scholarly journals Full-Length Transcriptome Sequencing: An Insight Into the Dog Model of Heart Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoyan Liang ◽  
Zechen Bai ◽  
Feifei Wang ◽  
Yafan Han ◽  
Huaxin Sun ◽  
...  
Keyword(s):  
Heart Failure ◽  
Flow Cytometry ◽  
Th17 Cell ◽  
Transcriptome Sequencing ◽  
Full Length ◽  
Control Groups ◽  
Qrt Pcr ◽  
Dog Model ◽  
Th17 Cell Differentiation ◽  
And Control

Heart failure (HF) leads to a progressive increase in morbidity and mortality rates. This study aimed to explore the transcriptional landscape during HF and identify differentially expressed transcripts (DETs) and alternative splicing events associated with HF. We generated a dog model of HF (n = 3) using right ventricular pacemaker implantation. We performed full-length transcriptome sequencing (based on nanopore platform) on the myocardial tissues and analyzed the transcripts using differential expression analysis and functional annotation methods [Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses]. Additionally, we estimated the expression of the selected genes by quantitative real-time PCR (qRT-PCR) and detected the proportion of immune cells using flow cytometry. We found that increased B-type natriuretic peptide reduced ejection fraction, and apparent clinical signs were observed in the dog model of HF. We identified 67,458 transcripts using full-length transcriptome sequencing. A total of 785 DETs were obtained from the HF and control groups. These DETs were mainly enriched in the immune responses, especially Th1, Th2, and Th17 cell differentiation processes. Furthermore, flow cytometry results revealed that the proportion of Th1 and Th17 cells increased in patients with HF compared to controls, while the proportion of Th2 cells decreased. Differentially expressed genes in the HF and control groups associated with Th1, Th2, and Th17 cell differentiation were quantified using qRT-PCR. We also identified variable splicing events of sarcomere genes (e.g., MYBPC3, TNNT2, TTN, FLNC, and TTNI3). In addition, we detected 4,892 transcription factors and 406 lncRNAs associated with HF. Our analysis based on full-length transcript sequencing provided an analysis perspective in a dog model of HF, which is valuable for molecular research in an increasingly relevant large animal model of HF.

The use of peripherally inserted central catheter reduced the incidence of phlebitis in heart failure patients: A randomized trial

2021 ◽  
pp. 112972982110596
Author(s):  
Eunice Vieira Cavalcante Silva ◽  
Marcelo Eidi Ochiai ◽  
Kelly Regina Novaes Vieira ◽  
Antonio Carlos Pereira Barretto
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Severe Heart Failure ◽  
Decompensated Heart Failure ◽  
Venous Access ◽  
Control Group ◽  
Control Groups ◽  
Heart Failure Patients ◽  
Peripheral Venous Access ◽  
And Control

Background: During decompensated heart failure, the use of intravenous inotropes can be necessary. With peripheral venous access, prolonged inotrope infusion can cause phlebitis. However, traditional central venous catheters have possible complications. Peripherally inserted central catheters (PICCs) may be an alternative to traditional catheters. Aim: Our objective was to compare the incidence of phlebitis between patients with PICC and those with peripheral venous access catheter indwelling. Methods: In a randomized clinical trial, the patients were randomized to PICC and control groups, with 40 patients in each group. The inclusion criteria were hospitalized patients with advanced heart failure, ejection fraction of <0.45, and platelet count of >50,000/mm3 and current use of continuous intravenous infusion of dobutamine. The patients were randomly assigned to receive a PICC or keep their peripheral venous access. The primary end point was the occurrence of phlebitis. Results: The PICC and control groups included 40 patients each. The median age was 61.5 years; ejection fraction, 0.24; and dobutamine dose, 7.73 µg/(kg min). Phlebitis occurred in 1 patient (2.5%) in the PICC group and in 38 patients (95.0%) in the control group, with an odds ratio of 0.10% (95% confidence interval: 0.01%–1.60%, p < 0.001). Conclusion: In conclusion, in severe heart failure patients who received intravenous dobutamine, PICC use reduced the incidence of phlebitis when compared to patients with peripheral venous access. Therefore, the PICC use should considered over peripheral venous access for prolonged intravenous therapy in heart failure patients.

