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Actinomycosis of the central nervous system is extremely rare. A 73-year-old woman with a history of abdominal actinomycosis presented with sudden-onset headache. Magnetic resonance imaging demonstrated a nodular lesion at the left precentral gyrus. A cerebral angiogram confirmed a fusiform aneurysm arising from the precentral branch of the left middle cerebral artery. High-resolution vessel wall imaging revealed circumferential wall enhancement of the aneurysm and multifocal enhancement of the M3 and M4 segments of both middle cerebral arteries. The patient had received a 4-week course of antibiotics, but follow-up angiography demonstrated no shrinkage or resolution of the aneurysm. Trapping combined with revascularization was successfully performed for refractory mycotic aneurysms. [ABSTRACT FROM AUTHOR]

Although vascular abnormality is an uncommon comorbidity of neurofibromatosis type 1 (NF1), it is potentially fatal. We present spontaneous hemothorax caused by rupture of a vertebral artery (VA) aneurysm in a patient with NF1. A 36-year-old man with a history of NF1 was transferred to the emergency department with dyspnea. Chest computed tomography scan revealed hemothorax in the left lung field with mediastinal shifting and aneurysmal dilatation of the left VA at the C6 vertebra level. Immediate drainage of the hematoma by chest tube insertion was performed. Diagnostic angiogram showed a 3- to 4-cm fusiform aneurysm of the VA. After the angiogram, cardiopulmonary arrest occurred after a rebleed of the VA aneurysm. The aneurysmal segment of the VA was urgently occluded with detachable coils. Postoperatively, the patient was in intensive care for 1 month because of fulminant pneumonia. After the patient regained consciousness, he was found to have right hemiparesis from a small infarction at the pons. The patient's function improved to near normal after 1 year of recovery. Hemothorax caused by VA rupture in a patient with NF1 is an extremely rare condition that can be fatal. Careful examination with suspicion for early detection and treatment is required for this urgent condition. Endovascular coiling was safe even for an unstable patient with massive bleeding. [ABSTRACT FROM AUTHOR]

Tussilagonone is a compound derived from the medicinal plant Tussilago farfara L., which is used as a traditional medicine for respiratory diseases, including asthma and pneumonia. Recent reports suggest that tussilagonone exhibits anti-inflammatory effects; however, the scope of protective functions has not been elucidated yet. In this study, we demonstrate that tussilagonone enhances cellular detoxification by increasing quinone reductase activity in Hepa1c1c7 cells. In addition, tussilagonone decreased tert -butyl hydroperoxide( t -BHP)-induced ROS production and cell death, suggesting that it also acts as a potent antioxidant. To verify the molecular mechanism underlying tussilagonone activity, we examined the expression of nuclear factor erythroid 2-related factor 2(Nrf2)—a transcription factor that regulates antioxidant protein expression—in HepG2 cells. Significantly, these results showed that tussilagonone induces Nrf2 activation and nuclear accumulation, resulting in the upregulation of the detoxifying enzymes NAD(P)H quinone dehydrogenase 1(NQO1) and heme oxygenase-1(HO-1) that protect cells from oxidative stress. Further molecular analyses revealed that tussilagonone-induced Nrf2 activation was mediated by ERK1/2 in HepG2 cells. Collectively, these data indicate that tussilagonone attenuates t -BHP-induced ROS and activates quinone reductase activity via Nrf2 pathway activation and target gene expression, and thereby acts as an antioxidant that protects HepG2 cells from oxidative stress and associated damage. [ABSTRACT FROM AUTHOR]

Background: Periventricular collaterals are associated with high risk of hemorrhagic stroke in adult moyamoya disease (MMD). However, the clinical significance of the periventricular collateral enhancement sign (PCES), which indicates wall enhancement of periventricular collaterals on contrast-enhanced vessel wall imaging (VWI), has yet to be determined.Methods: Thirty-seven patients with MMD with acute neurological symptoms were consecutively recruited. Periventricular collaterals including lenticulostriatal artery, thalamic artery, and choroidal artery collaterals were evaluated on digital subtraction angiography, and then PCES was detected on pre- and postcontrast VWI. First, the association between PCES and hemorrhagic presentation was evaluated using multivariate analyses. Second, two raters investigated the culprit vessels responsible for bleeding in hemorrhagic MMD using the Cohen kappa statistic.Results: Fifteen sites of PCES on postcontrast VWI were observed in 15 patients. Multivariate analysis revealed that hemorrhagic presentation was the only independent factor for PCES (OR = 37.3, 95%CI = 3.9-113, p =.002). In patients with hemorrhagic presentation (n = 20), the identification rate of the ruptured vessel was 80% by rater 1, with excellent agreement. (inter-rater, κ = 0.86, 95%CI = 0.59-1.00; intra-rater, κ = 0.83, 95%CI = 0.50-1.00). Choroidal (50%) and thalamic artery collaterals (15%) were the most common and the second most common types of culprit vessels. Inter-rater and intra-rater reliabilities for the classification of culprit vessels were also excellent (intra-rater, κ = 0.86, 95%CI = 0.67-1.00; inter-rater, κ = 0.93, 95%CI = 0.79-1).Conclusion: Acute hemorrhagic stroke in MMD is independently associated with PCES on postcontrast VWI. PCES can help to detect the culprit vessels that are responsible for hemorrhage in patients with MMD. [ABSTRACT FROM AUTHOR]

Enhanced oxalic acid production was investigated in semi-solid state fermentation of methanol-resistant Aspergillus niger using corncob. Methanol-resistant A. niger was selected from the sector of colony showing phenotypically intact growth despite 5% methanol in solid medium (PDA) and finally obtained through the adaptation process for 22 weeks. Oxalic acid production of methanol-resistant A. niger was dramatically enlarged in liquid culture (CZB) by 9.14 folds compared with that of parent cells. Semi-solid state fermentation of corncob has been developed for the application of low-cost and environment friendly biomass waste to organic acid production. Oxalic acid production was dependent of inoculum size and initial substrate concentration, which was optimized at 10 6 spores/g dry weight and 5% (w/v) corncob in 0.1 N NaOH solution, respectively, which led to the maximum productivity (123.0 g/kg dry weight of corncob). Results demonstrate that methanol-resistant A. niger has great potentials for oxalic acid production from biomass. [ABSTRACT FROM AUTHOR]

