Glutamate hypothesis in schizophrenia

Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d ‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability.     

The influence of configuration factors on cavity adaptation in compomer restorations

The effect of configuration factor (C-factor) on cavity adaptation was investigated in three compomer and one resin composite restorations. Eighty-four cylindrical dentin cavities (C-factor: approximately 2.5, 3.0 or 4.0) prepared on flat coronal dentin surfaces were filled with the materials in combination with their proprietary adhesive systems. Cavity adaptation was microscopically examined after 15 minutes storage in water at the top surface and at other four sites along the cavity walls. Additionally, indentation testing was performed for each material at 20 minutes and 24 hours after irradiation. Regression analysis revealed no relationship between C-factor and gap dimension in compomer restorations at any of the measuring sites, while a logarithmic relation was found only at the cavity floor of the composite fillings. All materials showed maturation of mechanical properties. The elastic component of the indentation was smaller in compomers than in the composite. It was concluded that C-factor had no influence on the cavity adaptation for compomer restorations. This might be due to reduced stress generation at the bonding interface caused by relatively low mechanical properties immediately after curing, less elasticity, and water absorption in compomers.     

Regional brain imaging of vesicular acetylcholine transporter using o‐[125I]iodo‐trans‐decalinvesamicol as a new potential imaging probe

In this study, the regional rat brain distribution of radioiodinated o‐iodo‐trans‐decalinvesamicol ([¹²⁵I]OIDV) was determined in vivo to evaluate its potential as a single‐photon emission computed tomography (SPECT) imaging probe for vesicular acetylcholine transporter (VAChT). Following intravenous injection, [¹²⁵I]OIDV passed freely across the blood–brain barrier and accumulated in rat brain. The accumulation of [¹²⁵I]OIDV in rat brain was significantly reduced by coadministration of (+/?)‐vesamicol (0.125 µmol). In contrast, the coadministration of σ‐receptor ligands, such as (+)‐pentazocine (0.125 µmol) as a σ‐1 receptor ligand and (+)?3‐(3‐hydroxyphenyl)‐N‐propylpiperidine (0.125 µmol) as a σ‐1 and σ‐2 receptor ligands, barely affected the accumulation of [¹²⁵I]OIDV in rat brain. These findings in vivo were corroborated by autoradiographic analysis ex vivo. The authors found that the tracer binds with pharmacological selectivity to VAChT in rat brain and predicted that it may likewise serve in translational SPECT imaging studies of this marker in the integrity of cholinergic innervations. Synapse 68:107–113, 2014. © 2013 Wiley Periodicals, Inc.     

Hemodynamic factor evaluation using computational fluid dynamics analysis for de novo bleb formation in unruptured intracranial aneurysms

Neurological Sciences - Although bleb formation increases the risk of rupture of intracranial aneurysms, previous computational fluid dynamic (CFD) studies have been unable to identify robust...     

On-treatment C-reactive protein control could predict response to subsequent anti-PD-1 treatment in metastatic renal cell carcinoma

Objective

The aim of this study was to evaluate the clinical significance of the on-treatment C-reactive protein (CRP) status during systemic treatment as the predictive marker for the response of subsequent nivolumab monotherapy in patients with refractory metastatic renal cell carcinoma (mRCC).

Patients and methods

A total of 73 mRCC patients treated with nivolumab were retrospectively reviewed. We evaluated the serum CRP levels before and after molecular-targeted treatments. Patients whose CRP did not exceed baseline value were defined as the CRP-control group and the others were defined as the CRP-progression group. The clinical impact of CRP-control on the efficacy of nivolumab was assessed.

Results

Twenty-four patients (33%) were categorized into the CRP-control group. The CRP-control group patients (median PFS not reached) had significantly longer PFS than the CRP-progression group (median PFS 11.9 months, 95% confidence interval, CI 4.1–19.8, p?=?0.038). The CRP-control group had a tendency of longer OS from nivolumab initiation than the CRP-progression group (p?=?0.071). By multivariate analysis, the on-treatment CRP-control was the independent predictive factor for PFS (hazard ratio HR 0.37, 95% CI 0.14–0.99, p?=?0.047).

Conclusion

The on-treatment CRP-control could be the predictive factor for the efficacy of nivolumab in refractory mRCC patients.