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2,334,700 |
Asystole in Orthognathic Surgery: A Case Report.
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A previously healthy 26-year-old man presented for elective Le Fort I osteotomy, bilateral mandibular osteotomy, and genioplasty. During the intraoperative course, the patient developed sudden bradycardia and asystole on placement of a bite block. Asystole is an extremely rare consequence of the trigeminocardiac reflex, and awareness of this potentially life-threatening complication is pivotal in its management.
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2,334,701 |
Randomised controlled trial of dexmedetomidine sedation vs general anaesthesia for inguinal hernia surgery on perioperative outcomes in infants.
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Neonates and infants undergoing general anaesthesia for hernia surgery are at risk of perioperative cardiorespiratory adverse events. The use of regional anaesthesia with dexmedetomidine preserves airway tone and may potentially avoid these complications. This study compares the perioperative conditions and adverse events between dexmedetomidine sedation with caudal block and general anaesthesia with caudal block for inguinal hernia surgery in infants.</AbstractText>A randomised controlled trial was conducted in a tertiary hospital in Singapore involving 104 infants younger than 3 months, who were randomised to receive either dexmedetomidine sedation (DEX) with caudal block or general sevoflurane anaesthesia with tracheal intubation and caudal block (GA) for inguinal hernia surgery. Perioperative conditions, haemodynamics and adverse events were compared between groups.</AbstractText>Fifty-one infants received DEX and 48 infants received GA. In the DEX group, 46 infants (90.2%) had their operations completed solely under this technique, two (3.9%) were converted to general anaesthesia with intubation, and three (5.9%) required brief administration of nitrous oxide or low-dose sevoflurane. Overall, 96.1% of infants in the DEX group did not require intubation. Perioperative conditions were similar in both groups. The DEX group had significantly lower heart rates and higher mean arterial pressures intraoperatively. Two infants in the DEX group (3.9%) required postoperative intensive care admission compared with six infants (12.5%) in the GA group.</AbstractText>Dexmedetomidine sedation with caudal block provides a feasible alternative to general anaesthesia in infants undergoing hernia surgery. This technique avoids the need for tracheal intubation, which may be beneficial in neonates.</AbstractText>NCT02559102.</AbstractText>Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,334,702 |
Complete Heart Block due to Octreotide Infusion in Patient with Cryptogenic Cirrhosis.
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A 62-year-old man was admitted to the emergency department (ED) with the complaint of intense hematemesis. He was admitted to intensive care unit because of acute esophageal variceal hemorrhage. He underwent sclerotherapy followed by a slow infusion of intravenous octreotide. Complete heart block occured in the patient during octreotide infusion and infusion was stopped. Temporary pacemaker was placed in the patient's heart. Normal sinus rhythm was observed in the follow up one day later and the pacemaker was removed from patient. He was discharged upon recommendation.
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2,334,703 |
A case of esophagogastroduodenoscopy induced Takotsubo cardiomyopathy with complete heart block.
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Takotsubo cardiomyopathy (TC) describes a reversible left ventricular dysfunction characterized by apical ballooning and basal hyperkinesis, commonly triggered by emotional or physical distress. TC associated with an esophagogastroduodenoscopy (EGD) has rarely been reported. We report a case of TC with complete heart block (CHB) in a patient receiving an EGD, who had no underlying cardiac disease, had previously tolerated both local and general anesthesia, and who had previously undergone similar endoscopic procedures without complications. The concurrence of both TC and CHB is unique in this case pertaining to a patient with no significant risk factors. The incidence, mechanism and prognosis of TC-associated arrhythmias are also reviewed.
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2,334,704 |
Accelerating cardiac diffusion tensor imaging combining local low-rank and 3D TV constraint.
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Diffusion tensor magnetic resonance imaging (DT-MRI, or DTI) is a promising technique for invasively probing biological tissue structures. However, DTI is known to suffer from much longer acquisition time with respect to conventional MRI and the problem is worsened when dealing with in vivo acquisitions. Therefore, faster DTI for both ex vivo and in vivo scans is highly desired.</AbstractText>This paper proposes a new compressed sensing (CS) reconstruction method that employs local low-rank (LLR) model and three-dimensional (3D) total variation (TV) constraint to reconstruct cardiac diffusion-weighted (DW) images from highly undersampled k-space data. The LLR model takes the set of DW images corresponding to different diffusion gradient directions as a 3D image volume and decomposes the latter into overlapping 3D blocks. Then, the 3D blocks are stacked as two-dimensional (2D) matrix. Finally, low-rank property is applied to each block matrix and the 3D TV constraint to the 3D image volume. The underlying constrained optimization problem is finally solved using the first-order fast method. The proposed method is evaluated on real ex vivo cardiac DTI data as a prerequisite to in vivo cardiac DTI applications.</AbstractText>The results on real human ex vivo cardiac DTI images demonstrate that the proposed method exhibits lower reconstruction errors for DTI indices, including fractional anisotropy (FA), mean diffusivities (MD), transverse angle (TA), and helix angle (HA), compared to existing CS-based DTI image reconstruction techniques.</AbstractText>The proposed method provides better reconstruction quality and more accurate DTI indices in comparison with the state-of-the-art CS-based DW image reconstruction methods.</AbstractText>
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2,334,705 |
Is Interleukin-38 a key player cytokine in atherosclerosis immune gene therapy?
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Atherosclerosis, a chronic inflammatory disease of the arteries associated with lipids and other metabolic alterations is a leading cause of death all around the world and its rate is raising as a result of unhealthy lifestyles. Reports by World Health Organization indicate that 31% of all death occurrences are due to heart attacks and strokes. Today, the most common medicines for treating atherosclerosis are statins which are HMG-coA reductase inhibitors. Beside their benefits in treating atherosclerosis, some side effects have been reported as well. Thus, therapeutic methods based on statins should be evaluated to result in more beneficial effects. Since atherosclerosis is an inflammatory disorder, an anti-inflammatory component can decrease the impact of this disease. Interleukin-38, a newly discovered anti-inflammatory cytokine, which acts as an Interleukin-36 receptor antagonist can block Nuclear Factor KB and Activator protein-1 signaling pathways, and block atherogenic core formation accordingly. This novel proposed immune gene therapy can be applied to atherosclerosis treatment in a trial study. In this hypothesis, Interleukin-38 gene is transferred into bone marrow Mesenchymal Stem Cells of atherosclerotic mouse model Apo E-/- via an adenoviral vector. It is expected that Interleukin-38 gene expression by Mesenchymal Stem Cells can efficiently remedy atherosclerosis without the side effects of statins.
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2,334,706 |
Glycerol derived process contaminants in refined coconut oil induce cholesterol synthesis in HepG2 cells.
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Despite its 50-year history, the conventional diet-heart hypothesis holding that dietary saturated fats raise serum cholesterol, and with it, cardiovascular risk, remains controversial. Harsh chemical and physical treatment generates process contaminants, and refined oils raise serum and tissue cholesterol in vivo independent of saturated fat content. We developed an in vitro bioassay for rapidly assessing the influence of oils on cholesterol metabolism in the human liver HepG2 cell line, and tested it using coconut oil (CO) of various stages of refinement. CO was dissolved with dipalmitoyl phosphatidylcholine (DPPC) surfactant, solvent evaporated, and emulsified into fat-free cell culture media. After 24 h treatment cellular cholesterol and triacylglycerol increased; HMG-CoA Reductase (HMGCR) increased and CYP7A1 (cholesterol 7α-hydroxylase) decreased with sequential processing steps, deacidification, bleaching, deodorization, while fatty acid profiles were not affected. Glycerol-derived process contaminants glycidyl esters and monochloropropandiol (MCPD) increased with processing. Addition of glycidyl or MCPD to virgin CO (VCO) had similar effects to processing, while addition of phenolic antioxidants to fully refined CO reduced HMGCR and increased CYP7A1. We conclude that harsh processing creates contaminants that raise cholesterol levels in vitro, consistent with a role as a contributing atherosclerotic factor.
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2,334,707 |
The immunocytochemical expression of VE-1 (BRAF V600E-related) antibody identifies the aggressive variants of papillary thyroid carcinoma on liquid-based cytology.
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The recently introduced monoclonal V600E antibody (clone VE1) is likely to be an alternative strategy for detecting this mutation in thyroid lesions. Although VE1 immunostaining and molecular methods used to assess papillary thyroid carcinoma in surgical specimens are in good agreement, evaluation of VE1 in cytology and cell block samples is rarely performed, and its diagnostic value in cytology has not been well established. In this study, we sought to determine if VE1 is suitable for fine needle aspiration (FNA) and cell block methods.</AbstractText>A total of 86 patients who had BRAF V600E mutations were investigated with molecular and immunocytochemical (ICC) analysis in 45 FNA and 41 cell blocks. In total, 83 (96.5%) patients underwent surgical treatment. Assessment of BRAF V600E mutation status was performed in 72 (83.7%) cases.</AbstractText>Among the 72 cases analysed, 54 cases agreed (ICC+/BRAF+ or ICC-/BRAF-), seven cases were false positive (ICC+/BRAF-) and 11 cases were false negative (ICC-/BRAF+). False negative cases were not detected in the cell block method. The statistical analysis showed that sensitivity and specificity of ICC for detecting the BRAF V600E mutation were 61% and 77% in FNA samples and 100% and 73% in cell block.</AbstractText>The use of antibody VE-1 is a reliable method and a negative result of VE1 immunostaining might help to save time and money, restricting the molecular test to antibody-positive cases only. The identification of the aggressive variants of papillary carcinoma might be enabled by the expression of the antibody in neoplastic cells with tall cell features.</AbstractText>© 2019 John Wiley & Sons Ltd.</CopyrightInformation>
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2,334,708 |
The FBXW7-SHOC2-Raptor Axis Controls the Cross-Talks between the RAS-ERK and mTORC1 Signaling Pathways.
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FBXW7 is a tumor suppressive E3 ligase, whereas RAS-ERK and mechanistic target of rapamycin kinase (mTORC1) are two major oncogenic pathways. Whether and how FBXW7 regulates these two oncogenic pathways are unknown. Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr<sup>507</sup> by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation. FBXW7-mediated SHOC2 degradation terminates the RAS-MAPK signals and inhibits proliferation. Furthermore, SHOC2 selectively binds to Raptor to competitively inhibit the Raptor-mTOR binding to inactivate mTORC1 and induce autophagy, whereas Raptor binding of SHOC2 inhibits the SHOC2-RAS binding to block the MAPK pathway and proliferation. Finally, SHOC2 is overexpressed in pancreatic cancer, which correlated with poor patient survival. SHOC2 mutations were found in lung cancer tissues with gain-of-function activity. Collectively, the SHOC2-Raptor interaction triggers negative cross-talk between RAS-ERK and mTORC1 pathways, whereas FBXW7 regulates both pathways by targeting SHOC2 for ubiquitylation and degradation.
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2,334,709 |
Naproxen Nanoparticle-Loaded Thermosensitive Chitosan Hydrogel for Prevention of Postoperative Adhesions.
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Postoperative adhesions are the most common complications of peri-abdominal surgery; they not only affect the patient's quality of life but also increase the risk of a subsequent surgery. The use of implantable dressings to physically block surgical wounds is the primary solution to prevent postoperative adhesions. In this study, we prepared naproxen nanoparticles that were loaded with chitosan hydrogel (CS/Nap hydrogel) to prevent postoperative adhesions. Our data confirmed that the prepared CS/Nap hydrogel was thermosensitive and suitable for injection. The efficacy of anti-adhesion in a rat model revealed that the hydrogel effectively separated from the wounds of the abdominal wall and cecum. On day 7 postsurgery, the wounds were completely covered by a new epithelial layer, whereas wounds in the negative control group were glued together. Additionally, the in vivo toxicity study showed that the CS/Nap hydrogel had fewer toxic and side effects on major tissues and organs, including the liver, spleen, heart, lung, and kidney. We showed that a drug delivery system based on CS/Nap hydrogel has the potential not only to prevent postoperative abdominal adhesions and relieve pain but also to contribute to the administration of the hydrophobic drug naproxen.
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2,334,710 |
Enzymatic preparation of monoubiquitinated FANCD2 and FANCI proteins.
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In higher eukaryotes, DNA damage repair response pathways are orchestrated by several molecular signals including ubiquitination. In particular the repair of DNA interstrand crosslinks, toxic to transcription and replication processes, involve the activation of the Fanconi anemia repair pathway. At the heart of this pathway lies the monoubiquitination of FANCD2 and FANCI proteins, which triggers the recruitment of DNA repair factors. A major road block in our understanding of this fundamental repair pathway arises from the challenge with generating sufficient quantities of site-specifically monoubiquitinated FANCD2 and FANCI proteins to enable mechanistic and molecular studies. Current in vitro methods rely on the purification of a large (~0.8MDa), multiprotein E3 complex that can only partially monoubiquitinate a FANCD2-FANCI-DNA complex. In this chapter, we describe detailed protocols for the preparation of homogeneously and natively monoubiquitinated FANCD2 and FANCI proteins in isolation. The method relies on the use of a minimal E3 module and an engineered E2 variant that together drive site-specific ubiquitination of the isolated substrates, without the requirement of DNA cofactors. Using the enzymatic approach, we also demonstrate how added functionalities such as a fluorescently labeled ubiquitin can be conjugated on the FANCD2 and FANCI substrates, thus enabling multiple downstream applications.
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2,334,711 |
Acute Effects of Interrupting Prolonged Sitting With Intermittent Physical Activity on Blood Pressure in Preadolescent Children.
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To compare the acute effects of intermittent physical activity (PA) across 4 different intensities on blood pressure.</AbstractText>Thirty children (12 males and 18 females; aged 7-11 y; 33% overweight/obese; 53% nonwhite) completed 4 experimental conditions in random order: 8 hours sitting interrupted with 20, 2-minute low-, moderate-, high-intensity PA breaks, or sedentary screen-time breaks. PA intensity corresponded with 25%, 50%, and 75% of heart rate reserve. Blood pressure was measured during each condition in the morning (0800 h), noon (1200 h), and afternoon (1600 h).</AbstractText>There were no significant differences across conditions for systolic blood pressure (SBP; all Ps > .05). There was a significant effect of time with SBP decreasing throughout the day for all conditions (average morning SBP: 106 [1] mm Hg, average noon SBP: 101 [2] mm Hg, average afternoon SBP: 103 [1] mm Hg; P = .01). There were no significant effects of condition or time on diastolic blood pressure (all Ps > .05).</AbstractText>While sedentary behavior is known to be associated with hypertension in both adults and children, a single bout of prolonged sitting may be insufficient to produce hypertensive effects in otherwise healthy children. Future research should examine the appropriate dose of intermittent PA to accrue hypotensive responses in preadolescent children.</AbstractText>
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2,334,712 |
BRD4 directs hematopoietic stem cell development and modulates macrophage inflammatory responses.
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BRD4 is a BET family protein that binds acetylated histones and regulates transcription. BET/BRD4 inhibitors block blood cancer growth and inflammation and serve as a new therapeutic strategy. However, the biological role of BRD4 in normal hematopoiesis and inflammation is not fully understood. Analysis of Brd4 conditional knockout (KO) mice showed that BRD4 is required for hematopoietic stem cell expansion and progenitor development. Nevertheless, BRD4 played limited roles in macrophage development and inflammatory response to LPS ChIP-seq analysis showed that despite its limited importance, BRD4 broadly occupied the macrophage genome and participated in super-enhancer (SE) formation. Although BRD4 is critical for SE formation in cancer, BRD4 was not required for macrophage SEs, as KO macrophages created alternate, BRD4-less SEs that compensated BRD4 loss. This and additional mechanisms led to the retention of inflammatory responses in macrophages. Our results illustrate a context-dependent role of BRD4 and plasticity of epigenetic regulation.
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2,334,713 |
GNAI1 and GNAI3 Reduce Colitis-Associated Tumorigenesis in Mice by Blocking IL6 Signaling and Down-regulating Expression of GNAI2.
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<AbstractText Label="BACKGROUND & AIMS">Interleukin 6 (IL6) and tumor necrosis factor contribute to the development of colitis-associated cancer (CAC). We investigated these signaling pathways and the involvement of G protein subunit alpha i1 (GNAI1), GNAI2, and GNAI3 in the development of CAC in mice and humans.</AbstractText>B6;129 wild-type (control) or mice with disruption of Gnai1, Gnai2, and/or Gnai3 or conditional disruption of Gnai2 in CD11c+</sup> or epithelial cells were given dextran sulfate sodium (DSS) to induce colitis followed by azoxymethane (AOM) to induce carcinogenesis; some mice were given an antibody against IL6. Feces were collected from mice, and the compositions of microbiomes were analyzed by polymerase chain reactions. Dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) isolated from spleen and colon tissues were analyzed by flow cytometry. We performed immunoprecipitation and immunoblot analyses of colon tumor tissues, MDSCs, and mouse embryonic fibroblasts to study the expression levels of GNAI1, GNAI2, and GNAI3 and the interactions of GNAI1 and GNAI3 with proteins in the IL6 signaling pathway. We analyzed the expression of Gnai2 messenger RNA by CD11c+</sup> cells in the colonic lamina propria by PrimeFlow, expression of IL6 in DCs by flow cytometry, and secretion of cytokines in sera and colon tissues by enzyme-linked immunosorbent assay. We obtained colon tumor and matched nontumor tissues from 83 patients with colorectal cancer having surgery in China and 35 patients with CAC in the United States. Mouse and human colon tissues were analyzed by histology, immunoblot, immunohistochemistry, and/or RNA-sequencing analyses.</AbstractText>GNAI1 and GNAI3 (GNAI1;3) double-knockout (DKO) mice developed more severe colitis after administration of DSS and significantly more colonic tumors than control mice after administration of AOM plus DSS. Development of increased tumors in DKO mice was not associated with changes in fecal microbiomes but was associated with activation of nuclear factor (NF) κB and signal transducer and activator of transcription (STAT) 3; increased levels of GNAI2, nitric oxide synthase 2, and IL6; increased numbers of CD4+</sup> DCs and MDSCs; and decreased numbers of CD8+</sup> DCs. IL6 was mainly produced by CD4+</sup>/CD11b+</sup>, but not CD8+</sup>, DCs in DKO mice. Injection of DKO mice with a blocking antibody against IL6 reduced the expansion of MDSCs and the number of tumors that developed after CAC induction. Incubation of MDSCs or mouse embryonic fibroblasts with IL6 induced activation of either NF-κB by a JAK2-TRAF6-TAK1-CHUK/IKKB signaling pathway or STAT3 by JAK2. This activation resulted in expression of GNAI2, IL6 signal transducer (IL6ST, also called GP130) and nitric oxide synthase 2, and expansion of MDSCs; the expression levels of these proteins and expansion of MDSCs were further increased by the absence of GNAI1;3 in cells and mice. Conditional disruption of Gnai2 in CD11c+</sup> cells of DKO mice prevented activation of NF-κB and STAT3 and changes in numbers of DCs and MDSCs. Colon tumor tissues from patients with CAC had reduced levels of GNAI1 and GNAI3 and increased levels of GNAI2 compared with normal tissues. Further analysis of a public human colorectal tumor DNA microarray database (GSE39582) showed that low Gani1 and Gnai3 messenger RNA expression and high Gnai2 messenger RNA expression were significantly associated with decreased relapse-free survival.</AbstractText>GNAI1;3 suppresses DSS-plus-AOM-induced colon tumor development in mice, whereas expression of GNAI2 in CD11c+</sup> cells and IL6 in CD4+</sup>/CD11b+</sup> DCs appears to promote these effects. Strategies to induce GNAI1;3, or block GNAI2 and IL6, might be developed for the prevention or therapy of CAC in patients.</AbstractText>Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,334,714 |
Relationship of Neighborhood Greenness to Heart Disease in 249 405 US Medicare Beneficiaries.
