Noninflammatory Changes of Microglia Are Sufficient to Cause Epilepsy.

Microglia are well known to play a critical role in maintaining brain homeostasis. However, their role in epileptogenesis has yet to be determined. Here, we demonstrate that elevated mTOR signaling in mouse microglia leads to phenotypic changes, including an amoeboid-like morphology, increased proliferation, and robust phagocytosis activity, but without a significant induction of pro-inflammatory cytokines. We further provide evidence that these noninflammatory changes in microglia disrupt homeostasis of the CNS, leading to reduced synapse density, marked microglial infiltration into hippocampal pyramidal layers, moderate neuronal degeneration, and massive proliferation of astrocytes. Moreover, the mice thus affected develop severe early-onset spontaneous recurrent seizures (SRSs). Therefore, we have revealed an epileptogenic mechanism that is independent of the microglial inflammatory response. Our data suggest that microglia could be an opportune target for epilepsy prevention

Percutaneous balloon aortic valvuloplasty in the era of transcatheter aortic valve implantation: a narrative review

The role of percutaneous balloon aortic valvuloplasty (BAV) in the management of severe symptomatic aortic stenosis has come under the spotlight following the development of the transcatheter aortic valve implantation (TAVI) technique. Previous indications for BAV were limited to symptom palliation and as a bridge to definitive therapy for patients undergoing conventional surgical aortic valve replacement (AVR). In the TAVI era, BAV may also be undertaken to assess the ‘therapeutic response’ of a reduction in aortic gradient in borderline patients often with multiple comorbidities, to assess symptomatic improvement prior to consideration of definitive TAVI intervention. This narrative review aims to update the reader on the current indications and practical techniques involved in undertaking a BAV procedure. In addition, a summary of the haemodynamic and clinical outcomes, as well as the frequently encountered procedural complications is presented for BAV procedures conducted during both the pre-TAVI and post-TAVI era

Chromospheric activity as age indicator

Chromospheric activity has been calibrated and widely used as an age indicator. However, it has been suggested that the viability of this age indicator is, in the best case, limited to stars younger than about 1.5 Gyr. I aim to define the age range for which chromospheric activity is a robust astrophysical clock. I collected literature measurements of the S-index in field stars, which is a measure of the strength of the H and K lines of the Ca II and a proxy for chromospheric activity, and exploited the homogeneous database of temperature and age determinations for field stars provided by the Geneva-Copenhagen survey of the solar neighbourhood. Field data, inclusive data previously used to calibrate chromospheric ages, confirm the result found using open cluster data, i.e. there is no decay of chromospheric activity after about 2 Gyr. The only existing indication supporting the viability of chromospheric ages older than 2 Gyr is the similarity of chromospheric activity levels in the components of 35 dwarf binaries. However, even in the most optimistic scenario, uncertainty in age determination for field stars and lack of sufficient data in open clusters make any attempt of calibrating an age activity relationship for old stars premature. The hypothesis that chromospheric activity follows the Skumanich law, i.e. that it is proportional to the inverse square root of the age, should be relaxed.Comment: 5 pages, 2 figures, A&A letters, accepte

Bone Marrow Stem Cell Treatment for Ischemic Heart Disease in Patients with No Option of Revascularization: A Systematic Review and Meta-Analysis

PMCID: PMC3686792This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Helicity-dependent generalized parton distributions in constituent quark models

Helicity-dependent generalized parton distributions of the nucleon are derived from the overlap representation of generalized parton distributions using light-cone wave functions obtained in constituent quark models. Results from two different quark models are used also to study the angular momentum sum rule and the spin asymmetry in polarized electron scattering.Comment: 20 pages, 5 figures, 2 table

The Giant Chalukou Porphyry Mo Deposit, Northeast China: The Product of a Short-Lived, High Flux Mineralizing Event

