Case Report Asystole after Orthotopic Lung Transplantation: Examining the Interaction of Cardiac Denervation and Dexmedetomidine

Dexmedetomidine is an α 2 -receptor agonist commonly used for sedation and analgesia in ICU patients. Dexmedetomidine is known to provide sympatholysis and also to have direct atrioventricular and sinoatrial node inhibitory effects. In rare instances, orthotopic lung transplantation has been associated with disruption of autonomic innervation of the heart. The combination of this autonomic disruption and dexmedetomidine may be associated with severe bradycardia and/or asystole. Since orthotopic lung transplant patients with parasympathetic denervation will not respond with increased heart rate to anticholinergic therapy, bradyarrhythmias must be recognized and promptly treated with direct acting beta agonists to avoid asystolic cardiac events

How much will precipitation increase with global warming?

Copyright © 2008 American Geophysical UnionThe advent of meteorological satellites during the 1970s made possible the observation of the seasonally shifting patterns of global precipitation. It was not until recently, however, that the record could be considered long enough to investigate longer-term trends and the relationship between global precipitation and global warming. Using data from the Special Sensor Microwave Imager (SSM/I) instrument, Wentz et al. [2007] reported that global mean precipitation increased at a rate of 7.4±2.6% per °C between 1987 and 2006. Meanwhile, general circulation models (GCMs) used to predict climate change simulate twentieth- and 21st-century mean precipitation increases of about 13% per °C [Held and Soden, 2006]. This difference seems surprising because some GCMs can adequately reproduce the much longer twentieth- century surface-based land-mean precipitation record [Lambert et al., 2005]. Global precipitation changes are tied to the surface energy budget through evaporation and to the tropospheric energy budget through condensation. Thus, if GCMs do underestimate global precipitation changes, the simulation of other climate variables will be affected

Alternative lengthening of telomeres, ATRX loss and H3â K27M mutations in histologically defined pilocytic astrocytoma with anaplasia

Anaplasia may be identified in a subset of tumors with a presumed pilocytic astrocytoma (PA) component or piloid features, which may be associated with aggressive behavior, but the biologic basis of this change remains unclear. Fiftyâ seven resections from 36 patients (23 M, 13 F, mean age 32 years, range 3â 75) were included. A clinical diagnosis of NF1 was present in 8 (22%). Alternative lengthening of telomeres (ALT) was assessed by telomereâ specific FISH and/or CISH. A combination of immunohistochemistry, DNA sequencing and FISH were used to study BRAF, ATRX, CDKN2A/p16, mutant IDH1 p.R132H and H3â K27M proteins. ALT was present in 25 (69%) cases and ATRX loss in 20 (57%), mostly in the expected association of ALT+/ATRXâ (20/24, 83%) or ALTâ /ATRX+ (11/11, 100%). BRAF duplication was present in 8 (of 26) (31%). H3â K27M was present in 5 of 32 (16%) cases, all with concurrent ATRX loss and ALT. ALT was also present in 9 (of 11) cases in the benign PA precursor, 7 of which also had ATRX loss in both the precursor and the anaplastic tumor. In a single pediatric case, ALT and ATRX loss developed in the anaplastic component only, and in another adult case, ALT was present in the PAâ A component only, but ATRX was not tested. Features associated with worse prognosis included subtotal resection, adult vs. pediatric, presence of a PA precursor preceding a diagnosis of anaplasia, necrosis, presence of ALT and ATRX expression loss. ALT and ATRX loss, as well as alterations involving the MAPK pathway, are frequent in PA with anaplasia at the time of development of anaplasia or in their precursors. Additionally, a small subset of PA with anaplasia have H3â K27M mutations. These findings further support the concept that PA with anaplasia is a neoplasm with heterogeneous genetic features and alterations typical of both PA and diffuse gliomas.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/1/bpa12646_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147190/2/bpa12646.pd

Capturing, sharing and analysing biophysical data from protein engineering and protein characterization studies

Large amounts of data are being generated annually on the connection between the sequence, structure and function of proteins using site-directed mutagenesis, protein design and directed evolution techniques. These data provide the fundamental building blocks for our understanding of protein function, molecular biology and living organisms in general. However, much experimental data are never deposited in databases and is thus ‘lost’ in journal publications or in PhD theses. At the same time theoretical scientists are in need of large amounts of experimental data for benchmarking and calibrating novel predictive algorithms, and theoretical progress is therefore often hampered by the lack of suitable data to validate or disprove a theoretical assumption. We present PEAT (Protein Engineering Analysis Tool), an application that integrates data deposition, storage and analysis for researchers carrying out protein engineering projects or biophysical characterization of proteins. PEAT contains modules for DNA sequence manipulation, primer design, fitting of biophysical characterization data (enzyme kinetics, circular dichroism spectroscopy, NMR titration data, etc.), and facilitates sharing of experimental data and analyses for a typical university-based research group. PEAT is freely available to academic researchers at http://enzyme.ucd.ie/PEAT

Fusion Learning Conference 2021 - Supplement

This is a supplement to the proceedings of the 2021 Fusion Learning Conference held at Bournemouth University in the UK and contains material not previously published

Principal role of adenylyl cyclase 6 in K+ channel regulation and vasodilator signalling in vascular smooth muscle cells

AIMS: Membrane potential is a key determinant of vascular tone and many vasodilators act through the modulation of ion channel currents [e.g. the ATP-sensitive potassium channel (K(ATP))] involved in setting the membrane potential. Adenylyl cyclase (AC) isoenzymes are potentially important intermediaries in such vasodilator signalling pathways. Vascular smooth muscle cells (VSMCs) express multiple AC isoenzymes, but the reason for such redundancy is unknown. We investigated which of these isoenzymes are involved in vasodilator signalling and regulation of vascular ion channels important in modulating membrane potential. METHODS AND RESULTS: AC isoenzymes were selectively depleted (by >75%) by transfection of cultured VSMCs with selective short interfering RNA sequences. AC6 was the predominant isoenzyme involved in vasodilator-mediated cAMP accumulation in VSMCs, accounting for ∼60% of the total response to β-adrenoceptor (β-AR) stimulation. AC3 played a minor role in β-AR signalling, whereas AC5 made no significant contribution. AC6 was also the principal isoenzyme involved in β-AR-mediated protein kinase A (PKA) signalling (determined using the fluorescent biosensor for PKA activity, AKAR3) and the substantial β-AR/PKA-dependent enhancement of K(ATP) current. K(ATP) current was shown to play a vital role in setting the resting membrane potential and in mediating the hyperpolarization observed upon β-AR stimulation. CONCLUSION: AC6, but not the closely related AC5, plays a principal role in vasodilator signalling and regulation of the membrane potential in VSMCs. These findings identify AC6 as a vital component in the vasodilatory apparatus central to the control of blood pressure

Finding a niche? Challenger parties and issue emphasis in the 2015 televised leaders' debates

Do leaders of challenger parties adopt a ?niche? strategy in national televised debates? This paper answers this question by analysing the content of the two multiparty televised leaders? debates that took place ahead of the 2015 British general election. Using computer-aided text analysis (CATA), it provides reliable and valid measures of what the leaders said in both debates and develops our theoretical understanding of how challenger-party leaders make their pitches. It finds that the UKIP, Green, SNP and Plaid Cymru leaders all demonstrated a degree of ?nicheness? in their contributions in comparison with the Conservative, Liberal Democrat and Labour leaders. It also finds that the challenger-party leaders placed a greater emphasis on their core concerns. Nevertheless, the debates covered much policy ground. Their structure obliged all party leaders to talk about mainstream issues

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy