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Surgical repair of Tetralogy of Fallot (TOF) involves a series of steps to remove right ventricular outflow tract and pulmonary artery obstruction. However, the large degree of anatomic variability among preoperative TOF patients may impact the effectiveness of different repair strategies and, subsequently, different geometric modifications for different patients. Metabolism inhibitor This study investigates the relationships between geometric and hemodynamic parameters and mechanical energy efficiency for a patient-specific dataset of 16 postoperative TOF repairs, using morphometric and statistical shape analyses, as well as computational fluid dynamics simulations with physiologically-relevant inlet and outlet boundary conditions. Quantitatively, negative correlations were found between the right and left pulmonary artery centerline tract cumulative torsion and energy efficiency (r = - 0.65, p = 0.01, for both). A positive correlation was also found for a statistical shape mode associated with skewing of the geometric sub-regions (r = 0.61, p = 0.01). Qualitatively, medium- and low-efficiency geometries exhibit disturbed flow and much more proximal vortex formation as compared to a high-efficiency geometry. Thus, it is recommended, as much as possible, to both relieve and avoid the introduction of torsion into the patient's anatomy during surgical repair of TOF.Ischemic mitral regurgitation (IMR) is a prevalent cardiac disease associated with substantial morbidity and mortality. Contemporary surgical treatments continue to have limited long-term success, in part due to the complex and multi-factorial nature of IMR. There is thus a need to better understand IMR etiology to guide optimal patient specific treatments. Herein, we applied our finite element-based shape-matching technique to non-invasively estimate peak systolic leaflet strains in human mitral valves (MVs) from in-vivo 3D echocardiographic images taken immediately prior to and post-annuloplasty repair. From a total of 21 MVs, we found statistically significant differences in pre-surgical MV size, shape, and deformation patterns between the with and without IMR recurrence patient groups at 6 months post-surgery. Recurrent MVs had significantly less compressive circumferential strains in the anterior commissure region compared to the recurrent MVs (p = 0.0223) and were significantly larger. A logistic regression analysis revealed that average pre-surgical circumferential leaflet strain in the Carpentier A1 region independently predicted 6-month recurrence of IMR (optimal cutoff value - 18%, p = 0.0362). Collectively, these results suggest greater disease progression in the recurrent group and underscore the highly patient-specific nature of IMR. Importantly, the ability to identify such factors pre-surgically could be used to guide optimal treatment methods to reduce post-surgical IMR recurrence.Developmental coordination disorder (DCD) is often comorbid with attention-deficit/hyperactivity disorder (ADHD). While children with DCD engage in less moderate-to-vigorous physical activity (MVPA) compared to typically developing (TD) children, research pertaining to how ADHD affects this relationship is limited. We investigated the effect of ADHD on MVPA among children at risk for DCD (DCDr). 507 children aged 4-5 years (DCDr = 233, TD = 274) participated. Motor skills were assessed using the Movement Assessment Battery for Children-2nd edition (DCDr; ≤ 16th percentile), ADHD symptoms were assessed using the Child Behaviour Checklist, and Actigraph accelerometers measured MVPA over seven days. DCD did not negatively affect MVPA, however, after adjusting for ADHD symptoms, the effect of DCD became significant and was driven by symptoms of inattention. Symptoms of ADHD may be suppressing the negative effects of DCD on MVPA, highlighting the importance of assessing and controlling for ADHD symptoms in this population.MiR-499a-5p was significantly downregulated in degenerative tissues and correlated with apoptosis. Nonetheless, the biological function of miR-499a-5p in acute ischemic stroke has been still unclear. In this study, we found that the plasma levels of miR-499a-5p were significantly downregulated in 64 ischemic stroke patients and negatively correlated with the National Institutes of Health Stroke Scale score. Then, we constructed cerebral ischemia/reperfusion (I/R) injury in rats after middle cerebral artery occlusion and subsequent reperfusion and oxygen-glucose deprivation and reoxygenation (OGD/R)-treated SH-SY5Y cell model. Transfection with miR-499a-5p mimic was accomplished by intracerebroventricular injection in the in vivo I/R injury model. We further found that miR-499a-5p overexpression decreased infarct volumes and cell apoptosis in the in vivo I/R stroke model using TTC and TUNEL staining. PDCD4 was a direct target of miR-499a-5p by luciferase report assay and Western blotting. Knockdown of PDCD4 reduced the infarct damage and cortical neuron apoptosis caused by I/R injury. MiR-499a-5p exerted neuroprotective roles mainly through inhibiting PDCD4-mediated apoptosis by CCK-8 assay, LDH release assay, and flow cytometry analysis. These findings suggest that miR-499a-5p might represent a novel target that regulates brain injury by inhibiting PDCD4-mediating apoptosis.More than 2.5 million people in the United States develop pressure injuries annually, which are one of the most common complications occurring in hospitals. Despite being common, hospital-acquired pressure injuries (HAPIs) are largely considered preventable by regular patient turning. Although current methodologies to prompt on-time repositioning have limited efficacy, a wearable patient sensor has been shown to optimize turning practices and improve clinical outcomes. The purpose of this study was to assess the cost-effectiveness of patient-wearable sensor in the prevention of HAPIs in acutely ill patients when compared to standard practice alone. A decision analytic model was developed to simulate the expected costs and outcomes from the payer's perspective using data from published literature, including a recently published randomized controlled trial. Both univariate and probabilistic sensitivity analysis were conducted. The patient-wearable sensor was found to be cost saving (dominant). It resulted in better clinical outcomes (77% reduction in HAPIs) compared to standard care and an expected cost savings of $6,621 per patient over a one-year period. Applying the model to a cohort of 1,000 patients, an estimated 203 HAPIs would be avoided with annualized cost reduction of $6,222,884 through all patient treatment settings. The probabilistic analysis returned similar results. In conclusion, the patient-wearable sensor was found to be cost-effective in the prevention of HAPIs and cost-saving to payers and hospitals. These results suggest that patient-wearable sensors should be considered as a cost-effective alternative to standard care in the prevention of HAPIs.

