Infection clusters can elevate risk of diagnostic target failure for detection of SARS-CoV-2.

The C29197T mutation is one of 4 point mutations known to cause N-gene target failure (NGTF) in the Xpert Xpress SARS-CoV-2 and Xpert Omni SARS-CoV-2 assays from Cepheid (Sunnyvale, CA). We describe a high local prevalence in January of 8.5% (CI 4.9-14.2%) for the C29197T mutation, which was over 3-fold higher than the prevalence estimated statewide in California during the same time frame, 2.5% (CI 2.1-2.8%). Using phylogenetic analysis, we discovered that this increase in prevalence was due, at least in part, to a disproportionately large infection cluster of unknown origin. This study emphasizes the importance of sequencing at the local jurisdictional level and demonstrates the impact that regional variation can have when assessing risk due to point mutations that impact clinical test performance. It also reinforces the need for diligent reporting of abnormal test results by clinical laboratories, especially during Emergency Use Authorization (EUA) periods, as additional information is gathered about the target organism and the performance of EUA-authorized tests over time.

Regional biomechanical and failure properties of healthy human ascending aorta and root.

PURPOSE: Aortic dissection (AD) is a life-threatening event that occurs when the intimal entry tear propagates and separates inner from outer layers of the aorta. Diameter, the current criterion for aneurysm repair, is far from ideal and additional evidence to optimize clinical decision would be extremely beneficial. Biomechanical investigation of the regional failure properties of aortic tissue is essential to understand and proactively prevent AD. We previously studied biaxial mechanical properties of healthy human aorta. In this study, we investigated the regional failure properties of healthy human ascending aorta (AscAo) including sinuses of Valsalva (SOV), and sinotubular junction (STJ). RESULTS: A total of 430 intact tissue samples were harvested from 19 healthy donors whose hearts were excluded from heart transplantation. The donors had mean age of 51 ± 11.7 years and nearly equal gender distribution. Samples were excised from aortic regions and subregions at defined locations. Tissue strips were subjected to either biaxial or uniaxial failure testing. Wall thickness varied regionally being thickest at AscAo (2.08 ± 0.66 mm) and thinnest at SOV (1.46 ± 0.31 mm). Biaxial testing demonstrated hyperplastic behavior of aortic tissues. Posterior and lateral STJ subregions were found to be stiffer than anterior and medial subregions in both circumferential and longitudinal directions. Failure stresses were significantly higher in the circumferential than longitudinal directions in each subregion of AscAo, STJ, and SOV. Longitudinal failure stresses were significantly greater in AscAo than those in STJ or SOV. Longitudinal failure stresses in AscAo were much smaller anteriorly than posteriorly, and medially than laterally. CONCLUSIONS: The finding of weakest region at the sinotubular junction along the longitudinal direction corroborates clinical observations of that region being commonly involved as the initial site of intimal tear in aortic dissections. Failure stretch ratios correlated to elastic modulus at each region. Furthermore, strong correlation was seen between STJ failure stresses and elastic modulus at physiological pressure along both circumferential and longitudinal directions. Correlating in-vivo aortic elastic modulus based on in-vivo imaging with experimentally determined elastic modulus at physiological pressure and failure stresses may potentially provide valuable information regarding aortic wall strength. Better understanding of aortic biomechanics in normal physiologic and aneurysmal pathologic states may aid in determining risk factors for predicting dissection in patient-specific fashion.

Wall stress analyses in patients with ≥5 cm versus <5 cm ascending thoracic aortic aneurysm.

OBJECTIVE: Current guidelines for elective surgery of ascending thoracic aortic aneurysms (aTAAs) use aneurysm size as primary determinant for risk stratification of adverse events. Biomechanically, dissection may occur when wall stress exceeds wall strength. Determining patient-specific aTAA wall stresses by finite element analysis can potentially predict patient-specific risk of dissection. This study compared peak wall stresses in patients with ≥5.0 cm versus <5.0 cm aTAAs to determine correlation between diameter and wall stress. METHODS: Patients with aTAA ≥5.0 cm (n = 47) and <5.0 cm (n = 53) were studied. Patient-specific aneurysm geometries obtained from echocardiogram-gated computed tomography were meshed and prestress geometries determined. Peak wall stresses and stress distributions were determined using LS-DYNA finite element analysis software (LSTC Inc, Livermore, Calif), with user-defined fiber-embedded material models under systolic pressure. RESULTS: Peak circumferential stresses at systolic pressure were 530 ± 83 kPa for aTAA ≥5.0 cm versus 486 ± 87 kPa for aTAA <5.0 cm (P = .07), whereas peak longitudinal stresses were 331 ± 57 kPa versus 310 ± 54 kPa (P = .08), respectively. For aTAA ≥5.0 cm, correlation between peak circumferential stresses and size was 0.41, whereas correlation between peak longitudinal wall stresses and size was 0.33. However, for aTAA <5.0 cm, correlation between peak circumferential stresses and size was 0.23, whereas correlation between peak longitudinal stresses and size was 0.14. CONCLUSIONS: Peak patient-specific aTAA wall stresses overall were larger for ≥5.0 cm than aTAA <5.0 cm. Although some correlation between size and peak wall stresses was found in aTAA ≥5.0 cm, poor correlation existed between size and peak wall stresses in aTAA <5.0 cm. Patient-specific wall stresses are particularly important in determining patient-specific risk of dissection for aTAA <5.0 cm.

