Genetics of hereditary nephrotic syndrome: a clinical review

Advances in podocytology and genetic techniques have expanded our understanding of the pathogenesis of hereditary steroid-resistant nephrotic syndrome (SRNS). In the past 20 years, over 45 genetic mutations have been identified in patients with hereditary SRNS. Genetic mutations on structural and functional molecules in podocytes can lead to serious injury in the podocytes themselves and in adjacent structures, causing sclerotic lesions such as focal segmental glomerulosclerosis or diffuse mesangial sclerosis. This paper provides an update on the current knowledge of podocyte genes involved in the development of hereditary nephrotic syndrome and, thereby, reviews genotype-phenotype correlations to propose an approach for appropriate mutational screening based on clinical aspects

Alpha-tocopherol exerts protective function against the mucotoxicity of particulate matter in amphibian and human goblet cells

Exposure to particulate matter (PM) in ambient air is known to increase the risk of cardiovascular disorders and mortality. The cytotoxicity of PM is mainly due to the abnormal increase of reactive oxygen species (ROS), which damage cellular components such as DNA, RNA, and proteins. The correlation between PM exposure and human disorders, including mortality, is based on long-term exposure. In this study we have investigated acute responses of mucus-secreting goblet cells upon exposure to PM derived from a heavy diesel engine. To this end, we employed the mucociliary epithelium of amphibian embryos and human Calu-3 cells to examine PM mucotoxicity. Our data suggest that acute exposure to PM significantly impairs mucus secretion and results in the accumulation of mucus vesicles in the cytoplasm of goblet cells. RNA-seq analysis revealed that acute responses to PM exposure significantly altered gene expression patterns; however, known regulators of mucus production and the secretory pathway were not significantly altered. Interestingly, pretreatment with alpha-tocopherol nearly recovered the hyposecretion of mucus from both amphibian and human goblet cells. We believe this study demonstrates the mucotoxicity of PM and the protective function of alpha-tocopherol on mucotoxicity caused by acute PM exposure from heavy diesel engines

2021 KSCCM clinical practice guidelines for pain, agitation, delirium, immobility, and sleep disturbance in the intensive care unit

We revised and expanded the “2010 Guideline for the Use of Sedatives and Analgesics in the Adult Intensive Care Unit (ICU).” We revised the 2010 Guideline based mainly on the 2018 “Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) in Adult Patients in the ICU,” which was an updated 2013 pain, agitation, and delirium guideline with the inclusion of two additional topics (rehabilitation/mobility and sleep). Since it was not possible to hold face-to-face meetings of panels due to the coronavirus disease 2019 (COVID-19) pandemic, all discussions took place via virtual conference platforms and e-mail with the participation of all panelists. All authors drafted the recommendations, and all panelists discussed and revised the recommendations several times. The quality of evidence for each recommendation was classified as high (level A), moderate (level B), or low/very low (level C), and all panelists voted on the quality level of each recommendation. The participating panelists had no conflicts of interest on related topics. The development of this guideline was independent of any industry funding. The Pain, Agitation/Sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep Disturbance panels issued 42 recommendations (level A, 6; level B, 18; and level C, 18). The 2021 clinical practice guideline provides up-to-date information on how to prevent and manage pain, agitation/sedation, delirium, immobility, and sleep disturbance in adult ICU patients. We believe that these guidelines can provide an integrated method for clinicians to manage PADIS in adult ICU patients

Effect of Technological Atmosphere of Fashion Store on Online Behavior Intention: Focusing on AIDMSAS Model

Since the 1960s in-store atmospheric stimuli (e.g. color, music, and scent) have been investigated in the fashion retailing literature by reason of the great influence on consumers\u27 emotion and purchase behavior. Moreover, to increase consumers\u27 positive emotion, the experience economy by Pine and Gilmore (1999) indicates the importance of consumers\u27 in-store experiences. Enhancing consumer experience often links to in-store design aspects. To maximize consumers\u27 experience, various retailers try to adopt technology such as digital display, touch screen, augmented reality space and 3D virtual model in an offline store. Entering the era of omni-channel as seamless integrated channel from multi-channel retail environment, this study is considerably significant in that in-store experience affect customers\u27 online behavior. Technology has steadily and rapidly developed, and the use of technology in fashion retail will likely continue to spread. However, there are only few studies on the effect of technological atmosphere of a store on consumer behavior. This study, therefore, aims to identify the influence of technological atmospheric fashion store on consumer behavior including online behavior intention and purchase intention. This research demonstrates the pivotal role of in-store technology application in that purchase enhancement or an effect of e-word-of-mouth by sharing one\u27s experience. Also, it can even redound to products at stores. Hence, from the practical standpoint, implementing innovative technology features enhances customers\u27 positive attitude toward stores and products as well as the online application intention