Impact of Pharmacy Student and Resident-Led Discharge Counseling on Heart Failure Patients

2013 ◽  
Vol 26 (6) ◽  
pp. 574-579 ◽  
Author(s):  
Andrew Szkiladz ◽  
Katherine Carey ◽  
Kimberly Ackerbauer ◽  
Mark Heelon ◽  
Jennifer Friderici ◽  
...  
Keyword(s):  
Heart Failure ◽  
Medication Errors ◽  
Pharmacy Student ◽  
Control Groups ◽  
Readmission Rates ◽  
Cost Avoidance ◽  
Significant Difference ◽  
Heart Failure Readmissions ◽  
And Control ◽  
The Impact

Purpose: Many health systems have implemented interventions to reduce the rate of heart failure readmissions. Pharmacists have the training and expertise to provide effective medication-related education. However, few studies have examined the impact of discharge education provided by pharmacy students and residents on patients hospitalized with heart failure exacerbations. Methods: This was a nonrandomized intervention study evaluating the impact of a pharmacy student and resident-led discharge counseling program on heart failure readmissions. The primary end point was the 30-day heart failure readmission rate. Secondary end points included self-reported patient understanding of medications, number of medication errors documented, and estimated associated cost avoidance. Results: A total of 86 and 94 patients were enrolled into the intervention and control groups, respectively. No statistically significant difference in readmission rates was detected between the intervention and the control groups. Thirty-four medication errors and discrepancies were documented, or 1 for every 2.5 patients counseled, resulting in an estimated cost avoidance of $4241 for the institution. Eighty-nine percent of patients who received discharge counseling agreed they had a better understanding of their medications after speaking with a pharmacy resident or student. Conclusions: There was no statistically significant difference in readmission rates; however, several medication errors were prevented, and a large percentage of patients expressed an improved understanding of their medications.

Abnormal nailfold videocapillaroscopic findings in heart failure patients with preserved ejection fraction

2020 ◽  
pp. 1-7
Author(s):  
Serkan Yüksel ◽  
Esra Pancar Yüksel ◽  
Murat Meriç
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Control Group ◽  
Preserved Ejection Fraction ◽  
Control Groups ◽  
Nailfold Videocapillaroscopy ◽  
Heart Failure Patients ◽  
Significant Difference ◽  
Patients With Heart Failure ◽  
And Control

BACKGROUND: Microvascular dysfunction is one of the pathophysiological mechanisms in heart failure. Nailfold videocapillaroscopy is a noninvasive technique used to examine the microvasculature. OBJECTIVE: In this study; we aimed to investigate the nailfold capillaroscopic abnormalities in heart failure patients with reduced and preserved ejection fraction and compare those with control group. METHODS: Three groups of patients were recruited for the study: HFrEF group includes the patients with heart failure with reduced ejection fraction (HFrEF), HFpEF group, patients with heart failure with preserved ejection fraction (HFpEF) and control group, healthy asymptomatic individuals. Nailfold videocapillaroscopy was performed with a videodermatoscope and all nailfold images were evaluated for enlargement and hemorrhages. RESULTS: Abnormal videocapillaroscopic findings including enlargement and/or hemorrhages were present in 7 (24%) patients in HFrEF group, 19 (66%) patients in HFpEF group and 11 (37%) in control group. The number of patients with abnormal videocapillaroscopic findings were significantly greater in HFpEF group compared to HFrEF (p <  0.05) and control groups (p <  0.05). However, no significant difference was observed in videocapillaroscopic findings between HFrEF and control groups. CONCLUSIONS: Our study showed that microvascular abnormalities demonstrated by videodermatoscopic examination of nailfold capillaries are considerably more common in HFpEF patients compared to HFrEF and control groups.

scholarly journals circUSP42 Is Downregulated in Triple-Negative Breast Cancer and Associated With Poor Prognosis

2020 ◽  
Vol 19 ◽  
pp. 153303382095082
Author(s):  
Jinling Yu ◽  
Weida Shen ◽  
Jinping Xu ◽  
Bo Gong ◽  
Beimin Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Clinical Stage ◽  
Rank Test ◽  
Circular Rnas ◽  
Sequencing Data ◽  
Control Groups ◽  
Qrt Pcr ◽  
And Control