Cancer progression following chemotherapy is a significant barrier to effective cancer treatment. We aimed to evaluate the role of drug-exposed cancer-associated fibroblasts (CAFs) in the growth and progression of drug-exposed gastric cancer (GC) cells and to explore the underlying molecular mechanism.

The human GC cell line 44As3 and CAFs were treated with 5-fluorouracil and oxaliplatin (5FU + OX). 5FU + OX-pretreated 44As3 cells were then cultured in a conditioned medium (CM) from 5FU + OX-pretreated CAFs, and the growth and migration/invasion ability of the cells were evaluated. We also compared the clinicopathological characteristics of the GC patients treated with S1 + OX in accordance with the properties of their resected specimens, focusing on the number of CAFs. Changes in gene expression in CAFs and 44As3 cells were comprehensively analyzed using RNA-seq analysis.

The CM from 5FU + OX-pretreated CAFs promoted the migration and invasion of 5FU + OX-pretreated 44As3 cells. Although the number of cases was relatively small (n = 21), the frequency of positive cases of lymphovascular invasion and the recurrence rate were significantly higher in those with more residual CAF. RNA-seq analysis revealed 5FU + OX-pretreated CAF-derived glycoprotein 130 (gp130) as a candidate factor contributing to the increased migration of 5FU + OX-pretreated 44As3 cells. Administration of the gp130 inhibitor SC144 prevented the increased migration ability of 5FU + OX-pretreated 44As3 cells owing to drug-treated CAFs.

Our findings provide evidence regarding the interactions between GC cells and CAFs in the tumor microenvironment following chemotherapy, suggesting that ligands for gp130 may be novel therapeutic targets for suppressing or preventing metastasis in GC.

Our findings provide evidence regarding the interactions between GC cells and CAFs in the tumor microenvironment following chemotherapy, suggesting that ligands for gp130 may be novel therapeutic targets for suppressing or preventing metastasis in GC.Lynch syndrome is an inherited cancer predisposition syndrome caused by germline defects in any of the mismatch repair (MMR) genes. Diagnosis of carriers makes precision prevention, early detection, and tailored treatment possible. Herein we report a novel founder deletion of 18,758 bp, mediated by Alu repeats on both sides, detected in Ethiopian Jews. The deletion, which encompasses exon 9-10 of the MSH2 coding sequence, is associated mainly with early-onset MSH2/MSH6-deficient colorectal cancer (CRC) and liposarcoma. Testing of 35 members of 5 seemingly unrelated families of Ethiopian origin yielded 10/21 (48%) carriers, of whom 9 had CRC. Age at first tumor diagnosis ranged from 16 to 89 years. Carriers from the oldest generations were diagnosed after age 45 years (mean 57), and carriers from the younger generation were diagnosed before age 45 years (mean 30). Awareness of this founder deletion is important to improve patient diagnosis, institute surveillance from an early age, and refer patients for genetic counseling addressing the risk of bi-allelic constitutional MMR deficiency syndrome.The purpose of the study was to characterize repetitive phenomena in Williams syndrome (WS). The parents of 60 subjects with WS completed the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) or Children's Y-BOCS, the Yale Global Tic Severity Scale, the Stereotyped Behavior Scale, and the Spence Children's Anxiety Scale-Parent Version. Nineteen males and 41 females participated in the study. Six subjects (10%) had obsessions only, six (10%) had compulsions only, and eleven (18%) had at least one obsession and at least one compulsion. None of the subjects had tics. Fifty subjects (83.3%) endorsed at least one stereotypy. Increased anxiety was associated with increased severity of obsessions, but not severity of compulsions or stereotypies.Recent guidelines for diagnosing acute pulmonary embolism (PE) are based on clinical decision rules and D-dimer. D-dimer measurement is recommended only for patients who are 'PE-unlikely'. We aimed to assess the current guidelines for cancer patients and to determine an optimal D-dimer cut-off level. This retrospective observational study was conducted in the emergency department of Asan Medical Center (Seoul, Korea) between 02/2017 and 09/2017 for the development cohort and between 06/2018 and 02/2019 for the validation cohort. Among adult active cancer patients with suspected PE, we included those who were 'PE-unlikely' according to Wells' criteria and who underwent D-dimer testing and computed tomographic pulmonary angiography (CTPA). A total of 498 patients (227 in the development cohort and 271 in the validation cohort) were included, and PE was diagnosed in 8.8% and 18.5% of patients, respectively. The optimal D-dimer cut-off level was 2.0 μg/mL. This elevated cut-off level showed a much higher specificity of 21.