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Objective: Neurophysiological changes related to meditation have recently attracted scientific attention. We aimed to detect changes in electroencephalography (EEG) parameters induced by a meditative intervention in subjects with post-traumatic residual disability (PTRD), which has been confirmed for effectiveness and safety in a previous study. This will allow us to estimate the objective effect of this intervention at the neurophysiological level. Methods: Ten subjects with PTRD were recruited and underwent psychological assessment and EEG recordings before and after the meditative intervention. Furthermore, 10 additional subjects were recruited as normal controls. Source current density as an EEG parameter was estimated by exact Low Resolution Electromagnetic Tomography (eLORETA). Comparisons of source current density in PTRD subjects after the meditative intervention with normal controls were investigated. Additionally, we compared source current density in PTRD subjects between before and after meditative intervention. Correlations between psychological assessments and source current density were also explored. Results: After meditative intervention, PTRD subjects exhibited increased gamma activity in the left inferior parietal lobule relative to normal controls. In addition, changes of delta activity in the right precuneus correlated with changes in the psychological score on role physical item, one of the quality of life scales reflecting the work or daily difficulty due to physical problems. Conclusions: These results show that the meditative intervention used in this study produces neurophysiological changes, in particular the modulation of oscillatory activity of the brain. Significance: Our meditative interventions might induce the neurophysiological changes associated with the improvement of psychological symptoms in the PTRD subjects. Keywords: EEG, Meditation, eLORETA, PTRD, Gamma band, Delta band

BackgroundRenal medullary carcinoma (RMC) is a rare but aggressive tumor often complicated by early lung metastasis with few treatment options and very poor outcomes. There are currently no verified RMC patient-derived xenograft (PDX) mouse models established from metastatic pleural effusion (PE) available to study RMC and evaluate new therapeutic options.MethodsRenal tumor tissue and malignant PE cells from an RMC patient were successfully engrafted into 20 NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. We evaluated the histopathological similarity of the renal tumor and PE PDXs with the original patient renal tumor and PE, respectively. We then evaluated the molecular integrity of the renal tumor PDXs between passages, as well as the PE PDX compared to two generations of renal tumor PDXs, by microarray analysis. The therapeutic efficacy of sunitinib and temsirolimus was tested in a serially-transplanted generation of 27 PE PDX mice.ResultsThe pathologic characteristics of the patient renal tumor and patient PE were retained in the PDXs. Gene expression profiling revealed high concordance between the two generations of renal tumor PDXs (RMC-P0 vs. RMC-P1, r=0.865), as well as between the first generation PE PDX and each generation of the renal tumor PDX (PE-P0 vs. RMC-P0, r=0.919 and PE-P0 vs. RMC-P1, r=0.843). A low number (626) of differentially-expressed genes (DEGs) was seen between the first generation PE PDX and the first generation renal tumor PDX. In the PE-P1 xenograft, sunitinib significantly reduced tumor growth (p

Background and study aims The relationship between acute colonic diverticulitis and colorectal cancer (CRC) is unclear, but colonoscopy is recommended to exclude malignancy. We compared the detection rates for colorectal neoplasia in patients with colonic diverticulitis and asymptomatic patients who had positive fecal immunochemical tests (FITs). Patients and methods In total, 282 patients with acute colonic diverticulitis were hospitalized in our hospital from February 2011 to December 2019. Of them, 143 patients with diverticulitis and 1819 with positive FITs patients during the same period underwent colonoscopy without a prior colonoscopy within 5 years. We retrospectively compared these patients in terms of the invasive CRC rate, advanced neoplasia detection rate (ANDR), adenoma detection rate (ADR), and polyp detection rate (PDR). Results Compared to the diverticulitis group, the FIT-positive group had a significantly higher CRC rate (0 vs 2.7 %, P = 0.0061), ANDR (5.6 vs. 14.0 %, P = 0.0017), ADR (19.6 vs. 53.2 %, P

