Clinical Images - An Incidental EKG

A routine employment stress test reveals Brugada syndrome, a rare abnormality

GIGI: An Approach to Effective Imputation of Dense Genotypes on Large Pedigrees

Recent emergence of the common-disease-rare-variant hypothesis has renewed interest in the use of large pedigrees for identifying rare causal variants. Genotyping with modern sequencing platforms is increasingly common in the search for such variants but remains expensive and often is limited to only a few subjects per pedigree. In population-based samples, genotype imputation is widely used so that additional genotyping is not needed. We now introduce an analogous approach that enables computationally efficient imputation in large pedigrees. Our approach samples inheritance vectors (IVs) from a Markov Chain Monte Carlo sampler by conditioning on genotypes from a sparse set of framework markers. Missing genotypes are probabilistically inferred from these IVs along with observed dense genotypes that are available on a subset of subjects. We implemented our approach in the Genotype Imputation Given Inheritance (GIGI) program and evaluated the approach on both simulated and real large pedigrees. With a real pedigree, we also compared imputed results obtained from this approach with those from the population-based imputation program BEAGLE. We demonstrated that our pedigree-based approach imputes many alleles with high accuracy. It is much more accurate for calling rare alleles than is population-based imputation and does not require an outside reference sample. We also evaluated the effect of varying other parameters, including the marker type and density of the framework panel, threshold for calling genotypes, and population allele frequencies. By leveraging information from existing genotypes already assayed on large pedigrees, our approach can facilitate cost-effective use of sequence data in the pursuit of rare causal variants

Diversion of the inferior vena cava following repair of atrial septal defect causing hypoxemia

Atrial septal defects (ASDs) are a common congenital abnormality, and operative repair is a routine, safe procedure. Diversion of the inferior vena cava (IVC) into the left atrium is an unusual complication following ASD closure. We report a case that illustrates the problem created by this right-to-left shunt. A middle-aged woman underwent ASD repair. She developed hypoxemia postoperatively. A transthoracic echocardiogram confirmed a right-to-left shunt, found only with agitated saline injected into the femoral vein, not into the basilic vein. Surgical reexploration revealed a residual ASD diverting IVC flow into the left atrium, which was repaired with a pericardial patch. Echocardiography with agitated saline injected from the femoral vein is an easy method to diagnose this uncommon complication

A Partnership to Improve Health Care in Kosovo: Dartmouth Medical School and Kosovar nurses worked together on a two-year project to rebuild primary health care in the postconflict city of Gjilan

Partnership between a health municipality in Kosova, in the former Republic of Yugoslavia and Dartmouth Medical School, New Hampshire, to rebuild the primary care system after the war. The project, which included nurses from both countries, is described, focusing on the changing roles of nurses

Metabarcoding assays for the detection of freshwater mussels (Unionida) with environmental DNA

Freshwater mussels of the order Unionida are a widely distributed taxon that are important in maintaining freshwater ecosystems and are also highly imperiled throughout the world. Monitoring of mussel populations with environmental DNA (eDNA) is an attractive alternative to traditional methods because it is noninvasive and requires less labor and taxonomic knowledge from field personnel. We developed eDNA metabarcoding assays specific to freshwater mussels and tested them at six sites in the Clinch River, located in the southeastern United States. Our objective was to determine the utility of eDNA metabarcoding for future monitoring of mussel populations and restoration efforts in this watershed. Two metabarcoding assays that target the mitochondrial DNA regions of the cytochrome c oxidase subunit I (COI) and NADH dehydrogenase subunit (ND1) genes were developed and tested. Our assays appear to be order specific, amplifying members from the two families found in North America, Unionidae and Margaritiferidae, while not amplifying nontarget fish or other bivalve species. From the field collected samples, our assays together detected 19 species, eight of which are listed as federally endangered. The assays also detected 42%, 58%, and 54% of the species identified by recent quantitative visual mussel surveys at three sampling sites. Increased sampling effort by processing a greater water volume or number of samples will likely increase species detections. These eDNA metabarcoding assays may enable enhanced monitoring of freshwater mussel assemblages and subsequently inform conservation efforts

Cardiomyopathy Secondary to Thyroid and Parathyroid Dysfunction: Case Report and Literature Review

Heart failure due to metabolic derangements is not common in clinical practice. However, outcome is usually positive given that the precipitating factor is recognized and treatment is initiated in a timely fashion. We report an unusual case of reduced left ventricular systolic function as a result of hypocalcemia and long standing untreated primary hypothyroidism in a patient without structural heart disease. Delay in seeking appropriate medical attention for both disorders has culminated in cardiac dysfunction that was favorably altered with correction of underlying etiologies. Therefore, early recognition and expedient management of hypocalcemia and hypothyroidism can result in an imminent improvement of cardiac function

An Unusual Migration of A Stent: A Case Report

Stent dislodgment and embolization is a rare complication of coronary stenting. There are reports of intra-coronary stent entrapment, stripping, and dislodgement during percutaneous coronary interventions causing potentially life threatening complications, including intra-coronary or systemic embolization. Reports of dislodgment and migration of previously placed drug eluting intra-coronary stent several months after deployment are very limited in the literature. We describe a drug eluting stent dislodgment and migration in an 88 year-old male 10 months after its deployment

Outcomes of Transcutaneous Aortic Valve Replacement among high risk WV sample population.

Introduction:Transcatheter aortic valve replacement (TAVR) is a relatively new strategy for replacing the aortic valve. We elected to review our early experience to see if we could identify clinical characteristics at baseline or immediately following the procedure that would predict death within one year. Methods:Charts for all patients assigned to receive TAVR procedure at St Mary’s medical center, Huntington, West Virginia between April, 2013 till November, 2016 were identified and reviewed. A total of seventy-two (72) cases were included. Results: All cause mortality rate at index hospitalization, 30 days, and 12 months was 5.6%(N=4), 6.9%(N=5), 19.4%(N=14) respectively. Stroke rate at index hospitalization, 30 days, and 12 months was 2.8%(N=2), 2.8%(N=2), 8.3%(N=6) respectively. Major predictors of death were post procedure GFR, Contrast volume, and number of antiplatelet agents therapy (AUC= 0.638, 0.632, 0.637 respectively). Conclusion: We found that post procedure GFR, less number of antiplatelet agents post procedure, and contrast volume may predict mortality within first 12 months post TAVR. Further studies focused on the above factors may be warranted

Approaches to mapping genetically correlated complex traits

Our Markov chain Monte Carlo (MCMC) methods were used in linkage analyses of the Framingham Heart Study data using all available pedigrees. Our goal was to detect and map loci associated with covariate-adjusted traits log triglyceride (lnTG) and high-density lipoprotein cholesterol (HDL) using multipoint LOD score analysis, Bayesian oligogenic linkage analysis and identity-by-descent (IBD) scoring methods. Each method used all marker data for all markers on a chromosome. Bayesian linkage analysis detected a linkage signal on chromosome 7 for lnTG and HDL, corroborating previously published results. However, these results were not replicated in a classical linkage analysis of the data or by using IBD scoring methods. We conclude that Bayesian linkage analysis provides a powerful paradigm for mapping trait loci but interpretation of the Bayesian linkage signals is subjective. In the absence of a LOD score method accommodating genetically complex traits and linkage heterogeneity, validation of these signals remains elusive