Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity

The Value of Measuring Eustachian Tube Aeration on Temporal Bone CT in Patients with Chronic Otitis Media

ObjectivesTo evaluate that the cross-sectional area of the air space in the Eustachian tube (ET) on computed tomography (CT) images could be useful for predicting the postoperative aeration of the middle ear.MethodsThe patient group consisted of 80 patients (80 ears) with chronic otitis media and who underwent middle ear surgery from 2006-2007 and who were followed up for more than 1 yr. The control group consisted of 100 ears of 50 individuals with normal tympanic membranes and who underwent CT for other causes (such as tinnitus or hearing loss). The largest cross-sectional areas of the aerated ET were measured on the coronal images of the temporal bone CT by a single otologist using the computer-based "Region of Interest" picture archiving and communications system. The patient group was divided into two subgroups, 1) those with good postoperative aeration and 2) those with poor postoperative aeration. The largest cross-sectional areas of the aerated ETs were compared between the patients and the controls, and between the patients with good aeration and the patients with poor aeration.ResultsThe mean cross-sectional areas significantly differed between the patient group and the control group, and between the good and poor aeration subgroups (P<0.05 each). The mean area of the poor aeration subgroup was smaller than that of the control group (P<0.05), but the mean area of the good aeration subgroup did not significantly differ from that of the controls.ConclusionThe cross-sectional area of the aerated ET, as measured on the preoperative coronal images of temporal bone CT scans, may be useful for predicting the postoperative condition of the tympanic cavity

Novel Smart N95 Filtering Facepiece Respirator with Real-time Adaptive Fit Functionality and Wireless Humidity Monitoring for Enhanced Wearable Comfort

The widespread emergence of the COVID-19 pandemic has transformed our lifestyle, and facial respirators have become an essential part of daily life. Nevertheless, the current respirators possess several limitations such as poor respirator fit because they are incapable of covering diverse human facial sizes and shapes, potentially diminishing the effect of wearing respirators. In addition, the current facial respirators do not inform the user of the air quality within the smart facepiece respirator in case of continuous long-term use. Here, we demonstrate the novel smart N-95 filtering facepiece respirator that incorporates the humidity sensor and pressure sensory feedback-enabled self-fit adjusting functionality for the effective performance of the facial respirator to prevent the transmission of airborne pathogens. The laser-induced graphene (LIG) constitutes the humidity sensor, and the pressure sensor array based on the dielectric elastomeric sponge monitors the respirator contact on the face of the user, providing the sensory information for a closed-loop feedback mechanism. As a result of the self-fit adjusting mode along with elastomeric lining, the fit factor is increased by 3.20 and 5 times at average and maximum respectively. We expect that the experimental proof-of-concept of this work will offer viable solutions to the current commercial respirators to address the limitations.Comment: 20 pages, 5 figures, 1 table, submitted for possible publicatio

Analysis of significant protein abundance from multiple reaction-monitoring data

Background Discovering reliable protein biomarkers is one of the most important issues in biomedical research. The ELISA is a traditional technique for accurate quantitation of well-known proteins. Recently, the multiple reaction-monitoring (MRM) mass spectrometry has been proposed for quantifying newly discovered protein and has become a popular alternative to ELISA. For the MRM data analysis, linear mixed modeling (LMM) has been used to analyze MRM data. MSstats is one of the most widely used tools for MRM data analysis that is based on the LMMs. However, LMMs often provide various significance results, depending on model specification. Sometimes it would be difficult to specify a correct LMM method for the analysis of MRM data. Here, we propose a new logistic regression-based method for Significance Analysis of Multiple Reaction Monitoring (LR-SAM). Results Through simulation studies, we demonstrate that LMM methods may not preserve type I error, thus yielding high false- positive errors, depending on how random effects are specified. Our simulation study also shows that the LR-SAM approach performs similarly well as LMM approaches, in most cases. However, LR-SAM performs better than the LMMs, particularly when the effects sizes of peptides from the same protein are heterogeneous. Our proposed method was applied to MRM data for identification of proteins associated with clinical responses of treatment of 115 hepatocellular carcinoma (HCC) patients with the tyrosine kinase inhibitor sorafenib. Of 124 candidate proteins, LMM approaches provided 6 results varying in significance, while LR-SAM, by contrast, yielded 18 significant results that were quite reproducibly consistent. Conclusion As exemplified by an application to HCC data set, LR-SAM more effectively identified proteins associated with clinical responses of treatment than LMM did.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI16C2037, HI15C2165). Publication of this article was sponsored by HI16C2037 grant

