Endothelial cell (EC) Ca ²⁺-activated K channels (SK Cₐ and IK Cₐ channels) generate hyperpolarization that passes to the adjacent smooth muscle cells causing vasodilation. IK Cₐ channels focused ...within EC projections toward the smooth muscle cells are activated by spontaneous Ca ²⁺ events (Ca ²⁺ puffs/pulsars). We now show that transient receptor potential, vanilloid 4 channels (TRPV4 channels) also cluster within this microdomain and are selectively activated at low intravascular pressure. In arterioles pressurized to 80 mmHg, ECs generated low-frequency (∼2 min ⁻¹) inositol 1,4,5-trisphosphate receptor-based Ca ²⁺ events. Decreasing intraluminal pressure below 50 mmHg increased the frequency of EC Ca ²⁺ events twofold to threefold, an effect blocked with the TRPV4 antagonist RN1734. These discrete events represent both TRPV4-sparklet- and nonsparklet-evoked Ca ²⁺ increases, which on occasion led to intracellular Ca ²⁺ waves. The concurrent vasodilation associated with increases in Ca ²⁺ event frequency was inhibited, and basal myogenic tone was increased, by either RN1734 or TRAM-34 (IK Cₐ channel blocker), but not by apamin (SK Cₐ channel blocker). These data show that intraluminal pressure influences an endothelial microdomain inversely to alter Ca ²⁺ event frequency; at low pressures the consequence is activation of EC IK Cₐ channels and vasodilation, reducing the myogenic tone that underpins tissue blood-flow autoregulation.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Many studies have assessed perspectives of medical students toward institutional diversity, but few of them have attempted to map changes in diversity climate over time.
This study aims to ...investigate changes in diversity climate at a Jesuit medical institution over a 12-year period.
In 1999, 334 medical students completed an anonymous self-administered online survey, and 12 years later, 406 students completed a comparable survey in 2011. Chi-square tests assessed the differences in percent responses to questions of the two surveys, related to three identities: gender, race, and sexual orientation.
The 1999 versus 2011 samples were 46% versus 49% female, 61% versus 61% Caucasian, and 41% vs. 39% aged 25 years or older. Findings suggested improvements in medical students' perceptions surrounding equality 'in general' across the three identities (p<0.001); 'in the practice of medicine' based on gender (p<0.001), race/ethnicity (p=0.60), and sexual orientation (p=0.43); as well as in the medical school curriculum, including course text content, professor's delivery and student-faculty interaction (p<0.001) across the three identities. There was a statistically significant decrease in experienced or witnessed events related to gender bias (p<0.001) from 1999 to 2011; however, reported events of bias based on race/ethnicity (p=0.69) and sexual orientation (p=0.58) only showed small decreases.
