Evaluation of Teratogenic Activity of Antiepileptic Drug Lamotrigine in Mouse Fetuses

BACKGROUND: Use of antiepileptic drugs during pregnancy can be associated with an increased risk of teratogenicity as well as congenital abnormalities. However, there are numerous discrepancies to determine whether lamotrigine, as an antiepileptic drug, can significantly induce malformation in newborn infants or not. Thus, the purpose of the study was to evaluate the teratogenic effects of lamotrigine on mouse fetuses. MATERIALS AND METHODS: In the present study, 21 pregnant mice were assigned to four groups. Groups 1 and 2 (controls) received mock treatment and ethanol 20%, respectively. Groups 3 and 4 (treatment) were intraperitoneally administered with 25 and 75 mg/kg lamotrigine for three days, respectively. The treatment protocol was performed within the gestational days of 9-18 in all groups. On gestational day 18, 117 fetuses were taken out of the fallopian tube of studied mice and then examined for any anomalies (vertebral, limbs and cranial), followed by a measurement of their height and weight. RESULTS: The results revealed that, in the treated groups, the weight and the height had significantly decreased (p<0.01) and also various anomalies were evident. Moreover, as the dose of lamotrigine increased, the decrease in the weight and the height and rising trend in anomalies were intensified. CONCLUSION: According to the findings, lamotrigine (LTG) could be considered as a risk factor for the development of the anomalies examined

Biological and Clinical Relevance of Long Non-Coding RNA PCAT-1 in Cancer, A Systematic Review and Meta-Analysis

Long non-coding RNA (lncRNA) prostate cancer associated transcript 1 (PCAT-1) has been identified as a potential biomarker for the diagnosis and prognosis of various cancers. We performed this systematic review and meta-analysis to evaluate the role of dysregulation as well as the biological and clinical significance of lnc-PCAT-1 for predicting the malignancy status in several cancers. Two independent reviewers conducted an extensive search in electronic databases of Medline, Embase, Scopus, Web of Science and PubMed until the December of 2017. Five articles investigating the clinical significance of lncRNA PCAT-1, including 996 patients, were analyzed. Our results revealed that the increased PCAT-1 expression was related to overall survival (OS) (HR = 1.9, 95%CI: 1.13-3.18, P=0.015). Also, pooled results of the diagnostic data analysis demonstrated that PCAT-1 has a sensitivity of 0.59 and specificity of 0.66 for cancer diagnosis. Moreover, pooled area under curve was 0.62 (95% CI: 0.58–0.69). This meta-analysis revealed that lncRNA PCAT-1 could be served as a potential diagnostic and prognostic biomarker in various solid tumors

Possible involvement of PI3K/AKT/mTOR signaling pathway in the protective effect of selegiline (deprenyl) against memory impairment following ischemia reperfusion in rat

Short-term cerebral ischemia led to memory dysfunction. There is a pressing need to introduce effective agents to reduce complications of the ischemia. Involvement of PI3K/AKT/mTOR signaling pathway has been determined in the neuroprotective effect of various agents. Selegiline (deprenyl) possessed neuroprotective properties. In this study global ischemia/reperfusion was established in rats. Selegiline (5 mg/kg for 7 consecutive days) administrated via intraperitoneal route. Possible involvement of PI3K/AKT/mTOR signaling pathway was evaluated using qRT-PCR, immunohistochemistry and histophatologic evaluations in the hippocampus. Spatial memory was evaluated by morris water maze (MWM). Results showed that ischemia impaired the memory and ischemic rats spent more time to find hidden platform in the MWM. Ischemia significantly decreased levels of PI3K, AKT and mTOR in the hippocampus. Histopathologic assessment revealed that the percent of dark neurons significantly increased in the CA1 area of the hippocampus of ischemic rats. Selegiline improved the memory as ischemic rats spent fewer time to find hidden platform in the MWM. Findings showed that selegiline increased the level and expression of PI3K, AKT and mTOR as well as decreased the proportion of dark neurons in the CA1 area of the pyramidal layer of the hippocampus. We concluded that selegiline, partially at least, through increases the expression of PI3K, AKT and mTOR as well as decreases the percent of dark neurons in the hippocampus could improve the memory impairment following the ischemia in rat

Delay aversion but preference for large and rare rewards in two choice tasks: implications for the measurement of self-control parameters

