关键词： Cardiogenic shock   CICU   doppler   echocardiography   hemodynamics   mortality   shock   stroke volume  

摘要： Background: Prior studies have shown worse outcomes in patients with cardiogenic shock (CS) who have reduced left ventricular ejection fraction (LVEF), but the association between other transthoracic echocardiogram (TTE) findings and mortality in CS patients remains uncertain. We hypothesized that Doppler TTE measurements would outperform LVEF for risk stratification. Methods: Retrospective analysis of cardiac intensive care unit patients with an admission diagnosis of CS and a TTE within 1 day of admission. Hospital survivors and inpatient deaths were compared, and multivariable logistic regression was used to analyze the associations between TTE variables and hospital mortality. Results: We included 1,085 patients, with a median age of 69.5 (59.6, 77.5) years;37% were females and 62% had an acute coronary syndrome. Most patients (66%) had moderate or severe left ventricular (LV) systolic dysfunction, and 48% had moderate or severe right ventricular (RV) systolic dysfunction. Hospital mortality occurred in 31%, and inpatient deaths had a lower median LVEF (29% vs. 35%, P < 0.001). Patients with mild or no LV or RV dysfunction were at lower risk of adjusted hospital mortality (P < 0.01). The LV outflow tract (LVOT) velocity-time integral (VTI) was the single best predictor of hospital mortality. After multivariable adjustment, both the LVEF and LVOT VTI remained strongly associated with hospital mortality (P < 0.001). Conclusions: Early comprehensive Doppler TTE can provide important prognostic insights in CS patients, highlighting its potential utility in clinical practice. The LVOT VTI, reflecting forward flow, is an important measurement to obtain on bedside TTE.

关键词： rodenticide   control   Mus musculus domesticus   bait substrate   food preference   zinc phosphide  

摘要： BACKGROUND: House mice (Mus musculus) cause significant, ongoing losses to grain crops in Australia, particularly during mouse plagues. Zinc phosphide (ZnP) coated grain is used for control, but with variable success. In a laboratory setting, we tested if mice would (i) switch from consumption of one grain type to another when presented with an alternative and (ii) consume ZnP-treated grains when presented as a choice with a different grain. RESULTS: Mice readily switched from their background grain to an alternative grain, preferring cereals (wheat or barley) over lentils. Mice readily consumed ZnP-coated barley grains. Their mortality rate was significantly higher (86%, n = 30) in the presence of a less-favoured grain (lentils) compared to their mortality rate (47%, n = 29;53%, n = 30) in the presence of a more-favoured grain (wheat and barley, respectively). Mice died between 4 and 112 h (median = 18 h) after consuming one or more toxic grains. Independent analysis of ZnP-coated grains showed variable toxin loading indicating that consumption of a single grain would not guarantee intake of a lethal dose. There was also a strong and rapid behavioural aversion if mice did not consume a lethal dose on the first night. CONCLUSIONS: The registered dose rate of 25 g of ZnP/kg wheat (similar to 1 mg of ZnP/grain) in Australia needs to be re-evaluated to determine what factors may be contributing to variation in efficacy. Further field research is also required to understand the complex association between ZnP dose, and quantity and quality of background food on efficacy of ZnP baits. (C) 2021 Commonwealth Scientific & Industrial Research Organisation. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

关键词： endoscopic surgical procedure   endoscopy   glioma   thalamic disease  

摘要： Background Surgery for thalamic lesions has been considered challenging due to their deep-seated location. Endoscopic excision of deep-seated brain tumors using tubular retractor has been shown to be safe and effective in prior studies;however, there are limited reports regarding its use for thalamic tumors. We present our experience of endoscope-controlled resection of thalamic tumors using a tubular retractor. Material and Methods This was a prospective observational case series done at a tertiary center specialized for endoscopic neurosurgery during the period from 2010 to 2019. Surgeries were performed under the endoscopic control using a silicon tubular retractor. Lesions were approached transcortically or trans-sulcally. Data were collected for the extent of resection, amount of blood loss, operative time, need for conversion to microscopy, and complications. Results Twenty-one patients of thalamic masses of 14- to 60-year age underwent the surgeries. Pathologies ranged from grade I to IV gliomas. Gross total and near-total resection could be done in 42.85% of cases for each group. The average blood loss and operative time were164.0483.63mL and 157.14 +/- 28.70minutes, respectively. Complications included a small brain contusion, two transient hemipareses, and one transient speech deficit. Conclusion Endoscopic excision of thalamic tumors using a tubular retractor was found to be a safe and effective alternative to microscopic resection.