We previously showed that microRNA-182 (miR-182) might promote cell proliferation and migration in triple-negative breast cancer (TNBC). This study aimed to investigate circular RNAs (circRNAs) that interact with miR-182 and play important roles in TNBC. Thirty patients with TNBC were enrolled. One pair of tumor and adjacent tissue samples (control) were submitted for circRNA sequencing to establish the expression profile of circRNAs. Concomitantly, circRNAs aberrantly expressed between TNBC and control groups were identified, and these differentially expressed circRNAs (DEcircRNAs) were subjected to Gene Ontology and KEGG pathway enrichment analyses, as well as prediction of interactions with miRNAs. The expression levels of 5 circRNAs interacting with miR-182 were validated using qRT-PCR. Associations between the expression of circUSP42 and clinicopathological features and prognosis were evaluated. A total of 825 upregulated and 1127 downregulated DEcircRNAs were identified between tumor and control groups. Upregulated DEcircRNAs were significantly involved in proteoglycans in cancer, and endocytosis. Downregulated DEcircRNAs were involved in the pathway of resistance to EGFR tyrosine kinase inhibitors. Prediction of circRNA-miRNA interactions showed that hsa_circ_0002032, chr6:131973682-132047340+, hsa_circ_0005982, hsa_circ_0007823 (circUSP42), and hsa_circ_0001777 might act as miRNA sponges for miR-182. qRT-PCR showed consistent results with circRNA sequencing data ( P < 0.05). Downregulation of circUSP42 was significantly associated with lymph node metastasis ( P = 0.005) and advanced clinical stage ( P = 0.032). Furthermore, Kaplan-Meier plots showed that low expression of circUSP42 was closely associated with poor outcome (log-rank test, P < 0.001). Our data suggested that dysregulation of circUSP42 might contribute to the development and progression of TNBC.

P4518Cerebral blood flow is lower in heart failure patients with reduced ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Babayigit ◽  
Y Cavusoglu ◽  
M Dural ◽  
K U Mert ◽  
T Ulus ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ejection Fraction ◽  
Control Group ◽  
Mean Flow ◽  
Control Groups ◽  
Reduced Ejection Fraction ◽  
And Control ◽  
Flow Velocities

Abstract Purpose Heart and brain interaction is a well-known entity in heart failure (HF) and left ventricular systolic dysfunction poses an increased risk for stroke and cognitive impairment. Transcranial Doppler (TCD) provides valuable information on cerebral blood flow and detects microembolic signals that can be used to determine the risk of cerebrovascular events. However, less is known about cerebral blood flow in HF patients with reduced EF. So, we aimed to evaluate cerebral blood flow rates by means of TCD in HF patients with reduced ejection fraction (EF). Methods This study included 46 HF patients with an EF less than 35% (mean age 65.2±11 years, mean EF 20.1±3.8%) who underwent to TCD examination. In addition, 26 healthy individuals with sinus rhythm and EF >50% (mean age 64.4±9.0 years, mean EF 63.5±2.38%) were included in the study as a control group. Minimum, maximum and mean flow velocities of the both right middle cerebral artery (RMCA) and left middle cerebral artery (LMCA) determined by TCD were analyzed. Results The average of RMCA maximum and mean flow velocities were found to be significantly lower in HF patients than those in control group (76,06±23,7 cm/s and 48,49±16,4 cm/s in HF group vs 87,84±14,5 cm/s and 56,41±10,7 cm/s in control group, p=0,025 and p=0,016, respectively). The average of LMCA maximum and mean flow velocities were also significantly lower in HF patients than those in control group (75,1±22,3 cm/s and 47,57±14.8 cm/s in HF group vs 88,73±17,7 cm/s and 57,15±12,4 cm/s in control group, p=0,009 and p=0,007, respectively). However, there was no significant difference in minimum RMCA or LMCA flow velocities between HF group and control groups (33,5±10,6 cm/s and 32,86±9,58 cm/s in HF group vs 36,34±9,2 cm/s and 36,53±10,4 cm/s in control group, p=0,226 and p=0,157, respectively). No significant microembolic signals were detected in HF and control groups. Conclusions The results of this study showed that HF patients with reduced EF have lower cerebral blood flow velocities as compared to healthy controls, which might be one of the explanations of the adverse interaction between heart and brain in HF.

scholarly journals Exosomes Derived from Stem Cells from Apical Papilla Ameliorate Sjogren's Syndrome by Suppressing Th17 Cell Differentiation

2021 ◽  
Author(s):  
Aochen Wang ◽  
Jie Liu ◽  
Si Yu ◽  
Xuemei Liu ◽  
Xueying Zhuang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Cell Differentiation ◽  
Th17 Cell ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Lymphocyte Infiltration ◽  
Th17 Cell Differentiation ◽  
Apical Papilla

