Open total arch replacement (TAR) has become safer with refinements in cerebral protection techniques. The frequent extension of aortic arch aneurysms into the descending thoracic aorta customarily ...requires a two-staged conventional elephant trunk procedure, carrying relatively high mortality and morbidity risks and high rates of rupture in the interval between the two open surgeries. The technical demands and invasive nature of TAR has therefore precluded many high-risk patients from being surgical candidates for aneurysm repair. As a result, hybrid techniques and approaches to the aortic arch have become common since the adoption of thoracic endovascular aortic repair (TEVAR) and advancement in the commercial grafts that are available. The results of hybrid aortic arch repairs have been encouraging, though with higher rates of re-interventions than TAR and variable reported rates of stroke and spinal cord ischemia. The aim of this publication is to review the current literature on hybrid repair of aortic arch aneurysms.
The LIGO Open Science Center Vallisneri, Michele; Kanner, Jonah; Williams, Roy ...
Journal of physics. Conference series,
05/2015, Volume:
610, Issue:
1
Journal Article
Peer reviewed
Open access
The LIGO Open Science Center (LOSC) fulfills LIGO's commitment to release, archive, and serve LIGO data in a broadly accessible way to the scientific community and to the public, and to provide the ...information and tools necessary to understand and use the data. In August 2014, the LOSC published the full dataset from Initial LIGO's "S5" run at design sensitivity, the first such large-scale release and a valuable testbed to explore the use of LIGO data by non-LIGO researchers and by the public, and to help teach gravitational-wave data analysis to students across the world. In addition to serving the S5 data, the LOSC web portal (losc.ligo.org) now offers documentation, data-location and data-quality queries, tutorials and example code, and more. We review the mission and plans of the LOSC, focusing on the S5 data release.
The use of minimally, or less invasive, approaches to cardiac valve surgery has increased over the past decade. Because of its less traumatic nature, early studies in lower risk patients demonstrated ...the approach to be associated with an enhanced recovery, increased patient satisfaction, and good operative outcomes. With time, despite a steep learning curve, surgeons expanded this approach to perform more complex procedures, and include patients with more co-morbidity. The aim of this publication is to review the current literature involving the use of minimally invasive valve surgery (MIVS) in higher-risk patients.
Epigenetic parameters (DNA methylation, histone modifications, and miRNAs) play a significant role in cancer. To identify the common epigenetic signatures of both the individual matrix ...metalloproteinases (MMPs) and the additional genes, the function of which is also linked to proteolysis, migration, and tumorigenesis, we performed epigenetic profiling of 486 selected genes in unrelated non-migratory MCF-7 breast carcinoma and highly migratory U251 glioma cells. Genome-wide transcriptional profiling, quantitative reverse transcription-PCR, and microRNA analyses were used to support the results of our epigenetic studies. Transcriptional silencing in both glioma and breast carcinoma cells predominantly involved the repressive histone H3 Lys-27 trimethylation (H3K27me3) mark. In turn, epigenetic stimulation was primarily performed through a gain in the histone H3 Lys-4 dimethylation (H3K4me2) and H3 hyperacetylation and by a global reduction of H3K27me3. Inactive pro-invasive genes in MCF-7 cells but not in U251 cells frequently exhibited a stem cell-like bivalent mark (enrichment in both H3K27me3 and H3K4me2), a characteristic of developmental genes. In contrast with other MMPs, MMP-8 was epigenetically silenced in both cell types, thus providing evidence for the strict epigenetic control of this anti-tumorigenic proteinase in cancer. Epigenetic stimulation of multiple collagen genes observed in cultured glioma cells was then directly confirmed using orthotopic xenografts and tumor specimens. We suggest that the epigenetic mechanisms allow gliomas to deposit an invasion-promoting collagen-enriched matrix and then to use this matrix to accomplish their rapid migration through the brain tissue.
The Ets2 transcription factor is essential for the development of the mouse placenta and for generating signals for embryonic mesoderm and axis formation. Using a conditional targeted Ets2 allele, we ...show that Ets2 is essential for trophoblast stem (TS) cells self-renewal. Inactivation of Ets2 results in TS cell slower growth, increased expression of a subset of differentiation-associated genes and decreased expression of several genes implicated in TS self-renewal. Among the direct TS targets of Ets2 is
Cdx2, a key master regulator of TS cell state. Thus Ets2 contributes to the regulation of multiple genes important for maintaining the undifferentiated state of TS cells and as candidate signals for embryonic development.
Compounds with the stilbene pharmacophore and other nonsteroidal estrogens have previously been shown to inhibit thrombin-induced elevation of intracellular free calcium (Cai) in human platelets. ...Thrombin elevates Cai in platelets predominantly by activating a store-operated Ca entry (SOCE) mechanism, probably involving STIM1 and Orai1 although other components may be involved.
Human platelets were loaded with the Ca sensitive indicator fura-2, various concentrations of stilbene compounds and other nonsteroidal estrogens were added to the platelets, and thrombin was added to elevate Cai. The degree of inhibition by each compound was determined at the peak increase in Cai induced by thrombin.
