Vascular endothelial growth factor (VEGF) has a crucial role in the angiogenesis of various tumors, including glioma. As the levels of VEGF would change in patients with glioma, we conducted the current systematic review and meta-analysis to more clearly determine the VEGF level alterations in different grades of glioma. PubMed and Scopus databases were sensitively searched for all the possible keywords addressing glioma and VEGF. Case–control and cohort studies on human subjects, which measured VEGF levels were eligible to be included in the study. Out of a total number of 3,612 studies, 22 studies were included and 12 studies entered the meta-analysis. This review revealed that serum levels of VEGF in glioma patients were 1.56 pg/dL higher compared to healthy controls (P = 0.05). Besides, immunohistochemistry (IHC) measurement of VEGF in surgical biopsies indicated significant difference in these two groups as well (P = 0.02). Yet, there was not a significant difference between patients with low-grade gliomas (World Health Organization (WHO) grades I-II, LGG) and those with high-grade gliomas (WHO grades III-IV, HGG) (P = 0.43). The results of this systematic review and meta-analysis demonstrate that VEGF levels would significantly increase in glioma, and therefore, could be potentially considered as a biomarker for this cancer.

Background In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of the possible protection of physical activity against disease progression in multiple sclerosis (MS). However, the question arises if acute or regular exercise has any impact on the immune system in PwMS. To answer this question, we performed a systematic review and meta-analysis on both plasma and serum cytokine levels (IL-6 and TNF-α) before and after acute and regular exercise among PwMS and compared to healthy controls. Method We performed an online search via PubMed, EMBASE, SCOPUS, Web of Science, and Cochrane Library till September 2021 to identify original studies on IL-6 and TNF-α changes after acute and regular exercise in PwMS and controls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 original studies were included in the meta-analysis. Sensitivity analyses were used to identify the origins of heterogeneity. R 4.0.4 was used to perform the meta-analysis of IL-6 and TNF-α levels before and after acute and regular exercise in PwMS, compared to controls. This study does not qualify for a clinical trial number. Results IL-6 levels did neither increase nor decrease after acute and regular exercise in PwMS, and compared to controls (pre- vs. post-intervention: Standardized Mean Difference (SMD) -0.09, 95% CI [−0.29; 0.11], p-value = 0.37, PwMS vs. Control: SMD −0.08, 95% CI [−0.33; 0.16], p-value = 0.47). In PwMS, TNF-α levels decreased after regular exercise and when TNF-α levels of both acute and regular exercise were pooled (pre- vs. post-intervention: SMD −0.51, 95% CI [-0.91; 0.11], p-value = 0.01, PwMS vs. Control: SMD −0.23, 95% CI [−0.66; 0.18], p-value = 0.26). TNF-α levels did neither increase nor decrease after acute and regular exercise in PwMS, when compared to controls. Conclusion This systematic review and meta-analysis show that exercise does not lead to significant changes in peripheral levels of IL-6 in PwMS in contrast to the observed response in healthy subjects and other medical contexts. However, regular exercise had a specific anti-inflammatory effect on blood TNF-α levels in PwMS. It remains to be investigated why PwMS display this different exercise-induced pattern of cytokines.

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Diffusion‐weighted imaging has been applied to investigate alterations in multiple sclerosis (MS). In the last years, advanced diffusion models were used to identify subtle changes and early lesions in MS. Among these models, neurite orientation dispersion and density imaging (NODDI) is an emerging approach, quantifying specific neurite morphology in both grey (GM) and white matter (WM) tissue and increasing the specificity of diffusion imaging. In this systematic review, we summarized the NODDI findings in MS. A search was conducted on PubMed, Scopus, and Embase, which yielded a total number of 24 eligible studies. Compared to healthy tissue, these studies identified consistent alterations in NODDI metrics involving WM (neurite density index), and GM lesions (neurite density index), or normal‐appearing WM tissue (isotropic volume fraction and neurite density index). Despite some limitations, we pointed out the potential of NODDI in MS to unravel microstructural alterations. These results might pave the way to a deeper understanding of the pathophysiological mechanism of MS.Evidence Level2.Technical EfficacyStage 3.

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Major depressive disorder (MDD) is a common psychiatric illness with a wide range of symptoms such as mood decline, loss of interest, and feelings of guilt and worthlessness. Women develop depression more often than men, and the diagnostic criteria for depression mainly rely on female patients' symptoms. By contrast, male depression usually manifests as anger attacks, aggression, substance use, and risk-taking behaviors. Various studies have focused on the neuroimaging findings in psychiatric disorders for a better understanding of their underlying mechanisms. With this review, we aimed to summarize the existing literature on the neuroimaging findings in depression, separated by male and female subjects. A search was conducted on PubMed and Scopus for magnetic resonance imaging (MRI), functional MRI (fMRI), and diffusion tensor imaging (DTI) studies of depression. After screening the search results, 15 MRI, 12 fMRI, and 4 DTI studies were included. Sex differences were mainly reflected in the following regions: 1) total brain, hippocampus, amygdala, habenula, anterior cingulate cortex, and corpus callosum volumes, 2) frontal and temporal gyri functions, along with functions of the caudate nucleus and prefrontal cortex, and 3) frontal fasciculi and frontal projections of corpus callosum microstructural alterations. Our review faces limitations such as small sample sizes and heterogeneity in populations and modalities. But in conclusion, it reflects the possible roles of sex-based hormonal and social factors in the depression pathophysiology. Supplementary Information The online version contains supplementary material available at 10.1007/s11682-023-00772-8.

We aimed to evaluate cilostazol therapeutic effects on aberrant behaviors of autism spectrum disorder (ASD) children and its safety profile in a double-blind, randomized clinical trial. Sixty-six children with confirmed ASD were allocated to receive either daily 50-mg cilostazol (increased to 100 mg/day after 2 weeks) or matched placebo in addition to risperidone. The Aberrant Behavior Checklist-Community Edition (ABC-C) scale and a checklist of probable adverse effects were used to assess the behavioral outcomes and safety profile at weeks 0, 5, and 10 of the study. Sixty-one participants, with comparable baseline characteristics, completed the trial. Unlike other ABC-C subscales, repeated-measures analysis showed significant effect for time × treatment interaction in the hyperactivity subscale (P = 0.047; partial eta squared = 0.06). We used the median value for the baseline score hyperactivity subscale [median (interquartile range) = 31 (24-37)] to stratify participants to higher hyperactivity and lower hyperactivity subgroups and found that only participants with higher hyperactivity benefit from cilostazol adjunctive therapy (P = 0.028; partial eta squared = 0.14). Cilostazol could be considered as a safe agent with beneficial effects on hyperactivity in children with ASD and higher levels of hyperactivity.