High Fat Relative to Low Fat Ground Beef Consumption Lowers Blood Pressure and Does Not Negatively Alter Arterial Stiffness

Beef consumption has been stigmatized as an unhealthy dietary choice. However, randomized control trials to support this claim are lacking. PURPOSE: To examine the effect of low-fat (5%) and high-fat (25%) ground beef consumption on blood pressure (BP) and carotid-femoral pulse wave velocity (PWV).METHODS: Twenty-three male subjects (age 40±11 yrs, height 177.4±6.7 cm, weight 97.3±25.0 kg, lean mass 64.5±9.5 kg, fat mass 30.6±19.1 kg) volunteered to participate in this cross-over design study. Each participant completed two, 5-week ground beef interventions in a randomized order with a 4-week washout period in-between. All participants visited the lab four times after an overnight fast. Each visit to the lab consisted of supine BP, dual energy x-ray absorptiometry (DXA) scan to assess body composition, and PWV analysis. The PWV recording was assessed on the right carotid and femoral arteries. The distance used for the PWV calculation was 80% of the actual distance between carotid and femoral sites. All PWV measures were completed according to previously published procedures (Van Bortel, 2011). BP and PWV results were analyzed separately via 2x2 repeated measures ANOVA. RESULTS: Our results indicate there was a significant decrease in systolic BP (p=0.01) following the high-fat ground beef intervention compared to the low-fat. The BP values for low-fat beef and high-fat beef are 120/74 and 116/73 mmHg, respectively. Further, there were no significant differences between the PWV measures. CONCLUSION: Based on our results, high fat ground beef favorably alters systolic BP and does not negatively affect PWV measures

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

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