Autism is a neurodevelopmental condition diagnosed by impaired social interaction, abnormal communication and, stereotyped behaviors. While post-mortem and imaging studies have provided good insights into the neurobiological symptomology of autism, animal models can be used to study the neuroanatomical, neurophysiological and molecular mediators in more detail and in a more controlled environment. The valproic acid (VPA) rat model is an environmentally triggered model with strong construct and clinical validity. It is based on VPA teratogenicity in humans, where mothers who are medicated with VPA during early pregnancy show an increased risk for giving birth to an autistic child. In rats, early embryonic exposure, around the time of neural tube closure, leads to autism-like anatomical and behavioral abnormalities in the offspring. Considering the increasing use of the VPA rat model, we present our observations of the general health of Wistar dams treated with a single intraperitoneal injection of 500 or, 600 mg/kg VPA on embryonic day E12.5, as well as their male and female offspring, in comparison to saline-exposed controls. We report increased rates of complete fetal reabsorption after both VPA doses. VPA 500 mg/kg showed no effect on dam body weight during pregnancy or, on litter size. Offspring exposed to VPA 500 mg/kg showed smaller brain mass on postnatal days 1 (P1) and 14 (P14), in addition to abnormal nest seeking behavior at P10 in the olfactory discrimination test, relative to controls. We also report increased rates of physical malformations in the offspring, rare occurrences of chromodacryorrhea and, developmentally similar body mass gain. Further documentation of developmental health may guide sub-grouping of individuals in a way to better predict core symptom severity.

Childhood neuroblastoma is one of the most common types of extra-cranial cancer affecting children with a clinical spectrum ranging from spontaneous regression to malignant and fatal progression. In order to improve the clinical outcomes of children with high-risk neuroblastoma, it is crucial to understand the tumorigenic mechanisms that govern its malignant behaviors. MYCN proto-oncogene, bHLH transcription factor (MYCN) amplification has been implicated in the malignant, treatment-evasive nature of aggressive, high-risk neuroblastoma. In this study, we used a SILAC approach to compare the proteomic signatures of MYCN-amplified IMR-32 and non-MYCN-amplified SK-N-SH human neuroblastoma cells. Tumorigenic proteins, including fatty-acid binding protein 5 (FABP5), L1-cell adhesion molecule (L1-CAM), baculoviral IAP repeat containing 5 [BIRC5 (survivin)] and high mobility group protein A1 (HMGA1) were found to be significantly upregulated in the IMR-32 compared to the SK-N-SH cells and mapped to highly tumorigenic pathways including, MYC, MYCN, microtubule associated protein Tau (MAPT), E2F transcription factor 1 (E2F1), sterol regulatory element binding transcription factor 1 or 2 (SREBF1/2), hypoxia-inducible factor 1α (HIF-1α), Sp1 transcription factor (SP1) and amyloid precursor protein (APP). The transcriptional knockdown (KD) of MYCN, HMGA1, FABP5 and L1-CAM significantly abrogated the proliferation of the IMR-32 cells at 48 h post transfection. The early apoptotic rates were significantly higher in the IMR-32 cells in which FABP5 and MYCN were knocked down, whereas cellular migration was significantly abrogated with FABP5 and HMGA1 KD compared to the controls. Of note, L1-CAM, HMGA1 and FABP5 KD concomitantly downregulated MYCN protein expression and MYCN KD concomitantly downregulated L1-CAM, HMGA1 and FABP5 protein expression, while survivin protein expression was significantly downregulated by MYCN, HMGA1 and FABP5 KD. In addition, combined L1-CAM and FABP5 KD led to the concomitant downregulation of HMGA1 protein expression. On the whole, our data indicate that this inter-play between MYCN and the highly tumorigenic proteins which are upregulated in the malignant IMR-32 cells may be fueling their aggressive behavior, thereby signifying the importance of combination, multi-modality targeted therapy to eradicate this deadly childhood cancer.

Summary: Three consecutive daily sessions of cathodal transcranial direct current stimulation (tDCS) was sufficient to show a significant decrease in headache duration and intensity as well as tablets consumption, in patients suffering from episodic migraine. Background: Migraine prophylaxis is recommended in patients with frequent and/or intense headaches, but poor tolerability and lack of efficacy of preventive drugs are common in clinical practice. Hence, new prophylactic strategies are needed. Objective: The aim of this study was to evaluate the efficacy of tDCS in terms of migraine prophylaxis. Methods: This was a double blind and sham-controlled trial. Forty-two migraine patients were randomly assigned in a crossover design to receive three consecutive daily sessions of both sham and cathodal tDCS stimulation (2.0 mA, 20 min) over the occipital cortex of the dominant side of the migraine pain (O1/O2). Migraine duration and intensity, number of analgesic tablets, and number of headache-free days (where no headache abortive medications are taken) were recorded one week before and two weeks after treatment. A washout period of one week was allowed before crossing to the other treatment arm. Results: Relative to sham, cathodal stimulation was associated with a significant reduction in the number of headache days, tablets consumption, and pain intensity; and a significant increase in the number of headache-free days. These beneficial effects were sustained over two weeks. No serious side effects were observed, and the procedure was well tolerated. Conclusion: Based on these findings, cathodal tDCS applied to the occipital cortex seems to be an effective and well tolerated alternative to pharmacotherapy in patients with episodic migraine.

The onset of coronary artery disease (CAD) is influenced by cardiovascular risk factors that often occur in clusters and may build on one another. The objective of this study is to examine the relationship between hypertension and CAD age of onset in the Lebanese population. This retrospective analysis was performed on data extracted from Lebanese patients (n = 3,753). Logistic regression examined the association of hypertension with the age at CAD diagnosis after controlling for other traditional risk factors. The effect of antihypertensive drugs and lifestyle changes on the onset of CAD was also investigated. Results showed that hypertension is associated with late onset CAD (OR=0.656, 95% CI=0.504-0.853, p=0.001). Use of antihypertensive drugs showed a similar association with delayed CAD onset. When comparing age of onset in CAD patients with traditional risk factors such as hypertension, diabetes, hyperlipidemia, obesity, smoking and family history of CAD, the age of onset was significantly higher for patients with hypertension compared to those with any of the other risk factors studied (p < 0.001). In conclusion, hypertension and its treatment are associated with late coronary atherosclerotic manifestations in Lebanese population. This observation is currently under investigation to clarify its genetic and/or environmental mechanisms.

Background: Medication overuse headache (MOH) is a chronic pain syndrome that arises from the frequent use of acute antimigraine drugs. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with a possible therapeutic effect in this particular context. Methods: This was a randomized, sham-controlled, cross-over study. Eighteen patients with MOH (17 women, age range: 20–38 years) received three sets of three consecutive daily sessions of tDCS: anodal tDCS over the prefrontal cortex, cathodal tDCS over the occipital cortex ipsilateral to the dominant side of migraine pain, and sham. The order in which the tDCS blocks were delivered was randomly defined based on a 1:1:1 ratio. Patients filled in a migraine diary that allowed recording of the pain intensity (visual analogue scale) and the daily consumption of analgesic pills from one week before to two weeks after each condition. Results: Both prefrontal and occipital tDCS lowered the total number of migraine days and the number of severe migraine days per week at week 1, but only the effects of occipital tDCS on these two outcomes lasted until week 2. Only occipital tDCS decreased the daily analgesic pills consumption, at weeks 1 and 2. Conclusion: Three consecutive days of cathodal occipital tDCS appear to improve the clinical outcomes in patients with MOH.