Predator and restraint stress during gestation facilitates pilocarpine-induced seizures in prepubertal rats

Stress during gestation can result in early and long-term developmental aberrations. This study aimed to assess the impact of prenatal restraint or predator stress on pilocarpine-induced epileptic behavior. Pregnant rats were exposed to stressors on gestational days 15, 16, and 17. Restraint stress consisted of daily restraint of the dam. During predator stress, caged rats were exposed to a cat in a cage. On postnatal day 25, male pups were injected with pilocarpine and the behavior of each rat was observed. Prenatal stress led to low birth weight and increased blood corticosterone levels. Both stressors significantly potentiated pilocarpine-induced seizures. Predator-stressed pups exhibited significantly severe tonic-clonic seizures compared with restraint-stressed animals. These data emphasize the impact of prenatal stress on fetal growth, and neural and endocrine function. The results also suggest that psychosocial stressors have a greater impact on neural and endocrine function than physical stressors do.     

Impact of obesity on autoimmune arthritis and its cardiovascular complications

Obesity can instigate and sustain a systemic low-grade inflammatory environment that can amplify autoimmune disorders and their associated comorbidities. Metabolic changes and inflammatory factors produced by the adipose tissue have been reported to aggravate autoimmunity and predispose the patient to cardiovascular disease (CVD) and metabolic comorbidities. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are autoimmune arthritic diseases, often linked with altered body mass index (BMI). Severe joint inflammation and bone destruction have a debilitating impact on the patient's life; there is also a staggering risk of cardiovascular morbidity and mortality. Furthermore, these patients are at risk of developing metabolic symptoms, including insulin resistance resulting in type 2 diabetes mellitus (T2DM). In addition, arthritis severity, progression and response to therapy can be markedly affected by the patient's BMI. Hence, a complex integrative pathogenesis interconnects autoimmunity with metabolic and cardiovascular disorders. This review aims to shed light on the network that connects obesity with RA, PsA, systemic lupus erythematosus and Sj?gren's syndrome. We have focused on clarifying the mechanism by which obesity affects different cell types, inflammatory factors and traditional therapies in these autoimmune disorders. We conclude that to further optimize arthritis therapy and to prevent CVD, it is imperative to uncover the intricate relation between obesity and arthritis pathology.     

Anti-Vibriocholerae IgY Antibody Inhibits Mortality in Suckling Mice Model

Background

Regarding to the importance of cholera in Iran and the potential advantages of egg yolk antibody (IgY) for immunotherapy, the aim of this study was to produce IgY antibody against V. cholerae Lipopolysaccharide (LPS) and determine its potential for V. cholerae treatment.

Evidence of DNA methylation in the neurofibromatosis type 1 (NF1) gene region of 17q11.2

Modification of mammalian DNA by the methylation of cytosinein CpG dinucleotides is a complex phenomenon involved in a numberof cellular and developmental processes. In a particular, thecharacteristic hypermutability of CpGs may be a major contributorof point mutations leading to human genetic disease. We havehypothesized that DNA methylation contributes to mutations inthe gene causing neurofibromatosis type 1 (NF1), one of themost common genetic disorders in humans and a disease whereup to half of all cases are the result of sporadic germlinemutations, usually in the paternally-derived allele. We haveused two experimental approaches to analyze patterns of DNAmethylation at CpG dinucleotides in the NF1 gene region. Southernanalyses using isoschizomeric restriction pairs have revealedDNA methylation in areas flanking the NF1 gene region, whilePCR-methylation assays have shown that methylation occurs bothon genomic sequences flanking the NF1 gene and within the codingregion of the gene itself. We suggest that methylated CpG dinucleotideswithin and around the highly mutable NF1 gene serve as a reservoirwithin which C-T transitions contribute to the high frequencyof spontaneous germline mutations associated with the disease.     

