Workplace Digital Health Is Associated with Improved Cardiovascular Risk Factors in a Frequency-Dependent Fashion: A Large Prospective Observational Cohort Study

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the US. Emerging employer-sponsored work health programs (WHP) and Digital Health Intervention (DHI) provide monitoring and guidance based on participants’ health risk assessments, but with uncertain success. DHI–mobile technology including online and smartphone interventions–has previously been found to be beneficial in reducing CVD outcomes and risk factors, however its use and efficacy in a large, multisite, primary prevention cohort has not been described to date. We analyzed usage of DHI and change in intermediate markers of CVD over the course of one year in 30,974 participants of a WHP across 81 organizations in 42 states between 2011 and 2014, stratified by participation log-ins categorized as no (n = 14,173), very low (<12/yr, n = 12,260), monthly (n = 3,360), weekly (n = 651), or semi-weekly (at least twice per week). We assessed changes in weight, waist circumference, body mass index (BMI), blood pressure, lipids, and glucose at one year, as a function of participation level. We utilized a Poisson regression model to analyze variables associated with increased participation. Those with the highest level of participation were slightly, but significantly (p<0.0001), older (48.3±11.2 yrs) than non-participants (47.7±12.2 yr) and more likely to be females (63.7% vs 37.3% p<0.0001). Significant improvements in weight loss were demonstrated with every increasing level of DHI usage with the largest being in the semi-weekly group (-3.39±1.06 lbs; p = 0.0013 for difference from weekly). Regression analyses demonstrated that greater participation in the DHI (measured by log-ins) was significantly associated with older age (p<0.001), female sex (p<0.001), and Hispanic ethnicity (p<0.001). The current study demonstrates the success of DHI in a large, community cohort to modestly reduce CVD risk factors in individuals with high participation rate. Furthermore, participants previously underrepresented in WHPs (females and Hispanics) and those with an increased number of CVD risk factors including age and elevated BMI show increased adherence to DHI, supporting the use of this low-cost intervention to improve CVD health.     

A simple algorithm for on-line prediction of BOD(5) by a microprocessor-based system

A novel algorithm for predicting BOD(5) from the dissolved oxygen (DO) concentration after a relatively short incubation period is presented and evaluated experimentally. Test runs on synthetic and experimentally derived raw data suggest that BOD(5) can be predicted to within 15% ca. 36 h. The method can be improved by filtering out, via a digital filter, noise from the raw data. The suggested algorithm does not require elaborate computations or large data storage and can therefore be implemented on a low-cost microcomputer for fast on-line determination of BOD(5).     

Cell encapsulation utilizing PEG-fibrinogen hydrogel supports viability and enhances productivity under stress conditions

Recent advances in the bioengineering field have introduced new opportunities enabling cell encapsulation in three-dimensional (3D) structures using either various natural or synthetic materials. However, such hydrogel scaffolds have not been fully biocompatible for cell cultivation due to the lack of physical stability or bioactivity. Here, we utilized a uniquely fabricated semi-synthetic 3D polyethylene glycol-fibrinogen (PEG-Fb) hydrogel scaffold, which exhibits both high stability and high bioactivity, to encapsulate HEK293 cells for the production of human recombinant acetylcholine esterase (AChE). To examine the beneficial bioactive effect of the PEG-Fb scaffold over 2D surfaces, an experimental system was established to compare the viability, proliferation and AChE secretion of encapsulated cells versus non-encapsulated surface-adherent cells in serum starvation. Our results show that the transfer of surface-adherent HEK293 cells from fully enriched medium with 10% FCS to 0.2% FCS resulted in an eightfold reduction in cell number and a fourfold reduction in AChE production. In contrast, the encapsulated cells were highly viable and about twofold more efficient in AChE production. In addition, they had round morphology with a twofold larger cell diameter, supporting the observation of increased AChE production. These results suggest a role of the PEG-Fb scaffold in providing a supportive microenvironment in reduced serum conditions that enhances encapsulated cell functions, opening new directions to study the implementation of this platform in large-scale pharmaceutical protein production.     

