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Introduction

Cystic fibrosis (CF) is a multi-organ disorder characterized by chronic sino-pulmonary infections and inflammation. Many patients with CF suffer from repeated pulmonary exacerbations that are predictors of worsened long-term morbidity and mortality. There are no reliable markers that associate with the onset or progression of an exacerbation or pulmonary deterioration. Previously, we found that the Mirc1/Mir17–92a cluster which is comprised of 6 microRNAs (Mirs) is highly expressed in CF mice and negatively regulates autophagy which in turn improves CF transmembrane conductance regulator (CFTR) function. Therefore, here we sought to examine the expression of individual Mirs within the Mirc1/Mir17–92 cluster in human cells and biological fluids and determine their role as biomarkers of pulmonary exacerbations and response to treatment.

Methods

Mirc1/Mir17–92 cluster expression was measured in human CF and non-CF plasma, blood-derived neutrophils, and sputum samples. Values were correlated with pulmonary function, exacerbations and use of CFTR modulators.

Results

Mirc1/Mir17–92 cluster expression was not significantly elevated in CF neutrophils nor plasma when compared to the non-CF cohort. Cluster expression in CF sputum was significantly higher than its expression in plasma. Elevated CF sputum Mirc1/Mir17–92 cluster expression positively correlated with pulmonary exacerbations and negatively correlated with lung function. Patients with CF undergoing treatment with the CFTR modulator Ivacaftor/Lumacaftor did not demonstrate significant change in the expression Mirc1/Mir17–92 cluster after six months of treatment.

Conclusions

Mirc1/Mir17–92 cluster expression is a promising biomarker of respiratory status in patients with CF including pulmonary exacerbation.  相似文献   
3.

Background

The aim of this study was to evaluate the acute and short-term outcomes of transcatheter closure of secundum atrial septal defect (ASD) in children and adolescents in the first 4-year experience in two institutional centers in Upper Egypt.

Methods

This was a retrospective cohort study including 135 children and adolescents who underwent ASD closure between April 2012 and May 2016. A review of the acute and short-term outcomes and adverse events was performed.

Results

The patients had a median age of 5 years (interquartile range: 3–9 years), 71% of patients were ≤5 years, and median weight was 17 kg (interquartile range: 13–30 kg). Single defects were observed in 113 patients (84%). The remainder had multiple or multifenestrated defects that were closed by a single device. The mean defect size of single defects and the mean interatrial septum length were 15.24 ± 5.16 mm and 38.13 ± 6.3 mm, respectively. The ratio of device to TEE (Transoesophageal echocardiography) size of ASD was 1.19 ± 0.12. The devices were implanted successfully in 98.5% of patients. Six cases had concordant PS (Pulmonary stenosis), patent ductus arteriosus or perimembranous ventricular septal defect and were treated with balloon dilation, or closure. No residual flow was seen after device placement except in one patient with multiple fenestrations. There were five high-severity adverse events (3.7%) with no mortality. Device erosion was confirmed in one of two patients with massive haemopericardium; embolization of the device with retrieval in one patient; and heart block was detected in two cases. No cardiac perforation, device erosion, embolization, thrombus formation, or clinical evidence of bacterial endocarditis was observed during follow-up.

Conclusions

Transcatheter closure of ASDs in children and adolescents was feasible and safe in the first 4 years experience in our centers, with good short-term outcome. Balloon sizing is not necessary for transcatheter closure of secundum ASD. Multiple defects can be safety closed by a single device.  相似文献   
4.
ABO blood group incompatibility (ABO-I) was historically considered an absolute contraindication to kidney transplantation due to the significant risk of acute antibody-mediated rejection and early graft loss. Nevertheless, the urge to minimize the gap between the candidates’ number on the waitlist for kidney transplants and the available kidney donors encourage investigation into finding ways to use organs from ABO-I kidney donors, especially in the era of using more potent immunosuppression therapies. This review aims to discuss a general overview of ABO-I kidney transplantation and the different protocols adopted by some transplant centers to meaningfully overcome this barrier.  相似文献   
5.
Abstract

Background: There are limited data on suicidal behaviour in obsessive-compulsive disorder (OCD). This study aimed to evaluate several aspects affecting suicidality in OCD patients and determine whether impulsivity or hostility are associated with suicide attempts in this vulnerable group.

