Pronounced maternal parent-of-origin bias for type-1 NF1 microdeletions

Abstract

Neurofibromatosis type 1 (NF1) is caused, in 4.7–11% of cases, by large deletions encompassing the NF1 gene and its flanking regions within 17q11.2. Different types of large NF1 deletion occur which are distinguishable by their breakpoint location and underlying mutational mechanism. Most common are the type-1 NF1 deletions of 1.4 Mb which exhibit recurrent breakpoints caused by nonallelic homologous recombination (NAHR), also termed unequal crossover. Here, we analyzed 37 unrelated families of patients with de novo type-1 NF1 deletions by means of short tandem repeat (STR) profiling to determine the parental origin of the deletions. We observed that 33 of the 37 type-1 deletions were of maternal origin (89.2% of cases; p < 0.0001). Analysis of the patients' siblings indicated that, in 14 informative cases, ten (71.4%) deletions resulted from interchromosomal unequal crossover during meiosis I. Our findings indicate a strong maternal parent-of-origin bias for type-1 NF1 deletions. A similarly pronounced maternal transmission bias has been reported for recurrent copy number variants (CNVs) within 16p11.2 associated with autism, but not so far for any other NAHR-mediated pathogenic CNVs. Region-specific genomic features are likely to be responsible for the maternal bias in the origin of both the 16p11.2 CNVs and type-1 NF1 deletions.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2ju993U
via IFTTT

Superiority of metal stents in the endoscopic management of pancreatic walled-off necrosis: inferences from recent systematic reviews and meta-analyses of the literature

from Gastroenterology via xlomafota13 on Inoreader https://ift.tt/2rl8RRm
via IFTTT

Evidence of distinct RELN and TGFB1 genetic associations in familial and non-familial otosclerosis in a British population

Abstract

Otosclerosis is a common form of hearing loss which typically presents in young adults. The disease has a familial, monogenic form and a non-familial form with a more complex aetiology. A previous genome wide association study identified evidence that variants within RELN are associated with the condition. Other genes in which an association has been reported include BMP2, COL1A1, FGF2, PPP2R5B and TGFB1. However, follow up studies have often failed to replicate initial positive results. The aim of this study was to establish if an association exists between eight single nucleotide polymorphisms (SNPs) in these six previously implicated genes and otosclerosis in a British case–control cohort (n = 748). Evidence of an association between rs1800472 in TGFB1 and otosclerosis was found (p = 0.034), this association was strongest amongst non-familial cases (p = 0.011). No evidence of an association was detected with variants in COL1A1, FGF2, BMP2, and PPP2R5B. No association between variation in RELN and otosclerosis was observed in the whole cohort. However, a significant association (p = 0.0057) was detected between one RELN SNP (rs39399) and otosclerosis in familial patients. Additionally, we identify expression of one RELN transcript in 51 of 81 human stapes tested, clarifying previous conflicting data as to whether RELN is expressed in the affected tissue. Our findings strengthen the association of TGFB1 (rs1800472) with otosclerosis and support a relationship between RELN and familial otosclerosis only, which may explain previous variable replications.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2KxMoIJ
via IFTTT

Radiological and clinical outcome of selective thoracic fusion (STF) for Lenke 1C and 2C adolescent idiopathic scoliosis (AIS) patients with a minimum follow-up of 2 years

In Lenke 1C and 2C curves, the choice between selective thoracic fusion (STF) versus non-selective thoracic fusion (NSTF) as the optimal surgical treatment is controversial.

from Sports Medicine via xlomafota13 on Inoreader https://ift.tt/2rljcMp
via IFTTT

Usefulness of controlled attenuation parameter for detecting increased arterial stiffness in general population

Liver fibroscan has recently been suggested as an alternative method to measure liver steatosis noninvasively. In this study, we evaluated usefulness of controlled attenuation parameter (CAP) for detecting increased arterial stiffness in general population.

from Gastroenterology via xlomafota13 on Inoreader https://ift.tt/2jzPAYl
via IFTTT

Small-vessel intestinal vasculitis as an initial manifestation of systemic lupus erythematosus

from Gastroenterology via xlomafota13 on Inoreader https://ift.tt/2wdis1n
via IFTTT

Inter-replicon Gene Flow Contributes to Transcriptional Integration in the Sinorhizobium meliloti Multipartite Genome

Integration of newly acquired genes into existing regulatory networks is necessary for successful horizontal gene transfer (HGT). Ten percent of bacterial species contain at least two DNA replicons over 300 kilobases in size, with the secondary replicons derived predominately through HGT. The Sinorhizobium meliloti genome is split between a 3.7 Mb chromosome, a 1.7 Mb chromid consisting largely of genes acquired through ancient HGT, and a 1.4 Mb megaplasmid consisting primarily of recently acquired genes. Here, RNA-sequencing is used to examine the transcriptional consequences of massive, synthetic genome reduction produced through the removal of the megaplasmid and/or the chromid. Removal of the pSymA megaplasmid influenced the transcription of only six genes. In contrast, removal of the chromid influenced expression of ~8% of chromosomal genes and ~4% of megaplasmid genes. This was mediated in part by the loss of the ETR DNA region whose presence on pSymB is due to a translocation from the chromosome. No obvious functional bias among the up-regulated genes was detected, although genes with putative homologs on the chromid were enriched. Down-regulated genes were enriched in motility and sensory transduction pathways. Four transcripts were examined further, and in each case the transcriptional change could be traced to loss of specific pSymB regions. In particularly, a chromosomal transporter was induced due to deletion of bdhA likely mediated through 3-hydroxybutyrate accumulation. These data provide new insights into the evolution of the multipartite bacterial genome, and more generally into the integration of horizontally acquired genes into the transcriptome.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2jyBNkp
via IFTTT

Inducible Genome Editing with Conditional CRISPR/Cas9 Mice

Genetically engineered mouse models (GEMMs) are powerful tools by which to probe gene function in vivo, obtain insight into disease etiology, and identify modifiers of drug response. Increased sophistication of GEMMs has led to the design of tissue-specific and inducible models in which genes of interest are expressed or ablated in defined tissues or cellular subtypes. Here we describe the generation of a transgenic mouse harboring a doxycycline-regulated Cas9 allele for inducible genome engineering. This model provides a flexible platform for genome engineering since editing is achieved by exogenous delivery of sgRNAs and should allow for the modeling of a range of biological and pathological processes.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2FHC1yx
via IFTTT

Robust {Phi}C31-Mediated Genome Engineering in Drosophila melanogaster Using Minimal attP/attB Phage Sites

Effective genome engineering should lead to a desired locus change with minimal adverse impact to the genome itself. However, flanking loci with site-directed recombinase recognition sites, such as those of the phage C31 integrase, allows for creation of platforms for cassette exchange and manipulation of genomic regions in an iterative manner, once specific loci have been targeted. Here we show that a genomic locus engineered with inverted minimal phage C31 attP/attB sites can undergo efficient recombinase-mediated cassette exchange (RMCE) in the fruit fly Drosophila melanogaster.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2jwNZCi
via IFTTT

Vps74 Connects the Golgi Apparatus and Telomeres in Saccharomyces cerevisiae

In mammalian cell culture, the Golgi apparatus fragment upon DNA damage. GOLPH3, a Golgi component, is a phosphorylation target of DNA-PK after DNA damage and contributes to Golgi fragmentation. The function of the yeast (Saccharomyces cerevisiae) ortholog of GOLPH3, Vps74, in the DNA damage response has been little studied, although genome-wide screens suggested a role at telomeres. In this study we investigated the role of Vps74 at telomeres and in the DNA damage response. We show that Vps74 decreases the fitness of telomere defective cdc13-1 cells and contributes to the fitness of yku70 cells. Importantly, loss of Vps74 in yku70 cells exacerbates the temperature dependent growth defects of these cells in a Chk1 and Mec1-dependent manner. Furthermore, Exo1 reduces the fitness of vps74yku70 cells suggesting that ssDNA contributes to the fitness defects of vps74yku70 cells. Systematic genetic interaction analysis of vps74, yku70 and yku70vps74 cells suggests that vps74 causes a milder but similar defect to that seen in yku70 cells. vps74 cells have slightly shorter telomeres and loss of VPS74 in yku70 or mre11 cells further shortens the telomeres of these cells. Interestingly, loss of Vps74 leads to increased levels of Stn1, a partner of Cdc13 in the CST telomere capping complex. Overexpression of Stn1 was previously shown to cause telomere shortening, suppression of cdc13-1 and enhancement of yku70 growth defects, suggesting that increased levels of Stn1 may be the route by which Vps74 affects telomere function. These results establish Vps74 as a novel regulator of telomere biology.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2FJw6Jn
via IFTTT