Venous malformations are benign vascular lesions that can occur in any part of the body. Esophageal venous malformations can extend into the peritoneum, so preoperative imaging can be decisive in diagnosis and treatment. The characteristic manifestations of venous malformations are transmural phleboliths, centripetal enhancement on dynamic CT, and bluish mucosa on endoscopy. We report a rare case of female patient diagnosed with venous malformations involving laryngoesophagus, mediastinum, and peritoneum, which mimicked carcinomatosis, in addition to a left subclavian vein aneurysm. [ABSTRACT FROM AUTHOR]

Influenza infection increases the risk of ischemic stroke. Here, we represent a case of a 32 year-old female who presented with acutely developed altered mental status after influenza A infection. The clinical manifestation and initial lesion on brain DWI mimicked top of basilar syndrome, but without an arterial occlusion or stenosis. Follow-up neuro imaging analysis suggested cerebral venous infarction. It is valuable to report this case of venous infarction in a healthy young adult, as an uncommon complication of adult influenza infection. [ABSTRACT FROM AUTHOR]

Abstract: Phytochemicals are well known to have cancer chemopreventive effects by induction of phase II detoxification enzymes including quinone reductase (NQO-1) and glutathione-S-transferases. These detoxification enzymes are commonly regulated by nuclear factor-E2 (Nrf2), which is a representative antioxidant and cytoprotective factor involved in cancer chemoprevention. As one of the known quinone reductase (QR) inducers and Nrf2 activators, Gymnasterkoreayne B (GKB) isolated from Gymnaster (Aster) koraiensis was used to elucidate the upstream signalling pathway for Nrf2 regulation. In this study, we confirmed that GKB significantly increases expression levels of Nrf2 in HCT116 human colon cancer cells. We found the probable mechanism of upstream signalling pathways to activate Nrf2 by GKB. To reveal the pathway that affects Nrf2 translocation by GKB, we examined changes in various kinases in HCT116 cells treated with GKB. We observed that ERK and PKC pathways are particularly involved in the activation of Nrf2 by GKB, followed by translocation of Nrf2 and induction of NQO-1. These results suggest that GKB induces Nrf2 translocation and expression by differential regulation of ERK and PKC pathways in HCT116 cells. [Copyright &y& Elsevier]

Abstract: Acute responses of gill mitochondria-rich (MR) cells to direct transfer from freshwater to 70% seawater were examined in a euryhaline teleost Mozambique tilapia (Oreochromis mossambicus). Scanning electron microscopic (SEM) observations revealed that apical openings of MR cells were morphologically classified into an apical pit, a convex apical surface, a concave apical surface, and a transitory apical surface. Meanwhile, in whole-mount immunocytochemistry with anti-Na+/K+-ATPase (NKA), T4 antibody (detecting apical Na+/Cl− cotransporter (NCC) and basolateral Na+/K+/2Cl− cotransporter (NKCC)), and anti-Na+/H+ exchanger-3 (NHE3), NKA-immunoreactive MR cells were functionally classified into immature cells without both NKCC/NCC and NHE3 (type I), ion-absorptive cells with apical NCC (type II), those with apical NHE3 (type III), and ion-secretory cells with basolateral NKCC (type IV). Dual observations of whole-mount immunocytochemistry and SEM clearly showed morphofunctional alterations in MR cells. After transfer to 70% seawater, type-II MR cells with a convex surface or pit closed their apical openings to suspend ion absorption. Type-III MR cells with a concave surface or pit were transformed into type-IV MR cells with an enlarged pit, via a transitory surface. Our findings indicate functional plasticity of type-III/IV MR cells to switch ion-transport functions, whereas type-II MR cells are considered to be specific for freshwater adaptation. [ABSTRACT FROM AUTHOR]

Abstract: Ultraviolet (UV) radiation is the primary environmental risk factor in the development of nonmelanoma skin cancer, and UVB in particular promotes tumor growth through various signaling pathways. Kaempferol, a flavonoid with anti-inflammatory and anti-oxidative properties, has been studied as a chemopreventive agent; however, little is known regarding its effects on UVB-induced photo-carcinogenesis. Here, we examined the effect of kaempferol on UVB-induced skin inflammation. We found that kaempferol suppressed UVB-induced cyclooxygenase-2 (COX-2) protein expression in mouse skin epidermal JB6 P+ cells and attenuated the UVB-induced transcriptional activities of cox-2 and activator protein-1 (AP-1). Kaempferol attenuated the UVB-induced phosphorylation of several mitogen-activated protein kinases (MAPKs), including ERKs, p38, and JNKs, but had no effect on the phosphorylation of the upstream MAPK regulator Src. However, in vitro and ex vivo kinase assays demonstrated that kaempferol suppressed Src kinase activity. Furthermore, in vivo data from mouse skin support the idea that kaempferol suppresses UVB-induced COX-2 expression by blocking Src kinase activity. A pull-down assay revealed that kaempferol competes with ATP for direct binding to Src. Docking data suggest that kaempferol docks easily into the ATP-binding site of Src, which is located between the N and the C lobes of the kinase domain. Taken together, these results suggest that kaempferol is a potent chemopreventive agent against skin cancer through its inhibitory interaction with Src. [ABSTRACT FROM AUTHOR]

