Excess Mortality Rate During Adulthood Among Danish Adoptees

BACKGROUND AND OBJECTIVE: Adoption studies have been used to disentangle the influence of genes from shared familial environment on various traits and disease risks. However, both the factors leading to adoption and living as an adoptee may bias the studies with regard to the relative influence of genes and environment compared to the general population. The aim was to investigate whether the cohort of domestic adoptees used for these studies in Denmark is similar to the general population with respect to all-cause mortality and cause-specific mortality rates. METHODS: 13,111 adoptees born in Denmark in 1917, or later, and adopted in 1924 to 1947 were compared to all Danes from the same birth cohorts using standardized mortality ratios (SMR). The 12,729 adoptees alive in 1970 were similarly compared to all Danes using SMR as well as cause-specific SMR. RESULTS: The excess in all-cause mortality before age 65 years in adoptees was estimated to be 1.30 (95% CI 1.26-1.35). Significant excess mortality before age 65 years was also observed for infections, vascular deaths, cancer, alcohol-related deaths and suicide. Analyses including deaths after age 65 generally showed slightly less excess in mortality, but the excess was significant for all-cause mortality, cancer, alcohol-related deaths and suicides. CONCLUSION: Adoptees have an increased all-cause mortality compared to the general population. All major specific causes of death contributed, and the highest excess is seen for alcohol-related deaths

Routine clinical cardiovascular magnetic resonance in paediatric and adult congenital heart disease: patients, protocols, questions asked and contributions made

<p>Abstract</p> <p>Background</p> <p>Cardiovascular Magnetic Resonance (CMR) of patients with congenital heart disease (CHD) has become routine clinical practice. However, existing CMR protocols focus predominantly on patients with ischemic heart disease, and information is limited on the types of patient with CHD who benefit from CMR investigation, and in what ways. Therefore the aim of this study was to answer the questions: What type of patients were studied by CMR in a centre specializing in paediatric and adult CHD management? What questions were asked, which protocols were used and were the questions successfully answered? To answer these questions, we conducted a cohort study of all 362 patients that received routine clinical CMR during 2007 at the Department of Paediatric Cardiology and Congenital Heart Disease at the Deutsches Herzzentrum München.</p> <p>Results</p> <p>Underlying diagnosis was in 33% Fallot's tetralogy, 17% aortic coarctation, 8% Ebstein's disease, 6% Marfan's disease, 4% single ventricle with Fontan-like circulation, and 32% others. Median age was 26 years (7 days – 75 years). Ventricular volumes were assessed in 67% of the patients; flow in 74%; unknown anatomy only in 9%; specific individual morphology of known anatomy in 83%; myocardial fibrosis in 8%; stress-induced myocardial perfusion defects in 1%. Only in 3% of the cases the question could not be fully answered.</p> <p>Conclusion</p> <p>Contrary to common belief, routine CMR of patients with CHD was not requested to address global anatomical questions so much as to clarify specific questions of morphology and function of known anatomy. The CMR protocols used differed markedly from those widely used in patients with ischemic heart disease.</p

A new 2D-based method for myocardial velocity strain and strain rate quantification in a normal adult and paediatric population: assessment of reference values

<p>Abstract</p> <p>Background</p> <p>Recent advances in technology have provided the opportunity for off-line analysis of digital video-clips of two-dimensional (2-D) echocardiographic images.</p> <p>Commercially available software that follows the motion of cardiac structures during cardiac cycle computes both regional and global velocity, strain, and strain rate (SR).</p> <p>The present study aims to evaluate the clinical applicability of the software based on the tracking algorithm feature (studied for cardiology purposes) and to derive the reference values for longitudinal and circumferential strain and SR of the left ventricle in a normal population of children and young adults.</p> <p>Methods</p> <p>45 healthy volunteers (30 adults: 19 male, 11 female, mean age 37 ± 6 years; 15 children: 8 male, 7 female, mean age 8 ± 2 years) underwent transthoracic echocardiographic examination; 2D cine-loops recordings of apical 4-four 4-chamber (4C) and 2-chamber (2C) views and short axis views were stored for off-line analysis.</p> <p>Computer analyses were performed using specific software relying on the algorithm of optical flow analysis, specifically designed to track the endocardial border, installed on a Windows™ based computer workstation. Inter and intra-observer variability was assessed.</p> <p>Results</p> <p>The feasibility of measurements obtained with tissue tracking system was higher in apical view (100% for systolic events; 64% for diastolic events) than in short axis view (70% for systolic events; 52% for diastolic events). Longitudinal systolic velocity decreased from base to apex in all subjects (5.22 ± 1.01 vs. 1.20 ± 0.88; p < 0.0001). Longitudinal strain and SR significantly increased from base to apex in all subjects (-12.95 ± 6.79 vs. -14.87 ± 6.78; p = 0.002; -0.72 ± 0.39 vs. -0.94 ± 0.48, p = 0.0001, respectively). Similarly, circumferential strain and SR increased from base to apex (-21.32 ± 5.15 vs. -27.02 ± 5.88, p = 0.002; -1.51 ± 0.37 vs. -1.95 ± 0.57, p = 0.003, respectively).</p> <p>Values of global systolic SR, both longitudinal and circumferential, were significantly higher in children than in adults (-1.3 ± 0.2, vs. -1.11 ± 0.2, p = 0.006; -1.9 ± 0.6 vs. -1.6 ± 0.5, p = 0.0265, respectively). No significant differences in longitudinal and circumferential systolic velocities were identified for any segment when comparing adults with children.</p> <p>Conclusion</p> <p>This 2D based tissue tracking system used for computation is reliable and applicable in adults and children particularly for systolic events. Measured with this technology, we have established reference values for myocardial velocity, Strain and SR for both young adults and children.</p

