High Tail Hall 2 Full 134
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As targeting integrin αIIbβ3 has improved outcomes in some sepsis studies,29,30 we next examined associations between increased ITGA2B expression in platelets and adverse outcomes in sepsis. Consistent with prior reports,33 mortality was more than threefold higher in septic patients with thrombocytopenia upon ICU admission (Figure 6A). Thrombocytopenia was also modestly but significantly and inversely associated with platelet size (eg, mean platelet volume [MPV]), suggesting a release of new platelets during sepsis (Figure 6B). These findings in septic patients were not due to differences in patient age or illness severity (not shown). Consistent with the release of new platelets, MPV was significantly and positively associated with the expression of ITGA2B (Figure 6C). Increase ITGA2B expression in platelets from septic patients could not be attributed solely to increased platelet size in sepsis, as the MPV in septic patients and healthy donors was similar (supplemental Figure 6). Levels of ITGA2B expression were almost twofold higher in patients who did not survive sepsis, although differences did not reach statistical significance (Figure 6D). We next examined αIIb protein expression experimentally in mice subject to CLP. Whole blood was sampled from the tail vein and flow cytometry was performed following CLP to measure platelet surface expression of αIIb, and mice were monitored for survival over 96 hours (Figure 6E). Consistent with our findings of ITGA2B transcript levels in platelets from septic patients (Figure 6D), the expression of αIIb protein on platelets following CLP was significantly higher in animals that did not survive (Figure 6F).
Increased ITGA2B and αIIb expression in sepsis is associated with both clinical and experimentally induced sepsis-related mortality. (A) In septic patients (n = 94), sepsis-related mortality is more than threefold higher in patients with thrombocytopenia at ICU admission (day 1). (B) Platelet counts in septic patients are inversely associated with MPV. (C) ITGA2B expression is significantly higher in newly released platelets (ie, platelets with a larger MPV) from septic patients. Quartiles for MPV were determined a priori and assigned as follows: quartile 1 (Q1), MPV 8.7 fL. (D) ITGA2B expression is higher in septic patients who did not survive. Quartiles of ITGA2B mRNA expression were determined a priori and assigned as follows: Q1, 6.95 fold-change. Analyses in panels C-D were performed by analysis of variance. (E) Kaplan-Meier curve of mortality in mice following CLP (n = 20 mice). (F) Whole blood (2 μL) sampled from the tail vein 24 hours following CLP. Platelet αIIb surface protein was assessed 24 hours following CLP by flow cytometry, stratified for mice that subsequently did not survive (dead) or survived (alive) CLP. MFI, mean fluorescence intensity.
Extras: Private Heated Pool (16 x 32, pool heat available see cost below), Kiddie Pool, Hot Tub (6), ELEVATOR, Movie Theater with ROKU, high speed internet, wine storage, gas grill, gas fireplace (available November 1-April 30), hand painted murals, custom tile, 5 whirlpool tubs, pool table, bumper pool, book and game libraries, poolside bar, private beach walkway, full court basketball, fish cleaning station, 2 Pack-n-Play, 2 high chairs, linens and towels provided, parking for 9 Vehicles, community water and Pine Island Community Amenities. No Smoking. No Pets. Special Events Welcome, 50 people. Distance to beach access: Oceanfront. House Address: 379 Deep Neck Road. Beds: 5 Kings, 3 Queens, Bunk Set, 2 Trundles, DuoBunk. Key Type: Keyless entry. CHECK IN LOCATION: 1213-C Duck Road, Duck Office. *SPARKLE CLUB
Kilmarlic Golf Club Member: This program offers guests a variety of activities that include discounted golf access, wild horse tours, golf lessons and clinics, and shuttle service to the club from your rental home. The K Club will also have a full time concierge to assist in planning your activities. You can also receive special rates for the newest attraction on the Outer Banks, the H2OBX Waterpark and Kitty Hawk Kites activities including hang gliding, paragliding, kayak tours, kite boarding, jet-ski rentals and more! CLICK HERE for details, rates and reservations! (252) 491-2841. 153554b96e