Development of an investigation form for hemodialysis infection outbreak: Identifying sources in the early stage.

BACKGROUND: There are many infectious factors causing the outbreak of hemodialysis infection, which may easily lead to the delay of investigation and treatment. This study aimed to develop an investigation form for hemodialysis infection outbreak (HIO), and to identify sources of outbreak in early stage. METHODS: After an exhaustive literature review, we used the Delphi method to determine the indicators and relative risk scores of the assessment tools through 2 rounds of specialist consultation and overall consideration of the opinions and suggestions of 18 specialists. RESULTS: A total of 87 studies of HIOs were eligible for inclusion. The mean authority coefficient (Cr) was 0.89. Kendall's W coefficient of the specialist consultation was 0.359 after 2 rounds of consultation (P < .005), suggesting that the specialists had similar opinions. Based on 4 primary items and 13 secondary items of the source of HIO, and tripartite distribution characteristics of infected patients, we constructed the investigation form. CONCLUSIONS: The investigation form may be implemented during the initial phase of an outbreak investigation, it is a prerequisite for taking effective control measures, avoiding HIO occurrence. However, the efficacy of the investigation form needs to be further evaluated.

Anti-tau single domain antibodies clear pathological tau and attenuate its toxicity and related functional defects.

Tauopathies are a group of neurodegenerative diseases characterized by the presence of tau inclusions. We have developed over fifty anti-tau single-domain antibodies (sdAbs) derived from phage display libraries of a llama immunized with recombinant and pathological tau immunogens. We examined the therapeutic potential of four of these sdAbs in a Drosophila tauopathy model following their transgenic expression either in all neurons or neuronal subtypes. Three of these sdAbs showed therapeutic potential in various assays, effectively clearing pathological tau and attenuating or preventing tau-induced phenotypes that typically manifest as defects in neuronal axonal transport, neurodegeneration, functional impairments, and shortened lifespan. Of these three, one sdAb was superior in every assay, which may at least in part be attributed to its tau-binding epitope. These findings support its development as a gene therapy for tauopathies.

The role of CO2 in the genesis of Dabie-type porphyry molybdenum deposits.

Porphyry-type molybdenum deposits, many of which are in China, supply most of the World's molybdenum. Of particular importance are the molybdenum deposits located in the Qinling-Dabie region that are responsible for more than half of China's molybdenum production. A feature that distinguishes this suite of deposits from the better-known Climax and Endako sub-types of porphyry molybdenum deposits is their formation from CO2-rich magmatic-hydrothermal fluids. The role of CO2, if any, in the transport of molybdenum by these fluids, however, is poorly understood. We conducted experiments on the partitioning of molybdenum between H2O-CO2, H2O-NaCl, and H2O-NaCl-CO2 fluids and a felsic melt at 850 °C and 100 and 200 MPa. Here we show that the exsolution of separate (immiscible) brine and vapor leads to the very high brine DMo values needed for efficient extraction of Mo from the magmas forming Dabie-type porphyry molybdenum deposits.

RhIII-Catalyzed Direct Heteroarylation of Unactivated C(sp3)-H with N-Heteroaryl Boronates.

Disclosed herein is a rhodium(III)-catalyzed direct heteroarylation reaction between unactivated aliphatic C(sp3)-H bonds in 2-alkylpyridines and heteroaryl organoboron reagents. This catalytic protocol is compatible with various heterocyclic boronates containing ortho- and meta-pyridine, pyrazoles, furan, and quinoline with strong coordination capability. The achievement of this methodology provides an efficient route to build new C(sp3)-heteroaryl bonds.

Construction of a postoperative infection outbreak investigation form: A tool for early detection and control measures.

BACKGROUND: To develop an investigation form for postoperative infection outbreak (PIO), and to identify sources of the outbreak in the early stage. METHODS: After an exhaustive literature review, we used the Delphi method to determine the indicators and relative risk scores of the assessment tools through 2 rounds of specialist consultation and overall consideration of the opinions and suggestions of 20 specialists. RESULTS: A total of 203 studies of PIO were eligible for inclusion. The mean authority coefficient (Cr) was 0.87. Kendall's W coefficient of the specialist consultation was 0.704 after 2 rounds of consultation (P < .005), suggesting that the specialists had similar opinions. Based on 4 primary items and 19 secondary items of the source of PIO, and tripartite distribution characteristics of infected patients, we constructed the PIO investigation form. CONCLUSIONS: The PIO investigation form can be used in the investigation of the early-stage cluster of cases, it's a prerequisite for taking effective control measures, avoiding PIO occurrence. However, the effect of the investigation form needs to be further evaluated.

