Κυριακή 10 Ιανουαρίου 2021

MicroRNA-520c-3p suppresses vascular endothelium dysfunction by targeting RELA and regulating the AKT and NF-κB signaling pathways

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Abstract

Endothelial injury, which can cause endothelial inflammation and dysfunction, is an important mechanism for the development of atherosclerotic plaque. This study aims to investigate the functional role of miR-520c-3p in vascular endothelium during inflammatory diseases such as atherosclerosis. Quantitative real-time PCR was used to detect miR-520c-3p expression in in human umbilical vein endothelial cells (HUVECs) after treatment with platelet-derived growth factor (PDGF). Furthermore, the effects of miR-520c-3p overexpression and silencing on cell proliferation, adhesion, and apoptosis were assessed. Bioinformatics analysis and Biotin-labeled miRNA pull-down assay were used to confirm the targets of miR-520-3p. Then, the effects of miR-520c-3p on AKT and NF-κB signaling pathways were detected by western blot. Herein, we observed that the expression level of miR-520c-3p was downregulated in HUVECs under PDGF stimulation. Overexpression of miR-520c-3p not only de creased cell adhesion but also promoted proliferation and inhibited apoptosis to protect the viability of endothelial cells. It was confirmed that RELA is the target of miR-520c-3p. MiR-520c-3p inhibited the protein phosphorylation of AKT and RELA, and si-RELA reversed the promotion of AKT and RELA protein phosphorylation by anti-miR-520c-3p. In summary, our study suggested that miRNA-520c-3p targeting RELA through AKT and NF-κB signaling pathways regulated the proliferation, apoptosis, and adhesion of vascular endothelial cells. We conclude that miR-520c-3p may play an important role in the suppression of endothelial injury, which could serve as a biomarker and therapeutic target for atherosclerosis.

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Comorbidities in psoriatic arthritis

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Abstract

The aims of this systematic review and meta-analysis were to: (1) describe the prevalence of commonly reported comorbidities in psoriatic arthritis (PsA), (2) compare the incidence and/or prevalence of comorbidities between PsA and control populations; and (3) examine the impact of comorbidities on PsA outcomes. We systematically searched Medline, PubMed, Scopus, and Web of Science using a predefined protocol in accordance with PRISMA guidelines. Studies reporting only one comorbidity, or a few closely related diseases within one organ system, were excluded. Where possible, meta-analysis was performed using random-effects models. We included 39 studies amounting to over 152 thousand PsA patients. We performed meta-analysis for the prevalence of 21 commonly reported comorbidities. The most prevalent comorbidities were hypertension (pooled prevalence 34%), metabolic syndrome (29%), obesity (27%), hyperlipidaemia (24%) and any cardiovascular diseases (19%). Eleven s tudies consistently showed higher prevalence of comorbidities in PsA than controls. Five studies showed that comorbid patients had more severe disease, poorer quality of life, and increased discontinuation of treatment. Comorbidities, particularly cardiometabolic disorders, were highly prevalent in PsA and more common than in healthy controls. Comorbidities were associated with adverse disease features, but more research is needed on their impact on longitudinal outcomes such as treatment response, work productivity and mortality.

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Antiarrhythmic Treatment Duration and Tachycardia Recurrence in Infants with Supraventricular Tachycardia

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Abstract

We sought to assess the effect of a shorter medication treatment course (up to 4–6 months of age) on the recurrence of infantile supraventricular tachycardia (SVT). This was a retrospective review of infants with SVT diagnosed at age 0–12 months at Rady Children's Hospital (2010–2017). Infants with structural congenital heart disease, automatic tachycardias, atrial flutter, or lack of follow-up data were excluded. Seventy-four infants met criteria. Median age at diagnosis was 6 days (IQR 0–21 days); 28.4% presented with fetal tachycardia. Median gestational age was 38.4 weeks (IQR 36–40), 30% were preterm. Median age at medication discontinuation was 6.7 months (IQR 4.6–9.8). Therapy was stopped at younger age in patients managed by pediatric electrophysiologist (vs. general pediatric cardiologist): 4.9 vs. 8.6 months (p = 0.03). Thirty-eight patients (51.4%) were treated for < 6 months; 32 .4% for 6–12 months, and 16.2% for > 12 months. SVT recurrence was similar for these groups: 13.2% vs. 16.7%, and 33.3%, respectively, (p = 0.27). Most patients with recurrence required emergency care, though none had significant adverse outcomes. Infants with SVT and structurally normal cardiac anatomy, who remain recurrence free on a single agent, have no increased risk of recurrence with shorter treatment courses of 4–6 months, compared to traditional treatment duration of 6–12 months.