In the murine liver, there are two major macrophage populations, namely resident Kupffer cells (resKCs) with phagocytic activity and recruited macrophages (recMφs) with cytokine-producing capacity. This study was performed to clarify the functional differences between these two populations, focusing on their susceptibility to radiation and response to stimulation via liver X receptors (LXRs), which are implicated in cholesterol metabolism and immune regulation. Liver mononuclear cells (MNCs) were obtained from C57BL/6 (WT) mice with or without 2 Gy irradiation, and the phagocytic activity against Escherichia coli (E. coli) as well as TNF-α production were compared between the two macrophage populations. To assess LXR functions, phagocytosis, TNF-α production, and endocytosis of acetylated low-density lipoprotein (LDL) were compared after synthetic LXR ligand stimulation. Furthermore, LXRα/β knockout (KO) mice and LXRα KO mice were compared with WT mice. Irradiation decreased intracellular TNF-α production by recMφs but did not affect the phagocytic activity of resKCs. In vitro LXR stimulation enhanced E. coli phagocytosis by resKCs but decreased E. coli-stimulated TNF-α production by recMφs. Phagocytic activity and acetylated LDL endocytosis were decreased in both LXRα/β KO mice and LXRα KO mice, with serum TNF-α levels after E. coli injection in the former being higher than those in WT mice. In conclusion, resKCs and recMφs exhibited different functional features in response to radiation and LXR stimulation, highlighting their distinct roles liver immunity and lipid metabolism.

Structural and thermodynamic factors which may influence burnt bone survivorship in archaeological contexts have not been fully described. A highly controlled experimental reference collection of fresh, modern bone burned in temperature increments 100-1200˚C is presented here to document the changes to bone tissue relevant to preservation using Fourier transform infrared spectroscopy and X-ray diffraction. Specific parameters investigated here include the rate of organic loss, amount of bone mineral recrystallization, and average growth in bone mineral crystallite size. An archaeological faunal assemblage ca. 30,000 years ago from Tolbor-17 (Mongolia) is additionally considered to confirm visibility of changes seen in the modern reference sample and to relate structural changes to commonly used zooarchaeological scales of burning intensity. The timing of our results indicates that the loss of organic components in both modern and archaeological bone burnt to temperatures up to 700˚C are not accompanied by growth changes in the average crystallite size of bone mineral bioapatite, leaving the small and reactive bioapatite crystals of charred and carbonized bone exposed to diagenetic agents in depositional contexts. For bones burnt to temperatures of 700˚C and above, two major increases in average crystallite size are noted which effectively decrease the available surface area of bone mineral crystals, decreasing reactivity and offering greater thermodynamic stability despite the mechanical fragility of calcined bone. We discuss the archaeological implications of these observations within the context of Tolbor-17 and the challenges of identifying anthropogenic fire.

Postural control in quiet standing is often explained by a reflexive response to optical flow, the apparent motion of environmental objects in a visual scene. However, moving room experiments show that even small-amplitude body sway can evoke odd sensations or motion sickness, indicating that a consciousness factor may also be involved. Studies targeting perception of self-motion, vection, typically use rapid visual stimuli moving in a single direction to maintain a constant feeling of vection, and there are few studies of vection using low-speed sinusoidal visual stimuli similar to human pendular movement. In the present study we searched for changes in postural control during periods of vection during quiet standing. Participants (N = 19, age = 20.4 ±1.1 years) were shown dynamic visual stimuli in the form of sinusoidally expanding and contracting random dots, and the stimuli speed and visual field were manipulated. Posture was continually evaluated using Center of Pressure (CoP) measurements. Participants were also asked to report feelings of vection, both by pressing a button during the trial and through an overall rating at the end of each trial. Using repeated-measures ANOVA, we assessed changes in the CoP and vection variables between experimental conditions, as well as possible interactions between the variables. The results show that postural reaction and vection were both affected by the visual stimuli and varied with speed. The peripheral visual field was found to couple to stronger feeling of vection and better quality of postural control. However, no significant relationship between postural control and vection, nor evidence of vection interaction to the relationship between optical flow and postural control, was found. Based on our results we conclude that for postural stability during quiet standing, visual cues dominate over any potential consciousness factor arising due to vection.