Abstract: We investigated a change in tissue fluid osmolality and developmental sequences of mitochondria-rich (MR) cells during embryonic and larval stages of Mozambique tilapia, Oreochromis mossambicus, developing in freshwater. Tissue osmolality, representing body fluid osmolality, ranged from 300 to 370mOsm/kg during embryonic and larval stages. This suggests that tilapia embryos and larvae are also able to regulate body fluid osmolality to some extent, although the levels are somewhat higher and fluctuate more greatly in embryos and larvae than in adults. Na+/K+-ATPase-immunoreactive MR cells were first detected in the yolk-sac membrane 3days before hatching (day −3), followed by their appearance in the body skin on day −2. Subsequently, MR cells in both the yolk-sac membrane and body skin increased in number, and most densely observed on days −1 and 0. Whereas yolk-sac and skin MR cells decreased after hatching, MR cells in turn started developing in the gills after hatching. Thus, the principal site for MR cell distribution shifted from the yolk-sac membrane and body skin during embryonic stages to the gills during larval stages, and tilapia could maintain continuously their ion balance through those MR cells during early life stages. [Copyright &y& Elsevier]

Abstract: Part of pathogen-associated molecular pattern (PAMP) and damage-associated molecular pattern (DAMP) activate antigen-presenting cells through Toll-like receptors (TLRs) to initiate immune responses. However, controversy remains if TLR4 mediates DAMP signaling due to the confounding effects of potential LPS contamination. To test if TLR4 functions as a true receptor for DAMP, we compared TLR4pos- and TLR4neg-responders in vitro and in vivo after stimulation with whole necrotic cell (NC) lysates. Using CHO reporter cells transfected with anti-TLR4-siRNAs, TLR4 was found to partially mediate NF-κB activation in response to NC lysates. TLR4neg DCs exhibited less I-Ab expression and nitric oxide secretion than TLR4pos DCs upon NC stimulation and this defect was well correlated with diminished presentation of H-Y antigen by TLR4neg DCs to I-Ab-restricted CD4pos Marilyn T cells in vitro. Similarly, TLR4neg DCs showed significantly less expression of I-Ab, CD80, CD86, and CD40 than TLR4pos DCs when NC lysates were injected into peritoneal cavity. Finally, delayed type hypersensitivity response to OVA was significantly decreased in TLR4neg mice when NCs were used as an adjuvant. Taken together, our data support the idea that part of the endogenous ligands presented by NCs could activate APCs thru TLR4 and contribute to the development of antigen-specific adaptive immunity. Therefore, endogenous DAMP ligands themselves, not contaminated LPS, activate TLR4 signaling leading to activation of professional antigen-presenting cells. [Copyright &y& Elsevier]

Abstract: Although the health benefits of dietary antioxidants have been extensively studied, their potential negative effects remain unclear. L-Ascorbic acid 6-palmitate (AAP), a synthetic derivative of ascorbic acid (AA), is widely used as an antioxidant and preservative in foods, vitamins, drugs, and cosmetics. Previously, we found that AA exerted an antitumor effect by protecting inhibition of gap-junctional intercellular communication (GJIC), which is closely associated with tumor progression. In this study, we examined whether AAP, an amphipathic derivative of AA, has chemopreventive effects using a GJIC model. AAP and AA exhibited dose-dependent free radical-scavenging activities and inhibited hydrogen peroxide (H2O2)-induced intracellular reactive oxygen species (ROS) production in normal rat liver epithelial cells. Unexpectedly, however, AAP did not protect against the inhibition of GJIC induced by H2O2; instead, it inhibited GJIC synergistically with H2O2. AAP inhibited GJIC in a dose-dependent and reversible manner. This inhibitory effect was not due to the conjugated lipid structure of AAP, as treatment with palmitic acid alone failed to inhibit GJIC under the same conditions. The inhibition of GJIC by AAP was restored in the presence of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126, but not in the presence of other signal inhibitors and antioxidant (PKC inhibitors, EGFR inhibitor, NADPH oxidase inhibitor, catalase, vitamin E, or AA), indicating the critical involvement of MEK signaling in the GJIC inhibitory activity of AAP. Phosphorylation of ERK and connexin 43 (Cx43) was observed following AAP treatment, and this was reversed by U0126. These results suggest that the AAP-induced inhibition of GJIC is mediated by the phosphorylation of Cx43 via activation of the MEK–ERK pathway. Taken together, our results indicate that AAP has a potent carcinogenic effect, and that the influence of dietary antioxidants on carcinogenesis may be paradoxical. [Copyright &y& Elsevier]

Abstract: This paper reviews the concept of filter quality (q F) for dust filtration media composed of different structures: metal fiber beds (MFB), fabric filters (BF), and fly ash filters (FAF). Filter quality is a useful index of the filtration performance, which incorporates both pressure drop and filtration efficiency. Major parameters affecting the filter quality are filtration velocity in the range of 0.06–0.19 m/s, dust loading, porosity of the medium in the range of 75–93%, and internal structure of the medium. The experimental observation showed that filter quality decreased with increasing filtration velocity or dust concentration. A unique increase in filter quality during the initial stage of filtration appeared with the FAF as a result of the predominately surface filtration with less pore clogging. Nevertheless, the filter quality cannot be taken as an absolute indicator of filter performance, but rather it should be used just as a reference parameter depending on operating conditions. The results of this work show that fly ash filters are capable of providing more stable performance, particularly during the initial stage of filtration, and thereafter of a certain time filter quality initiates to decline as other filters. [Copyright &y& Elsevier]

Abstract: This paper describes a new personalized advertisement selection technique based on a customer’s preference scores for product categories. This method performs well, despite having low data and analysis requirements, relative to other methods in use. Customer preference scores are updated based on a customer’s initial profile, purchase history, and behavior in an Internet storefront, and are then used to select and display appropriate advertisements on Internet web pages when the customer visits the Internet storefront. Compared with currently available recommendation techniques such as collaborative filtering or rule-based methods, preference scoring techniques use only a single customer’s data to select appropriate advertisements and do not require a learning data set, and yet have competitive performance and can reflect changes in a customers’ preference. An experiment is performed to compare two alternative data storage structures, the preference table and the preference tree, with random selection and collaborative filtering. [Copyright &y& Elsevier]