关键词： mRNA alternative splicing   Exon GC content   Chromatin remodelling   SWI   SNF   BRGG1   hnRNPL   hnRNPU   SAM68  

摘要： BRG1 and BRM are ATPase core subunits of the human SWI/SNF chromatin remodelling complexes mainly associated with transcriptional initiation. They also have a role in alternative splicing, which has been shown for BRM-containing SWI/SNF complexes at a few genes. Here, we have identified a subset of genes which harbour alternative exons that are affected by SWI/SNF ATPases by expressing the ATPases BRG1 and BRM in C33A cells, a BRG1- and BRM-deficient cell line, and analysed the effect on splicing by RNA sequencing. BRG1- and BRM-affected sub-sets of genes favouring both exon inclusion and exon skipping, with only a minor overlap between the ATPase. Some of the changes in alternative splicing induced by BRG1 and BRM expression did not require the ATPase activity. The BRG1-ATPase independent included exons displayed an exon signature of a high GC content. By investigating three genes with exons affected by the BRG-ATPase-deficient variant, we show that these exons accumulated phosphorylated RNA pol II CTD, both serine 2 and serine 5 phosphorylation, without an enrichment of the RNA polymerase II. The ATPases were recruited to the alternative exons, together with both core and signature subunits of SWI/SNF complexes, and promoted the binding of RNA binding factors to chromatin and RNA at the alternative exons. The interaction with the nascent RNP, however, did not reflect the association to chromatin. The hnRNPL, hnRNPU and SAM68 proteins associated with chromatin in cells expressing BRG1 and BRM wild type, but the binding of hnRNPU to the nascent RNP was excluded. This suggests that SWI/SNF can regulate alternative splicing by interacting with splicing-RNA binding factor and influence their binding to the nascent pre-mRNA particle.

关键词： Auricular vagus nerve stimulation   lipopolysaccharide   lung injury   neutrophil extracellular traps   neutrophils  

摘要： Vagus nerve stimulation has been shown to exert anti-inflammation activities in sepsis. However, surgical implantation of stimulation devices is performed under general anesthesia, which limits its clinical application. Auricular vagus nerve stimulation (AVNS) is a minimal invasive technique that delivers electrical currents to the auricular branch of the vagus nerve. The purpose of this study was to determine the effects of AVNS on systemic inflammation, lung injury, neutrophil infiltration, and neutrophil extracellular traps (NETs) formation in the lung. In a LPS challenge lung-injury mice model, AVNS was applied to bilateral ears. Twelve hours after LPS administration, samples of blood, bronchoalveolar lavage fluid (BALF), and lung tissues were processed for investigations. We found that the treatment with AVNS significantly attenuated histopathological changes and neutrophil infiltration in the lung tissue, inhibited inflammatory cytokine elevations in serum and BALF, and decreased protein concentrations in BALF. Besides, AVNS decreased leukocyte and neutrophil accounts in BALF. Furthermore, colocalization of citrullination of histone H3 and myeloperoxidase expressions (highly specific marker of NETs) was reduced in AVNS mice. In conclusion, AVNS reduced systemic inflammation, attenuated lung edema, and inhibited neutrophil infiltration and NETs formation in the lung in LPS mice.

关键词： Gut dysbiosis   Neuropathology   Neurodegenerative disease   Neurotoxin   Alzheimer's disease   Parkinson's disease  

摘要： The late onset neuropathologies, including Alzheimer's disease and Parkinson's disease, have become increasingly prevalent. Their causation has been linked to genetics, gut microbiota dysbiosis (gut dysbiosis), autoimmune diseases, pathogens and exposures to neurotoxins. An alternative explanatory hypothesis is provided for their pathogenesis. Virtually everyone has pervasive daily exposures to neurotoxins, through inhalation, skin contact, direct blood transmission and through the gastrointestinal tract by ingestion. As a result, every individual has substantial and fluctuating neurotoxin blood levels. Two major barriers to neurotoxin entry into the central nervous system are the blood-brain barrier and the intestinal wall, in the absence of gut dysbiosis. Inflammation from gut dysbiosis, induced by antibiotic usage, can increase the intestinal wall permeability for neurotoxins to reach the bloodstream, and also increase the blood-brain barrier permeability to neurotoxins. Gut dysbiosis, including gut dysbiosis caused by antibiotic treatments, is an especially high risk for neurotoxin entry into the brain to cause late onset neuropathologies. Gut dysbiosis has far-reaching immune system and central nervous system effects, and even a transient gut dysbiosis can act in combination with neurotoxins, such as aluminum, mercury, lead, arsenic, cadmium, selenium, manganese, organophosphate pesticides and organochlorines, to reach neurotoxin blood levels that can initiate a late onset neuropathology, depending on an individual's age and genetic vulnerability.