Elucidating the mechanisms of mild traumatic brain injuries (mild TBIs), including concussions, is important for developing brain injury criteria and designing head protection devices. Using a finite element (FE) model of the human brain to predict the deformation of the brain parenchyma during a head impact could provide mechanical insights on mild TBIs. However, most conventional brain FE models do not consider how fluid behavior and the perfusion pressure of the cerebrospinal fluid (CSF) will affect brain deformation. This study proposes a novel brain FE model that uses incompressible fluid dynamics (ICFD) to represent the fluid behavior of CSF in the ventricle. In the model with ICFD, the validation accuracy scores on the brain strain during a head impact with a rotational acceleration were significantly higher than those in the model without ICFD. Reconstruction simulations based on two reported mild TBI cases from a rear-end collision and an American football game were conducted using the model with and without ICFD. We found that the maximum principal strain values in the subcortical region and corpus callosum of the model with ICFD were higher and lasted longer than those of the model without ICFD, and this tendency was further enhanced when perfusion pressure was applied. These findings suggested that the fluid behavior and perfusion pressure of the intraventricular CSF could significantly affect the deformation of the brain parenchyma during head impacts. The proposed brain multiphysical FE model could enhance the understanding of mild TBI mechanisms. Statement of Significance: Mild TBIs or concussions can result from brain deformations caused by the rapid acceleration of the head in the situations such as falls, vehicular accidents, and collisions in sports-related activities. A FE analysis is an effective tool for simulating head impact scenarios associated with mild TBIs and estimating the brain strain. Accurate prediction of mild TBIs requires a brain FE model with high biofidelity. Here, we firstly revealed that the validation accuracy of the model on the brain strain can be improved by considering the fluid behavior of intraventricular CSF. By analyzing existing mild TBI cases using the proposed model, the fluid behavior and perfusion pressure of the CSF were found to significantly affect the brain strain history, resulting in an outcome similar to the clinical symptom. The proposed multiphysical brain model could potentially provide new mechanical insights and further understanding of mild TBIs. Additionally, these findings in this study could be useful in developing brain injury criteria and designing protective equipment.

Background and study aims Fluoroscopy-guided gastrointestinal procedures (FGPs) are increasingly common. However, the radiation exposure (RE) to patients undergoing FGPs is still unclear. We examined the actual RE of FGPs. Patients and methods This retrospective, single-center cohort study included consecutive FGPs, including endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasound (EUS), enteral stenting, balloon-assisted enteroscopy, tube placement, endoscopic injection sclerotherapy (EIS), esophageal balloon dilatation and repositioning for sigmoid volvulus, from September 2012 to June 2019. We measured the air kerma (AK, mGy), dose area product (DAP, Gycm2), and fluoroscopy time (FT, min) for each procedure. Results In total, 3831 patients were enrolled. Overall, 2778 ERCPs were performed. The median AK, DAP, and FT were as follows: ERCP: 109 mGy, 13.3 Gycm2 and 10.0 min; self-expandable enteral stenting (SEMS): 62 mGy, 12.4 Gycm2 and 10.4 min; tube placement: 40 mGy, 13.8 Gycm2 and 11.1 min; balloon-assisted enteroscopy: 43 mGy, 22.4 Gycm2 and 18.2 min; EUS cyst drainage (EUS-CD): 96 mGy, 18.3 Gycm2 and 10.4 min; EIS: 36 mGy, 8.1 Gycm2 and 4.4 min; esophageal balloon dilatation: 9 mGy, 2.2 Gycm2 and 1.8 min; and repositioning for sigmoid volvulus: 7 mGy, 4.7 Gycm2 and 1.6 min. Conclusion This large series reporting actual RE doses of various FGPs could serve as a reference for future prospective studies.

