ABCG2, SCN1A and CYP3A5 genes polymorphism and drug-resistant epilepsy in children: A case-control study.

PURPOSE: Drug Resistant -Epilepsy is still a major challenge in pharmacotherapy of epilepsy. Pharmacogenetic pathways are one of the most important elements that can help clinicians determine medication response and provide more efficient drug therapy, especially in cases of drug resistance. Genetic alterations in drug target and transporter proteins, in part, could explain the development of drug-resistant epilepsy. We sought to assess the association of CYP3A5 (rs776746), SCN1A (rs2298771) and ABCG2 (rs2231137) candidate polymorphisms with drug-resistant epilepsy among Iranian children with epilepsy. METHODS: In a hospital-based case-control study, 93 participants, including 45 men and 48 women aged 1.5 to 14 years old were recruited. Genotyping of CYP3A5 (rs776746), SCN1A (rs2298771) and ABCG2 (rs2231137) polymorphisms using the high-resolution melting (HRM) method were measured in 46 children with drug-resistant epilepsy and 47 healthy control subjects. The binary logistic regression model was used to estimate the odds ratio (OR) for each polymorphism per effect allele increase. RESULTS: The mean (standard deviation [SD]) age of the drug-resistant patients was 10.7 (9.0) years versus 7.3 (3.6) in the control group. In the case group, most of the patients with epilepsy were diagnosed with generalized seizure (about 87%) and negative epileptic history status (63%). Furthermore, idiopathic epilepsy was dominant in the case group (69%). There was a clinically meaningful increase in the chance of drug-resistant epilepsy in participants with candidate polymorphism in ABCG2 gene (per allele T increase, adjusted odds ratio [OR] 2.41, confidence interval [CI] 0.99 to 5.87, P=0.05). No significant association was found between CYP3A5 (per allele C increase, OR 0.92, CI 0.33 to 2.60, P= 0.88) and SCN1A (per allele *1 increase, OR 0.65, 95% CI 0.34 to 1.23, P= 0.19) with drug-resistant epilepsy. CONCLUSION: We found evidence for the relationship between the ABCG2 gene polymorphism and a higher chance of drug-resistant epilepsy in children. This finding may have important implications for understanding the role of ABCG2 gene polymorphism in children with drug-resistant epilepsy.

Evaluation of the Effect of Platelet-Rich Fibrin on Wound Healing at Split-Thickness Skin Graft Donor Sites: A Randomized, Placebo-Controlled, Triple-Blind Study.

Split-thickness skin grafting (STSG) is widely used to heal wounds resulting from trauma, burns, and chronic wounds. This study aimed to determine the true effect of platelet-rich fibrin (PRF) on patients with burn wounds requiring STSG during treatment of donor wounds. This randomized, triple-blind clinical trial was conducted on patients who referred to the burn ward of Vasei Hospital of Sabzevar, Iran, from May 2017 to May 2018. The donor site was randomly divided into 2 groups: PRF and control (Vaseline petrolatum gauze) using Vaseline gauze. In the intervention group, the PRF gel was applied to the wound and covered with Vaseline gauze and wet dressing. Conversely, only Vaseline gauze and wet dressing were applied to the control group. Outcome evaluation was conducted using paired t test and Wilcoxon signed rank-sum test, as appropriate, on days 8 and 15. The mean age of the patients was 33.10 ± 2.60 years, and 51.50% were male. The mean wound healing time in the PRF and control groups was 11.80 ± 3.51 and 16.30 ± 4.32 days, respectively (P < .001). The PRF group showed significantly higher wound healing rates than the control group at 8 and 15 days dressing (P < .001 and P < .001, respectively). Moreover, the mean wound healing for all wound healing indices diagnosed by 2 specialists in PRF was higher than control group on days 8 and 15 (P < .001). We found a statistically significant difference on days 8 and 15 regarding the mean pain levels between the 2 groups (P < .001). The findings showed that PRF can significantly increase the time and rate of donor wound healing compared with conventional treatment and also reduce the severity of pain.

Adaptive neuro-fuzzy sliding mode control of multi-joint movement using intraspinal microstimulation.

During the last decade, intraspinal microstimulation (ISMS) has been proposed as a potential technique for restoring motor function in paralyzed limbs. A major challenge to restoration of a desired functional limb movement through the use of ISMS is the development of a robust control strategy for determining the stimulation patterns. Accurate and stable control of limbs by functional intraspinal microstimulation is a very difficult task because neuromusculoskeletal systems have significant nonlinearity, time variability, large latency and time constant, and muscle fatigue. Furthermore, the controller must be able to compensate the effect of the dynamic interaction between motor neuron pools and electrode sites during ISMS. In this paper, we present a robust strategy for multi-joint control through ISMS in which the system parameters are adapted online and the controller requires no offline training phase. The method is based on the combination of sliding mode control with fuzzy logic and neural control. Extensive experiments on six rats are provided to demonstrate the robustness, stability, and tracking accuracy of the proposed method. Despite the complexity of the spinal neuronal networks, our results show that the proposed strategy could provide accurate tracking control with fast convergence and could generate control signals to compensate for the effects of muscle fatigue.

Potential of human umbilical cord matrix and rabbit bone marrow-derived mesenchymal stem cells in repair of surgically incised rabbit external anal sphincter.

PURPOSE: Anal sphincter defects and fecal incontinence are complicated surgical problems. We investigated the ability of human umbilical cord matrix (hUCM) and rabbit bone marrow (rBM) stem cells to improve anal sphincter incontinence due to induced sphincter defects without surgical repair. METHODS: We harvested hUCM cells from human Wharton's jelly and rBM stem cells from rabbit femurs and tibias. To induce sphincter defects, we made an incision in the external anal sphincter. Rabbits were randomly allocated to 5 groups to receive either no intervention (n = 3) or injections of 10 hUCM cells in medium (10 microL RPMI-1640), rBM cells in medium, medium only, or normal saline (n = 7 per group), 2 weeks after sphincterotomy. Transplanted cells were tracked in the injured sphincters by prelabeling with bromodeoxyuridine. Electromyography was performed before and 2 weeks after the external anal sphincterotomy, and 2 weeks after cell transplantation. We also evaluated the proliferation and differentiation of injected cells with histopathologic techniques. RESULTS: Electromyography showed significant improvement in sphincter function 2 weeks after local injection of rBM stem cells compared with pretreatment values and controls. Moderate, nonsignificant improvement was observed with hUCM cell injection. Cells with incorporated bromodeoxyuridine were detected at the site of injury after transplantation of hUCM and rBM. Histopathologic evaluation showed normal or muscle-dominant sphincter structure in all animals receiving rBM and fibrous-dominant sphincter structure in most animals receiving hUCM. CONCLUSIONS: Stem cell injection at the site of injury can enhance contractile function of the anal sphincter without surgical repair. Transplantation of stem cells, particularly bone marrow mesenchymal cells, may provide an effective tool for treating anal sphincter injuries in humans.