Abstract: 2B4 (CD244) is expressed by memory-phenotype CD8+ T cells and all natural killer (NK) cells. The ligand for 2B4, CD48, is expressed on hematopoietic cells. 2B4 is conserved in humans and mice, and a number of reports have linked 2B4 with activation of lymphocytes. We have employed 2B4-deficient mice and antibody blocking to analyze 2B4 function both in vitro and in vivo and found that 2B4 is a receptor with multiple functions. 2B4 is required for optimal activation of CD8+ T cells and NK cells – in this context 2B4 requires interaction with CD48 on neighboring lymphocytes, demonstrating that homotypic interaction within NK cell or T cell populations augments immunity. When 2B4 is engaged by CD48 on a target cell, 2B4 conversely inhibits NK effector function. As an inhibitory receptor, 2B4 is unconventional as it is not regulated by MHC class I molecules. In this review we will discuss the significance of these multiple functions and the events that may regulate differential 2B4 signaling outcome. [Copyright &y& Elsevier]

Purpose: Cerebral microbleeds (CMBs) are considered essential indicators for the diagnosis of cerebrovascular disease and cognitive disorders. Traditionally, CMBs are manually interpreted based on criteria including the shape, diameter, and signal characteristics after an MR examination, such as susceptibility-weighted imaging or gradient echo imaging (GRE). In this paper, an efficient method for CMB detection in GRE scans is presented.Materials and Methods: The proposed framework consists of the following phases: (1) pre-processing (skull extraction), (2) the first training with the ground truth labeled using CMB, (3) the second training with the ground truth labeled with CMB mimicking the same subjects, and (4) post-processing (cerebrospinal fluid (CSF) filtering). The proposed technique was validated on a dataset of 1133 CBMs that consisted of 5284 images for training and 1737 images for testing. We applied a two-stage approach using a region-based CNN method based on You Only Look Once (YOLO) to investigate a novel CMB detection technique.Results: The sensitivity, precision, F1-score and false positive per person (FPavg) were evaluated as 80.96, 60.98, 69.57 and 6.57, 59.69, 62.70, 61.16 and 4.5, 66.90, 79.75, 72.76 and 2.15 for YOLO with a single label, YOLO with double labels, and YOLO + CSF filtering, respectively, and YOLO + CSF filtering showed the highest precision performance, F1-score and lowest FPavg.Conclusions: Using proposed framework, we developed an optimized CMB learning model with low false positives and a balanced performance in clinical practice. [ABSTRACT FROM AUTHOR]

Background and Purpose: Strategy for secondary prevention of ischemic stroke depends on the mechanism of stroke. The aim of this study was to compare the stroke mechanism according to the location and severity of middle cerebral artery (MCA) disease.Methods: We analyzed acute ischemic stroke patients within 7 days of onset with symptomatic MCA disease. The location of MCA disease was classified into proximal MCA M1 (pMCA) and distal MCA M1/proximal M2 (dMCA). The mechanism of stroke was categorized according to the pattern of ischemic lesion: local branch occlusion, artery-to-artery embolism/hemodynamic infarction, in situ-thrombosis, or a combined mechanism. The mechanism and imaging characteristics of stroke were compared according to the location and severity. The factors associated with the stroke mechanism were also investigated.Results: A symptomatic MCA disease was observed in 126 patients (74 pMCA and 52 dMCA). The mechanism of stroke differed according to the location (p < 0.001); the combined mechanism was most common in pMCA disease (54.1%), especially in those who presented with MCA occlusion and with a susceptible vessel sign. Artery-to-artery embolism/hemodynamic infarction was most common in dMCA disease (46.2%). A longer length of stenosis was observed in local branch occlusion than in other mechanisms (p = 0.04) and was an independent factor associated with local branch occlusion (OR=1.631, 95% CI=1.161-2.292; p = 0.005).Conclusions: The mechanism of stroke differed according to the location of MCA disease: occlusion caused by plaque rupture with combined mechanism of stroke type was predominant in pMCA. Longer length of stenosis was associated with local branch occlusion. [ABSTRACT FROM AUTHOR]

An intraosseous lipoma is a rare histologic variant of lipoma, accounting for only 0.1% of all primary bone tumors. This may not be the actual incidence because most of these lesions are frequently asymptomatic, but imaging modalities, such as computed tomography or magnetic resonance imaging (MRI) seem to have increased the detection rate. Lipoma occasionally undergoes osseous metaplasia and becomes an osseous lipoma. Although there are numerous papers discussing intraosseous lipoma and some authors have tried to differentiate lipomas from osseous lipomas, there is still a great deal of confusion with regard to characteristic radiologic features and the use of terms. Use of the mDixon sequence in MRI could be an effective, noninvasive method of lesion detection and differential diagnosis. Texture analysis is a useful technique for capturing intratumoral characteristics. We report what is possibly the first use of the mDixon MRI sequence in the measurement of tumoral texture in a case of the extremely rare inferior nasal turbinate intraosseous lipoma in a 58-year-old female. We conclude that mDixon and texture analysis are helpful methods for differentiating intraosseous lipomas from other masses and confirming the benign characteristics of lipoma. Our review of head and neck intraosseous lipoma could be of particular interest to head and neck surgeons and dental clinicians. [ABSTRACT FROM AUTHOR]

Complex regional pain syndrome (CRPS) is one of the most challenging chronic pain conditions and is characterized by burning pain, allodynia, hyperalgesia, autonomic changes, trophic changes, edema, and functional loss involving mainly the extremities. Until recently, very few reports have been published concerning CRPS involving the orofacial area. We report on a 50-year-old female patient who presented with unbearable pain in all of her teeth and hypersensitivity of the facial skin. She also reported intractable pain in both extremities accompanied by temperature changes and orofacial pain that increased when the other pains were aggravated. In the case of CRPS with trigeminal neuropathic pain, protocols for proper diagnosis and prompt treatment have yet to be established in academia or in the clinical field. We performed functional magnetic resonance imaging for a thorough analysis of the cortical representation of the affected orofacial area immediately before and immediately after isolated light stimulus of the affected hand and foot and concluded that CRPS can be correlated with trigeminal neuropathy in the orofacial area. Furthermore, the patient was treated with carbamazepine administration and stellate ganglion block, which can result in a rapid improvement of pain in the trigeminal region. [ABSTRACT FROM AUTHOR]

