Combined Endovascular/Surgical Management of a Ruptured Para-Anastomotic Aneurysm of the Left Common Iliac Artery#

A 75-year old man presented with signs and symptoms of acute abdomen and a clinical picture of hypovolemic shock. An emergency CT scan revealed a ruptured para-anastomotic left common iliac artery aneurysm. The patient had undergone an elective abdominal aortic aneurysm repair operation and placement of an aortoiliac bifurcated graft 10 years before. Para-anastomotic aneurysms had developed in all 3 (aortic and the 2 iliac) anastomosis. As the patient was highrisk, a combined endovascular/surgical approach was undertaken. The patient was discharged 4 days later

The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ATP Carrier to Bongkrekate in Yeast

The ADP/ATP carrier protein (AAC) expressed in Artemia franciscana is refractory to bongkrekate. We generated two strains of Saccharomyces cerevisiae where AAC1 and AAC3 were inactivated and the AAC2 isoform was replaced with Artemia AAC containing a hemagglutinin tag (ArAAC-HA). In one of the strains the suppressor of ΔAAC2 lethality, SAL1, was also inactivated but a plasmid coding for yeast AAC2 was included, because the ArAACΔsal1Δ strain was lethal. In both strains ArAAC-HA was expressed and correctly localized to the mitochondria. Peptide sequencing of ArAAC expressed in Artemia and that expressed in the modified yeasts revealed identical amino acid sequences. The isolated mitochondria from both modified strains developed 85% of the membrane potential attained by mitochondria of control strains, and addition of ADP yielded bongkrekate-sensitive depolarizations implying acquired sensitivity of ArAAC-mediated adenine nucleotide exchange to this poison, independent from SAL1. However, growth of ArAAC-expressing yeasts in glycerol-containing media was arrested by bongkrekate only in the presence of SAL1. We conclude that the mitochondrial environment of yeasts relying on respiratory growth conferred sensitivity of ArAAC to bongkrekate in a SAL1-dependent manner. © 2013 Wysocka-Kapcinska et al

The role of the fat mass and obesity associated gene (FTO) in breast cancer risk

<p>Abstract</p> <p>Background</p> <p>Obesity has been shown to increase breast cancer risk. <it>FTO </it>is a novel gene which has been identified through genome wide association studies (GWAS) to be related to obesity. Our objective was to evaluate tissue expression of FTO in breast and the role of FTO SNPs in predicting breast cancer risk.</p> <p>Methods</p> <p>We performed a case-control study of 354 breast cancer cases and 364 controls. This study was conducted at Northwestern University. We examined the role of single nucleotide polymorphisms (SNPs) of intron 1 of <it>FTO </it>in breast cancer risk. We genotyped cases and controls for four SNPs: rs7206790, rs8047395, rs9939609 and rs1477196. We also evaluated tissue expression of FTO in normal and malignant breast tissue.</p> <p>Results</p> <p>We found that all SNPs were significantly associated with breast cancer risk with rs1477196 showing the strongest association. We showed that FTO is expressed both in normal and malignant breast tissue. We found that <it>FTO </it>genotypes provided powerful classifiers to predict breast cancer risk and a model with epistatic interactions further improved the prediction accuracy with a receiver operating characteristic (ROC) curves of 0.68.</p> <p>Conclusion</p> <p>In conclusion we have shown a significant expression of FTO in malignant and normal breast tissue and that <it>FTO </it>SNPs in intron 1 are significantly associated with breast cancer risk. Furthermore, these <it>FTO </it>SNPs are powerful classifiers in predicting breast cancer risk.</p

Nitric Oxide-Induced Activation of the AMP-Activated Protein Kinase α2 Subunit Attenuates IκB Kinase Activity and Inflammatory Responses in Endothelial Cells

