Magnetic Resonance Imaging Assessment of Ventricular Dyssynchrony Current and Emerging Concepts

Despite the numerous documented benefits of cardiac resynchronization therapy (CRT), a significant proportion of patients undergoing CRT do not demonstrate symptomatic or morphologic improvement, triggering the search to improve targeting of this therapy. Many studies now support direct assessment of mechanical dyssynchrony as a method to better identify CRT responders. Among the methods used, echo-Doppler imaging has taken center stage and is covered in other articles in this special issue; however, these methods have several inherent limitations, and other alternatives are also being explored such as magnetic resonance imaging (MRI). This review discusses the concepts and clinical use of MRI methods for quantitative assessment of mechanical dyssynchrony, highlighting newer acquisition and analysis methods and focusing on how the data can be synthesized into robust indexes of dyssynchronous heart failure

Surface warming during the 2018/Mars Year 34 Global Dust Storm

The impact of Mars’ 2018 Global Dust Storm (GDS) on surface and near‐surface air temperatures was investigated using an assimilation of Mars Climate Sounder (MCS) observations. Rather than simply resulting in cooling everywhere from solar absorption (average surface radiative flux fell 26 Wm‐2), the globally‐averaged result was a 0.9 K surface warming. These diurnally‐averaged surface temperature changes had a novel, highly non‐uniform spatial structure, with up to 16 K cooling/19 K warming. Net warming occurred in low thermal inertia (TI) regions, where rapid night‐time radiative cooling was compensated by increased longwave emission and scattering. This caused strong nightside warming, outweighing dayside cooling. The reduced surface‐air temperature gradient closely coupled surface and air temperatures, even causing local dayside air warming. Results show good agreement with MCS surface temperature retrievals. Comparisons with the 2001 GDS and free‐running simulations show that GDS spatial structure is crucial in determining global surface temperature effects

What Policymakers Should Know About the Fiscal Impact of COVID-19 on Illinois

We model the fiscal impacts of the COVID-19 pandemic and stay at home orders on Illinois’ fiscal situation. Prominent forecasters’ recently published estimates range from short and modest declines in U.S. GDP to declines of almost 6%. We model the impact of these economic disruptions on the revenues of the individual income, corporate income, and sales taxes considering what we know about the past history of the revenue sources. We estimate revenue losses from $6.4 billion in the severe pandemic scenario to$1.9 billion in the low severity scenario. We also expect large increases in public health expenditures but a modest impact on Illinois’ fiscal situation since these expenditures are a small portion of the budget. Over the next several years, annual Medicaid expenditures could increase by $4 to$5 billion (21% to 26%). We expect increases in expenditures on human services as economic pressures require residents impacted by the pandemic to rely on these services. Potential declines in the value of public pension funds’ assets could result in increased unfunded liabilities and required state contributions. However, these increased contributions would be phased in gradually due to “asset smoothing,” and immediate fiscal effects would be modest. Local governments with a sales tax are likely to see immediate revenue shortfalls resulting from the sharp COVID-19 related economic downturn. Economic disruption may result in decreased property tax collections, but these impacts would lag significantly. To date, federal responses have been significant but are unlikely to fully insulate Illinois from the fiscal damage.Ope

A new restriction-site polymorphism in exon 18 of the low density lipoprotein receptor (LDLR) gene

Abstract A new restriction fragment length polymorphism (RFLP) in exon 18 of the low density lipoprotein receptor (LDLR) gene is described. It should be a useful marker in linkage to familial hypercholesterolemia. Source~description. Primers, based on the nucleotide sequence of the low density lipoprotein receptor (LDLR) gene exon 18 PCR conditions. Genomic DNA (500 ng) was added to a 50-~tl volume reaction mix containing 1 x Taq buffer (Promega), 3.0 mM MgCI2, 200 gM dNTPs, 250 nM each primer [1019 (5"-ACTTCAAAGCCGTGATCGTGA-3") and 2029 (5"-TGCAACAGTAACACGGCGATT-3")] and 1 unit Taq polymerase (Promega) and amplified using Hybaid (Omnigene) thermal cycler (block control) under the following conditions: 94~ 3 min 1 x; 94~ 1:30 min., 52~ 1:30 min, 72~ 3 min, 30 x; 72~ 3 min. An 8-~tl sample of the PCR reaction mix was digested in a 20-~1 reaction using excess enzyme and 1 x buffer (NEB) and examined following electrophoresis on ethidium bromide stained 1.5% agarose gels. Frequency. In 20 unrelated caucasians A1 = 0.70, A2 = 0.30, observed heterozygosity = 0.50; in 22 unrelated African Americans A1 = 0.30, A2 = 0.70, observed heterozygosity = 0.41

Combined TRPC3 and TRPC6 blockade by selective small-molecule or genetic deletion inhibits pathological cardiac hypertrophy

Chronic neurohormonal and mechanical stresses are central fea-tures of heart disease. Increasing evidence supports a role forthe transient receptor potential canonical channels TRPC3 andTRPC6 in this pathophysiology. Channel expression for both is nor-mally very low but is increased by cardiac disease, and geneticgain- or loss-of-function studies support contributions to hypertro-phy and dysfunction. Selective small-molecule inhibitors remainscarce, and none target both channels, which may be useful giventhe high homology among them and evidence of redundant sig-naling. Here we tested selective TRPC3/6 antagonists (GSK2332255Band GSK2833503A; IC50,3–21 nM against TRPC3 and TRPC6) andfound dose-dependent blockade of cell hypertrophy signaling trig-gered by angiotensin II or endothelin-1 in HEK293T cells as well as inneonatal and adult cardiac myocytes. In vivo efficacy in mice andrats was greatly limited by rapid metabolism and high protein bind-ing, although antifibrotic effects with pressure overload were ob-served. Intriguingly, although gene deletion of TRPC3 or TRPC6alone did not protect against hypertrophy or dysfunction frompressure overload, combined deletion was protective, support-ing the value of dual inhibition. Further development of thispharmaceutical class may yield a useful therapeutic agent forheart disease management.Fil: Seo, Kinya. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Rainer, Peter P.. Johns Hopkins Medical Institutions. Department of Medicine; Estados Unidos. Medical University of Graz. Department of Medicine; AustriaFil: Shalkey Hahn, Virginia. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Lee, Dong-ik. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Jo, Su-Hyun. Kangwon National University School of Medicine; Corea del Sur. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Andersen, Asger. Aarhus University Hospital. Department of Cardiology; DinamarcaFil: Liu, Ting. Johns Hopkins Medical Institutions. Department of Medicine; Estados UnidosFil: Xu, Xiaoping. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Willette, Robert N.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Lepore, John J.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Marino, Joseph P.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Birnbaumer, Lutz. ational Institute of Environmental Health Sciences; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Schnackenberg, Christine G.. GlaxoSmithKline Heart Failure Discovery Performance Unit; Estados UnidosFil: Kass, David A.. Johns Hopkins Medical Institutions. Department of Medicine; Estados Unido