关键词： Fish   Alternative splicing   Heat stress   RNA sequencing   Genome  

摘要： Rainbow trout (Oncorhynchus mykiss) is one of the most economically important cold-water farmed species in the world, and transcriptomic studies in response to heat stress have been conducted and will be studied in depth. Alternative splicing (AS), a post-transcriptional regulatory process that regulates gene expression and increases proteomic diversity, is still poorly understood in rainbow trout under heat stress. In the present study, 18,623 alternative splicing events were identified from 9936 genes using RNA transcriptome sequencing technology (RNA-Seq) and genomic information. A total of 2731 differential alternative splicing (DAS) events were found among 2179 differentially expressed genes (DEGs). Gene ontology analysis revealed that the DEGs were mainly enriched in cellular metabolic process, cell part, and organic cyclic compound binding under heat stress. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis displayed that the DEGs were enriched for 39 pathways, and some key pathways, such as lysine degradation, are involved in the regulation of heat stress in liver tissues of rainbow trout. The results were validated by qRT-PCR, confirming reliability of our bioinformatics analysis.

关键词： Chorioallantoic membrane   Tumor   Cancer   Patient-derived xenograft  

摘要： A variety of in vivo experimental models have been established for the studies of human cancer using both cancer cell lines and patient-derived xenografts (PDXs). In order to meet the aspiration of precision medicine, the in vivomurine models have been widely adopted. However, common constraints such as high cost, long duration of experiments, and low engraftment efficiency remained to be resolved. The chick embryo chorioallantoic membrane (CAM) is an alternative model to overcome some of these limitations. Here, we provide an overview of the applications of the chick CAM model in the study of oncology. The CAM model has shown significant retention of tumor heterogeneity alongside increased xenograft take rates in several PDX studies. Various imaging techniques and data analysis have been applied to study tumor metastasis, angiogenesis, and therapeutic response to novel agents. Lastly, to practically illustrate the feasibility of utilizing the CAM model, we summarize the general protocol used in a case study utilizing an ovarian cancer PDX.

关键词： Acute myocardial infarction   basophil   cardiogenic shock   eosinophil   leukocyte   short-term outcome  

摘要： Background: Patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) are at high risk of death. Inflammation is involved in both CS and AMI, and our present study aimed to investigate the changes of leukocyte and its subtypes as well as their prognostic value in patients with CS complicating AMI. Methods: Data of 217 consecutive patients with CS complicating AMI were analyzed. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was the composite events of major adverse cardiovascular events (MACE) including 30-day all-cause mortality, ventricular tachycardia/ventricular fibrillation, atrioventricular block, gastrointestinal hemorrhage and nonfatal stroke. The association of leukocyte and its subtypes with the endpoints was analyzed by Cox regression analysis. Results: Leukocyte and its subtypes including neutrophil, eosinophil, lymphocyte, monocyte and basophil were all statistically significant between survivors and nonsurvivors (all P < 0.05). Among the leukocyte subtypes, eosinophil had the highest predictive value for 30-day all-cause mortality (AUC = 0.799) and the composite of leukocyte and its subtypes improved the predictive power (AUC = 0.834). The 30-day mortality and MACE K-M curves of leukocyte and its subtypes reveal a distinct trend based on the cut-off value determined by Youden Index (all log rank P < 0.001). After multivariable adjustment, high leukocyte (>11.6 x 10(9)/L) (HR 1.815;95%CI 1.134, 2.903;P = 0.013), low eosinophil (<0.3%) (HR 2.562;95%CI 1.412, 4.648;P = 0.002) and low basophil (<= 0.1%) (HR 1.694;95%CI 1.106, 2.592;P = 0.015) were independently associated with increased risk of 30-day mortality. Similarly, high leukocyte (>11.6 x 10(9)/L) (HR 1.894;95%CI 1.285, 2.791;P = 0.001), low eosinophil (<0.3%) (HR 1.729;95%CI 1.119, 2.670;P = 0.014) and low basophil (<= 0.1%) (HR 1.560;95%CI 1.101, 2.210;P = 0.012) were independently associated with increased risk of 30-day MACE. Conclusions: L