Norwoodoneill7310
Dennd1a could be involved in multiple signal pathways in the somatic cells that are critical for various processes of oogenesis and meiosis in the fetal ovary.
Dennd1a could be involved in multiple signal pathways in the somatic cells that are critical for various processes of oogenesis and meiosis in the fetal ovary.
Parkinson's disease (PD) is caused by the interplay of genetic and environmental factors during brain aging. About 90 single nucleotide polymorphisms (SNPs) have been recently discovered associations with PD, but whether they associate with the clinical features of PD have not been fully addressed yet.
Clinical data of 365 patients with PD who enrolled in Parkinson's Progression Markers Initiative (PPMI) study were obtained. Patients with rapid motor progression were determined through clinical assessments over five years follow-up. In addition, genetic information of 44 targeted SNPs was extracted from the genetic database of NeuroX for the same cohort. Logistic regression was used to analyze the genetic associations with rapid motor progression of PD.
Among 365 patients with PD, there are more male (66%) than female (34%). Seven SNPs (rs6808178, rs115185635, rs12497850, rs34311866, rs3793947, rs11060180, rs9568188) were associated with faster motor progression (p < 0.05), and only rs6808178 passed multiple comparison correction (p < 0.0011). In addition, the extended 44 SNPs with autonomic dysfunction reach a fair prediction of AUC at 0.821.
Genetics and autonomic function factors contribute to the motor progression at the clinical initiation of PD.
Genetics and autonomic function factors contribute to the motor progression at the clinical initiation of PD.
Despite the fact that the clinical efficacy of hydroxychloroquine is still controversial, it has been demonstrated in vitro to control SARS-CoV-2 multiplication on Vero E6 cells. In this study, we tested the possibility that some patients with prolonged virus excretion could be infected by less susceptible strains.
Using a high-content screening method, we screened 30 different selected isolates of SARS-CoV-2 from different patients who received azithromycin ± hydroxychloroquine. We focused on patients with viral persistence, i.e., positive virus detection in a nasopharyngeal sample ≥10 days, and who were tested during two French epidemic waves, late winter-spring of 2020 and the summer of 2020. Dose-response curves in single-molecule assays with hydroxychloroquine were created for isolates with suspected reduced susceptibility. Genome clustering was performed for all isolates.
Of 30 tested strains, three were detected as replicating in the presence of azithromycin + hydroxychloroquine, each at 5 μM. The dose-response model showed a decrease in susceptibility of these three strains to hydroxychloroquine. Whole genome sequencing revealed that these three strains are all from the second epidemic wave and two cluster with isolates from Africa.
Reduced susceptibility to hydroxychloroquine was not associated with viral persistence in naso-pharyngeal samples. Rather, it was associated with occurring during the second epidemic wave, which began in the summer and with strains clustering with those with a common genotype in Africa, where hydroxychloroquine was the most widely used.
Reduced susceptibility to hydroxychloroquine was not associated with viral persistence in naso-pharyngeal samples. Rather, it was associated with occurring during the second epidemic wave, which began in the summer and with strains clustering with those with a common genotype in Africa, where hydroxychloroquine was the most widely used.
Patients with primary biliary cholangitis (PBC) are at increased risk for development of hepatocellular carcinoma (HCC), particularly in the presence of comorbidities such as excessive alcohol consumption. Although liver fibrosis is an important risk factor for HCC development, earlier predictors of future HCC development in livers with little fibrosis are needed but not well defined. The transforming growth factor (TGF)-β/Smad signaling pathway participates importantly in hepatic carcinogenesis. Phosphorylated forms (phospho-isoforms) in Smad-related pathways can transmit opposing signals cytostatic C-terminally-phosphorylated Smad3 (pSmad3C) and carcinogenic linker-phosphorylated Smad3 (pSmad3L) signals.
To assess the balance between Smad signals as a biomarker of risk, we immunohistochemically compared Smad domain-specific Smad3 phosphorylation patterns among 52 PBC patients with various stages of fibrosis and 25 non-PBC patients with chronic hepatitis C virus infection. HCC developed in 7 of 11 PBC patients showing high pSmad3L immunoreactivity, but in only 2 of 41 PBC patients with low pSmad3L. In contrast, 9 of 20 PBC patients with minimal Smad3C phosphorylation developed HCC, while HCC did not occur during follow-up in 32 patients who retained hepatic tumor-suppressive pSmad3C. Further, PBC patients whose liver specimens showed high pSmad3L positivity were relatively likely to develop HCC even when little fibrosis was evident.
In this study, Smad phospho-isoform status showed promise as a biomarker predicting likelihood of HCC occurrence in PBC. Eventually, therapies to shift favorably Smad phospho-isoforms might decrease likelihood of PBC-related HCC.
In this study, Smad phospho-isoform status showed promise as a biomarker predicting likelihood of HCC occurrence in PBC. Eventually, therapies to shift favorably Smad phospho-isoforms might decrease likelihood of PBC-related HCC.