The Draft Genome of the Invasive Walking Stick, Medauroidea extradendata, Reveals Extensive Lineage-Specific Gene Family Expansions of Cell Wall Degrading Enzymes in Phasmatodea

Plant cell wall components are the most abundant macromolecules on Earth. The study of the breakdown of these molecules is thus a central question in biology. Surprisingly, plant cell wall breakdown by herbivores is relatively poorly understood, as nearly all early work focused on the mechanisms used by symbiotic microbes to breakdown plant cell walls in insects such as termites. Recently, however, it has been shown that many organisms make endogenous cellulases. Insects, and other arthropods, in particular have been shown to express a variety of plant cell wall degrading enzymes in many gene families with the ability to break down all the major components of the plant cell wall. Here we report the genome of a walking stick, Medauroidea extradentata, an obligate herbivore that makes uses of endogenously produced plant cell wall degrading enzymes. We present a draft of the 3.3Gbp genome along with an official gene set that contains a diversity of plant cell wall degrading enzymes. We show that at least one of the major families of plant cell wall degrading enzymes, the pectinases, have undergone a striking lineage-specific gene family expansion in the Phasmatodea. This genome will be a useful resource for comparative evolutionary studies with herbivores in many other clades and will help elucidate the mechanisms by which metazoans breakdown plant cell wall components.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2jux9Eb
via IFTTT

Russian Doll Genes and Complex Chromosome Rearrangements in Oxytricha trifallax

Ciliates have two different types of nuclei per cell, with one acting as a somatic, transcriptionally active nucleus (macronucleus; abbr. MAC) and another serving as a germline nucleus (micronucleus; abbr. MIC). Furthermore, Oxytricha trifallax undergoes extensive genome rearrangements during sexual conjugation and post-zygotic development of daughter cells. These rearrangements are necessary because the precursor MIC loci are often both fragmented and scrambled, with respect to the corresponding MAC loci. Such genome architectures are remarkably tolerant of encrypted MIC loci, because RNA-guided processes during MAC development reorganize the gene fragments in the correct order to resemble the parental MAC sequence. Here, we describe the germline organization of several nested and highly scrambled genes in Oxytricha trifallax. These include cases with multiple layers of nesting, plus highly interleaved or tangled precursor loci that appear to deviate from previously described patterns. We present mathematical methods to measure the degree of nesting between precursor MIC loci, and revisit a method for a mathematical description of scrambling. After applying these methods to the chromosome rearrangement maps of O. trifallax we describe cases of nested arrangements with up to five layers of embedded genes, as well as the most scrambled loci in O. trifallax.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2FKe8pX
via IFTTT

QTL Mapping of Genome Regions Controlling Manganese Uptake in Lentil Seed

This study evaluated Mn concentration in the seeds of 120 RILs of lentil developed from the cross "CDC Redberry" x "ILL7502". Micronutrient analysis using atomic absorption spectrometry indicated mean seed manganese (Mn) concentrations ranging from 8.5 to 26.8 mg/kg, based on replicated field trials grown at three locations in Turkey in 2012 and 2013. A linkage map of lentil was constructed and consisted of seven linkage groups with 5,385 DNA markers. The total map length was 973.1 cM, with an average distance between markers of 0.18 cM. A total of 6 QTL for Mn concentration were identified using composite interval mapping (CIM). All QTL were statistically significant and explained 15.3–24.1% of the phenotypic variation, with LOD scores ranging from 3.00 to 4.42. The high-density genetic map reported in this study will increase fundamental knowledge of the genome structure of lentil, and will be the basis for the development of micronutrient-enriched lentil genotypes to support biofortification efforts.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2KCfA1t
via IFTTT

Distinguishing Among Evolutionary Forces Acting on Genome-Wide Base Composition: Computer Simulation Analysis of Approximate Methods for Inferring Site Frequency Spectra of Derived Mutations

Inferred ancestral nucleotide states are increasingly employed in analyses of within- and between -species genome variation. Although numerous studies have focused on ancestral inference among distantly related lineages, approaches to infer ancestral states in polymorphism data have received less attention. Recently developed approaches that employ complex transition matrices allow us to infer ancestral nucleotide sequence in various evolutionary scenarios of base composition. However, the requirement of a single gene tree to calculate a likelihood is an important limitation for conducting ancestral inference using within-species variation in recombining genomes. To resolve this problem, and to extend the applicability of ancestral inference in studies of base composition evolution, we first evaluate three previously proposed methods to infer ancestral nucleotide sequences among within- and between-species sequence variation data. The methods employ a single allele, bifurcating tree, or a star tree for within-species variation data. Using simulated nucleotide sequences, we employ ancestral inference to infer fixations and polymorphisms. We find that all three methods show biased inference. We modify the bifurcating tree method to include weights to adjust for an expected site frequency spectrum, "bifurcating tree with weighting" (BTW). Our simulation analysis show that the BTW method can substantially improve the reliability and robustness of ancestral inference in a range of scenarios that include non-neutral and/or non-stationary base composition evolution.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2FJTaYs
via IFTTT

Genome-Wide Analysis of Mycoplasma bovirhinis GS01 Reveals Potential Virulence Factors and Phylogenetic Relationships

Mycoplasma bovirhinis is a significant etiology in bovine pneumonia and mastitis, but our knowledge about the genetic and pathogenic mechanisms of M. bovirhinis is very limited. In this study, we sequenced the complete genome of M. bovirhinis strain GS01 isolated from the nasal swab of pneumonic calves in Gansu, China, and we found that its genome forms a 847,985 bp single circular chromosome with a GC content of 27.57% and with 707 protein-coding genes. The putative virulence determinants of M. bovirhinis were then analyzed. Results showed that three genomic islands and 16 putative virulence genes, including one adhesion gene enolase, seven surface lipoproteins, proteins involved in glycerol metabolism, and cation transporters, might be potential virulence factors. Glycerol and pyruvate metabolic pathways were defective. Comparative analysis revealed remarkable genome variations between GS01 and a recently reported HAZ141_2 strain, and extremely low homology with others mycoplasma species. Phylogenetic analysis demonstrated that M. bovirhinis was most genetically close to M. canis, distant from other bovine Mycoplasma species. Genomic dissection may provide useful information on the pathogenic mechanisms and genetics of M. bovirhinis.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2KBdb6U
via IFTTT

Improved Genome Assembly and Annotation for the Rock Pigeon (Columba livia)

The domestic rock pigeon (Columba livia) is among the most widely distributed and phenotypically diverse avian species. C. livia is broadly studied in ecology, genetics, physiology, behavior, and evolutionary biology, and has recently emerged as a model for understanding the molecular basis of anatomical diversity, the magnetic sense, and other key aspects of avian biology. Here we report an update to the C. livia genome reference assembly and gene annotation dataset. Greatly increased scaffold lengths in the updated reference assembly, along with an updated annotation set, provide improved tools for evolutionary and functional genetic studies of the pigeon, and for comparative avian genomics in general.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2FLGYWX
via IFTTT

A Strategy To Isolate Modifiers of Caenorhabditis elegans Lethal Mutations: Investigating the Endoderm Specifying Ability of the Intestinal Differentiation GATA Factor ELT-2