Abstract Background: Sjogren's syndrome (SS) is a chronic autoimmune disease that is characterized by progressive lymphocyte infiltration and a decrease in the secretory function of the salivary glands. Mesenchymal stem cell (MSCs) transplantation has shown great potential in the treatment of SS. Exosomes are one of the key paracrine factors that allow MSCs to perform their functions, and are more stable and safer than MSCs. Stem cells from apical papilla (SCAP), a kind of dental stem cells that are derived from the neural crest, have a wide range of immunoregulatory properties. However, the roles of exosomes derived from SCAP (SCAP-Exo) in the treatment of SS are not clear. This study investigated the effects of SCAP-Exo on ameliorating SS and the underlying mechanisms.Methods: SCAP-Exo were isolated and characterized by western blotting, transmission electron microscopy and nanoparticle tracking analysis. SCAP-Exo were systemically infused into SS mice via the tail vein. H&E staining, saliva flow rate tests, flow cytometry and enzyme-linked immunosorbent assays (ELISA) were performed to verify the therapeutic effects of SCAP-Exo. PIWI-interacting RNA (piRNA) array analysis was conducted to determine the piRNA expression profiles of SCAP-Exo, and the key pathways were analysed. A luciferase reporter assay was performed to reveal the molecular role of the exosomal hsa-piR-15254 target interleukin-6 receptor (IL-6R). Furthermore, the molecular mechanism by which hsa-piR-15254 regulated T helper 17 (Th17) cell differentiation in vitro was tested by flow cytometry, ELISA, and reverse transcription-quantitative polymerase chain reaction.Results: We found that SCAP-Exo transplantation successfully improved saliva secretion, alleviated lymphocyte infiltration in the submandibular glands and reduced the proportion of Th17 cells in SS mice. Mechanistically, hsa-piR-15254 was enriched in SCAP-Exo; a luciferase reporter assay demonstrated that hsa-piR-15254 directly targeted the IL-6R mRNA 3’ untranslated region. Furthermore, we revealed that hsa-piR-15254 inhibited Th17 differentiation and downregulated the level of IL-17A in the supernatant and the expression levels of Th17-related genes in vitro.Conclusion: This study demonstrated that SCAP-Exo had a superior therapeutic effect on SS by inhibiting Th17 cell differentiation. These data suggested that SCAP-Exo could be used in a cell-free approach for the clinical treatment of autoimmune disease.

Abstract 109: Transparent Plastic Medication Bag to Improve Medication Reconciliation and Transitional Care In Geriatric Patients With Heart Failure At the time of Discharge from Heart Failure Quality Improvement Prospective Cohort Study in Harlem, New York

2017 ◽  
Vol 10 (suppl_3) ◽  
Author(s):  
Hong Seok Lee ◽  
Keerthana Paladugu ◽  
Hans Cativo ◽  
Ayoola Oladejo ◽  
Sophi Lin
Keyword(s):  
Heart Failure ◽  
Cohort Study ◽  
Medication Reconciliation ◽  
Geriatric Patients ◽  
Resident Physician ◽  
Control Groups ◽  
Transparent Plastic ◽  
Patients With Heart Failure ◽  
Heart Failure Exacerbation ◽  
And Control

Background: Heart failure readmission has been national public health problems for many years. Medication reconciliation in elderly patients is important because the impact of medication intervention in elderly is critical to reduce readmission. There was no enough study to assess readmission or emergency room visit for elderly patients after resident physician level medication reconciliation at the time of discharge. The aim of this study is to determine whether providing a bag to hospitalized geriatric patients for heart failure exacerbation at the time of discharge will improve the rate of hospital readmission or visiting emergency department within 30 days after hospital discharge. Method: We conducted a randomized prospective cohort study with 265 patients with heart failure exacerbation above 65 years of age for one year. When patients were discharged to home, the family member or home attendants were called to bring all bottles to the hospital prior to discharge. Patients and their caregivers were educated by residents in charge about the discharge medications to bring the medications to their next clinic visits. We designed small transparent plastic bags for patients to recognize the medication easily through the bag. The interventional group was provided with a plastic bag to carry the newly reconciled medications along with teaching about the medications and the control group was only given information about their medications. Results: 265 patients with heart failure exacerbation for admission were enrolled in our study. The mean age in our study population was 73.4±8.1 and 74.8±8.1 years old in the intervention and control groups, respectively (P=0.82). There was 66/141 (46.8%) and 63/124(54.8%) males in the intervention and control groups, respectively (P = 0.81). 3/141(2.12 %) of intervention patients and 7/124(5.64%) of control patients were readmitted (P = 0.11). And 2/124(1.61 %) of control patients and 0/141(0.0%) of intervention patients revisited walk-in clinic respectively (P = 0.13). There were no reported adverse medication events. Conclusion: In this study, the use of a bag to facilitate medication reconciliation at the level of medical resident physician was not associated with a significant difference in unplanned readmissions or in revisiting walk-in clinics within 30 days after discharge. We may conclude that patients with chronic medical condition might not be reversible only by medication reconciliation. It may need personalized discharge planning as well as medication reconciliation beyond only physician level because heart failure patients were basically at the high risk of readmission by themselves.

