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Mechanisms underlying arteriovenous malformations (AVMs) are poorly understood. Using mice with endothelial cell (EC) expression of constitutively active Notch4 (Notch4*EC), we show decreased arteriolar tone in vivo during brain AVM initiation. Reduced vascular tone is a primary effect of Notch4*EC, as isolated pial arteries from asymptomatic mice exhibited reduced pressure-induced arterial tone ex vivo. The nitric oxide (NO) synthase (NOS) inhibitor NG-nitro-l-arginine (L-NNA) corrected vascular tone defects in both assays. L-NNA treatment or endothelial NOS (eNOS) gene deletion, either globally or specifically in ECs, attenuated AVM initiation, assessed by decreased AVM diameter and delayed time to moribund. Administering nitroxide antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl also attenuated AVM initiation. Increased NOS-dependent production of hydrogen peroxide, but not NO, superoxide, or peroxynitrite was detected in isolated Notch4*EC brain vessels during AVM initiation. Our data suggest that eNOS is involved in Notch4*EC-mediated AVM formation by up-regulating hydrogen peroxide and reducing vascular tone, thereby permitting AVM initiation and progression.

• Lower respiratory tract infections are the top cause of infectious disease-related deaths in the world.• The causative pathogen is detectable in only 38% of adults with community acquired pneumonia.• Time to diagnosis of pathogen is directly correctly with mortality.• The widespread use of broad-spectrum empiric treatment contributes to the proliferation of antimicrobial resistance.• Next Generation Sequencing could offer potential for early identification.

Ebola virus disease (EVD) is a potentially fatal infectious disease, easily transmitted through direct contact with infected body fluids. Children exhibit a range of nonspecific clinical signs that mirror common [...]

The functions of blood flow in the morphogenesis of mammalian arteries and veins are not well understood. We examined the development of the dorsal aorta (DA) and the cardinal vein (CV) in Ncx1 -/- mutants, which lack blood flow due to a deficiency in a sodium calcium ion exchanger expressed specifically in the heart. The mutant DA and CV were abnormally connected. The endothelium of the Ncx1 -/- mutant DA lacked normal expression of the arterial markers ephrin-B2 and Connexin-40. Notch1 activation, known to promote arterial specification, was decreased in mutant DA endothelial cells (ECs), which ectopically expressed the venous marker Coup-TFII. These findings suggest that flow has essential functions in the DA by promoting arterial and suppressing venous marker expression. In contrast, flow plays a lesser role in the CV, because expression of arterial-venous markers in CV ECs was not as dramatically affected in Ncx1 -/- mutants. We propose a molecular mechanism by which blood flow mediates DA and CV morphogenesis, by regulating arterial-venous specification of DA ECs to ensure proper separation of the developing DA and CV.

The Chiral Polymer Stabilized Vertical Alignment (C‐PS‐VA) technology enables up to 10% increase in transmittance leading to potentially lower power consumption of final devices and energy saving compared to conventional Polymer Stabilized Vertical Alignment (PS‐VA) technology. Self‐Aligned Vertical Alignment (SA‐VA) enables the simplification of the process to achieve energy saving by eliminating high‐temperature baking. This paper summarizes the recent developments of liquid crystal mixtures for C‐PS‐VA & SA‐VA technologies in terms of performance and reliability. [ABSTRACT FROM AUTHOR]

Arteriovenous (AV) malformation (AVM) is a devastating condition characterized by focal lesions of enlarged, tangled vessels that shunt blood from arteries directly to veins. AVMs can form anywhere in the body and can cause debilitating ischemia and life-threatening hemorrhagic stroke. The mechanisms that underlie AVM formation remain poorly understood. Here, we examined the cellular and hemodynamic changes at the earliest stages of brain AVM formation by time-lapse two-photon imaging through cranial windows of mice expressing constitutively active Notch4 (Notch4*). AVMs arose from enlargement of preexisting microvessels with capillary diameter and blood flow and no smooth muscle cell coverage. AV shunting began promptly after Notch4* expression in endothelial cells (ECs), accompanied by increased individual EC areas, rather than increased EC number or proliferation. Alterations in Notch signaling in ECs of all vessels, but not arteries alone, affected AVM formation, suggesting that Notch functions in the microvasculature and/or veins to induce AVM. Increased Notch signaling interfered with the normal biological control of hemodynamics, permitting a positive feedback loop of increasing blood flow and vessel diameter and driving focal AVM growth from AV connections with higher blood velocity at the expense of adjacent AV connections with lower velocity. Endothelial expression of constitutively active Notch1 also led to brain AVMs in mice. Our data shed light on cellular and hemodynamic mechanisms underlying AVM pathogenesis elicited by increased Notch signaling in the endothelium.

In considering the potential to reduce the carbon footprint of our emergency department (ED) via decreasing plastic waste, we aimed to evaluate the effects of changing certain common emergency department medications from an intravenous (IV) piggyback administration route to IV push. Our team queried hospital pharmacy data to determine the number of doses of several frequently utilized antibiotics administered over a six-month time period, then calculated the resultant cost savings of a switch to IV push. Based upon our modeling calculations, switching certain medication administration routes to IVP can have significant impacts on cost, with an estimated cost savings of about $47,000 every six months. Maximizing the use of push administration could result in even more dramatic cost savings. In some scenarios, using IVP administration results in less than half the amount of plastic waste generated. Future research including a full life-cycle analysis is needed in order to precisely determine the impact on carbon footprint created by making this change. [ABSTRACT FROM AUTHOR]

Purpose: Prior to COVID, thousands of medical school and residency applicants traversed their countries for in‐person interviews each year. However, data on the greenhouse gas emissions from in‐person interviews is limited. This study estimated greenhouse gas emissions associated with in‐person medical school and residency interviews and explored applicant interview structure preferences. Methods: From March to June 2022, we developed and distributed a nine‐question, website‐based survey to collect information on applicant virtual interview schedule, demographics and preference for future interview format. We calculated theoretical emissions for all interviews requiring air travel and performed a content analysis of interview preference explanations. Results: We received responses from 258 first‐year and 253 fourth‐year medical students at 26 allopathic US medical schools who interviewed virtually in 2020–2021 and 2021–2022, respectively. Residency applicants participating in the study were interviewed at a mean of 15.3 programs (SD 5.4) and had mean theoretical emissions of 4.31 tons CO2eq. Medical school applicants participating in the study were interviewed at a mean of 6.9 programs and had mean theoretical emissions of 2.19 tons CO2eq. Ninety percent of medical school applicants and 91% of residency applicants participating in the study expressed a preference for hybrid or virtual interviews going forward. Conclusion: In‐person medical training interviews have significant greenhouse gas emissions. Virtual and hybrid alternatives have a high degree of acceptability among applicants. Hampshire et al. quantify the impact of emissions created by in‐person medical school and residency interviews. [ABSTRACT FROM AUTHOR]