This data article presents supplementary material for our report “Role of obstetricians in promoting pregnancy-related knowledge among women with epilepsy in Japan” (Egawa et al. 2020). To provide more effective preconception counseling and perinatal care, we surveyed the attitude of epileptologists and obstetricians about pregnancy-related issues in women with epilepsy (WWE). Obstetricians said they needed information from epileptologists about seizure for management of WWE. Half of epileptologists did not feel the need to communicate with obstetricians before their patients’ pregnancy; they only contacted obstetricians after their patients became pregnant, and they only referred patients to an obstetrician if requested by the patient.

Hematopoietic cell transplantation (HCT) is established as a curative treatment for severe chronic granulomatous disease (CGD). However, outcomes of HCT for CGD in Japan had not been precisely reported. We evaluated the outcome of HCT for CGD in Japan by means of a nationwide survey. A total of 91 patients (86 males and 5 females) with CGD who received HCT between 1992 and 2013 was investigated. Their median age at HCT was 11 years (0–39). Sixty-four patients had X-linked CGD caused by CYBB gene mutations, 13 had autosomal recessive CGD (7 CYBA and 6 NCF2), and 14 were genetically undetermined. Seventy patients are still alive at a median follow-up of 38.9 (3.7–230) months. Three-year OS and EFS was 73.7 and 67.6%, respectively. Twenty-one patients died mainly from transplant-related mortality. The cumulative incidence of grade II to IV acute GVHD and extensive chronic GVHD was 27.2 and 17.9%, respectively. Risk factors for EFS after HCT for CGD were age >30 years (P < 0.01), non-CYBB gene mutations (P < 0.01) and CBT (P < 0.01). Regarding the reduced intensity conditioning (RIC) regimen, risk factors for EFS included anti-thymocyte globulin (P = 0.048) and not using low-dose irradiation therapy (P < 0.01), in addition to the preceding risk factors. We report outcomes of HCT for CGD in Japan. Future studies are needed to improve such outcomes, especially for patients harboring non-CYBB gene mutations and suffering from adult CGD. A RIC regimen including low-dose irradiation may be a good option to explore further.

Along with the tumor progression, the bone marrow microenvironment is skewed in multiple myeloma (MM), which underlies the unique pathophysiology of MM and confers aggressiveness and drug resistance in MM cells. TGF-β-activated kinase-1 (TAK1) mediates a wide range of intracellular signaling pathways. We demonstrate here that TAK1 is constitutively overexpressed and phosphorylated in MM cells, and that TAK1 inhibition suppresses the activation of NF-κB, p38MAPK, ERK and STAT3 to decrease the expression of critical mediators for MM growth and survival, including PIM2, MYC, Mcl-1, IRF4, and Sp1, along with a substantial reduction in the angiogenic factor VEGF in MM cells. Intriguingly, TAK1 phosphorylation was also induced along with upregulation of vascular cell adhesion molecule-1 (VCAM-1) in bone marrow stromal cells (BMSCs) in cocultures with MM cells, which facilitated MM cell-BMSC adhesion while inducing IL-6 production and receptor activator of nuclear factor κ-Β ligand (RANKL) expression by BMSCs. TAK1 inhibition effectively impaired MM cell adhesion to BMSCs to disrupt the support of MM cell growth and survival by BMSCs. Furthermore, TAK1 inhibition suppressed osteoclastogenesis enhanced by RANKL in cocultures of bone marrow cells with MM cells, and restored osteoblastic differentiation suppressed by MM cells or inhibitory factors for osteoblastogenesis overproduced in MM. Finally, treatment with the TAK1 inhibitor LLZ1640-2 markedly suppressed MM tumor growth and prevented bone destruction and loss in mouse MM models. Therefore, TAK1 inhibition may be a promising therapeutic option targeting not only MM cells but also the skewed bone marrow microenvironment in MM.

Coverage path planning technique is an essential ingredient in every floor cleaning robotic systems. Even though numerous approaches demonstrate the benefits of conventional coverage motion planning techniques, they are mostly limited to fixed morphological platforms. In this article, we put forward a novel motion planning technique for a Tetris-inspired reconfigurable floor cleaning robot named “hTetro” that can reconfigure its morphology to any of the seven one-sided Tetris pieces. The proposed motion planning technique adapts polyomino tiling theory to tile a defined space, generates reference coordinates, and produces a navigation path to traverse on the generated tile-set with an objective of maximizing the area coverage. We have summarized all these aspects and concluded with experiments in a simulated environment that benchmarks the proposed technique with conventional approaches. The results show that the proposed motion planning technique achieves significantly higher performance in terms of area recovered than the traditional methods.