RhIII-promoted directed C-H N-heteroarylation of 2-pyridones.

A catalytic protocol for the Cp*RhIII-promoted C6-selective N-heteroarylation of 2-pyridones with N-heterocyclic boronates has been successfully developed utilizing a removable pyridine auxiliary. This system features high efficiency with mild conditions and also tolerates ortho- and meta-substituted pyridines, pyrazoles, pyrimidine, non-substituted quinolines, thiophene and furan well. The easy synthetic approach could potentially be applied to construct heterocyclic drug molecules bearing 2-pyridone-heteroaryl motifs.

An FMEA model for risk assessment of university sustainability: using a combined ITARA with TOPSIS-AL approach based neutrosophic sets.

It is necessary to emphasize both the process and results of performance management to find the balance between quality and quantity needed to ensure the sustainable development of universities to make the best use of limited educational resources and meet the diverse needs of students. This study applies failure mode and effects analysis (FMEA) to analyze obstacles to university sustainability by constructing complete risk assessment modes and reference indicators. The neutrosophic set theory was incorporated into the FMEA to account for information uncertainty and asymmetry. A specialist team then evaluated the importance of the risk factors using neutrosophic indifference threshold-based attribute ratio analysis to determine objective weights for the risk factors. Furthermore, the neutrosophic technique for order preference by similarity to the ideal solution based on aspiration level (N-TOPSIS-AL) is employed to aggregate the total risk scores of the failure modes. Using neutrosophic sets to measure truth, falsity, and indeterminacy in the assessment significantly improve the adaptability of the fuzzy theory to real-world problems. The study results indicate that when assessing university affairs management and analyzing possible risks, priority must be given to the occurrence of risks and that the lack of educational facilities is the riskiest item in the specialist assessment. The proposed assessment model can be applied as a basis for university sustainability assessments to accelerate the development of other forward-looking approaches.

Research progress on influence of PM2.5 on allergic rhinitis / 环境与职业医学

Allergic rhinitis (AR) is one of the main chronic inflammatory diseases that pose a global threat. Its symptoms persist for a long time, recur, and seriously affect the physical and mental health of the patients. Existing research has shown that the occurrence and development of AR are related to genetic and environmental factors. In recent years, the harm of air pollution to human health has received increasing attention, and fine particulate matter (PM2.5) is the main harmful component of air pollutants. Its small particle size makes it easy to absorb various harmful substances, enter the respiratory tract, damage the nasal mucosa, and participate in the occurrence and development process of AR. At present, a large number of epidemiological studies have confirmed that PM2.5 is positively related to the incidence rate and severity of symptoms of AR, but its exact mechanism is still unclear. Therefore, studying the mechanism of PM2.5 exposure on AR damage is expected to provide new clues for exploring the pathogenesis and deterioration of AR. This article reviewed the epidemiological studies and toxicological mechanisms of PM2.5 exposure and AR in recent years; discussed the potential biological mechanisms of PM2.5 induced AR occurrence and development, including nasal mucositis damage, oxidative stress, and immune damage. Furthermore, a new research direction was proposed, which suggested that neuroimmune disorders and bacterial imbalance may be involved in the progression of AR and play a certain role in the toxic effects induced by PM2.5. We aim to provide ideas and a theoretical basis for developing effective measures to prevent and treat AR.

One-Pot Construction of Heteroarylation/Esterification Products of Acrylic Acids via Iridium(III)-Catalyzed C-H Activation.

A carboxylate-assisted iridium(III)-catalyzed regioselective C(sp2)-H heteroarylation/esterification reaction of acrylic acid is disclosed herein for the first time. This catalytic protocol tolerates various α-substituted, ß-substituted, and α, ß-disubstituted acrylic acids as well as heteroaromatic boronates well. The resulting 3,4-dihydro-2H-pyran-6-carboxylic acid derivative 3r highlighted the AIE-active luminophore with multiple emission signal properties and a high quantum yield of 28%, exhibiting the potential application of this methodology for the synthesis of nitrogen-containing organic functional materials.

Circulating plasma galectin-3 predicts new-onset atrial fibrillation in patients after acute myocardial infarction during hospitalization.

