Recent Advances in Basic Research for Brain Arteriovenous Malformation.

Arteriovenous malformations (AVMs) are abnormal connections of vessels that shunt blood directly from arteries into veins. Rupture of brain AVMs (bAVMs) can cause life-threatening intracranial bleeding. Even though the majority of bAVM cases are sporadic without a family history, some cases are familial. Most of the familial cases of bAVMs are associated with a genetic disorder called hereditary hemorrhagic telangiectasia (HHT). The mechanism of bAVM formation is not fully understood. The most important advances in bAVM basic science research is the identification of somatic mutations of genes in RAS-MAPK pathways. However, the mechanisms by which mutations of these genes lead to AVM formation are largely unknown. In this review, we summarized the latest advance in bAVM studies and discussed some pathways that play important roles in bAVM pathogenesis. We also discussed the therapeutic implications of these pathways

Nearly Massless Electrons in the Silicon Interface with a Metal Film

We demonstrate the realization of nearly massless electrons in the most widely used device material, silicon, at the interface with a metal film. Using angle-resolved photoemission, we found that the surface band of a monolayer lead film drives a hole band of the Si inversion layer formed at the interface with the film to have nearly linear dispersion with an effective mass about 20 times lighter than bulk Si and comparable to graphene. The reduction of mass can be accounted for by repulsive interaction between neighboring bands of the metal film and Si substrate. Our result suggests a promising way to take advantage of massless carriers in silicon-based thin-film devices, which can also be applied for various other semiconductor devices.Comment: 4 pages, 4 figures, accepted for publication in Physical Review Letter

Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis

<p>Abstract</p> <p>Background</p> <p>In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1), and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood.</p> <p>Results</p> <p>In the present study, we show that Distal-less 2 (Dlx-2), a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS) in response to glucose deprivation (GD), one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an <it>in vitro </it>model of solid tumors. Dlx-2 short hairpin RNA (shRNA) inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH) release, indicating the important role(s) of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis.</p> <p>Conclusions</p> <p>These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.</p

Anticholinesterase Therapy for Patients with Ophthalmoplegia Following Snake Bites: Report of Two Cases

Although ophthalmoplegia following snake bites is not indicative of a serious neurotoxic complication, symptoms of diplopia, dizziness and ocular discomfort can be emotionally devastating for patients. The authors experienced two cases of ophthalmoplegia following snake bites in Korea. The patients complained of diplopia that had developed several hours after the snake bites. The diplopia did not improve with antivenom treatment, but resolved completely after several injections of neostigmine

System of integrating biosignals during hemodialysis: the CONTINUAL (Continuous mOnitoriNg viTal sIgN dUring hemodiALysis) registry

Background Appropriate monitoring of intradialytic biosignals is essential to minimize adverse outcomes because intradialytic hypotension and arrhythmia are associated with cardiovascular risk in hemodialysis patients. However, a continuous monitoring system for intradialytic biosignals has not yet been developed. Methods This study investigated a cloud system that hosted a prospective, open-source registry to monitor and collect intradialytic biosignals, which was named the CONTINUAL (Continuous mOnitoriNg viTal sIgN dUring hemodiALysis) registry. This registry was based on real-time multimodal data acquisition, such as blood pressure, heart rate, electrocardiogram, and photoplethysmogram results. Results We analyzed session information from this system for the initial 8 months, including data for some cases with hemodynamic complications such as intradialytic hypotension and arrhythmia. Conclusion This biosignal registry provides valuable data that can be applied to conduct epidemiological surveys on hemodynamic complications during hemodialysis and develop artificial intelligence models that predict biosignal changes which can improve patient outcomes

Purification of plant-derived anti-virus mAb through optimized pH conditions for coupling between protein A and epoxy-activated beads

The main goal of this research was to determine optimum pH conditions for coupling between protein A and epoxy-activated Sepharose beads for purification of monoclonal antibodies (mAbs) expressed in plants. To confirm the effect of pH conditions on purification efficacy, epoxy-activated agarose beads were coupled to protein A under the pH conditions of 8.5, 9.5, 10.5, and 11.5 (8.5R, 9.5R, 10.5R, and 11.5R, respectively). A total of 300 g of fresh leaf tissue of transgenic Arabidopsis expressing human anti-rabies mAb (mAbP) SO57 were harvested to isolate the total soluble protein (TSP). An equal amount of TSP solution was applied to five resin groups including commercial protein A resin (GR) as a positive control. The modified 8.5R, 9.5R, 10.5R, and 11.5R showed delayed elution timing compared to the GR control resin. Nano-drop analysis showed that the total amount of purified mAbPSO57 mAbs from 60 g of fresh leaf mass were not significantly different among 8.5R (400 μg), 9.5R (360 μg), 10.5R (380 μg), and GR (350 μg). The 11.5R (25 μg) had the least mAbPSO57. SDS–PAGE analysis showed that the purity of mAbPSO57 was not significantly different among the five groups. Rapid fluorescent focus inhibition tests revealed that virus-neutralizing efficacies of purified mAbPSO57 from all the five different resins including the positive control resin were similar. Taken together, both pH 8.5 and 10.5 coupling conditions with high recovery rate should be optimized for purification of mAbPSO57 from transgenic Arabidopsis plant, which will eventually reduce down-stream cost required for mAb production using the plant system

Allopurinol-induced DRESS syndrome mimicking biliary obstruction

An 84-year-old man was admitted to our hospital with fever, jaundice, and itching. He had been diagnosed previously with chronic renal failure and diabetes, and had been taking allopurinol medication for 2 months. A physical examination revealed that he had a fever (38.8℃), jaundice, and a generalized maculopapular rash. Azotemia, eosinophilia, atypical lymphocytosis, elevation of liver enzymes, and hyperbilirubinemia were detected by blood analysis. Magnetic resonance cholangiography revealed multiple cysts similar to choledochal cysts in the liver along the biliary tree. Obstructive jaundice was suspected clinically, and so an endoscopic ultrasound examination was performed, which ruled out a diagnosis of obstructive jaundice. The patient was diagnosed with DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome due to allopurinol. Allopurinol treatment was stopped and steroid treatment was started. The patient died from cardiac arrest on day 15 following admission

Clinicopathologic Characteristics of IgA Nephropathy with Steroid-responsive Nephrotic Syndrome

Nephrotic syndrome is an unusual manifestation of IgA Nephropathy (IgAN). Some cases respond to steroid treatment. Here we describe a case-series of IgAN patients with steroid-responsive nephrotic syndrome. Twelve patients with IgAN with steroid-responsive nephrotic syndrome were evaluated and followed up. All patients presented with generalized edema. Renal insufficiency was found in two patients. The renal biopsy of eight patients revealed wide foot process effacement in addition to the typical features of IgAN. They showed complete remission after steroid therapy. Seven relapses were reported in five patients; six of the relapsed cases responded to steroid therapy. Compared with steroid-non-responsive patients, the patients with steroid-responsive nephrotic syndrome had shorter symptom duration, more weight gain, more proteinuria, and lower histologic grade than did those that had steroid-non-responsive nephrotic syndrome at presentation. None of the responders progressed to end stage renal disease, whereas five (38%) non-responders required dialysis or renal transplantation. Patients with IgAN who have steroid-responsive nephrotic syndrome likely have both minimal change disease and IgAN. The clinical features of sudden onset of generalized edema, initial heavy proteinuria and initial severe hypoalbuminemia might help identify the subset of patients, especially in low grade IgAN