A novel insight into differential expression profiles of sporadic cerebral cavernous malformation patients with different symptoms.

Cerebral cavernous malformation (CCM) is a vascular lesion of the central nervous system that may lead to distinct symptoms among patients including cerebral hemorrhages, epileptic seizures, focal neurologic deficits, and/or headaches. Disease-related mutations were identified previously in one of the three CCM genes: CCM1, CCM2, and CCM3. However, the rate of these mutations in sporadic cases is relatively low, and new studies report that mutations in CCM genes may not be sufficient to initiate the lesions. Despite the growing body of research on CCM, the underlying molecular mechanism has remained largely elusive. In order to provide a novel insight considering the specific manifested symptoms, CCM patients were classified into two groups (as Epilepsy and Hemorrhage). Since the studied patients experience various symptoms, we hypothesized that the underlying cause for the disease may also differ between those groups. To this end, the respective transcriptomes were compared to the transcriptomes of the control brain tissues and among each other. This resulted into the identification of the differentially expressed coding genes and the delineation of the corresponding differential expression profile for each comparison. Notably, some of those differentially expressed genes were previously implicated in epilepsy, cell structure formation, and cell metabolism. However, no CCM1-3 gene deregulation was detected. Interestingly, we observed that when compared to the normal controls, the expression of some identified genes was only significantly altered either in Epilepsy (EGLN1, ELAVL4, and NFE2l2) or Hemorrhage (USP22, EYA1, SIX1, OAS3, SRMS) groups. To the best of our knowledge, this is the first such effort focusing on CCM patients with epileptic and hemorrhagic symptoms with the purpose of uncovering the potential CCM-related genes. It is also the first report that presents a gene expression dataset on Turkish CCM patients. The results suggest that the new candidate genes should be explored to further elucidate the CCM pathology. Overall, this work constitutes a step towards the identification of novel potential genetic targets for the development of possible future therapies.

Intracytoplasmic morphologically selected sperm injection, but for whom?

Intracytoplasmic sperm injection (ICSI) is performed in cases of infertility by injecting a motile and morphologically normal sperm cell under a routine ×400 magnification at which is hard to distinguish morphologically healthy sperm. Recently, the use of high-powered differential interference contrast optics gave the opportunity to select a sperm under ultra-high magnification of ×10,160. The aim of the present study was to evaluate the efficacy of the intracytoplasmic morphologically selected sperm injection (IMSI) technique in different infertility populations undergoing ICSI. Main outcome measures of routine ICSI were compared with IMSI in three different groups of patients (1, non-selected; 2, male infertility; and 3, repeated implantation failure group). Results were analysed to evaluate the effects of the IMSI procedure and to find the most suitable group of patients who may benefit from the procedure. IMSI caused a significant increase in the fertilization and top quality embryo rates in the male infertility group and a significant increase in fertilization and pregnancy rates in the repeated implantation failure group, whereas no effect was observed in the non-selected group with patients of various indications. A positive effect of IMSI on the outcome of male factor infertility and repeated implantation failure patients was observed. Data observed confirmed that the application of IMSI was beneficial for a selected group of patients with male factor infertility and repeated implantation failure.