Lunaterrell4052

Correlation between different CMR criteria varied from moderate to very strong. In multivariate binary logistic regression analysis with CMR and non-CMR parameters, independent positive predictors for a (L)PV were familial cardiomyopathy, trabecular mass, and meeting Petersen criteria in ≥2 out of 3 long axis views, while left bundle branch block and hypertension were negative predictors. The ROC-curve of this multivariate model had an area under the curve of 0.89 (95%CI 0.82-0.97). Conclusion CMR criteria together with family history help to distinguish those patients in whom a (L)PV can be identified, consequently leading to referral for genetic diagnostics and cascade screening.Objective This study aimed to identify outcome determinants for extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (BTT) at our institution. Methods This retrospective single-center study reviewed patients on ECMO between 2010 and 2018 and compared clinical characteristics between patients who underwent successful-BTT and those who did not. Additionally, we examined differences between actively vs. emergently listed patients and reasons for failure-to-list. Results 76 patients were placed on ECMO with the intent to bridge to transplant. Of those, 42 were actively on the waitlist (AWL) prior to ECMO initiation, 20 were emergently evaluated and waitlisted (EWL) after ECMO initiation, and 14 failed-to-list. Of the 62 listed patients, 42 (68%) were successfully transplanted. Risk factors of failed-BTT included RV dysfunction prior to ECMO initiation, longer ECMO duration, reduced mobility status, shorter stature, higher prevalence of blood type B, worse kidney and liver function, and increased transfusion requirements. The number of patients transitioned to central VA-ECMO was higher in the failed-BTT group. Thirty-day survival post-transplantation was 98%, with 90% successfully discharged; 1-year survival conditional upon discharge was 97%. AWL and EWL groups had comparable outcomes. Reasons for failure-to-list are not readily modifiable. Conclusions ECMO-BTT has become a viable option with satisfactory 1-year survival in patients with irreversible lung injury. Our results support rescue transplant for emergently evaluated and waitlisted patients on ECMO. Our data suggests that modification in national organ allocation policies especially as they pertain to high-acuity recipients with rare blood types and short stature could enhance successful outcome.Schizophrenia patients are at higher risk of engaging in violent behavior than the general population. Schizophrenia is also regarded as a highly heritable disorder. This study aims to analyze genome-wide the effect of SNPs on violence in schizophrenia. We recruited 205 subjects between the age of 18-75 from the Centre for Addiction and Mental Health (CAMH), who had a diagnosis of schizophrenia or schizoaffective disorder. We recorded physical, verbal and lifetime violence scores indicating any violent actions to inflict pain, bodily harm, or death on another individual from the standardized scale, Modified Overt Aggression Scale (MOAS). We genotyped each participant DNA using the Illumina Omni 2.5, and the SNPs were analyzed using the whole genome analysis tool-set, PLINK. We probed for single nucleotide polymorphisms (SNPs) correlated with violence in schizophrenia patients. We found one SNP (rs2188177) on chromosome 7 which showed a trend for association with physical violence (p = 7.80E-06). This study is the first of its kind to investigate genome-wide, the polymorphisms associated with violence in schizophrenia. The findings of this study may promote collaborative efforts to understand the genetic basis of violent behavior in psychosis.In this paper we explore the phenomenon of pleiotropy in neurodegenerative diseases, focusing on Alzheimer's disease (AD). We summarize the various techniques developed to investigate pleiotropy among traits, elaborating in the polygenic risk scores (PRS) analysis. PRS was designed to assess a cumulative effect of a large number of SNPs for association with a disease and, later for disease risk prediction. Since genetic predictions rely on heritability, we discuss SNP-based heritability from genome-wide association studies and its contribution to the prediction accuracy of PRS. We review work examining pleiotropy in neurodegenerative diseases and related phenotypes and biomarkers. We conclude that the exploitation of pleiotropy may aid in the identification of novel genes and provide further insights in the disease mechanisms, and along with PRS analysis, may be advantageous for precision medicine.Dravet syndrome is a severe infantile-onset epileptic encephalopathy which begins with febrile seizures and is caused by heterozygous loss-of-function mutations of the voltage-gated sodium channel gene SCN1A. We designed a CRISPR-based gene therapy for Scn1a-haplodeficient mice using multiple guide RNAs (gRNAs) in the promoter regions together with the nuclease-deficient Cas9 fused to transcription activators (dCas9-VPR) to trigger the transcription of SCN1A or Scn1a in vitro. We tested the effect of this strategy in vivo using an adeno-associated virus (AAV) mediated system targeting inhibitory neurons and investigating febrile seizures and behavioral parameters. In both the human and mouse genes multiple guide RNAs (gRNAs) in the upstream, rather than downstream, promoter region showed high and synergistic activities to increase the transcription of SCN1A or Scn1a in cultured cells. Intravenous injections of AAV particles containing the optimal combination of 4 gRNAs into transgenic mice with Scn1a-haplodeficiency and inhibitory