Evolution of Bilateral Mammary Arterial Grafting Program in Veterans Affairs Medical Center.

BACKGROUND: Coronary revascularization with bilateral internal mammary arteries is associated with increased long-term survival, but underutilized due to sternal wound infection concerns. Dedicated bilateral mammary grafting programs are typically high-volume academic or private practices, rather than lower-volume federal institutions whose results are not captured in the Society of Thoracic Surgeons database. Our institution used only single internal mammary arterial grafting in the year prior to implementing a dedicated bilateral grafting program using skeletonized technique. We describe our experience transitioning to bilateral mammary grafting and its impact on sternal wound infection. METHODS: Retrospective cohort study at San Francisco Veterans Affairs Medical Center in 200 patients undergoing first-time isolated, multi-vessel coronary artery bypass from August 2014 to October 2017. Sternal wound infection was defined broadly to include any patient receiving antibiotics for suspicion of sternal infection. Patients were followed for wound complications until 3 post-operative months. RESULTS: Of 200 total patients, 45.5% (n=91) were diabetic, 44% (n=88) had BMI >30, and 61.5% (n=123) underwent bilateral mammary grafting. Bilateral mammary grafting population had 2.4% (n=3/123) deep sternal wound infection with 1.6% (n=2/123) requiring sternal reconstruction while single mammary population had 1.3% (n=1/77, p=1.0). Bilateral mammary grafting population had 6.5% (n=8/123) superficial sternal wound infection compared to 5.2% (n=4/77, p=0.77) in single mammary grafting population. CONCLUSIONS: Transitioning to high rates of bilateral mammary utilization was possible in a year with low rates of complications. Based on our experience, surgeons should consider adopting a skeletonized bilateral mammary grafting approach given potential long-term survival benefit.

Strategies for the acquisition of transcriptional and epigenetic information in single cells.

As the basic unit of living organisms, each single cell has unique molecular signatures and functions. Our ability to uncover the transcriptional and epigenetic signature of single cells has been hampered by the lack of tools to explore this area of research. The advent of microfluidic single cell technology along with single cell genome-wide DNA amplification methods had greatly improved our understanding of the expression variation in single cells. Transcriptional expression profile by multiplex qPCR or genome-wide RNA sequencing has enabled us to examine genes expression in single cells in different tissues. With the new tools, the identification of new cellular heterogeneity, novel marker genes, unique subpopulations, and spatial locations of each single cell can be acquired successfully. Epigenetic modifications for each single cell can also be obtained via similar methods. Based on single cell genome sequencing, single cell epigenetic information including histone modifications, DNA methylation, and chromatin accessibility have been explored and provided valuable insights regarding gene regulation and disease prognosis. In this article, we review the development of strategies to obtain single cell transcriptional and epigenetic data. Furthermore, we discuss ways in which single cell studies may help to provide greater understanding of the mechanisms of basic cardiovascular biology that will eventually lead to improvement in our ability to diagnose disease and develop new therapies.

Evaluación de la suceptibilidad/resistencia del adulto aedes aegypti a la cipermetrina / Evaluation of susceptibility / resistance of adult aedes aegypti to cipermetrina

Objetivos: Determinar el efecto de la cipermetrina en la sensibilidad/resistencia de las formas adultas de Aedes aegypti. Evaluar la sensibilidad/resistencia del adulto Aedes aegypti a la cipermetrina. Material y métodos: Estudio de tipo cuantitativo y diseño pre-experimental en el cual se hizo uso del informe técnico del Instituto Nacional de Salud (INS), los resultados fueron expresados como dosis diagnostica que indican el porcentaje de mortalidad de los mosquitos muertos a las 24 horas post ­ exposición del piretroide. Los datos obtenidos fueron ingresados en Excel 2013 y se utilizó programa de análisis epidemiológico EPIDAT v. 3.1. Resultados: Los mosquitos procedentes del distrito de Tumán mostraron una frecuencia de resistencia de 27,5% y los procedentes del distrito de Motupe de 36,25%, con una diferencia estadísticamente significativa (p<0,001) al ser comparado a los datos teóricos que es del 98%. Conclusiones: Existe resistencia a la cipermetrina en los mosquitos procedentes de Motupe y Tumán del departamento de Lambayeque.

Objetives: To determine the effect of cypermethrin on the sensitivity / resistance of adult forms of Aedes aegypti. To evaluate the sensitivity / resistance of the adult Aedes aegyptito cypermethrin. Material and methods: Quantitative study and pre-experimental designusing the technical report of the National Institute of Health (INS), the results were expressed as a diagnostic dose that indicates the mortality rate of dead mosquitoes at 24 hours post - exposure of the pyrethroid. The data obtained were entered in Excel 2013 and an epidemiological analysis program EPIDATv. 3.1. Results: Mosquitoes from the Tuman district showed a resistance frequency of 27.5% and those from the Motupe district of 36.25%, with a statistically significant difference (p <0.001) when compared to the data Theoretical is 98%. Conclusions: Resistance to cypermethrin exists in mosquitoes from Motupe and Tumán in the department of Lambayeque.