The ELT-2 GATA factor normally functions in differentiation of the C. elegans endoderm, downstream of endoderm specification. We have previously shown that, if ELT-2 is expressed sufficiently early, it is also able to specify the endoderm and to replace all other members of the core GATA-factor transcriptional cascade (END-1, END-3, ELT-7). However, such rescue requires multiple copies (and presumably overexpression) of the end-1p::elt-2 cDNA transgene; a single copy of the transgene does not rescue. We have made this observation the basis of a genetic screen to search for genetic modifiers that allow a single copy of the end-1p::elt-2 cDNA transgene to rescue the lethality of the end-1end-3 double mutant. We performed this screen on a strain that has a single copy insertion of the transgene in an end-1end-3 background. These animals are kept alive by virtue of an extrachromosomal array containing multiple copies of the rescuing transgene; the extrachromosomal array also contains a toxin under heat shock control to counterselect for mutagenized survivors that have been able to lose the rescuing array. A screen of ~14,000 mutagenized haploid genomes produced 17 independent surviving strains. Whole genome sequencing was performed to identify genes that incurred independent mutations in more than one surviving strain. The C. elegans gene tasp-1 was mutated in four independent strains. tasp-1 encodes the C. elegans homolog of Taspase, a threonine-aspartic acid protease that has been found, in both mammals and insects, to cleave several proteins involved in transcription, in particular MLL1/trithorax and TFIIA. A second gene, pqn-82, was mutated in two independent strains and encodes a glutamine-asparagine rich protein. tasp-1 and pqn-82 were verified as loss-of-function modifiers of the end-1p::elt-2 transgene by RNAi and by CRISPR/Cas9-induced mutations. In both cases, gene loss leads to modest increases in the level of ELT-2 protein in the early endoderm although ELT-2 levels do not strictly correlate with rescue. We suggest that tasp-1 and pqn-82 represent a class of genes acting in the early embryo to modulate levels of critical transcription factors or to modulate the responsiveness of critical target genes. The screen's design, rescuing lethality with an extrachromosomal transgene followed by counterselection, has a background survival rate of <10^–4 without mutagenesis and should be readily adapted to the general problem of identifying suppressors of C. elegans lethal mutations.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2jxChHI
via IFTTT

Rapid Multiplex Small DNA Sequencing on the MinION Nanopore Sequencing Platform

Real-time sequencing of short DNA reads has a wide variety of clinical and research applications including screening for mutations, target sequences and aneuploidy. We recently demonstrated that MinION, a nanopore-based DNA sequencing device the size of a USB drive, could be used for short-read DNA sequencing. In this study, an ultra-rapid multiplex library preparation and sequencing method for the MinION is presented and applied to accurately test normal diploid and aneuploidy samples' genomic DNA in under three hours, including library preparation and sequencing. This novel method shows great promise as a clinical diagnostic test for applications requiring rapid short-read DNA sequencing.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2FJw5Fj
via IFTTT

Cold Shock as a Screen for Genes Involved in Cold Acclimatization in Neurospora crassa

When subjected to rapid drops of temperature (cold shock), Neurospora responds with a temporary shift in its morphology. This report is the first to examine this response genetically. We report here the results of a screen of selected mutants from the Neurospora knockout library for alterations in their morphological response to cold shock. Three groups of knockouts were selected to be subject to this screen: genes previously suspected to be involved in hyphal development as well as knockouts resulting in morphological changes; transcription factors; and genes homologous to E. coli genes known to alter their expression in response to cold shock. A total of 344 knockout strains were subjected to cold shock. Of those, 118 strains were identified with altered responses. We report here the cold shock morphologies and GO categorizations of strains subjected to this screen. Of strains with knockouts in genes associated with hyphal growth or morphology, 33 of 131 tested (25%) showed an altered response to cold shock. Of strains with knockouts in transcription factor genes, 30 of 145 (20%) showed an altered response to cold shock. Of strains with knockouts in genes homologous to E. coli genes which display altered levels of transcription in response to cold shock, a total of 55 of 68 tested (81%) showed an altered cold shock response. This suggests that the response to cold shock in these two organisms is largely shared in common.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2jxgBLZ
via IFTTT

Haplotype-Based Genome-Wide Prediction Models Exploit Local Epistatic Interactions Among Markers

Genome-wide prediction approaches represent versatile tools for the analysis and prediction of complex traits. Mostly they rely on marker-based information, but scenarios have been reported in which models capitalizing on closely-linked markers that were combined into haplotypes outperformed marker-based models. Detailed comparisons were undertaken to reveal under which circumstances haplotype-based genome-wide prediction models are superior to marker-based models. Specifically, it was of interest to analyze whether and how haplotype-based models may take local epistatic effects between markers into account. Assuming that populations consisted of fully homozygous individuals, a marker-based model in which local epistatic effects inside haplotype blocks were exploited (LEGBLUP) was linearly transformable into a haplotype-based model (HGBLUP). This theoretical derivation formally revealed that haplotype-based genome-wide prediction models capitalize on local epistatic effects among markers. Simulation studies corroborated this finding. Due to its computational efficiency the HGBLUP model promises to be an interesting tool for studies in which ultra-high-density SNP data sets are studied. Applying the HGBLUP model to empirical data sets revealed higher prediction accuracies than for marker-based models for both traits studied using a mouse panel. In contrast, only a small subset of the traits analyzed in crop populations showed such a benefit. Cases in which higher prediction accuracies are observed for HGBLUP than for marker-based models are expected to be of immediate relevance for breeders, due to the tight linkage a beneficial haplotype will be preserved for many generations. In this respect the inheritance of local epistatic effects very much resembles the one of additive effects.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2FKze7F
via IFTTT

Fast Ordered Sampling of DNA Sequence Variants

Explosive growth in the amount of genomic data is matched by increasing power of consumer-grade computers. Even applications that require powerful servers can be quickly tested on desktop or laptop machines if we can generate representative samples from large data sets. I describe a fast and memory-efficient implementation of an on-line sampling method developed for tape drives 30 years ago. Focusing on genotype files, I test the performance of this technique on modern solid-state and spinning hard drives, and show that it performs well compared to a simple sampling scheme. I illustrate its utility by developing a method to quickly estimate genome-wide patterns of linkage disequilibrium (LD) decay with distance. I provide open-source software that samples loci from several variant format files, a separate program that performs LD decay estimates, and a C++ library that lets developers incorporate these methods into their own projects.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2jwjY5O
via IFTTT

Comparison of the Relative Potential for Epigenetic and Genetic Variation To Contribute to Trait Stability

The theoretical ability of epigenetic variation to influence the heritable variation of complex traits is gaining traction in the study of adaptation. This theory posits that epigenetic marks can control adaptive phenotypes but the relative potential of epigenetic variation in comparison to genetic variation in these traits is not presently understood. To compare the potential of epigenetic and genetic variation in adaptive traits, we analyzed the influence of DNA methylation variation on the accumulation of chemical defense compounds glucosinolates from the order Brassicales. Several decades of work on glucosinolates has generated extensive knowledge about their synthesis, regulation, genetic variation and contribution to fitness establishing this pathway as a model pathway for complex adaptive traits. Using high-throughput phenotyping with a randomized block design of ddm1 derived Arabidopsis thaliana epigenetic Recombinant Inbred Lines, we measured the correlation between DNA methylation variation and mean glucosinolate variation and within line stochastic variation. Using this information, we identified epigenetic Quantitative Trait Loci that contained specific Differentially Methylated Regions associated with glucosinolate traits. This showed that variation in DNA methylation correlates both with levels and variance of glucosinolates and flowering time with trait-specific loci. By conducting a meta-analysis comparing the results to different genetically variable populations, we conclude that the influence of DNA methylation variation on these adaptive traits is much lower than the corresponding impact of standing genetic variation. As such, selective pressure on these traits should mainly affect standing genetic variation to lead to adaptation.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2FKzdR9
via IFTTT

Comparative Transcriptomics Among Four White Pine Species

Conifers are the dominant plant species throughout the high latitude boreal forests as well as some lower latitude temperate forests of North America, Europe, and Asia. As such, they play an integral economic and ecological role across much of the world. This study focused on the characterization of needle transcriptomes from four ecologically important and understudied North American white pines within the Pinus subgenus Strobus. The populations of many Strobus species are challenged by native and introduced pathogens, native insects, and abiotic factors. RNA from the needles of western white pine (Pinus monticola), limber pine (Pinus flexilis), whitebark pine (Pinus albicaulis), and sugar pine (Pinus lambertiana) was sampled, Illumina short read sequenced, and de novo assembled. The assembled transcripts and their subsequent structural and functional annotations were processed through custom pipelines to contend with the challenges of non-model organism transcriptome validation. Orthologous gene family analysis of over 58,000 translated transcripts, implemented through Tribe-MCL, estimated the shared and unique gene space among the four species. This revealed 2025 conserved gene families, of which 408 were aligned to estimate levels of divergence and reveal patterns of selection. Specific candidate genes previously associated with drought tolerance and white pine blister rust resistance in conifers were investigated.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2KxVCF3
via IFTTT

Effects of Larval Density on Gene Regulation in Caenorhabditis elegans During Routine L1 Synchronization

Bleaching gravid C. elegans followed by a short period of starvation of the L1 larvae is a routine method performed by worm researchers for generating synchronous populations for experiments. During the process of investigating dietary effects on gene regulation in L1 stage worms by single-worm RNA-Seq, we found that the density of resuspended L1 larvae affects expression of many mRNAs. Specifically, a number of genes related to metabolism and signaling are highly expressed in worms arrested at low density, but are repressed at higher arrest densities. We generated a GFP reporter strain based on one of the most density-dependent genes in our dataset – lips-15 – and confirmed that this reporter was expressed specifically in worms arrested at relatively low density. Finally, we show that conditioned media from high density L1 cultures was able to downregulate lips-15 even in L1 animals arrested at low density, and experiments using daf-22 mutant animals demonstrated that this effect is not mediated by the ascaroside family of signaling pheromones. Together, our data implicate a soluble signaling molecule in density sensing by L1 stage C. elegans, and provide guidance for design of experiments focused on early developmental gene regulation.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2FKTfel
via IFTTT

Germline Variants in the POT1-Gene in High-Risk Melanoma Patients in Austria

Risk of melanoma is in part determined by genetic factors. Currently the only established high penetrance familial melanoma genes are CDKN2A and CDK4. Recent studies reported germline variants in POT1 in melanoma families. In the present study, we sequenced the entire POT1 gene in 694 patients from the M3-study. Patients with multiple primary melanomas (n = 163) or with a positive family history (n = 133) were classified as high-risk melanoma patients. Additionally, 200 single primary melanoma patients and 198 non-melanoma controls were sequenced. For prediction analysis 10 different tools were used.

In total 53 different variants were found, of which 8 were detected in high-risk melanoma patients, only. Two out of these 8 variants were located in exons and were non-synonymous: g.124510982 G>A (p.R80C) and g.124491977 T>G (p.N300H). While g.124491977 T>G was predicted to be neutral, 80% of the prediction tools classified g.124510982 G>A as deleterious. The variant, g.124467236 T>C, which possibly causes a change in the splice site was identified in a case with a positive family history in the present study. Another variant in the 5-UTR, g.124537261 A>G, was found in 2 high-risk patients. So, in conclusion, melanoma associated POT1 germline variants seem to be rare. Further studies are required to evaluate the role of POT1 for genetic counseling.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2jumt8A
via IFTTT

H3K4 Methylation Dependent and Independent Chromatin Regulation by JHD2 and SET1 in Budding Yeast

Set1 and Jhd2 regulate the methylation state of histone H3 lysine-4 (H3K4me) through their opposing methyltransferase and demethylase activities in the budding yeast Saccharomyces cerevisiae. H3K4me associates with actively transcribed genes and, like both SET1 and JHD2 themselves, is known to regulate gene expression diversely. It remains unclear, however, if Set1 and Jhd2 act solely through H3K4me. Relevantly, Set1 methylates lysine residues in the kinetochore protein Dam1 while genetic studies of the S. pombe SET1 ortholog suggest the existence of non-H3K4 Set1 targets relevant to gene regulation. We interrogated genetic interactions of JHD2 and SET1 with essential genes involved in varied aspects of the transcription cycle. Our findings implicate JHD2 in genetic inhibition of the histone chaperone complexes Spt16-Pob3 (FACT) and Spt6-Spn1. This targeted screen also revealed that JHD2 inhibits the Nrd1-Nab3-Sen1 (NNS) transcription termination complex. We find that while Jhd2's impact on these transcription regulatory complexes likely acts via H3K4me, Set1 governs the roles of FACT and NNS through opposing H3K4-dependent and -independent functions. We also identify diametrically opposing consequences for mutation of H3K4 to alanine or arginine, illuminating that caution must be taken in interpreting histone mutation studies. Unlike FACT and NNS, detailed genetic studies suggest an H3K4me-centric mode of Spt6-Spn1 regulation by JHD2 and SET1. Chromatin immunoprecipitation and transcript quantification experiments show that Jhd2 opposes the positioning of a Spt6-deposited nucleosome near the transcription start site of SER3, a Spt6-Spn1 regulated gene, leading to hyper-induction of SER3. In addition to confirming and extending an emerging role for Jhd2 in the control of nucleosome occupancy near transcription start sites, our findings suggest some of the chromatin regulatory functions of Set1 are independent of H3K4 methylation.

from Genetics via xlomafota13 on Inoreader https://ift.tt/2jv2o23
via IFTTT

Exercise Prescription in Patients with Different Combinations of Cardiovascular Disease Risk Factors: A Consensus Statement from the EXPERT Working Group

Abstract

Whereas exercise training is key in the management of patients with cardiovascular disease (CVD) risk (obesity, diabetes, dyslipidaemia, hypertension), clinicians experience difficulties in how to optimally prescribe exercise in patients with different CVD risk factors. Therefore, a consensus statement for state-of-the-art exercise prescription in patients with combinations of CVD risk factors as integrated into a digital training and decision support system (the EXercise Prescription in Everyday practice & Rehabilitative Training (EXPERT) tool) needed to be established. EXPERT working group members systematically reviewed the literature for meta-analyses, systematic reviews and/or clinical studies addressing exercise prescriptions in specific CVD risk factors and formulated exercise recommendations (exercise training intensity, frequency, volume and type, session and programme duration) and exercise safety precautions, for obesity, arterial hypertension, type 1 and 2 diabetes, and dyslipidaemia. The impact of physical fitness, CVD risk altering medications and adverse events during exercise testing was further taken into account to fine-tune this exercise prescription. An algorithm, supported by the interactive EXPERT tool, was developed by Hasselt University based on these data. Specific exercise recommendations were formulated with the aim to decrease adipose tissue mass, improve glycaemic control and blood lipid profile, and lower blood pressure. The impact of medications to improve CVD risk, adverse events during exercise testing and physical fitness was also taken into account. Simulations were made of how the EXPERT tool provides exercise prescriptions according to the variables provided. In this paper, state-of-the-art exercise prescription to patients with combinations of CVD risk factors is formulated, and it is shown how the EXPERT tool may assist clinicians. This contributes to an appropriately tailored exercise regimen for every CVD risk patient.

from Sports Medicine via xlomafota13 on Inoreader https://ift.tt/2IhzvEm
via IFTTT

IAED releases Performance Standards 10th Edition

Brought to you by Priority Dispatch The International Academies of Emergency Dispatch® (IAED™) ED-Q Council of Standards has approved the release of Performance Standards 10th Edition, an updated version of performance requirements for all medical, fire, and police emergency calltaking. These new standards are integrated seamlessly into AQUA® 7 Ascent and will enhance a communication center's ...

from EMS via xlomafota13 on Inoreader https://ift.tt/2HPJPEm
via IFTTT

Yeast KEOPS complex regulates telomere length independently of its t6A modification function

Publication date: Available online 4 May 2018
Source:Journal of Genetics and Genomics
Author(s): Ying-Ying Liu, Ming-Hong He, Jia-Cheng Liu, Yi-Si Lu, Jing Peng, Jin-Qiu Zhou
In Saccharomyces cerevisiae, the highly conserved Sua5 and KEOPS complex (including five subunits Kae1, Bud32, Cgi121, Pcc1 and Gon7) catalyze a universal tRNA modification, namely N⁶-threnoylcarbamoyladenosine (t⁶A), and regulate telomere replication and recombination. However, whether telomere regulation function of Sua5 and KEOPS complex depends on the t⁶A modification activity remains unclear. Here we show that Sua5 and KEOPS regulate telomere length in the same genetic pathway. Interestingly, the telomere length regulation by KEOPS is independent of its t⁶A biosynthesis activity. Cytoplasmic overexpression of Qri7, a functional counterpart of KEOPS in mitochondria, restores cytosolic tRNA t⁶A modification and cell growth, but is not sufficient to rescue telomere length in the KEOPS mutant kae1Δ cells, indicating that a t⁶A modification-independent function is responsible for the telomere regulation. The results of our in vitro biochemical and in vivo genetic assays suggest that telomerase RNA TLC1 might not be modified by Sua5 and KEOPS. Moreover, deletion of KEOPS subunits results in a dramatic reduction of telomeric G-overhang, suggesting that KEOPS regulates telomere length by promoting G-overhang generation. These findings support a model in which KEOPS regulates telomere replication independently of its function on tRNA modification.