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Background Nature exposures may be associated with reduced risk of heart disease. The present study examines the relationship between objective measures of neighborhood greenness (vegetative presence) and 4 heart disease diagnoses (acute myocardial infarction, ischemic heart disease, heart failure, and atrial fibrillation) in a population-based sample of Medicare beneficiaries. Methods and Results The sample included 249 405 Medicare beneficiaries aged 65 years and older whose location ( ZIP +4) in Miami-Dade County, Florida, did not change from 2010 to 2011. Analyses examined relationships between greenness, measured by mean block-level normalized difference vegetation index from satellite imagery, and 4 heart disease diagnoses. Hierarchical regression analyses, in a multilevel framework, assessed the relationship of greenness to each heart disease diagnosis, adjusting successively for individual sociodemographics, neighborhood income, and biological risk factors (diabetes mellitus, hypertension, and hyperlipidemia). Higher greenness was associated with reduced heart disease risk, adjusting for individual sociodemographics and neighborhood income. Compared with the lowest tertile of greenness, the highest tertile of greenness was associated with reduced odds of acute myocardial infarction by 25% (odds ratio, 0.75; 95% CI , 0.63-0.90), ischemic heart disease by 20% (odds ratio, 0.80; 95% CI , 0.77-0.83), heart failure by 16% (odds ratio, 0.84; 95% CI , 0.80-0.88), and atrial fibrillation by 6% (odds ratio, 0.94; 95% CI , 0.87-1.00). Associations were attenuated after adjusting for biological risk factors, suggesting that cardiometabolic risk factors may partly mediate the greenness to heart disease relationships. Conclusions Neighborhood greenness may be associated with reduced heart disease risk. Strategies to increase area greenness may be a future means of reducing heart disease at the population level.
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2,334,715 |
Cardiovascular Risk in Middle-Aged and Older Immigrants: Exploring Residency Period and Health Insurance Coverage.
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It is reported that while immigrants are, initially, healthier than the native-born upon resettlement, this advantage erodes over time. In the United States, uninsured aging immigrants are increasingly experiencing severe complications of cardiovascular disease (CVD). The purpose of this study was to compare overall CVD risk and explore the importance of health insurance coverage on CVD risk relative to other health access barriers, from 2007 to 2012, in recent and long-term immigrants >50 years of age.</AbstractText>This study was based on secondary cross-sectional analysis of the National Health and Nutrition Examination Survey (N = 1,920). The primary outcome, CVD risk category (high or low), was determined using the American College of Cardiology and American Heart Association Pooled Cohort equation. Differences between immigrant groups were examined using independent-samples t tests and chi-square analysis. The association between insurance and CVD risk was explored using a hierarchical block logistic regression model, in which variables were entered in a predetermined order. Changes in pseudo R2</sup> measured whether health insurance explained variance in cardiac risk beyond other variables.</AbstractText>Recent immigrants had lower overall CVD risk than long-term immigrants but were twice as likely to be uninsured and had higher serum glucose and lipid levels. Based on regression models, being uninsured contributed to CVD risk beyond other health access determinants, and CVD risk was pronounced among recent immigrants who were uninsured.</AbstractText>Health insurance coverage plays an essential part in a comprehensive approach to mitigating CVD risk for aging immigrants, particularly recent immigrants whose cardiovascular health is susceptible to deterioration.</AbstractText>Nurses are tasked with recognizing the unique social and physical vulnerabilities of aging immigrants and accounting for these in care plans. In addition to helping them access healthcare coverage and affordable medication, nurses and clinicians should prioritize low-cost lifestyle interventions that reduce CVD risk, especially diet and exercise programs.</AbstractText>© 2019 Sigma Theta Tau International.</CopyrightInformation>
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2,334,716 |
Glycosphingolipids promote pro-atherogenic pathways in the pathogenesis of hyperglycemia-induced accelerated atherosclerosis.
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Three out of four people with diabetes will die of cardiovascular disease. However, the molecular mechanisms by which hyperglycemia promotes atherosclerosis, the major underlying cause of cardiovascular disease, are not clear.</AbstractText>Three distinct models of hyperglycemia-associated accelerated atherosclerosis were used to identify commonly altered metabolites and pathways associated with the disease.</AbstractText>Normoglycemic apolipoprotein-E-deficient mice served as atherosclerotic control. Hyperglycemia was induced by multiple low-dose streptozotocin injections, or by introducing a point-mutation in one copy of insulin-2 gene. Glucosamine-supplemented mice, which experience accelerated atherosclerosis to a similar extent as hyperglycemia-induced models without alterations in glucose or insulin levels, were also included in the analysis. Untargeted plasma metabolomics were used to investigate hyperglycemia-associated accelerated atherosclerosis in three disease models. The effect of specific significantly altered metabolites on pro-atherogenic processes was investigated in cultured human vascular cells.</AbstractText>Hyperglycemic and glucosamine-supplemented mice showed distinct metabolomic profiles compared to controls. Meta-analysis of three disease models revealed 62 similarly altered metabolite features (FDR-adjusted p < 0.05). Identification of shared metabolites revealed alterations in glycerophospholipid and sphingolipid metabolism, and pro-atherogenic processes including inflammation and oxidative stress. Post-multivariate and pathway analyses indicated that the glycosphingolipid pathway is strongly associated with hyperglycemia-induced accelerated atherosclerosis in these atherogenic mouse models. Glycosphingolipids induced oxidative stress and inflammation in cultured human vascular cells.</AbstractText>Glycosphingolipids are strongly associated with hyperglycemia-induced accelerated atherosclerosis in three distinct models. They also promote pro-atherogenic processes in cultured human cells. These results suggest glycosphingolipid pathway may be a potential therapeutic target to block or slow atherogenesis in diabetic patients.</AbstractText>
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2,334,717 |
Real-Time Ultrasound Improves Accuracy of Caudal Block in Children.
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Caudal block, the most common regional anesthetic in children, is predominantly performed using palpation to determine placement. The efficacy of the palpation technique is unknown with respect to block success. While ultrasound has been suggested for use during caudal block, its use is infrequent.</AbstractText>A single-blinded prospective observational trial was performed evaluating provider success rate of caudal blocks placed by palpation alone. After needle insertion and partial local anesthetic injection, an ultrasound was performed to confirm correct location.</AbstractText>A total of 109 caudal blocks were performed during the prospective observational study. Success rate for caudal blocks done by palpation alone was 78.9% as confirmed by ultrasound. In 21.1% of caudal blocks, the provider incorrectly judged the needle to be in the caudal space as confirmed with ultrasound.</AbstractText>Real-time ultrasound visualization of local anesthetic injection provides reliable and immediate confirmation during caudal block in children.</AbstractText>
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2,334,718 |
Clinical comparison of two techniques of brachial plexus block for forelimb surgery in dogs.
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The objective of this study was to compare two different local anaesthesia techniques for intraoperative analgesia in dogs undergoing surgical procedures distal to the mid humeral diaphysis. Thirty-two dogs were divided into two groups: the US group received an ultrasound-guided brachial plexus block at the level of the first rib and the N group received a neurostimulation-guided paravertebral brachial plexus block. Ropivacaine 0.75% at 1.5mg/kg was injected in each case. Dogs were monitored during the surgical procedure, and rescue analgesia was administered whenever the heart rate, respiratory rate or blood pressure increased more than 20% from the basal values. Success rate was defined as no need for rescue analgesia during surgery and complete blockade of the operated leg evaluated just after anaesthesia recovery. Complications were also recorded. Data was analysed using Fisher exact and Mann/Whitney tests. Success rate was observed in 14/16 (87%) dogs and in 12/16 (75%) dogs in the US and N groups, respectively (P=0.65). Complications recorded were hypotension in three cases (US group, n=1; N group, n=2) and Horner's syndrome in three cases (US group, n=1; N group, n=2; P=0.65). Both techniques were found to provide good level of analgesia that allowed performing the orthopaedic procedures from the mid humeral diaphysis and distal in the limb, without the need for further analgesia.
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2,334,719 |
Serial Cardiac FDG-PET for the Diagnosis and Therapeutic Guidance of Patients With Cardiac Sarcoidosis.
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Cardiac fluorodeoxyglucose positron-emission tomography (FDG-PET) has emerged as a standard imaging modality for the diagnosis of cardiac sarcoidosis (CS); however, there is a scarcity of data on the use of serial FDG-PET to guide immunosuppressive therapy. The aim of this work was to report our experience using serial FDG-PET for the diagnosis and management of patients with CS, focusing on its utility in ongoing immunosuppression management.</AbstractText>We studied consecutive patients with CS managed at Stanford University from 2010 to 2017. We evaluated our experience using FDG-PET for diagnosis and guidance of immunosuppressive therapy titration in CS. Among 34 patients diagnosed with CS, 16 (47%), 12 (35%) and 14(41%) presented with heart block, heart failure, and ventricular arrhythmias, respectively. FDG-PET proved beneficial in the initial diagnosis in 21 patients (62%). A total of 128 FDG-PET scans were performed (median 3 per patient). Ninety-four FDG-PET scans (73%) resulted in a change in therapy, with 42FDG-PET scans (33%) instrumental for tapering prednisone. Among patients who were initiated on prednisone, the mean dose of prednisone at 1 year was 9.5mg/d. Over a median follow-up of 2.3years, 48% of patients were successfully weaned from prednisone completely, and 20% were weaned to a maintenance dosage of 5-10mg/d. During the follow-up period, transplant-free survival was 88%.</AbstractText>The use of serial cardiac FDG-PET for the diagnosis and management of CS was critical for guiding immunosuppression management and resulted in low chronic steroid doses and good disease control within 1 year of diagnosis.</AbstractText>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,334,720 |
Use of atracurium and its reversal with neostigmine in 14 pet rabbits undergoing ophthalmic surgery: a retrospective study.
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The objective of this retrospective study was to report the clinical use of atracurium and its reversal with neostigmine in pet rabbits. The medical records of 14 rabbits undergoing anaesthesia for ophthalmic surgery were located through a search of the hospital's database. Demographic data and data pertaining to the use of the neuromuscular blocker and its reversal were analysed. After intravenous administration of 0.44±0.4 mg/kg atracurium (total dose), 11 rabbits experienced at least one of the following cardiovascular responses: hypotension, defined as systolic arterial pressure less than 75 mmHg (n=6), hypotension with decreased heart rate (HR) (n=1), hypotension with increased HR (n=1), decreased arterial blood pressure (ABP) without hypotension (n=6), decreased ABP with decreased HR (n=1), or increased HR (n=2, ABP reading could not be taken). Two of these 11 rabbits also experienced severe intraoperative hypothermia. The neuromuscular block was monitored with a train-of-four nerve-stimulation pattern, and reversed, with intramuscular 0.01-0.045 mg/kg neostigmine and 0.01-0.02 mg/kg glycopyrronium, after the return of at least two out of four muscular twitches following nerve stimulation. Decrease in ABP and possibly hypothermia are likely intraoperative complications when clinical doses of atracurium are administered to pet rabbits. Measures should be taken to detect their occurrence in order to treat them promptly.
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2,334,721 |
Single Synapse Indicators of Impaired Glutamate Clearance Derived from Fast iGlu <i><sub>u</sub></i> Imaging of Cortical Afferents in the Striatum of Normal and Huntington (Q175) Mice.
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Changes in the balance between glutamate (Glu) release and uptake may stimulate synaptic reorganization and even synapse loss. In the case of neurodegeneration, a mismatch between astroglial Glu uptake and presynaptic Glu release could be detected if both parameters were assessed independently and at a single-synapse level. This has now become possible due to a new imaging assay with the genetically encoded ultrafast Glu sensor iGlu <i><sub>u</sub></i> We report findings from individual corticostriatal synapses in acute slices prepared from mice of either sex that were >1 year of age. Contrasting patterns of short-term plasticity and a size criterion identified two classes of terminals, presumably corresponding to the previously defined IT (intratelencephalic) and PT (pyramidal tract) synapses. The latter exhibited a higher degree of frequency potentiation/residual Glu accumulation and were selected for our first iGlu <i><sub>u</sub></i> single-synapse study in Q175 mice, a model of Huntington's disease (HD). In HD mice, the decay time constant of the perisynaptic Glu concentration (TauD), as an indicator of uptake, and the peak iGlu <i><sub>u</sub></i> amplitude, as an indicator of release, were prolonged and reduced, respectively. Treatment of WT preparations with the astrocytic Glu uptake blocker TFB-TBOA (100 nm) mimicked the TauD changes in homozygotes. Considering the largest TauD values encountered in WT, ∼40% of PT synapses tested in Q175 heterozygotes can be classified as dysfunctional. Moreover, HD but not WT synapses exhibited a positive correlation between TauD and the peak amplitude of iGlu <i><sub>u</sub></i> Finally, EAAT2 (excitatory amino acid transport protein 2) immunoreactivity was reduced next to corticostriatal terminals. Thus, astrocytic Glu transport remains a promising target for therapeutic intervention.<b>SIGNIFICANCE STATEMENT</b> Alterations in astrocytic Glu uptake can play a role in synaptic plasticity and neurodegeneration. Until now, the sensitivity of synaptic responses to pharmacological transport block and the resulting activation of NMDA receptors were regarded as reliable evidence for a mismatch between synaptic uptake and release. But the latter parameters are interdependent. Using a new genetically encoded sensor to monitor extracellular glutamate concentration ([Glu]) at individual corticostriatal synapses, we can now quantify the time constant of perisynaptic [Glu] decay (as an indicator of uptake) and the maximal [Glu] elevation next to the active zone (as an indicator of Glu release). The results provide a positive answer to the hitherto unresolved question of whether neurodegeneration (e.g., Huntington's disease) associates with a glutamate uptake deficit at tripartite excitatory synapses.
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2,334,722 |
Comparison of intraperitoneal bupivacaine, acetazolamide, and placebo on pain relief after laparoscopic cholecystectomy surgery: A clinical trial.
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<b>Background:</b> Given the importance of patients' pain after laparoscopic surgeries, this study was conducted to compare the effectiveness of intraperitoneal bupivacaine, acetazolamide, and placebo on pain relief after laparoscopic cholecystectomy surgery. <b>Methods:</b> Patients admitted to Rasool Akram hospital with physical status I or II, based on the American Society of Anesthesiologists (ASA) system, who were candidates for laparoscopic cholecystectomy surgery due to gallstones, were included in this study. Patients were divided into 3 groups (each group containing 20 patients) using block randomization with foursome blocks. Group 1 received bupivacaine, group 2 acetazolamide, and group 3 intravenous saline as placebo. After surgery, pain score was assessed by visual analogue scale, and shoulder pain and analgesic doses were also measured. The mentioned parameters were assessed at 1, 4, 8, 12, and 24 hours after surgery. <b>Results:</b> In this study, 60 patients were included in 3 groups. The mean pain recorded (VAS) at 1, 4, and 8 hours after surgery was not significantly different between acetazolamide and bupivacaine groups, but their score was significantly lower than the placebo group (p<0.05). However, the score recorded at 12 and 24 hours after surgery was not significantly different between the 3 groups (p>0.05). Mean of pain reliever (acetaminophen) injected to the patients when needed was not significantly different among the 3 intervention groups (p<0.05). The highest prevalence of shoulder pain (70%) belonged to the placebo group and the lowest (25%) to acetazolamide (p<0.05). Mean heart rate, systolic blood pressure, diastolic blood pressure, and the respiratory rate were not significantly different among intervention groups in 1, 4, 8, 12, and 24 hours after surgery (p>0.05). <b>Conclusion:</b> According to the results, acetazolamide and bupivacaine injection reduced pain in early hours after laparoscopy. However, pain intensity was not different between intervention groups and the control group after 12 hours, so re-prescription seems to be appropriate at this time. Acetazolamide injection significantly reduces shoulder pains after surgery.
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2,334,723 |
A Wavelet Transform-Based Neural Network Denoising Algorithm for Mobile Phonocardiography.
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Cardiovascular pathologies cause 23.5% of human deaths, worldwide. An auto-diagnostic system monitoring heart activity, which can identify the early symptoms of cardiac illnesses, might reduce the death rate caused by these problems. Phonocardiography (PCG) is one of the possible techniques able to detect heart problems. Nevertheless, acoustic signal enhancement is required since it is exposed to various disturbances coming from different sources. The most common denoising enhancement is based on the Wavelet Transform (WT). However, the WT is highly susceptible to variations in the noise frequency distribution. This paper proposes a new adaptive denoising algorithm, which combines WT and Time Delay Neural Networks (TDNN). The acquired signal is decomposed by means of the WT using the coif five-wavelet basis at the tenth decomposition level and then provided as input to the TDNN. Besides the advantage of adaptive thresholding, the reason for using TDNNs is their capacity of estimating the Inverse Wavelet Transform (IWT). The best parameters of the TDNN were found for a NN consisting of 25 neurons in the first and 15 in the second layer and the delay block of 12 samples. The method was evaluated on several pathological heart sounds and on signals recorded in a noisy environment. The performance of the developed system with respect to other wavelet-based denoising approaches was validated by the online questionnaire.
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2,334,724 |
Emergency Medicine Palliative Care Access (EMPallA): protocol for a multicentre randomised controlled trial comparing the effectiveness of specialty outpatient versus nurse-led telephonic palliative care of older adults with advanced illness.
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Emergency department (ED)-initiated palliative care has been shown to improve patient-centred outcomes in older adults with serious, life-limiting illnesses. However, the optimal modality for providing such interventions is unknown. This study aims to compare nurse-led telephonic case management to specialty outpatient palliative care for older adults with serious, life-limiting illness on: (1) quality of life in patients; (2) healthcare utilisation; (3) loneliness and symptom burden and (4) caregiver strain, caregiver quality of life and bereavement.</AbstractText>This is a protocol for a pragmatic, multicentre, parallel, two-arm randomised controlled trial in ED patients comparing two established models of palliative care: nurse-led telephonic case management and specialty, outpatient palliative care. We will enrol 1350 patients aged 50+ years and 675 of their caregivers across nine EDs. Eligible patients: (1) have advanced cancer (metastatic solid tumour) or end-stage organ failure (New York Heart Association class III or IV heart failure, end-stage renal disease with glomerular filtration rate <15 mL/min/m2</sup>, or global initiative for chronic obstructive lung disease stage III, IV or oxygen-dependent chronic obstructive pulmonary disease); (2) speak English; (3) are scheduled for ED discharge or observation status; (4) reside locally; (5) have a working telephone and (6) are insured. Patients will be excluded if they: (1) have dementia; (2) have received hospice care or two or more palliative care visits in the last 6 months or (3) reside in a long-term care facility. We will use patient-level block randomisation, stratified by ED site and disease. Effectiveness will be compared by measuring the impact of each intervention on the specified outcomes. The primary outcome will measure change in patient quality of life.</AbstractText>Institutional Review Board approval was obtained at all study sites. Trial results will be submitted for publication in a peer-reviewed journal.</AbstractText>NCT03325985; Pre-results.</AbstractText>© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</CopyrightInformation>
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2,334,725 |
Multiscale Fine-Grained Heart Rate Variability Analysis for Recognizing the Severity of Hypertension.
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Hypertension is a common and chronic disease and causes severe damage to patients' health. Blood pressure of a human being is controlled by the autonomic nervous system. Heart rate variability (HRV) is an impact of the autonomic nervous system and an indicator of the balance of the cardiac sympathetic nerve and vagus nerve. HRV is a good method to recognize the severity of hypertension due to the specificity for prediction. In this paper, we proposed a novel fine-grained HRV analysis method to enhance the precision of recognition. In order to analyze the HRV of the patient, we segment the overnight electrocardiogram (ECG) into various scales. 18 HRV multidimensional features in the time, frequency, and nonlinear domain are extracted, and then the temporal pyramid pooling method is designed to reduce feature dimensions. Multifactor analysis of variance (MANOVA) is applied to filter the related features and establish the hypertension recognizing model with relevant features to efficiently recognize the patients' severity. In this paper, 139 hypertension patients' real clinical ECG data are applied, and the overall precision is 95.1%. The experimental results validate the effectiveness and reliability of the proposed recognition method in the work.