Under natural environment plants experience different light intensities which can affect photosynthesis and consequently the availability of carbohydrates for daytime growth and their transient storage to supply night growth. We grew a spring barley cultivar, Propino, under three different light intensities under warm days and nights, and evaluated the spatial and diurnal adjustments occurring in the transient carbon stores. Leaves under high light at the end of the day accumulated mainly sucrose (30%) and malate (35%), with lower content of hexoses (5%), starch (15%) and fructans (15%). Under low light, plants presented reduced photosynthesis, with lower metabolite contents at end of day. The malate represented 51% of the total carbon accumulated at end of the day, at the expense of sucrose (12%), other metabolite contributions remaining similar to high light. The percentage of metabolites consumed at night was similar for all light intensities with around 75% of the sucrose and starch being mobilized whilst malate and fructans were only partially mobilized with 56 and 44%, respectively. Altogether, sucrose and malate were the main contributors of the total carbon used at night by barley plants, sucrose being predominant under high light (35% vs. 27%), but malate being the major metabolite used under low light with 40% of the total carbon consumed. Interestingly, light intensity also influenced the location of the C transient stores, the plants under low light prioritizing the accumulation of the metabolites, mostly malate, in the youngest tissues. Therefore, light influences quantitatively, but also qualitatively and spatially the carbon stores in the spring barley cv. Propino, suggesting a tight regulation of the primary metabolism.

IntroductionRecently, the use of various endoscopic procedures under X-ray fluoroscopic guidance, such as endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasonography (EUS), enteral endoscopy and stenting, has been rapidly increasing because of the minimally invasive nature of these procedures compared with that of surgical intervention. With the spread of CT and fluoroscopic interventions, including endoscopic procedures under X-ray guidance, high levels of radiation exposure (RE) from medical imaging have led to major concerns throughout society. However, information about RE related to these image-guided procedures in gastrointestinal endoscopy is scarce, and the RE reference levels have not been established. The aim of this study is to prospectively collect the actual RE dose and to help establish diagnostic reference levels (DRLs) in the field of gastroenterology in Japan.Methods and analysisThis is a multicentre, prospective observational study that is being conducted to collect the actual RE from treatments and diagnostic procedures, including ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement. We will measure the total fluoroscopy time (min), the total dose–area product (Gycm2) and air-kerma (mGy) of those procedures. Because we are collecting the actual RE data and identifying the influential factors through a prospective, nationwide design, this study will provide guidance regarding the DRLs of ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement.Ethics and disseminationApproval was obtained from the Institutional Review Board of Toyonaka Municipal Hospital (25 April 2019). The need for informed consent will be waived via the opt-out method of each hospital website.Trial registration numberThe UMIN Clinical Trials Registry, UMIN000036525.

A 37-year-old man had an asymptomatic 17-mm mass in the liver by health check with ultrasonography. Five years later, he was referred to our hospital because the mass was slightly enlarged with a peripancreatic lymph node. We performed endoscopic ultrasonography fine-needle aspiration (EUS-FNA) to evaluate a lymph node, but it showed amorphous eosinophilic material and eosinophilic infiltrate in necrotic tissue of toothpaste-like white specimen. However, we diagnosed as potentially malignant liver mass with lymph node metastasis because of 2-deoxy-2-(fluorine-18) fluorodeoxyglucose uptake. We then performed hepatectomy and enucleation of the pancreas. DNA polymerase chain reaction analysis revealed Echinococcus multilocularis infection. Retrospectively, we could find a part of Echinococcus in the specimens of EUS-FNA.

