Coronary Artery Disease: An Analysis of its Biochemical, Physiological, and Sociological Causes and Effects

Coronary Artery Disease (CAD) is a serious condition caused by a buildup of plaque in your coronary arteries, the blood vessels that bring oxygen-rich blood to your heart. It disproportionately affects millions of Americans and thousands of Mississippians. This study presents the results of an evaluation of causation factors of CAD, the physiological impact on the body, and the contributing determinants of CAD on Mississippi populations. Data on Mississippi populations were collected using the Center for Population Studies at the University of Mississippi. A multitude of individuals were evaluated when examining the causes and effects of CAD including men, women, children, and the elderly. The evaluation processes and procedures of all facets of CAD are given in great detail, so that this paper depicts the evolution of the evaluation, including changes in methodologies and treatment instruments in dealing with CAD. The findings of this research reflect the challenges faced by providers / public health officials in dealing with CAD in Mississippi. Findings for each of the aforementioned results are presented along with a discussion of what changes have been made or not made to aid the issue and why. While the findings of CAD’s effect on Mississippi populations is not generally quite positive, the improvement in the detrimental effects of CAD in recent years clearly allows the possibility of removing the disease as an issue in our state

Developing an Exoskeleton Test Plan for the TALOS Program

As America’s global adversaries increase their capabilities on the battlefield, US military forces must enhance warfighter’s survivability, lethality, and mobility. These needs can be met by augmenting warfighters with additional equipment. The increased use of equipment, however, creates an additional need for an exoskeleton that can support the added equipment, while also augmenting the warfighter’s mobility. Traditionally, exoskeletons have had acceptance issues related to poor operational mobility. USSOCOM is building the Tactical Assault Light Operator Suit (TALOS) as the next generation of these armored exoskeletons.  This paper explains the methodology for developing a test plan to ensure adequate mobility for the warfighter wearing the TALOS system. Operational missions were decomposed into tasks which were further broken down into individual movements.  Motion capture data was used to determine the angles and angular velocities imposed on relevant joints during these movements. This information was mapped to a set of exercises that were then compiled into a test plan, which can be used during the testing phase to ensure proper mobility for operators utilizing the system

Experimental study on the thermal control of a roof-top collective building antenna using a porous matrix filled with Water-Copper nanofluid

This experimental work addressed the thermal control a roof-top collective building antenna meant to control home equipment in smart buildings. The antenna was placed inside a concentric quasi-cylindrical cavity maintained at low temperature. Cooling was provided by a Water-Copper nanofluid saturated porous matrix placed between the antenna and the enclosure. The ratio of the thermal conductivity of the porous material to that of the water varied from 4 up to 41.2. The nanoparticles volume fraction varied between 0% and 5%. The main result was a new semi-empirical correlation that allows for the determination of the antenna's average surface temperature as a function of the governing parameters: ratios of nanofluid to water and porous media to water thermal conductivities, nanoparticles volume fraction, and Rayleigh number. The applicability of the correlation was illustrated for a practical application case. It was found that, for some cases, the proposed thermal control system improves power dissipation by a factor of 33% as compared with the case of pure water (2 kW versus 1.5 kW).Partial funding for open access charge: Universidade de Vigo/CISUG

The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial

AIMS: Co-trimoxazole maintains a well-established role in the treatment of Pneumocystis jirovecii and Toxoplasma gondii, as well as urinary tract infections. Observational studies report hyperkalemia associated with co-trimoxazole which may stem from an amiloride-like potassium sparing effect. Our study reports on changes in serum potassium on patients without acute infections, and the influence of concomitant anti-kaliuretic drugs on this effect.  METHODS: Post-hoc analysis of a randomised controlled trial in patients with interstitial lung disease who were assigned to placebo or 960 mg twice daily co-trimoxazole. Serum potassium and creatinine were measured at baseline, six weeks, 6, 9 and 12 months. Primary outcome was difference in mean serum potassium concentrations between co-trimoxazole and placebo at six weeks.  RESULTS: Mean serum potassiums were similar at baseline, 4.24 (±0.44) mmol/L in the 87 co-trimoxazole group participants and 4.25 (±0.39) mmol/L in the 83 control participants. Co-trimoxazole significantly increased mean serum potassium at 6 weeks, difference between means compared to placebo of 0.21 mmol/L (95% Confidence Intervals [CI] 0.09-0.34; p = 0.001). This significant increase in serum potassium was detectable even after exclusion of patients on anti-kaliuretic drugs, difference between means for co-trimoxazole compared to placebo 0.23 mmol/L (95% CI 0.09-0.38, p = 0.002). There were 5/87 (5.7%) patients on co-trimoxazole whose serum potassium reached concentrations ≥5.5 mmol/L during the study period.  CONCLUSIONS: Co-trimoxazole significantly increases serum potassium concentration, even in participants not using anti-kaliuretic drugs. Whilst the magnitude of increase is often minor, a small proportion in our outpatient cohort developed hyperkalaemia of clinical importance

The Acute Effects of 5 Fluorouracil on Skeletal Muscle Resident and Infiltrating Immune Cells in Mice