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2,334,726 |
The heart rate variability-derived Newborn Infant Parasympathetic Evaluation (NIPE™) Index in pediatric surgical patients from 0 to 2 years under sevoflurane anesthesia-A prospective observational pilot study.
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The heart rate variability-derived Newborn Infant Parasympathetic Evaluation (NIPE™) Index is a continuous noninvasive tool to assess pain and discomfort in infants <2 years. Initial studies focused on pain monitoring in the neonatal intensive care unit environment.</AbstractText>The aim of this study was to investigate the performance of the NIPE in infants under sevoflurane anesthesia. The primary objective of this study was to compare the NIPE and heart rate as tools to help recognize the need for additional opioid drugs. Secondary objectives were the course of the NIPE and heart rate around specific standardized noxious procedural mile-stones.</AbstractText>NIPE and heart rate values recorded during a 120 seconds interval before the anesthetist's decision to administer additional opioid due to the perceived insufficient antinociception and during a 120 seconds interval after drug administration were analyzed by means of a repeated measures ANOVA. The same analyses were performed for datasets around per protocol administration of morphine for postoperative analgesia, performance of a caudal block and surgical incision.</AbstractText>In patients with a NIPE value <50, an additional opioid drug administration resulted in a rise of NIPE values, reaching a maximum increase of 5.1 (95% CI: 0.22-9.99) units 120 seconds after drug administration (P = 0.041). There was no evidence of a change in heart rate during these two 120 seconds periods. Per protocol administration of morphine, caudal block, and surgical incision did not result in changes of the NIPE, which was around 65 units on these occasions, and heart rate.</AbstractText>In infants anesthetized with sevoflurane, NIPE values <50 might be indicative of insufficient antinociception. The results of this observational pilot study might suggest that the NIPE could be a better measure of the nociception/antinociception balance than heart rate.</AbstractText>© 2019 The Authors. Pediatric Anesthesia Published by John Wiley & Sons Ltd.</CopyrightInformation>
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2,334,727 |
Persistent Postsurgical Pain Following Thoracotomy: A Comparison of Thoracic Epidural and Paravertebral Blockade as Preventive Analgesia.
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Persistent postsurgical pain (PPP) is common following thoracotomy. Thoracic epidural (TEB) and paravertebral blockade (PVB) are both established forms of perioperative analgesia for thoracotomy. There is currently a lack of data on their influence on PPP; this study aims to evaluate both techniques on PPP.</AbstractText>Observational study, prospectively collected data.</AbstractText>Adults who underwent thoracotomy had either TEB or PVB for analgesia and were prospectively interviewed at six months. A numerical rating scale, the short form of the Leeds Assessment of Neuropathic Symptoms and Signs, and the EuroQol-5 dimension (EQ-5D) index were used to assess pain, neuropathic pain, and quality of life.</AbstractText>Eighty-two patients who underwent a thoracotomy were recruited (TEB N = 36, PVB N = 46). Pain scores had a median (interquartile range [IQR]) of 1 (0 to 4.5) and 1.5 (0 to 4, P = 0.89), presence of PPP was 58.3% (95% confidence interval [CI] = 40.0-74.5%) and 60.9% (95% CI = 45.4-74.9%, P = 0.81), and presence of neuropathic pain was 30.6% (95% CI = 16.3-48.1%) and 28.2% (95% CI = 16.0-43.5%, P = 0.85). Reported quality of life was 0.71 (0.14-0.85) and 0.80 (0.19-0.91, P = 0.21). Patients who had PPP reported worse quality of life measures compared with those who were pain free, with a median (IQR) EQ-5D index of 0.69 (-0.15 to 0.85) and 0.85 (0.72 to 1, P = 0.0007); quality of life was worst when there was a neuropathic component (median = 0.39, IQR = -0.24 to 0.75).</AbstractText>There was no statistical difference in the development of persistent postsurgical pain between patients who received a TEB or a PVB; however, patients who developed PPP had a significantly lower quality of life, which was worse with a neuropathic component.</AbstractText>© Crown copyright 2019.</CopyrightInformation>
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2,334,728 |
PFKFB3 promotes endotoxemia-induced myocardial dysfunction through inflammatory signaling and apoptotic induction.
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Cardiac dysfunction is a vital complication during endotoxemia (ETM). Accumulating evidence suggests that enhanced glycolytic metabolism promotes inflammatory and myocardial diseases. In this study, we performed deep mRNA sequencing analysis on the hearts of control and lipopolysaccharide (LPS)-challenged mice (40 mg/kg, i.p.) and identified that the glycolytic enzyme, 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase 3 (PFKFB3) might play an indispensable role in ETM-induced cardiac damage. Quantitative real-time PCR validated the transcriptional upregulation of PFKFB3 in the myocardium of LPS-challenged mice and immunoblotting and immunostaining assays confirmed that LPS stimulation markedly increased the expression of PFKFB3 at the protein level both in vivo and in vitro. The potent antagonist 3-(3pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) was used to block PFKFB3 activity in vivo (50 mg/kg, i.p.) and in vitro (10 μM). Echocardiographic analysis and TUNEL staining showed that 3PO significantly alleviated LPS-induced cardiac dysfunction and apoptotic injury in vivo. 3PO also suppressed the LPS-induced secretion of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and lactate in the serum, in addition to lactate in the myocardium. PFKFB3 inhibition also diminished the nuclear translocation and phosphorylation of transcription factor nuclear factor-κB (NF-κB) in both adult cardiomyocytes and HL-1 cells. Furthermore, immunoblotting analysis showed that 3PO inhibited LPS-induced apoptotic induction in cardiomyocytes. Taken together, these findings demonstrate that PFKFB3 participates in LPS-induced cardiac dysfunction via mediating inflammatory and apoptotic signaling pathway.
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2,334,729 |
Risk factors of clinical mastitis and antimicrobial susceptibility test results of mastitis milk from dairy cattle in western Thailand: Bayesian network analysis.
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Using Bayesian network analysis, this cross-sectional study aimed to identify the conditional probability among dairy farm practices, cow characteristics, bacteriological culture results, and antimicrobial susceptibility test results of milk from dairy cows with clinical mastitis in western Thailand. Data associated with risk factors and clinical signs were collected using a structured questionnaire that was administered to 34 small dairy holders. In total, 100 quarters of milk samples from 100 cows were used for Bayesian network analysis. Conditional probability results showed that the following variables had the highest probabilities relevant to the occurrence of clinical mastitis pathogens: parity, concrete and rubber floor, hand stripping after using machine milking, dry cow therapy, and routine cleaning of milking machines. These variables were associated with the first four highest posterior probabilities of the occurrence of Streptococcus spp. (16.68%; reachable range or the minimum and maximum posterior probability values for the occurrence of Streptococcus spp., 15.45%-17.91%), Staphylococcus spp. (11.87%; reachable range, 11.06%-12.67%), Escherichia coli (7.53%; reachable range, 6.95%-8.17%), and Streptococcus dysgalactiae (7.28%; reachable range, 6.73%-7.83%), which were the most frequently isolated pathogens. Conditional probability results indicated these pathogens were most sensitive to amoxicillin/clavulanic acid (80.58%) and cloxacillin (64.28%). Most pathogens were resistant to penicillin G (40.37%). In this study, Bayesian network analysis revealed several clinically significant risk factors of mastitis associated with various pathogens and farming characteristics. Simple statistics could not provide sufficient information for the successful control of mastitis. In contrast, through in-depth data analysis, Bayesian networks could identify risk factors in various situations, hence providing information that will be crucial to help farmers reduce the cost of farming.
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2,334,730 |
Revealing the structure of the associations between housing system, facilities, management and welfare of commercial laying hens using Additive Bayesian Networks.
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After the ban of battery cages in 1988, a welfare control programme for laying hens was developed in Sweden. Its goal was to monitor and ensure that animal welfare was not negatively affected by the new housing systems. The present observational study provides an overview of the current welfare status of commercial layer flocks in Sweden and explores the complexity of welfare aspects by investigating and interpreting the inter-relationships between housing system, production type (i.e. organic or conventional), facilities, management and animal welfare indicators. For this purpose, a machine learning procedure referred to as structure discovery was applied to data collected through the welfare programme during 2010-2014 in 397 flocks housed in 193 different farms. Seventeen variables were fitted to an Additive Bayesian Network model. The optimal model was identified by an exhaustive search of the data iterated across incremental parent limits, accounting for prior knowledge about causality, potential over-dispersion and clustering. The resulting Directed Acyclic Graph shows the inter-relationships among the variables. The animal-based welfare indicators included in this study - flock mortality, feather condition and mite infestation - were indirectly associated with each other. Of these, severe mite infestations were rare (4% of inspected flocks) and mortality was below the acceptable threshold (< 0.6%). Feather condition scored unsatisfactory in 21% of the inspected flocks; however, it seemed to be only associated to the age of the flock, ruling out any direct connection with managerial and housing variables. The environment-based welfare indicators - lighting and air quality - were an issue in 5 and 8% of the flocks, respectively, and showed a complex inter-relationship with several managerial and housing variables leaving room for several options for intervention. Additive Bayesian Network modelling outlined graphically the underlying process that generated the observed data. In contrast to ordinary regression, it aimed at accounting for conditional independency among variables, facilitating causal interpretation.
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2,334,731 |
Goals-of-Care Conversations for Older Adults With Serious Illness in the Emergency Department: Challenges and Opportunities.
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During the last 6 months of life, 75% of older adults with preexisting serious illness, such as advanced heart failure, lung disease, and cancer, visit the emergency department (ED). ED visits often mark an inflection point in these patients' illness trajectories, signaling a more rapid rate of decline. Although most patients are there seeking care for acute issues, many of them have priorities other than to simply live as long as possible; yet without discussion of preferences for treatment, they are at risk of receiving care not aligned with their goals. An ED visit may offer a unique "teachable moment" to empower patients to consider their ability to influence future medical care decisions. However, the constraints of the ED setting pose specific challenges, and little research exists to guide clinicians treating patients in this setting. We describe the current state of goals-of-care conversations in the ED, outline the challenges to conducting these conversations, and recommend a research agenda to better equip emergency physicians to guide shared decisionmaking for end-of-life care. Applying best practices for serious illness communication may help emergency physicians empower such patients to align their future medical care with their values and goals.
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2,334,732 |
Comparative evaluation of anaesthetic efficacy and haemodynamic effects of a combination of isobaric bupivacaine with buprenorphine vs. isobaric levobupivacaine with buprenorphine for spinal anaesthesia - A double blinded randomised clinical trial.
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Bupivacaine is the most frequently used local anaesthetic for spinal anaesthesia, however, use of levobupivacaine in clinical practice has advanced recently. This study aimed to compare the anaesthetic potency and haemodynamic effects of intrathecal bupivacaine with buprenorphine versus levobupivacaine with buprenorphine in infraumbilical surgeries.</AbstractText>This prospective randomised double blind study was conducted in seventy patients aged 18-65 years, American Society of Anesthesiologists grade I-II, scheduled for lower abdominal and lower limb surgery under spinal anaesthesia. The patients either received 0.5% isobaric racemic bupivacaine 3 ml with 2 μg/kg of buprenorphine (Group B) or 0.5% isobaric levobupivacaine 3 ml with 2 μg/kg of buprenorphine (Group L). The time for onset of sensory block between the two groups was the priomary end-point. Other measurements included haemodynamic variables, sensory and motor blockade characteristics, postoperative analgesia, and complications in the first 24 h.</AbstractText>There was no significant difference in the onset of sensory block between the two groups. Sensory and motor blockade characteristics were similar between the two groups. However, there was significant fall in the heart rate at 5 min in Group B compared to Group L. There was statistically significant fall in systolic blood pressure in group B compared to Group L from 5 min up to 60 min and fall in diastolic blood pressure from 10 min to 45 min.</AbstractText>Our study showed that onset of sensory block is similar between isobaric levobupivacaine with buprenorphine 37 38 and isobaric bupivacaine with buprenorphine.</AbstractText>
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2,334,733 |
Effectiveness of Augmented Reality Mobile Simulator in Teaching Local Anesthesia of Inferior Alveolar Nerve Block.
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The aim of this study was to evaluate the effectiveness of a mobile augmented reality simulator for local anesthesia training with dental students who are administering inferior alveolar nerve block (IANB) for the first time. Participants in this prospective study conducted in 2016 were 41 fourth- and fifth-year students randomly divided into two groups: a control group with 19 students and an experimental group with 22 students. In addition to theoretical instruction and exercises, students in the experimental group used the mobile augmented reality simulator in a dental office 2h weekly for four weeks. The Sony SmartBand-2 was used to measure all students' heart rate five minutes before and during anesthesia administration. After anesthesia, students in both groups completed a post-clinical questionnaire evaluating their knowledge and skills. The experimental group had a higher average score and/or a more limited range of responses on each item of the questionnaire than the control group. The average time for performing IANB in the experimental group was 50.0±14.3 seconds, while the control group's average was 68.4±25.5 seconds. In addition, the group that used the augmented reality simulator had an anesthesia success rate of 90.9% compared to 73.7% for the control group. Students in both groups had a statistically significant increase in heart rate while performing anesthesia. Overall, the students who used the mobile simulator in addition to their education in augmented reality carried out anesthetic procedures for IANB in a shorter period of time and had greater success than the students who used only the conventional educational methods.
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2,334,734 |
Interatrial block in prediction of all-cause mortality after first-ever ischemic stroke.
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Interatrial block (IAB) is an ECG indicator of atrial fibrosis related to atrial remodeling and thrombus formation thus leading to embolic stroke and increasing mortality. We aimed to assess weather IAB predicted all-cause mortality during 10 years after ischemic stroke.</AbstractText>The study sample comprised 235 patients (median age 74 (interquartile range 25-75% 65-81) years, 95 female) included in the Lund Stroke Register in 2001-2002, who had sinus rhythm ECGs at stroke admission. IAB was defined as a P-wave duration ≥120 ms without = partial IAB (n = 56) or with = advanced IAB (n = 41) biphasic morphology (±) in the inferior ECG leads. All-cause mortality was assessed via linkage with the Swedish Causes of Death Register.</AbstractText>During follow-up 126 patients died (54%). Advanced IAB, but not partial, was associated with all-cause mortality in univariate Cox regression analysis (hazard ratio (HR) 1.98, 95% CI 1.27-3.09, p = 0.003). After adjustment for age, gender, severity of stroke measured by NIHSS scale and smoking status in patients without additional comorbidities advanced IAB independently predicted all-cause mortality (HR 7.89, 95% CI 2.01-30.98, p = 0.003), while in patients with comorbidities it did not (HR 1.01 95% CI 0.59-1.72, p = 0.966).</AbstractText>Advanced IAB predicted all-cause mortality after ischemic stroke, but mostly in patients without additional cardiovascular comorbidities.</AbstractText>
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2,334,735 |
Supplementation of sodium butyrate to postweaned heifer diets: Effects on growth performance, nutrient digestibility, and health.
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The objective of this study was to determine the effect of varying levels of sodium butyrate (SB) supplementation in feed on the growth, digestibility, and health of postweaned heifers. Forty Holstein dairy heifers with a mean age of 84 d and average body weight (BW) of 100.9 ± 11.2 kg were housed in a naturally ventilated freestall barn. Heifers were blocked by birth date and randomly assigned to 1 of 4 treatments in a completely randomized block design: (1) 100 g of soybean meal carrier (control), (2) 0.25 g of SB/kg of BW plus carrier, (3) 0.50 g of SB/kg of BW plus carrier, and (4) 0.75 g of SB/kg of BW plus carrier. Carrier with or without SB was top-dressed and hand-mixed into a total mixed ration once daily. Heifers were fed to provide 10% orts. Initial BW, hip and withers heights, heart girth, and body length were measured before the start of the study and every week thereafter until the 14-wk trial was over. Blood samples were obtained and plasma urea nitrogen, plasma glucose, and whole-blood β-hydroxybutyrate concentrations were determined before the start of treatment and weekly thereafter until the conclusion of the study. Fecal samples were taken before treatment and every other week from each heifer for coccidia counts. Apparent total-tract nutrient digestibility was determined using acid detergent insoluble ash as an internal marker. Each heifer underwent this phase from d 47 until d 54 of the study. Sodium butyrate had a positive effect on average BW and overall BW gain. Feed efficiency tended to improve as SB supplementation increased. Coccidia counts were lowest in the treatment with 0.25 g of SB/kg of BW plus carrier. Sodium butyrate had no effects on skeletal growth or plasma urea nitrogen concentration. Blood glucose concentration decreased linearly and β-hydroxybutyrate increased linearly with increasing levels of SB supplementation. Sodium butyrate supplementation did not affect apparent total-tract nutrient digestibility. Sodium butyrate supplementation offers positive results in the growth performance and feed efficiency of postweaned heifers.
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2,334,736 |
An integrated, collaborative healthcare model for the early diagnosis and management of dementia: Preliminary audit results from the first transdisciplinary service integrating family medicine and geriatric psychiatry services to the heart of patients' homes.
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The number of dementia cases is expected to rise exponentially over the years in many parts of the world. Collaborative healthcare partnerships are envisaged as a solution to this problem. Primary care physicians form the vanguard of early detection of dementia and influence clinical care that these patients receive. However, evidence suggests that they will benefit from closer support from specialist services in dementia care. An interdisciplinary, collaborative memory clinic was established in 2012 as a collaborative effort between a large family medicine based service and a specialist geriatric psychiatry service in Singapore. It is the first service in the world that integrates a family medicine based service with geriatric psychiatry expertise in conjunction with community-based partnerships in an effort to provide holistic, integrated care right into the heart of patients' homes as well as training in dementia care for family medicine physicians. We describe our model of care and the preliminary findings of our audit on the results of this new model of care.</AbstractText>This was a retrospective audit done on the electronic medical records of all patients seen at the Memory Clinic in Choa Chu Kang Polyclinic from August 2013 to March 2016. The information collected included gender, referral source, patient trajectories, presence of behavioural and psychological symptoms of dementia and percentage of caregivers found to be in need of support. A detailed outline of the service workflow and processes were described.</AbstractText>A majority (93.5%) of the patients had their memory problems managed at the memory clinic without escalation to other specialist services. 22.7% of patients presented with behavioural and psychological symptoms of dementia. When initially assessed, a majority (82.2%) of patients' caregivers were found to be in need of support with 99.5% of such caregivers' needs addressed with memory clinic services.</AbstractText>Our model of care has the potential to shape future dementia care in Singapore and other countries with a similar healthcare setting. Redesigning and evolving healthcare services to promote close collaboration between primary care practitioners and specialist services for dementia care can facilitate seamless delivery of care for the benefit of patients.</AbstractText>
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2,334,737 |
Modelling the impact of a tax on sweetened beverages in the Philippines: an extended cost-effectiveness analysis.
