New Plants, New Resources, New Knowledge: Early Introductions of Exotic Plants to Indigenous Territories in Northwestern North America.

Plants have always been important for the Indigenous Peoples of Northwestern North America. Collectively, these peoples named and used hundreds of different native plant species, along with diverse animal species. When traders and settlers from Europe and other parts of the world arrived in the region, they brought many new species of plants with them. Some (e.g., turnips (Brassica rapa) and onions (Allium cepa)), were from Europe, and some (e.g., potatoes (Solanum tuberosum)) were from South America or elsewhere. Other plants, like dandelion, Taraxacum officinale, probably arrived unintentionally, as weeds. Examining the ways in which the Indigenous Peoples have incorporated these new species into their lexicons and lifestyles provides insight into processes of acquiring and embracing new products and expanding the cultural knowledge base for human societies in general.

Heat-inactivated Factor B inhibits alternative pathway fluid-phase activation and convertase formation on endothelial cell-secreted ultra-large von Willebrand factor strings.

Defective regulation of the alternative complement pathway (AP) causes excessive activation and promotes the inflammation and renal injury observed in atypical hemolytic-uremic syndrome (aHUS). The usefulness of heat-inactivated Factor B (HFB) in reducing AP activation was evaluated in: fluid-phase reactions, using purified complement proteins and Factor H (FH)-depleted serum; and in surface-activated reactions using human endothelial cells (ECs). C3a and Ba levels, measured by quantitative Western blots, determined the extent of fluid-phase activation. In reactions using C3, FB, and Factor D proteins, HFB addition (2.5-fold FB levels), reduced C3a levels by 60% and Ba levels by 45%. In reactions using FH-depleted serum (supplemented with FH at 12.5% normal levels), Ba levels were reduced by 40% with HFB added at 3.5-fold FB levels. The effectiveness of HFB in limiting AP convertase formation on activated surfaces was evaluated using stimulated ECs. Fluorescent microscopy was used to quantify endogenously released C3, FB, and C5 attached to EC-secreted ultra-large VWF strings. HFB addition reduced attachment of C3b by 2.7-fold, FB by 1.5-fold and C5 by fourfold. Our data indicate that HFB may be of therapeutic value in preventing AP-mediated generation of C3a and C5a, and the associated inflammation caused by an overactive AP.

"When the Wild Roses Bloom": Indigenous Knowledge and Environmental Change in Northwestern North America.

Indigenous Peoples in Northwestern North America have always worked with predictable cycles of day and night, tides, moon phases, seasons, and species growth and reproduction, including such phenological indicators as the blooming of flowers and the songs of birds. Negotiating variability has been constant in people's lives. Long-term monitoring and detailed knowledge of other lifeforms and landscapes of people's home territories have assisted in responding and adapting to change. Aspects of cultural knowledge and practice that have helped Indigenous Peoples navigate nature's cycles at different scales of time and space include kin ties and social relationships, experiential learning, language, storytelling and timing of ceremonies such as "First Foods" celebrations. Working with ecological processes, Indigenous Peoples have been able to maintain optimal conditions for preferred species, reducing variability and uncertainty through taking care of productive habitats, leaving ecosystems intact, and allowing other species to change in their own cycles. Since the onset of colonization, however, Indigenous Peoples' lifeways have been changed drastically, culminating with the current impacts of global climate change and biodiversity loss. This paper, based on contributions of numerous Indigenous Knowledge holders from across Northwestern North America, outlines some of the key ways in which Indigenous Peoples have embraced predictability and change in their environments and lifeways, and addresses the particular threat of climate change: its recognition, ways of adapting to it, and, ultimately, how it might be reversed through developing more careful, respectful relationships with and responsibilities for the other-than-human world.

Chlorogenic Acid and Quercetin in a Diet with Fermentable Fiber Influence Multiple Processes Involved in DSS-Induced Ulcerative Colitis but Do Not Reduce Injury.

