Presenilins are required for maintenance of neural stem cells in the developing brain

The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to generate presenilin conditional double knockout (PS cDKO) mice, in which expression of both presenilins is inactivated in neural progenitor cells (NPC) or neural stem cells and their derivative neurons and glia beginning at embryonic day 11 (E11). In PS cDKO mice, dividing NPCs labeled by BrdU are decreased in number beginning at E13.5. By E15.5, fewer than 20% of NPCs remain in PS cDKO mice. The depletion of NPCs is accompanied by severe morphological defects and hemorrhages in the PS cDKO embryonic brain. Interkinetic nuclear migration of NPCs is also disrupted in PS cDKO embryos, as evidenced by displacement of S-phase and M-phase nuclei in the ventricular zone of the telencephalon. Furthermore, the depletion of neural progenitor cells in PS cDKO embryos is due to NPCs exiting cell cycle and differentiating into neurons rather than reentering cell cycle between E13.5 and E14.5 following PS inactivation in most NPCs. The length of cell cycle, however, is unchanged in PS cDKO embryos. Expression of Notch target genes, Hes1 and Hes5, is significantly decreased in PS cDKO brains, whereas Dll1 expression is up-regulated, indicating that Notch signaling is effectively blocked by PS inactivation. These findings demonstrate that presenilins are essential for neural progenitor cells to re-enter cell cycle and thus ensure proper expansion of neural progenitor pool during embryonic neural development

THE POSSIBILITY OF CLASSIFYING V1 AND V2 SUB-TECHNIQUES OF A SINGLE IMU SENSOR THROUGH COMPARISON OF MOTION-SPECIFIC DATA(PITCH, YAW AND ROLL ANGLE VALUES-ORIENTATION ANGLE VALUE) IN XC SKI

The purpose of this study is to confirm whether the single IMU sensor module(LGE developing and providing for the experiments) that attached to the pelvis can distinguish the motion of the sub-techniques (V1, V2, V2A) with the accuracy of commercial XSENS(equipment consisting of 17 sensors) in freestyle(skate) xc skiing. Therefore, one elite male xc skier with eleven years experience was investigated by measuring the three-directional rotation angle for each of the three sub-techniques used in XC ski freestyle. Through this method, we could found not only the difference of motion patterns of each sub-techniques but also the possibility for replacement of multiple sensor system by a single IMU sensor module from LGE. Thus, it is expected that a single LGE IMU sensor module could be applied to repetitive and periodic sports such as XC ski

Could Fractional Exhaled Nitric Oxide Test be Useful in Predicting Inhaled Corticosteroid Responsiveness in Chronic Cough? A Systematic Review

© 2016 Background Fractional exhaled nitric oxide (FENO) is a safe and convenient test for assessing T H 2 airway inflammation, which is potentially useful in the management of patients with chronic cough. Objective To summarize the current evidence on the diagnostic usefulness of FENO for predicting inhaled corticosteroid (ICS) responsiveness in patients with chronic cough. Methods A systematic literature review was conducted to identify articles published in peer-reviewed journals up to February 2015, without language restriction. We included studies that reported the usefulness of FENO (index test) for predicting ICS responsiveness (reference standard) in patients with chronic cough (target condition). The data were extracted to construct a 2 × 2 accuracy table. Study quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Results We identified 5 original studies (2 prospective and 3 retrospective studies). We identified considerable heterogeneities in study design and outcome definitions, and thus were unable to perform a meta-analysis. The proportion of ICS responders ranged from 44% to 59%. Sensitivity and specificity ranged from 53% to 90%, and from 63% to 97%, respectively. The reported area under the curve ranged from abou t 0.60 to 0.87; however, studies with a prospective design and a lower prevalence of asthma had lower area under the curve values. None measured placebo effects or objective cough frequency. Conclusions We did not find strong evidence to support the use of FENO tests for predicting ICS responsiveness in chronic cough. Further studies need to have a randomized, placebo-controlled design, and should use validated measurement tools for cough. Standardization would facilitate the development of clinical evidence

Toll-Like Receptor 4 Decoy, TOY, Attenuates Gram-Negative Bacterial Sepsis

Lipopolysaccharide (LPS), the Gram-negative bacterial outer membrane glycolipid, induces sepsis through its interaction with myeloid differentiation protein-2 (MD-2) and Toll-like receptor 4 (TLR4). To block interaction between LPS/MD-2 complex and TLR4, we designed and generated soluble fusion proteins capable of binding MD-2, dubbed TLR4 decoy receptor (TOY) using ‘the Hybrid leucine-rich repeats (LRR) technique’. TOY contains the MD-2 binding ectodomain of TLR4, the LRR motif of hagfish variable lymphocyte receptor (VLR), and the Fc domain of IgG1 to make it soluble, productive, and functional. TOY exhibited strong binding to MD-2, but not to the extracellular matrix (ECM), resulting in a favorable pharmacokinetic profile in vivo. TOY significantly extended the lifespan, when administered in either preventive or therapeutic manners, in both the LPS- and cecal ligation/puncture-induced sepsis models in mice. TOY markedly attenuated LPS-triggered NF-κB activation, secretion of proinflammatory cytokines, and thrombus formation in multiple organs. Taken together, the targeting strategy for sequestration of LPS/MD-2 complex using the decoy receptor TOY is effective in treating LPS- and bacteria-induced sepsis; furthermore, the strategy used in TOY development can be applied to the generation of other novel decoy receptor proteins

Domain Walls and Anchoring Transitions Mimicking Nematic Biaxiality in the Oxadiazole Bent-Core Liquid Crystal C7