BACKGROUND: New-onset atrial fibrillation (NOAF) is a common complication in patients with acute myocardial infarction (AMI) during hospitalization. Galectin-3 (Gal-3) is a novel inflammation marker that is significantly associated with AF. The association between post-AMI NOAF and Gal-3 during hospitalization is yet unclear. OBJECTIVE: The present study aimed to investigate the predictive value of plasma Gal-3 for post-AMI NOAF. METHODS: A total of 217 consecutive patients admitted with AMI were included in this retrospective study. Peripheral venous blood samples were obtained within 24 h after admission and plasma Gal-3 concentrations were measured. RESULTS: Post-AMI NOAF occurred in 18 patients in this study. Patients with NOAF were older (p < 0.001) than those without. A higher level of the peak brain natriuretic peptide (BNP) (p < 0.001) and Gal-3 (p < 0.001) and a lower low-density lipoprotein cholesterol level (LDL-C) (p = 0.030), and an estimated glomerular filtration rate (e-GFR) (p = 0.030) were recorded in patients with post-AMI NOAF. Echocardiographic information revealed that patients with NOAF had a significantly decreased left ventricular eject fraction (LVEF) (p < 0.001) and an increased left atrial diameter (LAD) (p = 0.004) than those without NOAF. The receiver operating characteristic (ROC) curve analysis revealed a significantly higher value of plasma Gal-3 in the diagnosis of NOAF for patients with AMI during hospitalization (area under the curve (p < 0.001), with a sensitivity of 72.22% and a specificity of 72.22%, respectively. Multivariate logistic regression model analysis indicated that age (p = 0.045), plasma Gal-3 (p = 0.018), and LAD (p = 0.014) were independent predictors of post-MI NOAF. CONCLUSIONS: Plasma Gal-3 concentration is an independent predictor of post-MI NOAF.

RhIII-Catalyzed C-H N-Heteroarylation and Esterification Cascade of Carboxylic Acid with Organoboron Reagents and 1,2-Dichloroethane in One-Pot Synthesis.

A RhIII-catalyzed C(sp2)-H N-heteroarylation and esterification cascade of aryl carboxylic acids with N-heteroaromatic boronates and 1,2-dichloroethane in a one-pot synthesis has been disclosed. The strong coordinating ability of ortho- and meta-substituted pyridine boronates and pyrazoles as well as unsubstituted pyrimidine allows them to serve as the coupling partners. This protocol allows late-stage modification of the key precursor of roflumilast and compounds of pharmaceutical interest, which highlights the potential application of this synthetic method.

Exploring the mutual influence among the social innovation factors amid the COVID-19 pandemic.

From the triple bottom line, the social aspect has received relatively limited attention during the Corona Virus Disease (COVID-19) pandemic, particularly in the emerging economies. Social innovation factors help improve the sustainability performance of the companies. This study develops a social innovation decision framework and analyses the interrelationships among social innovation factors considering the COVID-19 situation. For this purpose, the Decision-Making Trial and Evaluation Laboratory (DEMATEL) is extended by integrating the Z numbers and rough fuzzy set theory into its computational procedure. Z-numbers address the uncertainty of the decision and experts' confidence in the evaluation and rough numbers are used for aggregating the experts' opinions. On this basis, the mutual influence of social innovation factors and the influence weights of these factors are investigated. The results suggest that a quick response to market demand for sustainable products is the most influential factor in attaining social sustainability innovation during the pandemic. This article is concluded by providing insights for industrial experts and decision-makers to understand the underpinnings of social sustainability innovation during unforeseen situations.

A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oogenesis and wing development.

Metazoans have evolved various quality control mechanisms to cope with cellular stress inflicted by external and physiological conditions. ATF4 is a major effector of the integrated stress response, an evolutionarily conserved pathway that mediates adaptation to various cellular stressors. Loss of function of Drosophila ATF4, encoded by the gene cryptocephal (crc), results in lethality during pupal development. The roles of crc in Drosophila disease models and in adult tissue homeostasis thus remain poorly understood. Here, we report that a protein-trap Minos-mediated integration cassette insertion in the crc locus generates a Crc-GFP fusion protein that allows visualization of Crc activity in vivo. This allele also acts as a hypomorphic mutant that uncovers previously unknown roles for crc. Specifically, the crc protein-trap line shows Crc-GFP induction in a Drosophila model for retinitis pigmentosa. This crc allele renders flies more vulnerable to amino acid deprivation and age-dependent retinal degeneration. These mutants also show defects in wing veins and oocyte maturation. Together, our data reveal previously unknown roles for crc in development, cellular homeostasis and photoreceptor survival. This article has an associated First Person interview with the first author of the paper.

The synthesis of aryl-heteroaryl derivatives via the RhIII-catalyzed heteroarylation of arenes and heteroaromatic boronates.