Ulcerative colitis (UC) patients often avoid foods containing fermentable fibers as some can promote symptoms during active disease. Pectin has been identified as a more protective fermentable fiber, but little has been done to determine the interaction between pectin and bioactive compounds present in foods containing that fiber type. Quercetin and chlorogenic acid, two bioactives in stone fruits, may have anti-cancer, anti-oxidant, and anti-inflammatory properties. We hypothesized that quercetin and chlorogenic acid, in the presence of the fermentable fiber pectin, may suppress the expression of pro-inflammatory molecules, alter the luminal environment, and alter colonocyte proliferation, thereby protecting against recurring bouts of UC. Rats (n = 63) received one of three purified diets (control, 0.45% quercetin, 0.05% chlorogenic acid) containing 6% pectin for 3 weeks before exposure to dextran sodium sulfate (DSS, 3% for 48 h, 3x, 2 wk separation, n = 11/diet) in drinking water to initiate UC, or control (no DSS, n = 10/diet) treatments prior to termination at 9 weeks. DSS increased the fecal moisture content (p < 0.05) and SCFA concentrations (acetate, p < 0.05; butyrate, p < 0.05). Quercetin and chlorogenic acid diets maintained SLC5A8 (SCFA transporter) mRNA levels in DSS-treated rats at levels similar to those not exposed to DSS. DSS increased injury (p < 0.0001) and inflammation (p < 0.01) scores, with no differences noted due to diet. Compared to the control diet, chlorogenic acid decreased NF-κB activity in DSS-treated rats (p < 0.05). Quercetin and chlorogenic acid may contribute to the healthy regulation of NF-κB activation (via mRNA expression of IκΒα, Tollip, and IL-1). Quercetin enhanced injury-repair molecule FGF-2 expression (p < 0.01), but neither diet nor DSS treatment altered proliferation. Although quercetin and chlorogenic acid did not protect against overt indicators of injury and inflammation, or fecal SCFA concentrations, compared to the control diet, their influence on the expression of injury repair molecules, pro-inflammatory cytokines, SCFA transport proteins, and NF-κB inhibitory molecules suggests beneficial influences on major pathways involved in DSS-induced UC. Therefore, in healthy individuals or during periods of remission, quercetin and chlorogenic acid may promote a healthier colon, and may suppress some of the signaling involved in inflammation promotion during active disease.

Introduction to the thematic issue: Recognition of women leaders in Science.

This thematic issue of Experimental Biology and Medicine is dedicated to the incredibly important contributions made by women leaders in the biomedical sciences throughout recent history. Scientists from many disciplines have contributed papers, both original research and state of the art reviews, to demonstrate the type of work being performed every day by women leaders committed to advancing scientific knowledge in their respective fields of specialization. In this introduction, we provide readers with a brief highlight of the information to be found in the invited papers.

Human endothelial cells and fibroblasts express and produce the coagulation proteins necessary for thrombin generation.

In a previous study, we reported that human endothelial cells (ECs) express and produce their own coagulation factors (F) that can activate cell surface FX without the additions of external proteins or phospholipids. We now describe experiments that detail the expression and production in ECs and fibroblasts of the clotting proteins necessary for formation of active prothrombinase (FV-FX) complexes to produce thrombin on EC and fibroblast surfaces. EC and fibroblast thrombin generation was identified by measuring: thrombin activity; thrombin-antithrombin complexes; and the prothrombin fragment 1.2 (PF1.2), which is produced by the prothrombinase cleavage of prothrombin (FII) to thrombin. In ECs, the prothrombinase complex uses surface-attached FV and γ-carboxyl-glutamate residues of FX and FII to attach to EC surfaces. FV is also on fibroblast surfaces; however, lower fibroblast expression of the gene for γ-glutamyl carboxylase (GGCX) results in production of vitamin K-dependent coagulation proteins (FII and FX) with reduced surface binding. This is evident by the minimal surface binding of PF1.2, following FII activation, of fibroblasts compared to ECs. We conclude that human ECs and fibroblasts both generate thrombin without exogenous addition of coagulation proteins or phospholipids. The two cell types assemble distinct forms of prothrombinase to generate thrombin.

Omega-3 fatty acid modulation of serum and osteocyte tumor necrosis factor-α in adult mice exposed to ionizing radiation.

Chronic inflammation leads to bone loss and fragility. Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) consistently promote bone resorption. Dietary modulation of proinflammatory cytokines is an accepted therapeutic approach to treat chronic inflammation, including that induced by space-relevant radiation exposure. As such, these studies were designed to determine whether an anti-inflammatory diet, high in omega-3 fatty acids, could reduce radiation-mediated bone damage via reductions in the levels of inflammatory cytokines in osteocytes and serum. Lgr5-EGFP C57BL/6 mice were randomized to receive diets containing fish oil and pectin (FOP; high in omega-3 fatty acids) or corn oil and cellulose (COC; high in omega-6 fatty acids) and then acutely exposed to 0.5-Gy 56Fe or 2.0-Gy gamma-radiation. Mice fed the FOP diet exhibited consistent reductions in serum TNF-α in the 56Fe experiment but not the gamma-experiment. The percentage osteocytes (%Ot) positive for TNF-α increased in gamma-exposed COC, but not FOP, mice. Minimal changes in %Ot positive for sclerostin were observed. FOP mice exhibited modest improvements in several measures of cancellous microarchitecture and volumetric bone mineral density (BMD) postexposure to 56Fe and gamma-radiation. Reduced serum TNF-α in FOP mice exposed to 56Fe was associated with either neutral or modestly positive changes in bone structural integrity. Collectively, these data are generally consistent with previous findings that dietary intake of omega-3 fatty acids may effectively mitigate systemic inflammation after acute radiation exposure and facilitate maintenance of BMD during spaceflight in humans.NEW & NOTEWORTHY This is the first investigation, to our knowledge, to test the impact of a diet high in omega-3 fatty acids on multiple bone structural and biological outcomes following space-relevant radiation exposure. Novel in biological outcomes is the assessment of osteocyte responses to this stressor. These data also add to the growing evidence that low-dose exposures to even high-energy ion species like 56Fe may have neutral or even small positive impacts on bone.