We investigate the origin of secondary disclinations that were recently described as a new evidence of a biaxial nematic phase in an oxadiazole bent-core thermotropic liquid crystal C7. With an assortment of optical techniques such as polarizing optical microscopy, LC PolScope, and fluorescence confocal polarizing microscopy, we demonstrate that the secondary disclinations represent non-singular domain walls formed in an uniaxial nematic during the surface anchoring transition, in which surface orientation of the director changes from tangential (parallel to the bounding plates) to tilted. Each domain wall separates two regions with the director tilted in opposite azimuthal directions. At the centre of the wall, the director remains parallel to the bonding plates. The domain walls can be easily removed by applying a modest electric field. The anchoring transition is explained by the balance of (a) the intrinsic perpendicular surface anchoring produced by the polyimide aligning layer and (b) tangential alignment caused by ionic impurities forming electric double layers. The model is supported by the fact that the temperature of the tangential-tilted anchoring transition decreases as the cell thickness increases and as the concentration of ionic species (added salt) increases. We also demonstrate that the surface alignment is strongly affected by thermal degradation of the samples. The study shows that C7 exhibits only a uniaxial nematic phase and demonstrate yet another mechanism (formation of secondary disclinations) by which a uniaxial nematic can mimic a biaxial nematic behaviour.Comment: 21 pages, 9 Figures, 1 Tabl

Risk of all-cause and cause-specific mortality associated with immune-mediated inflammatory diseases in Korea

ObjectiveImmune-mediated inflammatory disease (IMID) is associated with an increased risk of mortality. It is unclear whether the higher mortality is attributable to the IMIDs themselves or to the higher prevalence of comorbidities in IMIDs. We aimed to investigate whether IMIDs per se confer a higher risk of mortality.MethodsFrom the Korean National Health Insurance Service-National Sample Cohort database, this population-based cohort study included 25,736 patients newly diagnosed with IMIDs between January 2007 and December 2017, and 128,680 individuals without IMIDs who were matched for age, sex, income, hypertension, type 2 diabetes, dyslipidemia, and the Charlson comorbidity index. All individuals were retrospectively observed through December 31, 2019. The outcomes included all-cause and cause-specific mortalities. Adjustments for age, sex, and comorbidities were performed using multivariable Cox proportional hazard regression analyses, and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the outcomes were estimated.ResultsThe adjusted risk of all-cause mortality was significantly lower in patients with IMIDs than that in those without (aHR, 0.890; 95% CI, 0.841–0.942). Regarding cause-specific mortality, cancer-specific (aHR, 0.788; 95% CI, 0.712–0.872) and cardiovascular disease-specific (aHR, 0.798; 95% CI, 0.701–0.908) mortalities were the two causes of death that showed significantly lower risks in patients with IMIDs. A similar trend was observed when organ based IMIDs were analyzed separately (i.e., gut, joint, and skin IMIDs).ConclusionAfter adjusting for comorbidities, IMIDs were associated with a lower risk of all-cause mortality compared to those without IMIDs. This was attributable to the lower risks of cancer-and cardiovascular disease-specific mortalities

Serum Ethanol Levels after Alcohol Sclerotherapy of Arteriovenous Malformations

We analyzed the effects of several factors on the serum ethanol levels after alcohol sclerotherapy in the arteriovenous malformations (AVMs) retrospectively. Blood ethanol level, amounts of given alcohol, location of lesions, methods of flow control, and Doppler resistive index (RI) were analyzed. The results of linear regression analysis showed that the amount of alcohol administered was the predictor of serum ethanol level (r2=0.75, p<0.001). The average amount of injected alcohol was 0.89 mL/kg in the patients with the serum levels above the legal intoxication level (>80 mg/dL). Location of the lesions was not related with the serum ethanol level (p=0.643), and other variables such as forms of flow control and RI were not related to the serum ethanol level after controlling for injected amounts of alcohol (analysis of covariance). It is recommended to keep an eye on the possibility of intoxication when using the amounts of alcohol exceeding 0.89 mL/kg in the sclerotherapy of AVMs

Cough persistence in adults with chronic cough: a 4-year retrospective cohort study

BackgroundThere is very limited evidence regarding long-term prognosis of chronic cough. We examined longitudinal outcomes among patients with chronic cough, and explored predictors of cough persistence.MethodsA retrospective cohort was constructed of adults who had newly visited a specialist cough clinic in 2012–2013. All had undergone systematic investigation for chronic cough. The Hull Airway Reflux Questionnaire (HARQ) was administered to assess reflux cough symptoms. A follow-up survey was conducted in 2016–2017 to assess cough persistence.ResultsFrom 418 candidates, 323 participated in the follow-up study; main analyses focused on patients with chronic persistent cough (n=64; 19.8%) and remitted cough (n=193; 59.8%). Compared with remitted cough, chronic persistent cough group had more family history of chronic cough (17.2% vs. 4.7%, p=0.001) and cold air-sensitive cough (62.5% vs. 44.6%, p=0.013). The total HARQ score did not differ; however, two items (cough with eating and cough with certain foods) scored significantly higher in chronic persistent cough. In multivariate analyses, a family history of chronic cough (adjusted odds ratio 4.27 [95% confidence interval 1.35-9.89]), cold air-sensitive cough (2.01 [1.09-3.73]), and cough with eating (1.22 [1.02–1.45]) were associated with chronic persistent cough at 4 years.Conclusions Cough persists in about 20% of patients after 4 years following systematic assessment and treatments. Several cough characteristics, such as family history, cold air-sensitivity, or reflux cough, may be associated with cough persistence. Larger cohort studies are warranted to further understand long-term prognosis and confirm predictors of persistence in patients with chronic cough