Biallelic MFSD2A variants associated with congenital microcephaly, developmental delay, and recognizable neuroimaging features

Major Facilitator Superfamily Domain containing 2a (MFSD2A) is an essential endothelial lipid transporter at the blood-brain barrier. Biallelic variants affecting function in MFSD2A cause autosomal recessive primary microcephaly 15 (MCPH15, OMIM# 616486). We sought to expand our knowledge of the phenotypic spectrum of MCPH15 and demonstrate the underlying mechanism of inactivation of the MFSD2A transporter. We carried out detailed analysis of the clinical and neuroradiological features of a series of 27 MCPH15 cases, including eight new individuals from seven unrelated families. Genetic investigation was performed through exome sequencing (ES). Structural insights on the human Mfsd2a model and in-vitro biochemical assays were used to investigate the functional impact of the identified variants. All patients had primary microcephaly and severe developmental delay. Brain MRI showed variable degrees of white matter reduction, ventricular enlargement, callosal hypodysgenesis, and pontine and vermian hypoplasia. ES led to the identification of six novel biallelic MFSD2A variants (NG_053084.1, NM_032793.5: c.556+1G>A, c.748G>T; p.(Val250Phe), c.750_753del; p.(Cys251SerfsTer3), c.977G>A; p.(Arg326His), c.1386_1435del; p.(Gln462HisfsTer17), and c.1478C>T; p.(Pro493Leu)) and two recurrent variants (NM_032793.5: c.593C>T; p.(Thr198Met) and c.476C>T; p.(Thr159Met)). All these variants and the previously reported NM_032793.5: c.490C>A; p.(Pro164Thr) resulted in either reduced MFSD2A expression and/or transport activity. Our study further delineates the phenotypic spectrum of MCPH15, refining its clinical and neuroradiological characterization and supporting that MFSD2A deficiency causes early prenatal brain developmental disruption. We also show that poor MFSD2A expression despite normal transporter activity is a relevant pathomechanism in MCPH15

INVESTIGATION OF THE RELATIONSHIP BETWEEN PLANTAR PRESSURE DISTRIBUTION AND LUMBAR MULTIFIDUS MUSCLE THICKNESS

Congress of the European-League-Against-Rheumatism (EULAR) -- JUN 13-16, 2018 -- Amsterdam, NETHERLANDSWOS: 000444351002345…European League Against Rheumatis

Effect of Positive Surgical Margin on Biochemical Recurrence and Overall Survival After Radical Prostatectomy: Median Long-Term Results

WOS: 000209846801281

Significance of Surgical Margin in Patients with Clinical Localized Prostate Carcinoma Who Underwent Radical Prostatectomy

WOS: 000209846801282

Choroidal thickness in asymptomatic patients with carotid artery stenosis

Aim: To measure the choroidal thickness (CT) with enhanced-depth imaging optic coherence tomography (EDI-OCT) in patients with internal carotid artery (ICA) stenosis and to investigate the relationship between the CT and ICA stenosis. Material and methods: We included 36 eyes of 25 asymptomatic patients with 50% or higher ICA stenosis and 36 eyes of 21 healthy controls in the study. The CT was measured with EDI-OCT from a total of 6 points in both groups. The results were compared statistically between the groups. Results: There were no significant differences between patients with asymptomatic ICA stenosis and non-stenotic healthy individuals at subfoveal CT (P = 0.085), at 500 μm nasal to the fovea (P = 0.076), at 1,000 μm nasal to the fovea (P = 0.052), at 500 μm temporal to the fovea (P = 0.182), at 1,000 μm temporal to the fovea (P = 0.115) and at 1,500 μm temporal to the fovea (P = 0.174). Additionally, no significant difference was observed in CT values measured from 6 points between the stenotic side and the non-stenotic side in 14 patients with unilateral ICA stenosis (P > 0.05 for all points). Conclusion: The CT may not alter in asymptomatic ICA stenosis compared with healthy non-stenotic individuals. However, more studies are needed to corroborate our findings. © 2020, Czech Medical Association J.E. Purkyne. All rights reserved

Oral misoprostol does not protect the kidneys from diclofenac induced toxicity: data from an unilateral ureteral obstructive rat model

WOS: 000362577000033PubMed ID: 26439053OBJECTIVE: Ureteral obstruction leads to permanent changes in the structure of the kidney by several mechanisms. In this study, it was hypothesized that there would be a protective effect of misoprostol against diclofenac in rats with unilateral ureteral obstruction (UUO). MATERIALS AND METHODS: Twenty-two female rats were randomized into 5 groups of 4 and 2 rats for the control group. The right ureter was sutured. The rats were grouped as control, contrast agent, contrast agent +N-acetylcysteine (NAC), diclofenac and diclofenac + misoprostol groups. Radiographic contrast agent was given iv on the 3rd day and other agents were administered orally for 1 week. The rats were sacrified after 1 week and histopathological and biochemical oxidative stress markers were evaluated. RESULTS: The contrast agent and NAC group had lower rates of hemorrhage, inflammation, obstructive dilatation and fatty degeneration compared to the contrast agent only group (p 0.05). The contrast agent and NAC group had higher rates of antioxidant SH level compared to the contrast agent only group (p 0.05). Statistically no difference was seen between the diclofenac group and the diclofenac and misoprostol group neither pathologically nor chemically (p > 0.05). CONCLUSIONS: These results showed that NAC is protective against radiographic contrast agent toxicity when given before and after administration in obstructed kidneys as in previous data. Misoprostol was not observed to have any protective effect against diclofenac in obstructed kidneys

Cardiomyopathy of Friedreich's Disease. Modern Methods of Diagnostic

Friedreich's disease is a hereditary neurodegenerative multiple organ disease, primarily affecting the most energy-dependent tissues (cells of the nervous system, myocardium, pancreas), the lesion of which is characterized by progressive ataxia, dysarthria, dysphagia, oculomotor disorders, loss of deep tendon reflexes, pyramid signs, diabetes mellitus, visual impairment. Friedreich's ataxia is the most common of all hereditary ataxias; nevertheless, this disease is considered orphan. By its pathogenesis, Friedreich's disease is mitochondrial ataxia, caused by a deficiency in the transcription of the FXN gene, leading to a decrease in the synthesis of the frataxin protein. Frataxin is a protein associated with the inner mitochondrial membrane, which in turn is involved in the formation of iron-sulfur clusters, the lack of which leads to a decrease in the production of mitochondrial ATP, an increase in the level of mitochondrial iron and oxidative stress. The basis of the clinical picture of Friedreich's disease is ataxia of a mixed (sensitive and cerebellar) nature. The steady and gradual progression of neurological symptoms significantly affects the quality of life of patients and is most often the leading reason for seeking medical attention. However, the prognosis is primarily due to the involvement of cardiac tissue in the pathological process. The main causes of death in patients with Friedreich's ataxia are severe heart failure and sudden cardiac death due to cardiomyopathy. The overwhelming majority of foreign and domestic publications on Friedreich's ataxia are devoted to the neurological manifestations of this disease, and little attention is paid to this problem in the cardiological scientific and practical society. The purpose of this review is to provide up-to-date information on modern methods of diagnosing myocardial damage at various stages of Friedreich's disease