COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation

Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.     

Closure of a persistant femoral artery pseudoaneurysm complicating coronary angioplasty using the femostop compression device and direct ultrasound visualization

Nonsurgical closure of femoral artery pseudoaneurysm (PSA), using ultrasound guidance and compression with the ultrasound probe or a C-clamp, has been previously described. We report a patient in whom a different compression device was used (the Femostop ^TM ) which also allows direct ultrasound visualization of the PSA and femoral vessels at the site of compression. This resulted in adequate PSA with preservation of flow in both artery and vein throughout the procedure.     

Hospital readmission of persons with hip fracture following medical rehabilitation

A significant percentage of older adults hospitalized and treated for hip fracture are readmitted to a hospital within six months. We analyzed information from a national database, the Uniform Data System for Medical Rehabilitation. Records for 8,236 patients (1994-98) who received inpatient medical rehabilitation following treatment for hip fracture were examined. Mean age was 76.51 years (S.D. = 12.48) with 71% female and 79% non-Hispanic White. The primary outcome measure was incidence of hospital readmission 0-180 days post-discharge. The hospital readmission rate was 16.7%. A Cox regression model predicting rehospitalization included the following variables (p < 0.05): basic daily living skills, age, length of stay, ethnicity, and gender. There was a statistically significant difference in the percent of male versus female patients rehospitalized for Hispanic subjects but not for non-Hispanic white or African American subjects. The greatest variability occurred among male patients. A total of 18.1% of non-Hispanic White males and 16.8% of African American males were rehospitalized. In contrast, only 10.1% of Hispanic males were rehospitalized. Basic daily living skills, length of hospital stay, age, ethnicity and gender were variables associated with hospital readmission following medical rehabilitation in persons with hip fracture. These variables should be considered in developing intervention programs to reduce the risk of hospital readmission.     

Chronic suppression of insulin by diazoxide alters the activities of key enzymes regulating hepatic gluconeogenesis in Zucker rats

OBJECTIVES: Chronic attenuation of hyperinsulinemia by diazoxide (DZ), an inhibitor of glucose-mediated insulin secretion, improved insulin sensitivity and glucose tolerance and caused down-regulation of lipid metabolizing enzymes in adipose tissue and decreased the rate of weight gain in mildly hyperglycemic obese Zucker rats. Since the liver plays a central role in glucose homeostasis, we studied the effect of chronic insulin suppression on key insulin-sensitive enzymes regulating hepatic gluconeogenesis. METHODS: DZ (150 mg/kg per day) or vehicle (control) was administered to 7-week-old female obese and lean Zucker rats for a period of 4 weeks. RESULTS: DZ-treated animals showed lower fasting plasma insulin levels (P<0.001) than their controls. Plasma glucose levels were lower in DZ obese rats than in controls (P<0.001), without a significant change in DZ lean animals. DZ had no effect on glucose transporter 2 protein expression in either strain. DZ treatment resulted in lower hepatic glucokinase (P<0.001) and glucose-6-phosphatase (P<0.0001) and phosphoenolpyruvate carboxykinase (PEPCK) activities only in obese rats compared with controls (P<0.001). However, DZ-treated lean rats demonstrated higher PEPCK activity than controls (P<0.002). DZ-treated animals demonstrated enhanced hepatic glucose-6-phosphate content (P<0.01), glycogen synthase activity (P<0.0001) and glycogen content (P<0.02) compared with their controls despite increased hepatic glycogen phosphorylase a activity in these animals (P<0.02). CONCLUSIONS: Chronic suppression of hyperinsulinemia in obese Zucker rats by DZ decreased the activities of key enzymes regulating hepatic gluconeogenesis, implying that attenuation of the hyperinsulinemic state by DZ may be therapeutically beneficial.     

Blood Lead Concentration and Thyroid Function during Pregnancy: Results from the Yugoslavia Prospective Study of Environmental Lead Exposure

Background: Although maternal hypothyroidism increases the risk of adverse neonatal and obstetric outcomes as well as lower IQ in children, the environmental determinants of maternal thyroid dysfunction have yet to be fully explored.Objectives: We aimed to examine associations between mid-pregnancy blood lead (BPb) and concomitant measures of thyroid function among participants in the Yugoslavia Prospective Study of Environmental Lead Exposure.Methods: As part of a population-based prospective study of two towns in Kosovo—one with high levels of environmental lead and one with low—women were recruited during the second trimester of pregnancy, at which time blood samples and questionnaire data were collected. We measured concentrations of BPb, free thyroxine (FT₄), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibodies (TPOAb) in archived serum samples.Results: Compared with women from the unexposed town, women from the exposed town had lower mean FT₄ (0.91 ± 0.17 vs. 1.03 ± 0.16 ng/dL), higher mean TPOAb (15.45 ± 33.08 vs. 5.12 ± 6.38 IU/mL), and higher mean BPb (20.00 ± 6.99 vs. 5.57 ± 2.01 μg/dL). No differences in TSH levels were found. After adjustment for potential confounders, for each natural log unit increase in BPb, FT₄ decreased by 0.074 ng/dL (95% CI: –0.10, –0.046 ng/dL), and the odds ratio for testing positive to TPOAb was 2.41 (95% CI: 1.53, 3.82). We found no association between BPb and TSH.Conclusions: Prolonged lead exposure may contribute to maternal thyroid dysfunction by stimulating autoimmunity to the thyroid gland.Citation: Kahn LG, Liu X, Rajovic B, Popovac D, Oberfield S, Graziano JH, Factor-Litvak P. 2014. Blood lead concentration and thyroid function during pregnancy: results from the Yugoslavia Prospective Study of Environmental Lead Exposure. Environ Health Perspect 122:1134–1140; http://dx.doi.org/10.1289/ehp.1307669     

Genetic Diversity and Population Structure of Kenyan Common Bean ( Phaseolus vulgaris L.) Germplasm Using Peroxidase Gene Markers

Common bean (Phaseolus vulgaris L.) is a vital legume used as human food, source of cash income, feed for livestock, and it increases the fertility of soil by its ability to fix nitrogen. The aim of this research was to determine the genetic diversity and population structure of 40 common bean germplasm cultivated in Kenya, using peroxidase gene (POX)-based molecular markers. The loci analyzed showed high diversity and amplified 624 alleles, ranging from 3 to 9 on every locus, with an average of 7.20. The PIC of the POX markers varied from 0.6204 to 0.9110, with an average of 0.7677. The range of the observed heterozygosity was from 0.6667 to 0.9150 with a mean of 0.7945, while the values of the mean genetic diversity ranged from 0.3072 to 0.4425 with a mean of 0.3972. The UPGMA phenogram separated the genotypes into two main genetic clusters, and the genotypes showed no grouping by geographical origins. The highest value of genetic variation was observed between the genotypes obtained from Western, Rift valley and Central regions of Kenya. Population structure analysis grouped the germplasm into 7 gene pools and showed that the genotypes have a common genetic lineage. AMOVA revealed higher genetic diversity (99%) within population than among population (1%), and this offers a reliable base for the design of genetic improvement schemes. Results of the present study can be used in future breeding programs and for the genetic improvement in common bean.