Methods: Eighty-one patients with OCD were assessed by structured clinical interview for DSM-IV (SCID I), Yale-Brown Obsessive–Compulsive Scale (Y-BOCS), Suicide Probability Scale (SPS), Barratt impulsivity scale-11 (BIS) and Scale for suicide ideation (SSI).

Results: Of the 81 patients, 22 (27%) had suicide ideation, 29 (33%) attempted suicides with OCD and 30 (37%) OCD patients who never experienced suicide ideation nor attempted suicide. Suicide ideation was associated with high hopelessness, higher severity of OCD and the presence of aggressive obsessions. On the other hand, suicide attempts were associated with longer duration of untreated illness, cognitive impulsivity, higher severity of OCD symptoms and the presence of religious obsessions.

Conclusion: Higher severity of OCD symptoms is associated with both suicide ideation and attempts. And while hopelessness was related to suicidal thoughts, cognitive impulsivity may have acted as a facilitating factor for suicide attempts. Higher frequency of symptoms like religious/ aggressive obsessions was also associated with suicidality. It is vital that patients with OCD undergo detailed assessment for suicide risk.
  • Key points
  • OCD is associated with a high risk for suicidal behaviour.

  • Suicide ideation was associated with high levels of hopelessness, OCD severity, and the presence of aggressive obsessions.

  • Suicide attempts were associated with longer duration of untreated illness, cognitive impulsivity, severity of OCD, and the presence of religious obsessions.

  相似文献   
6.
Cancer immunotherapy targeting programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) pathway has shown promising results in treatment of non-small cell lung cancer (NSCLC) patients. T cells play a major role in tumor-associated immune response. This study aimed to investigate PD-L1 expression alone and combined with CD8 tumor infiltrating lymphocytes (TILs) density in relation to clinicopathologic parameters and survival in NSCLC patients. Immunohistochemical analysis was used to evaluate PD-L1 expression and CD8 TILs density in 55 NSCLC patients. PD-L1 immunopositivity was detected in 36 (65.5%) of NSCLC cases. PD-L1 expression was significantly related to high tumor grade (p value?=?0.038) and low CD8 TILs density (p value?=?0.004), whereas no significant relations were detected between PD-L1 expression and tumor stage (p value?=?0.121), overall survival (OS) (p value?=?0.428) and progression-free survival (PFS) (p value?=?0.439). Among PD-L1/CD8 TILs density groups, PD-L1+/CD8Low group was significantly associated with high tumor grade compared to PD-L1?/CD8high group (pairwise p?=?0.016). PD-L1+/CD8Low group was significantly related to advanced tumor stage compared to PD-L1+/CD8high and PD-L1?/CD8Low groups (pairwise p?=?0.001 and 0.013 respectively). PD-L1?/CD8high group exhibited the best OS and PFS whereas PD-L1+/CD8low group had the poorest OS and PFS (p value?=?0.032 and 0.001 respectively). Assessment of PD-L1 combined with CD8 TILs density, instead of PD-L1 alone, suggested important prognostic relevance in NSCLC patients.  相似文献   
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9.
Abstract

Curcumin, the active ingredient of the rhizome curcuma longa has been extensively studied as an anticancer agent for various types of tumours. However, its efficacy as an anticancer agent is restricted due to poor absorption from the gastrointestinal tract, rapid metabolism and degradation in acidic medium. In the present study, we encapsulated curcumin in chitosan-pectinate nanoparticulate system (CUR-CS-PEC-NPs) for deployment of curcumin to the colon, whereby curcumin is protected against degradative effects in the upper digestive tract, and hence, maintaining its anticancer properties until colon arrival. The CUR-CS-PEC-NPs was taken up by HT-29 colorectal cancer cells which ultimately resulted in a significant reduction in cancer cell propagation. The anti-proliferative effect of the encapsulated curcumin was similar to that of free curcumin at equivalent doses which confirms that the encapsulation process did not impede the anticancer activity of curcumin. The oral bioavailability (Cmax, and AUC) of curcumin in CUR-CS-PEC-NPs was enhanced significantly by 4-folds after 6?hours of treatment compared to free curcumin. Furthermore, the clearance of curcumin from the CUR-CS-PEC-NPs was lower compared to free curcumin. These findings point to the potential application of the CUR-CS-PEC-NPs in the oral delivery of curcumin in the treatment of colon cancer.  相似文献   
10.
International Journal of Mental Health and Addiction - This study investigated the effects of COVID-19-related social distancing practices on parents and children’s mental health and explored...  相似文献   
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