Impaired myocardial perfusion reserve in experimental hypercholesterolemia is independent of myocardial neovascularization

Our objective was to investigate the functional role of hypercholesterolemia-associated myocardial neovascularization in early atherosclerosis using the antiangiogenic thalidomide. Experimental atherosclerosis is characterized by myocardial neovascularization, associated with a decrease in myocardial perfusion response to challenge, coronary endothelial dysfunction, and high oxidative stress. However, the functional significance of these neovessels is not known. Three groups of pigs (n = 6 each) were studied after 12 wk of normal or hypercholesterolemic diet without (HC) or with thalidomide (HC + Thal). Myocardial perfusion and permeability were assessed at baseline and in response to cardiac challenge, using electron beam computed tomography, and coronary endothelial function was assessed using organ chambers. Myocardial samples were scanned ex vivo with a three-dimensional microscopic computed tomography scanner, and the spatial density of the myocardial microvessels was quantified. Growth factors and oxidative stress were measured in the myocardial tissue. As a results of these procedures, myocardial perfusion response to adenosine and dobutamine was blunted in both HC and HC + Thal pigs compared with normal pigs (P < 0.05, HC and HC + Thal vs. normal) as was the coronary endothelial function. Myocardial permeability response to adenosine was increased in both HC and HC + Thal pigs compared with normal pigs (P < 0.05, HC and HC + Thal vs. normal, and HC + Thal vs. HC). The microvascular density was increased in HC pigs compared with normal pigs but normalized in HC + Thal pigs (P < 0.001 HC vs. normal and HC + Thal). HC + Thal pigs showed decreased expression of Flk-1 and basic FGF but increased expression of VEGF compared with normal and HC pigs. Oxidative stress was increased in both HC and HC + Thal pigs compared with normal pigs. In conclusion, chronic administration of thalidomide attenuates myocardial neovascularization in experimental HC pigs without affecting myocardial perfusion response to stimulation. This suggests that the myocardial neovascularization may not contribute to the attenuated myocardial perfusion response in hypercholesterolemia.     

Lipoprotein-associated phospholipase A(2) : review of its role as a marker and a potential participant in coronary endothelial dysfunction

The role of inflammation in atherosclerosis continues to emerge. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), a novel plasma biomarker, circulates in the blood bound mainly to low-density lipoprotein (LDL) and promotes vascular inflammation. Several epidemiological studies have shown that circulating levels of Lp-PLA(2) are an independent risk factor for cardiovascular events. Recent studies demonstrate that Lp-PLA(2) is also associated with endothelial dysfunction and early atherosclerosis. This review provides an overview of these studies, suggests plausible mechanisms for the association between endothelial dysfunction and Lp-PLA(2), and highlights future potential therapies.     

Flowers respond to pollinator sound within minutes by increasing nectar sugar concentration

Can plants sense natural airborne sounds and respond to them rapidly? We show that Oenothera drummondii flowers, exposed to playback sound of a flying bee or to synthetic sound signals at similar frequencies, produce sweeter nectar within 3 min, potentially increasing the chances of cross pollination. We found that the flowers vibrated mechanically in response to these sounds, suggesting a plausible mechanism where the flower serves as an auditory sensory organ. Both the vibration and the nectar response were frequency‐specific: the flowers responded and vibrated to pollinator sounds, but not to higher frequency sound. Our results document for the first time that plants can rapidly respond to pollinator sounds in an ecologically relevant way. Potential implications include plant resource allocation, the evolution of flower shape and the evolution of pollinators sound. Finally, our results suggest that plants may be affected by other sounds as well, including anthropogenic ones.     