Objective Intracranial aneurysm (IA) is the leading cause of subarachnoid hemorrhage. The pathomechanisms of IA are poorly understood but can be related to arterial tortuosity resulting from underlying systemic factors leading to arterial wall weakening. We aimed to analyze the tortuosity of the intracranial artery in a cohort with IA, hypothesizing that the tortuosity of intracranial arteries differs depending on the characteristics of the IA. Methods Patients with saccular IA were consecutively enrolled. Clinical factors and vascular tortuosity of the right and left middle cerebral arteries and basilar artery (BA) of all patients with IA were compared according to the characteristics of the IA: 1) ruptured versus unruptured, 2) multiple versus single, and 3) large (>5 cm) versus small (≤5 cm). Unruptured IAs were comparatively analyzed according to aneurysm size and aspect ratio, whereas ruptured IAs were analyzed according to aneurysm size. Results Two hundred eighty-five patients were enrolled (mean age, 59 years; 71.2% women). The tortuosity of the BA was higher in the large IA group (5.63 ± 6.26; n = 133; P = 0.009), large unruptured IA group (6.64 ± 6.32; n = 53; P = 0.039), and large ruptured IA group (5.50 ± 6.52; n = 80; P = 0.033) compared with the small IA, small unruptured IA, and small ruptured IA group. In multivariate analysis, increased BA tortuosity was significantly associated with large IAs (β = 1.066; P = 0.008), unruptured large IAs (β = 1.077; P = 0.033), and ruptured large IAs (β = 1.086; P = 0.025). Conclusions The BA tortuosity was higher in patients with large IAs, which may represent an imaging biomarker of aneurysm growth. Highlights • The pathomechanism of intracranial aneurysms (IA) are related to arterial wall remodeling. • The BA tortuosity was higher in patients with large IAs. • Tortuosity of the BA may be associated with the growth mechanism of IA. [ABSTRACT FROM AUTHOR]

Summary: Liposuction is the most widely performed cosmetic procedure in the world, and is considered safe and without serious complications. However, necrotising fasciitis has been documented as a rare complication following abdomen and thigh liposuction. We present a case of necrotising fasciitis in a 22-year-old female who underwent cosmetic liposuction in both calves. The diagnosis of necrotising fasciitis was delayed, leading to multi-organ dysfunction and skin necrosis with consequent massive skin loss. Non-cosmetic physicians are generally unfamiliar with liposuction-induced complications, and may not suspect necrotising fasciitis due to its rarity. However, awareness of its clinical features is critical since early diagnosis and prompt surgical debridement can prevent significant morbidity and even death. [ABSTRACT FROM AUTHOR]

Objective: Mammography is the initial examination to detect breast cancer symptoms, and quality control of mammography devices is crucial to maintain accurate diagnosis and to safeguard against degradation of performance. The objective of this study was to assist radiologists in mammography phantom image evaluation by developing and validating an interpretable deep learning model capable of objectively evaluating the quality of standard phantom images for mammography.Materials and Methods: A total of 2,208 mammography phantom images were collected for periodic accreditation of the scanner from 1,755 institutions. The dataset was randomly split into training (1,808 images) and testing (400 images) datasets with subgroups (76 images) for the multi-reader study. To develop an interpretable model that contains two deep learning networks in series, five processing steps were performed: mammography phantom detection, phantom object detection, post-processing, score evaluation, and a report with a comment about ambiguous results.Results: For phantom detection, the accuracy and mean intersection over union (mIOU) were 1.00 and 0.938 in the test dataset, respectively. During phantom object detection, a total of 6,369 out of 6,400 objects were detected as the correct object class, and the accuracy and mIOU were 0.995 and 0.813, respectively. The predicted score for each object showed a consensus of 97.40% excluding ambiguous points and 59.10% for ambiguous points of the groups.Conclusions: The interpretable deep learning model using large-scale data from multiple centers shows high performance and reasonable object scoring, successfully validating the reliability and feasibility of mammography phantom image quality management. [ABSTRACT FROM AUTHOR]

Abstract: The potential health benefits of tea have long been studied. This study examined the role of powdered sea buckthorn leaf tea (SLT) in high-fat diet-induced obese mice. The mice were fed two different doses of SLT (1% and 5%, wt/wt) for six weeks. SLT suppressed body weight gain in a dose-dependent manner and significantly reduced visceral fat, plasma levels of leptin, triglyceride and total cholesterol and ALT activity compared with the high-fat-fed control mice. SLT also decreased hepatic triglyceride and cholesterol concentrations and lipid accumulation, whereas elevated fecal lipid excretion. High-fat feeding resulted in simultaneously decreasing hepatic FAS and G6PD activities and increasing PAP, β-oxidation and CPT activities. However, SLT supplementation during high-fat feeding led to a significant decrease in PAP, β-oxidation and CPT activities with a simultaneous increase in G6PD activity. The hepatic CYP2E1 activity and hepatic and erythrocyte lipid peroxides were significantly lowered with SLT supplements. Hepatic and erythrocyte SOD and CAT activities were also increased with SLT supplements in a dose-dependent manner, whereas GSH-Px activity was increased in erythrocytes only. These results indicate that SLT has potential anti-visceral obesity and antioxidant effects mediated by the regulation of lipid and antioxidant metabolism in high-fat diet-induced obese mice. [Copyright &y& Elsevier]

Abstract: Cocoa, a good source of dietary antioxidative polyphenols, exhibited anticarcinogenic activity in animal models, but the molecular mechanisms of the chemopreventive potential of cocoa remain unclear. Inhibition of gap-junction intercellular communication (GJIC) is strongly related to tumorigenesis. Cocoa polyphenol extracts (CPE) dose dependently attenuated hydrogen peroxide (H2O2)-induced inhibition of GJIC in rat liver epithelial (RLE) cells. CPE inhibited the H2O2-induced phosphorylation and internalization of connexin 43, which is a regulating protein of GJIC in RLE cells. The H2O2-induced accumulation of reactive oxygen species and activation of extracellular signal-regulated kinase were inhibited by CPE treatment. However, CPE did not block H2O2-induced phosphorylation of p38 mitogen-activated protein kinase. An ex vivo kinase assay demonstrated that CPE inhibited the H2O2-induced mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) 1 activity in RLE cell lysates. Ex vivo pull-down assay data revealed that CPE directly bound with MEK1 to inhibit MEK1 activity. These results indicate that CPE protects against the H2O2-induced inhibition of GJIC through antioxidant activity and direct inhibition of MEK activity, which may contribute to its chemopreventive potential. [Copyright &y& Elsevier]