BACKGROUND: In endothelial cells, activation of the AMP-activated protein kinase (AMPK) has been linked with anti-inflammatory actions but the events downstream of kinase activation are not well understood. Here, we addressed the effects of AMPK activation/deletion on the activation of NFκB and determined whether the AMPK could contribute to the anti-inflammatory actions of nitric oxide (NO). METHODOLOGY/PRINCIPAL FINDINGS: Overexpression of a dominant negative AMPKα2 mutant in tumor necrosis factor-α-stimulated human endothelial cells resulted in increased NFκB activity, E-selectin expression and monocyte adhesion. In endothelial cells from AMPKα2(-/-) mice the interleukin (IL)-1β induced expression of E-selectin was significantly increased. DETA-NO activated the AMPK and attenuated NFκB activation/E-selectin expression, effects not observed in human endothelial cells in the presence of the dominant negative AMPK, or in endothelial cells from AMPKα2(-/-) mice. Mechanistically, overexpression of constitutively active AMPK decreased the phosphorylation of IκB and p65, indicating a link between AMPK and the IκB kinase (IKK). Indeed, IKK (more specifically residues Ser177 and Ser181) was found to be a direct substrate of AMPKα2 in vitro. The hyper-phosphorylation of the IKK, which is known to result in its inhibition, was also apparent in endothelial cells from AMPKα2(+/+) versus AMPKα2(-/-) mice. CONCLUSIONS: These results demonstrate that the IKK is a direct substrate of AMPKα2 and that its phosphorylation on Ser177 and Ser181 results in the inhibition of the kinase and decreased NFκB activation. Moreover, as NO potently activates AMPK in endothelial cells, a portion of the anti-inflammatory effects of NO are mediated by AMPK

An analysis of factors that influence personal exposure to toluene and xylene in residents of Athens, Greece

BACKGROUND: Personal exposure to pollutants is influenced by various outdoor and indoor sources. The aim of this study was to evaluate the exposure of Athens citizens to toluene and xylene, excluding exposure from active smoking. METHODS: Passive air samplers were used to monitor volunteers, their homes and various urban sites for one year, resulting in 2400 measurements of toluene and xylene levels. Since both indoor and outdoor pollution contribute significantly to human exposure, volunteers were chosen from occupational groups who spend a lot of time in the streets (traffic policemen, bus drivers and postmen), and from groups who spend more time indoors (teachers and students). Data on individual and house characteristics were obtained using a questionnaire completed at the beginning of the study; a time-location-activity diary was also completed daily by the volunteers in each of the six monitoring campaigns. RESULTS: Average personal toluene exposure varied over the six monitoring campaigns from 53 to 80 μg/m(3). Urban and indoor concentrations ranged from 47 – 84 μg/m(3 )and 30 – 51 μg/m(3), respectively. Average personal xylene exposure varied between 56 and 85 μg/m(3 )while urban and indoor concentrations ranged from 53 – 88 μg/m(3 )and 27 – 48 μg/m(3), respectively. Urban pollution, indoor residential concentrations and personal exposures exhibited the same pattern of variation during the measurement periods. This variation among monitoring campaigns might largely be explained by differences in climate parameters, namely wind speed, humidity and amount of sunlight. CONCLUSION: In Athens, Greece, the time spent outdoors in the city center during work or leisure makes a major contribution to exposure to toluene and xylene among non-smoking citizens. Indoor pollution and means of transportation contribute significantly to individual exposure levels. Other indoor residential characteristics such as recent painting and mode of heating used might also contribute significantly to individual levels. Groups who may be subject to higher exposures (e.g. those who spent more time outdoors because of occupational activities) need to be surveyed and protected against possible adverse health effects

Toxicogenomic Analysis Suggests Chemical-Induced Sexual Dimorphism in the Expression of Metabolic Genes in Zebrafish Liver

10.1371/journal.pone.0051971PLoS ONE712

Implementation of Guidelines for the Management of Arterial Hypertension. The Impulsion Study

This study assessed the effects of a pilot best practice implementation enhancement program on the control of hypertension. We enrolled 697 consecutive known hypertensive patients with other vascular risk factors but free from overt vascular disease. There was no “control” group because it was considered unethical to deprive high-risk patients from “best medical treatment”. Following a baseline visit, previously trained physicians aimed to improve adherence to lifestyle measures and drug treatment for hypertension and other vascular risk factors. Both at baseline and at study completion (after 6 months), a 1-page form was completed showing if patients achieved treatment targets. If not, the reasons why were recorded. This program enhanced compliance with lifestyle measures and increased the use of evidence-based medication. There was a substantial increase in the number of patients who achieved treatment targets for blood pressure (p<0.0001) and other vascular risk factors. In non-diabetic patients (n=585), estimated vascular risk (PROCAM risk engine) was significantly reduced by 41% (p<0.0001). There was also a 12% reduction in vascular risk according to the Framingham risk engine but this did not achieve significance (p=0.07). In conclusion, this is the first study to increase adherence to multiple interventions in hypertensive patients on an outpatient basis, both in primary care and teaching hospitals. Simple, relatively low cost measures (e.g. educating physicians and patients, distributing printed guidelines/brochures and completing a 1-page form) motivated both physicians and patients to achieve multiple treatment goals. Further work is needed to establish if the improvement observed is sustained. [ClinicalTrials.gov NCT00416611]