The Association between Circulating MicroRNA Levels and Coronary Endothelial Function

Human microRNAs (miRs) have been implicated in human diseases presumably through the downregulation and silencing of targeted genes via post-translational modifications. However, their role in the early stage of coronary atherosclerosis is not known. The aim of this study was to test the hypothesis that patients with early atherosclerosis and coronary endothelial dysfunction (CED) have alterations in transcoronary miR gradients. Patients underwent coronary angiography and endothelial function testing in the cardiac catheterization laboratory. Patients were divided into abnormal (n = 26) and normal (n = 22) microvascular coronary endothelial function based on intracoronary response to infused acetylcholine measured as a percent change in coronary blood flow (CBF) and arterial diameter. Blood samples were obtained simultaneously from the aorta and coronary sinus at the time of catheterization for RNA isolation, and miR subsequently assessed. Baseline characteristics were similar in both groups. Patients with microvascular CED displayed transcoronary gradients significantly elevated in miR-92a and miR-133 normalized to C-elegans-39 miR. Percent change in CBF and the transcoronary gradient of miR-133 displayed a significant inverse correlation (r² = 0.11, p = 0.03). Thus, we present novel data whereupon selected miRs demonstrate elevated transcoronary gradients in patients with microvascular CED. The current findings support further studies on the mechanistic role of miRs in coronary atherosclerosis and in humans.     

Mutability and importance of a hypermutable cell subpopulation that produces stress-induced mutants in Escherichia coli

In bacterial, yeast, and human cells, stress-induced mutation mechanisms are induced in growth-limiting environments and produce non-adaptive and adaptive mutations. These mechanisms may accelerate evolution specifically when cells are maladapted to their environments, i.e., when they are are stressed. One mechanism of stress-induced mutagenesis in Escherichia coli occurs by error-prone DNA double-strand break (DSB) repair. This mechanism was linked previously to a differentiated subpopulation of cells with a transiently elevated mutation rate, a hypermutable cell subpopulation (HMS). The HMS could be important, producing essentially all stress-induced mutants. Alternatively, the HMS was proposed to produce only a minority of stress-induced mutants, i.e., it was proposed to be peripheral. We characterize three aspects of the HMS. First, using improved mutation-detection methods, we estimate the number of mutations per genome of HMS-derived cells and find that it is compatible with fitness after the HMS state. This implies that these mutants are not necessarily an evolutionary dead end, and could contribute to adaptive evolution. Second, we show that stress-induced Lac⁺ mutants, with and without evidence of descent from the HMS, have similar Lac⁺ mutation sequences. This provides evidence that HMS-descended and most stress-induced mutants form via a common mechanism. Third, mutation-stimulating DSBs introduced via I-SceI endonuclease in vivo do not promote Lac⁺ mutation independently of the HMS. This and the previous finding support the hypothesis that the HMS underlies most stress-induced mutants, not just a minority of them, i.e., it is important. We consider a model in which HMS differentiation is controlled by stress responses. Differentiation of an HMS potentially limits the risks of mutagenesis in cell clones.     

Identification of trafficking determinants for polytopic rhomboid proteases in Toxoplasma gondii

Rhomboids (ROMs) constitute a family of polytopic serine proteases conserved throughout evolution. The obligate intracellular parasite Toxoplasma gondii possesses six genes coding for ROM-like proteases that are targeted to distinct subcellular compartments: TgROM1 localizes to regulated secretory organelles, micronemes, TgROM2 is present in the Golgi, while TgROM4 and TgROM5 are found in the pellicle of the parasite. The targeting mechanism/s of ROM proteins is an aspect that has not yet been assessed. The existence of TgROM family members localized to different subcellular compartments provides a convenient system to study their sorting mechanisms in a genetically tractable organism that possesses an elaborate secretory pathway and conserved trafficking machineries. In this study, we experimentally established the topology of TgROM1 and TgROM4 at the plasma membrane and applied domain-exchange and site-directed mutagenesis approaches to identify critical sorting determinants on the N-terminal cytosolic domains of TgROM2 and TgROM1 that confer their Golgi and post-Golgi localizations, respectively.