Abstract: Fusarium graminearum virus–DK21 (FgV-DK21), which infects the plant pathogenic F. graminearum, perturbs host developmental processes such as sporulation, morphology, pigmentation, and attenuates the virulence (hypovirulence) of the host. To identify the differentially expressed F. graminearum proteins by FgV-DK21 infection, we have used two-dimensional electrophoresis with mass spectrometry using proteins extracted from virus-free and FgV-DK21-infected strains. A total of 148 spots showing an altered expression were identified by PDQuest™ program. Among these spots, 33 spots were exclusively analyzed including 14 spots from FgV-DK21-infected and 19 spots from virus-free strains by ESI-MS/MS analyses and successfully identified 23 proteins. Seven proteins including sporulation-specific gene SPS2, triose phosphate isomerase, nucleoside diphosphate kinase, and woronin body major protein precursor were induced or significantly up-regulated by FgV-DK21 infection. A significant decrease or down regulation of 16 proteins including enolase, saccharopine dehydrogenase, flavohemoglobin, mannitol dehydrogenase and malate dehydrogenase caused by FgV-DK21 infection was also identified. Variations of protein expression were also further investigated at the mRNA level by real-time RT-PCR analysis, which confirmed the proteomic data for 9 out of the representative 11 selected proteins including 5 proteins from up-regulated group and 6 proteins from down-regulated group. Further investigation of these differentially expressed proteins will provide novel insights into the molecular responses of F. graminearum to FgV-DK21 infection. [Copyright &y& Elsevier]

Although new imaging tools have been developed for the detection of smaller aneurysms, angiographically negative microaneurysms are still encountered during cerebral microsurgery. Currently, only limited information regarding incidence and efficacy of treatment of these microaneurysms is available. We investigated the incidence and treatment of incidental microaneurysms (IMAs) in the last 5 years. IMAs are unidentifiable and invisible on preoperative angiography, but are detected during microvascular surgery. The inclusion criteria were aneurysm cases treated with microsurgery via transsylvian approaches, and those undergoing preoperative digital subtraction angiography. This study enrolled 484 surgical cases (248 cases of subarachnoid hemorrhage and 236 cases of unruptured aneurysms) in 460 patients, and 33 tiny aneurysms were found in 31 operative cases (6.4% incidence per operation). The most typical type was located on another branching site of the middle cerebral artery found during neck clipping of the middle cerebral artery bifurcation aneurysm. A patient with multiple aneurysms presented a statistically significant risk (375/78 vs. 15/16; P < 0.001) of IMA identification. IMAs were treated by clipping and wrapping in 18 and 15 cases, respectively, without complications. This study revealed a 6.4% incidence of IMAs; however, this could be underestimated because of the limited range of inspection. Early detection of an IMA through careful inspection during microvascular surgery could be beneficial, especially in patients with multiple aneurysms. [ABSTRACT FROM AUTHOR]

Biologically and environmentally resorbable electronic devices support application possibilities that cannot be addressed with conventional technologies. This paper presents highly conductive, water-soluble composites that can be printed to form contacts, interconnects, antennas, and other important features that are essential to nearly all systems of this type. An optimized material formulation involves in situ polymerization to yield a polyanhydride containing a dispersion of molybdenum microparticles at appropriate concentrations. Comparisons of essential physical and electrical properties of these materials to those of composites formed with other polymers and other metal microparticles reveal the relevant considerations. Various functional demonstrations of screen-printed test structures and devices illustrate the suitability of these conductive inks for use in water-soluble electronic devices. A key advantage of the material introduced here compared to alternatives is its ability to maintain conductance over significant periods of time while immersed in relevant aqueous solutions. Studies involving live animal models establish the biocompatibility. [ABSTRACT FROM AUTHOR]

Background There are several treatment modalities for vertebral dissecting aneurysms. The purpose of this study was to evaluate the efficacy and safety of triple stent therapy for intracranial vertebral dissecting aneurysm (VDA). Methods Eight patients with 9 VDAs underwent multiple stent insertion therapy. Seven patients who presented with progressive ischemic symptoms and showed changes in follow-up images underwent triple stent insertion therapy, and 1 patient who presented with subarachnoid hemorrhage underwent double stent therapy twice and 1 additional single stent therapy with coil embolization (total 5 stents). Safety, technical feasibility, clinical, and imaging follow-up data for triple stent therapy were retrospectively evaluated. Results Triple stent deployment for VDAs was successfully performed in all 9 VDAs without any procedure-related complication. Among them, 8 unruptured VDAs showed near normalization on follow-up imaging studies within 90 days after the procedure. One case of ruptured VDA showed repeated recurrence without new symptoms and delayed normalization after insertion of 5 stents. Seven patients with long-term follow-up (median clinical follow-up, 22.6 months; median imaging follow-up, 17.1 months) showed clinical and imaging improvement without development of new symptoms. Conclusions Triple stent therapy for VDAs was safe and effective. This technique showed favorable results in clinical and imaging follow-up for unruptured VDAs, although caution is advised for ruptured VDAs. [ABSTRACT FROM AUTHOR]