BACKGROUND: Impulsivity is defined as intolerance/aversion to waiting for reward. In intolerance-to-delay (ID) protocols, animals must choose between small/soon (SS) versus large/late (LL) rewards. In the probabilistic discount (PD) protocols, animals are faced with choice between small/sure (SS) versus large/luck-linked (LLL) rewards. It has been suggested that PD protocols also measure impulsivity, however, a clear dissociation has been reported between delay and probability discounting. RESULTS: Wistar adolescent rats (30- to 46-day-old) were tested using either protocol in drug-free state. In the ID protocol, animals showed a marked shift from LL to SS reward when delay increased, and this despite adverse consequences on the total amount of food obtained. In the PD protocol, animals developed a stable preference for LLL reward, and maintained it even when SS and LLL options were predicted and demonstrated to become indifferent. We demonstrate a clear dissociation between these two protocols. In the ID task, the aversion to delay was anti-economical and reflected impulsivity. In the PD task, preference for large reward was maintained despite its uncertain delivery, suggesting a strong attraction for unitary rewards of great magnitude. CONCLUSION: Uncertain delivery generated no aversion, when compared to delays producing an equivalent level of large-reward rarefaction. The PD task is suggested not to reflect impulsive behavior, and to generate patterns of choice that rather resemble the features of gambling. In summary, present data do indicate the need to interpret choice behavior in ID and PD protocols differently

Serotonin Differentially Regulates Short- and Long-Term Prediction of Rewards in the Ventral and Dorsal Striatum

BACKGROUND: The ability to select an action by considering both delays and amount of reward outcome is critical for maximizing long-term benefits. Although previous animal experiments on impulsivity have suggested a role of serotonin in behaviors requiring prediction of delayed rewards, the underlying neural mechanism is unclear. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the role of serotonin in the evaluation of delayed rewards, we performed a functional brain imaging experiment in which subjects chose small-immediate or large-delayed liquid rewards under dietary regulation of tryptophan, a precursor of serotonin. A model-based analysis revealed that the activity of the ventral part of the striatum was correlated with reward prediction at shorter time scales, and this correlated activity was stronger at low serotonin levels. By contrast, the activity of the dorsal part of the striatum was correlated with reward prediction at longer time scales, and this correlated activity was stronger at high serotonin levels. CONCLUSIONS/SIGNIFICANCE: Our results suggest that serotonin controls the time scale of reward prediction by differentially regulating activities within the striatum

Correction to: "Comparative repair capacity of knee osteochondral defects using regenerated silk fiber scaffolds and fibrin glue with/without autologous chondrocyes during 36 weeks in rabbit model (Cell and Tissue Research, (2016), 364, 3, (559-572), 10.1007/s00441-015-2355-9)

In this paper, figure 1 and its associated text were erroneously identical to that of another article from our group (Mobini et al., 2016, Journal of Biomaterial Application, SAGE publications). Unfortunately, copyright permission to re-use figure 1 and its related data were not requested. The authors would like to apologize for any confusion caused in this regard. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature

Is preference for mHealth intervention delivery platform associated with delivery platform familiarity?

Published online: 22 July 2016Background: The aim of this paper was to ascertain whether greater familiarity with a smartphone or tablet was associated with participants’ preferred mobile delivery modality for eHealth interventions. Methods: Data from 1865 people who participated in the Australian Health and Social Science panel study were included into two multinomial logistic regression analyses in which preference for smartphone and tablet delivery for general or personalised eHealth interventions were regressed onto device familiarity and the covariates of sex, age and education. Results: People were more likely to prefer both general and personalised eHealth interventions presented on tablets if they reported high or moderate tablet familiarity (compared to low familiarity) and people were more likely to prefer both general and personalised eHealth interventions presented on smartphones if they reported high or moderate smartphone familiarity, were younger, and had university education (compared to completing high school or less). Conclusion: People prefer receiving eHealth interventions on the mobile devices they are most familiar with. These findings have important implications that should be considered when developing eHealth interventions, and demonstrates that eHealth interventions should be delivered using multiple platforms simultaneously to optimally cater for as many people as possible.Daniel Granger, Corneel Vandelanotte, Mitch J. Duncan, Stephanie Alley, Stephanie Schoeppe, Camille Short and Amanda Reba

Sterol Intermediates of Cholesterol Biosynthesis Inhibit Hair Growth and Trigger an Innate Immune Response in Cicatricial Alopecia

Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders

Anxiety Disorders and Sensory Over-Responsivity in Children with Autism Spectrum Disorders: Is There a Causal Relationship?

Anxiety disorders and sensory over-responsivity (SOR) are common in children with autism spectrum disorders (ASD), and there is evidence for an association between these two conditions. Currently, it is unclear what causal mechanisms may exist between SOR and anxiety. We propose three possible theories to explain the association between anxiety and SOR: (a) SOR is caused by anxiety; (b) Anxiety is caused by SOR; or (c) SOR and anxiety are causally unrelated but are associated through a common risk factor or diagnostic overlap. In this paper, we examine support for each theory in the existing anxiety, autism, and neuroscience literature, and discuss how each theory informs choice of interventions and implications for future studies