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To assess the potential impact of a new tax on sweetened beverages on premature deaths associated with noncommunicable diseases in the Philippines.</AbstractText>In January 2018, the Philippines began imposing a tax of 6 Philippine pesos per litre (around 13%) on sweetened beverages to curb the obesity burden. Using national data sources, we conducted an extended cost-effectiveness analysis to estimate the effect of the tax on the numbers of premature deaths averted attributed to type 2 diabetes mellitus, ischaemic heart disease and stroke, across income quintiles over the period 2018-2037. We also estimated the financial benefits of the tax from reductions in out-of-pocket payments, direct medical costs averted and government health-care cost savings.</AbstractText>The tax could avert an estimated 5913 deaths related to diabetes, 10 339 deaths from ischaemic heart disease and 7950 deaths from stroke over 20 years. The largest number of deaths averted could be among the fourth and fifth (highest) income quintiles. The tax could generate total health-care savings of 31.6 billion Philippine pesos (627 million United States dollars, US$) over 20 years, and raise 41.0 billion Philippine pesos (US$ 813 million) in revenue per annum. The poorest quintile could bear the smallest tax burden increase (14% of the additional tax; 5.6 billion Philippine pesos) and have the lowest savings in out-of-pocket payments due to relatively large health-care subsidies. Finally, we estimated that 13 890 cases of catastrophic expenditure could be averted.</AbstractText>The new sweetened beverage tax may help to reduce obesity-related premature deaths and improve financial well-being in the Philippines.</AbstractText>
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2,334,738 |
Electronic health records accurately predict renal replacement therapy in acute kidney injury.
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Electronic health records (EHR) detect the onset of acute kidney injury (AKI) in hospitalized patients, and may identify those at highest risk of mortality and renal replacement therapy (RRT), for earlier targeted intervention.</AbstractText>Prospective observational study to derive prediction models for hospital mortality and RRT, in inpatients aged ≥18 years with AKI detected by EHR over 1 year in a tertiary institution, fulfilling modified KDIGO criterion based on serial serum creatinine (sCr) measures.</AbstractText>We studied 3333 patients with AKI, of 77,873 unique patient admissions, giving an AKI incidence of 4%. KDIGO AKI stages at detection were 1(74%), 2(15%), 3(10%); corresponding peak AKI staging in hospital were 61, 20, 19%. 392 patients (12%) died, and 174 (5%) received RRT. Multivariate logistic regression identified AKI onset in ICU, haematological malignancy, higher delta sCr (sCr rise from AKI detection till peak), higher serum potassium and baseline eGFR, as independent predictors of both mortality and RRT. Additionally, older age, higher serum urea, pneumonia and intraabdominal infections, acute cardiac diseases, solid organ malignancy, cerebrovascular disease, current need for RRT and admission under a medical specialty predicted mortality. The AUROC for RRT prediction was 0.94, averaging 0.93 after 10-fold cross-validation. Corresponding AUROC for mortality prediction was 0.9 and 0.9 after validation. Decision tree analysis for RRT prediction achieved a balanced accuracy of 70.4%, and identified delta-sCr ≥ 148 μmol/L as the key factor that predicted RRT.</AbstractText>Case fatality was high with significant renal deterioration following hospital-wide AKI. EHR clinical model was highly accurate for both RRT prediction and for mortality; allowing excellent risk-stratification with potential for real-time deployment.</AbstractText>
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2,334,739 |
The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells.
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The mechanisms controlling CD4<sup>+</sup> T cell switching from an effector to an anti-inflammatory (IL-10<sup>+</sup>) phenotype play an important role in the persistence of chronic inflammatory diseases. Here, we identify the cholesterol biosynthesis pathway as a key regulator of this process. Pathway analysis of cultured cytokine-producing human T cells reveals a significant association between IL-10 and cholesterol metabolism gene expression. Inhibition of the cholesterol biosynthesis pathway with atorvastatin or 25-hydroxycholesterol during switching from IFNγ<sup>+</sup> to IL-10<sup>+</sup> shows a specific block in immune resolution, defined as a significant decrease in IL-10 expression. Mechanistically, the master transcriptional regulator of IL10 in T cells, c-Maf, is significantly decreased by physiological levels of 25-hydroxycholesterol. Strikingly, progression to rheumatoid arthritis is associated with altered expression of cholesterol biosynthesis genes in synovial biopsies of predisposed individuals. Our data reveal a link between sterol metabolism and the regulation of the anti-inflammatory response in human CD4<sup>+</sup> T cells.
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2,334,740 |
Systemic lupus erythematosus in pregnancy: high risk, high reward.
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The aim of this study was to describe risks of systemic lupus erythematosus (SLE) in pregnancy and the importance of preconception counselling, medication optimization and close surveillance.</AbstractText>Advances in care for pregnant patients with SLE have led to improved obstetric outcomes, but maternal and foetal risks continue to be elevated. Conception during periods of disease quiescence and continuation of most medications decrease adverse pregnancy outcomes. Hydroxychloroquine (HCQ) appears protective against flares in pregnancy, neonatal congenital heart block and preterm birth.</AbstractText>SLE in pregnancy confers increased maternal and foetal risks, including disease flares, preeclampsia, preterm birth, foetal growth restriction, neonatal lupus erythematosus (NLE) and congenital heart block. Disease control on an effective medication regimen mitigates many of these risks, but pregnancy in women with SLE remains a high-risk condition requiring multidisciplinary care and an individualized approach to each patient.</AbstractText>
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2,334,741 |
Effects of Thoracic Epidural Anesthesia on Neuronal Cardiac Regulation and Cardiac Function.
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Cardiac sympathetic blockade with high-thoracic epidural anesthesia is considered beneficial in patients undergoing major surgery because it offers protection in ischemic heart disease. Major outcome studies have failed to confirm such a benefit, however. In fact, there is growing concern about potential harm associated with the use of thoracic epidural anesthesia in high-risk patients, although underlying mechanisms have not been identified. Since the latest review on this subject, a number of clinical and experimental studies have provided new information on the complex interaction between thoracic epidural anesthesia-induced sympatholysis and cardiovascular control mechanisms. Perhaps these new insights may help identify conditions in which benefits of thoracic epidural anesthesia may not outweigh potential risks. For example, cardiac sympathectomy with high-thoracic epidural anesthesia decreases right ventricular function and attenuates its capacity to cope with increased right ventricular afterload. Although the clinical significance of this pathophysiologic interaction is unknown at present, it identifies a subgroup of patients with established or pending pulmonary hypertension for whom outcome studies are needed. Other new areas of interest include the impact of thoracic epidural anesthesia-induced sympatholysis on cardiovascular control in conditions associated with increased sympathetic tone, surgical stress, and hemodynamic disruption. It was considered appropriate to collect and analyze all recent scientific information on this subject to provide a comprehensive update on the cardiovascular effects of high-thoracic epidural anesthesia and cardiac sympathectomy in healthy and diseased patients.This review provides a comprehensive update on the cardiovascular effects of high-thoracic epidural anesthesia and cardiac sympathectomy in healthy and diseased patients.
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2,334,742 |
Sphingosine-1-phosphate attenuates hypoxia/reoxygenation-induced cardiomyocyte injury via a mitochondrial pathway.
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Our previous study showed that Sphingosine-1-phosphate (S1P) could protect cardiomyocytes against hypoxia/reoxygenation (H/R) injury via the JAK-STAT pathway and maintain normal myocardial mitochondria integrity in vivo. However, it is not known yet whether S1P can relieve mitochondrial dysfunction via the mitochondrial apoptotic pathway and its detailed mechanism remains to be investigated. The aim of this study was to demonstrate the mitochondrial protective effects of S1P in a cardiomyocyte H/R injury model. In the present study, we established a H/R model in H9c2 cells. Cell viability was determined by the MTT assay, and apoptosis was evaluated by annexin V-FITC/PI staining. Mitochondrial calcium ion concentration, mitochondrial membrane potential (ΔΨm), opening of the mitochondrial permeability transition pore (mPTP), and release of cytochrome C were detected by laser confocal microscopy. The results showed that S1P inhibited the decrease in cell viability induced by H/R injury and reduced apoptosis. Confocal microscopy showed that S1P prevented loss of ΔΨm, relieved mitochondrial calcium overload, and inhibited opening of the mPTP and release of cytochrome C. The STAT3 inhibitor STATTIC can reverse the antiapoptotic effects of S1P and block the effect of S1P on mitochondria. Taken together, our results indicate that S1P protects cardiomyocytes against H/R injury by relieving mitochondrial dysfunction via the STAT3 pathway.
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2,334,743 |
PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study.
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Increased-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated</sub>) improves progression-free survival in patients with advanced Hodgkin lymphoma compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), but is associated with increased risks of haematological toxicity, secondary myelodysplasia or leukaemia, and infertility. We investigated whether PET monitoring during treatment could allow dose de-escalation by switching regimen (BEACOPPescalated</sub> to ABVD) in early responders without loss of disease control compared with standard treatment without PET monitoring.</AbstractText>AHL2011 is a randomised, non-inferiority, phase 3 study done in 90 centres across Belgium and France. Eligible patients were aged 16-60 years and had newly diagnosed Hodgkin lymphoma, excluding nodular lymphocyte predominant subtype, an Eastern Cooperative Oncology Group performance status score less than 3, a life expectancy of at least 3 months, an Ann Arbor disease stage III, IV, or IIB with mediastinum-to-thorax ratio of 0·33 or greater than or extranodal localisation, and had received no previous treatment for Hodgkin lymphoma. Randomisation was unmasked and done centrally by the permuted block method. Patients were randomly assigned to standard treatment (BEACOPPescalated</sub> given every 21 days for six cycles) or PET-driven treatment. All patients received two cycles of upfront BEACOPPescalated</sub>, after which PET assessment was done (PET2). In the standard treatment group, PET2 patients completed two additional cycles of BEACOPPescalated</sub> induction therapy irrespective of PET2 findings. In the PET-driven treatment group, patients with positive PET2 scans received the further two cycles of BEACOPPescalated</sub> and those with a negative PET2 scan switched to two cycles of ABVD for the remaining induction therapy. In both treatment groups, PET at the end of induction therapy was used to decide whether to continue with consolidation therapy in those with negative scans or start salvage therapy in patients with positive scans (either two cycles of ABVD in PET2-negative patients in the PET-driven arm or two cycles of BEACOPPescalated</sub>). BEACOPPescalated</sub> consisted of bleomycin 10 mg/m2</sup> and vincristine 1·4 mg/m2</sup> intravenously on day 8, etoposide 200 mg/m2</sup> intravenously on days 1-3, doxorubicin 35 mg/m2</sup> and cyclophosphamide 1250 mg/m2</sup> intravenously on day 1, 100 mg/m2</sup> oral procarbazine on days 1-7, and 40 mg/m2</sup> oral prednisone on days 1-14. ABVD was given every 28 days (doxorubicin 25 mg/m2</sup>, bleomycin 10 mg/m2</sup>, vinblastine 6 mg/m2</sup>, and dacarbazine 375 mg/m2</sup> intravenously on days 1 and 15). The primary endpoint was investigator-assessed progression-free survival. Non-inferiority analyses were done by intention to treat and per protocol. The study had a non-inferiority margin of 10%, to show non-inferiority of PET-guided treatment versus standard care with 80% power and an alpha of 2·5% (one-sided). This study is registered with ClinicalTrials.gov, number NCT01358747.</AbstractText>From May 19, 2011, to April 29, 2014, 823 patients were enrolled-413 in the standard care group and 410 in the PET-driven group. 346 (84%) of 410 patients in the PET-driven treatment group were assigned to receive ABVD and 51 (12%) to continue receiving BEACOPPescalated</sub> after PET2. With a median follow-up of 50·4 months (IQR 42·9-59·3), 5-year progression-free survival by intention to treat was 86·2%, 95% CI 81·6-89·8 in the standard treatment group versus 85·7%, 81·4-89·1 in the PET-driven treatment group (hazard ratio [HR] 1·084, 95% CI 0·737-1·596; p=0·65) and per protocol the values were 86·7%, 95% CI 81·9-90·3 and 85·4%, 80·7-89·0, respectively (HR 1·144, 0·758-1·726; p=0·74). The most common grade 3-4 adverse events were leucopenia (381 [92%] in the standard treatment group and 387 [95%] in the PET-driven treatment group), neutropenia (359 [87%] and 366 [90%]), anaemia (286 [69%] vs 114 [28%]), thrombocytopenia (271 [66%] and 163 [40%]), febrile neutropenia (145 [35%] and 93 [23%]), infections (88 [22%] and 47 [11%]), and gastrointestinal disorders (49 [11%] and 48 [11%]). Serious adverse events related to treatment were reported in 192 (47%) patients in the standard treatment group and 114 (28%) in the PET-driven treatment group, including infections (84 [20%] of 412 vs 50 [12%] of 407) and febrile neutropenia (21 [5%] vs 23 [6%]). Six (1%) patients in the standard care group died from treatment-related causes (two from septic shock, two from pneumopathy, one from heart failure, and one from acute myeloblastic leukaemia), as did two (<1%) in the PET-driven treatment group (one from septic shock and one from acute myeloblastic leukaemia).</AbstractText>PET after two cycles of induction BEACOPPescalated</sub> chemotherapy safely guided treatment in patients with advanced Hodgkin lymphoma and allowed the use of ABVD in early responders without impairing disease control and reduced toxicities. PET staging allowed accurate monitoring of treatment in this trial and could be considered as a strategy for the routine management of patients with advanced Hodgkin lymphoma.</AbstractText>Programme Hospitalier de Recherche Clinique.</AbstractText>Copyright © 2019 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,334,744 |
A randomized-controlled, double-blind study to evaluate the efficacy of caudal midazolam, ketamine and neostigmine as adjuvants to bupivacaine on postoperative analgesic in children undergoing lower abdominal surgery.
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• Background: Caudal epidural is the most commonly used technique for the management of postoperative pain in children. The aim of the present study was to assess and compare the efficacy of caudal bupivacaine as a postoperative analgesic alone or combined with midazolam, ketamine, and neostigmine in pediatric patients undergoing lower abdominal surgery.</AbstractText>Eighty pediatric patients categorized under the American Society of Anesthesiologists Physical Status I and II Classification System, who have been scheduled to undergo lower abdominal surgery were randomly designated into four groups to receive caudal block with either 1 ml/kg of 0.25% caudal bupivacaine for group B, 1 ml/kg of 0.25% caudal bupivacaine mixed with 2 μg/kg neostigmine for group BN, 1 ml/kg of 0.25% caudal bupivacaine mixed with 0.5 mg/kg ketamine for group BK or 1 ml/kg of 0.25% caudal bupivacaine mixed with 50 mcg/kg midazolam for group BM. Postoperative analgesia was examined by a blinded anesthetist utilizing a Revised Faces Pain Scale.Consumption of the total amount of rescue analgesic each 24 h, postoperative time to requirement of the first dose and any adverse effects were noted.</AbstractText>The four groups were comparable as regards age, sex, weight, duration of surgery, heart rate, blood pressure and the time from induction of anesthesia to response to voice. The Revised Faces Pain Scale was 2.6±1.5 in group BN, 3.1±1.8 in group BM, 4.4±2.4 in group BK, and 5.6±1.3 in group B (p=0.005). Postoperative duration of analgesia was 433±68 min, 769±118 min, 1097±126 min and 1254±176 min in groups B, BK, BM and BN respectively (P=0.001). The dose of rescue analgesic within 24 h in group B was significantly higher than those of the other three groups (P<0.05).</AbstractText>Addition of either neostigmine, midazolam, or ketamine to caudal bupivacaine extended analgesia time and decreased rescue analgesic compared to bupivacaine alone in children who underwent lower abdominal surgery.</AbstractText>
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2,334,745 |
Peri-arterial specification of vascular mural cells from naïve mesenchyme requires Notch signaling.
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Mural cells (MCs) are essential for blood vessel stability and function; however, the mechanisms that regulate MC development remain incompletely understood, in particular those involved in MC specification. Here, we investigated the first steps of MC formation in zebrafish using transgenic reporters. Using <i>pdgfrb</i> and <i>abcc9</i> reporters, we show that the onset of expression of <i>abcc9</i>, a pericyte marker in adult mice and zebrafish, occurs almost coincidentally with an increment in <i>pdgfrb</i> expression in peri-arterial mesenchymal cells, suggesting that these transcriptional changes mark the specification of MC lineage cells from naïve <i>pdgfrb</i><sup>low</sup> mesenchymal cells. The emergence of peri-arterial <i>pdgfrb</i><sup>high</sup> MCs required Notch signaling. We found that <i>pdgfrb</i>-positive cells express <i>notch2</i> in addition to <i>notch3</i>, and although depletion of <i>notch2</i> or <i>notch3</i> failed to block MC emergence, embryos depleted of both <i>notch2</i> and <i>notch3</i> lost mesoderm- as well as neural crest-derived <i>pdgfrb</i><sup>high</sup> MCs. Using reporters that read out Notch signaling and Notch2 receptor cleavage, we show that Notch activation in the mesenchyme precedes specification into <i>pdgfrb</i><sup>high</sup> MCs. Taken together, these results show that Notch signaling is necessary for peri-arterial MC specification.
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2,334,746 |
Effect of Deep Inspiration and Expiration on QTc Interval in Normal Healthy Subjects.
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Background It is a well known fact that phases of respiration cause change in heart rate and autonomic tone of the heart. But how cardiovascular autonomic reflexes affect the electrocardiographic Heart rate-corrected QT interval (QTc) during the inspiratory and expiratory phase of respiration also need to be established. Objective To determine whether the respiratory phases influence the QTc interval or not. Method This was a quantitative, observational, cross-sectional study done at Kathmandu University School of Medical Sciences, Pre-Clinical Basic Science Block, Chaukot. Total one hundred students between 18 to 25 years of age, studying at KUSMS Pre-clinical science Block were included. QTc interval was recorded for normal respiration, deep inspiration and deep expiration by electrographic recording using ADInstruments. The values obtained were later analyzed using paired t-test in SPSS 16.0. Result The mean QTc interval during normal respiration was 392.1±21.6 milliseconds, during deep inspiration was 384.2±15.5 milliseconds and that following deep expiration was 395.0±13.1 milliseconds. There was no significant difference between QTc interval at the end of deep inspiration (p value < 0.05) and QTc interval at the end of deep inspiration (p value < 0.05) when compared with normal respiration. Conclusion This study shows that neither the inspiratory phase nor expiratory phase alters the QTc interval in normal healthy individual. Thus, it can also be implied that alteration in inspiratory and expiratory phase in various respiratory diseases does not cause any change in QTc interval.
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2,334,747 |
Long noncoding RNA AK088388 regulates autophagy through miR-30a to affect cardiomyocyte injury.
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Finding ways to reduce myocardial ischemia/reperfusion injury in the process of myocardial infarction has been an area of intense study in the field of heart disease. Recent studies have shown that long noncoding RNA (lncRNA) and autophagy play important roles in cardiovascular diseases. In our study, software analysis and dual-luciferase reporter assays have shown that miR-30a has binding sites on both AK088388 and Beclin-1. Continuing experiments found that miR-30a expression is downregulated, while the expressions of AK088388, Beclin-1, and LC3-II are upregulated in hypoxia/reoxygenation (H/R) cardiomyocytes; miR-30a inhibits the expression of AK088388, Beclin-1, and LC3-II in H/R cardiomyocytes, while AK088388 promotes the expression of Beclin-1 and LC3-II and inhibits miR-30a expression. AK088388 small interfering RNA and miR-30a mimics can promote the viability of H/R cardiomyocytes, reduce lactate dehydrogenase release, and reduce apoptosis. Mutations of the miR-30a binding site in AK088388 could not block the effects of miR-30a mentioned above. Therefore, AK088388 can competitively bind to miR-30a, promoting the expression of Beclin-1 and LC3-II, autophagy, and eventually cell damage. This finding provides new evidence for understanding the role of lncRNA in myocardial ischemia/reperfusion injury.
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2,334,748 |
[Diagnosis and treatment of kidney involvement in plasma cell diseases : Renal involvement in multiple myeloma and monoclonal gammopathies].
