Mitochondrial structure and function are not different between nonfailing donor and end‐stage failing human hearts

During human heart failure, the balance of cardiac energy use switches from predominantly fatty acids (FAs) to glucose. We hypothesized that this substrate shift was the result of mitochondrial degeneration; therefore, we examined mitochondrial oxidation and ultrastructure in the failing human heart by using respirometry, transmission electron microscopy, and gene expression studies of demographically matched donor and failing human heart left ventricular (LV) tissues. Surprisingly, respiratory capacities for failing LV isolated mitochondria (n = 9) were not significantly diminished compared with donor LV isolated mitochondria (n = 7) for glycolysis (pyruvate + malate)‐ or FA (palmitoylcarnitine)‐derived substrates, and mitochondrial densities, assessed via citrate synthase activity, were consistent between groups. Transmission electron microscopy images also showed no ultrastructural remodeling for failing vs. donor mitochondria; however, the fraction of lipid droplets (LDs) in direct contact with a mitochondrion was reduced, and the average distance between an LD and its nearest neighboring mitochondrion was increased. Analysis of FA processing gene expression between donor and failing LVs revealed 0.64‐fold reduced transcript levels for the mitochondrial‐LD tether, perilipin 5, in the failing myocardium (P = 0.003). Thus, reduced FA use in heart failure may result from improper delivery, potentially via decreased perilipin 5 expression and mitochondrial‐LD tethering, and not from intrinsic mitochondrial dysfunction.—Holzem, K. M., Vinnakota, K. C., Ravikumar, V. K., Madden, E. J., Ewald, G. A., Dikranian, K., Beard, D. A., Efimov, I. R. Mitochondrial structure and function are not different between nonfailing donor and end‐stage failing human hearts. FASEB J. 30, 2698‐2707 (2016). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154292/1/fsb2fj201500118r.pd

Detailed Enzyme Kinetics in Terms of Biochemical Species: Study of Citrate Synthase

The compulsory-ordered ternary catalytic mechanism for two-substrate two-product enzymes is analyzed to account for binding of inhibitors to each of the four enzyme states and to maintain the relationship between the kinetic constants and the reaction equilibrium constant. The developed quasi-steady flux expression is applied to the analysis of data from citrate synthase to determine and parameterize a kinetic scheme in terms of biochemical species, in which the effects of pH, ionic strength, and cation binding to biochemical species are explicitly accounted for in the analysis of the data. This analysis provides a mechanistic model that is consistent with the data that have been used support competing hypotheses regarding the catalytic mechanism of this enzyme

Free Expression in America Post-2020 A Landmark Survey of Americans Views on Speech Rights

Free expression and the freedom of speech are cornerstones of American democracy. Yet the interpretation of the First Amendment continues to be a flashpoint in the 21st century as the nation debates how to apply these rights to our society. For the 2021 "Free Expression in America Post-2020" report, Knight Foundation commissioned Ipsos to conduct a survey with a nationally representative sample of more than 4,000 American adults, including an additional sample of 1,000 undergraduate college students. The Knight Foundation-Ipsos study provides a comprehensive look at American attitudes toward freedom of speech in a post-2020 environment, building on Knight Foundation's long-standing work studying free speech views among students since 2004. The findings described in this report cover many but not all of the rich insights possible from this complex dataset. We invite the public and researchers to explore this publicly available resource in further detail. This study finds that all Americans hold to the ideal of free speech, but putting free expression into practice reveals significant differences in experiences and attitude. It examines how Americans view free expression issues, events and the application of our First Amendment rights in an increasingly digital, diverse, and politically driven society.

Studies on Sexual Behavior During COVID-19 Pandemic: A Bibliometric Analysis

Sexual relations suffered from a drastic change because of the pandemic of the COVID-19 and its controlling measures. We performed a bibliometric review of articles conducted on sexual behavior through this COVID-19 pandemic. We performed a search in the Scopus database on August 14, 2021. The search was carried out by the mentioned search terms: “sex* act*” OR “Sex* Behav*” AND “COVID-19.” A total of 230 published articles was identified in the Scopus database, out of which 130 research works were funded and 23.91% (n = 55) articles had international collaborations. R Stephenson published the highest number of papers (n = 4) whilst SK Kar had the maximum number of citations (n = 39) and the highest number of citations per article (13). Universidade de São Paulo and the University of California were the most productive organizations whilst the USA outnumbered the other countries. Sexually Transmitted Infections (n = 13) and Elsevier (61) published the highest number of papers as a journal and publisher, respectively. It is the first bibliometric review on studies that assessed impact of the COVID-19 pandemic on human sexual activities during which identified that more than half of the articles were funded which is a promising sign for the researchers from this field and for those who are keen to work in this field