An efficient RhIII-catalyzed strategy for constructing aryl-heteroaryl derivatives with removable ketoxime ether auxiliaries via direct C-H heteroarylation based on arenes and heteroaromatic boronates has been disclosed. This protocol could tolerate various pyridine, pyrimidine, pyrazole, thiophene, and furan heteroaromatic boronates well, providing the desired products with high reactivities and excellent regioselectivity. The easy synthetic accessibility may offer potential for application in the synthesis of heterocyclic drug molecules containing aryl-heteroaryl motifs.

An Exploration and Technical Notes for Advanced Airway Management on the Ski Slope: A Simulation Experiment.

BACKGROUND: Skiing is a high-risk winter sport, and the rate of injury fatality is the highest compared to other winter sports. During skiing rescue, the harsh natural environments will increase the difficulty of artificial airway establishment. There has been no research focusing on the establishment of the artificial airway during skiing rescue site. This study aims to simulate the real-world scenario, calculating and comparing the operation time of different artificial airways on the cold slope, and to explore the optimal method of establishing artificial airway on the cold slope, sharing our experience, technical notes, and pitfalls we encountered, hoping to help establish a standard operating procedure in advanced airway management on the ski slope. METHODS: The simulated human was placed on the cold slope with the head under the feet. Artificial airway was established by the same anesthesiologist using endotracheal intubation (endotracheal intubation group), LMA Supreme laryngeal mask (LMA group), and I-gel laryngeal mask (I-gel group). Each method was repeated 5 times, and the operation time and whether it was successful by one attempt were recorded and compared between groups. RESULTS: Three groups of artificial airway were successful by one attempt.. The bite block dropped and drifted away for one time in the endotracheal intubation group. Operation time is 209.2 ± 32.7 seconds in the endotracheal intubation group, 72.2 ± 3.1 seconds in the LMA group, and 52.6 ± 4.2 seconds in the I-gel group. ANOVA showed that there was a significant difference in the operation time among the three groups (p < 0.001). Tukey's post hoc test showed that there were statistically significant differences between the endotracheal intubation group and the other two groups in operation time, p < 0.001, while there was no significant difference between the LMA group and I-gel group (p=0.275). CONCLUSION: The artificial airway can be completed by endotracheal intubation and LMA and I-gel laryngeal mask insertion on the cold slope. Artificial airway with the I-gel laryngeal mask takes the shortest time in this study. Extra caution should be paid to slippery and drifting.

Drosophila fabp is required for light-dependent Rhodopsin-1 clearance and photoreceptor survival.

Rhodopsins are light-detecting proteins coupled with retinal chromophores essential for visual function. Coincidentally, dysfunctional Rhodopsin homeostasis underlies retinal degeneration in humans and model organisms. Drosophila ninaEG69D mutant is one such example, where the encoded Rh1 protein imposes endoplasmic reticulum (ER) stress and causes light-dependent retinal degeneration. The underlying reason for such light-dependency remains unknown. Here, we report that Drosophila fatty acid binding protein (fabp) is a gene induced in ninaEG69D/+ photoreceptors, and regulates light-dependent Rhodopsin-1 (Rh1) protein clearance and photoreceptor survival. Specifically, our photoreceptor-specific gene expression profiling study in ninaEG69D/+ flies revealed increased expression of fabp together with other genes that control light-dependent Rh1 protein degradation. fabp induction in ninaEG69D photoreceptors required vitamin A and its transporter genes. In flies reared under light, loss of fabp caused an accumulation of Rh1 proteins in cytoplasmic vesicles. The increase in Rh1 levels under these conditions was dependent on Arrestin2 that mediates feedback inhibition of light-activated Rh1. fabp mutants exhibited light-dependent retinal degeneration, a phenotype also found in other mutants that block light-induced Rh1 degradation. These observations reveal a previously unrecognized link between light-dependent Rh1 proteostasis and the ER-stress imposing ninaEG69D mutant that cause retinal degeneration.

RhIII-Catalyzed Direct Heteroarylation of C(sp3)-H and C(sp2)-H Bonds in Heterocycles with N-Heteroaromatic Boronates.

Herein, we disclose a RhIII-catalyzed heteroarylation of C(sp3)-H and C(sp2)-H bonds in heterocycles with organoboron reagents. This protocol displays high efficiency and excellent functional group tolerance. A range of heterocyclic boronates with strong coordinating atoms, including pyridine, pyrimidine, pyrazole, thiophene, and furan derivatives, can be extensively served as the coupling reagents. The direct heteroarylation method could supply potential application in terms of the synthesis of drug molecules with multiple heterocycles.

