Distortion-free diffusion tensor imaging for evaluation of lumbar nerve roots: Utility of direct coronal single-shot turbo spin-echo diffusion sequence

Publication date: June 2018
Source:Magnetic Resonance Imaging, Volume 49
Author(s): Takayuki Sakai, Kunio Doi, Masami Yoneyama, Atsuya Watanabe, Tosiaki Miyati, Noriyuki Yanagawa
PurposeDiffusion tensor imaging (DTI) based on a single-shot echo planer imaging (EPI-DTI) is an established method that has been used for evaluation of lumbar nerve disorders in previous studies, but EPI-DTI has problems such as a long acquisition time, due to a lot of axial slices, and geometric distortion. To solve these problems, we attempted to apply DTI based on a single-shot turbo spin echo (TSE-DTI) with direct coronal acquisition. Our purpose in this study was to investigate whether TSE-DTI may be more useful for evaluation of lumbar nerve disorders than EPI-DTI.Materials and methodsFirst, lumbar nerve roots of five healthy volunteers were evaluated for optimization of imaging parameters with TSE-DTI including b-values and the number of motion proving gradient (MPG) directions. Subsequently, optimized TSE-DTI was quantitatively compared with conventional EPI-DTI by using fractional anisotropy (FA) values and visual scores in subjective visual evaluation of tractography. Lumbar nerve roots of six patients, who had unilateral neurologic symptoms in one leg, were evaluated by the optimized TSE-DTI.ResultsTSE-DTI with b-value of 400 s/mm² and 32 diffusion-directions could reduce the image distortion compared with EPI-DTI, and showed that the average FA values on the symptomatic side for six patients were significantly lower than those on the non-symptomatic side (P < 0.05).ConclusionTractography with TSE-DTI might show damaged areas of lumbar nerve roots without severe image distortion. TSE-DTI might improve the reproducibility in measurements of FA values for quantification of a nerve disorder, and would become a useful tool for diagnosis of low back pain.



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Development and Validation of the Mastocytosis Activity Score: MAS

Abstract

Background

Mastocytosis is a heterogeneous disease characterized by a clonal expansion of mast cells in various organs. The vast majority of patients suffer from signs and symptoms caused by mediator release from mast cells. Although the disease burden is high, there is currently no specific and validated instrument to measure and monitor signs and symptoms in patients with mastocytosis.

Objective

To develop and validate a disease-specific tool to measure and monitor the activity of signs and symptoms in patients with mastocytosis, the Mastocytosis Activity Score (MAS).

Methods

Nineteen potential MAS items were developed in a combined approach consisting of semi-structured patient interviews, expert input, and literature research. Item selection was performed by impact analysis with 76 patients followed by a review for face validity. The resulting MAS was tested for validity, reliability and influence factors. In parallel, a US American-English version of the MAS was developed.

Results

68 mastocytosis patients took part in the MAS validation study. The final 9-item MAS was found to have a three-domain structure ('skin', 'gastrointestinal tract', 'other'), a valid total score and an excellent test-retest-reliability. Multiple regression analysis revealed that disease duration, age, or gender are no significant determinant of the MAS results.

Conclusions

The MAS is a disease-specific, valid and reliable patient reported outcome measure for adult patients with cutaneous and indolent systemic mastocytosis. It may serve as a valuable tool to measure and monitor mastocytosis activity, both, in clinical trials and in routine care.

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Repeated restraint stress reduces the acquisition and relapse of methamphetamine-conditioned place preference but not behavioral sensitization

Publication date: Available online 5 February 2018
Source:Brain Research Bulletin
Author(s): Jee-Yeon Seo, Yong-Hyun Ko, Shi-Xun Ma, Bo-Ram Lee, Seok-Yong Lee, Choon-Gon Jang
The studies for the effects of stress on drug addiction were mostly obtained using sequential exposure to stress and drugs. However, few studies have been conducted on the effects of simultaneous exposure to stress and methamphetamine (METH) on METH-induced reward effects and behavioral sensitization. Thus, we examined the effects of simultaneous exposure to restraint stress and METH on METH-induced addictive behaviors using conditioned place preference (CPP) in mice. During the conditioning period, the mice were exposed to 2 h restraint stress before administration of METH or saline for 4 days. To investigate the effect of restraint stress on drug relapse, the mice were exposed to 2 h of restraint stress for 4 days during the late period of withdrawal. The results showed that the acquisition of METH CPP was impaired by simultaneous exposure to restraint stress and METH administration and the impairment of METH CPP was retained until METH-induced reinstatement. Additionally, based on locomotor activity data measured during METH reinstatement, simultaneous stress exposure during the conditioning phase increased METH-induced locomotor sensitization. We also found that the magnitude of METH-primed relapse was reduced in mice exposed to restraint stress during the late period of withdrawal. Taken together, these findings suggest that simultaneous exposure to restraint stress and METH can reduce the acquisition and relapse of METH-induced addictive behaviors but not behavioral sensitization.