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Kidney involvement is a common complication in patients with plasma cell diseases.</AbstractText>This article outlines the spectrum of renal involvement in plasma cell dyscrasia and describes diagnostic and therapeutic measures to guide clinical management.</AbstractText>Evaluation and discussion of the current literature as well as existing guidelines and recommendations of professional societies.</AbstractText>The clinical manifestations of renal involvement in plasma cell disorders are heterogeneous and range from acute cast nephropathy in multiple myeloma to rare forms of glomerulonephritis. The term monoclonal gammopathy of renal significance (MGRS) was introduced to describe kidney involvement caused by monoclonal gammopathy but without evidence for underlying malignancy. Light chain cast nephropathy is the most common renal manifestation in multiple myeloma, whereas monoclonal immunoglobulin deposition disease (MIDD) and renal light chain (AL) amyloidosis can be found in multiple myeloma and MGRS. Decisive is the extended hematological diagnostics in order to exclude the presence of a hematological neoplasm. The treatment of renal involvement in monoclonal gammopathies involves the reduction of the plasma cell clone with cytoreductive treatment. The reduction of the monoclonal protein in serum is prognostically relevant for the renal response to treatment. In the case of histological evidence of a light chain cast nephropathy, high cut-off dialysis is recommended to reduce the free light chains in serum.</AbstractText>The spectrum of renal manifestations in plasma cell dyscrasia has been expanded, particularly since the introduction of the term MGRS. Diagnostic and therapeutic management remain an interdisciplinary challenge.</AbstractText>
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2,334,749 |
Music Interventions in Pediatric Surgery (The Music Under Surgery In Children Study): A Randomized Clinical Trial.
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Perioperative music interventions have been shown to reduce anxiety and pain in adults. This inexpensive, easily applicable intervention could be of benefit to children as well. Our objective was to determine the effects of music interventions on distress, anxiety, and postoperative pain in infants undergoing surgery.</AbstractText>The Music Under Surgery In Children study was designed as a parallel, single-blind, randomized controlled trial with an a priori formulated hypothesis. Data were collected between August 2015 and October 2016 in a single tertiary care children's hospital. There was a 24-hour follow-up with blind primary outcome assessment. A random sample of 432 eligible 0-3 years of age infants admitted for orchidopexy, hypospadias, or inguinal hernia repair receiving general anesthesia and caudal block were asked for participation. Subjects were assigned to a preoperative music intervention, pre- and intraoperative music intervention, or no music intervention (control) via random allocation using a computer-generated list with the use of opaque envelopes. The main outcome measure was the postoperative level of distress assessed with the COMFORT-Behavior scale, which is an observational scale; furthermore, preoperative level of distress, preoperative anxiety, and physiological measurements such as heart rate (HR) and blood pressure were measured. The trial was registered at the Dutch Trial Register, number NTR5402 (www.trialregister.nl).</AbstractText>One hundred ninety-five infants with median age 6.9 months (interquartile range, 3.3-11.1) were randomized, 178 of whom were included in the primary analysis. A nonsignificant difference in COMFORT-Behavior scale scores between the pre- and intraoperative music intervention group and control group at 4 hours after surgery was found (mean difference, -1.22; 95% CI, 2.60-0.17; P = .085). Additional analysis showed weak nonsignificant evidence for an interaction effect between music exposure and COMFORT-Behavior score at baseline (P = .027 with a Bonferroni-adjusted significance level of .025). General linear modeling showed a statistically significantly reduced HR after the preoperative music intervention in the holding area in the combined preoperative music intervention and intraoperative music intervention group compared to the control group (P = .003). The differences in HR among the 3 study arms at all time points were not statistically significant (P = .069).</AbstractText>Music interventions do not seem to benefit all young infants undergoing surgery. The potential benefits of music interventions in the preoperative period and in more distressed children warrant further exploration.</AbstractText>
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2,334,750 |
8-Aminoguanine Induces Diuresis, Natriuresis, and Glucosuria by Inhibiting Purine Nucleoside Phosphorylase and Reduces Potassium Excretion by Inhibiting Rac1.
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Background 8-Aminoguanosine and 8-aminoguanine are K<sup>+</sup>-sparing natriuretics that increase glucose excretion. Most effects of 8-aminoguanosine are due to its metabolism to 8-aminoguanine. However, the mechanism by which 8-aminoguanine affects renal function is unknown and is the focus of this investigation. Methods and Results Because 8-aminoguanine has structural similarities with inhibitors of the epithelial sodium channel (ENaC), Na<sup>+</sup>/H<sup>+</sup> exchangers, and adenosine A<sub>1</sub> receptors, we examined the effects of 8-aminoguanine on EN aC activity in mouse collecting duct cells, on intracellular pH of human proximal tubular epithelial cells, on responses to a selective A<sub>1</sub>-receptor agonist in vivo, and on renal excretory function in A<sub>1</sub>-receptor knockout rats. These experiments showed that 8-aminoguanine did not block EN aC, Na<sup>+</sup>/H<sup>+</sup> exchangers, or A<sub>1</sub> receptors. Because Rac1 enhances activity of mineralocorticoid receptors and some guanosine analogues inhibit Rac1, we examined the effects of 8-aminoguanine on Rac1 activity in mouse collecting duct cells. Rac1 activity was significantly inhibited by 8-aminoguanine. Because in vitro 8-aminoguanine is a purine nucleoside phosphorylase ( PNP ase) inhibitor, we examined the effects of a natriuretic dose of 8-aminoguanine on urinary excretion of PNP ase substrates and products. 8-Aminoguanine increased and decreased, respectively, urinary excretion of PNP ase substrates and products. Next we compared in rats the renal effects of intravenous doses of 9-deazaguanine ( PNP ase inhibitor) versus 8-aminoguanine. 8-Aminoguanine and 9-deazaguanine induced similar increases in urinary Na<sup>+</sup> and glucose excretion, yet only 8-aminoguanine reduced K<sup>+</sup> excretion. Nsc23766 (Rac1 inhibitor) mimicked the effects of 8-aminoguanine on K<sup>+</sup> excretion. Conclusions 8-Aminoguanine increases Na<sup>+</sup> and glucose excretion by blocking PNP ase and decreases K<sup>+</sup> excretion by inhibiting Rac1.
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2,334,751 |
The Effect of Family-Centered Empowerment Model on the Illness Perception in Heart Failure Patients: a Randomized Controlled Clinical Trial.
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<b><i>Introduction:</i></b> Heart failure is a chronic medical condition that, despite the existing therapies, involves different aspects of an individual's life (such as self-care capability). Illness perception is one of the most important variables which seem to improve the self-efficacy skills in chronic diseases such as heart failure. Therefore, this study aimed to investigate the effect of family-centered empowerment model on the perception of the illness in heart failure patients. <b><i>Methods:</i></b> This interventional study was performed on 70 heart failure patients, assigned into control and experimental groups, admitted to the heart clinic of Hazrate Fatemeh hospital in Shiraz. After the convenience sampling, the patients were divided into two control and intervention groups by block randomization method. For experimental group, the family-centered empowerment modeling was done in 5 sessions. The research materials included demographic information and Brief illness perception questionnaires (B-IPQ). Data were analyzed using SPSS v.13 software. The statistical tests included Wilcoxon, Man-Whitney, and Independent t-test. P value less than 0.05 was considered as significant. <b><i>Results:</i></b> In this study, both control and experimental groups were homogeneous with demographic information. Before the intervention in different dimensions of illness perception, all of the values in both groups were the same; However, after the intervention, a significant difference was observed in all of the dimensions of illness perception, except for Time line; so that the most and the least changes were related to the concern (1.09 (0.61) vs 3 (0.93)), and identity dimensions (0.97 (0.61) vs 2.11 (0.67)), respectively. <b><i>Conclusion:</i></b> On the basis of the above, it can be concluded that this model modifies the illness perceptions in heart failure patients. Cardiac nurses should consider family- based empowerment model as a treatment for heart failure patients.
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2,334,752 |
Sphenopalatine ganglion block: an external gate to modulate cardiac autonomic tone and suppress premature ventricular beats?
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Autonomic modulation is used for treating various cardiovascular diseases, such as cardiac arrhythmias. Sphenopalatine ganglion (SPG) block is an easy, non-invasive therapy for migraine with a potential cardiovascular impact that remains unclear. In this study, we sought to assess the effect of SPG block on cardiac autonomic tone, as expressed by heart rate variability (HRV), and on ventricular arrhythmogenesis.</AbstractText>Forty patients (14 male and 26 female) suffering from migraine were randomized by 1:1 to SPG block or placebo (controls) and HRV parameters were evaluated 1 hour before and hourly after the intervention. Twenty-four additional patients (11 men and 13 women) with premature ventricular contractions (PVCs) from the right ventricular outflow tract underwent the same randomization and the number of PVCs was assessed during 1 hour before and every hour after treatment. Values were summarized as median (1st-3rd quartile).</AbstractText>During the first four hours after SPG block, an increase in mean RR [883 (IQR, 869-948) vs.</i> 839 (IQR, 806-887) ms at baseline, P<0.01], SDNN [64 (IQR, 59-69) vs.</i> 51 (IQR, 47-55) ms, P<0.01], SDANN [39 (IQR, 36-43) vs.</i> 27 (IQR, 22-29) ms, P<0.01], ASDNN [51 (IQR, 47-53) vs.</i> 40 (IQR, 37-44) ms, P<0.01], rMSSD [30 (IQR, 27-32) vs.</i> 25 (IQR, 23-27) ms, P<0.01], VLF [26 (IQR, 24-29) vs.</i> 23 (IQR, 22-25) ms2</sup>, P<0.01] and HF [14 (IQR, 11-16) vs.</i> 11 (IQR, 9-12) ms2</sup>, P<0.01], along with a decrease in LF/HF ratio [1.7 (IQR, 1.4-1.9) vs.</i> 2.0 (IQR, 1.7-2.5), P<0.01] was observed in patients with migraine. In patients with PVCs, the number of ectopic ventricular beats per hour was decreased for the first five hours following SPG block [360 (IQR, 264-850) from 956 (IQR, 545-1,412), P<0.001]. No such differences were observed in controls.</AbstractText>SPG block is associated with a transient increase in those HRV parameters that mainly express parasympathetic activity. It is also followed by a significant decrease in ventricular arrhythmic burden. These findings imply an effect on cardiac autonomic tone with a potential favorable clinical impact on arrhythmogenesis.</AbstractText>
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2,334,753 |
Efficacy of erbium-doped yttrium aluminium garnet for achieving pre-emptive dental laser analgesia in children: A study protocol for a randomized clinical trial.
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A current non-pharmacological mean for attaining painless conservative treatment is presented by laser analgesia (LA), considered as bio-photomodulation of pulp reactivity aiming reduction of nociceptive impulse formation. Currently no consensus is reached regarding a detailed protocol with laser parameter settings for pre-emptive LA. The purpose of this study is determining the efficacy of erbium-doped yttrium aluminium garnet (Er:YAG) laser in achieving pulpal analgesia and quantifying duration and extent of any effects assessed.</AbstractText>The proposed study is a double-blind placebo-controlled randomized split-mouth clinical trial with 2-way repeated measures design. Eligible patients of age 10 to 12 years undergo 2 single-visit treatments, receiving LA or placebo analgesia (PA) prior to caries ablation, randomized via computer-generated, permuted-block sequence. Primary outcome measure is pain felt during treatment, reported by patient on visual-analogue scale.</AbstractText>changes in pulpal sensibility to electrical and cold-stimuli; patient experience during LA/PA; pain-related behavior according to Faces, Legs, Activity, Cry, Consolabilty (FLACC) scale; heart-rate dynamics. Data will be analyzed with intention-to-treat concept by Student t test for paired samples, P < .05. Pre-test on 20 subjects resulted in n = 41 patients needing to be recruited.</AbstractText>This study protocol has been approved by the Committee for Scientific Research Ethics, Medical University - Plovdiv, Bulgaria (Reference number P-8604, Protocol of approval N:6/23.11.2017) and registered on a publically accessible database. This research received institutional funding from the Medical University - Plovdiv, Bulgaria under project SPD-03/2017. Findings will be reported in scientific publications and at research conferences, and in project summary papers for participants.</AbstractText>ClinicalTrials.gov (Registration number: NCT03412721).</AbstractText>
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2,334,754 |
High-Resolution Fast Ultrasound Imaging With Adaptive-Lag Filtered Delay-Multiply-and-Sum Beamforming and Multiline Acquisition.
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Multiline acquisition (MLA) is a well-established method for a high-frame-rate cardiac ultrasound imaging, which is commonly used in conjunction with delay-and-sum (DAS) beamforming. The block-like artifacts that occur secondary to the use of MLA can be reduced using interpolation of the data acquired from adjacent transmitted beams-a method called synthetic transmit beamforming (STB). A recently proposed filtered delay-multiply-and-sum (F-DMAS) is a novel beamforming method, based on modified autocorrelation of the aperture data, which provides superior contrast resolution compared to the DAS beamforming. In this study, we demonstrate that a combination of the F-DMAS with the STB compensated MLA results in superior contrast as compared to both DAS beamformed STB and DAS beamformed single-line acquisition. Moreover, we propose a novel formulation for adaptive-lag F-DMAS that outperforms both DAS and F-DMAS in terms of contrast and lateral resolutions. The results are demonstrated in tissue-mimicking phantom and in human cardiac data.
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2,334,755 |
Cardiovascular, psychiatric, and neurological phenomena seen in mad honey disease: A clinical case report.
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Mad Honey Disease is characterized by intoxication symptoms secondary to over-ingestion of grayanotoxin found in honey produced from rhododendron nectar. Cardiovascular symptoms are common, but psychiatric and neurological phenomena are rarely seen in this condition. Our case details a patient who presented with florid symptomology in all three aforementioned areas.
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2,334,756 |
Association of Genetic Variation at <i>AQP4</i> Locus with Vascular Depression.
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Despite its substantial clinical importance, specific genetic variants associated with depression have not yet been identified. We sought to identify genetic variants associated with depression by (a) focusing on a more homogenous subsample (vascular depression) and (b) applying a three-stage approach. First, we contacted 730 participants with a confirmed atherosclerotic disease (coronary artery disease) from a population-based study population (German Myocardial Infarction Family Study IV) for psychiatric assessment with the Mini International Neuropsychiatric Interview. Second, we genotyped these patients using genome-wide single nucleotide polymorphism (SNP) arrays. Third, we characterized the SNP via in-silico analysis. The final sample consisted of 342 patients (78.3% male, age = 63.2 ± 9.9 years), 22.8% with a severe depressive disorder. Variant rs528732638 on chromosome 18q11.2 was a genome-wide significant variant and was associated with 3.6-fold increase in the odds of lifetime depression. The locus belongs to a linkage disequilibrium block showing expression quantitative trait loci effects on three putative <i>cis</i>-regulated genes, including the aquaporin 4 (<i>AQP4</i>) locus. <i>AQP4</i> is already known to mediate the formation of ischemic edema in the brain and heart, increasing the size and extent of resulting lesions. Our findings indicate that <i>AQP4</i> may also play a role in the etiopathology of vascular depression.
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2,334,757 |
Local infiltration anaesthesia versus sciatic nerve and adductor canal block for fast-track knee arthroplasty: A randomised controlled clinical trial.
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Local infiltration anaesthesia (LIA) was introduced as an innovative analgesic procedure for enhanced recovery after primary total knee arthroplasty (TKA). However, LIA has never been compared with analgesia based on an adductor canal catheter and a single-shot sciatic nerve block.</AbstractText>To evaluate two analgesic regimens for TKA comparing mobility, postoperative pain and patient satisfaction.</AbstractText>Two-group randomised, controlled clinical trial.</AbstractText>Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Germany between April and August 2017.</AbstractText>Adults undergoing primary TKA under general anaesthesia were eligible for study participation. Exclusion criteria were heart insufficiency (New York Heart Association class >2), liver insufficiency (Child Pugh Score >B), evidence of diabetic polyneuropathy, severe obesity (BMI > 40 kg m), chronic opioid therapy for more than 3 months before scheduled surgery and allergy to local anaesthetics.</AbstractText>Nerve block patients group (n=20) underwent surgery with two ultrasound-guided regional anaesthesia blocks: a single-shot sciatic nerve block with 20 ml of ropivacaine 0.75% combined with an adductor canal block with a catheter placed for less than 4 days with an infusion of ropivacaine 0.2% at a rate of 6 ml h. LIA patients (LIA group, n=20) received LIA of the knee capsule at the end of surgery with 150 ml of ropivacaine 0.2%.</AbstractText>The primary endpoint was postoperative time to patient mobilisation (ability to walk) on the ward.</AbstractText>Baseline characteristics were similar in each study group. Patients in both groups were mobilised to walk after TKA in similar time frames (LIA 24.0 h versus nerve block 27.1 h, 95% CI of difference -9.6 to 3.3 h). Maximum postoperative pain scores on exertion were higher in LIA patients with a mean 1.3 of 10 numerical rating scale points (95% CI 0.3 to 2.3, P = 0.010) as were intra-operative opioid requirements (LIA median 107 [IQR 100 to 268] mg versus nerve block median 78 [60 to 98] mg, P < 0.001). Patient satisfaction, postoperative oral morphine-equivalents and resting pain levels were comparable between groups. Anaesthesia induction time was reduced in LIA patients (LIA 10 min versus nerve block 35 min, 95% CI of difference 13 to 38 min, P < 0.001).</AbstractText>Both analgesic regimens allow early mobilisation after TKA with high patient satisfaction. LIA shortened peri-operative time. Further research is required to optimise especially pain control during the later postoperative period with LIA.</AbstractText>Clinicaltrials.gov identifier NCT03114306.</AbstractText>
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2,334,758 |
Shedding light on the link between early life sun exposure and risk of multiple sclerosis: results from the EnvIMS Study.
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Lower levels of sun exposure in childhood have been suggested to be associated with increased risk of multiple sclerosis (MS). In this paper we extend previous work, using two novel analytical strategies.</AbstractText>Data collected in the Environmental risk factors In MS (EnvIMS) study, a case-control study with MS cases and population-based controls from Canada, Italy and Norway, were used. Participants reported on sun exposure behaviours for 5-year age intervals from birth; we focused on the first three age intervals (≤15 years). We compared two life course epidemiology conceptual models, the critical period and the accumulation model. We also used latent class analysis to estimate MS risk for different latent sun exposure behaviour groups.</AbstractText>The analyses included 2251 cases and 4028 controls. The accumulation model was found to be the best model, which demonstrated a nearly 50% increased risk of MS comparing lowest reported summer sun exposure with highest [risk ratio (RR) = 1.47 (1.24, 1.74)]. The latent sun exposure behaviour group, characterized by low sun exposure during summer and winter and high sun protection use, had the highest risk of MS; a 76% increased risk as compared with the group with high sun exposure and low sun protection use [RR = 1.76 (1.27, 2.46)].</AbstractText>Our analyses provide novel insights into the link between sun exposure and MS. We demonstrate that more time indoors during childhood and early adolescence is linked with MS risk, and that sun protection behaviours in those who spend most time indoors may play a key role in increasing risk.</AbstractText>© The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.</CopyrightInformation>
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2,334,759 |
Horner's Syndrome and Upper Extremity Weakness After Quadratus Lumborum Block for Postcesarean Section Analgesia: A Case Report.
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A healthy, 34-year-old primigravida at 41 weeks gestational age presented for cesarean delivery due to a category 2 fetal heart tracing remote from delivery. After completion of the surgery under epidural anesthesia, bilateral quadratus lumborum blocks were performed for postoperative pain. Approximately 4 hours later, the patient developed left-sided arm weakness, left miosis, and ptosis. These symptoms resolved within 24 hours. Considering the time course of her symptoms, we believe that the quadratus lumborum block was the likely culprit.
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2,334,760 |
Triacylglycerol Metabolism in <i>Drosophila melanogaster</i>.