CK-3, A Novel Methsulfonyl Pyridine Derivative, Suppresses Hepatocellular Carcinoma Proliferation and Invasion by Blocking the PI3K/AKT/mTOR and MAPK/ERK Pathways.

Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis that highly expresses phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (ERK). The PI3K/AKT/mTOR and MAPK/ERK signaling pathways play a crucial role in HCC tumor formation, cell cycle, apoptosis and survival. However, no effective targeted therapies against these pathways is available, mainly due to the extensive and complex negative feedback loops between them. Here we used CK-3, a dual blocker of the PI3K/AKT/mTOR and MAPK/ERK pathways, against HCC cell lines to verify its anti-tumor activity in vitro. CK-3 exhibited cytotoxic activity against HCC, as demonstrated with MTT and colony formation assays. The anti-metastatic potential of CK-3 was demonstrated with wound healing and cell invasion assays. The ability of CK-3 to block both the PI3K/AKT/mTOR and MAPK/ERK pathways was also confirmed. CK-3 induced the apoptosis of Hep3B cells, while Bel7402 cells died via mitotic catastrophe (MC). Oral administration of CK-3 also inhibited the subcutaneous growth of BEL7402 cells in nude mice. Simultaneous PI3K/AKT/mTOR and MAPK/ERK pathway inhibition with CK-3 may be superior to single pathway monotherapies by inhibiting their feedback-regulation, and represents a potential treatment for HCC.

Erector Spinae Plane Block Similar to Paravertebral Block for Perioperative Pain Control in Breast Surgery: A Meta-Analysis Study.

BACKGROUND: Erector spinae plane block could be a potential alternative to paravertebral block or other analgesic techniques for breast surgery, but the current evidence on erector spinae plane block in breast surgery is conflicting. OBJECTIVE: To compare the analgesic effectiveness between erector spinae plane block, systemic analgesic, and paravertebral block for breast surgery. STUDY DESIGN: Meta-analysis. SETTING: The literature search was performed from 2016 to August 2020 using the MEDLINE, EMBASE, Cochrane library, and ClinicalTrials.gov databases. METHODS: Clinical trials comparing erector spinae plane block to systemic analgesic and paravertebral block were included from the aforementioned databases. Primary outcomes were 24-hour postoperative opioid administration and postoperative pain score. Secondary outcomes were patient satisfaction levels, post-anesthesia care unit and hospital stay, block-related side effects, and opioid-related side effects. Systematic search, critical appraisal, and pooled analysis were performed according to the PRISMA statement. RESULTS: We analyzed 495 cases in 8 randomized controlled trials. Compared with a systemic analgesic, the use of erector spinae plane block resulted in a reduced 24-hour postoperative intravenous morphine equivalent dose by a mean difference of 7.59 mg (P < 0.00001). Compared with paravertebral block, no statistical difference was found in opioid administration. No differences were observed in pain score, opioid-related side effects, or analgesic technique-related complications. Between the trials, heterogeneity existed and could not be evaluated using meta-regression owing to inadequate reported data. LIMITATIONS: Moderate heterogeneity among the included trials could not be assessed by potential covariates owing to the limited reported data in each trial. CONCLUSION: Erector spinae plane block is superior to systemic analgesic within 24 hours after breast surgery and can serve as an alternative to paravertebral block with similar analgesic effects.

Periphery signals generated by Piezo-mediated stomach stretch and Neuromedin-mediated glucose load regulate the Drosophila brain nutrient sensor.

Nutrient sensors allow animals to identify foods rich in specific nutrients. The Drosophila nutrient sensor, diuretic hormone 44 (DH44) neurons, helps the fly to detect nutritive sugar. This sensor becomes operational during starvation; however, the mechanisms by which DH44 neurons or other nutrient sensors are regulated remain unclear. Here, we identified two satiety signals that inhibit DH44 neurons: (1) Piezo-mediated stomach/crop stretch after food ingestion and (2) Neuromedin/Hugin neurosecretory neurons in the ventral nerve cord (VNC) activated by an increase in the internal glucose level. A subset of Piezo+ neurons that express DH44 neuropeptide project to the crop. We found that DH44 neuronal activity and food intake were stimulated following a knockdown of piezo in DH44 neurons or silencing of Hugin neurons in the VNC, even in fed flies. Together, we propose that these two qualitatively distinct peripheral signals work in concert to regulate the DH44 nutrient sensor during the fed state.