Hellerkristensen2891
Despite age at diagnosis has been suggested as a major determinant of disease-specific survival in the recent TNM staging system, it is not included in the recent American Thyroid Association (ATA) guidelines to estimate the risk of recurrence. Nevertheless, the effect of sex on DTC recurrence is controversial. Therefore, this multicenter study was conducted to assess whether age at diagnosis and sex can improve the performance of the ATA three-tiered risk stratification system in DTC patients with at least five years of follow-up.
In this study, the computer-recorded data of the patients diagnosed with DTC between January 1985-January 2016 were analyzed. Only patients with a proven structural persistent/recurrent disease were selected for comparisons.
This study consisted of 1691 patients (1367 females) with DTC. In Kaplan-Meier analysis, disease-free survival (DFS) was markedly longer in females only in the ATA low-risk category (p=0.045). Nevertheless, a markedly longer DFS was observed in patients <45 years old in the ATA low and intermediate-risk categories (p=0.004 and p=0.009), while in patients <55 years old, DFS was markedly longer only in the ATA low-risk category (p <0.001). In Cox's proportional hazards model, age ≥45 and ≥55 as well as ATA risk system were all independent predictors of persistent/recurrent disease.
Applying the age cut-off of 45 in the ATA intermediate and low-risk categories may identify patients at higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system while sex may only improve the performance of ATA low-risk category.
Applying the age cut-off of 45 in the ATA intermediate and low-risk categories may identify patients at higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system while sex may only improve the performance of ATA low-risk category.
Impaired response inhibition in individuals with cocaine use disorder (CUD) is hypothesised to depend on deficient noradrenergic signalling in cortico-striatal networks. Remediation of noradrenergic neurotransmission with selective norepinephrine reuptake inhibitors such as atomoxetine may therefore have clinical utility to improve response inhibitory control in CUD.
We carried out a randomised, double-blind, placebo-controlled, crossover study with 26 CUD participants and 28 control volunteers investigating the neural substrates of stop-signal inhibitory control. The effects of a single dose of atomoxetine (40 mg) were compared with placebo on stop-signal reaction time performance and functional network connectivity using dynamic causal modelling.
We found that atomoxetine speeded Go response times in both control and CUD participants. Improvements in stopping efficiency on atomoxetine were conditional on baseline (placebo) stopping performance and were directly associated with increased inferior frontal gyrus activation. Further, stopping performance, task-based brain activation and effective connectivity were similar in the two groups. Dynamic causal modelling of effective connectivity of multiple prefrontal and basal ganglia regions replicated and extended previous models of network function underlying inhibitory control to CUD and control volunteers and showed subtle effects of atomoxetine on prefrontal-basal ganglia interactions.
These findings demonstrate that atomoxetine improves response inhibition in a baseline-dependent manner in control and in CUD participants. Our results emphasize inferior frontal cortex function as a future treatment target due to its key role in improving response inhibition in CUD.
These findings demonstrate that atomoxetine improves response inhibition in a baseline-dependent manner in control and in CUD participants. Our results emphasize inferior frontal cortex function as a future treatment target due to its key role in improving response inhibition in CUD.The homeoboxB9 (HOXB9) gene is necessary for specification of the anterior-posterior body axis during embryonic development and expressed in various types of cancer. Here we show that the Wilms tumor transcription factor WT1 regulates the HOXB9 gene in a bidirectional manner. Silencing of WT1 activates HOXB9 in Wt1 expressing renal cell adenocarcinoma-derived 786-0 cells, mesonephric M15 cells and ex vivo cultured murine embryonic kidneys. In contrast, HOXB9 expression in U2OS osteosarcoma and human embryonic kidney (HEK) 293 cells, which lack endogenous WT1, is enhanced by overexpression of WT1. Consistently, Hoxb9 promoter activity is stimulated by WT1 in transiently transfected U2OS and HEK293 cells, but inhibited in M15 cells with CRISPR/Cas9-mediated Wt1 deletion. Electrophoretic mobility shift assay and chromatin immunoprecipitation demonstrate binding of WT1 to the HOXB9 promoter in WT1-overexpressing U2OS cells and M15 cells. BASP1, a transcriptional co-repressor of WT1, is associated with the HOXB9 promoter in the chromatin of these cell lines. Co-transfection of U2OS and HEK293 cells with BASP1 plus WT1 prevents the stimulatory effect of WT1 on the HOXB9 promoter. Our findings identify HOXB9 as a novel downstream target gene of WT1. Depending on the endogenous expression of WT1, forced changes in WT1 can either stimulate or repress HOXB9, and the inhibitory effect of WT1 on transcription of HOXB9 involves BASP1. Consistent with inhibition of Hoxb9 expression by WT1, both transcripts are distributed in an almost non-overlapping pattern in embryonic mouse kidneys. Regulation of HOXB9 expression by WT1 might become relevant during kidney development and cancer progression.