The Clinical Outcome of FLAG Chemotherapy without Idarubicin in Patients with Relapsed or Refractory Acute Myeloid Leukemia

A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m2, days 1-5), cytarabine (2.0 g/m2, days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05). The recovery time of both neutrophils (≥500/µL) and platelets (≥20,000/µL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT

SEALONE (Safety and Efficacy of Coronary Computed Tomography Angiography with Low Dose in Patients Visiting Emergency Room) trial: study protocol for a randomized controlled trial

Objective Chest pain is one of the most common complaints in the emergency department (ED). Cardiac computed tomography angiography (CCTA) is a frequently used tool for the early triage of patients with low- to intermediate-risk acute chest pain. We present a study protocol for a multicenter prospective randomized controlled clinical trial testing the hypothesis that a low-dose CCTA protocol using prospective electrocardiogram (ECG)-triggering and limited-scan range can provide sufficient diagnostic safety for early triage of patients with acute chest pain. Methods The trial will include 681 younger adult (aged 20 to 55) patients visiting EDs of three academic hospitals for acute chest pain or equivalent symptoms who require further evaluation to rule out acute coronary syndrome. Participants will be randomly allocated to either low-dose or conventional CCTA protocol at a 2:1 ratio. The low-dose group will undergo CCTA with prospective ECG-triggering and restricted scan range from sub-carina to heart base. The conventional protocol group will undergo CCTA with retrospective ECG-gating covering the entire chest. Patient disposition is determined based on computed tomography findings and clinical progression and all patients are followed for a month. The primary objective is to prove that the chance of experiencing any hard event within 30 days after a negative low-dose CCTA is less than 1%. The secondary objectives are comparisons of the amount of radiation exposure, ED length of stay and overall cost. Results and Conclusion Our low-dose protocol is readily applicable to current multi-detector computed tomography devices. If this study proves its safety and efficacy, dose-reduction without purchasing of expensive newer devices would be possible

Comparison of carnivore, omnivore, and herbivore mammalian genomes with a new leopard assembly.

BACKGROUND: There are three main dietary groups in mammals: carnivores, omnivores, and herbivores. Currently, there is limited comparative genomics insight into the evolution of dietary specializations in mammals. Due to recent advances in sequencing technologies, we were able to perform in-depth whole genome analyses of representatives of these three dietary groups. RESULTS: We investigated the evolution of carnivory by comparing 18 representative genomes from across Mammalia with carnivorous, omnivorous, and herbivorous dietary specializations, focusing on Felidae (domestic cat, tiger, lion, cheetah, and leopard), Hominidae, and Bovidae genomes. We generated a new high-quality leopard genome assembly, as well as two wild Amur leopard whole genomes. In addition to a clear contraction in gene families for starch and sucrose metabolism, the carnivore genomes showed evidence of shared evolutionary adaptations in genes associated with diet, muscle strength, agility, and other traits responsible for successful hunting and meat consumption. Additionally, an analysis of highly conserved regions at the family level revealed molecular signatures of dietary adaptation in each of Felidae, Hominidae, and Bovidae. However, unlike carnivores, omnivores and herbivores showed fewer shared adaptive signatures, indicating that carnivores are under strong selective pressure related to diet. Finally, felids showed recent reductions in genetic diversity associated with decreased population sizes, which may be due to the inflexible nature of their strict diet, highlighting their vulnerability and critical conservation status. CONCLUSIONS: Our study provides a large-scale family level comparative genomic analysis to address genomic changes associated with dietary specialization. Our genomic analyses also provide useful resources for diet-related genetic and health research

Bioinspired Soft Robotic Fish for Wireless Underwater Control of Gliding Locomotion