Whether giant porphyry ore deposits are the products of single, short-lived magmatic-hydrothermal events or multiple events over a prolonged interval is a topic of considerable debate. Previous studies, however, have all been devoted to porphyry Cu and Cu-Mo deposits. In this paper, we report high-precision isotope dilution-negative-thermal ionization mass spectrometric (ID-N-TIMS) molybdenite Re-Os ages for the newly discovered, world-class Chalukou porphyry Mo deposit (reserves of 2.46 Mt @ 0.087 wt % Mo) in NE China. Samples were selected based on a careful evaluation of the relative timing of the different vein types (i.e., A, B, and D veins), thereby ensuring that the suite of samples analyzed could be used to reliably determine the age and duration of mineralization. The molybdenite Re-Os geochronology reveals that hydrothermal activity at Chalukou involved two magmatic-hydrothermal events spanning an interval of 6.92 ± 0.16 m.y. The first event (153.96 ± 0.08/0.63/0.79 Ma, molybdenite ID-N-TIMS Re-Os age) was associated with the emplacement of a granite porphyry dated at 152.1 ± 2.2 Ma (zircon laser ablation-inductively coupled plasma-microscopic [LA-ICP-MS] U-Pb ages), and led to only minor Mo mineralization, accounting for 90%) was deposited in less than 650 kyr, between 147.67 ± 0.10/0.60/0.76 and 147.04 ± 0.12/0.72/0.86 Ma (molybdenite ID-N-TIMS Re-Os ages), coincident with the emplacement of a fine-grained porphyry at 148.1 ± 2.6 Ma (zircon LA-ICP-MS U-Pb ages). The high-precision Re-Os age determinations presented here show, contrary to the finding of a number of studies of porphyry Cu and Cu-Mo systems, that the giant Chalukou porphyry Mo deposit primarily formed in a single, short-lived (<650 kyr) hydrothermal event, suggesting that this may also have been the case for other giant porphyry Mo deposits

Rapid prediction of wall shear stress in stenosed coronary arteries based on deep learning

There is increasing evidence that coronary artery wall shear stress (WSS) measurement provides useful prognostic information that allows prediction of adverse cardiovascular events. Computational Fluid Dynamics (CFD) has been extensively used in research to measure vessel physiology and examine the role of the local haemodynamic forces on the evolution of atherosclerosis. Nonetheless, CFD modelling remains computationally expensive and time-consuming, making its direct use in clinical practice inconvenient. A number of studies have investigated the use of deep learning (DL) approaches for fast WSS prediction. However, in these reports, patient data were limited and most of them used synthetic data generation methods for developing the training set. In this paper, we implement 2 approaches for synthetic data generation and combine their output with real patient data in order to train a DL model with a U-net architecture for prediction of WSS in the coronary arteries. The model achieved 6.03% Normalised Mean Absolute Error (NMAE) with inference taking only 0.35 s; making this solution time-efficient and clinically relevant

Cardiovascular magnetic resonance imaging of myocardial oedema following acute myocardial infarction: Is whole heart coverage necessary?

© 2016 Hamshere et al. Background: AAR measurement is useful when assessing the efficacy of reperfusion therapy and novel cardioprotective agents after myocardial infarction. Multi-slice (Typically 10-12) T2-STIR has been used widely for its measurement, typically with a short axis stack (SAX) covering the entire left ventricle, which can result in long acquisition times and multiple breath holds. This study sought to compare 3-slice T2-short-tau inversion recovery (T2- STIR) technique against conventional multi-slice T2-STIR technique for the assessment of area at risk (AAR). Methods: CMR imaging was performed on 167 patients after successful primary percutaneous coronary intervention. 82 patients underwent a novel 3-slice SAX protocol and 85 patients underwent standard 10-slice SAX protocol. AAR was obtained by manual endocardial and epicardial contour mapping followed by a semi- automated selection of normal myocardium; the volume was expressed as mass (%) by two independent observers. Results: 85 patients underwent both 10-slice and 3-slice imaging assessment showing a significant and strong correlation (intraclass correlation coefficient = 0.92;p < 0.0001) and a low Bland-Altman limit (mean difference -0.03 ± 3.21 %, 95 % limit of agreement,- 6.3 to 6.3) between the 2 analysis techniques. A further 82 patients underwent 3-slice imaging alone, both the 3-slice and the 10-slice techniques showed statistically significant correlations with angiographic risk scores (3-slice to BARI r = 0.36, 3-slice to APPROACH r = 0.42, 10-slice to BARI r = 0.27, 10-slice to APPROACH r = 0.46). There was low inter-observer variability demonstrated in the 3-slice technique, which was comparable to the 10-slice method (z = 1.035, p = 0.15). Acquisition and analysis times were quicker in the 3-slice compared to the 10-slice method (3-slice median time: 100 seconds (IQR: 65-171 s) vs (10-slice time: 355 seconds (IQR: 275-603 s); p < 0.0001. Conclusions: AAR measured using 3-slice T2-STIR technique correlates well with standard 10-slice techniques, with no significant bias demonstrated in assessing the AAR. The 3-slice technique requires less time to perform and analyse and is therefore advantageous for both patients and clinicians