It may be postulated that the improvement in students' self-perceptions of equality and diversity over the past 12 years may have been influenced by a generational acceptance of cultural diversity and, the inclusion of diversity training courses within the medical curriculum. Diversity training related to race and sexual orientation should be expanded, including a follow-up survey to assess the effectiveness of any intervention.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract only
It is thought that sympathetic nerve activation stimulates arterial constriction predominately through the release of three neurotransmitters: norepinephrine (NE), adenosine ...triphosphate (ATP) and neuropeptide Y (NPY). The aim of the current study was to examine the composition of neurotransmitter released in response to sympathetic nerve stimulation in mesenteric arteries of two commonly used wild‐type animal models. Isolated mesenteric arteries from male C57BL/6J mice and Wistar rats were mounted in a Danish Myotechnology 2‐Channel Wire Myograph System and isometric force measurements were recorded. Electrical field stimulation (EFS) was used to stimulate sympathetic perivascular nerves (PVNs) to release neurotransmitters in the presence and absence of the adrenergic receptor blocker phentolamine and/or purinergic receptor blocker NF449. Phentolamine alone blocked a significant proportion of the contractile response evoked by EFS in both mice and rats, suggesting that NE is the main sympathetic neurotransmitter in both species. Treatment with NF449 alone blocked a small proportion of the contractile response evoked by EFS in mice but did not have a significant effect in rat, suggesting that ATP may play a more important role in mice. The application of both phentolamine and NF449 nearly completely blocked the contractile response to EFS in mouse mesenteric arteries; however, in rat, a proportion of the contractile response, roughly equivalent to the response obtained in the presence of phentolamine alone, was still observed. These data suggest that the neurotransmitter composition is different between mice and rats, in particular mouse mesenteric sympathetic PVNs release NE and ATP while rat mesenteric sympathetic PVNs release NE and another non‐purinergic neurotransmitter(s).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Privatization of military support functions continues to grow at an exponential rate and significant research has been devoted to the topic. Exploration and empirical analysis of how specialized ...medical support actors augment Peace Support Operations (PSOs) has been studied far less. Operational challenges span a wide range of factors, including strategic relationships, medical planning, interoperability, and increasing military manpower constraints. My thesis uncovers and analyzes many of the operational constraints and discusses the implications of augmenting peace engagement missions with private sector medical contractors. Case study analyses will provide evidence and insight in two operations utilizing private sector, specialized medical support: remote medical operations in the Ukraine, supported by the Organization Security for Cooperation in Europe (OSCE) ceasefire monitoring teams; and the current North Atlantic Treaty Organization (NATO) Kosovo peacekeeping mission. I evaluate the operational challenges experienced in each of these missions by drawing on both rationalist and functionalist frameworks, including field-level interviews and personal experience narrative (PEN). The discussion and results from this comparative analysis offer insights on strengths, weaknesses, opportunities, and potential areas of concern that provide valuable inference for scholars and practitioners. Analyzing the private medical sector challenges within a PSO also contributes to a better understanding of current medical support operations while offering direction for future scholarship in this area.
Proportional cardiovascular disease mortality rates are not different between US astronauts that have flown in low Earth orbit (LEO) and those that have never flown orbital missions in space. While ...these data suggest that spaceflight (SF) in LEO holds nominal long‐term cardiovascular health consequences, to date the acute effect of SF on coronary artery function has not been explored. The purpose of this study was to examine murine coronary artery contractile, dilatory, and mechanical properties following SF in LEO aboard the International Space Station (ISS). Twenty C57BL/6J mice were housed in a specially designed rodent habitat and were launched to the ISS aboard a Falcon 9 rocket (Space‐X CRS‐12). Following ~33 days of SF in LEO, the Dragon capsule containing the mice splashed down in the Pacific Ocean. Within 33–41 hours of returning to Earth, the left anterior descending (LAD) coronary arteries were cleared of surrounding cardiac tissue and mounted in a Danish Myotech wire myograph. LADs were then exposed to agonists that allowed for the examination of endothelial (EC) and smooth muscle cell (SMC) function. Vivarium controls (VC), consisting of mice housed in conventional vivarium cages, and habitat controls (HC), which were housed in the same type cages as those flown on orbit and maintained under similar pCO2, temperature, humidity, and light conditions, were used for comparison. The passive pressure‐diameter relationship was not different between SF and either control. SMC‐dependent vasoconstriction to U46619, a thromboxane receptor agonist, was significantly greater in HC versus SF at only a single dose, while vasoconstriction to isosmotic KCl was unaltered. LADs from SF mice preconstricted with U46619 exhibited similar EC‐dependent vasodilation to the muscarinic receptor agonist acetylcholine when compared to VC and HC. Acetylcholine and ADPβS (a P2Y1 receptor agonist)‐mediated vasodilation were completely absent in all LADs preconstricted with KCl in the presence of the nitric oxide synthase inhibitor, L‐NAME. In vessels preconstricted with U46619 vasodilation to the EC‐dependent vasodilator ADPβS was similar between SF and both controls, with SF LADs exhibiting less dependence on nitric oxide (NO)‐mediated mechanisms as observed in the presence of L‐NAME. LADs from SF mice exhibited a right‐ward shift to the NO donor and SMC‐dependent vasodilator, DEA NONOate. Collectively, these data suggest that subtle changes in LAD function occur following spaceflight in LEO. In particular, NO‐mediated signals were the most affected, as indicated by decreased SMC sensitivity to exogenous NO. In addition, while the magnitude of vasodilation to ADPβS was unchanged, SF animals exhibited less dependence on NO‐mediated signals. These ADPβS responses suggest a shift away from the canonical NO‐mediated pathway of vasodilation. These data represent the first examination of coronary artery function following SF and suggest that function is well maintained due to subtle mechanistic adaptations.