The additional compounds that were examined in the present study were analogs of diethylstilbestrol (DES), namely trans-resveratrol, hexestrol, tetrahydrochrysene (THC), indenestrol, isoflavones, flavones, and flavanones. DES, indenestrols, and substituted THC diols had the highest inhibitory activity. Dietary polyphenols were less active, and isoflavones were more active than flavones. Glycosides of flavones, flavanones, and isoflavones were inactive. Equol (a product of isoflavone metabolism) had low activity. Among the compounds with a stilbene moiety the presence of unsubstituted phenyl hydroxyls in the para- position were required for activity. Esterification of hydroxyls and bulky substituents at a hydroxyl group diminished or abolished activity. Presence of the ethyl side chains enhanced activity, and shortening or removal of these side chains was detrimental to activity. Presence of the conjugated double bound was necessary for activity. Reduction of the double bond (in fused rings such as equol, dihydrogenistein, indanestrol, or in open chain stilbene derivatives) or repositioning of this double bond outside the stilbene moiety was detrimental to activity, because phenyl rings are not co-planar and have to be at a certain angle to each other.
DES likely represents the pharmacophore of this group of nonsteroidal estrogens as an inhibitor of SOCE in platelets.
The optimal treatment for concomitant two-vessel coronary artery disease (CAD) and moderate to severe ischemic mitral regurgitation (IMR) remains unclear. We compared the results of a staged ...percutaneous coronary intervention followed by minimally invasive mitral valve surgery (PCI+MIVS) versus combined coronary artery bypass graft and mitral valve surgery (CABG+MVS) in this population.
All consecutive patients with two-vessel CAD and moderate to severe IMR, who underwent PCI+MIVS or CABG+MVS at our institution between February 2009 and April 2014, were retrospectively evaluated.
There were nine patients identified who underwent PCI+MIVS, and 15 who underwent CABG+MVS, with a mean age of 71±7, and 70±7 years, respectively (P=0.86). The remaining baseline characteristics were similar between both groups, with the exception of a higher prevalence of pre-operative clopidogrel administration (78% versus 27%, P=0.03) and left anterior descending plus left circumflex CAD (78% versus 27%, P=0.03), in those who underwent PCI+MIVS. The PCI+MIVS approach was associated with decreased mean cardiopulmonary bypass (111±41 versus 167±49 min, P=0.01) and aortic cross-clamp (79±32 versus 129±35 min, P=0.003) times, and less median number of intraoperative packed red blood transfusions {2 interquartile range (IQR), 0-2 versus 3 units (IQR, 1-4), P=0.05}, when compared with CABG+MVS. The rate of mitral valve repair, postoperative complications, 30-day mortality, and 1-year survival did not differ between the surgical approaches.
PCI+MIVS for two-vessel CAD and moderate to severe IMR is feasible, and associated with satisfactory outcomes, as compared with CABG+MVS.
Decreases in glial cell density and in GFAP mRNA in the anterior cingulate cortex have been reported in schizophrenia, bipolar disorder and major depressive disorder. Our study examines astrocyte and ...oligodendrocyte density in the white and grey matter of the subgenual cingulate cortex, and at the midline of the genu of the corpus callosum, in schizophrenia, bipolar disorder, depression and normal control cases. Serial coronal sections were stained with H and E for anatomical guidance, cresyl haematoxylin for oligodendrocyte identification and GFAP immunohistochemistry for astrocyte identification. Oligodendrocyte and astrocyte density was measured using systematic anatomical distinctions and randomised counting methods. A significant decrease in astrocyte density was observed in schizophrenia compared with normal controls in the cingulate grey matter, cingulate white matter and the midline of the corpus callosum (
p
= 0.025). Bipolar disorder and depression cases showed no significant changes in astrocyte density. Oligodendrocytes did not show any changes between diagnostic groups. In subgenual cingulate cortex, the ratio of oligodendrocytes to astrocytes was decreased between the controls and the three disease groups, suggesting a specific glial cell type specific change in schizophrenia.
Sepsis and septic shock are major healthcare problems that need early and appropriate management.
To evaluate the association of daily cefepime pharmacokinetic/pharmacodynamic (PK/PD) parameters with ...change in Sequential Organ Failure Assessment (SOFA) score and vasopressors requirement.
This is a retrospective study. Adult ICU patients who received cefepime for Gram-negative pneumonia or bloodstream infection (BSI) and had cefepime concentrations measured were included. Daily cefepime exposure was generated and PK/PD parameters calculated for patients. Repeated-measures mixed-effect modeling was used to evaluate the impact of PK/PD on the outcomes.
Change in daily SOFA score and vasopressors requirement.
A total of 394 and 207 patients were included in the SOFA and vasopressors analyses, respectively. The mean (±sd) age was 55 years (19) and weight 81 kg (29). For the change in SOFA score, daily SOFA score, mechanical ventilation, renal replacement therapy, and number of vasopressors were included. In the vasopressors analysis, daily SOFA score, day of therapy, and hydrocortisone dose were significant covariates in the final model. Achieving cefepime concentrations above the minimum inhibitory concentration (MIC) (T
) for 100% of the dosing interval was associated with 0.006 µg/kg/min decrease in norepinephrine-equivalent dose. Cefepime PK/PD did not have an impact on the daily change in SOFA score.
Achieving 100% T
was associated with negligible decrease in vasopressors requirement in ICU patients with Gram-negative pneumonia and BSI. There was no impact on the change in SOFA score.
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