from Genetics via xlomafota13 on Inoreader https://ift.tt/2HOTTNQ
via IFTTT

Postoperative renal function in parturients with severe preeclampsia who underwent cesarean delivery: a retrospective observational study

Abstract

Although postoperative renal dysfunction is relatively rare after cesarean delivery, preeclampsia is considered as the high-risk population. On the other hand, hydroxyethyl starch (HES) administration for preventing maternal hypotension induced by spinal anesthesia for cesarean delivery is a common practice. However, the effect of HES administration during cesarean delivery on postoperative kidney function in parturients with severe preeclampsia is not well investigated. We retrospectively reviewed both medical and anesthesia records of patients with severe preeclampsia who underwent cesarean delivery from January 2011 to December 2013. Preoperative blood examinations were compared with postoperative values. All parturients received 6% HES 70/0.5 for preventing anesthesia-induced hypotension or for volume resuscitation during cesarean delivery. A total of 87 severe preeclampsia parturients were underwent cesarean section during the period. The amounts of HES administration were 859 ± 206 mL. There was significant reduction in serum creatinine, from 0.70 ± 0.29 mg/dL preoperatively to 0.62 ± 0.17 mg/dL in 3–7 days after the cesarean. Only one patient had postoperatively elevated serum creatinine up to clinically significant level (from 0.64 mg/dL to 1.35 mg/kg).

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2JVM7OR
via IFTTT

Ambulance service shares quote from EMT killed in crash

Paramount Ambulance shared a story from fallen EMT Steve Warner about a particularly special call that reminded him why he loved his job

from EMS via xlomafota13 on Inoreader https://ift.tt/2HScDIl
via IFTTT

Double-outlet left atrium: Successful repair of an extremely rare anomaly

Yasser Ahmad Bhat, Himanshu Pratap, Kulbhushan Singh Dagar, Neeraj Awasthy

Annals of Pediatric Cardiology 2018 11(2):204-206

The clinical detail, echocardiographic features, angiographic evaluation, and surgical repair of double-outlet left atrium (LA) in a 2-year-old boy are discussed. In a solitus position and normally connected systemic and pulmonary venous drainage setting, the only outlet of the right atrium was a secundum atrial septal defect. The LA thus received the entire venous return and then drained into both ventricles through a common atrioventricular valve.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2jr3go8
via IFTTT

Ivabradine for congenital junctional ectopic tachycardia in siblings

Shyam S Kothari, Bharath Raj Kidambi, Rajnish Juneja

Annals of Pediatric Cardiology 2018 11(2):226-228



from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2wd8woD
via IFTTT

Long-term outcome of coronary artery dilatation in Kawasaki disease

Najib Advani, Sudigdo Sastroasmoro, Teddy Ontoseno, Cuno SPM Uiterwaal

Annals of Pediatric Cardiology 2018 11(2):125-129

Background: Kawasaki disease (KD) is an acute systemic vasculitis syndrome with a high incidence of coronary aneurysms in untreated children. The majority of aneurysms resulting from KD are known to regress with time. Aims: This study aimed to determine the course and outcome of coronary artery dilatation in patients with KD and ascertain whether there are any differences in the outcomes in the different branches. Setting and Design: This is a retrospective cohort study of patients diagnosed with KD with midterm follow-up data. Methods: Serial echocardiography was performed in all KD patients with coronary dilatation for 1–10½ years. The Kaplan–Meier curve was used for statistical analysis. Results: There were 154 patients with coronary dilatation studied. The frequency of coronary dilatation in acute phase was 33.3% and decreased to 7.9% 6–8 weeks later. Each patient could have dilatations at more than one branch, so the total number of dilatations was 245. The median time needed for regression was 2.6 months (mean: 10.5 months) while the median of follow-up duration was 41 months (mean: 23 months). Small- and medium-sized dilatations had more favorable outcomes compared to the giant ones. Location of dilatation did not influence the outcome. Conclusions: The majority (77.4%) of small- and medium-sized dilatations regress within 2 years, but giant aneurysms tend to persist. The outcome of coronary dilatation is determined by the diameter and not by the location. Regression rate is faster in smaller dilatations. Left main coronary artery is the most frequent location for dilatation.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2rfYNZ4
via IFTTT

Cardiac involvement in hypereosinophilic syndrome

Mohamad Jihad Mansour, Malek Rahal, Elie Chammas, Omar Hamoui, Wael Aljaroudi

Annals of Pediatric Cardiology 2018 11(2):217-218

A 9-year-old boy with hypereosinophilic syndrome (HES) was referred for cardiac magnetic resonance (CMR) imaging following an abnormal echocardiogram that showed a large mass layered on the inferolateral wall of the left ventricle, causing secondary severe mitral regurgitation. Cardiac involvement in HES usually affects the ventricular apex. In our case, CMR confirmed the presence of a large mural thrombus of 0.9 cm × 4.2 cm. This unusual cardiac involvement in HES was diagnosed in its intermediate thrombotic stage. CMR is very sensitive and specific in staging the disease. It explained the etiology of mitral regurgitation and guided therapy, especially when echocardiography was nonconclusive.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2KA55f1
via IFTTT

Simulation training improves team dynamics and performance in a low-resource cardiac intensive care unit

Sivaram Subaya Emani, Catherine K Allan, Tess Forster, Anna C Fisk, Christine Lagrasta, Bistra Zheleva, Peter Weinstock, Ravi R Thiagarajan

Annals of Pediatric Cardiology 2018 11(2):130-136

Introduction: Although simulation training has been utilized quite extensively in highincome medical environments, its feasibility and effect on team performance in lowresource pediatric Cardiac Intensive Care Unit (CICU) environments has not been demonstrated. We hypothesized that lowfidelity simulationbased crisis resource management training would lead to improvements in team performance in such settings. Methods: In this prospective observational study, the effect of simulation on team dynamics and performance was assessed in 23 healthcare providers in a pediatric CICU in Southeast Asia. A 5day training program was utilized consisting of various didactic sessions and simulation training exercises. Improvements in team dynamics were assessed using participant questionnaires, expert evaluations, and video analysis of time to intervention and frequency of closedloop communication. Results: In subjective questionnaires, participants noted significant (P < 0.05) improvement in team dynamics and performance over the training period. Video analysis revealed a decrease in time to intervention and significant (P < 0.05) increase in frequency of closedloop communication because of simulation training. Conclusions: This study demonstrates the feasibility and effectiveness of simulationbased training in improving team dynamics and performance in lowresource pediatric CICU environments, indicating its potential role in eliminating communication barriers in these settings.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2rjPNSQ
via IFTTT

Population-based treated prevalence, risk factors, and outcomes of bicuspid aortic valve in a pediatric Medicaid cohort

Avnish Tripathi, Yinding Wang, Jeanette M Jerrell

Annals of Pediatric Cardiology 2018 11(2):119-124

Background: We investigated the treated prevalence of bicuspid aortic valve in a pediatric population with congenital heart disease and its incident complications. Materials and Methods: A 15-year retrospective data set was analyzed. Selection criteria included age ≤17 years, enrollees in the South Carolina State Medicaid program and diagnosed as having bicuspid aortic valve on one or more service visits. Results: The 15-year-treated prevalence of predominantly isolated bicuspid aortic valve was 2% (20/1000) of pediatric congenital heart disease cases, with a non-African American: African-American ratio of 3.5:1, and a male:female ratio of 1.6:1. Aortic stenosis (28.0%), ventricular septal defect (20.6%), and coarctation of the aorta (20.6%) were the most prevalent coexisting congenital heart lesions. Of the 378 bicuspid aortic valve cases examined, 10.3% received aortic valve repair/replacement, which was significantly more likely to be performed in children with diagnosed aortic stenosis (adjusted odds ratio = 12.90; 95% confidence interval = 5.66–29.44). Cohort outcomes over the study period indicated that 9.5% had diagnosed heart failure, but <1% had diagnosed supraventricular tachycardia, infective endocarditis, aneurysm, dissection, or death. Conclusions: The majority of isolated bicuspid aortic valve cases without aortic stenosis did not require surgical intervention. Outcomes for cases requiring repair/replacement were relatively benign.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2HPCPao
via IFTTT

Predictive efficacy of procalcitonin, platelets, and white blood cells for sepsis in pediatric patients undergoing cardiac surgeries who are admitted to intensive care units: Single-center experience

Jigar Surti, Imelda Jain, Komal Shah, Amit Mishra, Yogini Kandre, Pankaj Garg, Jatin Shah, Ashok Shah, Payal Tripathi

