Endothelium-Dependent GenderDifferences inthe Response of the Rat Pulmonary Arteryto theThromboxane Mimic(U46619)1

ABSTRACT The pulmonaryarteriesof ratswere studiedinorderto determine the existence of sexual dimorphism. Gender differences, in the sensitivity (EC@)and maximum contractility (T,,,@) of ring prepa rations of the main pulmonary arteries of adult male and female rats, were evaluated with the syntheticendoperoxideanalog [(15S)-hydroxy-11a,9a-(epoxymethano)-prosta-5Z, I 3E-dienoic acid,] (U46619) and norepinephrine. There were no significant gender differences in the T@ values obtained with either U46619 or norepinephnne. However, when the intimal surface of vessel segments from female rats was rubbed, U46619 but not norep inephnne elicited a significantly lower T@. In contrast, no change inT@ was observedwithdenudedvesselsegmentsfrommales. Removal of the endothelium did not significantly affect the ECse of U46619 or norepinephnne in segmentsfrom either sex. The inhibitory effect of verapamil on the U46619-induced contractile responsewas studiedon both intactand denudedvesselsfrom rats of both gender. The T@ of intact vesselsfrom males but not femaleswas significantly attenuatedby verapamil(P < .05). The ECrevalues with verapamil were not significantly different in any of the vessel preparations. We suggest that the endothelium of the pulmonaryartery of female rats significantly potentiates the contractile response to U46619 and attenuates the inhibitory effectof verapamil. Sexual dimorphism in the vascular reactivity of isolated pulmonary blood vessels is of considerable interest owing to the reported gender differences in the incidence of primary pulmonary hypertension. After sexual maturation, women pres ent with this disease three times more frequently than men (Wagenvoort and Wagenvoort, 1970). Recent studies demonstrate that the endothelium mediates the response of the underlying smooth muscle to several ago nists (DeMey and Vanhoutte, 1982; Singer and Peach, 1983) and may be involved in the development of pulmonary hyper tension (Molteni et at., 1984). An EDRF was reported by Furchgott and Zawadski (1980) and has subsequently been verified in various vascular preparations including the human pulmonary artery In addition to EDRF, the pulmonary endothelium may also release a contractile substance. Exuded lung surface fluid and lymph fluid collected during vasoconstriction, caused by bilat eral and unilateral hypoxia, elicited contractile responses of isolated helical strip preparations of the canine pulmonary artery (Benumofet at., 1978). In addition, hypoxic vasoconstric tion of porcine pulmonary artery rings requires the presence of the endothelium and may involve the release of an endothe lium-dependent contractile factor The purpose of this study was to investigate in pulmonary this drug is currently used in the clinic for treating primary pulmonary hypertension Methods Animals. A total of 51 mature(12 weeksof age)Sprague-Dawley rats from the Charles River Breeding Laboratories (Wilmington, MA) were housed in a controlled environment with food and water ad libitum. The females and males weighed 234.2 ±6.42 and 260.83 Â

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Operationalizing integration: Examples of activity, policy, and organizational integration that link MNS research and care to other health-related programs.

<p>Note: Adapted from Grépin and Reich <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001434#pmed.1001434-Grepin1" target="_blank">[42]</a>. <i>Domain</i> indicates what is being integrated; <i>Level</i> indicates where integration is occurring. Text indicates the form of collaboration occurring.</p

Setting a National Agenda for Surgical Disparities Research: Recommendations From the National Institutes of Health and American College of Surgeons Summit

Health care disparities (differential access, care, and outcomes owing to factors such as race/ethnicity) are widely established. Compared with other groups, African American individuals have an increased mortality risk across multiple surgical procedures. Gender, sexual orientation, age, and geographic disparities are also well documented. Further research is needed to mitigate these inequities. To do so, the American College of Surgeons and the National Institutes of Health-National Institute of Minority Health and Disparities convened a research summit to develop a national surgical disparities research agenda and funding priorities. Sixty leading researchers and clinicians gathered in May 2015 for a 2-day summit. First, literature on surgical disparities was presented within 5 themes: (1) clinician, (2) patient, (3) systemic/access, (4) clinical quality, and (5) postoperative care and rehabilitation-related factors. These themes were identified via an exhaustive preconference literature review and guided the summit and its interactive consensus-building exercises. After individual thematic presentations, attendees contributed research priorities for each theme. Suggestions were collated, refined, and prioritized during the latter half of the summit. Breakout sessions yielded 3 to 5 top research priorities by theme. Overall priorities, regardless of theme, included improving patient-clinician communication, fostering engagement and community outreach by using technology, improving care at facilities with a higher proportion of minority patients, evaluating the longer-term effect of acute intervention and rehabilitation support, and improving patient centeredness by identifying expectations for recovery. The National Institutes of Health and American College of Surgeons Summit on Surgical Disparities Research succeeded in identifying a comprehensive research agenda. Future research and funding priorities should prioritize patients' care perspectives, workforce diversification and training, and systematic evaluation of health technologies to reduce surgical disparities