Performance of Sequoyah Containment Anchorage System

Deformation of a steel containment anchorage system during a severe accident may result in a leakage path at the containment boundaries. Current design criteria are based on either ductile or brittle failure modes of headed bolts that do not account for factors such as cracking of the containment basemat or deformation of the anchor bolt that may affect the behavior of the containment anchorage system. The purpose of this study was to investigate the performance of a typical ice condenser containment`s anchorage system. This was accomplished by analyzing the Sequoyah Containment Anchorage System. Based on a strength of materials approach and assuming that the anchor bolts are resisting the uplift caused by the internal pressure, one can estimate that the failure of the anchor bolts would occur at a containment pressure of 79 psig. To verify these results and to calibrate the strength of materials equation, the Sequoyah containment anchorage system was analyzed with the ABAQUS program using a three-dimensional, finite-element model. The model included portions of the steel containment building, shield building, anchor bolt assembly, reinforced concrete mat and soil foundation material

Minimally Invasive Video-Assisted Thyroidectomy and Parathyroidectomy with Intraoperative Recurrent Laryngeal Nerve Monitoring

Objective. Our goal is to study the feasibility of using intraoperative neuromonitoring (IONM) in minimally invasive video-assisted thyroidectomy and parathyroidectomy (MIVAT/P) with emphasis given to the identification of recurrent laryngeal nerve (RLN). Methods. Consecutive series of forty-seven patients with seventy-seven recurrent laryngeal nerves at risk undergoing both MIVAT/P and IONM were enrolled in this retrospective, nonrandomized analysis study. All operations were performed by the same surgeon within an academic institution setting. All patients underwent vocal cord evaluation postoperatively. Demographics and intraoperative and postoperative complications following surgery were collected. Results. Out of seventy-seven RLNs, there was one permanent unilateral RLN injury (1.29%) in a patient with advanced papillary thyroid cancer, managed by cord injection. There was another transient RLN paresis that resolved spontaneously (1.29%). There were no instances of equipment malfunction or interference. Conclusions. To our knowledge, this is the first reported MIVAT/P series from the United States of America with a standardized IONM technique. The technical feasibility of IONM seems acceptable and may serve as a meaningful adjunct to the visual identification of nerves. Neuromonitoring during MIVAT/P is effective in providing identification of laryngeal nerves and enables surgeons to feel more comfortable with MIVAT/P. Comparative series are needed for further evaluation

Antiphospholipid Antibodies Bind ATP: A putative Mechanism for the Pathogenesis of Neuronal Dysfunction

Antiphospholipid antibodies (aPL) generated in experimental animals cross-react with ATP. We therefore examined the possibility that aPL IgG from human subjects bind to ATP by affinity column and an enzyme linked immunosorbent assay (ELISA). Sera with high levels of aPL IgG were collected from 12 patients with the antiphospholipid syndrome (APS). IgG fractions from 10 of 12 APS patients contained aPL that could be affinity-bound to an ATP column and completely eluted with NaCl 0.5 M. A significant (>50%) inhibition of aPL IgG binding by ATP 5 mM was found in the majority. Similar inhibition was obtained with ADP but not with AMP or cAMP. All the affinity purified anti-ATP antibodies also bound β2-glycoprotein-I (β2-GPI, also known as apolipoprotein H) suggesting that, similar to most pathogenic aPL, their binding depends on this serum cofactor. We further investigated this possibility and found that the binding of β2-GPI to the ATP column was similar to that of aPL IgG in that most was reversed by NaCl 0.5 M. Furthermore, addition of β2-GPI to aPL IgG significantly increased the amount of aPL binding to an ATP column. We conclude that aPL IgG bind ATP, probably through β2-GPI. This binding could interfere with the normal extracellular function of ATP and similar neurotransmitters

Disease- and age-related changes in histone acetylation at gene promoters in psychiatric disorders