A whey protein supplement decreases post-prandial glycemia

<p>Abstract</p> <p>Background</p> <p>Incidence of diabetes, obesity and insulin resistance are associated with high glycemic load diets. Identifying food components that decrease post-prandial glycemia may be beneficial for developing low glycemic foods and supplements. This study explores the glycemic impact of adding escalating doses of a glycemic index lowering peptide fraction (GILP) from whey to a glucose drink.</p> <p>Methods</p> <p>Ten healthy subjects (3M, 7F, 44.4 ± 9.3 years, BMI 33.6 ± 4.8 kg/m²) participated in an acute randomised controlled study. Zero, 5, 10 and 20 g of protein from GILP were added to a 50 g glucose drink. The control (0 g of GILP) meal was repeated 2 times. Capillary blood samples were taken fasting (0 min) and at 15, 30, 45, 60, 90 and 120 minutes after the start of the meal and analyzed for blood glucose concentration.</p> <p>Results</p> <p>Increasing doses of GILP decreased the incremental areas under the curve in a dose dependant manner (Pearson's r = 0.48, p = 0.002). The incremental areas (iAUC) under the glucose curve for the 0, 5, 10, and 20 g of protein from GILP were 231 ± 23, 212 ± 23, 196 ± 23, and 138 ± 13 mmol.min/L respectively. The iAUC of the 20 g GILP was significantly different from control, 5 g GILP and 10 g GILP (p < 0.001). Average reduction in the glucose iAUC was 4.6 ± 1.4 mmol.min/L per gram of ingested GILP.</p> <p>Conclusion</p> <p>Addition of GILP to a oral glucose bolus reduces blood glucose iAUC in a dose dependent manner and averages 4.6 ± 1.4 mmol.min/L per gram of GILP. These data are consistent with previous research on the effect of protein on the glycemic response of a meal.</p

High frequency of Human Cytomegalovirus DNA in the Liver of Infants with Extrahepatic Neonatal Cholestasis

BACKGROUND: Biliary atresia (BA) is the most severe hepatic disorder in newborns and its etiopathogenesis remains unknown. Viral involvement has been proposed, including the human cytomegalovirus (HCMV). The aims of the study were to use the polymerase chain reaction (PCR) to screen the liver tissue of infants with extrahepatic cholestasis for HCMV and to correlate the results with serological antibodies against HCMV and histological findings. METHODS: A retrospective study in a tertiary care setting included 35 patients (31 BA, 1 BA associated with a choledochal cyst, 2 congenital stenosis of the distal common bile duct and 1 hepatic cyst). HCMV serology was determined by ELISA. Liver and porta hepatis were examined histologically. Liver samples from infants and a control group were screened for HCMV DNA. RESULTS: Twelve patients had HCMV negative serology, 9 were positive for IgG antibodies and 14 were positive for IgG and IgM. Nine liver and seven porta hepatis samples were positive for HCMV DNA but none of the control group were positive (general frequency of positivity was 34.3% – 12/35). There was no correlation between HCMV positivity by PCR and the histological findings. The accuracy of serology for detecting HCMV antibodies was low. CONCLUSION: These results indicate an elevated frequency of HCMV in pediatric patients with extrahepatic neonatal cholestasis. They also show the low accuracy of serological tests for detecting active HCMV infection and the lack of correlation between HCMV positivity by PCR and the histopathological changes

Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia

Craniofacial microsomia (CFM) is a rare congenital anomaly that involves immature derivatives from the first and second pharyngeal arches. The genetic pathogenesis of CFM is still unclear. Here we interrogate 0.9 million genetic variants in 939 CFM cases and 2,012 controls from China. After genotyping of an additional 443 cases and 1,669 controls, we identify 8 significantly associated loci with the most significant SNP rs13089920 (logistic regression P 1�4 2.15 � 10 � 120) and 5 suggestive loci. The above 13 associated loci, harboured by candidates of ROBO1, GATA3, GBX2, FGF3, NRP2, EDNRB, SHROOM3, SEMA7A, PLCD3, KLF12 and EPAS1, are found to be enriched for genes involved in neural crest cell (NCC) development and vasculogenesis. We then perform whole-genome sequencing on 21 samples from the case cohort, and identify several novel loss-of-function mutations within the associated loci. Our results provide new insights into genetic background of craniofacial microsomia

The TALE Class Homeobox Gene Smed-prep Defines the Anterior Compartment for Head Regeneration

Planaria continue to blossom as a model system for understanding all aspects of regeneration. They provide an opportunity to understand how the replacement of missing tissues from preexisting adult tissue is orchestrated at the molecular level. When amputated along any plane, planaria are capable of regenerating all missing tissue and rescaling all structures to the new size of the animal. Recently, rapid progress has been made in understanding the developmental pathways that control planarian regeneration. In particular Wnt/beta-catenin signaling is central in promoting posterior fates and inhibiting anterior identity. Currently the mechanisms that actively promote anterior identity remain unknown. Here, Smed-prep, encoding a TALE class homeodomain, is described as the first gene necessary for correct anterior fate and patterning during planarian regeneration. Smed-prep is expressed at high levels in the anterior portion of whole animals, and Smed-prep(RNAi) leads to loss of the whole brain during anterior regeneration, but not during lateral regeneration or homeostasis in intact worms. Expression of markers of different anterior fated cells are greatly reduced or lost in Smed-prep(RNAi) animals. We find that the ectopic anterior structures induced by abrogation of Wnt signaling also require Smed-prep to form. We use double knockdown experiments with the S. mediterranea ortholog of nou-darake (that when knocked down induces ectopic brain formation) to show that Smed-prep defines an anterior fated compartment within which stem cells are permitted to assume brain fate, but is not required directly for this differentiation process. Smed-prep is the first gene clearly implicated as being necessary for promoting anterior fate and the first homeobox gene implicated in establishing positional identity during regeneration. Together our results suggest that Smed-prep is required in stem cell progeny as they form the anterior regenerative blastema and is required for specifying anterior cell fates and correct patterning

Cardiovascular magnetic resonance imaging of myocardial oedema following acute myocardial infarction: Is whole heart coverage necessary?

© 2016 Hamshere et al. Background: AAR measurement is useful when assessing the efficacy of reperfusion therapy and novel cardioprotective agents after myocardial infarction. Multi-slice (Typically 10-12) T2-STIR has been used widely for its measurement, typically with a short axis stack (SAX) covering the entire left ventricle, which can result in long acquisition times and multiple breath holds. This study sought to compare 3-slice T2-short-tau inversion recovery (T2- STIR) technique against conventional multi-slice T2-STIR technique for the assessment of area at risk (AAR). Methods: CMR imaging was performed on 167 patients after successful primary percutaneous coronary intervention. 82 patients underwent a novel 3-slice SAX protocol and 85 patients underwent standard 10-slice SAX protocol. AAR was obtained by manual endocardial and epicardial contour mapping followed by a semi- automated selection of normal myocardium; the volume was expressed as mass (%) by two independent observers. Results: 85 patients underwent both 10-slice and 3-slice imaging assessment showing a significant and strong correlation (intraclass correlation coefficient = 0.92;p < 0.0001) and a low Bland-Altman limit (mean difference -0.03 ± 3.21 %, 95 % limit of agreement,- 6.3 to 6.3) between the 2 analysis techniques. A further 82 patients underwent 3-slice imaging alone, both the 3-slice and the 10-slice techniques showed statistically significant correlations with angiographic risk scores (3-slice to BARI r = 0.36, 3-slice to APPROACH r = 0.42, 10-slice to BARI r = 0.27, 10-slice to APPROACH r = 0.46). There was low inter-observer variability demonstrated in the 3-slice technique, which was comparable to the 10-slice method (z = 1.035, p = 0.15). Acquisition and analysis times were quicker in the 3-slice compared to the 10-slice method (3-slice median time: 100 seconds (IQR: 65-171 s) vs (10-slice time: 355 seconds (IQR: 275-603 s); p < 0.0001. Conclusions: AAR measured using 3-slice T2-STIR technique correlates well with standard 10-slice techniques, with no significant bias demonstrated in assessing the AAR. The 3-slice technique requires less time to perform and analyse and is therefore advantageous for both patients and clinicians

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012