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Triacylglycerol (TAG) is the most important caloric source with respect to energy homeostasis in animals. In addition to its evolutionarily conserved importance as an energy source, TAG turnover is crucial to the metabolism of structural and signaling lipids. These neutral lipids are also key players in development and disease. Here, we review the metabolism of TAG in the <i>Drosophila</i> model system. Recently, the fruit fly has attracted renewed attention in research due to the unique experimental approaches it affords in studying the tissue-autonomous and interorgan regulation of lipid metabolism <i>in vivo</i> Following an overview of the systemic control of fly body fat stores, we will cover lipid anabolic, enzymatic, and regulatory processes, which begin with the dietary lipid breakdown and <i>de novo</i> lipogenesis that results in lipid droplet storage. Next, we focus on lipolytic processes, which mobilize storage TAG to make it metabolically accessible as either an energy source or as a building block for biosynthesis of other lipid classes. Since the buildup and breakdown of fat involves various organs, we highlight avenues of lipid transport, which are at the heart of functional integration of organismic lipid metabolism. Finally, we draw attention to some "missing links" in basic neutral lipid metabolism and conclude with a perspective on how fly research can be exploited to study functional metabolic roles of diverse lipids.
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2,334,761 |
Acute Pulmonary Edema in a Pregnant Patient with Undiagnosed Levo-Transposition of the Great Arteries.
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BACKGROUND Levo-transposition of the great arteries (L-TGA) is a rare form of congenital heart disease that may go unrecognized until adulthood. Parturient women with L-TGA have a high likelihood of developing acute pulmonary edema and cardiac dysrhythmias during the peri-partum period. CASE REPORT We present the case of a 32-year-old primigravida patient with previously unknown diagnosis of L-TGA, presenting with preeclampsia, whose peri-partum course was complicated by the development of acute pulmonary edema, complete heart block, and acute hypoxic respiratory failure. CONCLUSIONS This case report highlights the predisposition of parturient women with undiagnosed congenital heart disease to develop acute hypoxic respiratory failure in the perioperative period and the importance of meticulous fluid management in such patients.
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2,334,762 |
Siglec-1 Macrophages and the Contribution of IFN to the Development of Autoimmune Congenital Heart Block.
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Given that diseases associated with anti-SSA/Ro autoantibodies, such as systemic lupus erythematosus and Sjögren syndrome, are linked with an upregulation of IFN and type I IFN-stimulated genes, including sialic acid-binding Ig-like lectin 1 (Siglec-1), a receptor on monocytes/macrophages, recent attention has focused on a potential role for IFN and IFN-stimulated genes in the pathogenesis of congenital heart block (CHB). Accordingly, three approaches were leveraged to address the association of IFN, IFN-stimulated genes, and the phenotype of macrophages in affected fetal cardiac tissue: 1) cultured healthy human macrophages transfected with hY3, an anti-SSA/Ro-associated ssRNA, 2) RNA isolated from freshly sorted human leukocytes/macrophages after Langendorff perfusion of three fetal hearts dying with CHB and three healthy gestational age-matched hearts, and 3) autopsy tissue from three additional human CHB hearts and one healthy heart. TLR ligation of macrophages with hY3 led to the upregulation of a panel of IFN transcripts, including SIGLEC1, a result corroborated using quantitative PCR. Using independent and agnostic bioinformatics approaches, CD45<sup>+</sup>CD11c<sup>+</sup> and CD45<sup>+</sup>CD11c<sup>-</sup> human leukocytes flow sorted from the CHB hearts highly expressed type I IFN response genes inclusive of SIGLEC1. Furthermore, Siglec-1 expression was identified in the septal region of several affected fetal hearts. These data now provide a link between IFN, IFN-stimulated genes, and the inflammatory and possibly fibrosing components of CHB, positioning Siglec-1-positive macrophages as integral to the process.
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2,334,763 |
Structurally Simple, Readily Available Peptidomimetic 1-Benzyl-5-methyl-4-( n-octylamino)pyrimidin-2(1 H)-one Exhibited Efficient Cardioprotection in a Myocardial Ischemia (MI) Mouse Model.
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TLR4, a member of the Toll-like receptor (TLR) family, serves as a pattern recognition receptor in the innate immune response to microbial pathogens. TLR4 also regulates the inflammatory reaction to ischemic injury in the heart. The TRIF-related adaptor molecule (TRAM) is an adapter that recruits the Toll/interleukin 1 receptor (TIR) domain, which contains adapter-inducing IFN-β (TRIF), to activate TLR4, following TRIF-dependent cytokine gene transcription. On the basis of a known TRAM-derived decoy peptide, 10 of its peptidomimetics were synthesized. One of them, 1-benzyl-5-methyl-4-( n-octylamino)pyrimidin-2(1 H)-one (21), exhibited high potency and efficacy in vitro. In vitro results and in silico analysis provided evidence for the possible direct interaction of 21 with the TLR4 complex. Administered in mice, 21 was able to block the pathophysiological manifestation of MI, restoring the concomitant tissue damage, with a 100% survival rate. Thus, inhibition of TLR4-mediated inflammation in postischemic myocardium could be used as an approach for developing cardioprotective drugs.
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2,334,764 |
Role of dexamethasone in the para-vertebral block for pediatric patients undergoing aortic coarctation repair. randomized, double-blinded controlled study.
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Surgery for aortic coarctation requires special care during anesthesia due to severe pain during the lateral thoracotomy incision, intraoperative hemodynamic instability and the need for large doses of intra- and postoperative analgesics and vasodilators. Additionally, the postoperative care of patients is very important.</AbstractText>We aimed to compare ultrasound-guided paravertebral block performed using bupivacaine alone and bupivacaine with dexamethasone in terms of the intra- and postoperative analgesic requirements and hemodynamics, postoperative complications and ICU stay.</AbstractText>This was a prospective, randomized, controlled, double-blinded study.</AbstractText>Fifty patients aged four to 12 months scheduled for aortic coarctation surgery were randomly divided into two equal groups (n = 25). Patients in group D (dexamethasone) received 0.5 mg/kg bupivacaine 0.25% mixed with 0.1 mg/kg dexamethasone diluted with isotonic saline and those in group C (control) received 0.5 mg/kg bupivacaine 0.25% diluted with isotonic saline (total volume 15 ml in each group). Intraoperative fentanyl consumption and hemodynamics (heart rate, arterial blood pressure) at baseline, 1 min after induction, at skin incision, after 30 min, after clamping, after declamping and at the end of the surgery were recorded, along with the objective pain score (OPS) immediately postoperatively and at 4 h, 8 h, 12 h and 24 h postoperatively and the time to the first request for pethidine. The intra- and postoperative vasodilator doses, time to extubation, ICU stay duration and postoperative complications were also recorded.</AbstractText>The postoperative OPS was significantly lower at 12 and 24 h in group D than in group C. The time to the first request for analgesia was significantly longer in group D than in group C (3.9 ± 2.23 vs 8.6 ± 0.69). Additionally, the time to extubation was significantly shorter in group D.</AbstractText>The use of dexamethasone as an adjuvant in ultrasound-guided paravertebral block in paediatric patients undergoing surgery for aortic coarctation increased the duration of postoperative analgesia with a prolonged time to the first request for analgesics It was also associated with a decreased incidence of postoperative complications.</AbstractText>Trial registration number: NCT03074773 . (Prospectively registered). The initial registration date was 9/3/2017.</AbstractText>
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2,334,765 |
Association of estimated sleep duration and naps with mortality and cardiovascular events: a study of 116 632 people from 21 countries.
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To investigate the association of estimated total daily sleep duration and daytime nap duration with deaths and major cardiovascular events.</AbstractText>We estimated the durations of total daily sleep and daytime naps based on the amount of time in bed and self-reported napping time and examined the associations between them and the composite outcome of deaths and major cardiovascular events in 116 632 participants from seven regions. After a median follow-up of 7.8 years, we recorded 4381 deaths and 4365 major cardiovascular events. It showed both shorter (≤6 h/day) and longer (>8 h/day) estimated total sleep durations were associated with an increased risk of the composite outcome when adjusted for age and sex. After adjustment for demographic characteristics, lifestyle behaviours and health status, a J-shaped association was observed. Compared with sleeping 6-8 h/day, those who slept ≤6 h/day had a non-significant trend for increased risk of the composite outcome [hazard ratio (HR), 1.09; 95% confidence interval, 0.99-1.20]. As estimated sleep duration increased, we also noticed a significant trend for a greater risk of the composite outcome [HR of 1.05 (0.99-1.12), 1.17 (1.09-1.25), and 1.41 (1.30-1.53) for 8-9 h/day, 9-10 h/day, and >10 h/day, Ptrend < 0.0001, respectively]. The results were similar for each of all-cause mortality and major cardiovascular events. Daytime nap duration was associated with an increased risk of the composite events in those with over 6 h of nocturnal sleep duration, but not in shorter nocturnal sleepers (≤6 h).</AbstractText>Estimated total sleep duration of 6-8 h per day is associated with the lowest risk of deaths and major cardiovascular events. Daytime napping is associated with increased risks of major cardiovascular events and deaths in those with >6 h of nighttime sleep but not in those sleeping ≤6 h/night.</AbstractText>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: [email protected].</CopyrightInformation>
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2,334,766 |
An injectable alginate/extra cellular matrix (ECM) hydrogel towards acellular treatment of heart failure.
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As treatments for myocardial infarction (MI) continue to improve, the population of people suffering from heart failure (HF) is rising significantly. Novel treatment strategies aimed at achieving long-term functional stabilisation and improvement in heart function post MI include the delivery of biomaterial hydrogels and myocardial matrix-based therapies to the left ventricle wall. Individually alginate hydrogels and myocardial matrix-based therapies are at the most advanced stages of commercial/clinical development for this potential treatment option. However, despite these individual successes, the potential synergistic effect gained by combining the two therapies remains unexplored. This study serves as a translational step in evaluating the minimally invasive delivery of dual acting alginate-based hydrogels to the heart. We have successfully developed new production methods for hybrid alginate/extracellular matrix (ECM) hydrogels. We have identified that the high G block alginate/ECM hybrid hydrogel has appropriate rheological and mechanical properties (1.6 KPa storage modulus, 29 KPa compressive modulus and 14 KPa dynamic modulus at day 1) and can be delivered using a minimally invasive delivery device. Furthermore, we have determined that these novel hydrogels are not cytotoxic and are capable of enhancing the metabolic activity of dermal fibroblasts in vitro (p < 0.01). Overall these results suggest that an effective minimally invasive HF treatment option could be achieved by combining alginate and ECM particles.
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2,334,767 |
Atypical advanced interatrial blocks: Definition and electrocardiographic recognition.
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The diagnosis of advanced interatrial block (A-IAB) is done by surface ECG analysis when the P-wave ≥120 ms with biphasic (±) morphology in leads II, III and aVF. In this brief communication, we advance a new concept involving atypical patterns of A-IAB due to changes about the morphology or duration of the P-wave. It remains to be determined its real prevalence in different clinical scenarios, and whether these atypical ECG patterns should be considered as predictors of atrial fibrillation/stroke.
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2,334,768 |
Interethnic analyses of blood pressure loci in populations of East Asian and European descent.
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Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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2,334,769 |
Heart rate variability rebound following exposure to persistent and repetitive sleep restriction.
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While it is well established that slow-wave sleep electroencephalography (EEG) rebounds following sleep deprivation, very little research has investigated autonomic nervous system recovery. We examined heart rate variability (HRV) and cardiovagal baroreflex sensitivity (BRS) during four blocks of repetitive sleep restriction and sequential nights of recovery sleep. Twenty-one healthy participants completed the 22-day in-hospital protocol. Following three nights of 8-hr sleep, they were assigned to a repetitive sleep restriction condition. Participants had two additional 8-hr recovery sleep periods at the end of the protocol. Sleep EEG, HRV, and BRS were compared for the baseline, the four blocks of sleep restriction, and the second (R2) and third (R3) nocturnal recovery sleep periods following the last sleep restriction block. Within the first hour of each sleep period, vagal activation, as indexed by increase in high frequency (HF; HRV spectrum analysis), showed a rapid increase, reaching its 24-hr peak. HF was more pronounced (rebound) in R2 than during baseline (p < 0.001). The BRS increased within the first hour of sleep and was higher across all sleep restriction blocks and recovery nights (p = 0.039). Rebound rapid eye movement sleep was observed during both R2 and R3 (p = 0.004), whereas slow-wave sleep did not differ between baseline and recovery nights (p > 0.05). Our results indicate that the restoration of autonomic homeostasis requires a time course that includes at least three nights, following an exposure to multiple nights of sleep curtailed to about half the normal nightly amount.
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2,334,770 |
Slow and steady: Training induced improvements to response time consistency are due to overall slowing and minimized extremely slow responses.
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Previous studies on response time intraindividual variability (RT IIV) have focused on differences between groups, ignoring the potential for modification. The current study provides a detailed analysis of RT IIV training effects across three age groups. Healthy adults (40 young [aged 18-30], 40 young-old [aged 65-74], and 41 old-old [aged 75-85]) were assigned to feedback or no feedback (standard) conditions during a touch-screen feature integration task. In the feedback condition, participants were shown their performance on the previous block of trials and encouraged to improve going forward. Transfer was assessed by comparing pre- and posttraining performance on a 4-choice RT task. Data were analyzed with respect to RT IIV, ex-Gaussian distribution fitting, and the diffusion model of RT decision making. Significant feedback-related reductions were observed in Target RT IIV and the ex-Gaussian parameter τ, accompanied by an increase in μ. There was no significant change in σ, and no evidence of transfer to the 4-choice RT task. The diffusion model analysis indicated that feedback training promoted a reduction in response threshold for the young and young-old groups, as well as a modulation of drift rate throughout training in the young group. The findings indicate that training to improve consistency induces overall slowing, but also reduces the frequency of extremely slow responses that have been linked to brief attention lapses. The results provide evidence that RT consistency is malleable, but improvements are not necessarily transferable. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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2,334,771 |
Fully automated real-time PCR for EGFR testing in non-small cell lung carcinoma.
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Molecular testing for mutations in the EGFR gene is commonplace for patients with non-small cell lung cancer (NSCLC). These patients are often very sick and management decisions need to be made urgently. In many cases, the results of molecular testing are needed the same day, in order to start targeted therapy and allow maximum benefit for patients. The Idylla™ EGFR Mutation Test offers rapid results within three hours of requesting. This study aimed to assess the concordance of Idylla™ EGFR Mutation Test results with current standard tests. Forty formalin-fixed, paraffin-embedded NSCLC tumour cases (20 EGFR mutant and EGFR 20 wild type) were analysed by the Idylla™ EGFR Mutation Test (CE-IVD) and compared with PCR and NGS methodologies. The overall concordance between Idylla™ and standard testing was 92.5% (95% CI 80.14% to 97.42%) and the specificity of Idylla™ was 100% (95% CI 83.89% to 100%). The sensitivity was affected by loss of tumour content in tissue blocks in a small number of NGS cases; however, comparing Idylla™ with PCR alone, there was 100% concordance (95% CI 89.85% to 100%). The Idylla™ EGFR Mutation Test shows comparative accuracy to routine PCR testing for the most common EGFR mutations in NSCLC. The Idylla™ also offers significantly reduced turn-around times compared with existing modalities and therefore the platform would be a useful addition to many molecular diagnostics units.
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2,334,772 |
Autonomic reactivity in blood-injection-injury and snake phobia.
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This research aimed to study the salivary flow and other autonomic reactions -heart rate (HR) and skin conductance response (SCR)- in blood-injection-injury (BII) phobia and snake phobia participants, under the assumption that exposure to blood-related pictures in BII phobia will provoke an increase in parasympathetic activity that, in turn, will lead to a greater saliva production than other affective contents.</AbstractText>We selected 18 BII phobia and 14 snake phobia participants along with 22 non-phobia individuals. All participants were exposed to 3 blocks of pictures (12 pictures per block) depicting either mutilations, snakes or neutral, household objects. Saliva samples were taken in the 2-min interval before and after each block.</AbstractText>In comparison to other contents, blood-related pictures provoked an increase in salivary flow in BII phobia participants, as well as an increase in the number of SCRs. In the snake phobia group, snake pictures provoked HR acceleration, but the SCRs they elicited did not differ from the SCRs provoked by the blood-related pictures.</AbstractText>BII phobia individuals react to their phobic object with a series of physiological changes resulting from a sympathetic-parasympathetic co-activation. This is in contrast with other specific phobias (e.g., small animal phobias) that usually show a sympathetically mediated, defensive reactivity when exposed to their disorder-relevant stimuli. These data support the use of therapeutic interventions in BII phobia that may differ in some respect from those used in other specific phobias.</AbstractText>Copyright © 2018 Elsevier Inc. All rights reserved.</CopyrightInformation>
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2,334,773 |
Molecular characterization of the 2',5'-oligoadenylate synthetase family in the Chinese tree shrew (Tupaia belangeri chinensis).
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Virus infection induces type I interferons (IFNs) that in turn exert their pleiotropic effects through inducing a large number of interferon-stimulated genes (ISGs). The IFN-induced 2',5'-oligoadenylate synthetases (OASs) have been identified as a member of the ISGs family characterized by the ability to synthesize 2',5'-oligoadenylate (2-5A), which can induce the degradation of viral RNA by activating RNase L within the infected cells to block viral replications. In this study, we characterized the OASs of the Chinese tree shrew (Tupaia belangeri chinensis), a small mammal genetically close to primates and has the potential as animal model for viral infections. We identified 4 putative tree shrew OASs (tOASs, including tOAS1, tOAS2, tOASL1, and tOASL2) and characterized their roles in antiviral responses. Tree shrew lost tOAS3 that was presented in human and mouse. Phylogenetic analyses based on the protein sequences showed a close relationship of tOASs with those of mammals. Constitutive mRNA expression of tOASs was found in seven tissues (heart, liver, spleen, lung, kidney, small intestine and brain). Moreover, tOASs were significantly up-regulated upon various virus infections. Overexpression of tOASs significantly inhibited DNA virus and RNA virus replications in tree shrew primary renal cells. tOAS1 and tOAS2, but not tOASL1 and tOASL2, exerted their anti-HSV activity in an RNase L-dependent pathway. Collectively, our results revealed the evolutionary conservation of tOASs in tree shrew and might offer helpful information for creating viral infection models using the Chinese tree shrew.
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2,334,774 |
Modeling a bivariate residential-workplace neighborhood effect when estimating the effect of proximity to fast-food establishments on body mass index.
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Hierarchical modeling is the preferred approach of modeling neighborhood effects. When both residential and workplace neighborhoods are known, a bivariate (residential-workplace) neighborhood random effect that quantifies the extent that a neighborhood's residential and workplace effects are correlated may be modeled. However, standard statistical software for hierarchical models does not easily allow correlations between the random effects of distinct clustering variables to be incorporated. To overcome this challenge, we develop a Bayesian model and an accompanying estimation procedure that allows for correlated bivariate neighborhood effects and allows individuals to reside or work in multiple neighborhoods, cross-sectional and longitudinal heterogeneity between individuals, and serial correlation between repeated observations over time. Simulation studies that vary key model parameters evaluate how well each aspect of the model is identified by the data. We apply the model to the motivating Framingham Heart Study linked food establishment data to examine whether (i) proximity to fast-food establishments is associated with body mass index, (ii) workplace neighborhood exposure associations are larger than those for residential neighborhood exposure, and (iii) residential neighborhood exposure associations correlate with workplace neighborhood exposure. Comparisons of the full model to models with restricted versions of the covariance structure illustrate the impact of including each feature of the covariance structure.
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2,334,775 |
Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial.