Combination treatment of ledipasvir and sofosbuvir (LDV/SOF) is first‐line treatment for patients with chronic hepatitis C genotype 1 in the United States, Europe, and Japan. However, the influence of LDV/SOF on the cardiovascular system is poorly characterized. A total of 470 chronic hepatitis C patients who started LDV/SOF treatment between September 2015 and February 2016 at nine hospitals in Japan were prospectively enrolled in this study. Corrected QT (QTc) prolongation was defined as a QTc interval ≥450 milliseconds. The sustained virologic response rate was 96.0% (451/470), and the discontinuance rate due to adverse effects was 0.9% (4/470). Among 395 patients whose electrocardiogram was evaluated over time and compared with baseline, the QTc interval was significantly prolonged during treatment and returned to baseline levels 12 weeks after the end of treatment. Twenty‐four of 376 patients with baseline QTc intervals

Avoidance of frontal collisions by autonomous emergency braking (AEB) in sudden traffic jams has the potential to cause rear-end collisions by the following cars. In this study, finite element analyses using a human body model were performed to investigate how the muscle activations of drivers rear-ended by the following car could affect head-neck injury risks. Three muscle conditions of sleeping, relaxed, and braced drivers were assumed using a developed muscle controller. The simulation results suggest that vehicle systems that let drivers brace themselves at the onset of the AEB might be effective in reducing head-neck injury risks in this type of collisions.

Background/AimsVenous thromboembolism (VTE) is a major extraintestinal manifestation in inflammatory bowel disease (IBD), regarded as an independent risk factor for VTE according to reports from Western countries. However, the incidence and risk factors of VTE in Asian IBD patients are not fully understood. We aimed to reveal the incidence and risk factors of VTE in Japanese IBD inpatients.MethodsThe incidence of VTE in inpatients with IBD (n=340), gastrointestinal cancers (n=557), and other gastrointestinal diseases (n=569) treated at our hospital from 2009 to 2013 was retrospectively investigated. The characteristics and laboratory data of IBD inpatients with and without VTE were compared in univariate and multivariate analyses. Clinical courses of VTE in IBD were surveyed.ResultsVTE was detected in 7.1% of IBD inpatients, significantly higher than in gastrointestinal cancer inpatients (2.5%) and inpatients with other gastrointestinal diseases (0.88%). The incidence of VTE in ulcerative colitis (UC) patients (16.7%) was much higher than that in those with Crohn's disease (3.6%). In the univariate analysis, the risk factors were an older age, central venous catheter, prednisolone, surgery, low serum albumin, high serum C-reactive protein and D-dimer. According to a multivariate analysis, >50 years of age and surgery were the only risk factors. The in-hospital mortality rate of IBD inpatients with VTE was 4.2%.ConclusionsThe incidence of VTE with IBD, especially UC, was found to be high compared with other digestive disease, which was almost equivalent to that of Western countries. The efficacy of prophylaxis needs to be investigated in Asian IBD patients.

Abdominal aortic aneurysm (AAA) associated with periaortic malignant lymphoma is difficult to differentiate from aneurysmal rupture because of similarities in their clinical presentation and appearance on computed tomography images. We here report a case of AAA associated with periaortic malignant lymphoma diagnosed preoperatively with an absence of typical symptoms, showing that AAA in periaortic malignant lymphoma can present without any clinical correlates. Magnetic resonance imaging was used to confirm the diagnosis. The patient was treated by endovascular repair, which may be safer and more effective than open surgery for AAA associated with malignant lymphoma because of the tight adhesion between the aneurysm and the lymphoid tissue.

Abstract Background Takayasu’s arteritis (TA) is a large-vessel vasculitis pathologically characterized by granulomatous necrotizing vasculitis with giant cells. Although the cause of TA is still unclear, genetic factors as well as immunological abnormalities, particularly the overactivation of Th1 and Th-17, are considered to play important roles in the pathogenesis of this disease. Eosinophilic gastroenteritis (EGE) is a type of refractory inflammation in which numerous eosinophils infiltrate the inflammatory area. It is known that the overactivation of Th2 is associated with the pathogenesis of EGE, although the cause of EGE is still unclear. The immunological abnormalities in TA are therefore thought to be different from those in EGE. To date, no cases of complication of TA and EGE have been reported. Case presentations An 18 year-old female was diagnosed with EGE and treated with prednisolone. At 6 months after completion of the treatment, the patient experienced chest pain, and was diagnosed with TA. TH1 and TH17 immunity are thought to be involved with TA, while TH2 are considered to be involved with EGE. In this case, the expression of IL-17 mRNA in the colon mucosa greatly decreased after prednisolone treatment for EGE. Conclusions This is the first report of TA complicated with EGE, and the overactivation of TH17 is considered to be associated with the pathogenesis of these two diseases.

