Alteración del strain auricular izquierdo como predictor de fibrilación auricular de nuevo comienzo tras recambio valvular aórtico,independientemente del tamaño de la aurícula izquierda

Introduction and objectives

Left atrial dysfunction in aortic stenosis may precede atrial enlargement and predict the occurrence of atrial fibrillation (AF). To test this hypothesis, we assessed left atrial function and determined its impact on the incidence of AF after aortic valve replacement.

Comparison of Sagittal Spinopelvic Alignment between Lumbar Degenerative Spondylolisthesis and Degenerative Spinal Stenosis

Objective

The purpose of this study was to evaluate the differences in sagittal spinopelvic alignment between lumbar degenerative spondylolisthesis (DSPL) and degenerative spinal stenosis (DSS).

Methods

Seventy patients with DSPL and 72 patients with DSS who were treated with lumbar interbody fusion surgery were included in this study. The following spinopelvic parameters were measured on whole spine lateral radiographs in a standing position : pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis angle (LL), L4-S1 segmental lumbar angle (SLL), thoracic kyphosis (TK), and sagittal vertical axis from the C7 plumb line (SVA). Two groups were subdivided by SVA value, respectively. Normal SVA subgroup and positive SVA subgroup were divided as SVA value (<50 mm and ≥50 mm). Spinopelvic parameters/PI ratios were assessed and compared between the groups.

Results

The PI of DSPL was significantly greater than that of DSS (p=0.000). The SVA of DSPL was significantly greater than that of DSS (p=0.001). In sub-group analysis between the positive (34.3%) and normal SVA (65.7%), there were significant differences in LL/PI and SLL/PI (p<0.05) in the DSPL group. In sub-group analysis between the positive (12.5%) and normal SVA (87.5%), there were significant differences in PT/PI, SS/PI, LL/PI and SLL/PI ratios (p<0.05) in the DSS group.

Conclusion

Patients with lumbar degenerative spondylolisthesis have the propensity for sagittal imbalance and higher pelvic incidence compared with those with degenerative spinal stenosis. Sagittal imbalance in patients with DSPL is significantly correlated with the loss of lumbar lordosis, especially loss of segmental lumbar lordosis.     

Insertion of an SVA element, a nonautonomous retrotransposon, in PMS2 intron 7 as a novel cause of Lynch syndrome

Heterozygous germline mutations in the mismatch repair gene PMS2 predispose carriers for Lynch syndrome, an autosomal dominant predisposition to cancer. Here, we present a LINE-1-mediated retrotranspositional insertion in PMS2 as a novel mutation type for Lynch syndrome. This insertion, detected with Southern blot analysis in the genomic DNA of the patient, is characterized as a 2.2 kb long 5' truncated SVA_F element. The insertion is not detectable by current diagnostic testing limited to MLPA and direct Sanger sequencing on genomic DNA. The molecular nature of this insertion could only be resolved in RNA from cultured lymphocytes in which nonsense-mediated RNA decay was inhibited. Our report illustrates the technical problems encountered in the detection of this mutation type. Especially large heterozygous insertions will remain unnoticed because of preferential amplification of the smaller wild-type allele in genomic DNA, and are probably underreported in the mutation spectra of autosomal dominant disorders.     

Simvastatin inhibition of mevalonate pathway induces apoptosis in human breast cancer cells via activation of JNK/CHOP/DR5 signaling pathway

Simvastatin (SVA) was shown to up-regulate expression of death receptor-5 (DR5), CCAAT/enhancer binding protein homologous protein (CHOP) and phosphorylated c-Jun N-terminal kinase (pJNK) in human breast cancer cell lines. siRNA knockdown of DR5, CHOP or JNK significantly blocked SVA-induced apoptosis, demonstrating the importance of JNK/CHOP/DR5 signaling pathway in SVA-induced apoptosis. Exogenous addition of either mevalonate or geranylgeranyl pyrophosphate (GGPP) inhibited SVA activation of JNK/CHOP/DR5 pro-apoptotic pathway, indicating that activation of JNK/CHOP/DR5 pro-apoptotic pathway is dependent on SVA inhibition of 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase and its intermediate GGPP. Data provide novel insight into better understanding the anticancer mechanisms of SVA.     