scholarly journals Features of Microparticle-Associated Procoagulant Activity in Patients with Thrombocytopenias of Immune and Central Origin

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1462-1462
Author(s):  
Nora V. Butta ◽  
M T Alvarez Román ◽  
Ihosvany Fernández Bello ◽  
Elena Arias-Salgado ◽  
Raquel de Paz ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Platelet Count ◽  
Plasma Levels ◽  
Procoagulant Activity ◽  
Monocyte Count ◽  
Red Cell ◽  
Control Groups ◽  
Platelet Destruction ◽  
Central Origin ◽  
And Control

Abstract Introduction: The risk of bleeding in patients with thrombocytopenia is increased with platelet counts less than 20 or 30 x 109/L. Nevertheless, some patients with thrombocytopenia of peripheral and central origin (immune thrombocytopenia [ITP] and myelodysplastic syndromes [MDS] respectively) have fewer bleeding symptoms than expected. This fact suggests there may be compensatory mechanisms for the thrombocytopenia, such as the presence of microparticles (MPs). Objective: The aim of this study was to evaluate and characterize the microparticle-associated procoagulant activity in ITP and MDS patients with thrombocytopenia. Methods: Thirty-five patients with chronic ITP and twenty-six patients with MDS with a platelet count less than 50 x109/L and twenty-five healthy controls were included. Blood cell counts were determined with a Coulter Ac. T Diff cell counter (Beckman Coulter, Madrid, Spain). Citrated blood was centrifuged at 1,500 g for 15 min at 23°C. Platelet-poor plasma obtained was additionally centrifuged twice at 23°C (15 min at 1,500 g, and 2 min at 13,000 g, [PFP]) and aliquots were stored at -70ºC until analysis. Phosphatidylserine-MP (Ph-MP) and tissue factor-MP (TF-MP)-dependent procoagulant activities were determined with the ZYMUPHEN kits (Hyphen BioMed, Neuville sur Oise, France) following the manufacturer’s instructions. The identification of MP’s cell origin was determined by flow cytometry labeling MPs with Annexin-V-fluorescein and the following specific monoclonal antibodies (mAb) conjugated with phycoerythrin: anti CD41 mAb for platelets, anti CD14 mAb for monocytes, anti CD144 mAb for endothelial cells, anti CD235 mAb for red cells and anti CD45 mAb for leukocytes. APRIL plasma levels were determined by ELISA (DuoSet ELISA, R&D Systems, Minneapolis, MN, USA). Results: Ph-MP associated procoagulant capacity in MDS and ITP patients was higher than in controls (p<0.01) whereas MP-TF associated procoagulant activity was only increased in MDS patients and practically negligible in ITP and control groups (p<0.01). MPs analysis by flow cytometry of seventeen controls, twenty ITP and six MDS patients showed that ITP patients had an increased percentage of MPs from platelets and red cells, whereas MDS had an increased percentage of monocytes derived MPs. Proportion of MPs derived from other cell types were similar to the control group. Increased percentage of monocyte-derived MPs in MDS patients is in accordance with the higher MP-TF-associated capacity observed in this group since monocytes are tissue factor rich cells. Nevertheless, no differences were found in monocyte count with control and ITP groups and monocyte count did not correlate with MPs associated procoagulant activity and the percentage of monocyte-derived MPs. In the ITP group neither MP-Ph-associated procoagulant activity nor the percentage of red cell-derived MPs correlated with red cell count. On the contrary, MP-Ph-associated procoagulant activity and the percentage of platelet-derived MPs inversely correlated with platelet count. ITP is an antibody-mediated autoimmune disease characterized by accelerated platelet destruction. A proliferation-inducing ligand (APRIL) is a factor that promotes B-cell maturation and survival. All patients with ITP and thrombocytopaenia showed higher APRIL plasma levels than MDS and control groups (p<.01), which inversely correlated with platelet count and correlated to MP-Ph-associated procoagulant activity. These observations support the proposed pathogenic role of APRIL in the development of this disease and that the increase in platelet-derived MPs was due to peripheral platelet destruction. Conclusion: Peripheral and central thrombocytopenias might present a MP-associated procoagulant activity to compensate bleeding risk present in these patients. Cellular origin of these MPs differed according to thrombocytopaenia etiology. Disclosures No relevant conflicts of interest to declare.

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