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Surgical Timing and Outcomes of Unilateral Versus Bilateral Superior Cavopulmonary Anastomosis: An Analysis of Pediatric Heart Network Public Databases

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Abstract

Requiring bilateral superior cavopulmonary anastomosis (bSCPA) instead of unilateral superior cavopulmonary anastomosis (uSCPA) could influence surgical timing and outcomes. We compared surgical timing and outcomes for patients who underwent uSCPA to those who underwent bSCPA through use of the Pediatric Heart Network's public datasets for the Infant Single Ventricle trial and Single Ventricle Reconstruction trial. There was no statistically significant difference in median age at SCPA (158 vs. 150 days, p = 0.68), hospital length of stay (LOS) (7 vs. 7 days, p = 0.74), intensive care unit (ICU) LOS (4 vs. 5 days, p = 0.53), time requiring ventilator support (2 vs. 2 days, p = 0.51), or oxygen saturation at discharge (82 vs. 81%, p = 0.22) between the uSCPA and bSCPA groups, respectively. However, sub-analysis comparing only those who underwent early SCPA, at < 120 days of age, revealed significantly longer ho spital LOS (8 vs. 13 days, p = 0.04), ICU LOS (5 vs. 11 days, p = 0.01), and time requiring ventilator support (2 vs. 4 days, p = 0.03) for the early bSCPA group when compared to the early uSCPA group. A multivariable logistic regression revealed bSCPA to be the only significant predictor of prolonged hospital LOS for patients who underwent early SCPA (odds ratio 4.1, 95% CI 1.2–14.2). Overall, there was no difference in surgical timing or outcome measures between uSCPA and bSCPA. However, early bSCPA, performed at < 120 days, had worse outcome measures than early uSCPA. Delaying elective bSCPA until at least 120 days of age could minimize morbidity in infants with bilateral superior venae cavae.

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Systemic Artery Vasoconstrictor Therapy in Fontan Patients with High Cardiac Output-Heart Failure: A Single-Center Experience

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Abstract

Failed Fontan Patients with high cardiac output (CO) heart failure (HF) might have vasodilatory syndrome and markedly high mortality rates. The aim of this study was to review the clinical effects of vasoconstrictor therapy (VCT) for failed Fontan hemodynamics. We retrospectively reviewed 10 consecutive patients with Fontan failure (median age, 33 years) and high CO–HF who had received VCT. The hemodynamics were characterized by high central venous pressure (CVP: median, 16 mm Hg), low systolic blood pressure (median, 83 mm Hg), low systemic vascular resistance (median, 8.8 U·m2), high cardiac index (median, 4.6 L/min/m2), and low arterial oxygen saturation (median, 89%). VCT included intravenous noradrenaline infusion for five unstable patients, oral midodrine administration for nine stable patients, and both for four patients. After VCT introduction with a median interval of 1.7 months, the median systolic blood pres sure (102 mm Hg, p = 0.004), arterial oxygen saturation (90%, p = 0.03), and systemic vascular resistance (12.1 U·m2, p = 0.13) increased without significant changes in CVP or cardiac index. After a median follow-up of 21 months, the number of readmissions per year decreased from 4 (1–11) to 1 (0–9) (p = 0.25), and there were no VCT-related complications; however, five patients (50%) developed hepatic encephalopathy, and six patients (60%) eventually died. VCT was safely introduced and could prevent the rapidly deteriorating Fontan hemodynamics. VCT could be an effective therapeutic strategy for failed Fontan patients with high CO–HF.