Animal locomotion offers valuable references as it is a critical component of survival as animals adapting to a specific environment. Especially, underwater locomotion poses a challenge because water exerts a high antagonistic drag force against the direction of progress. However, marine vertebrates usually use much lower aerobic energy for locomotion than aerial or terrestrial vertebrates due to their unique intermittent gliding locomotion. None of the prior works demonstrate the locomotive strategies of marine vertebrates. Herein, an untethered soft robotic fish capable of reconstructing the marine vertebrates’ effective locomotion and traveling underwater by controlling localized buoyancy with thermoelectric pneumatic actuators is introduced. The actuators enable both heating and cooling to control a localized buoyancy while providing a substantial driving force to the system. Besides mimicking the locomotion, the bidirectional communication system enables the untethered delivery of commands to the underwater subject and real‐time acquisition of the robotic fish's physical information. Underwater imaging validates the fish's practical use as a drone, allowing for inspecting the aquatic environment that is not easily accessible to humans. Future work studies the operation of the robotic fish as a collective swarm to examine a broader range of the underwater area and conduct various strategic missions

Public Interest in Cognitive Impairment: An Analysis of the Top 50 Articles on Cognitive Impairment on Altmetric

Background. As the average life expectancy continues to increase, interest in cognitive impairment is increasing. Nowadays, as social media expands its reach, academic research is spreading through social media, changing the way and speed by which research is propagated and also who consumes this content. Therefore, using Altmetric, a new web-based set of metrics that analyzes the impact of content on social media platforms, we investigated the characteristics of influential research articles on the topic of cognitive impairment in social media. Methods. An Altmetric Explorer search was performed on May 25, 2018, to extract the following information: (i) journal name, (ii) journal impact factor (IF), (iii) year of publication, (iv) article topic, (v) article type, and (vi) cognitive impairment subtype. Results. The journal “Neurology” was the most cited journal for cognitive impairment articles shared on social media. Among the various types of cognitive impairment, most articles were related to dementia (all subtypes), Alzheimer’s disease, and aging. The most common article type was original scientific paper, especially cohort study. The most popular topic was the identification of protective or risk factors for cognitive impairment. Conclusion. The characteristics of articles with a high Altmetric Attention Score were somewhat different from those of articles with a high number of traditional citations. Social media had the disadvantage that it was difficult to verify the authenticity of the primary source in question, but the advantage was that it could immediately determine the trends regarding how information about that source was being shared and consumed. Therefore, it may be advisable to use Altmetric analysis in combination with traditional methods of evaluating the research articles to understand the dissemination of scientific research and to direct future research

Ginseng Saponin Enriched in Rh1 and Rg2 Ameliorates Nonalcoholic Fatty Liver Disease by Inhibiting Inflammasome Activation

Nonalcoholic fatty liver disease (NAFLD) is becoming one of the most common chronic liver diseases in the world. One of the features of NAFLD is hepatic fat accumulation, which further causes hepatic steatosis, fibrosis, and inflammation. Saponins, the major pharmacologically active ingredients isolated from Panax notoginseng, contain several ginsenosides, which have various pharmacological and therapeutic functions. However, the ginsenoside-specific molecular mechanism of saponins in NAFLD remains unknown. This study aimed to elucidate the effects of ginseng saponin extract and its ginsenosides on hepatic steatosis, fibrosis, and inflammation and their underlying action mechanism in NAFLD. Mice were fed a fast food diet (FFD) for 16 weeks to induce NAFLD and then treated with saponin extract (50 or 150 mg/kg) for the remaining nine weeks to determine the effects of saponin on NAFLD. Saponin extract administration significantly alleviated FFD-induced hepatic steatosis, fibrosis, and inflammation. Particularly, saponin extract, compared with conventional red ginseng, contained significantly increased amounts of ginsenosides (Rh1 (10.34-fold) and Rg2 (7.1-fold)). In vitro Rh1 and Rg2 treatments exerted an anti-steatotic effect in primary hepatocytes, an antifibrotic effect in hepatic stellate cells, and anti-inflammatory and pro-mitophagy effects in immortalized mouse Kupffer cells. Mechanistically, saponin extract alleviated lipopolysaccharide-induced NLRP3 inflammasome activation by promoting mitophagy. In conclusion, saponin extract inhibited inflammation-mediated pathological inflammasome activation in macrophages, thereby preventing NAFLD development. Thus, saponin extract administration may be an alternative method for NAFLD prevention