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Treatment with bone-marrow-derived mesenchymal stromal cells (MSCs) has shown benefits in preclinical models of acute respiratory distress syndrome (ARDS). Safety has not been established for administration of MSCs in critically ill patients with ARDS. We did a phase 2a trial to assess safety after administration of MSCs to patients with moderate to severe ARDS.</AbstractText>We did a prospective, double-blind, multicentre, randomised trial to assess treatment with one intravenous dose of MSCs compared with placebo. We recruited ventilated patients with moderate to severe ARDS (ratio of partial pressure of oxygen to fractional inspired oxygen <27 kPa and positive end-expiratory pressure [PEEP] ≥8 cm H2</sub>O) in five university medical centres in the USA. Patients were randomly assigned 2:1 to receive either 10 × 106</sup>/kg predicted bodyweight MSCs or placebo, according to a computer-generated schedule with a variable block design and stratified by site. We excluded patients younger than 18 years, those with trauma or moderate to severe liver disease, and those who had received cancer treatment in the previous 2 years. The primary endpoint was safety and all analyses were done by intention to treat. We also measured biomarkers in plasma. MSC viability was tested in a post-hoc analysis. This trial is registered with ClinicalTrials.gov, number NCT02097641.</AbstractText>From March 24, 2014, to Feb 9, 2017 we screened 1038 patients, of whom 60 were eligible for and received treatment. No patient experienced any of the predefined MSC-related haemodynamic or respiratory adverse events. One patient in the MSC group died within 24 h of MSC infusion, but death was judged to be probably unrelated. 28-day mortality did not differ between the groups (30% in the MSC group vs 15% in the placebo group, odds ratio 2·4, 95% CI 0·5-15·1). At baseline, the MSC group had numerically higher mean scores than the placebo group for Acute Physiology and Chronic Health Evaluation III (APACHE III; 104 [SD 31] vs 89 [33]), minute ventilation (11·1 [3·2] vs 9·6 [2·4] L/min), and PEEP (12·4 [3·7] vs 10·8 [2·6] cm H2</sub>O). After adjustment for APACHE III score, the hazard ratio for mortality at 28 days was 1·43 (95% CI 0·40-5·12, p=0·58). Viability of MSCs ranged from 36% to 85%.</AbstractText>One dose of intravenous MSCs was safe in patients with moderate to severe ARDS. Larger trials are needed to assess efficacy, and the viability of MSCs must be improved.</AbstractText>National Heart, Lung, and Blood Institute.</AbstractText>Copyright © 2019 Elsevier Ltd. All rights reserved.</CopyrightInformation>
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2,334,776 |
An EigenECG Network Approach Based on PCANet for Personal Identification from ECG Signal.
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We herein propose an EigenECG Network (EECGNet) based on the principal component analysis network (PCANet) for the personal identification of electrocardiogram (ECG) from human biosignal data. The EECGNet consists of three stages. In the first stage, ECG signals are preprocessed by normalization and spike removal. The R peak points in the preprocessed ECG signals are detected. Subsequently, ECG signals are transformed into two-dimensional images to use as the input to the EECGNet. Further, we perform patch-mean removal and PCA algorithm similar to the PCANet from the transformed two-dimensional images. The second stage is almost the same as the first stage, where the mean removal and PCA process are repeatedly performed in the cascaded network. In the final stage, the binary quantization, block sliding, and histogram computation are performed. Thus, this EECGNet performs well without the use of back-propagation to obtain features from the visual content. We constructed a Chosun University (CU)-ECG database from an ECG sensor implemented by ourselves. Further, we used the well-known MIT Beth Israel Hospital (BIH) ECG database. The experimental results clearly reveal the good performance and effectiveness of the proposed method compared with conventional algorithms such as PCA, auto-encoder (AE), extreme learning machine (ELM), and ensemble extreme learning machine (EELM).
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2,334,777 |
[A Super-Aged Patient with Advanced ALK-Positive NSCLC and Malignant Pericardial Effusion Causing Cardiac Tamponade].
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Here we report the case of an 88-year-old female with serious respiratory discomfort who exhibited significant heart enlargement and left pleural effusion in her chest X-ray. She developed cardiac tamponade with massive pericardial effusion, and the cytological analysis and diagnostic imaging revealed adenocarcinoma of an unknown primary site. Although supportive care was offered, due to her super-age and malignant pericardial effusion presenting cardiac tamponade, she and her family requested a detailed examination and active treatment. She was enrolled into our medical oncology department, and we immediately performed a cell block cytological examination procedure and drained the pleural effusion. The immunohistochemical and FISH analyses revealed anaplastic lymphoma kinase(ALK)-rearranged non-small cell lung cancer. An ALK tyrosine kinase inhibitor, alectinib, was administered and resulted in a prompt and effective improvement in clinical outcome. This case indicates that we should attempt to achieve an accurate diagnosis, even when patients are super-aged and exhibit serious progress disease conditions. The pleural effusion cell block analysis may be highly useful for the prompt and precise diagnosis of malignancies.
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2,334,778 |
Nasal allergen-neutralizing IgG<sub>4</sub> antibodies block IgE-mediated responses: Novel biomarker of subcutaneous grass pollen immunotherapy.
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Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG4</sub>-associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells.</AbstractText>We sought to determine whether SCIT induces nasal allergen-specific IgG4</sub> antibodies with inhibitory activity that correlates closely with clinical response.</AbstractText>In a cross-sectional controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergic patients (with seasonal allergic rhinitis [SAR]), and 12 nonatopic control subjects. Nasal and serum IgE and IgG4</sub> levels to Phleum pratense components were measured by using the Immuno Solid Allergen Chip microarray. Inhibitory activity was measured by IgE-facilitated allergen binding assay. IL-10+</sup> regulatory B cells were quantified in peripheral blood by using flow cytometry.</AbstractText>Nasal and serum Phl p 1- and Phl p 5-specific IgE levels were increased in patients with SAR compared to nonatopic control subjects (all, P < .001) and SCIT-treated patients (nasal, P < .001; serum Phl p 5, P = .073). Nasal IgG4</sub> levels were increased in the SCIT group compared to those in the SAR group (P < .001) during the pollen season compared to out of season. IgG-associated inhibitory activity in nasal fluid and serum was significantly increased in the SCIT group compared to that in the SAR (both, P < .01). The magnitude of the inhibitory activity was 93% (P < .001) in nasal fluid compared to 66% (P < .001) in serum and was reversed after depletion of IgG. Both nasal fluid (r = -0.69, P = .0005) and serum (r = -0.552, P = .0095) blocking activity correlated with global symptom improvement. IL-10+</sup> regulatory B cells were increased in season compared to out of season in the SCIT group (P < .01).</AbstractText>For the first time, we show that nasal IgG4</sub>-associated inhibitory activity correlates closely with the clinical response to allergen immunotherapy in patients with allergic rhinitis with or without asthma.</AbstractText>Copyright © 2018. Published by Elsevier Inc.</CopyrightInformation>
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2,334,779 |
Sevoflurane versus isoflurane in shoulder arthroscopy in beach chair position in patients with prior interscalene brachial plexus block: A prospective randomised equivalency-based haemodynamic evaluation trial.
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There is a paucity of literature on comparative effects of different inhalational anaesthetics in beach chair position (BCP) for shoulder arthroscopy. We aimed to investigate and compare the haemodynamic effects, anaesthetic and surgical outcomes between two inhalational agents.</AbstractText>In this randomised study, patients of age 18-60 years, were allotted to two groups (29, sevoflurane and 28, isoflurane) and received protocol-based anaesthesia. Intraoperatively, different haemodynamic and other data were recorded.</AbstractText>All mean of averages of individual subject's vitals were comparable between the groups [P = 0.681, 0.325, 0.803, and 0.051, respectively for systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR)]. Higher mean HR was recorded for maximum readings of isoflurane (P</i> = 0.028). Equivalency was observed for SBP, MBP, and DBP (P</i> = 0.000, 002, and 0.027, respectively). Process capability indices indicated that sevoflurane had better values (Pp: 0.55 versus 0.41, Ppk: 0.35 versus 0.22) for SBP as with MBP (Pp: 0.62 versus 0.51, Ppk: 0.36 versus 0.33). For achieving optimal vision, higher pump pressures (PPs) were demanded by surgeon (P</i> = 0.025) and higher differences observed between initial and highest PPs (P</i> = 0.027), in isoflurane subjects. Multivariable analysis revealed that no continuous predictor was able to predict the quality of vision except additional pump flow factor, for both groups.</AbstractText>Both inhalational agents demonstrated equivalent haemodynamic effects. Increased arthroscopic PP requirements were observed with isoflurane anaesthesia. Sevoflurane may be superior to isoflurane during BCP arthroscopy.</AbstractText>
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2,334,780 |
Two novel, putative mechanisms of action for citalopram-induced platelet inhibition.
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Citalopram, a selective serotonin reuptake inhibitor (SSRI), inhibits platelet function in vitro. We have previously shown that this action is independent of citalopram's ability to block serotonin uptake by the serotonin transporter and must therefore be mediated via distinct pharmacological mechanisms. We now report evidence for two novel and putative mechanisms of citalopram-induced platelet inhibition. Firstly, in platelets, citalopram blocked U46619-induced Rap1 activation and subsequent platelet aggregation, but failed to inhibit U46619-induced increases in cytosolic Ca<sup>2+</sup>. Similarly, in neutrophils, citalopram inhibited Rap1 activation and downstream functions but failed to block PAF-induced Ca<sup>2+</sup> mobilisation. In a cell-free system, citalopram also reduced CalDAG-GEFI-mediated nucleotide exchange on Rap1B. Secondly, the binding of anti-GPVI antibodies to resting platelets was inhibited by citalopram. Furthermore, citalopram-induced inhibition of GPVI-mediated platelet aggregation was instantaneous, reversible and displayed competitive characteristics, suggesting that these effects were not caused by a reduction in GPVI surface expression, but by simple competitive binding. In conclusion, we propose two novel, putative and distinct inhibitory mechanisms of action for citalopram: (1) inhibition of CalDAG-GEFI/Rap1 signalling, and (2) competitive antagonism of GPVI in platelets. These findings may aid in the development of novel inhibitors of CalDAG-GEFI/Rap1-dependent nucleotide exchange and novel GPVI antagonists.
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2,334,781 |
The Analgesic Efficacy of Transverse Abdominis Plane Block versus Epidural Block after Caesarean Delivery: Which One Is Effective? TAP Block? Epidural Block?
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TAP block has gained popularity to provide postoperative analgesia after abdominal surgery but its advantage over epidural analgesia is disputed. For lower abdominal surgeries, epidural analgesia has been the gold standard and time-tested technique for providing postoperative analgesia, but contraindications for the same would warrant need for other equally good analgesic techniques. The objective of this study is to compare the analgesic efficacy of both the techniques.</AbstractText>Eighty patients in the ASA I-II risk group, undergone an elective C-section, were randomly assigned to the study. In the TAP group, before the C-section, a single-dose spinal anaesthesia was performed by administering 3 ml of 0.5% hyperbaric bupivacaine to the patients when they were in the sitting position. After the C-section, an ultrasound-guided bilateral TAP block was performed in these patients in the recovery room for postoperative analgesia. In the single-dose EPI group, the patients received 16 cc of isobaric bupivacaine, 3 mg of morphine, and 50 mcg of fentanyl, making a total volume of 20 cc and being administered to the epidural space.</AbstractText>A higher level of patient satisfaction was observed in the EPI group (p</i>=0.003). The amount (mg) of total analgesics received by the patients in the first 24 hours of the postoperative period was statistically significantly higher (p</i>=0.021) in the TAP group compared to the EPI group. The visual analogue scale (VAS) scores of the EPI group were significantly lower compared to that of the TAP group (p</i> < 0.001).</AbstractText>The epidural anaesthesia is still the golden standard to achieve a postcaesarean analgesia. Epidural anaesthesia is a considerably effective method in controlling the postoperative pain. We are of the opinion that epidural anaesthesia should be preferred in the first place to achieve a successful postcaesarean analgesia as it provides more effective pain control.</AbstractText>
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2,334,782 |
In-depth study of lin-28 suggests selectively conserved let-7 independent mechanism in Drosophila.
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Lin-28 is a conserved RNA-binding protein that is involved in a wide range of developmental processes and pathogenesis. At the molecular level, Lin-28 blocks the maturation of let-7 and regulates translation of certain mRNA targets. In Drosophila, Lin-28 is reported to play a role in oogenesis, muscle formation, and the symmetric division of adult intestinal stem cells. In this study, we characterized Drosophila Lin-28 through a detailed examination of its temporal and spatial expression. Lin-28 is specifically expressed in embryonic nervous and cardiac systems. However, loss or gain of lin-28 function does not cause any abnormality during embryonic development. Instead, the ubiquitous overexpression of Lin-28 leads to lethality from late larval stage to pupal stage, and eye-specific overexpression causes severe cell loss. The ectopic expression of human Lin28A has the same effect as Drosophila Lin-28, indicating functional conservation in Lin-28 orthologs. We also examined the effect of Lin-28 on let-7 biogenesis through the mutant and overexpression analysis. Lin-28 does not block the production of let-7 in Drosophila, which suggests the let-7 independent pathway as a molecular mechanism of Lin-28.
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2,334,783 |
Comparison of Electrocardiographic Biomarkers for Differentiating Drug-Induced Single vs. Multiple Cardiac Ion Channel Block.
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Since introduction of the International Conference on Harmonization proarrhythmia guidelines in 2005, no new marketed drugs have been associated with unacceptable risk of Torsade de Pointes. Although cardiac safety improved, these guidelines had the unintended consequence of eliminating potentially beneficial drugs from pipelines early in development. More recently, it has been shown that a corrected QT (QTc) prolonging drug may be safe if it impacts multiple ion channels vs. only human ether-a-go-go related gene (hERG) and that this effect can be discriminated using QT subintervals. We compared the predictive power of four electrocardiogram (ECG) repolarization metrics to discriminate single vs. multichannel block: (i) traditional 10-second signal averaged triplicates, and (ii) three metrics that used increasing density of automatically measured beat-to-beat (btb) intervals. Predictive power was evaluated using logistic regression and quantified with receiver operating characteristic (ROC) area under the curve (AUC). Compared with the traditional 10-second signal averaged triplicates, the reduction in classification error ranged from 2-6 with increasing density of btb measurements.
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2,334,784 |
Acute Effects of an Ergometer-Based Dryland Alpine Skiing Specific High Intensity Interval Training.
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<b>Introduction:</b> To establish an alpine ski racing (ASR) specific dryland high intensity training protocol (HIT), we set out to analyze cardiorespiratory and metabolic responses of three ASR specific HIT modes using a ski ergometer compared with a running HIT. <b>Methods:</b> Ten healthy international FIS level subjects (18 ± 1 years) performed an incremental running VO<sub>2max</sub> test, three different ASR specific HIT modes [slalom (SL), giant slalom (GS), and SL/GS mix] and a running HIT with measurements of VO<sub>2</sub>, heart rate (HR), blood lactate, and rate of perceived exertion (RPE). The HIT protocols included 15 × 1-min intervals with >90% HR<sub>max</sub> and 30 s active rest. Furthermore, one elite alpine skier performed an 8-week, 17 session HIT block using the SL/GS mixed mode. <b>Results:</b> Running HIT resulted in greater VO<sub>2peak</sub> and whole-body RPE compared with the three ASR-specific HIT modes. During all four exercise modes participants were able to reach exercise intensities high enough to be classified as HIT (>90% HR<sub>max</sub> and >89% VO<sub>2max</sub>). Legs RPE was similar between the four HIT modes, while arms RPE was higher for the ski-specific HIT. For all studied parameters, similar results for the three skiing specific HIT modes were observed. The 8-week HIT block was feasible for the athlete and resulted in an 11% increase in VO<sub>2max</sub> at unchanged peak power output. <b>Conclusion:</b> Across all HIT protocols high cardiorespiratory and metabolic responses were achieved. Therefore, the ASR specific HIT was shown to be feasible, thus could offer new possibilities for endurance training in elite alpine skiers. It is suggested to use the SL/GS mixed mode in terms of movement variety. The reduced VO<sub>2</sub> in the ski-specific modifications can be attributed to the concentric and eccentric muscle activity resulting in mechanical hindrance for O<sub>2</sub> extraction. The long-term effectiveness of ASR specific HIT in elite alpine skiers needs to be proven in a future study.
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2,334,785 |
The metabolite BH4 controls T cell proliferation in autoimmunity and cancer.
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Genetic regulators and environmental stimuli modulate T cell activation in autoimmunity and cancer. The enzyme co-factor tetrahydrobiopterin (BH4) is involved in the production of monoamine neurotransmitters, the generation of nitric oxide, and pain<sup>1,2</sup>. Here we uncover a link between these processes, identifying a fundamental role for BH4 in T cell biology. We find that genetic inactivation of GTP cyclohydrolase 1 (GCH1, the rate-limiting enzyme in the synthesis of BH4) and inhibition of sepiapterin reductase (the terminal enzyme in the synthetic pathway for BH4) severely impair the proliferation of mature mouse and human T cells. BH4 production in activated T cells is linked to alterations in iron metabolism and mitochondrial bioenergetics. In vivo blockade of BH4 synthesis abrogates T-cell-mediated autoimmunity and allergic inflammation, and enhancing BH4 levels through GCH1 overexpression augments responses by CD4- and CD8-expressing T cells, increasing their antitumour activity in vivo. Administration of BH4 to mice markedly reduces tumour growth and expands the population of intratumoral effector T cells. Kynurenine-a tryptophan metabolite that blocks antitumour immunity-inhibits T cell proliferation in a manner that can be rescued by BH4. Finally, we report the development of a potent SPR antagonist for possible clinical use. Our data uncover GCH1, SPR and their downstream metabolite BH4 as critical regulators of T cell biology that can be readily manipulated to either block autoimmunity or enhance anticancer immunity.
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2,334,786 |
A multicenter REtrospective observational study of first-line treatment with PERtuzumab, trastuzumab and taxanes for advanced HER2 positive breast cancer patients. RePer Study.
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We carried out a retrospective observational study of 264 HER2-positive advanced breast cancer (ABC) patients to explore the efficacy of first-line treatment with pertuzumab/trastuzumab/taxane in real-world setting. Survival data were analyzed by Kaplan Meier curves and log rank test. Median follow-up, length of pertuzumab/trastuzumab/taxane treatment and of pertuzumab, trastuzumab maintenance were 21, 4 and 15 months, respectively. The response rate was 77.3%, and the clinical benefit rate 93.6%. Median progression-free survival (mPFS) was 21 months, and median overall survival (mOS) was not reached. When comparing patients by trastuzumab-pretreatment, similar PFS were observed, although a longer OS was reached in trastuzumab-naïve patients (p = 0.02). Brain metastases at baseline and their development in course of therapy were associated with significantly shorter PFS (p = 0.0006) and shorter OS, although at a not fully statistically relevant extent (p = 0.06). The addition of maintenance endocrine therapy (ET) to pertuzumab/trastuzumab maintenance was associated with longer PFS (p = 0.0001), although no significant differences were detected in OS (p = 0.31). Results were confirmed by propensity score analysis (p = 0.003 and p = 0.46, respectively). In multivariate models, longer PFS was related to lower Performance Status (PS) (p = 0.07), metastatic stage at diagnosis (p = 0.006) and single metastatic site (p < 0.0001). An OS advantage was observed with lower PS (p < 0.0001), single metastatic site (p = 0.004), no prior exposure to trastuzumab (p = 0.004) and response to pertuzumab-based treatment (p = 0.003). Our results confirm that trastuzumab/pertuzumab/taxane is the standard of care as first-line treatment of patients with HER2-positive ABC even in the real-world setting. Moreover, the double-maintenance therapy (HER2 block and ET) is strongly recommended when feasible.
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2,334,787 |
Anemia of inflammation.