neuron-specific expression of dCas9-VPR at four weeks of age increased Nav1.1 expression in parvalbumin-positive GABAergic neurons, ameliorated their febrile seizures and improved their behavioral impairments. Although the usage of transgenic mice and rather modest improvements in seizures and abnormal behaviors hamper direct clinical application, our results indicate that the upregulation of Scn1a expression in the inhibitory neurons can significantly improve the phenotypes, even when applied after the juvenile stages. Our findings also suggest that the decrease in Nav1.1 is directly involved in the symptoms seen in adults with Dravet syndrome and open a way to improve this condition.Objective Individuals from different socioeconomic status (SES) backgrounds may respond variably to stressful events, and such differences are likely to contribute to health disparities. The current study leveraged data collected before and after a petrochemical explosion and aimed to investigate how individuals from different SES backgrounds responded to this unexpected stressor in terms of perceived social support, perceived stress, and systemic inflammation. Methods Data were drawn from 124 participants (Mage = 55.9 ± 16.1 years, 69.4% female, 29.0% White) living close to a petrochemical complex where the explosion occurred in 2005. SES was assessed at baseline, and perceived stress and inflammatory markers (i.e., C-reactive protein [CRP], interleukin-6 [IL-6]) were assessed at both pre- and post-explosion. Perceived social support was assessed at post-explosion. Results Lower SES was associated with less perceived social support. Lower SES was also associated with a larger increase in perceived stress and higher levels of IL-6, but not CRP. Perceived social support did not moderate or mediate the effects of SES on changes in perceived stress, IL-6, or CRP. The associations between SES and inflammatory markers were also not explained by changes in perceived stress. Conclusion Findings from this study support the idea that individuals from different SES backgrounds respond differently to stressors at both the psychosocial (perceived social support and perceived stress) and biological (inflammation) levels. Our findings also suggest that these two processes appear to act independently from each other.Objective Neurological outcome prediction is crucial early after cardiac arrest. Serum biomarkers released from brain cells after hypoxic-ischemic injury may aid in outcome prediction. The only serum biomarker presently recommended in the European Resuscitation Council prognostication guidelines is neuron-specific enolase (NSE), but NSE has limitations. In this study, we therefore analysed the outcome predictive accuracy of the serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in patients after cardiac arrest. Methods Serum GFAP and UCH-L1 were collected at 24, 48 and 72hours after cardiac arrest. The primary outcome was neurological function at 6-month follow-up assessed by the cerebral performance category scale (CPC), dichotomized into good (CPC1-2) and poor (CPC3-5). Prognostic accuracies were tested with receiver-operating characteristics by calculating the area under the receiver-operating curve (AUROC) and compared to the AUROC of NSE. Results 717 patients were included in the study. GFAP and UCH-L1 discriminated between good and poor neurological outcome at all time-points when used alone (AUROC GFAP 0.88-0.89; UCH-L1 0.85-0.87) or in combination (AUROC 0.90-0.91). The combined model was superior to GFAP and UCH-L1 separately and NSE (AUROC 0.75-0.85) at all time-points. At specificities ≥95%, the combined model predicted poor outcome with a higher sensitivity than NSE at 24hours and with similar sensitivities at 48 and 72hours. Conclusion GFAP and UCH-L1 predicted poor neurological outcome with high accuracy. Their combination may be of special interest for early prognostication after cardiac arrest where it performed significantly better than the currently recommended biomarker NSE.Aim The Suppression Ratio (SR) estimates the percent of the electroencephalography (EEG) epoch with very low voltage, and is associated with neurological outcome after cardiac arrest. We aimed to compare the SR generated by two monitoring devices and determine the association between SR and patterns on amplitude integrated EEG (aEEG) and full conventional EEG (cEEG). Methods Consecutive adult patients treated with TTM after cardiac arrest were enrolled. CTx-648 order We compared the SR from the Medtronic Vista monitor (MSR) to the SR generated from the full montage cEEG with Persyst Magic-Marker software (PSR). A blinded neurologist, board certified in epilepsy, scored the 4-channel aEEG pattern and the cEEG background using standardized terminology. Values for SR were compared to aEEG and cEEG categories using Kruskal-Wallis ANOVA, and to each other using Altman-Bland methodology. Results 23 adults treated with TTM had a mean core temperature of 33.8°C at the time of SR and EEG background analysis. The MSR was 0% during continuous cEEG background, 23% when cEEG was discontinuous, and 64% during cEEG burst suppression (p=0.01). The MSR was 0% during aEEG continuous patterns, 34% during aEEG burst suppression, and 46% during flat aEEG (p less then 0.001). The MSR and PSR were highly correlated (0.88, p less then 0.0001), with minimal bias (0.3%) and excellent 95% limits of agreement (-2.9 to 2.4%). Conclusion The Suppression Ratio from the Medtronic Vista monitor is highly correlated with the full montage SR from Persyst software. The MSR values are valid, changing with different aEEG patterns and cEEG background categories.