Aims
Aggressive meningioma remains incurable with neither chemo‐ nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving ...the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression.
Methods
Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression‐free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked‐down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM‐Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)‐pretreated or control IOMM‐Lee cells were implanted subcutaneously in nude mice.
Results
FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of β‐catenin, cyclin D1, p21, interleukin‐8, vascular endothelial growth factor‐A, PLAU, and epithelial‐to‐mesenchymal transition‐related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model.
Conclusions
Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.
Background and purpose
We investigated the effect of celecoxib, a selective inhibitor of cyclo‐oxygenase 2, in patients with intracerebral hemorrhage (ICH).
Methods
We conducted a multicenter, ...randomized, controlled, and open with blinded end‐point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end‐point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut‐off value, 20%).
Results
The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end‐point analysis using cut‐off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end‐points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow‐up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058).
Conclusions
In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls.
Although capsule endoscopy has become a central diagnostic tool for small-bowel evaluation, retention of a capsule remains a major concern. This study attempted to investigate the incidence and ...clinical outcomes of capsule retention, and to determine the factors predictive of spontaneous capsule passage after retention.
Through a nationwide multicenter survey, we retrospectively reviewed the records of 1291 patients who had a capsule endoscopy between February 2002 and July 2006 in Korea. Clinical and procedural characteristics and postprocedural outcomes were analyzed for the cases with capsule retention.
Capsule retention occurred in 2.5 % of total cases (32/1291). The major diseases accompanying capsule retention were Crohn's disease, malignant tumors, and tuberculous enterocolitis, in decreasing order. In 11 of the 32 patients (34.4 %), early surgical or endoscopic interventions were instituted for diagnosis or treatment of diseases before retention symptoms developed. The remaining 21 (65.6 %) patients initially received medical treatments. Of these, 10 (31.3 %) ultimately underwent surgical intervention due to the development of symptoms of intestinal obstruction or medical treatment failure. The other 11 (34.4 %) eventually passed the capsule. The presence of a larger lumen diameter (greater than two-thirds of the capsule diameter) at the stricture site was associated with spontaneous passage.
Our large-scale study suggests that retention occurs infrequently during capsule endoscopy. Moreover, a retained capsule might indicate the best intervention for the offending pathology, or it may spontaneously pass in the long run, particularly in patients with less small bowel stricture.
Summary
The major hurdle for the clinical application of stem cell therapy is the heterogeneous nature of the isolated cells, which may cause different treatment outcomes. The aim of this study was ...to examine the effectiveness of mouse clonal bone marrow‐derived stem cells (BMSCs) obtained from a single colony by using subfractionation culturing method for erectile function in diabetic animals. Twelve‐week‐old C57BL/6J mice were divided into four groups: controls, diabetic mice, and diabetic mice treated with a single intracavernous injection of PBS (20 μL) or clonal BMSCs (3 × 105 cells/20 μL). Clonal BMSCs were isolated from 5‐week‐old C3H mice. Two weeks after treatment, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was stained with antibodies to PECAM‐1, smooth muscle α‐actin, neuronal nitric oxide synthase (nNOS), neurofilament, and phosphorylated endothelial NOS (phospho‐eNOS). We also performed Western blot for phospho‐eNOS, and eNOS in the corpus cavernosum tissue. Local delivery of clonal BMSCs significantly restored cavernous endothelial and smooth muscle cell contents, and penile nNOS and neurofilament contents, and induced eNOS phosphorylation (Ser1177) in diabetic mice. Intracavernous injection of clonal BMSCs induced significant recovery of erectile function, which reached 80–90% of the control values. Clonal BMSCs successfully restored erectile function through dual angiogenic and neurotrophic effects in diabetic mice. The homogenous nature of clonal mesenchymal stem cells may allow their clinical applications and open a new avenue through which to treat diabetic erectile dysfunction.
Autoimmune pancreatitis (AIP) is a treatable form of chronic pancreatitis that has been increasingly recognised over the last decade. We set out to better understand the current burden of AIP at ...several academic institutions diagnosed using the International Consensus Diagnostic Criteria, and to describe long-term outcomes, including organs involved, treatments, relapse frequency and long-term sequelae.