IQGAP1 Interacts with Components of the Slit Diaphragm Complex in Podocytes and Is Involved in Podocyte Migration and Permeability In Vitro

IQGAP1 is a scaffold protein that interacts with proteins of the cytoskeleton and the intercellular adhesion complex. In podocytes, IQGAP1 is associated with nephrin in the glomerular slit diaphragm (SD) complex, but its role remains ill-defined. In this work, we investigated the interaction of IQGAP1 with the cytoskeleton and SD proteins in podocytes in culture, and its role in podocyte migration and permeability. Expression, localization, and interactions between IQGAP1 and SD or cytoskeletal proteins were determined in cultured human podocytes by Western blot (WB), immunocytolocalization (IC), immunoprecipitation (IP), and In situ Proximity Ligation assay (IsPL). Involvement of IQGAP1 in migration and permeability was also assessed. IQGAP1 expression in normal kidney biopsies was studied by immunohistochemistry. IQGAP1 expression by podocytes increased during their in vitro differentiation. IC, IP, and IsPL experiments showed colocalizations and/or interactions between IQGAP1 and SD proteins (nephrin, MAGI-1, CD2AP, NCK 1/2, podocin), podocalyxin, and cytoskeletal proteins (α-actinin-4). IQGAP1 silencing decreased podocyte migration and increased the permeability of a podocyte layer. Immunohistochemistry on normal human kidney confirmed IQGAP1 expression in podocytes and distal tubular epithelial cells and also showed an expression in glomerular parietal epithelial cells. In summary, our results suggest that IQGAP1, through its interaction with components of SD and cytoskeletal proteins, is involved in podocyte barrier properties

Death and Science: The Existential Underpinnings of Belief in Intelligent Design and Discomfort with Evolution

The present research examined the psychological motives underlying widespread support for intelligent design theory (IDT), a purportedly scientific theory that lacks any scientific evidence; and antagonism toward evolutionary theory (ET), a theory supported by a large body of scientific evidence. We tested whether these attitudes are influenced by IDT's provision of an explanation of life's origins that better addresses existential concerns than ET. In four studies, existential threat (induced via reminders of participants' own mortality) increased acceptance of IDT and/or rejection of ET, regardless of participants' religion, religiosity, educational background, or preexisting attitude toward evolution. Effects were reversed by teaching participants that naturalism can be a source of existential meaning (Study 4), and among natural-science students for whom ET may already provide existential meaning (Study 5). These reversals suggest that the effect of heightened mortality awareness on attitudes toward ET and IDT is due to a desire to find greater meaning and purpose in science when existential threats are activated

Genes Expressed in Specific Areas of the Human Fetal Cerebral Cortex Display Distinct Patterns of Evolution

The developmental mechanisms through which the cerebral cortex increased in size and complexity during primate evolution are essentially unknown. To uncover genetic networks active in the developing cerebral cortex, we combined three-dimensional reconstruction of human fetal brains at midgestation and whole genome expression profiling. This novel approach enabled transcriptional characterization of neurons from accurately defined cortical regions containing presumptive Broca and Wernicke language areas, as well as surrounding associative areas. We identified hundreds of genes displaying differential expression between the two regions, but no significant difference in gene expression between left and right hemispheres. Validation by qRTPCR and in situ hybridization confirmed the robustness of our approach and revealed novel patterns of area- and layer-specific expression throughout the developing cortex. Genes differentially expressed between cortical areas were significantly associated with fast-evolving non-coding sequences harboring human-specific substitutions that could lead to divergence in their repertoires of transcription factor binding sites. Strikingly, while some of these sequences were accelerated in the human lineage only, many others were accelerated in chimpanzee and/or mouse lineages, indicating that genes important for cortical development may be particularly prone to changes in transcriptional regulation across mammals. Genes differentially expressed between cortical regions were also enriched for transcriptional targets of FoxP2, a key gene for the acquisition of language abilities in humans. Our findings point to a subset of genes with a unique combination of cortical areal expression and evolutionary patterns, suggesting that they play important roles in the transcriptional network underlying human-specific neural traits