To overcome the hurdles of immunotherapy, we investigated whether calcipotriol, a synthetic vitamin D analog, could overcome the immune evasion of glioblastoma multiforme (GBM) by modulating immune responses and the immunosuppressive tumor microenvironment. Administration of calcipotriol considerably reduced tumor growth. Both in vivo and in vitro studies revealed that CD8+T and natural killer (NK) cell gene signatures were enriched and activated, producing high levels of IFN-γ and granzyme B. In contrast, regulatory T cells (Treg) were significantly reduced in the calcipotriol-treated group. The expression of CD127, the receptor for thymic stromal lymphopoietin (TSLP), is elevated in CD4+T cells and potentially supports T-cell priming. Depleting CD4+T cells, but not NK or CD8+T cells, completely abrogated the antitumor efficacy of calcipotriol. These data highlight that the calcipotriol/TSLP/CD4+T axis can activate CD8+T and NK cells with a concomitant reduction in the number of Tregs in GBM. Therefore, calcipotriol can be a novel therapeutic modality to overcome the immune resistance of GBM by converting immunologically "cold" tumors into "hot" tumors. Data are available upon reasonable request. The RNA-seq dataset comparing the transcriptomes of control and calcipotriol-treated GL261 tumors is available from the corresponding author upon request. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Historical records reveal that in traditional medicine, a disease similar to diabetes was treated with ginseng. Korean red ginseng has been considered beneficial as a dietary supplement for its anti-diabetic potential. Aim: This study was designed to investigate the prophylactic potential of Korean red ginseng (KRG) extract (Panax ginseng C.A. Meyer Radix Rubra) in a well-established mouse model of Type 1 diabetes (T1D). Materials and methods: The prophylactic effect of KRG extract was evaluated in mice fed with KRG extract for two weeks prior to induction of diabetes by streptozotocin (STZ) administration. Glucose levels and glucose challenge test results of KRG-treated diabetic mice were compared to those of untreated diabetic mice and healthy control mice. Examination of the immune compartments in lymphoid organs and immunohistochemical staining of pancreas for islet cell morphology and insulin producing beta cells were performed. Results: KRG extract significantly lowered blood glucose levels to an average of 250mg/dl from 350mg/dl and improved glucose challenge testing when applied as prophylaxis. Histological findings indicated that KRG extract protected against STZ-induced destruction of pancreatic tissue and restored insulin secretion. Strikingly, this effect was accompanied by restoration of lymphocytes in secondary lymphoid organs, suggesting that KRG extract facilitated immune homeostasis. Conclusion: This is the first report to demonstrate the prophylactic function of KRG extract in ameliorating the hyperglycemia of T1D. Immune compartments of diabetic mice were found to be preserved in KRG-treated mice suggesting that Korean red ginseng may benefit T1D patients, not only for its hypoglycemic but also for its immunomodulatory effects. [Copyright &y& Elsevier]

Abstract: Benzo[a]pyrene-7,8-diol-9,10-epoxide (B[a]PDE) is a well-known carcinogen that is associated with skin cancer. Abnormal expression of cyclooxygenase-2 (COX-2) is an important mediator in inflammation and tumor promotion. We investigated the inhibitory effect of cyanidin-3-glucoside (C3G), an anthocyanin present in fruits, on B[a]PDE-induced COX-2 expression in mouse epidermal JB6 P+ cells. Pretreatment with C3G resulted in the reduction of B[a]PDE-induced expression of COX-2 and COX-2 promoter activity. The activation of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) induced by B[a]PDE was also attenuated by C3G. C3G attenuated the B[a]PDE-induced phosphorylation of MEK, MKK4, Akt, and mitogen-activated protein kinases (MAPKs), but no effect on the phosphorylation of the upstream MAPK regulator Fyn. However, kinase assays demonstrated that C3G suppressed Fyn kinase activity and C3G directly binds Fyn kinase noncompetitively with ATP. By using PP2, a pharmacological inhibitor for SFKs, we showed that Fyn kinase regulates B[a]PDE-induced COX-2 expression by activating MAPKs, AP-1 and NF-κB. These results suggest that C3G suppresses B[a]PDE-induced COX-2 expression mainly by blocking the activation of the Fyn signaling pathway, which may contribute to its chemopreventive potential. [Copyright &y& Elsevier]

Abstract: Dendritic cell (DC)-based cancer vaccines have become important as an immunotherapeutics in generating anti-tumor immune responses. Due to a short lifespan of DCs, however, clinical application of current DC vaccines has been limited. Recently, activation of AKT/protein kinase B (PKB), a major effector of phosphatidylinositol 3-kinase (PI3K), has been reported as a critical factor in both activation and survival of DCs. We here improved the potency of a DC vaccine with a small interfering RNA (siRNA) targeting phosphatase and tensin homologue (PTEN), which is known to be a central negative regulator of the PI3K/AKT signal transduction cascade. Down-regulation of PTEN in DCs resulted in AKT dependent maturation, which in turn caused a significant up-regulation of surface expression in co-stimulatory molecules and the chemokine receptor, CCR7, leading to an increase of in vitro T cell activation activity and in vivo migration to a draining lymph node, respectively. Moreover, these PTEN siRNA-transfected DCs (DC/siPTEN) acquired an increased survival from the apoptotic death caused by GM-CSF deprivation or antigen-specific CD8+ T cell killing. Most importantly, DC/siPTEN generated more tumor antigen-specific CD8+ T cells and stronger anti-tumor effects in vaccinated mice than did control DCs (DC/siGFP). Thus, our data indicate that manipulation of the PI3K/AKT pathway via siRNA system could improve the efficacy of a DC-based tumor vaccine. [ABSTRACT FROM AUTHOR]

Abstract: We developed a novel vaccine platform utilizing Bifidobacterium as an antigen delivery vehicle for mucosal immunization. Genetically modified Bifidobacterium longum displaying Salmonella-flagellin on the cell surface was constructed for the oral typhoid vaccine. The efficiency of this vaccine was evaluated in a murine model of typhoid fever. We then orally administered 2.5×107 CFU of the recombinant Bifidobacterium longum (vaccine) or parental Bifidobacterium longum, or PBS to BALB/C mice every other day for 2 weeks. After the administration, a total of 42 mice (14 mice in each group) were challenged with Salmonella Typhimurium (1.0×107 CFU/mouse). While 12 mice in the PBS group, and 9 in the parental Bifidobacterium longum group died (median survival: 14 and 25 days), only two in the vaccine group died. These data support that our genetically modified Bifidobacterium antigen delivery system offers a promising vaccine platform for inducing efficient mucosal immunity. [ABSTRACT FROM AUTHOR]

