Effects of dietary L -arginine on structure and function of flow-restricted vein grafts

AbstractPurpose: Experiments were designed to determine effects of dietary supplementation with L -arginine on structure and function of flow-restricted vein grafts. Methods: Saphenous veins were placed as bilateral interposition grafts in femoral arteries of two groups of adult male mongrel dogs; one group was maintained on a normal diet (control), the other group supplemented with L -arginine (200 mg/kg per day) beginning 1 week before surgery. In each dog, flow was reduced by 50% in one graft by placing an adjustable clamp on the artery distal to the distal anastomosis. Plasma amino acids and oxidized products of nitric oxide (NOx ) were measured before and after L -arginine feeding. At postoperative week 4, grafts were removed and prepared for organ chamber studies to determine functions of the endothelium or smooth muscle and for histology. Results: Plasma L -arginine increased within 3 hours after feeding and increased from 141 ± 8 nmol/mL to 169 ± 11 nmol/mL (n = 6) after 5 weeks of supplementation. Plasma ornithine and citrulline paralleled arginine, whereas circulating NOx was unchanged. Maximal contractions to 60 mmol/L KCl were reduced in grafts from L -arginine–fed dogs. Endothelium-dependent relaxations to the calcium ionophore A23187 and relaxations of the smooth muscle NO were reduced in grafts from L -arginine–fed dogs. Neointimal hyperplasia was increased in grafts with reduced flow and not affected by arginine feeding. Conclusions: Dietary supplementation with L -arginine did not increase plasma NO in dogs with peripheral vein grafts or increase endothelium-dependent relaxations in control or flow-restricted grafts. Therefore, dietary supplementation with L -arginine may not improve long-term functions of flow-restricted peripheral bypass grafts. (J Vasc Surg 2001;33:829-39.

Sex and Gender in Medical Education, and proceedings from the 2015 Sex and Gender Education Summit

The Sex and Gender Medical Education Summit: a roadmap for curricular innovation was a collaborative initiative of the American Medical Women\u27s Association, Laura W. Bush Institute for Women’s Health, Mayo Clinic, and Society for Women\u27s Health Research (www.sgbmeducationsummit.com). It was held on October 18–19, 2015 to provide a unique venue for collaboration among nationally and internationally renowned experts in developing a roadmap for the incorporation of sex and gender based concepts into medical education curricula. The Summit engaged 148 in-person attendees for the 1 1/2-day program. Pre- and post-Summit surveys assessed the impact of the Summit, and workshop discussions provided a framework for informal consensus building. Sixty-one percent of attendees indicated that the Summit had increased their awareness of the importance of sex and gender specific medicine. Other comments indicate that the Summit had a significant impact for motivating a call to action among attendees and provided resources to initiate change in curricula within their home institutions. These educational efforts will help to ensure a sex and gender basis for delivery of health care in the future

A Search for High-Energy Counterparts to Fast Radio Bursts

We report on a search for high-energy counterparts to fast radio bursts (FRBs) with the Fermi Gamma-ray Burst Monitor (GBM), Fermi Large Area Telescope (LAT), and the Neil Gehrels Swift Observatory Burst Alert Telescope (BAT). We find no significant associations for any of the 23 FRBs in our sample, but report upper limits to the high-energy fluence for each on timescales of 0.1, 1, 10, and 100 s. We report lower limits on the ratio of the radio to high-energy fluence, $\frac{f_{r}}{f_{\gamma}}$, for timescales of 0.1 and 100 s. We discuss the implications of our non-detections on various proposed progenitor models for FRBs, including analogs of giant pulses from the Crab pulsar and hyperflares from magnetars. This work demonstrates the utility of analyses of high-energy data for FRBs in tracking down the nature of these elusive sources

NIH Initiative to Balance Sex of Animals in Preclinical Studies: Generative Questions to Guide Policy, Implementation, and Metrics

In May of 2014, the NIH Director together with the Director of the Office of Research on Women’s Health announced plans to take a multi-dimensional approach to address the over reliance on male cells and animals in preclinical research. The NIH is engaging the scientific community in the development of policies to improve the sex balance in research. The present, past, and future presidents of the Organization for the Study of Sex Differences, in order to encourage thoughtful discussion among scientists, pose a series of questions to generate ideas in three areas: 1. research strategies, 2. educational strategies, and 3. strategies to monitor effectiveness of policies to improve the sex balance in research. By promoting discussion within the scientific community, a consensus will evolve that will move science forward in a productive and effective manner