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Anemia of inflammation (AI), also known as anemia of chronic disease (ACD), is regarded as the most frequent anemia in hospitalized and chronically ill patients. It is prevalent in patients with diseases that cause prolonged immune activation, including infection, autoimmune diseases, and cancer. More recently, the list has grown to include chronic kidney disease, congestive heart failure, chronic pulmonary diseases, and obesity. Inflammation-inducible cytokines and the master regulator of iron homeostasis, hepcidin, block intestinal iron absorption and cause iron retention in reticuloendothelial cells, resulting in iron-restricted erythropoiesis. In addition, shortened erythrocyte half-life, suppressed erythropoietin response to anemia, and inhibition of erythroid cell differentiation by inflammatory mediators further contribute to AI in a disease-specific pattern. Although the diagnosis of AI is a diagnosis of exclusion and is supported by characteristic alterations in iron homeostasis, hypoferremia, and hyperferritinemia, the diagnosis of AI patients with coexisting iron deficiency is more difficult. In addition to treatment of the disease underlying AI, the combination of iron therapy and erythropoiesis-stimulating agents can improve anemia in many patients. In the future, emerging therapeutics that antagonize hepcidin function and redistribute endogenous iron for erythropoiesis may offer additional options. However, based on experience with anemia treatment in chronic kidney disease, critical illness, and cancer, finding the appropriate indications for the specific treatment of AI will require improved understanding and a balanced consideration of the contribution of anemia to each patient's morbidity and the impact of anemia treatment on the patient's prognosis in a variety of disease settings.
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2,334,788 |
Development and internal validation of the multivariable CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) clinical risk prediction model.
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Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care.</AbstractText>A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration.</AbstractText>Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08).</AbstractText>The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.</AbstractText>
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2,334,789 |
[Clinical observation of ultrasound guided popliteal sciatic nerve combined saphenous nerve block for hallux valgus patients with metatarsophalangeal joint dislocation].
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To explore clinical effects of ultrasound guided popliteal sciatic nerve combined saphenous nerve block in patients with anterior foot orthopedics.</AbstractText>From January 2017 to October 2017, 60 hallux valgus patients with metatarsophalangeal joint dislocation were randomly divided into experimental and control group according to random number table. Thirty patients in experimental group were treated by ultrasound guided popliteal sciatic nerve combined saphenous nerve block, including 13 males and 17 females, aged 31 to 76 years old with an average of (59.23±10.07) years old;and body mass index ranged from 21 to 30 kg/m² with an average of (24.57±1.85) kg/m²; 12 cases were grade I and 18 cases were grade II according to ASA grading. Thirty patients in control group were treated by spinal anesthesia, including 12 males and 18 females, aged from 20 to 74 years old with an average of (54.20±15.87) years old; and body mass index ranged from 20 to 29 kg/m² with an average of (24.43 ± 3.15) kg/m²; 11 cases were grade I and 19 cases were grade II according to ASA grading. Block time of anesthesia, onset time of sensory nerve block, onset time of motor nerve block, invalid time of motor nerve block, invalid time of sensory nerve block were compared between two groups. Hemodynamic changes before anesthesia(T₀), 15 min after block(T₁), 30 min after block(T₂), at the beginning of the operation(T₃), 30 min after the beginning(T₄) of surgery and at the end of operation(T₅), adverse reactions and subjective satisfactory between two groups were also recorded.</AbstractText>Both of the anesthetic protocol could achieved satisfied clinical effects. In experimental group, block time of patients, onset time of sensory block, invalid time of motor nerve block and invalid time of sensory nerve block were longer than those in control group, and there were significant differences between two groups(P</i><0.001). There was no significant difference between two groups in onset time of motor nerve block(P</i>> 0.05). There were no significant differences of systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) in experimental group at different time points(P</i>> 0.05). There were significant differences of SBP, DBP in control group at different time points (P</i><0.05). There was no significant difference of HR in control group at different time points(P</i>> 0.05).</AbstractText>Ultrasound guided popliteal sciatic nerve combined saphenous nerve block could meet demand of hallux valgus patients with metatarsophalangeal joint dislocation. Compared with lumbar anesthesia, it could maintain hemodynamic stability, prolong effective analgesia time after operation, and improve patients' overall comfort and safety for free activity above the knee joint.</AbstractText>Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.</CopyrightInformation>
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2,334,790 |
Association Between CHADS<sub>2</sub> Score and the Development of Interatrial Block.
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Interatrial block (IAB) is associated with a multitude of medical conditions. The aim of this retrospective study was to investigate whether CHADS<sub>2</sub> (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) score is positively associated with the development of IAB. A total of 1072 patients (men, 555; women, 517; mean age, 61 ± 14 years) were included in the study. P-wave duration was measured manually using a caliper. IAB was defined as a P-wave duration of ≥ 120 ms on a 12-lead electrocardiogram. CHADS<sub>2</sub> scores were calculated retrospectively. Among the 1072 patients, the prevalence of IAB was 36.1% (387/1072). In multivariate analysis, increased CHADS<sub>2</sub> score (odds ratio [OR], 1.810; 95% confidence interval [CI], 1.577-2.077; P < 0.001), coronary artery disease (OR, 1.536; 95% CI, 1.065-2.216; P = 0.022), and increased left atrial diameter (OR, 1.039; 95% CI, 1.008-1.071; P = 0.013) were independently associated with IAB. The percentages of patients with IAB among those with a CHADS<sub>2</sub> score of 0, 1, 2, 3, 4, 5, and 6 were 20.6%, 33.0%, 45.0%, 55.9%, 61.9%, 77.8%, and 100%, respectively (P < 0.001). There was a greater percentage of patients with a CHADS<sub>2</sub> score of ≥ 2 with IAB compared with a CHADS<sub>2</sub> score of < 2 (26.5% vsrsus 52.0%; P < 0.001). In receiver operating curve (ROC) analysis, CHADS<sub>2</sub> score (area under the curve, 0.670; 95% CI, 0.636-0.704; P < 0.001) was predictive of IAB. In conclusion, CHADS<sub>2</sub> score was significantly associated with the development of IAB in this study population.
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2,334,791 |
Pyridostigmine induced heart block requiring ICU admission.
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Myasthenia gravis is an autoimmune disorder that effects an estimated 20 people per 100,000 in the USA per year. Pyridostigmine is a common drug used in the symptomatic treatment of myasthenia gravis. While generally safe and effective, a rare set of patients treated with pyridostigmine encounter cardiac conduction disorders. Here, we report a rare presentation of an adverse drug reaction due to pyridostigmine, which is important for its implications in the acute care setting.
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2,334,792 |
SNP-based heritability and genetic architecture of tarsal osteochondrosis in North American Standardbred horses.
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Osteochondrosis is a common developmental orthopedic disease characterized by a failure of endochondral ossification. Standardbred horses are recognized as being predisposed to tarsal osteochondrosis. Prior heritability estimates for tarsal osteochondrosis in European Standardbreds and related trotting breeds have been based on pedigree data and range from 17-29%. Here, we report on genetic architecture and heritability based on high-density genotyping data in a cohort of North American Standardbreds (n = 479) stringently phenotyped for tarsal osteochondrosis. Whole-genome array genotyping data were imputed to ~2 million single nucleotide polymorphisms (SNPs). SNP-based heritability of osteochondrosis in this population was explained by 2326 SNPs. The majority of these SNPs (86.6%) had small effects, whereas fewer SNPs had moderate or large effects (10% and 2.9% respectively), which is consistent with a polygenic/complex disease. Heritability was estimated at 0.24 ± 0.16 using two methods of restricted maximum likelihood analysis, as implemented in gcta (with and without a weighted relatedness matrix) and ldak software. Estimates were validated using bootstrapping. Heritability estimates were within the range previously reported and suggest that osteochondrosis is moderately heritable but that a significant portion of disease risk is due to environmental factors and/or genotype × environment interactions. Future identification of the genes/variants that have the most impact on disease risk may allow early recognition of high-risk individuals.
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2,334,793 |
Peripheral nerve block combined with general anesthesia for lower extremity amputation in hemodialysis patients: case series.
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Anesthetic management of lower extremity amputation in chronic hemodialysis (HD) patients can be challenging because of their poor cardiovascular status. As previously reported, peripheral nerve block (PNB) may be beneficial in these complicated cases. We report the effects of PNB combined with general anesthesia on hemodynamic stability in HD patients undergoing elective lower extremity amputation.</AbstractText>We retrospectively analyzed 13 HD patients who underwent lower extremity amputation. Patients received general anesthesia (GA group, n = 7) or general anesthesia combined with PNB (GA with PNB group, n = 6), as decided by the anesthesiologists. Mean blood pressure (MBP), systolic blood pressure (SBP), lowest BP, heart rate (HR), blood loss, fluid and blood infusion volumes, and doses of vasopressors required were compared for hemodynamic assessment. The coefficient of variation ([Formula: see text]) of MBP (CVMBP</sub>) and SBP (CVSBP</sub>) was calculated to compare hemodynamic stability. Intraoperative opioid use and postoperative pain scores at rest using a numerical rating scale (NRS) on postoperative days 0 and 1 were compared for pain assessment. We also assessed 30-day mortality.</AbstractText>CVMBP</sub> in the GA group was significantly higher than that in the GA with PNB group (0.15 ± 0.05 and 0.08 ± 0.04, respectively, p = 0.03). The CVSBP</sub> in the GA group was also significantly higher than that in the GA with PNB group (0.16 ± 0.02 and 0.09 ± 0.01, respectively, p = 0.03). No significant differences in other hemodynamic parameters were observed. Intraoperative fentanyl doses were significantly lower in the GA with PNB group (GA 210.7 ± 99.9 μg vs. GA with PNB 113.0 ± 75.6 μg, p = 0.04). There were no significant differences in other pain parameters and 30-day mortality between the groups.</AbstractText>Our results suggest that PNB combined with general anesthesia contributes to intraoperative hemodynamic stability through better pain control in HD patients undergoing lower extremity amputation.</AbstractText>
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2,334,794 |
[Severe bradycardia and asystole associated with sugammadex: case report].
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Sugamadex is a modified gamma-cyclodextrin, the first selective agent for reversal of neuromuscular blockade induced by steroidal non-depolarizing muscle relaxants, with greater affinity for rocuronium. In this article we present a case of severe bradycardia and asystole following sugammadex administration.</AbstractText>A 54-year-old male patient, ASA II, with a history of hypertension, dyslipidemia and obesity, who underwent an emergency umbilical herniorrhaphy under balanced general anesthesia. Intraoperative muscle relaxation was maintained with rocuronium. At the end of the surgery, the patient maintained a neuromuscular block with two TOF responses, and sugammadex (200 mg) was administered. About thirty seconds after its administration, the patient developed marked bradycardia (HR 30 bpm) followed by asystole.</AbstractText>Documented bradycardia and asystole were attributed to the administration of sugammadex. This case shows that, although rare, cardiac arrest is a possible adverse effect of this drug, and that the knowledge of this situation can be determinant for the patient's evolution.</AbstractText>Copyright © 2018 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.</CopyrightInformation>
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2,334,795 |
Clinical Performance of the DentalVibe® Injection System on Pain Perception During Local Anesthesia in Children.
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<b>Purpose:</b> The purpose of this study was to clinically compare injection pain experience in children using three methods.<b>Methods:</b> This was a randomized clinical trial conducted among 150 children (81 girls, 69 boys), from seven to 14 years of age, who required operative dental treatment. Fifty patients were randomized into one of three groups: DentalVibe<sup>®</sup>, manual stimulation, or no stimulation (control). During the injection, the pulse rate and perceived pain, using the Wong Baker FACES Pain Rating Scale were recorded. Generalized linear models were used to analyze the data.<b>Results:</b> We found a statistically significant decrease in the FACES score in the DentalVibe<sup>®</sup> group compared to the control group and the manual stimulation group (<i>P</i><0.001). Injection type (mandibular inferior alveolar block/long buccal injections versus maxillary infiltration injections) did not differ statistically in pain perception. The heart rate in the DentalVibe<sup>®</sup> group showed no significant difference compared to the other groups at all time points. <b>Conclusion:</b> The DentalVibe<sup>®</sup> may reduce pain for pediatric patients receiving dental injections.
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2,334,796 |
Serratus anterior plane block for minimal invasive heart surgery.
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Minimal invasive heart surgery (MIHS) presents several benefits, but provides intense and prolonged post-operative pain. Our objective was to compare efficacy of serratus anterior plane block (SAPB) with continuous wound infiltration (CWI) for management of post-operative pain following MIHS.</AbstractText>It's retrospective, monocentric study between November 2016 to April 2017. The study was performed at the University hospital of Dijon, Burgundy, France. All patients scheduled for MIHS was included. Data was collected retrospectively. During this period, 20 patients had SAPB and 26 had CWI. SAPB was performed before extubation with a single injection of 0.5 mg/kg of ropivacaïne (5 mg/ml). In the CWI group, catheter was inserted in the subcutaneous space by the surgeon at the end of the procedure. A 10 ml bolus of ropivacaïne (7.5 mg/mL) was followed by a continuous infusion (2 mg/ml) between 7 and 12 ml/h for 48 h. Morphine consumption and visual analog score (VAS) were recorded for 48 h. Length of stay in intensive care unit and hospital was also collected.</AbstractText>Morphine consumption and VAS score were significantly lower in SAPB group (p < 0.01). Length of stay in intensive care and hospital was significantly was decreased in SAPB group.</AbstractText>SAPB appears effective in reducing postoperative MIHS pain.</AbstractText>
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2,334,797 |
Cardiac-specific Mst1 deficiency inhibits ROS-mediated JNK signalling to alleviate Ang II-induced cardiomyocyte apoptosis.
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Apoptosis is associated with various myocardial diseases. Angiotensin II (Ang II) plays a central role in the pathogenesis of RAAS-triggered cardiac apoptosis. Our previous studies showed that mammalian Ste20-like kinase 1 (Mst1) aggravates cardiac dysfunction in cardiomyocyte under pathological conditions, but its role in Ang II-mediated cardiomyocyte apoptosis is not known. We addressed this in the present study by investigating whether cardiac-specific Mst1 knockout can alleviate Ang II-induced cardiomyocyte apoptosis along with the underlying mechanisms. In vitro and in vivo experiments showed that Ang II increased intracellular reactive oxygen species (ROS) production and cardiomyocyte apoptosis; these were reversed by administration of the ROS scavenger N-acetylcysteine and by Mst1 deficiency, which suppressed c-Jun N-terminal kinase (JNK) phosphorylation and downstream signaling. Interestingly, Mst1 knockout failed to alleviate Ang II-induced phosphorylation of extracellular signal-regulated kinase 1/2, and inactivated apoptosis signal-regulating kinase1 (ASK1) by promoting its association with thioredoxin (Trx), which reversed the Ang II-induced activation of the ASK1-JNK pathway and suppressed Ang II-induced cardiomyocyte apoptosis. Thus, cardiac-specific Mst1 knockout inhibits ROS-mediated JNK signalling to block Ang II-induced cardiomyocyte apoptosis, suggesting Mst1 as a potential therapeutic target for treatment of RAAS-activated heart failure.
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2,334,798 |
[Effect of dexmedetomidine on supraclavicular brachial plexus block: a randomized double blind prospective study].
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To evaluate the effect of dexmedetomidine combined with ropivacaine on brachial plexus block in patients scheduled for elective shoulder arthroscopy.</AbstractText>Ninety patients with American Society of Anesthesiologists (ASA) I or II, scheduled for elective shoulder arthroscopy, were randomly divided into three groups. In group R (n=30), the patients were given 10 mL of 0.375% ropivacaine in branchial plexus block (interscalene approach guided by ultrasound), in group D1 (n=30), the patients were given 10 mL of 0.375% ropivacaine (interscalene approach guided by ultrasound) + dexmedetomidine 0.2 μg/(kg×h) (intravenous pump infusion), and in group D2 (n=30), the patients were given 10 mL of 0.375% ropivacaine (interscalene approach guided by ultrasound) + dexedetomidine 0.7 μg/(kg×h) (intravenous pump infusion). To evaluate the effect of brachial plexus block before general anesthesia. Group D1 and group D2 were given dexmedetomidine intravenously for 1.0 μg/kg during 10 min, then the drug was pumped by 0.2 μg/(kg×h) and 0.7 μg/(kg×h) respectively until 30 min before the operation finished. Changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and before anesthesia (T0), 10 min (T1), 30 min (T2) after giving dexmedetomidine, discontinue medication (T3), after operation (T4), and extubation (T5) were investigated. Motor and sensory block onset times, block durations, and duration of analgesia were recorded. The scores of pain after operation and the adverse effects of shiver, hypopiesia, drowsiness, and blood loss were recorded during operation.</AbstractText>Compared with group R, the duration of analgesia and duration of sensory block in group D1 and group D2 were significant longer (P<0.01), there was no significant difference between groups D1 and D2 (P>0.05). Compared with group R, at each time point of T1-T5, the heart rate and systolic blood pressure in group D1 and group D2 were significantly decreased (P<0.01). Compared with D1 group, the incidence of hypotension and bradycardia in group D2 were significantly different (P<0.05).</AbstractText>Intravenous dexmedetomidine could prolong the duration of analgesia time and sensory block within the brachial plexus block, inhibiting the stress response during arthroscopic shoulder surgery. Compared with high-dose, low-dose can provide safer and better clinical effect and reduce the adverse effects of dexmedetomidine.</AbstractText>
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2,334,799 |
Norepinephrine Infusion for Preventing Postspinal Anesthesia Hypotension during Cesarean Delivery: A Randomized Dose-finding Trial.
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Norepinephrine has been recently introduced for prophylaxis against postspinal hypotension during cesarean delivery; however, no data are available regarding its optimum dose. The objective of this study is to compare three infusion rates of norepinephrine for prophylaxis against postspinal hypotension during cesarean delivery.</AbstractText>The authors conducted a double-blinded, randomized, controlled study including full-term pregnant women scheduled for cesarean delivery. Norepinephrine infusion was commenced after subarachnoid block. Patients were randomized into three groups, which received norepinephrine with starting infusion rates of 0.025 μg · kg(-1) · min(-1), 0.050 μg · kg(-1) · min(-1), and 0.075 μg · kg(-1) · min(-1). Infusion was stopped when intraoperative hypertension occurred. The primary outcome was the frequency of postspinal hypotension (defined as decreased systolic blood pressure less than 80% of the baseline reading). The three groups were compared according to the following: systolic blood pressure, heart rate, frequency of intraoperative hypertension, frequency of bradycardia, and neonatal outcomes.</AbstractText>Two hundred eighty-four mothers were included in the analysis. The frequency of postspinal hypotension was lower for both the 0.050-μg · kg(-1) · min(-1) dose group (23/93 [24.7%], odds ratio: 0.45 [95% CI: 0.24 to 0.82], P = 0.014) and the 0.075-μg · kg(-1) · min(-1) dose group (25/96 [26.0%], odds ratio: 0.48 [95% CI:0.26 to 0.89], P = 0.022) compared with the 0.025-μg · kg(-1) · min(-1) dose group (40/95 [42.1%]). The two higher-dose groups (the 0.050-μg · kg(-1) · min(-1) group and the 0.075-μg · kg(-1) · min(-1) group) had higher systolic blood pressure and lower heart rate compared with the 0.025 μg · kg(-1) · min(-1) group. The three groups were comparable in the frequency of intraoperative hypertension, incidence of bradycardia, and neonatal outcomes.</AbstractText>Both the 0.050-μg · kg(-1) · min(-1) and 0.075-μg · kg(-1) · min(-1) norepinephrine infusion rates effectively reduced postspinal hypotension during cesarean delivery compared with the 0.025-μg · kg(-1) · min(-1) infusion rate.</AbstractText>
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