Using Artificial Intelligence to Improve the Quality and Safety of Radiation Therapy

Within artificial intelligence, machine learning (ML) efforts in radiation oncology have augmented the transition from generalized to personalized treatment delivery. Although their impact on quality and safety of radiation therapy has been limited, they are increasingly being used throughout radiation therapy workflows. Various data-driven approaches have been used for outcome prediction, CT simulation, clinical decision support, knowledge-based planning, adaptive radiation therapy, plan validation, machine quality assurance, and process quality assurance; however, there are many challenges that need to be addressed with the creation and usage of ML algorithms as well as the interpretation and dissemination of findings. In this review, the authors present current applications of ML in radiation oncology quality and safety initiatives, discuss challenges faced by the radiation oncology community, and suggest future directions.     

Histone deacetylase inhibitors and candidate gene expression: An in vivo and in vitro approach to studying chromatin remodeling in a clinical population

Objective

The emerging field of psychiatric epigenetics is constrained by the dearth of research methods feasible in living patients. With this focus, we report on two separate approaches, one in vitro and one in vivo, developed in our laboratory.

Method

In the first approach, we isolated lymphocytes from 12 subjects and cultured their cells with either 0.7 mM valproic acid (VPA), 100 nM Trichostatin A (TSA), or DMSO (control) for 24 h based upon previous dose response experiments. We then measured GAD67 mRNA expression using realtime RT-PCR, total acetylated histone 3 (H3K9,K14ac) levels using Western blot analysis, and attachment of H3K9,K14ac to the GAD67 promoter using ChIP. In the second approach, we measured GAD67 mRNA and total H3K9,K14ac levels in lymphocytes from 11 schizophrenia and 7 bipolar patients before and after 4 weeks of clinical treatment with Depakote ER^® (VPA).

Results

In the first approach, VPA induced a 383% increase in GAD67 mRNA, an 89% increase in total H3K9,K14ac levels, and a 482% increase in H3K9,K14ac attachment to the GAD67 promoter. TSA induced comparable changes on all measures. In the second approach, bipolar subjects had significantly higher baseline levels of H3K9,K14ac compared to subjects with schizophrenia. Subjects with clinically relevant serum levels of VPA (?65 μg/mL) showed a significant increase in GAD67 mRNA expression.

Conclusions

Our results utilizing two separate approaches for examining chromatin remodeling in real clinical time provide possible means to investigate epigenetic events in living patients.     

Detection of intracranial aneurysms: multi-detector row CT angiography compared with DSA

PURPOSE: To prospectively compare the effectiveness of multi-detector row computed tomographic (CT) angiography with that of conventional intraarterial digital subtraction angiography (DSA) used to detect intracranial aneurysms in patients with nontraumatic acute subarachnoid hemorrhage. MATERIALS AND METHODS: Thirty-five consecutive adult patients with acute subarachnoid hemorrhage were recruited into the institutional review board-approved study and gave informed consent. All patients underwent both multi-detector row CT angiography and DSA no more than 12 hours apart. CT angiography was performed with a multi-detector row scanner (four detector rows) by using collimation of 1.25 mm and pitch of 3. Images were interpreted at computer workstations in a blinded fashion. Two radiologists independently reviewed the CT images, and two other radiologists independently reviewed the DSA images. The presence and location of aneurysms were rated on a five-point scale for certainty. Sensitivity and specificity were calculated independently for image interpretation performed by the two CT image readers and the second DSA image reader by using the first DSA reader's interpretation as the reference standard. RESULTS: A total of 26 aneurysms were detected at DSA in 21 patients, and no aneurysms were detected in 14 patients. Sensitivity and specificity for CT angiography were, respectively, 90% and 93% for reader 1 and 81% and 93% for reader 2. The mean diameter of aneurysms detected on CT angiographic images was 4.4 mm, and the smallest aneurysm detected was 2.2 mm in diameter. Aneurysms that were missed at initial interpretation of CT angiographic images were identified at retrospective reading. CONCLUSION: Multi-detector row CT angiography has high sensitivity and specificity for detection of intracranial aneurysms, including small aneurysms, in patients with nontraumatic acute subarachnoid hemorrhage.