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On-Air Slips of the Tongue: A Psycholinguistic-Acoustic Analysis

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Abstract

The sixteen SOTs examined are on-air ones produced by native English TV presenters and anchors. Although these SOTs seem funny, they reflect a great deal about how naturalistic speech is assembled and produced. Acoustic analysis is also brought to bear on the present investigation with the aim of providing accurate findings. Several psycholinguistic models are invoked in the analysis, and Praat 6 is used to provide spectrograms and waveforms for the errors detected. The present study concludes that the SOTs examined in the present corpus reveal much about the processing of erroneous speech. Substitution errors, being the most prominent, exhibit uniform processing through a replacement on phonemic or higher levels. As for anticipation errors, they prove to be irregular in their production. Other errors are sparse in the present corpus, and cannot be generalized over a wide range of instances, since they occur either once or twice.

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Characteristics and outcomes of overlap myositis

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Abstract

Overlap myositis (OM), an important subset of idiopathic inflammatory myopathies (IIM), is being increasingly recognized with wider myositis-specific autoantibody (MSA) testing. We studied the differences in clinical characteristics and long-term outcomes of OM with Dermatomyositis (DM), Polymyositis (PM), anti-synthetase syndrome (ASSD), and Cancer-associated IIM (CAM). Data from the MyoCite registry (Dec2017–May2020), a prospective dataset of IIM was extracted for the clinical profile, and MSAs, immunosuppressants received, disease activity (relapses and incomplete response), and treatment-related (drugs ADRs and infections) adverse events (DRAE and TRAE) were collected and analyzed between groups. Of 214 adults (58-OM,89-DM,27-ASSD,33-PM,7-CAM), OM had a greater female preponderance (13.5:1). Raynaud's and sclerodactyly were the prime distinguishing features of OM. OM could be distinguished from PM by frequent arthritis (OR-3.2) and infrequent dysphagia (O R-0.17); DM with greater nephritis (OR-20), infrequent dysphagia (OR-0.24) and rashes (OR-0.02); and ASSD by infrequent ILD (OR-0.07), and mechanic's hand (OR-0.05). 50% fulfilled the classification criteria for ASSD in the absence of MSA testing. ANA was positive more often (PM/DM: OR-6.7) and anti-Ro52 (OR-4.5) frequent in OM. Baseline serum creatinine and acute phase reactants were higher. OM received lower glucocorticoids (0 mg/kg, p < 0.001). Overall, 90% and 84% of OM at 12 and 24 months, respectively, achieved remission, with similar DRAE and TRAE as other IIM subsets. OM can be misdiagnosed as ASSD in the absence of MSA testing. Raynaud's, sclerodactyly, and a positive ANA may identify OM and prevent overtreatment.

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Lung surgery in children and their post-operative risk of respiratory infection

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Abstract

Purpose

Pediatric surgeons at our institution are often asked by families about a theoretical increased risk of severe common upper respiratory infections in children status post lung resection. No data exist on this topic. We, therefore, aimed to examine the risk of severe respiratory infection in children after pulmonary resection.

Methods

A chart review was conducted on all pediatric patients who underwent pulmonary resection between August 1st, 2009 and January 31st, 2019. Collected data included patient characteristics, operation, complications and any admission for respiratory infection.

Results

Fifty-seven patients met inclusion criteria. Resections included lobectomy (45.6%), segmentectomy (14.0%), and wedge resection (40.4%). Twelve (21.1%) were immunocompromised and 6 (10.5%) had post-operative complications. Within 1 year of surgery, 2 (3.5%) patients were hospitalized for a viral upper respiratory illness (URI), 1 (1.8%) for bacterial pneumonia, and none due to influenza.

Conclusion

In the general pediatric population, the risk of admission for respiratory illness is 3–21%. At this institution, overall risk of respiratory infection after lung resection appears comparable to baseline community risk. Our findings could aid counseling pediatric patients and their families regarding the 1-year risk of infection after lung resection.

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Optimal Rex shunt procedures as a treatment for pediatric extrahepatic portal hypertension

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Abstract

Purpose

To assess the long-term results after Rex bypass (RB) shunt and Rex transposition (RT) shunt and determine the optimal approach.