A call to improve the validity of criterion-based content analysis (CBCA): Results from a field-based study including 60 children's statements of sexual abuse

The growing awareness of sexually-abused children has led to a major shift: previously considered untrustworthy, children are now regarded as competent in providing medico-legal evidence. Professionals undertaking the challenging task of assessing the child's credibility need to rely upon approved evaluation methods. The Criteria-Based Content Analysis is a tool developed to assess the truthfulness of a child's verbal statement. This field-based study explores its validity and its limitations.Three independent experts rated the verbatim statements of 60 real-life alleged victims of sexual abuse. The CBCA scoring and final assessment of credibility were linked to the outcomes: confirmed or unconfirmed allegation of sexual abuse.Inter-rater reliability coefficient was 0.74. The average overall accuracy rate corresponding to confirmed and unconfirmed cases was 75%. Among the confirmed allegations, the accuracy rate reached 90%, whereas the probability of discriminating the true negative cases within the unconfirmed cases was lower than chance level. Of all the 19 criteria, items 6 “Reproduction of conversation” and 12 “Accounts of subjective mental state” were the strongest predictors of genuine accounts. A significant association between age and CBCA scores was noted, the effect of age on CBCA scores was strongest in the unconfirmed cases.Although some may argue that the validity of the CBCA is reasonably acceptable, results from this field study are less convincing. Increasing the diagnostic accuracy of the CBCA by adding new criteria, so as to raise the percentage of correct classifications in the confirmed accounts as well as in the unconfirmed accounts, would represent a major improvement.     

Development and validation of InnoQuant™, a sensitive human DNA quantitation and degradation assessment method for forensic samples using high copy number mobile elements Alu and SVA

There is a constant need in forensic casework laboratories for an improved way to increase the first-pass success rate of forensic samples. The recent advances in mini STR analysis, SNP, and Alu marker systems have now made it possible to analyze highly compromised samples, yet few tools are available that can simultaneously provide an assessment of quantity, inhibition, and degradation in a sample prior to genotyping. Currently there are several different approaches used for fluorescence-based quantification assays which provide a measure of quantity and inhibition. However, a system which can also assess the extent of degradation in a forensic sample will be a useful tool for DNA analysts. Possessing this information prior to genotyping will allow an analyst to more informatively make downstream decisions for the successful typing of a forensic sample without unnecessarily consuming DNA extract. Real-time PCR provides a reliable method for determining the amount and quality of amplifiable DNA in a biological sample.Alu are Short Interspersed Elements (SINE), approximately 300 bp insertions which are distributed throughout the human genome in large copy number. The use of an internal primer to amplify a segment of an Alu element allows for human specificity as well as high sensitivity when compared to a single copy target. The advantage of an Alu system is the presence of a large number (>1000) of fixed insertions in every human genome, which minimizes the individual specific variation possible when using a multi-copy target quantification system. This study utilizes two independent retrotransposon genomic targets to obtain quantification of an 80 bp “short” DNA fragment and a 207 bp “long” DNA fragment in a degraded DNA sample in the multiplex system InnoQuant™. The ratio of the two quantitation values provides a “Degradation Index”, or a qualitative measure of a sample's extent of degradation. The Degradation Index was found to be predictive of the observed loss of STR markers and alleles as degradation increases. Use of a synthetic target as an internal positive control (IPC) provides an additional assessment for the presence of PCR inhibitors in the test sample.In conclusion, a DNA based qualitative/quantitative/inhibition assessment system that accurately predicts the status of a biological sample, will be a valuable tool for deciding which DNA test kit to utilize and how much target DNA to use, when processing compromised forensic samples for DNA testing.     

Emergence and whole‐genome sequence of Senecavirus A in Colombia

In 2015 and 2016, Senecavirus A (SVA) emerged as an infectious disease in Brazil, China and the United States (US). In a Colombian commercial swine farm, vesicles on the snout and coronary bands were reported and tested negative for foot‐and‐mouth disease virus (FMDv), but positive for SVA. The whole‐genome phylogenetic analysis indicates the Colombian strain clusters with the strains from the United States, not with the recent SVA strains from Brazil.     

Germline Chromothripsis Driven by L1‐Mediated Retrotransposition and Alu/Alu Homologous Recombination

Chromothripsis (CTH) is a phenomenon where multiple localized double‐stranded DNA breaks result in complex genomic rearrangements. Although the DNA‐repair mechanisms involved in CTH have been described, the mechanisms driving the localized “shattering” process remain unclear. High‐throughput sequence analysis of a familial germline CTH revealed an inserted SVA_E retrotransposon associated with a 110‐kb deletion displaying hallmarks of L1‐mediated retrotransposition. Our analysis suggests that the SVA_E insertion did not occur prior to or after, but concurrent with the CTH event. We also observed L1‐endonuclease potential target sites in other breakpoints. In addition, we found four Alu elements flanking the 110‐kb deletion and associated with an inversion. We suggest that chromatin looping mediated by homologous Alu elements may have brought distal DNA regions into close proximity facilitating DNA cleavage by catalytically active L1‐endonuclease. Our data provide the first evidence that active and inactive human retrotransposons can serve as endogenous mutagens driving CTH in the germline.