Assess the role of tenting screws in the remodeling processes of autogenous bone blocks used for mandibular lateral augmentation in rabbits.
Eighteen rabbits, approximately 3.5-4.0kg of weight and 4-5 months of age, were included in this study. One lateral side of the angle of the mandible was augmented with block autografts. Animals were euthanized after 7, 20 and 60 days of healing, respectively. Biopsies were taken for each period and specimens underwent microtomographic scanning. The total volume (TV, mm
), bone volume (BV residual graft plus new bone, mm
), periimplant bone volume (PIBV), bone implant contact (BIC) along the screw and linear bone gain at five vertical points symmetrically dispersed from the fixation screw in the midline were measured. ANOVA and the t-test were performed.
The total volume (TV) of autografts decreased between 7 and 60 days from 258.13±15.3mm
to 107.2±17.5mm
(p < 0.05). Contraction rates of 58.5% were observed. BV was 52.8±7.7mm
, 27.2±11.1mm
, and 33.1±2.8mm
after 7, 20, and 60 days of healing, respectively. PIBV and BIC remained unchanged along time demonstrating no contraction around the screw. Total linear bone gain demonstrated a total of 18% linear contraction after 60 days. Point 1, demonstrated no changes along time representing no resorption along time. Points 2 and 4 demonstrate a minimum linear contraction (10-15%) with borderline significance. Resembling the total results, contraction starts after 20 days. Points 3 and 5 demonstrate a statistically significant contraction (p<0.05) of 35-40% starting at 20 days.
Tenting screws may reduce bone resorption symmetrically in a model of lateral block augmentation.
Tenting screws may reduce bone resorption symmetrically in a model of lateral block augmentation.The integration of modern neuroimaging methods with genetically informative designs and data can shed light on the molecular mechanisms underlying the structural and functional organization of the human connectome. Here, we review studies that have investigated the genetic basis of human brain network structure and function through three complementary frameworks (1) the quantification of phenotypic heritability through classical twin designs; (2) the identification of specific DNA variants linked to phenotypic variation through association and related studies; and (3) the analysis of correlations between spatial variations in imaging phenotypes and gene expression profiles through the integration of neuroimaging and transcriptional atlas data. We consider the basic foundations, strengths, limitations, and discoveries associated with each approach. We present converging evidence to indicate that anatomical connectivity is under stronger genetic influence than functional connectivity and that genetic influences are not uniformly distributed throughout the brain, with phenotypic variation in certain regions and connections being under stronger genetic control than others. We also consider how the combination of imaging and genetics can be used to understand the ways in which genes may drive brain dysfunction in different clinical disorders.Functional Quantitative Susceptibility Mapping (fQSM) allows for the quantitative measurement of time-varying magnetic susceptibility across cortical and subcortical brain structures with a potentially higher spatial specificity than conventional fMRI. While the usefulness of fQSM with General Linear Model and "On/Off" paradigms has been assessed, little is known about the potential applications and limitations of this technique in more sophisticated experimental paradigms and analyses, such as those currently used in modern neuroimaging. read more To thoroughly characterize fQSM activations, here we used 7T MRI, tonotopic mapping, as well as univariate (i.e., GLM and population Receptive Field) and multivariate (Representational Similarity Analysis; RSA) analyses. Although fQSM detected less tone-responsive voxels than fMRI, they were more consistently localized in gray matter. Also, the majority of active gray matter voxels exhibited negative fQSM response, signaling the expected oxyhemoglobin increase, whereas positive fQSM activations were mainly in white matter. Though fMRI- and fQSM-based tonotopic maps were overall comparable, the representation of frequency tunings in tone-sensitive regions was significantly more balanced for fQSM. Lastly, RSA revealed that frequency information from the auditory cortex could be successfully retrieved by using either methods. Overall, fQSM produces complementary results to conventional fMRI, as it captures small-scale variations in the activation pattern which inform multivariate measures. Although positive fQSM responses deserve further investigation, they do not impair the interpretation of contrasts of interest. The quantitative nature of fQSM, its spatial specificity and the possibility to simultaneously acquire canonical fMRI support the use of this technique for longitudinal and multicentric studies and pre-surgical mapping.In a study by Law and colleagues recently published in Neuroimage, the authors reported that wearing a surgical mask during an fMRI scan leads to a statistically significant subject-specific change (30%) in the baseline BOLD level in gray matter, although the response to a sensory-motor task was unaffected. An average increase in end-tidal CO2 of 7.4% was found when wearing a mask, despite little support in the literature for major effects of mask wearing on blood gas levels. We comment on these findings, point out a several relevant limitations of the study design and provide alternative interpretations of these data.
