Hippocampal CA3 Transcriptome Signature Correlates with Initial Precipitating Injury in Refractory Mesial Temporal Lobe Epilepsy

Background: Prolonged febrile seizures constitute an initial precipitating injury (IPI) commonly associated with refractory mesial temporal lobe epilepsy (RMTLE). in order to investigate IPI influence on the transcriptional phenotype underlying RMTLE we comparatively analyzed the transcriptomic signatures of CA3 explants surgically obtained from RMTLE patients with (FS) or without (NFS) febrile seizure history. Texture analyses on MRI images of dentate gyrus were conducted in a subset of surgically removed sclerotic hippocampi for identifying IPI-associated histo-radiological alterations.Methodology/Principal Findings: DNA microarray analysis revealed that CA3 global gene expression differed significantly between FS and NFS subgroups. An integrative functional genomics methodology was used for characterizing the relations between GO biological processes themes and constructing transcriptional interaction networks defining the FS and NFS transcriptomic signatures and its major gene-gene links (hubs). Co-expression network analysis showed that: i) CA3 transcriptomic profiles differ according to the IPI; ii) FS distinctive hubs are mostly linked to glutamatergic signalization while NFS hubs predominantly involve GABAergic pathways and neurotransmission modulation. Both networks have relevant hubs related to nervous system development, what is consistent with cell genesis activity in the hippocampus of RMTLE patients. Moreover, two candidate genes for therapeutic targeting came out from this analysis: SSTR1, a relevant common hub in febrile and afebrile transcriptomes, and CHRM3, due to its putative role in epilepsy susceptibility development. MRI texture analysis allowed an overall accuracy of 90% for pixels correctly classified as belonging to FS or NFS groups. Histological examination revealed that granule cell loss was significantly higher in FS hippocampi.Conclusions/Significance: CA3 transcriptional signatures and dentate gyrus morphology fairly correlate with IPI in RMTLE, indicating that FS-RMTLE represents a distinct phenotype. These findings may shed light on the molecular mechanisms underlying refractory epilepsy phenotypes and contribute to the discovery of novel specific drug targets for therapeutic interventions

Swimming pool granuloma: Six case series [Yüzme havuzu granülomu: Alti olgu serisi]

Swimming pool granuloma (SPG) which is caused by Mycobacterium marinum is a chronic infectious disease of the skin. This infection disease usually develops on people who are in contact with pool, thermal spring, aquarium without chlorine and lakes. Fresh water and salt wa ter fishes and other organisms are reported as to be vectors. Here, we report six SPG patients aged 21-65 who admitted to our outpatient clinic in a year. The duration of the symptoms altered bet ween two to six months. Sporotrichoid lesions are observed in three of them. The others are char acterized by solitary, nodular lesions. Diagnoses are confirmed histopathologically and microbiologically in all of them. This six cased series has been presented to pay attention to the im portance of SPG in the differential diagnosis of chronic granulomatous inflammation

The use of virtual reality in children undergoing vascular access procedures: a systematic review and meta-analysis

Venous access procedures are painful and feared by children and their parents. Virtual reality has become increasingly prominent and has been shown to be effective in various procedures. The aim of this meta-analysis was to examine virtual reality’s effect on pain and fear in children from 4 to 12 in the context of vascular access. From the 20th to the 26th December 2020, we searched Sciencedirect, Springerlink, CENTRAL, Pubmed and PMC. Studies using virtual reality versus a control in vascular access for children were included in a meta-analysis to evaluate the effect of virtual reality regarding pain as a primary and fear/anxiety as a secondary endpoint during the procedures. The Jadad scale and Delphi List were used to assess study quality. 20,894 citations were identified, 9 met our inclusion criteria. One publication was conducted in two different situations and was thus considered as 2 studies. Compared to standard of care, virtual reality significantly reduced pain (10 studies, 930 participants: standardized mean difference [SMD] 2.54, 95%CI 0.14–4.93, p = 0.038), and fear/anxiety (6 studies, 648 participants: SMD 0.89, 95%Cl 0.16–1.63, p = 0.017). For both parameters, we found significant heterogeneity between studies. This is the first meta-analysis to look at the use virtual reality in young children undergoing vascular access procedures, providing weak to moderate evidence for its use. Although large effect sizes provide evidence for a positive effect of virtual reality in reducing pain and fear, there is significant heterogeneity between studies. More research with larger groups and age stratification is required.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A novel form of recessive limb girdle muscular dystrophy with mental retardation and abnormal expression of α-dystroglycan

The limb girdle muscular dystrophies are a heterogeneous group of conditions characterized by proximal muscle weakness and disease onset ranging from infancy to adulthood. We report here eight patients from seven unrelated families affected by a novel and relatively mild form of autosomal recessive limb girdle muscular dystrophy (LGMD2) with onset in the first decade of life and characterized by severe mental retardation but normal brain imaging. Immunocytochemical studies revealed a significant selective reduction of α-dystroglycan expression in the muscle biopsies. Linkage analysis excluded known loci for both limb girdle muscular dystrophy and congenital muscular dystrophies in the consanguineous families. We consider that this represents a novel form of muscular dystrophy with associated brain involvement. The biochemical studies suggest that it may belong to the growing number of muscular dystrophies with abnormal expression of α-dystroglycan. © 2003 Published by Elsevier B.V

ß2-Microglobulin deficiency causes a complex immunodeficiency of the innate and adaptive immune system

PubMed ID: 25702838Background Most patients with MHC class I (MHC-I) deficiency carry genetic defects in transporter associated with antigen processing 1 (TAP1) or TAP2. The clinical presentation can vary, and about half of the patients have severe skin disease. Previously, one report described ß2-microglobulin (ß2m) deficiency as another monogenetic cause of MHC-I deficiency, but no further immunologic evaluation was performed. Objective We sought to describe the molecular and immunologic features of ß2m deficiency in 2 Turkish siblings with new diagnoses. Methods Based on clinical and serologic findings, the genetic defect was detected by means of candidate gene analysis. The immunologic characterization comprises flow cytometry, ELISA, functional assays, and immunohistochemistry. Results Here we provide the first extensive clinical and immunologic description of ß2m deficiency in 2 siblings. The sister had recurrent respiratory tract infections and severe skin disease, whereas the brother was fairly asymptomatic but had bronchiectasis. Not only polymorphic MHC-I but also the related CD1a, CD1b, CD1c, and neonatal Fc receptor molecules were absent from the surfaces of ß2m-deficient cells. Absent neonatal Fc receptor surface expression led to low serum IgG and albumin levels in both siblings, whereas the heterozygous parents had normal results for all tested parameters except ß2m mRNA (B2M) expression. Similar to TAP deficiency in the absence of a regular CD8 T-cell compartment, CD8+ ?? T cells were strongly expanded. Natural killer cells were normal in number but not "licensed to kill." Conclusion The clinical presentation of patients with ß2m deficiency resembles that of patients with other forms of MHC-I deficiency, but because of the missing stabilizing effect of ß2m on other members of the MHC-I family, the immunologic defect is more extensive than in patients with TAP deficiency. © 2015 American Academy of Allergy, Asthma & Immunology