5 fluorouracil (5FU) has been a first-choice chemotherapy drug for several cancer types (e.g., colon, breast, head, and neck); however, its efficacy is diminished by patient acquired resistance and pervasive side effects. Leukopenia is a hallmark of 5FU; however, the impact of 5FU-induced leukopenia on healthy tissue is only becoming unearthed. Recently, skeletal muscle has been shown to be impacted by 5FU in clinical and preclinical settings and weakness and fatigue remain among the most consistent complaints in cancer patients undergoing chemotherapy. Monocytes, or more specifically macrophages, are the predominate immune cell in skeletal muscle which regulate turnover and homeostasis through removal of damaged or old materials as well as coordinate skeletal muscle repair and remodeling. Whether 5FU-induced leukopenia extends beyond circulation to impact resident and infiltrating skeletal muscle immune cells has not been examined. The purpose of the study was to examine the acute effects of 5FU on resident and infiltrating skeletal muscle monocytes and inflammatory mediators. Male C57BL/6 mice were given a physiologically translatable dose (35 mg/kg) of 5FU, or PBS, i.p. once daily for 5 days to recapitulate 1 dosing cycle. Our results demonstrate that 5FU reduced circulating leukocytes, erythrocytes, and thrombocytes while inducing significant body weight loss (\u3e5%). Flow cytometry analysis of the skeletal muscle indicated a reduction in total CD45+ immune cells with a corresponding decrease in total CD45+CD11b+ monocytes. There was a strong relationship between circulating leukocytes and skeletal muscle CD45+ immune cells. Skeletal muscle Ly6cHigh activated monocytes and M1-like macrophages were reduced with 5FU treatment while total M2-like CD206+CD11c- macrophages were unchanged. Interestingly, 5FU reduced bone marrow CD45+ immune cells and CD45+CD11b+ monocytes. Our results demonstrate that 5FU induced body weight loss and decreased skeletal muscle CD45+ immune cells in association with a reduction in infiltrating Ly6cHigh monocytes. Interestingly, the loss of skeletal muscle immune cells occurred with bone marrow cell cycle arrest. Together our results highlight that skeletal muscle is sensitive to 5FU’s off-target effects which disrupts both circulating and skeletal muscle immune cells

A novel splice site variant in CYP11A1 in trans with the p.E314K variant in a male patient with congenital adrenal insufficiency

Background: The CYP11A1 gene encodes the cytochrome P450 side‐chain cleavage enzyme, which is essential for steroid formation. Recessive variants in this gene can lead to impairment of sexual differentiation caused by a complete or partial loss of steroid hormone production. The phenotypic spectrum in affected 46XY males may vary from surgically repairable defects including cryptorchidism and hypospadias to complete feminization of external gonads, accompanied by symptoms of adrenal dysfunction. Methods Whole‐exome sequencing (WES) of a 12‐year‐old male proband and his parents was performed after a protracted diagnostic odyssey failed to uncover the cause of his primary adrenal insufficiency. Of note, the proband had early symptomatology and corrective surgery for hypospadias, raising suspicion for a disorder of steroidogenesis. Results: WES identified compound heterozygous variants in CYP11A1 including a novel canonical splice site variant (c.425+1G>A) and a previously reported p.E314K variant, which were consistent with a diagnosis of congenital adrenal insufficiency with partial 46XY sex reversal. Conclusion: Congenital adrenal insufficiency with 46XY sex reversal is a rare disorder that is characterized by dysregulation of steroid hormone synthesis, leading to adrenal and gonadal dysfunction. In this report, we describe a patient with adrenal insufficiency, hypospadias, and skin hyperpigmentation who was found to have a novel c.425+1G>A variant in trans with the p.E314K variant in CYP11A1. We performed structural analyses to examine the effect of the p.E314K variant on protein function and show that it falls in the core of the protein may disrupt cholesterol binding in the active site

Sudden cardiac death in patients with ischemic heart failure undergoing coronary artery bypass grafting results from the STICH randomized clinical trial (Surgical Treatment for Ischemic Heart Failure)

Background—The risk of sudden cardiac death (SCD) in patients with heart failure following CABG has not been examined in a contemporary clinical trial of surgical revascularization. This analysis describes the incidence, timing and clinical predictors of SCD after CABG. Methods—Patients enrolled in the Surgical Treatment of Ischemic Heart Failure (STICH) trial who underwent CABG with or without surgical ventricular reconstruction (SVR) were included. We excluded patients with prior ICD and those randomized only to medical therapy. The primary outcome was SCD as adjudicated by a blinded committee. A Cox model was used to examine and identify predictors of SCD. The Fine and Gray method was used to estimate the incidence of SCD accounting for the competing risk of other deaths. Results—Over a median follow-up of 46 months, 113 patients of 1411 patients who received CABG without (n = 934) or with SVR (n = 477) had SCD; 311 died of other causes. The mean LVEF at enrollment was 28±9%. The 5-year cumulative incidence of SCD was 8.5%. Patients who had SCD and those who did not die were younger and had fewer comorbid conditions than those who died for reasons other than SCD. In the first 30 days after CABG, SCD (n=5) accounted for 7% of all deaths. The numerically greatest monthly rate of SCD was in the 31-90 day time period. In a multivariable analysis including baseline demographics, risk factors, coronary anatomy and LV function, ESVI and BNP were most strongly associated with SCD. Conclusions—The monthly risk of SCD shortly after CABG among patients with a low LVEF is highest between the first and third month, suggesting that risk stratification for SCD should occur early in the postoperative period, particularly in patients with increased preoperative ESVI and/or BNP