Abstract: Aggressive bladder cancer is a major cause of morbidity and mortality. Despite the fact that metastatic disease results in death in the majority of bladder cancer cases, the molecular events regulating the invasive phenotype of aggressive bladder cancer are not well understood. In this study, immunohistochemical examination showed that the leukotriene B4 receptor BLT2 is overexpressed in advanced malignant bladder cancers (human transitional cell carcinomas) in proportion to advancing stages, with high prognostic significance (p <0.001). Blockade of BLT2 with the specific antagonist LY255283 or siRNA knockdown significantly suppressed the invasiveness of highly aggressive 253J-BV bladder cancer cells. Moreover, our results demonstrated that BLT2 mediates invasiveness through a signaling pathway dependent on NAD(P)H oxidase (Nox) 1- and Nox4-induced generation of reactive oxygen species (ROS) and subsequent NF-κB stimulation. Metastasis of 253J-BV cells in mice was also dramatically suppressed by inhibition of BLT2 or its signaling. These findings suggest that a BLT2–Nox–ROS–NF–κB cascade plays a critical role in bladder cancer invasion and metastasis. [ABSTRACT FROM AUTHOR]

Buckwheat allergy cases are increasingly reported worldwide, coinciding with the increasing consumption of buckwheat due to its high nutritional content. To detect the presence of buckwheat contaminants in food, we designed a buckwheat allergen-specific primer targeting Fag e 1 for use in an ultrafast PCR assay. This method amplified only common and Tartary buckwheat, and showed no cross-reactivity against 22 other plant samples. The limit of detection is 10 copies of plasmid DNA and 0.001% of buckwheat in wheat noodles, similar to that obtained from real-time PCR. In addition, this ultrafast PCR assay successfully detected buckwheat in processed foods within 25 min. The practical application of this method is similar to that of real-time PCR or ELISA. Thus, the ultrafast PCR assay we developed could be utilized as a highly specific and sensitive method for buckwheat detection in processed foods. • Ultrafast PCR for was developed to detect buckwheat allergen Fag e 1. • Buckwheat-specific primer sets amplified both common and Tartary buckwheat. • The limit of detection of this assay was 0.001% buckwheat in wheat. • Practical application in processed foods is similar to that of real-time PCR or ELISA. • This assay takes only 25 min to identify buckwheat in processed products. [ABSTRACT FROM AUTHOR]

Abstract: We explored the feasibility of magnetite (Fe3O4)-gold (Au) core–shell nanocrystals as a useful vehicle for biomedical application such as cell separation. Streptavidin-fluorescein isothiocyanate (STA-FITC) was conjugated to the surface of the Fe3O4-Au core–shell nanocrystals using a carbodimide activation protocol. These nanocrystals were further tested for their ability to bind CD4+ T lymphocytes, bound to biotin-labeled anti-CD4 mAbs, isolated from the spleen of C57BL/6 mice. Our data show that the Fe3O4-Au nanocrystals successfully pulled down CD4+ T lymphocytes from the whole splenocytes with high specificity. Therefore, our nanocrystals provide an efficient tool for the cell separation process and further present the dramatic potential to be applied to other areas of biomedical application including diagnosis, monitoring, and treatment of human diseases. [Copyright &y& Elsevier]

Abstract: We explored molecular and morphological alteration in gill mitochondria-rich (MR) cells of Mozambique tilapia, Oreochromis mossambicus, acclimated to deionized freshwater (DFW), freshwater (FW), 1/3-diluted seawater (1/3 SW) and seawater (SW). Scanning electron microscopic observations revealed that the apical membrane of MR cells appeared as a flat or slightly projecting disk in DFW and FW, being larger in DFW than in FW. In contrast, the apical membrane typically formed a pit structure in 1/3 SW and SW. The mRNA expression levels of Na+/H+ exchanger-3 (NHE3) and Na+/Cl− cotransporter (NCC) in the gills were increased with decreasing environmental salinity, whereas Na+/K+/2Cl− cotransporter-1a (NKCC1a) expression was upregulated by increasing salinity. Immunofluorescence staining showed that the MR cell population of DFW- and FW-acclimated tilapia consisted mostly of MR cells with apical NHE3 and those with apical-NCC; MR cells with basolateral NKCC1a dominated in SW-acclimated tilapia. These results indicated that apical-NHE3 and apical-NCC MR cells were ion-absorbing cells, and that basolateral-NKCC1a MR cells were ion-secreting cells. In fish acclimated to 1/3 SW, both ion-absorbing and secreting cells existed in the gills, suggesting that fish in near-isotonic water were equipped with mechanisms of both hyper- and hypoosmoregulation to prepare for environmental salinity changes. [Copyright &y& Elsevier]

We have cloned and characterized a cDNA encoding the luciferase from the firefly, Hotaria unmunsana. The cDNA encoding the luciferase of H. unmunsana was isolated by RT-PCR with a gene-specific primer set. The cDNA encoding the luciferase of H. unmunsana is 1644 base pairs long with an open reading frame of 548 amino acid residues. The deduced amino acid sequence of the luciferase gene of H. unmunsana showed 98.0 and 96.8% identity to H. parvula and Luciola mingrelica, respectively. Phylogenetic analysis further confirmed that the deduced amino acid sequences of the H. unmunsana luciferase gene belonged to the same subfamily, Luciolinae. Southern blot analysis of genomic DNA suggested the presence of the H. unmunsana luciferase gene as a single copy and Northern blot analysis confirmed light organ-specific expression at the transcriptional level. The cDNA encoding the luciferase of H. unmunsana was expressed as a 61-kDa band in the baculovirus-infected insect cells and the extracts of the recombinant baculovirus-infected cells emitted luminescence in the luciferase activity assay. [Copyright &y& Elsevier]