Annals of Pediatric Cardiology 2018 11(2):137-142

Background: Sepsis is one of the major contributor of morbidity and mortality in pediatric cardiac surgeries. Aim: The aim of this study was to compare the predictive efficacy of total leukocyte counts (TC), platelet count (PC), and procalcitonin (PCT) for sepsis in patients undergoing cardiac surgeries who are admitted to the Intensive Care Unit. Materials and Methods: This prospective, single-center study included 300 neonates, infants, and pediatric patients who had undergone various open heart surgeries at our center from September 2014 to November 2015. Results: Overall, the incidence of sepsis was 14% in pediatric patients undergoing cardiac surgeries. TC of postoperative 48 h were significantly lower (11889.19 ± 5092.86 vs. 14583.22 ± 6562.96; P = 0.004) in septic patients. The low levels of platelets on postoperative 24 h and 72 h were observed in patients with sepsis as compared to patients without sepsis, whereas the levels of PCT at various time intervals (preoperative, postoperative - 24 h, 48 h, and 72 h) had shown no association with sepsis in the study population. Low PC (24 h) was the strongest predictor of sepsis showing an odds ratio of 1.9 (95% confidence interval [CI]: 1.42–3.51; P = 0.001) and area under curve of 0.688 with 95% CI of 0.54–0.83 (P = 0.018). Conclusion: We may conclude that in Indian pediatric population platelet levels are highly associated with sepsis as compared to any other hematological parameter. The immediate postoperative level of platelet is the strongest predictor of sepsis and could be effectively used in the clinical settings.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2riVU9W
via IFTTT

Pulmonary artery-to-left atrial fistula discovered after the closure of atrial septal defect: A rare clinical scenario

Akshay Chauhan, Saket Agarwal, Utsav Gupta, Nayem Raja, Muhammad Abid Geelani, Vijay Trehan

Annals of Pediatric Cardiology 2018 11(2):211-213

A case of the right pulmonary artery-to- left atrial fistula with atrial septal defect (ASD) is presented. The fistula was detected after the patient developed desaturation following surgical closure of the ASD. It was managed with a transcatheter (trans-RPA route) closure of the fistula using a 12-mm Amplatzer ventricular septal defect closure device.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2KAT1u7
via IFTTT

Percutaneous balloon dilatation for congenital aortic stenosis during infancy: A 15-year single-center experience

Abdulraouf M Z Jijeh, Muna Ismail, Aisha Al-Bahanta, Ahmed Alomrani, Omar Tamimi

Annals of Pediatric Cardiology 2018 11(2):143-147

Background: Congenital aortic stenosis (AS) is a rare disease. Treatment options for newborns are challenging. Newborns may have higher reintervention rate and mortality. Objectives: The study aimed to identify the factors predictive of reintervention following balloon aortic valvuloplasty (BAV) for AS during infancy. Methods: Retrospectively, between 2001 and 2016, echocardiography (echo) and cardiac catheterization data for infants with AS were analyzed, including follow-ups and reinterventions. Percentage reduction was defined as the ratio between the drop of aortic valve (AV) peak gradient and the baseline peak gradient. Results: Sixty infants were included and 48 were followed up. Sixteen (27%) patients were neonates. Peak-to-peak gradient at AV was 64 ± 27 mmHg, which was reduced to 27 ± 13 mmHg. Percentage reduction was 53% ±24%. Forty-nine (82%) patients had adequate results (residual AV gradient <35 mmHg). There was no significant aortic insufficiency (AI) before procedure, while 6 (10%) patients had increased AI immediately after BAV. Of 48 patients, 14 (29%) required an additional BAV. Of 48 patients, 8 (17%) required surgical interventions following BAV. Reintervention was associated more with small left ventricular outflow tract (LVOT), high residual AV, and low percentage reduction. Mortality was 8.3%. Conclusions: BAV in infancy has a reasonable success rate (82%) with high rate of reintervention. Patent ductus arteriosus-dependent neonates carried the highest risk of mortality. Small LVOT, high AV residual gradient, and low percentage reduction resulted in more reinterventions.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2rlwfgD
via IFTTT

Large nonapical right ventricular diverticulum in a patient with atrioventricular septal defect

Michael Weidenbach, Bardo Wannenmacher, Christian Paech, Robert Wagner

Annals of Pediatric Cardiology 2018 11(2):222-223

Congenital diveticula and aneurysm of the heart are rare and most often located at the apex of the left ventricle. They pose a significant risk for cardiac failure and arrhythmias. In contrast, nonapical diverticula of the right ventricle (RV) have a much more benign course. We present a child with Trisomy 21, atrioventricular septal defect, and large nonapical diverticulum of the RV that was neither addressed during surgery nor needed any medical treatment during 1-year follow-up.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2KvjUzv
via IFTTT

Fetal cardiac arrhythmias: Current evidence

Nathalie Jeanne Bravo-Valenzuela, Luciane Alves Rocha, Luciano Marcondes Machado Nardozza, Edward Araujo Júnior

Annals of Pediatric Cardiology 2018 11(2):148-163

This article reviews important features for improving the diagnosis of fetal arrhythmias by ultrasound in prenatal cardiac screening and echocardiography. Transient fetal arrhythmias are more common than persistent fetal arrhythmias. However, persistent severe bradycardia and sustained tachycardia may cause fetal hydrops, preterm delivery, and higher perinatal morbidity and mortality. Hence, the diagnosis of these arrhythmias during the routine obstetric ultrasound, before the progression to hydrops, is crucial and represents a challenge that involves a team of specialists and subspecialists on fetal ultrasonography. The images in this review highlight normal cardiac rhythms as well as pathologic cases consistent with premature atrial and ventricular contractions, heart block, supraventricular tachycardia (VT), atrial flutter, and VT. In this review, the details of a variety of arrhythmias in fetuses were provided by M-mode and Doppler ultrasound/echocardiography with high-quality imaging, enhancing diagnostic accuracy. Moreover, an update on the intrauterine management and treatment of many arrhythmias is provided, focusing on improving outcomes to enable planned delivery and perinatal management.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2riVCjm
via IFTTT

Is seeing believing: An obstructed bidirectional Glenn, that wasn't!

Himanshu Pratap, Neetu Vashisht, Neeraj Awasthy, Kulbhushan Singh Dagar

Annals of Pediatric Cardiology 2018 11(2):230-231



from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2KBPefR
via IFTTT

Anatomy of the normal fetal heart: The basis for understanding fetal echocardiography

Beatriz Picazo-Angelin, Juan Ignacio Zabala-Argüelles, Robert H Anderson, Damian Sánchez-Quintana

Annals of Pediatric Cardiology 2018 11(2):164-173

The rapid changes that have taken place in recent years in relation to techniques used to image the fetal heart have emphasized the need to have a detailed knowledge ofnormal cardiac anatomy. Without such knowledge, it is difficult, if not impossible, to recognize the multiple facets of congenital cardiac disease. From the inception of fetal echocardiographic screening, the importance of basic knowledge of cardiac anatomy has been well recognized. The current machines used for imaging, however, now make it possible potentially to recognize features not appreciated at the start of the specialty. So as to match the advances made in imaging, we have now revisited our understanding of normal cardiac anatomy in the mid-gestational fetus. This was made possible by our dissection of 10 fetal hearts, followed by production of addition histological sections that mimic the standard ultrasound views. The fetuses ranged in gestational age from between 20 and 28 weeks. We then correlated the obtained anatomic images with the corresponding ultrasonic images used in the standard fetal screening scan. We also interrogated the anatomic sections so as to clarify ongoing controversies regarding detailed features of the normal cardiac anatomy. We have been able to show that the views now obtained using current technology reveal many details of anatomy not always appreciated at earlier times. Knowledge of these features should now permit diagnosis of most congenital cardiac malformations. The anatomic-echocardiographic correlations additionally provide a valuable resource for both the understanding and teaching of fetal echocardiography.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2rjPM1e
via IFTTT

Three-dimensional printing in surgical planning: A case of aortopulmonary window with interrupted aortic arch

Ryan A Moore, William Jack Wallen, Kyle W Riggs, David LS Morales

Annals of Pediatric Cardiology 2018 11(2):201-203

Better anatomical understanding and conceptualization of complex congenital heart defects using three-dimensional (3D) printing may improve surgical planning, especially in rare defects. In this report, we utilized 3D printing to delineate the exact cardiac anatomy of a neonate with an aortopulmonary window associated with interrupted aortic arch to devise a novel approach to the repair.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2KxDv1Q
via IFTTT