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Involvement of NO/NMDA-R pathway in the behavioral despair induced by amphetamine withdrawal

Publication date: Available online 5 February 2018
Source:Brain Research Bulletin
Author(s): Arvin Haj-Mirzaian, Shayan Amiri, Hossein Amini-Khoei, Arya Haj-Mirzaian, Arsalan Hashemiaghdam, Kiana Ramezanzadeh, Maria Ghesmati, Khashayar Afshari, Ahmad Reza Dehpour
Abrupt discontinuation of chronic amphetamine consumption leads to withdrawal symptoms including depression, anhedonia, dysphoria, fatigue, and anxiety. These irritating symptoms may result in continuing to take the drug or can lead to suicidal behavior. Past studies have shown the involvement of various biologic systems in depression induced following amphetamine withdrawal (AW). However, there is no evidence about the relation between nitric oxide (NO) with NMDA receptors on depression following AW. In this study, we examined the involvement of the NO/NMDA pathways on depressive-like behaviors after 24 h withdrawal following 5 continuous days of amphetamine administration in male NMRI mice. Behavioral tasks used for depression assessment included the forced swimming test (FST), the Splash test and the open field test (OFT). In order to evaluate the role of NO/NMDA pathways animals treated with MK-801 (NMDA-R antagonist), Aminoguanidine (AG), a selective iNOS inhibitor, Nω-Nitro-L-arginine (L-NNA), a non-selective NOS inhibitor and 7-Nitro indazole (7-NI), a selective nNOS inhibitor. We also measured the level of nitrite in the hippocampus. Our data showed that AW induced the depressive-like effect in the FST and the Splash test. We showed that administration of AG, L-NNA, and MK-801 mitigated AW induced depression, however, 7-NI was failed to decrease depressive-like behaviors. Also, the antidepressant-like effect of co-injection of sub-effective doses of MK-801 with AG suggested that inducible nitric oxide synthase (iNOS) is associated with NMDA-R in AW induced depression. In conclusion, both NO and NMDA-R pathways are involved and related to each other in depression induced following AW.



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Effect of glucagon-like peptide-1 analogue; Exendin-4, on cognitive functions in type 2 diabetes mellitus; possible modulation of brain derived neurotrophic factor and brain Visfatin

Publication date: Available online 5 February 2018
Source:Brain Research Bulletin
Author(s): O.M. Abdelwahed, O.M. Tork, M.M. Gamal el Din, L. Rashed, M. Zickri
BackgroundBrain derived neurotrophic factor (BDNF) is one of the most essential neurotrophic factors in the brain. BDNF is involved in learning, memory and locomotion suggesting it as a target in type 2 diabetes mellitus (T2DM) associated cognitive changes. Visfatin; an adipokine discovered to be expressed in the brain; was found to have multiple effects including its participation in keeping energy supply to the cell and is consequentially involved in cell survival. Its role in cognitive functions in T2DM was not studied before. Recent studies point to the possible neuro-protective mechanisms of glucagon-like peptide 1 analogue: Exendin-4 (Ex-4) in many cognitive disorders, but whether BDNF or Visfatin are involved or not in its neuro-protective mechanisms; is still unknown.Aimsto study the changes in cognitive functions in T2DM, either not treated or treated with Glucagon-like peptide 1 (GLP-1) analogue: Ex-4, and to identify the possible underlying mechanisms of these changes and whether BDNF and brain Visfatin are involved.MethodsA total of 36 adult male wistar albino rats were divided into 4 groups; Control, Exendin-4 control, Diabetic and Exendin-4 treated groups. At the end of the study, Y-maze and open field tests were done the day before scarification to assess spatial working memory and locomotion, respectively. Fasting glucose and insulin, lipid profile and tumor necrosis factor- alpha (TNF-α) were measured in the serum. Homeostasis model assessment insulin resistance was calculated. In the brain tissue, malondialdehyde (MDA) level, gene expression and protein levels of BDNF and Visfatin, area of degenerated neurons, area of glial cells and area % of synaptophysin immunoexpression were assessed.ResultsCompared with the control, the untreated diabetic rats showed insulin resistance, dyslipidemia and elevation of serum TNF-α. The brain tissue showed down-regulation of BDNF gene expression and reduction of its protein level, up-regulation of Visfatin gene expression and elevation of its protein level, increase in MDA, area of degenerated neurons and area of glial cells and reduction in area % of synaptophysin immunoexpression. These changes were paralleled with significant deterioration in spatial working memory and locomotion. Treatment of diabetic rats with Ex-4 reversed all these changes.ConclusionT2DM has a negative impact on cognitive functions through different pathological and subcellular mechanisms. The current study provides evidence for involvement of BDNF and brain Visfatin in T2DM- associated cognitive dysfunction. BDNF and brain Visfatin were also found to contribute to the neuro-protective effect of Ex-4 via modulation of inflammation, oxidative stress, neuro-degeneration and synaptic function.



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Baseline neutrophil to lymphocyte ratio combined with serum LDH level associated with outcome of nivolumab immunotherapy in a Japanese advanced melanoma population

Abstract

Although immune checkpoint inhibitors (ICI) significantly improve the survival of advanced melanoma, more than half of the patients received no benefit. To predict outcomes, efforts to associate baseline peripheral blood biomarkers were started in patients given treatment with ipilimumab. Among the most critical markers is an increased neutrophil-to-lymphocyte ratio (NLR), which negatively correlates with outcome. Although several baseline factors have been reported to correlate with outcome in patients treated with nivolumab/pembrolizumab (eosinophil count, lymphocyte count, lactate dehydrogenase [LDH], and c-reactive protein [CRP]), a positive link between NLR and outcome has yet to be shown.

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Wide skin markings pattern - melanoma descriptor or patient-related factor?

Abstract

We are intrigued by the findings reported in the letter titled "Uncovering the diagnostic dermoscopic features of flat melanomas located on the lower limbs"(1). Bassoli et al investigated the association of the "wider skin marking pattern" with cutaneous melanoma. They state that this feature corresponds to "…linear intercepting furrows, lighter than the lesion's overall pigmentation and wider compared to the surrounding skin. The authors conclude that "recognition of wider skin markings may…prompt the clinician to obtain a biopsy specimen." We respectfully ask the authors to clarify several aspects of their study methodology.

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