Pornography and Sexual Violence Against Women in India: A Scoping Review

In recent decades, surge in the usage of pornography is promoting a severe negative impact on health and well-being throughout the world. In recent times, there is a surge in rape cases in India. There may be a relation between pornography addiction and an increase in sexual crime against women. This review aims to document the association between sexual violence and addiction to pornography in India. Six original articles were retrieved from databases for the initial review of the literature, such as PubMed, EMBASE, EBSCOhost, CINAHL plus, and PubMed Central. Out of the six included cross-sectional research, 50% reported primary (sample sizes range from 100 to 600), 33.3% secondary data, and 16.7% study assessed data from Google trend. Only 16.7% of included articles unveiled a significant association between the number of Internet users and increased sexual violence (rapes and or crimes) toward females that revealed an insignificant association when variables were controlled. About 33.3% of studies reported that the male gender was more vulnerable to pornography addiction among medical students than females. Pornography search had no significant association with literacy level. Female population ratio in Scheduled Castes and Scheduled Tribes positively and urbanization and female workforce participation negatively impacted crime against women

Compensated right ventricular function of the onset of pulmonary hypertension in a rat model depends on chamber remodeling and contractile augmentation.

Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geometric remodeling and intrinsic changes in myocardial mechanical properties in a monocrotaline (MCT) animal model. In a longitudinal study of PAH, ventricular morphology and function were assessed weekly during the first four weeks after MCT exposure. Using invasive measurements of RV pressure and volume, heart performance was evaluated at end of systole and diastole to quantify contractility (end-systolic elastance) and chamber stiffness (end-diastolic elastance). To distinguish between morphological and intrinsic mechanisms, a computational model of the RV was developed and used to determine the level of prediction when accounting for wall masses and unloaded volume measurements changes. By four weeks, mean pulmonary arterial pressure and elastance rose significantly. RV pressures rose significantly after the second week accompanied by significant RV hypertrophy, but RV stroke volume and cardiac output were maintained. The model analysis suggested that, after two weeks, this compensation was only possible due to a significant increase in the intrinsic inotropy of RV myocardium. We conclude that this MCT-PAH rat is a model of RV compensation during the first month after treatment, where geometric remodeling on EDPVR and increased myocardial contractility on ESPVR are the major mechanisms by which stroke volume is preserved in the setting of elevated pulmonary arterial pressure. The mediators of this compensation might themselves promote longer-term adverse remodeling and decompensation in this animal model

Network Modeling of Liver Metabolism to Predict Plasma Metabolite Changes During Short-Term Fasting in the Laboratory Rat

The liver—a central metabolic organ that integrates whole-body metabolism to maintain glucose and fatty-acid regulation, and detoxify ammonia—is susceptible to injuries induced by drugs and toxic substances. Although plasma metabolite profiles are increasingly investigated for their potential to detect liver injury earlier than current clinical markers, their utility may be compromised because such profiles are affected by the nutritional state and the physiological state of the animal, and by contributions from extrahepatic sources. To tease apart the contributions of liver and non-liver sources to alterations in plasma metabolite profiles, here we sought to computationally isolate the plasma metabolite changes originating in the liver during short-term fasting. We used a constraint-based metabolic modeling approach to integrate central carbon fluxes measured in our study, and physiological flux boundary conditions gathered from the literature, into a genome-scale model of rat liver metabolism. We then measured plasma metabolite profiles in rats fasted for 5–7 or 10–13 h to test our model predictions. Our computational model accounted for two-thirds of the observed directions of change (an increase or decrease) in plasma metabolites, indicating their origin in the liver. Specifically, our work suggests that changes in plasma lipid metabolites, which are reliably predicted by our liver metabolism model, are key features of short-term fasting. Our approach provides a mechanistic model for identifying plasma metabolite changes originating in the liver

Normal right- and left ventricular volumes and myocardial mass in children measured by steady state free precession cardiovascular magnetic resonance

BACKGROUND: Quantification of ventricular volume by steady state free precession (SSFP) cardiovascular magnetic resonance is accurate and reproducible. Normal values exist for adults, but are lacking for children.We sought to establish normal values for left and right ventricular volumes, mass and function in healthy children by using SSFP. METHODS AND RESULTS: Fifty children (27 females, 23 males) without cardiovascular disease were evaluated. Median age was 11 years (range 7 months - 18 years), weight 35 kg (range 7-77 kg), height 146 cm (range 66-181 cm). Thirty-six examinations were performed with breath holding, 14 in freely breathing sedated children.Ventricular volumes and mass were measured in the end systolic and end diastolic phase on SSFP cine images acquired in a short axis plane as a stack of 12 contiguous slices covering full length of both ventricles. Regression analysis showed an exponential relationship between body surface area (BSA) and ventricular volumes and mass (normal value = a*BSAb). Normative curves for males and females are presented in relation to BSA for the end-diastolic volume, end-systolic volume and mass of both ventricles. Intra- and interobserver variability of the measurements was within the limits of 2% and 7% respectively, except for right ventricular mass (10%). CONCLUSION: The exponential equation for calculation of normal values for each ventricular parameter and graphical display of normative curves for data acquired in healthy children by SSFP cardiovascular magnetic resonance are provided