Adolescent and young adult cancer patients (AYACPs) experience a high incidence of psychological distress. However, the effect of psychological distress on the functional connectivity between the hemispheres in AYACPs remains unknown. BV6 Voxel-mirrored homotopy connectivity detection is an effective way to explore the effects of psychological distress on functional connectivity throughout the brain in AYACPs.
Twenty-four AYACPs underwent structural magnetic resonance imaging.
Voxel-mirrored homotopy connectivity in the psychological distress group was significantly lower in the superior parietal gyrus, middle frontal gyrus (orbital part), superior frontal gyrus (dorsolateral), superior occipital gyrus, precuneus, lingual gyrus, calcarine fissure and surrounding cortex than in the non-psychological distress group, while in the inferior temporal gyrus and middle frontal gyrus (orbital part), voxel-mirrored homotopy connectivity was significantly higher (p < 0.05). ROC curve analysis showed that the decrease in voxel-mirrored homotopy connectivity in the following brain regions was helpful in distinguishing the psychological distress group from the non-psychological distress group left superior frontal gyrus (dorsolateral), left calcarine fissure and surrounding cortex, right postcentral gyrus, and left precuneus.
Activity imbalances in multiple brain regions exist in AYACPs with psychological distress. Voxel-mirrored homotopy connectivity detection is an effective way to explore the potential neural mechanisms of mental disorders in AYACPs and optimize the treatment of mental disorders.
Activity imbalances in multiple brain regions exist in AYACPs with psychological distress. Voxel-mirrored homotopy connectivity detection is an effective way to explore the potential neural mechanisms of mental disorders in AYACPs and optimize the treatment of mental disorders.
The purpose of the present study was to investigate the effects of various short-term cooling durations on the performance of both superelastic and thermally treated nickel titanium (NiTi) files, tested in a dynamic cyclic fatigue model.
Superelastic RaCe (FKG, La Chaux-de-Fonds, Switzerland) and thermally treated RaCe EVO (FKG, La Chaux-de-Fonds, Switzerland) files of the same size and taper (25, 0.06) (n = 45 each) were tested using a dynamic cyclic fatigue model, where the number of cycles to failure (Nf) was measured at simulated body temperature. In each group, the samples were tested as received, after 5 seconds of cooling treatment, and after 15 seconds of cooling treatment (n = 15 each). Fractured file surfaces were investigated via scanning electron microscopy. Statistical analysis was performed using a one-way ANOVA with Scheffe's post hoc test at a significance level of 0.05.
Significant differences in the Nf between the tested groups were found (p < 0.05) at each testing condition, where RaCe Evo files showed overall improved cyclic fatigue resistance. Only the RaCe groups at 5 second cooling showed significantly higher Nf than the control subgroup (p < 0.05). RaCe EVO group, showed no significant difference between the 3 subgroups (p > 0.05). Scanning Electron Microscope (SEM) images revealed typical features of cyclic fatigue behavior in both groups.
Short-term cooling application for 5 seconds on superelastic NiTi files showed an enhanced cyclic fatigue resistance.
Short-term cooling application for 5 seconds on superelastic NiTi files showed an enhanced cyclic fatigue resistance.
Statins have been linked to an increased risk for insomnia, but the literature is controversial. Moreover, it is unknown, if the potential effects are directly related to the inhibition of the statin target HMGCR, the subsequently lowered cholesterol levels, or other off-target effects of statins.
To investigate the association of statin treatment and genetic proxies of cholesterol lowering drugs with the risk for insomnia and chronotype in a large population-based cohort.
A cross-sectional cohort study based on baseline data collected between 2006-2010 in UK biobank cohort was conducted. European participants without any history of psychiatric/neurological disorders or of stroke and with available genetic data as well as information on statin use were included in the present study. Self-reported measures of insomnia and chronotype were analysed (a) in statin users versus control subjects, (b) subjects carrying single nucleotide polymorphisms (SNPs) in the HMGCR gene, which are associated with reduced eexplains why the literature on statin effects on sleep is not conclusive. Finally our data encourage further investigations into the molecular processes linking statins, HMGCR and PCSK9 to sleep behaviour.
The molecular mechanisms underlying acute exacerbations (AEs) of idiopathic pulmonary fibrosis (IPF) are poorly understood. To understand the gene expression patterns of the AEs of IPF, we studied gene expression profiling of AEs of IPF.
The GEO datasets included in this study are GSE44723 and GSE10667, and in-house RNA-seq data were used. DEG analysis used the limma package, and the STRING database was used to construct the protein-protein interaction (PPI) network, and its functional role was investigated through gene ontology analysis.
The results of DEG analysis indicated 76 upregulated and 135 downregulated genes associated with an AE of IPF compared to stable IPF. The PPI network included three core modules containing 24 of the 211 DEGs. Eleven upregulated and six downregulated genes were evident in AEs of IPF compared with stable IPF after validation. The upregulated genes were associated with cell division. The downregulated genes were related to skeletal muscle differentiation and development.
In previous studies, 17 genes were strongly associated with cell proliferation in various cell types.