Support or Funding Information
This work was supported by NASA Space Biology grant NNX16AC28G.
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective
This study was undertaken to characterize structural and pharmacological properties of the pig popliteal artery in order to develop a novel system for the examination of lower limb blood ...flow regulation in a variety of cardiovascular pathologies, such as diabetes‐induced peripheral artery disease.
Methods
Popliteal arteries were isolated from streptozocin‐induced diabetic pigs or age‐matched saline‐injected control pigs for morphological study using transmission electron microscopy and for examination of vasoreactivity to pharmacological agents using wire myography.
Results
Transmission electron microscopy of the porcine popliteal artery wall revealed the presence of endothelial cell‐smooth muscle cell interactions (myoendothelial junctions) and smooth muscle cell‐smooth muscle cell interactions, for which we have coined the term “myo‐myo junctions.” These myo‐myo junctions were shown to feature plaques indicative of connexin expression. Further, the pig popliteal artery was highly responsive to a variety of vasoconstrictors including norepinephrine, phenylephrine, and U46619, and vasodilators including acetylcholine, adenosine 5′‐β‐thio diphosphate, and bradykinin. Finally, 2 weeks after streptozocin‐induced diabetes, the normalized vasoconstriction of the pig popliteal artery to norepinephrine was unaltered compared to control.
Conclusions
The pig popliteal artery displays structural and pharmacological properties that might prove useful in future studies of diabetes‐associated peripheral artery disease and other lower limb cardiovascular diseases.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The purpose of this project was for the project director to design a strategy for increasing the number of adults in the small group ministry at Heartland Church, Winter Haven, Florida. The first ...chapter described the need for a small group growth strategy at Heartland Church. The description comes from a demographic study of the local community and the current state of the situation at Heartland Church. In chapter two, the project concentrated on the biblical and theological foundations for the project. The project director focused on Matt 28:16–20 and Acts 2:42–47 to explain the importance of disciple-making and biblical community. The project director applied the biblical and theological truths from the two passages of scripture to the design of a small group growth strategy for Heartland Church. The project director reviewed several articles of literature in chapter three. The project director discovered similar small group set-ups from two churches and surveyed two pastors responsible for small groups in their local ministry context. Also, chapter three included surveys by Heartland Church members currently leading a small group, involved in a small group, and members not involved in a small group. In chapter four, the project director provided a detailed description of the steps he took to implement a strategy for increasing the number of adults in the small group ministry at Heartland. The project director began the process by identifying two New Testament passages emphasizing the importance of disciple-making and numerical growth. The project director discussed the importance of small groups at Heartland with the executive leadership team consisting of Ed Kendrick, the lead pastor of Heartland, and Danny Moosbrugger, the executive pastor of Heartland. The project director overviewed the recruiting process and interaction had with the expert panel. He then detailed the strategy design process done with the executive leadership team. The project director and executive leadership team designed a small group growth strategy. The material in chapter five detailed the overall results of the project. The project director evaluated the project objectives. He also listed the projects strengths and weaknesses and discusses the future plans to implement the strategy. The project director also discussed the lessons learned from the project.
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