Developing congenital heart surgery in India: The travails and triumphs of a pioneer

Rao R Ivatury

Annals of Pediatric Cardiology 2018 11(2):174-180

Professor IM Rao, from All India Institute of Medical Sciences, New Delhi, was a pioneering cardiac surgeon who, against overwhelming odds, developed congenital heart surgery in India. He made many contributions to the evolution of his specialty, spanning more than four decades and three countries. This is a brief report of his professional life and accomplishments.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2rlB7T0
via IFTTT

Eosinophilia to endomyocardial fibrosis: Documentation of a case

Dinkar Bhasin, Saurabh Kumar Gupta, Sudheer Arava, Shyam S Kothari

Annals of Pediatric Cardiology 2018 11(2):207-210

Endomyocardial fibrosis (EMF) is an important cause of restrictive cardiomyopathy in tropical countries. The etiopathogenesis of EMF remains obscure. The role of eosinophilia in the etiopathogenesis of EMF has been debated extensively, but remains unproven. Accordingly, we present a case wherein a patient with documented eosinophilia and heart failure at the age of three-and-a-half years presented with endomyocardial fibrosis at the age of nine years. Such documentation is important to highlight the central role of eosinophils in the pathogenesis of EMF.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2HNaPo2
via IFTTT

Particle embolization of systemic-to-pulmonary collateral artery networks in congenital heart disease: Technique and special considerations

Sarosh P Batlivala, William E Briscoe, Makram R Ebeid

Annals of Pediatric Cardiology 2018 11(2):181-186

Systemic-to-pulmonary artery collateral networks commonly develop in patients with single-ventricle physiology and chronic hypoxemia. Although these networks augment pulmonary blood flow, much of the flow is ineffective and contributes to cardiac volume loading. This volume loading can have detrimental effects, especially for single-ventricle patients. Some data suggest that occluding collaterals may improve outcomes after subsequent operations, especially when the volume of collateral flow is significant. Traditional practice has been to coil occlude the feeding vessel. We perform particle embolization of these collateral networks for two primary reasons. First, access to the feeding vessel is not blocked as collaterals may redevelop. Second, particles occlude the most distal connections. Thus, embolization with particles should be considered as an alternative to coil occluding the proximal feeding vessel.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2rjo0So
via IFTTT

Homocystinuria presenting as a calcified right atrial mass

Tahleel Altaf Shera, Naseer Ahmed Choh, Faiz Altaf Shera, Azher Maqbool Khan

Annals of Pediatric Cardiology 2018 11(2):214-216

Homocystinuria is a genetic inborn error of metabolism due to the deficiency of cystathionine β-synthase resulting in increased serum homocysteine and methionine and decreased cysteine which predisposes affected individuals to arterial and venous thromboembolic phenomena. We present a case of homocystinuria who presented to us as a calcified right atrial mass during the evaluation for lower respiratory tract infection. Our case reveals an unusual mix of findings using imaging with multiple detector computed tomography and radiographs.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2HMMCy5
via IFTTT

Novel direct approach for placement of permanent transvenous pacing leads after Fontan procedure

Jess T Randall, Osamah T Aldoss, Ian H Law, Abhay A Divekar

Annals of Pediatric Cardiology 2018 11(2):187-190

The need for transvenous pacing (patients who have exhausted epicardial options) after a Fontan-type operation has been recognized. Many novel strategies have been proposed, but currently, all of them require additional maneuvers or rerouting of the leads to the pacemaker pocket. In this report, we describe a novel direct approach to transvenous pacing after a Fontan-type operation from a standard, prepectoral approach.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2rkP8R8
via IFTTT

T-wave alternans in long QT syndrome

Siddharth Narayan Gadage

Annals of Pediatric Cardiology 2018 11(2):219-221

Long QT syndrome (LQTS) is a congenital disorder characterized by prolongation of QT interval in the electrocardiogram (ECG) and a propensity to develop ventricular arrhythmias, which may lead to syncope, cardiac arrest or sudden death. T-wave alternans (TWA), a phenomenon of beat-to-beat variability in the repolarization phase of the ventricles, has been closely associated with an increased risk of ventricular tachyarrhythmic events (VTE) and sudden cardiac death (SCD).

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2HPq5AL
via IFTTT

Effects of p-Synephrine and Caffeine Ingestion on Substrate Oxidation during Exercise

Purpose Caffeine and p-synephrine are substances usually included in commercially-available products for weight loss because of their purported thermogenic effects. However, scientific information is lacking about the effects of combining these substances on substrate oxidation during exercise. The purpose of this investigation was to determine the isolated and combined effects of p-synephrine and caffeine on fat oxidation rate during exercise. Methods In a double-blind randomized experiment, 13 healthy subjects participated in 4 experimental trials after the ingestion of a capsule containing either a placebo, 3 mg·kg-1 of caffeine, 3 mg·kg-1 of p-synephrine, or the combination of these doses of caffeine and p-synephrine. Energy expenditure and substrate oxidation rates were measured by indirect calorimetry during a cycle ergometer ramp test from 30 to 90% of VO2max. Results In comparison to the placebo, the ingestion of caffeine, p-synephrine, or p-synephrine+caffeine did not alter total energy expenditure or heart rate during the whole exercise test. However, the ingestion of caffeine (0.44 ± 0.15 g·min–1, P = 0.03), p-synephrine (0.43 ± 0.19 g·min–1, P

from Sports Medicine via xlomafota13 on Inoreader https://ift.tt/2HNxNLD
via IFTTT

Nitrate Supplement Benefits Contractile Forces in Fatigued but Not Unfatigued Muscle

Purpose Evidence suggests dietary nitrate supplementation enhances low-frequency (≤20 Hz) involuntary, but not voluntary, forces in unfatigued human muscle. We investigated the hypotheses that nitrate supplementation would also attenuate low-frequency fatigue and the loss of explosive-voluntary forces in fatigued conditions. Methods In a counterbalanced double-blinded order, 17 male participants completed two experimental trials following 7 days of dietary supplementation with either nitrate-rich (NIT) or nitrate-depleted (PLA) beetroot juice. Each trial consisted of measuring isometric knee-extension forces during a series of explosive-maximal voluntary contractions (MVCs) and involuntary-tetanic contractions (at 10, 20 50, and 100 Hz) in unfatigued conditions, followed by a fatigue protocol of 60 MVCs and a repeat of the tetanic contractions immediately post the 60 MVCs. Results In unfatigued conditions, there was no effect of NIT on any of the measured dependent variables; including maximal voluntary force, explosive-impulse, and tetanic peak forces or peak rate of force developments (RFDs) at any frequency. In contrast, the percentage decline in explosive-voluntary impulse from the first to the last 6 MVCs in the fatigue protocol was lower in NIT (51.1 ± 13.9%) than PLA (57.3 ± 12.4%; P=0.039; d=0.51). Furthermore, low-frequency fatigue determined via the percentage decline in the 20:50 Hz ratio was attenuated in NIT, for tetanic peak force (NIT, 12.3 ± 12.0% vs. PLA, 17.0 ± 10.1%; P=0.110; d=0.46), and tetanic peak RFD (NIT, 12.3 ± 10.4% vs. PLA, 20.3 ± 9.5%; P=0.011; d=0.83). Conclusion Nitrate supplementation reduced the decline in explosive-voluntary forces during a fatiguing protocol, and attenuated low-frequency fatigue, likely due to reduced disruption of excitation-contraction coupling. However, contrary to previous findings, nitrate supplementation had no effect on contractile performance in unfatigued conditions. Correspondence: Neale A. Tillin, University of Roehampton, Whitelands College, Holybourne Avenue, London, UK, SW5 4JD, Email: neale.tillin@roehampton.ac.uk This work was funded by the University of Roehampton. Conflict of Interest: The authors have no professional relationships with companies or manufacturers that may benefit from the results of the present study. The results of the present study do not constitute endorsement by ACSM. The Authors declare the results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 24 April 2018 © 2018 American College of Sports Medicine

from Sports Medicine via xlomafota13 on Inoreader https://ift.tt/2wbRAyX
via IFTTT

The Associations between Adiposity, Cognitive Function, and Achievement in Children

