in 864 MRI slices of 119 participants. The mean sensitivity, specificity, and AUROC for the detection of sacroiliitis were 0.725 (95% CI, 0.705–0.745), 0.936 (95% CI, 0.924–0.947), and 0.830 (95%CI, 0.792–0.868), respectively, at the image level and 0.947 (95% CI, 0.912–0.982), 0.691 (95% CI, 0.603–0.779), and 0.816 (95% CI, 0.776–0.856), respectively, at the patient level. In the original model, without using MIP and dataset augmentation, the mean sensitivity, specificity, and AUROC were 0.517 (95% CI, 0.493–0.780), 0.944 (95% CI, 0.933–0.955), and 0.731 (95% CI, 0.681–0.780), respectively, at the image level and 0.806 (95% CI, 0.729–0.883), 0.617 (95% CI, 0.523–0.711), and 0.711 (95% CI, 0.660–0.763), respectively, at the patient level. The performance was improved by MIP techniques and data augmentation.ConclusionAn AI model was developed for the detection of sacroiliitis using MRI, compatible with the ASAS criteria for axSpA, with the potential to aid MRI application in a wider clinical setting

Pravastatin Attenuates Acute Radiation-Induced Enteropathy and Improves Epithelial Cell Function

Background and Aim: Radiation-induced enteropathy is frequently observed after radiation therapy for abdominal and pelvic cancer or occurs secondary to accidental radiation exposure. The acute effects of irradiation on the intestine might be attributed to inhibition of mitosis in the crypts, as the loss of proliferative functions impairs development of the small intestinal epithelium and its barrier function. Especially, oxidative damage to intestinal epithelial cells is a key event in the initiation and progression of radiation-induced enteropathy. Pravastatin is widely used clinically to lower serum cholesterol levels and has been reported to have anti-inflammatory effects on endothelial cells. Here, we investigated the therapeutic effects of pravastatin on damaged epithelial cells after radiation-induced enteritis using in vitro and in vivo systems.Materials and Methods: To evaluate the effects of pravastatin on intestinal epithelial cells, we analyzed proliferation and senescence, oxidative damage, and inflammatory cytokine expression in an irradiated human intestinal epithelial cell line (InEpC). In addition, to investigate the therapeutic effects of pravastatin in mice, we performed histological analysis, bacterial translocation assays, and intestinal permeability assays, and also assessed inflammatory cytokine expression, using a radiation-induced enteropathy model.Results: Histological damage such as shortening of villi length and impaired intestinal crypt function was observed in whole abdominal-irradiated mice. However, damage was attenuated in pravastatin-treated animals, in which normalization of intestinal epithelial cell differentiation was also observed. Using in vitro and in vivo systems, we also showed that pravastatin improves the proliferative properties of intestinal epithelial cells and decreases radiation-induced oxidative damage to the intestine. In addition, pravastatin inhibited levels of epithelial-derived inflammatory cytokines including IL-6, IL-1β, and TNF-α in irradiated InEpC cells. We also determined that pravastatin could rescue intestinal barrier dysfunction via anti-inflammatory effects using the mouse model.Conclusion: Pravastatin has a therapeutic effect on intestinal lesions and attenuates radiation-induced epithelial damage by suppressing oxidative stress and the inflammatory response

Enhanced Solubility of the Support in an FDM-Based 3D Printed Structure Using Hydrogen Peroxide under Ultrasonication

Fused deposition modeling (FDM), one of the archetypal 3D printing processes, typically requires support structures matched to printed model parts that principally have undercut or overhung features. Thus, the support removal is an essential postprocessing step after the FDM process. Here, we present an efficient and rapid method to remove the support part of an FDM-manufactured product using the phenomenon of oxidative degradation of hydrogen peroxide. This mechanism was significantly effective on polyvinyl alcohol (PVA), which has been widely used as a support material in the FDM process. Compared to water, hydrogen peroxide provided a two times faster dissolution rate of the PVA material. This could be increased another two times by applying ultrasonication to the solvent. In addition to the rapidness, we confirmed that amount of the support residues removed was enhanced, which was essentially caused by the surface roughness of the FDM-fabricated part. Furthermore, we demonstrated that there was no deterioration with respect to the mechanical properties or shape geometries of the obtained 3D printed parts. Taken together, these results are expected to help enhance the productivity of FDM by reducing the postprocessing time and to allow the removal of complicated and fine support structures, thereby improving the design capability of the FDM technique

Impact of the gate geometry on adiabatic charge pumping in InAs double quantum dots

We compare the adiabatic quantized charge pumping performed in two types of InAs nanowire double quantum dots (DQDs), either with tunnel barriers defined by closely spaced narrow bottom gates, or by well-separated side gates. In the device with an array of bottom gates of 100 nm pitch and 10 mu m lengths, the pump current is quantized only up to frequencies of a few MHz due to the strong capacitive coupling between the bottom gates. In contrast, in devices with well-separated side gates with reduced mutual gate capacitances, we find well-defined pump currents up to 30 MHz. Our experiments demonstrate that high frequency quantized charge pumping requires careful optimization of the device geometry, including the typically neglected gate feed lines

Use of the Putamen/Caudate Volume Ratio for Early Differentiation between Parkinsonian Variant of Multiple System Atrophy and Parkinson Disease

BACKGROUND AND PURPOSE: Neuropathological studies have demonstrated that multiple system atrophy (MSA) produces selective atrophy of the putamen with sparing of the caudate nucleus, while both structures are spared in idiopathic Parkinson's disease (PD). In this study we evaluated the clinical efficacy of using putaminal atrophy in brain MRI to differentiate MSA and PD. METHODS: We measured the putamen/caudate volume ratio on brain MRI in 24 patients with MSA and 21 patients with PD. Two clinicians who were blinded to the patients' diagnoses and to each other's assessments measured the volume ratio using a computer program. RESULTS: The measured volume ratios of the two investigators were highly correlated (r=0.72, p<0.0001). The volume ratio was significantly lower in MSA (1.29+/-0.28) than PD (1.91+/-0.29, p<0.0001). Setting an arbitrary cutoff ratio of 1.6 resulted in about 90% of patients with MSA falling into the group with a lower ratio, whereas more than 80% of patients with PD belonged to the other group. CONCLUSIONS: The present results demonstrate that putaminal atrophy in MSA as measured on brain MRI represents an effective tool for differentiating MSA from PD.ope

Primary Malignant Pericardial Mesothelioma Presenting as Acute Pericarditis

We report on a 21-year-old man with fever, dyspnea, and pleuritic chest pain. An electrocardiography showed ST elevation in multiple lead and thoracic echocardiography revealed moderate pericardial effusion. He was initially diagnosed with acute pericarditis, and treated with nonsteroidal anti-inflammatory drugs and colchicines with clinical and laboratory improvement. After 1 month of medication, his symptoms recurred. An echocardiography showed constrictive physiology and the patient was treated with steroid on the top of current medication. The patient had been well for 7 months until dyspnea and edema developed, when an echocardiography showed marked increased pericardial thickness and constriction. Pericardial biopsy was performed and primary malignant pericardial mesothelioma was diagnosed. Malignancy should be considered in the differential diagnosis of recurrent pericarditis