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A close follow-up by a dedicated aortic clinic is mandatory so that patients are referred for surgery when necessary.Reoperation after pediatric mitral valve replacement (MVR) is inevitable due to patient-prosthesis mismatch (PPM) associated with somatic growth. We analyzed potential metrics for PPM and outcomes of redo MVR for valve upsizing. Between 1999 and 2018, 15 children without obstructive left heart lesions other than mitral stenosis underwent initial MVR with a 16-mm ATS-Advanced Performance valve. We analyzed hemodynamic data from 28 postoperative catheterizations and concomitant echocardiograms. The median age and body weight at initial MVR were 4.9 months (25th, 75th percentile 3.6, 6.6) and 5.9 kg (5.0, 7.3). Redo MVR was planned when patients had congestive heart failure and postcapillary pulmonary hypertension (PH) due to PPM systolic pulmonary arterial pressure (SPAP) >35 mm Hg and pulmonary capillary wedge pressure (PCWP) >15 mm Hg on catheterization. Indexed effective orifice area (iEOA) and mean transmitral pressure gradient (TMPG) were strongly correlated with SPAP (r = -0.72, P less then 0.001 and r = 0.75, P less then 0.001) and PCWP (r = -082, P less then 0.001 and r = 0.84, P less then 0.001). Cut-off values for detecting postcapillary PH due to PPM were 1.0 cm2/m2 for iEOA and 18 mm Hg for mean TMPG. Nine patients underwent redo MVR for postcapillary PH due to PPM at a median postoperative interval of 10 years (9.2, 11.9). All the patients survived, and PH was improved one year after surgery. iEOA and mean TMPG can be metrics for PPM in children after MVR. Careful follow-up is required to confirm the improvement of preoperatively existing PH after redo MVR for valve upsizing.Mutations in PARK7, the gene encoding the DJ-1 protein, are associated with early onset of Parkinson's disease. The C106 residue of DJ-1 is highly susceptible to oxidation, and its oxidation status is essential for various in vivo neuroprotective roles. Since C106 is readily oxidized to sulfinic acid that is not reduced by dithiothreitol, no method to separate native DJ-1 protein from the oxidized one creates challenges in the in vitro study of the biological relevance of C106-oxidation state. Here, we report an efficient column chromatography method to purify native, C106-sulfinic, and mixed (combination of the priors) forms of DJ-1. This method will be useful for systematic in vitro studies of DJ-1 functions by providing specific native and C106-sulfinic DJ-1 proteins.Clusterin (CLU) is a glycoprotein that contains α- and β-chains. CLU exerts multifunctional activities and plays a role in different cell signaling pathways that are associated with various diseases such as proteotoxic and oxidative stress, as well as cell death and survival. However, its role in marine teleost fish remains unclear. Therefore, the present study was carried out to characterize and investigate the immune responses and anti-apoptotic effects of CLU of the big-belly seahorse (Hippocampus abdominalis) (HaCLU) on oxidative stress-induced cell death. The HaCLU open reading frame was 1389 bp long and encoded a protein with 462 amino acids, a molecular weight of 51.28 kDa and an isoelectric point of 5.41. In-silico results demonstrated that HaCLU has a signal peptide in the 1-29 amino acid region, while the α- and β-chains were in the 34-227 and 228-455 amino acid regions, respectively. Multiple sequence alignment clarified the low homology of the α-chain with other orthologs. The highest HaCLU mRNA expression level was observed in the liver, followed by the heart, spleen, and brain tissues of healthy big-belly seahorses. Further, HaCLU mRNA expression level was elevated in the liver in response to different stimuli, including lipopolysaccharides, polyinosinicpolycytidylic acid, Edwardsiella tarda, and Streptococcus iniae. HaCLU potentiates cell viability and weakens chromatin condensation in the nucleus of FHM cells following H2O2-induced oxidative stress and subsequent cell death. HaCLU overexpression resulted in a reduced Bax/Bcl-2 mRNA expression ratio. This study revealed the role of HaCLU in immune regulation against pathogenic infections and its anti-apoptotic effects on oxidative stress-induced cell death.Grouper iridovirus is a devastating pathogen that belongs to the genus Ranavirus. Based on the previous results that natural ingredient quercetin isolated from Illicium verum Hook. f. could effectively inhibit Singapore grouper iridovirus (SGIV) replication, suggesting that quercetin could serve as potential antiviral agent against grouper iridovirus. To know about whether quercetin has indirect antiviral activity against SGIV, this study made the investigation in vitro and in vivo, and the potential mechanism was also explored. Pretreating the cells with quercetin (12.5 μg/mL) significantly inhibited the replication of SGIV, similar results were also confirmed in vivo. Importantly, quercetin pretreatment could induce the expression of genes involved in type I interferon (IFN) system (IFN, STAT1, PKR, MxI and ISG15) and TLR9. It suggested that quercetin exerted the indirect antiviral activity against SGIV infection through promoting the recognition of SGIV and activating the IFN pathway to establish the antiviral status of host cell. Taken together, our results shedded light on the indirect antiviral function of natural ingredient quercetin, and clearly demonstrated that natural ingredient quercetin will be an excellent potential agent against SGIV infection in grouper aquaculture.The purpose of this study was to evaluate the effects of Cetobacterium somerae XMX-1 fermentation product on gut and liver health and resistance against bacterial infection in genetically improved farmed tilapia (GIFT, Oreochromis niloticus). Fingerling GIFTs (n = 120; initial weight 1.33 ± 0.00 g) were randomly assigned to twelve 90-L tanks (four tanks per diet, 10 fish per tank) with three groups control group (basal high fat diet), 1% XMX-1 group and 2% XMX-1 group (basal diet supplemented with 10 and 20 g XMX-1/kg feed respectively). After 49 days feeding trial, the growth performance and gut and liver health parameters of tilapia were evaluated. Also the gut microbiota and virome were detected by sequencing. 2% XMX-1 fermentation product had no effect on growth performance. For gut health, the expression of hypoxia-inducible factor-lα (Hif-1α) tend to increase in 1% XMX-1 group (P = 0.053). The expression of intestinal interleukin-6 (IL-6) and tumor growth factor β (TGF-β) was significantly down-regulatechallenge was delayed in 1% XMX-1 and 2% XMX-1 groups compared with control. To sum up, our results show that the dietary supplementation of XMX-1 fermentation product can improve the gut and liver health as well as the resistance against pathogenic bacteria of tilapia.G-protein coupled receptor (GPCR) kinases (GRKs) and β-arrestins play key roles in GPCR and non-GPCR cellular responses. In fact, GRKs and arrestins are involved in a plethora of pathways vital for physiological maintenance of inter- and intracellular communication. Here we review decades of research literature spanning from the discovery, identification of key structural elements, and findings supporting the diverse roles of these proteins in GPCR-mediated pathways. We then describe how GRK2 and β-arrestins partake in non-GPCR signaling and briefly summarize their involvement in various pathologies. We conclude by presenting gaps in knowledge and our prospective on the promising pharmacological potential in targeting these proteins and/or downstream signaling. Future research is warranted and paramount for untangling these novel and promising roles for GRK2 and arrestins in metabolism and disease progression.