Increasing evidence suggests that epigenetic factors have critical roles in gene regulation in neuropsychiatric disorders and in aging, both of which are typically associated with a wide range of gene expression abnormalities. Here, we have used chromatin immunoprecipitation-qPCR to measure levels of acetylated histone H3 at lysines 9/14 (ac-H3K9K14), two epigenetic marks associated with transcriptionally active chromatin, at the promoter regions of eight schizophrenia-related genes in n=82 postmortem prefrontal cortical samples from normal subjects and those with schizophrenia and bipolar disorder. We find that promoter-associated ac-H3K9K14 levels are correlated with gene expression levels, as measured by real-time qPCR for several genes, including, glutamic acid decarboxylase 1 (GAD1), 5-hydroxytryptamine receptor 2C (HTR2C), translocase of outer mitochondrial membrane 70 homolog A (TOMM70A) and protein phosphatase 1E (PPM1E). Ac-H3K9K14 levels of several of the genes tested were significantly negatively associated with age in normal subjects and those with bipolar disorder, but not in subjects with schizophrenia, whereby low levels of histone acetylation were observed in early age and throughout aging. Consistent with this observation, significant hypoacetylation of H3K9K14 was detected in young subjects with schizophrenia when compared with age-matched controls. Our results demonstrate that gene expression changes associated with psychiatric disease and aging result from epigenetic mechanisms involving histone acetylation. We further find that treatment with a histone deacetylase (HDAC) inhibitor alters the expression of several candidate genes for schizophrenia in mouse brain. These findings may have therapeutic implications for the clinical use of HDAC inhibitors in psychiatric disorders

Recovery of ζ-chain expression and changes in spontaneous IL-10 production after PSA-based vaccines in patients with prostate cancer

Circulating T lymphocytes of patients with prostate cancer have been reported to have functional deficits, including low or absent ζ-chain expression. To determine whether these functional impairments could be reversed by prostate specific antigen-based vaccination therapy, 10 patients treated with recombinant human prostate specific antigen plus GM-CSF and eight others receiving prostate specific antigen plus oil emulsion in two pilot clinical trials were evaluated prior to and after vaccination for several immunologic end points, including ζ-chain expression and cytokine production by circulating T cells as well as the frequency of T cells able to respond to prostate specific antigen in ELISPOT assays. The flow cytometry assay for ζ-chain expression was standardized to allow for a reliable comparison of pre- vs post-vaccination samples. Prior to therapy, the patients were found to have significantly lower ζ-chain expression in circulating CD3+ cells and a higher percentage of ζ-chain negative CD3+ and CD4+ cells than normal donors. The patients' peripheral blood mononuclear cells spontaneously produced more IL-10 ex vivo than those of normal controls. After vaccination, recovery of ζ-chain expression was observed in 50% of patients in both clinical trials. Also, spontaneous IL-10 secretion by peripheral blood mononuclear cells decreased following immunotherapy in patients treated with prostate specific antigen and GM-CSF. The frequency of prostate specific antigen-reactive T cells was detectable in 7 out of 18 patients vs 4 out of 18 patients prior to vaccination. Only one of 18 patients was a clinical responder. The vaccine had stimulatory effects on the patients' immune system, but post-vaccine immune recovery could not be correlated to progression-free survival in this small cohort of patients with prostate cancer

Epigenetic management of major psychosis

Epigenetic mechanisms are thought to play a major role in the pathogenesis of the major psychoses (schizophrenia and bipolar disorder), and they may be the link between the environment and the genome in the pathogenesis of these disorders. This paper discusses the role of epigenetics in the management of major psychosis: (1) the role of epigenetic drugs in treating these disorders. At present, there are three categories of epigenetic drugs that are being actively investigated for their ability to treat psychosis: drugs inhibiting histone deacetylation; drugs decreasing DNA methylation; and drugs targeting microRNAs; and (2) the role of epigenetic mechanisms in electroconvulsive therapy in these disorders

Metabolic Variation during Development in Culture of Leishmania donovani Promastigotes

