Extracorporeal cardiopulmonary resuscitation

AbstractECPR is defined as the rapidly-deployed application of venoarterial extracorporeal membrane oxygenation, in patients with cardiac arrest, during cardiopulmonary resuscitation before the return of ROSC. ECPR is one of the most rapidly growing segments of ECLS, and is becoming more widespread. Consideration for institution of ECPR is given to patients with witnessed arrest, good quality CPR instituted within 5min of arrest, in whom ROSC does not occur within 15min, and who can complete cannulation within 30–60min. Patients from both inpatient and out-of-hospital settings are candidates if they meet these criteria. Deep hypothermic cardiac arrest, such as cold-water drowning, should receive consideration for ECPR even after considerable duration of arrest. Available outcome data are based on retrospective observation studies, some with propensity matching, and suggests a higher chance for survival with ECPR. Published outcomes from ECPR, however, are difficult to interpret, since many centers classify their use of ECLS after ROSC, in addition to ECLS before ROSC, as ECPR. Both children and adults are candidates for ECPR, but the experience in children is weighted heavily toward those with a diagnosis of cardiac disease and arrest occurring within closely monitored units

Rare manifestation of a c.290 C\u3eT, p.Gly97Glu VCP mutation

Introduction. The valosin-containing protein (VCP) regulates several distinct cellular processes. Consistent with this, VCP mutations manifest variable clinical phenotypes among and within families and are a diagnostic challenge. Methods. A 60-year-old man who played ice hockey into his 50’s was evaluated by electrodiagnostics, muscle biopsy, and molecular genetics. Results. With long-standing pes cavus and toe walking, our patient developed progressive weakness, cramps, memory loss, and paresthesias at age 52. An axonal sensorimotor neuropathy was found upon repeated testing at age 58. Neuropathic histopathology was present in the quadriceps, and exome sequencing revealed the VCP mutation c.290 C>T, p.Gly97Glu. Conclusions. Our patient reflects the clinical heterogeneity of VCP mutations, as his neurological localization is a spectrum between a lower motor neuron disorder and a hereditary axonal peripheral neuropathy such as CMT2. Our case demonstrates a rare manifestation of the c.290 C>T, pGly97Glu VCP mutation

Estimating error models for whole genome sequencing using mixtures of Dirichlet-multinomial distributions

Motivation: Accurate identification of genotypes is an essential part of the analysis of genomic data, including in identification of sequence polymorphisms, linking mutations with disease and determining mutation rates. Biological and technical processes that adversely affect genotyping include copy-number-variation, paralogous sequences, library preparation, sequencing error and reference-mapping biases, among others. Results: We modeled the read depth for all data as a mixture of Dirichlet-multinomial distributions, resulting in significant improvements over previously used models. In most cases the best model was comprised of two distributions. The major-component distribution is similar to a binomial distribution with low error and low reference bias. The minor-component distribution is overdispersed with higher error and reference bias. We also found that sites fitting the minor component are enriched for copy number variants and low complexity regions, which can produce erroneous genotype calls. By removing sites that do not fit the major component, we can improve the accuracy of genotype calls. Availability and Implementation: Methods and data files are available at https://github.com/ CartwrightLab/WuEtAl2017/ (doi:10.5281/zenodo.256858). Contact: [email protected] Supplementary information: Supplementary data is available at Bioinformatics online

Ejercicio dosis-respuesta de la pendiente V? E / V?CO 2 en mujeres posmenopáusicas en el estudio DREW

Purpose: Being overweight/obese, having hypertension, and being postmenopausal are risk factors for the development of congestive heart failure (CHF). A characteristic of CHF is an abnormal V?E/V?CO2 slope, which is predictive of mortality in patients with CHF. Although the V?E/V?CO2 slope is well established in CHF patients, little is known regarding interventions for 'at-risk' populations. Methods: We examined the V?E/V?CO2 slope in 401 sedentary, overweight, moderately hypertensive women randomized to 6 m of nonexercise (control) or 4 kcal·kg?1·wk?1 (KKW), 8 KKW, or 12 KKW of exercise at an intensity corresponding to 50% of baseline V?O2max. We examined trends in exercise treatment dose versus change in mean V?E/V?CO2 slope using a linear regression model (KKW vs V?E/V?CO2 slope) and a linear mixed model. Results: Regression analysis showed a significant trend for a reduction in the V?E/V?CO2 slope from baseline (mean ± SD: 32.6 ± 6.3; P < 0.004). When expressed as mean change (95% confidence interval (CI)) from baseline, we observed significant reductions in the V?E/V?CO2 slope for the 8-KKW (?1.14; 95% CI, ?1.5 to ?0.2) and 12-KKW (?1.67; 95% CI, ?2.3 to ?0.3) groups. No significant effect was noted for the 4-KKW (?0.4; 95% CI, ?1.2 to 0.15) group. Conclusion: Moderate-intensity aerobic exercise at doses of 8 KKW or greater seems to present an adequate dose of exercise to promote small but significant reductions in the V?E/V?CO2 slope in postmenopausal women who exhibit risk factors associated with the development of CHF