Although obesity has been related to measures of academic achievement and cognition in children, the influence of fat distribution, specifically visceral adiposity, on select aspects of achievement and cognitive function remains poorly characterized among preadolescent children. Purpose The aim of this study was to evaluate the relation of adiposity, particularly visceral adipose tissue, on achievement and cognitive function among children. Methods Children with obesity (ages 7-9 years old, N= 55, 35 females) completed cognitive and academic tests. Normal weight children (N= 55, 35 females) were matched to this group on demographic characteristics and aerobic fitness. Covariate analyses included age, Brief Intellectual Ability (BIA), SES, and fat free VO2 (VO2 peak adjusted for lean mass; ml/kg lean/min). Adiposity (i.e., whole body percent fat, subcutaneous abdominal adipose tissue (SAAT), and visceral adipose tissue (VAT)) was assessed using dual energy X-ray absorptiometry. Results The results of this study revealed that, relative to their normal weight counterparts, children with obesity had significantly lower performance on tests of reading and math. Analyses revealed that among children with obesity, %Fat and SAAT were not related to cognitive abilities. However, higher VAT was associated with poorer intellectual abilities, p's≤0.04; and cognitive performance (i.e. Thinking Ability and Cognitive Efficiency), p's≤0.04. However, among normal weight children, VAT was positively associated with intellectual abilities and cognitive efficiency. Conclusion In conclusion, the results suggest that VAT was selectively and negatively related with cognition among children with obesity. Along with the dangerous metabolic nature of VAT, its detrimental relationship with obese children's intellectual and cognitive functioning is concerning. CONTACT INFO: Lauren B. Raine, Department of Psychology, 635 ISEC, 360 Huntington Ave, Northeastern University, Boston, MA 02115, E-mail: l.raine@northeastern.edu FUNDING SOURCE: Support for this project was provided by the National Institute of Food and Agriculture, U.S. Department of Agriculture, under award number 2011-67001-30101 and NICHD grant HD069381. These sources did not play a role in the study design, collection, analysis or interpretation of the data, nor in the writing of the report and decision to submit the article for publication. Conflict of Interest: The authors of this document report no conflicts of interest associated with the collection, dissemination, or interpretation of this research. No patents, copyrights, or royalties are involved or included in this work. The results of the present study do not constitute endorsement by ACSM. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 17 April 2018 © 2018 American College of Sports Medicine

from Sports Medicine via xlomafota13 on Inoreader https://ift.tt/2IchnvO
via IFTTT

Adipose Tissue Responses to Breaking Sitting in Men and Women with Central Adiposity

Purpose Breaking prolonged sitting reduces postprandial glucose and insulin concentrations and influences skeletal muscle molecular signalling pathways but it is unknown whether breaking sitting also affects adipose tissue. Methods Eleven central overweight participants (7 men and 4 post-menopausal women) aged 50 ± 5 years (means ± SD) completed two mixed-meal feeding trials (PROLONGED SITTING versus BREAKING SITTING) in a randomised, counterbalanced design. The BREAKING SITTING intervention comprised walking for 2 min every 20 min over 5.5 h. Blood samples were taken at regular intervals to examine metabolic biomarkers and adipokine concentrations. Adipose tissue samples were taken at baseline and at 5.5 h to examine changes in mRNA expression and secretion of selected adipokines ex-vivo. Results Postprandial glycaemia and insulinaemia were attenuated by approximately 50% and 40% in BREAKING SITTING compared to PROLONGED SITTING (iAUC: 359 ± 117 versus 697 ± 218 mmol·330 min·L-1, p = 0.001 and 202 ± 71 versus 346 ± 150 nmol·330 min·L-1, p = 0.001, respectively). Despite these pronounced and sustained differences in postprandial glucose and insulin concentrations, adipose tissue mRNA expression for various genes (IL-6, leptin, adiponectin, PDK4, IRS1/2, PI3K and Akt1, etc.) and ex-vivo adipose tissue secretion of IL-6, leptin and adiponectin were not different between trials. Conclusions: This study demonstrates that breaking sitting with short bouts of physical activity has very pronounced effects on systemic postprandial glucose and insulin concentrations but this does not translate into corresponding effects within adipose tissue. Corresponding author: Professor Dylan Thompson, Department for Health, University of Bath, Bath, BA2 7AY, United Kingdom, Email: d.thompson@bath.ac.uk This project was funded by Ministry of Education (Taiwan) and the University of Bath. The authors declare no competing interests. The results of the present study do not constitute endorsement by the American College of Sports Medicine. The results of this study are presented clearly, honestly, and without fabrications, falsification, or inappropriate data manipulation. Accepted for Publication: 5 April 2018 © 2018 American College of Sports Medicine

from Sports Medicine via xlomafota13 on Inoreader https://ift.tt/2HUHXpB
via IFTTT

ED50 of remifentanil for providing excellent intubating conditions when co-administered with a single standard dose of propofol without the use of muscle relaxants in children: dose-finding clinical trial

Abstract

Purpose

Previous studies evidenced that orotracheal intubation without neuromuscular blockers is feasible in children and has some potential advantages. Remifentanil has favorable pharmacodynamic and pharmacokinetic properties as an opioid for orotracheal intubation, but its dose for excellent intubation conditions when co-administered with propofol has not been established. This study was designed to find the minimum effective dose of remifentanil for excellent intubation conditions of children when co-administered with propofol, without neuromuscular relaxant drugs.

Method

Blinded adaptive clinical trial, with sequential allocation of 27 children between 2 and 9 years-old, American Society of Anesthesiologists' physical status PI or PII, scheduled for elective surgery under general anesthesia. Remifentanil dose began at 2 µg/kg and varied by 0.25 µg/kg according to the sequential allocation up-and-down rule designed by Dixon and Massey. Remifentanil was infused in 30 s and followed by propofol (3 mg/kg) in 20 s. Laryngoscopy and intubation were performed and assessed using Viby-Mogensen criteria, 90 s after the end of opioid administration. Inclusion of patients stopped after six crossovers, and remifentanil effective dose was estimated using pooled adjacent-violators algorithm.

Results

Remifentanil effective dose for 50% was established in 3.04 µg/kg (IC 95% 2.68–3.11, p < 0.05). The most frequent adverse effect was difficult positive pressure facial mask ventilation, which occurred in four children (15%).

Conclusion

Minimum remifentanil effective dose for providing excellent intubating conditions when co-administered with a single standard dose of propofol without the use of neuromuscular blockers in children is 3.04 µg/kg.

Trial registration

NCT02454868.

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2jsbzA5
via IFTTT

Open-circuit respirometry: real-time, laboratory-based systems

Abstract

This review explores the conceptual and technological factors integral to the development of laboratory-based, automated real-time open-circuit mixing-chamber and breath-by-breath (B × B) gas-exchange systems, together with considerations of assumptions and limitations. Advances in sensor technology, signal analysis, and digital computation led to the emergence of these technologies in the mid-20th century, at a time when investigators were beginning to recognise the interpretational advantages of nonsteady-state physiological-system interrogation in understanding the aetiology of exercise (in)tolerance in health, sport, and disease. Key milestones include the 'Auchincloss' description of an off-line system to estimate alveolar O₂ uptake B × B during exercise. This was followed by the first descriptions of real-time automated O₂ uptake and CO₂ output B × B measurement by Beaver and colleagues and by Linnarsson and Lindborg, and mixing-chamber measurement by Wilmore and colleagues. Challenges to both approaches soon emerged: e.g., the influence of mixing-chamber washout kinetics on mixed-expired gas concentration determination, and B × B alignment of gas-concentration signals with respired flow. The challenging algorithmic and technical refinements required for gas-exchange estimation at the alveolar level have also been extensively explored. In conclusion, while the technology (both hardware and software) underpinning real-time automated gas-exchange measurement has progressively advanced, there are still concerns regarding accuracy especially under the challenging conditions of changing metabolic rate.

from Physiology via xlomafota13 on Inoreader https://ift.tt/2HMIXjU
via IFTTT

The unique action of nicorandil on cerebral circulation

from Anaesthesiology via xlomafota13 on Inoreader https://ift.tt/2HRvsex
via IFTTT

Association between psychotropic medications and presence of sleep bruxism: A systematic review

Journal of Oral Rehabilitation, EarlyView.


from Rehabilitation via xlomafota13 on Inoreader https://ift.tt/2HOZ947
via IFTTT