Reporting of sex as a variable in cardiovascular studies using cultured cells

<p>Abstract</p> <p>Background</p> <p>Chromosomal complement, including that provided by the sex chromosomes, influences expression of proteins and molecular signaling in every cell. However, less than 50% of the scientific studies published in 2009 using experimental animals reported sex as a biological variable. Because every cell has a sex, we conducted a literature review to determine the extent to which sex is reported as a variable in cardiovascular studies on cultured cells.</p> <p>Methods</p> <p>Articles from 10 cardiovascular journals with high impact factors (<it>Circulation</it>, <it>J Am Coll Cardiol</it>, <it>Eur Heart J</it>, <it>Circ Res</it>, <it>Arterioscler Thromb Vasc Biol</it>, <it>Cardiovasc Res</it>, <it>J Mol Cell Cardiol</it>, <it>Am J Physiol Heart Circ Physiol</it>, <it>J Heart Lung Transplant and J Cardiovasc Pharmacol</it>) and published in 2010 were searched using terms 'cultured' and 'cells' in any order to determine if the sex of those cells was reported. Studies using established cell lines were excluded.</p> <p>Results</p> <p>Using two separate search strategies, we found that only 25 of 90 articles (28%) and 20 of 101 articles (19.8%) reported the sex of cells. Of those reporting the sex of cells, most (68.9%; n = 31) used only male cells and none used exclusively female cells. In studies reporting the sex of cells of cardiovascular origin, 40% used vascular smooth-muscle cells, and 30% used stem/progenitor cells. In studies using cells of human origin, 35% did not report the sex of those cells. None of the studies using neonatal cardiac myocytes reported the sex of those cells.</p> <p>Conclusions</p> <p>The complement of sex chromosomes in cells studied in culture has the potential to affect expression of proteins and 'mechanistic' signaling pathways. Therefore, consistent with scientific excellence, editorial policies should require reporting sex of cells used in <it>in vitro </it>experiments.</p

Human-derived nanoparticles and vascular response to injury in rabbit carotid arteries: Proof of principle

Self-calcifying, self-replicating nanoparticles have been isolated from calcified human tissues. However, it is unclear if these nanoparticles participate in disease processes. Therefore, this study was designed to preliminarily test the hypothesis that human-derived nanoparticles are causal to arterial disease processes. One carotid artery of 3 kg male rabbits was denuded of endothelium; the contralateral artery remained unoperated as a control. Each rabbit was injected intravenously with either saline, calcified, or decalcified nanoparticles cultured from calcified human arteries or kidney stones. After 35 days, both injured and control arteries were removed for histological examination. Injured arteries from rabbits injected with saline showed minimal, eccentric intimal hyperplasia. Injured arteries from rabbits injected with calcified kidney stone- and arterial-derived nanoparticles occluded, sometimes with canalization. The calcified kidney stone-derived nanoparticles caused calcifications within the occlusion. Responses to injury in rabbits injected with decalcified kidney stone-derived nanoparticles were similar to those observed in saline-injected animals. However, decalcified arterial-derived nanoparticles produced intimal hyperplasia that varied from moderate to occlusion with canalization and calcification. This study offers the first evidence that there may be a causal relationship between human-derived nanoparticles and response to injury including calcification in arteries with damaged endothelium

Neuroanatomy of expressive suppression: The role of the insula.

Expressive suppression is a response-focused regulatory strategy aimed at concealing the outward expression of emotion that is already underway. Expressive suppression requires the integration of interoception, proprioception, and social awareness to guide behavior in alignment with personal and interpersonal goals-all processes known to involve the insular cortex. Frontotemporal dementia (FTD) provides a useful patient model for studying the insula's role in socioemotional regulation. The insula is a key target of early atrophy in FTD, causing patients to lose the ability to represent the salience of internal and external conditions and to use these representations to guide behavior. We examined a sample of 59 patients with FTD, 52 patients with Alzheimer's disease (AD), and 38 neurologically healthy controls. Subjects viewed 2 disgust-eliciting films in the laboratory. During the first film, subjects were instructed to simply watch (emotional reactivity trial); during the second, they were instructed to hide their emotions (expressive suppression trial). Structural images from a subsample of participants (n = 42; 11 FTD patients, 11 AD patients, and 20 controls) were examined in conjunction with behavior. FreeSurfer was used to quantify regional gray matter volume in 41 empirically derived neural regions in both hemispheres. Of the 3 groups studied, FTD patients showed the least expressive suppression and had the smallest insula volumes, even after controlling for age, gender, and emotional reactivity. Among the brain regions examined, the insula was the only significant predictor of expressive suppression ability, with lower insula gray matter volume in both hemispheres predicting less expressive suppression. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Identification of B6SJL mSOD1(G93A) mouse subgroups with different disease progression rates

Disease progression rates among patients with amyotrophic lateral sclerosis (ALS) vary greatly. Although the majority of affected individuals survive 3-5 years following diagnosis, some subgroups experience a more rapidly progressing form, surviving less than 1 year, and other subgroups experience slowly progressing forms, surviving nearly 50 years. Genetic heterogeneity and environmental factors pose significant barriers in investigating patient progression rates. Similar to the case for humans, variation in survival within the mSOD1 mouse has been well documented, but different progression rates have not been investigated. The present study identifies two subgroups of B6SJL mSOD1(G93A) mice with different disease progression rates, a fast progression group (FPG) and slow progression group, as evidenced by differences in the rate of motor function decline. In addition, increased disease-associated gene expression within the FPG facial motor nucleus confirmed the presence of a more severe phenotype. We hypothesize that a more severe disease phenotype could be the result of 1) an earlier onset of axonal disconnection with a consistent degeneration rate or 2) a more severe or accelerated degenerative process. We performed a facial nerve transection axotomy in both mSOD1 subgroups prior to disease onset as a method to standardize the axonal disconnection. Instead of leading to comparable gene expression in both subgroups, this standardization did not eliminate the severe phenotype in the FPG facial nucleus, suggesting that the FPG phenotype is the result of a more severe or accelerated degenerative process. We theorize that these mSOD1 subgroups are representative of the rapid and slow disease phenotypes often experienced in ALS