Comparison of Internal and Total Optical Aberrations for 2 Aberrometers: iTrace and OPD Scan

PURPOSE: To compare and evaluate the total and internal aberrations measured by two aberrometers: the laser ray tracing aberrometer (iTrace, Tracey Technology) and the automatic retinoscope aberrometer (OPD Scan, Nidek). METHODS: A total of 54 healthy eyes were enrolled in the study. Following pupil dilation, aberrations were measured with the iTrace and OPD Scan. We compared the aberrations obtained from measurements obtained at pupillary diameters of 4 mm and 6 mm with the OPD Scan and iTrace. Aberrations of internal optics and total aberrations were compared for the two aberrometers. For each aberrometer and each eye, the averaged Zernike data were used to calculate various root-mean-square (RMS) data. These parameters, together with the refractive parameters, were then analyzed and complimented by paired t-tests. RESULTS: At a pupil diameter of 4 mm, the number of total aberrations in the entire eye showed significant differences for the mean values of spherical aberrations (Z4,0) obtained with the OPD Scan and iTrace aberrometers (p=0.001). Aberrations of the internal optics showed significant differences in the mean values of total RMS, coma (Z3,-1), and trefoil (Z3,3) between the iTrace and OPD Scan (p<0.001, p=0.01, p<0.001) for the same pupil diameter of 4 mm. At a pupil diameter of 6 mm, the two instruments showed a similar number of total aberrations. Aberrations of the internal optics showed significant differences in the mean values of total RMS, spherical aberration (Z4,0), and coma (Z3,-1) between the two devices (p<0.001, p=0.01, p<0.001). CONCLUSIONS: The iTrace and OPD Scan showed the largest number of differences for aberrations of internal optics rather than total aberrations for both pupil diameters. These results suggest that in healthy eyes, the two aberrometers may vary in some details. The aberrometers showed more agreement at a pupil diameter of 6 mm compared to 4 mmope

C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation

Hypertrophy is a prominent feature of damaged podocytes in diabetic kidney disease (DKD). mTORC1 hyperactivation leads to podocyte hypertrophy, but the detailed mechanism of how mTORC1 activation occurs under pathological conditions is not completely known. Moreover, reduced nephrin tyrosine phosphorylation has been observed in podocytes under pathological conditions, but the molecular mechanism linking nephrin phosphorylation and pathology is unclear so far. In this study, we observed a significant increase in C1-Ten level in diabetic kidney and in high glucose-induced damaged podocytes. C1-Ten acts as a protein tyrosine phosphatase (PTPase) at the nephrin-PI3K binding site and renders PI3K for IRS-1, thereby activating mTORC1. Furthermore, C1-Ten causes podocyte hypertrophy and proteinuria by increasing mTORC1 activity in vitro and in vivo. These findings demonstrate the relationship between nephrin dephosphorylation and the mTORC1 pathway, mediated by C1-Ten PTPase activity. We suggest that C1-Ten contributes to the pathogenesis of DKD by inducing podocyte hypertrophy under high glucose conditions.111Ysciescopu

An Approach to the Difference of Store Environments on Customer Experience Realms and Behaviors

The purpose of this study is to investigate the store environment if the presence of technology and different brand types have significant effect on customer experience realms and behavior intentions

The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms

Dangkwisoo-San (DS) is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO) production in human brain microvascular endothelial cells (HBMECs). DS (10–300 μg/mL) produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS) inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF), although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS) inhibitor, N5-(1-iminoethyl)-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation

S100a9 Knockdown Decreases the Memory Impairment and the Neuropathology in Tg2576 Mice, AD Animal Model

Inflammation, insoluble protein deposition and neuronal cell loss are important features in the Alzheimer's disease (AD) brain. To investigate the regulatory genes responsible for the neuropathology in AD, we performed microarray analysis with APPV717I-CT100 transgenic mice, an animal model of AD, and isolated the S100a9 gene, which encodes an inflammation-associated calcium binding protein. In another AD animal model, Tg2576 mouse brain, and in human AD brain, induction of S100a9 was confirmed. The endogenous expression of S100a9 was induced by treatment with Aβ or CT peptides in a microglia cell line, BV2 cells. In these cells, silencing study of S100a9 showed that the induction of S100a9 increased the intracellular calcium level and up-regulated the inflammatory cytokines (IL-1β and TNFα) and iNOS. S100a9 lentiviral short hairpin RNA (sh-S100a9) was injected into the hippocampus region of the brains of 13-month-old Tg2576 mice. At two months after injection, we found that knockdown of S100a9 expression had improved the cognition decline of Tg2576 mice in the water maze task, and had reduced amyloid plaque burden. These results suggest that S100a9 induced by Aβ or CT contributes to cause inflammation, which then affects the neuropathology including amyloid plaques burden and impairs cognitive function. Thus, the inhibition of S100a9 is a possible target for AD therapy