The genome sequencing of several Leishmania species has provided immense amounts of data and allowed the prediction of the metabolic pathways potentially operating. Subsequent genetic and proteomic studies have identified stage-specific proteins and putative virulence factors but many aspects of the metabolic adaptations of Leishmania remain to be elucidated. In this study, we have used an untargeted metabolomics approach to analyze changes in the metabolite profile as promastigotes of L. donovani develop during in vitro cultures from logarithmic to stationary phase. The results show that the metabolomes of promastigotes on days 3–6 of culture differ significantly from each other, consistent with there being distinct developmental changes. Most notable were the structural changes in glycerophospholipids and increase in the abundance of sphingolipids and glycerolipids as cells progress from logarithmic to stationary phase

The Endocrine Disruptor Mono-(2-Ethylhexyl) Phthalate Affects the Differentiation of Human Liposarcoma Cells (SW 872)

Esters of phthalic acid (phthalates) are largely used in industrial plastics, medical devices, and pharmaceutical formulations. They are easily released from plastics into the environment and can be found in measurable levels in human fluids. Phthalates are agonists for peroxisome proliferator-activated receptors (PPARs), through which they regulate translocator protein (TSPO; 18 kDa) transcription in a tissue-specific manner. TSPO is a drug- and cholesterol-binding protein involved in mitochondrial respiration, steroid formation, and cell proliferation. TSPO has been shown to increase during differentiation and decrease during maturation in mouse adipocytes. The purpose of this study was to establish the effect of mono-(2-ethylhexyl) phthalate (MEHP) on the differentiation of human SW 872 preadipocyte cells, and examine the role of TSPO in the process. After 4 days of treatment with 10 µM MEHP, we observed changes in the transcription of acetyl-CoA carboxylase alpha, adenosine triphosphate citrate lyase, glucose transporters 1 and 4, and the S100 calcium binding protein B, all of which are markers of preadipocyte differentiation. These observed gene expression changes coincided with a decrease in cellular proliferation without affecting cellular triglyceride content. Taken together, these data suggest that MEHP exerts a differentiating effect on human preadipocytes. Interestingly, MEHP was able to temporarily increase TSPO mRNA levels through the PPAR-α and β/δ pathways. These results suggest that TSPO can be considered an important player in the differentiation process itself, or alternatively a factor whose presence is essential for adipocyte development

Situational awareness within objective structured clinical examination stations in undergraduate medical training - a literature search

Background: Medical students may not be able to identify the essential elements of situational awareness (SA) necessary for clinical reasoning. Recent studies suggest that students have little insight into cognitive processing and SA in clinical scenarios. Objective Structured Clinical Examinations (OSCEs) could be used to assess certain elements of situational awareness. The purpose of this paper is to review the literature with a view to identifying whether levels of SA based on Endsley's model can be assessed utilising OSCEs during undergraduate medical training. Methods: A systematic search was performed pertaining to SA and OSCEs, to identify studies published between January 1975 (first paper describing an OSCE) and February 2017, in peer reviewed international journals published in English. PUBMED, EMBASE, PsycINFO Ovid and SCOPUS were searched for papers that described the assessment of SA using OSCEs among undergraduate medical students. Key search terms included "objective structured clinical examination", "objective structured clinical assessment" or "OSCE" and "non-technical skills", "sense-making", "clinical reasoning", "perception", "comprehension", "projection", "situation awareness", "situational awareness" and "situation assessment". Boolean operators (AND, OR) were used as conjunctions to narrow the search strategy, resulting in the limitation of papers relevant to the research interest. Areas of interest were elements of SA that can be assessed by these examinations. Results: The initial search of the literature retrieved 1127 publications. Upon removal of duplicates and papers relating to nursing, paramedical disciplines, pharmacy and veterinary education by title, abstract or full text, 11 articles were eligible for inclusion as related to the assessment of elements of SA in undergraduate medical students. Discussion: Review of the literature suggests that whole-task OSCEs enable the evaluation of SA associated with clinical reasoning skills. If they address the levels of SA, these OSCEs can provide supportive feedback and strengthen educational measures associated with higher diagnostic accuracy and reasoning abilities. Conclusion: Based on the findings, the early exposure of medical students to SA is recommended, utilising OSCEs to evaluate and facilitate SA in dynamic environment