Anaplastic thyroid carcinoma (ATC) was a rare and extremely malignant endocrine cancer. Recently, dysregulation of circadian rhythm genes was demonstrated to play an essential role in tumor progression, while its exact role and mechanism in ATC remained poorly clear.

4 ATC-related datasets were integrated to screen for differentially expressed circadian rhythm genes (DE-CRGs). Thereafter, Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) and network enrichment analysis were conducted to investigate the dynamic characteristics of circadian rhythm genes. Next, Lasso-logistic model and immunohistochemistry were applied for determining the candidates. 2,4-Thiazolidinedione clinical trial Finally, cell biological experiments and gene set enrichment analysis (GSEA) were used to confirm the roles of NPAS2 in ATC.

25 DE-CRGs were firstly identified in ATC. These DE-CRGs mainly regulated mitotic nuclear division, cytokinesis and DNA replication signals. Notably, NPAS2, CSNK1E, NAMPT, TYMS, SERPINE1, TOP2A, JUN, EGR3 and HEBP1 were identified as the dynamic signature in the malignant progression of ATC, which were confirmed by prognostic analysis. Furthermore, NPAS2 was found to be significantly up-regulated in ATC through clinical samples and cell experiments. Silencing NPAS2 effectively inhibited the proliferation, migration and invasion of ATC cells. GSEA showed that high expression of NPAS2 was mainly associated with cell cycle and focal adhesion, and silencing of NPAS2 suppressed these signals in our experiments.

In summary, we found a dynamic 9-DE-CRGs signature in ATC. And the aberrant expression of NPAS2 drove the malignant phenotypes of ATC, which facilitated to deepen our understanding of the roles of circadian rhythm genes in ATC.

In summary, we found a dynamic 9-DE-CRGs signature in ATC. And the aberrant expression of NPAS2 drove the malignant phenotypes of ATC, which facilitated to deepen our understanding of the roles of circadian rhythm genes in ATC.

The objective of this study was to determine the rates at which gynecologic history and related exams are performed among adolescent females presenting with abdominal pain and whether the rates differ between patients seeking care at a pediatric compared with a general emergency department (ED).

We conducted a retrospective cohort study of female patients aged 12-21 years who presented to the ED for a chief complaint of abdominal pain at either a single academic children's ED or a single general academic ED during 2016. We examined differences in the rates of gynecologic history and related exams between institutions, before and after adjustment with inverse probability weights.

A total of 837 females met the inclusion criteria for this study, and 627 patients were included in the adjusted analyses. Outcomes more commonly performed at the pediatric institution included documentation of contraception (28% at the general ED vs 43% at the pediatric ED, P < .001), sexually transmitted infection testing (ate history. These efforts would ensure adequate evaluation of adolescent women and reduce unnecessary health resource utilization.

The rates at which gynecologic history and pelvic examination were performed in adolescent females presenting for abdominal pain at both a general ED and a pediatric ED were low and inconsistent. Providers should have a low threshold for testing for sexually transmitted infections and pregnancy. Pelvic examination and diagnostic lab testing should be performed when indicated in the setting of a clinically appropriate history. These efforts would ensure adequate evaluation of adolescent women and reduce unnecessary health resource utilization.

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