Methods

Between 2010 and 2019, traditional RB shunt was performed in 24 patients, and modified RT shunt was performed in 23 children with extrahepatic portal hypertension (pHTN). A retrospective study was conducted based on comparative symptoms, platelet counts, color Doppler ultrasonography and computed tomographic portography of the portal system, and gastroscopic gastroesophageal varices postoperatively. The portal venous pressure was evaluated intraoperatively.

Results

The operation in the RB group was notably more time-consuming than that in the RT group (P < 0.05). Compared to RT shunt, the reduction in gastroesophageal varix grading, the increases in platelets, and the caliber of the bypass were greater in the RB group (P < 0.05). Although not statistically significant, higher morbidity of surgical complications was found after RT shunt (17.4%) compared with RB shunt (8.3%) with patency rates of 82.6 and 91.7%, respectively. Additionally, patients exhibited a lower rate of rebleeding under the RB procedure (12.5%) than under the RT procedure (21.7%).

Conclusions

The RT procedure is an alternative option for the treatment of pediatric extrahepatic pHTN, and RB shunt is the preferred procedure in our center.

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Usefulness of laparoscopic surgery and preoperative examinations for chronic recurrent small bowel obstruction

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Abstract

Purpose

The aim of this study was to investigate the usefulness of laparoscopic surgery for patients with postoperative abdominal symptoms, including chronic recurrent small-bowel obstruction (SBO), and preoperative examinations of barium follow-through and computed tomography (CT) to predict the postoperative outcomes of laparoscopic surgery.

Methods

Between 2016 and 2018, 49 patients with postoperative symptoms were treated by laparoscopic surgery at our institute. The data from two preoperative examinations were available for 42 patients. The patients were divided into 4 groups: CT-positive (CP, n = 18), barium follow-through-positive (BP, n = 1), both positive (AP [all positive] n = 13), and both negative (AN [all negative], n = 10).

Results

Among the 49 patients, 41 received pure laparoscopic surgery, 7 received laparoscopic-assisted surgery with mini-laparotomy, and 1 required conversion. Intra- and postoperative complications occurred in two and seven patients, respectively. Improvement of abdominal symptoms was observed in 40 patients. In terms of the medium-term outcomes, the rate of improvement of symptoms was poorer in the AN group than in the other three groups, but not to a significant degree.

Conclusion

Laparoscopic surgery was safe and feasible for patients with chronic recurrent abdominal symptoms, including SBO. Furthermore, in patients with negative results on both preoperative examinations, laparoscopic surgery may yield only poor improvement of symptoms.

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Serrated precancerous colorectal lesions

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Abstract

Background

Approximately 60% of colorectal cancer (CRC) precursor lesions are the genuinely-dysplastic conventional adenomas (cADNs). The others include hyperplastic polyps (HPs), sessile serrated lesions (SSL), and traditional serrated adenomas (TSAs), subtypes of a class of lesions collectively referred to as "serrated." Endoscopic and histologic differentiation between cADNs and serrated lesions, and between serrated lesion subtypes can be difficult.

Methods

We used in situ hybridization to verify the expression patterns in CRC precursors of 21 RNA molecules that appear to be promising differentiation markers on the basis of previous RNA sequencing studies.

Results

SSLs could be clearly differentiated from cADNs by the expression patterns of 9 of the 12 RNAs tested for this purpose (VSIG1, ANXA10, ACHE, SEMG1, AQP5, LINC00520, ZIC5/2, FOXD1, NKD1). Expression patterns of all 9 in HPs were similar to those in SSLs. Nine putatively HP-specific RNAs were also investigated, but none could be confirmed as such: most (e.g., HOXD13 and HOXB13), proved instead to be markers of the normal mucosa in the distal colon and rectum, where most HPs arise. TSAs displayed mixed staining patterns reflecting the presence of serrated and dysplastic glands in the same lesion.

Conclusions

Using a robust in situ hybridization protocol, we identified promising tissue-staining markers that, if validated in larger series of lesions, could facilitate more precise histologic classification of CRC precursors and, consequently, more tailored clinical follow-up of their carriers. Our findings should also fuel functional studies on the pathogenic significance of specific gene expression alterations in the initiation and evolution of CRC precursor subtypes.

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