Background/Aims The research of genes implicated in kidney glomerular function, eliciting cell fate program, is always at the forefront in nephrological studies. Several neurological molecules have been recently the object of study not only for their involvement in the central nervous system differentiation but also for their importance in the functionality of other organs and for mature phenotype, as in kidney. NeuroD, in CNS, is related to two functional roles, the early survival and the differentiation. The aim of our study was to ascertain the presence of NeuroD transcription factor in glomeruli and to understand which targets and mechanisms NeuroD controls. Methods: We used immunofluorescence (IF) studies on both human and mice renal tissues and on cultured podocytes to describe NeuroD distribution; then we investigated NeuroD binding to the nephrin promoter region in cultured podocytes by chromatin-immuno-precipitation (ChIP) assay. The overexpression of NeuroD in podocytes was used to establish first its role in nephrin synthesis, evaluated by real-time quantitative (RTq) PCR and western-blot (WB) and successively to determine the recovery of cell morphology after adriamycin injury, measuring foot processes length. Results: We identified NeuroD transcription factor in glomeruli, in the same cells positive for WT1 and synaptopodin, namely podocytes; subsequently we observed a differentiation dependent NeuroD distribution in cultured podocytes, and a consistent link of NeuroD with the Nephrin promoter leading to the regulation of Nephrin translation and transcription. Our data also describes NeuroD expression in cytoplasm as phosphoprotein linked to nephrin and actinin4. Preliminary experiments seem to indicate NeuroD involved in dynamics of cell shape regulation after adriamycin injury. Conclusion: we propose that NeuroD possess in podocytes a dual ability acting in the nucleus as a transcription factor and in cytoplasm stabilizing cell shape.

Abstract Aberrant activation of Notch signaling contributes to the pathogenesis of several different types of cancer, and Notch pathway inhibitors may have significant therapeutic potential. Using a unique cell-based assay system, we isolated twelve compounds, including one new natural product from Garcinia speciosa, that inhibit the Notch signaling pathway. HES1 and HES5 are target genes of the Notch cascade, and compound 2, referred to as cowanin, decreased the protein levels of HES1 and HES5 in assay cells. Furthermore, cowanin (2) showed potent cytotoxicity against human leukemic HPB-ALL cells. The Notch signaling inhibitory activity of cowanin (2) is linked to the increased degradation of nicastrin, which is one of the components of the γ-secretase complex. To the best of our knowledge, this is the first example of a compound with Notch pathway inhibitory activity mediated by nicastrin degradation.

Abstract Background Pancreatic cancer is associated with an extremely poor prognosis, so new biomarkers that can detect the initial stages are urgently needed. The significance of serum microRNA (miR) levels in pancreatic neoplasm such as pancreatic cancer and intraductal papillary mucinous neoplasm (IPMN) diagnosis remains unclear. We herein evaluated the usefulness of miRs enclosed in serum exosomes (ExmiRs) as diagnostic markers. Methods The ExmiRs from patients with pancreatic cancer (n = 32) or IPMN (n = 29), and patients without neoplasms (controls; n = 22) were enriched using ExoQuick-TC™. The expression of ExmiRs was evaluated using a next-generation sequencing analysis, and the selected three miRs through this analysis were confirmed by a quantitative real-time polymerase chain reaction. Results The expression of ExmiR-191, ExmiR-21 and ExmiR-451a was significantly up-regulated in patients with pancreatic cancer and IPMN compared to the controls (p