Circadian Clocks Are Resounding in Peripheral Tissues

Circadian rhythms are prevalent in most organisms. Even the smallest disturbances in the orchestration of circadian gene expression patterns among different tissues can result in functional asynchrony, at the organism level, and may to contribute to a wide range of physiologic disorders. It has been reported that as many as 5%–10% of transcribed genes in peripheral tissues follow a circadian expression pattern. We have conducted a comprehensive study of circadian gene expression on a large dataset representing three different peripheral tissues. The data have been produced in a large-scale microarray experiment covering replicate daily cycles in murine white and brown adipose tissues as well as in liver. We have applied three alternative algorithmic approaches to identify circadian oscillation in time series expression profiles. Analyses of our own data indicate that the expression of at least 7% to 21% of active genes in mouse liver, and in white and brown adipose tissues follow a daily oscillatory pattern. Indeed, analysis of data from other laboratories suggests that the percentage of genes with an oscillatory pattern may approach 50% in the liver. For the rest of the genes, oscillation appears to be obscured by stochastic noise. Our phase classification and computer simulation studies based on multiple datasets indicate no detectable boundary between oscillating and non-oscillating fractions of genes. We conclude that greater attention should be given to the potential influence of circadian mechanisms on any biological pathway related to metabolism and obesity

Observation of an oxygen isotope effect in YBa\u3csub\u3e2\u3c/sub\u3eCu\u3csub\u3e3\u3c/sub\u3eO\u3csub\u3e7\u3c/sub\u3e

A small decrease in Tc of 0.3 K to 0.5 K is observed when as much as 90% of the 16O in YBa2Cu3O7 is substituted with18O. This result is consistent with our observation that there is an oxygen isotope effect in La1.85Sr0.15CuO4, but in contrast with previous reports that there is no isotope effect for YBa2Cu3O7. This new result suggests that phonons play an important role in the electron-pairing mechanism in YBa2Cu3O7

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants

Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress

Abstract Age-related macular degeneration (AMD) is a major cause of blindness and is associated with complement dysregulation. The disease is a potential target for stem cell therapy but success is likely to be limited by the inflammatory response. We investigated the innate immune properties of human induced-pluripotent stem cell (iPSC)-derived RPE cells, particularly with regard to the complement pathway. We focused on collectin-11 (CL-11), a pattern recognition molecule that can trigger complement activation in renal epithelial tissue. We found evidence of constitutive and hypoxia-induced expression of CL-11 in iPS-RPE cells, and in the extracellular fluid. Complement activation on the cell surface occurred in conjunction with CL-11 binding. CL-11 has been shown to activate inflammatory responses through recognition of L-fucose, which we confirmed by showing that fucosidase-treated cells, largely, failed to activate complement. The presence of CL-11 in healthy murine and human retinal tissues confirmed the biological relevance of CL-11. Our data describe a new trigger mechanism of complement activation that could be important in disease pathogenesis and therapeutic interventions

Observation of an Isotope Shift in the Superconducting Transition Temperature of La\u3csub\u3e1.85\u3c/sub\u3eSr\u3csub\u3e0.15\u3c/sub\u3eCuO\u3csub\u3e4\u3c/sub\u3e

An oxygen isotope shift is observed in superconducting La1.85Sr0.15CuO4 when 18O is substituted partially for 16O; the superconducting transition temperature Tc is lowered by 0.3 to 1.0 K in different samples. We examine these results using conventioanl phonon-mediated BCS theory and conclude that, for La1.85Sr0.15CuO4, phonons play an important role in the pairing mechanism