23 institutions from 10 different countries participated in this multinational analysis. A total of 1064 patients meeting the International Consensus Diagnostic Criteria for type 1 (n=978) or type 2 (n=86) AIP were included. Data regarding treatments, relapses and sequelae were obtained.
The majority of patients with type 1 (99%) and type 2 (92%) AIP who were treated with steroids went into clinical remission. Most patients with jaundice required biliary stent placement (71% of type 1 and 77% of type 2 AIP). Relapses were more common in patients with type 1 (31%) versus type 2 AIP (9%, p<0.001), especially those with IgG4-related sclerosing cholangitis (56% vs 26%, p<0.001). Relapses typically occurred in the pancreas or biliary tree. Retreatment with steroids remained effective at inducing remission with or without alternative treatment, such as azathioprine. Pancreatic duct stones and cancer were uncommon sequelae in type 1 AIP and did not occur in type 2 AIP during the study period.
AIP is a global disease which uniformly displays a high response to steroid treatment and tendency to relapse in the pancreas and biliary tree. Potential long-term sequelae include pancreatic duct stones and malignancy, however they were uncommon during the study period and require additional follow-up. Additional studies investigating prevention and treatment of disease relapses are needed.
We propose a real-time hand gesture interface based on combining a stereo pair of biologically inspired event-based dynamic vision sensor (DVS) silicon retinas with neuromorphic event-driven ...postprocessing. Compared with conventional vision or 3-D sensors, the use of DVSs, which output asynchronous and sparse events in response to motion, eliminates the need to extract movements from sequences of video frames, and allows significantly faster and more energy-efficient processing. In addition, the rate of input events depends on the observed movements, and thus provides an additional cue for solving the gesture spotting problem, i.e., finding the onsets and offsets of gestures. We propose a postprocessing framework based on spiking neural networks that can process the events received from the DVSs in real time, and provides an architecture for future implementation in neuromorphic hardware devices. The motion trajectories of moving hands are detected by spatiotemporally correlating the stereoscopically verged asynchronous events from the DVSs by using leaky integrate-and-fire (LIF) neurons. Adaptive thresholds of the LIF neurons achieve the segmentation of trajectories, which are then translated into discrete and finite feature vectors. The feature vectors are classified with hidden Markov models, using a separate Gaussian mixture model for spotting irrelevant transition gestures. The disparity information from stereovision is used to adapt LIF neuron parameters to achieve recognition invariant of the distance of the user to the sensor, and also helps to filter out movements in the background of the user. Exploiting the high dynamic range of DVSs, furthermore, allows gesture recognition over a 60-dB range of scene illuminance. The system achieves recognition rates well over 90% under a variety of variable conditions with static and dynamic backgrounds with naïve users.
Background and purpose
The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion‐weighted magnetic ...resonance imaging (DWI‐MRI) and whether ischaemic core size affects this rate remain to be investigated.
Methods
This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI‐MRI that was categorized into three groups: small Diffusion‐Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI‐ASPECTS) (8–10), moderate (5–7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0–2). The interaction between onset‐to‐groin puncture time (OTP) and DWI‐ASPECTS categories regarding functional outcomes was investigated.
Results
Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI‐ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction = 0.06). Every 60‐min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity = 0.15).
Conclusions
Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI‐ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.
New limits are presented on the cross section for weakly interacting massive particle (WIMP) nucleon scattering in the KIMS CsI(Tℓ) detector array at the Yangyang Underground Laboratory. The exposure ...used for these results is 24 524.3 kg·days. Nuclei recoiling from WIMP interactions are identified by a pulse shape discrimination method. A low energy background due to alpha emitters on the crystal surfaces is identified and taken into account in the analysis. The detected numbers of nuclear recoils are consistent with zero and 90% confidence level upper limits on the WIMP interaction rates are set for electron equivalent energies from 3 to 11 keV. The 90% upper limit of the nuclear recoil event rate for 3.6-5.8 keV corresponding to 2-4 keV in NaI(Tℓ) is 0.0098 counts/kg/keV/day, which is below the annual modulation amplitude reported by DAMA. This is incompatible with interpretations that enhance the modulation amplitude such as inelastic dark matter models. We establish the most stringent cross section limits on spin-dependent WIMP-proton elastic scattering for the WIMP masses greater than 20 GeV/c2.
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