Several lines of evidence have implicated prenatal stress and the hippocampal GABA system in the pathophysiology of schizophrenia, and prenatal stress is believed to increase the risk for schizophrenia through alterations of this neurotransmitter. To explore this hypothesis, we treated male rats pre- and/or postnatally (P48 and P60) with either corticosterone (CORT) or vehicle to establish three study groups: VVV, receiving vehicle at all three time points; VCC, receiving vehicle prenatally and CORT at both postnatal timepoints; and CCC, receiving CORT at all three timepoints. Animals were sacrificed at either 24 h or 5 days after final injection and examined for mRNA levels of GAD65, GAD67, and the GABA(A) receptor subunits alpha2 and gamma2. At 24 h, GAD65 mRNA was decreased in CA1, CA2, CA4, and dentate gyrus (DG) of VCC rats; this effect was either decreased or reversed in CCC-treated animals. No effect was detected in GAD67 mRNA at 24 h. At 5 days, CORT treatment increased GAD67 mRNA levels in CA1, CA3, and DG. Prenatal treatment with CORT was associated with increased responsiveness only in CA3 and DG. For the GABAA receptor, alpha2 subunit mRNA did not show any change in response to CORT treatment, while that for the gamma2 subunit was decreased in CA2 of both VCC- and CCC-treated animals. Consistent with gamma2 subunit mRNA decreases, benzodiazepine (BZ) receptor binding activity was decreased in CA2 with CORT treatment. Prenatal CORT exposure neither increased nor decreased this effect. These results demonstrate that CORT administration is associated with a complex regulation of mRNA expression for pre- and postnatal aspects of the hippocampal GABA system. Under these conditions, prenatal exposure to CORT may sensitize some of these effects, but does not fundamentally alter the nature of this response.
Objectives: The healthcare profession has been long considered an excellent career choice. Pre-medical experience is documented to be important in shaping future medical landscape. In the wake of the pandemic, there has been intense media spotlight on the healthcare profession and change in academic environment, necessitating analyses of student experience. This project aims to assess change in undergraduate student interest in healthcare career using cross-sectional survey study.
Background: Studies of Caucasian patients with rheumatoid arthritis (RA) to identify genetic biomarkers of anti-tumor necrosis factor (TNF) response have used response at a single time point as the phenotype with which single nucleotide polymorphism (SNP) associations have been tested.The findings have been inconsistent across studies.Among Japanese patients, only a few SNPs have been investigated.We report here the first genome-wide association study (GWAS) to identify genetic biomarkers of anti-TNF response among Japanese RA patients, using response at 2 time-points for a more reliable clinical phenotype over time.Methods: Disease Activity Scores based on 28 joint counts (DAS28) were assessed at baseline (before initial therapy), and after 3 and 6 months in 487 Japanese RA patients starting anti-TNF therapy for the first time or switching to a new anti-TNF agent.A genome-wide panel of SNPs was genotyped and additional SNPs were imputed.Using change in DAS28 scores from baseline at both 3 (ΔDAS-3) and 6 months (ΔDAS-6) as the response phenotype, a longitudinal genome-wide association analysis was conducted using generalized estimating equations (GEE) models, adjusting for baseline DAS28, treatment duration, type of anti-TNF agent and concomitant methotrexate.Cross-sectional analyses were performed using multivariate linear regression models, with response from a single time point (ΔDAS-3 or ΔDAS-6) as phenotype; all other variables were the same as in the GEE models.Results: In the GEE models, borderline significant association was observed at 3 chromosomal regions (6q15: rs284515, p = 6.6x10 -7 ; 6q27: rs75908454, p = 6.3x10 -7 and 10q25.3:rs1679568, p = 8.1x10 -7 ), extending to numerous SNPs in linkage disequilibrium (LD) across each region.Potential candidate genes in these regions include MAP3K7, BACH2 (6q15), GFRA1 (10q25.3),and WDR27 (6q27).The association at GFRA1 replicates a previous finding from a Caucasian dataset.In the cross-sectional analyses, ΔDAS-6 was significantly associated with the 6q15 locus (rs284511, p = 2.5x10 -8 ).No other significant or borderline significant associations were identified. Conclusion:Three genomic regions demonstrated significant or borderline significant associations with anti-TNF response in our dataset of Japanese RA patients, including a locus previously associated among Caucasians.Using repeated measures of response as phenotype enhanced the power to detect these associations.
Background/Aim: To identify prognostic imaging biomarkers from staging chest computed tomography (CT) in patients with sarcomas. Patients and Methods: CT scans for baseline staging, and surveillance 1-year CT scans in patients newly diagnosed with sarcoma were evaluated. Pectoralis muscle area (PMA), pectoralis muscle index (PMI) and pectoralis CT attenuation density (PMT) were measured. Cox proportional-hazard models were used to determine the association with progression-free survival (PFS) and overall survival (OS). Results: There were 147 patients (53.1% male) who were followed for a median 1,414 days (range=219-4851 days). Approximately 47.6% (70/147) of patients progressed and 29.9% (44/147) died. Multivariable Cox-proportional hazards models adjusting for gender, tumor grade and chemotherapy treatment showed that a higher baseline PMT and baseline PMI were associated with increased OS. Conclusion: Higher baseline PMI and PMT are associated with increased overall survival in patients with sarcoma.
Direct MR arthrography of the shoulder is a safe, relatively easy procedure that can increase diagnostic confidence in the evaluation of rotator cuff and labroligamentous disorders compared with conventional MR imaging of the shoulder. Surgeons more often request MR arthrography in younger patients who may have internal impingement or subtle shoulder subluxation rather than obvious cuff rupture, repeated dislocation, or arthropathy. This article describes the advances in glenohumeral injection and MR protocol techniques, imaging pitfalls, anatomical variants, common lesions associated with internal derangement of the shoulder, and MR arthrography of the postoperative shoulder.