Beyond acute stroke: Rate of stroke transfers to a tertiary centre following the implementation of a dedicated inpatient teleneurology network.

INTRODUCTION: This study evaluated the impact of establishing an inpatient teleneurology consultation service alongside an already established telestroke network on the stroke transfers to the hub. The study also aimed to assess the financial impact of establishing this network. METHODS: Prospectively collected data on all stroke patients evaluated through our telestroke and teleneurology networks between January 2008 and March 2018 were interrogated. For all spokes (eight sites) that had both teleneurology and telestroke services, we compared the rate of transfers to the hub before and after the establishment of the teleneurology network in August 2014. The cost reduction was estimated using the Medicare 5% standard analytic files. RESULTS: A total of 4296 stroke patients were evaluated during the study period. Of these, 2493 were seen before and 1803 were seen after the implementation of the teleneurology network at the included sites. Patients in the pre-teleneurology group were older (66.4 years (SD = 14.7 years) vs. 67.8 years (SD = 15.1 years); p = 0.002). Otherwise, there were no differences in baseline characteristics. Patients in the pre-teleneurology group were more likely to be transferred to the telestroke hub (29.4% vs. 20.2%; p < 0.001). The estimated mean cost reduction for each one minus the cost of transfer was estimated to be US$4997. DISCUSSION: The implementation of an inpatient teleneurology network was associated with a significant reduction in the transfer rate of stroke patients to hospitals with a higher level of care and could lead to a significant cost reduction.

Outcomes of interfacility helicopter transportation in acute stroke care.

OBJECTIVE: To evaluate the long-term functional outcome of interhospital transfer of patients with stroke with suspected large vessel occlusion (LVO) using Helicopter Emergency Medical Services (HEMS). METHODS: Records of consecutive patients evaluated through 2 telestroke networks and transferred to thrombectomy-capable stroke centers between March 2017 and March 2018 were reviewed. Inverse probability of treatment weighting (IPTW) using the propensity score was performed to address confounding factors. Multivariate logistic regression analysis with IPTW was used to determine whether HEMS were associated with good long-term functional outcome (modified Rankin scale score ≤ 2). RESULTS: A total of 199 patients were included; median age was 67 years (interquartile range [IQR] 55-79 years), 90 (45.2%) were female, 120 (60.3%) were white, and 100 (50.3%) were transferred by HEMS. No significant differences between the 2 groups were found in mean age, sex, race, IV tissue plasminogen activator (tPA) receipt, and thrombectomy receipt. The median baseline NIH Stroke Scale score was 14 (IQR 9-18) in the helicopter group vs 11 (IQR 6-18) for patients transferred by ground (p = 0.039). The median transportation time was 60 minutes (IQR 49-70 minutes) by HEMS and 84 minutes (IQR 25-102 minutes) by ground (p < 0.001). After weighting baseline characteristics, the use of HEMS was associated with higher odds of good long-term outcome (OR 4.738, 95% CI 2.15-10.444, p < 0.001) controlling for transportation time, door-in-door-out time, and thrombectomy and tPA receipt. The magnitude of the HEMS effect was larger in thrombectomy patients who had successful recanalization (OR 1.758, 95% CI 1.178-2.512, p = 0.027). CONCLUSIONS: HEMS use was associated with better long-term functional outcome in patients with suspected LVO, independently of transportation time.

Erratum: Deficiency of complement factor H-related proteins and autoantibody-positive hemolytic uremic syndrome in an infant with combined partial deficiencies and autoantibodies to complement factor H and ADAMTS13.

[This corrects the article DOI: 10.1093/ckj/sfy010.].

Production and control of coagulation proteins for factor X activation in human endothelial cells and fibroblasts.

Human endothelial cells (ECs) synthesize, store, and secrete von Willebrand factor multimeric strings and coagulation factor (F) VIII. It is not currently known if ECs produce other coagulation factors for active participation in coagulation. We found that 3 different types of human ECs in primary culture produce clotting factors necessary for FX activation via the intrinsic (FVIII-FIX) and extrinsic (tissue factor [TF]-FVII) coagulation pathways, as well as prothrombin. Human dermal fibroblasts were used as comparator cells. TF, FVII, FIX, FX, and prothrombin were detected in ECs, and TF, FVII, FIX, and FX were detected in fibroblasts. In addition, FVII, FIX, FX, and prothrombin were detected by fluorescent microscopy in EC cytoplasm (associated with endoplasmic reticulum and Golgi proteins). FX activation occurred on human umbilical vein EC surfaces without the addition of external coagulation proteins, proteolytic enzymes, or phospholipids. Tumour necrosis factor, which suppresses the generation of activated protein C and increases TF, augmented FX activation. Fibroblasts also produced TF, but (in contrast to ECs) were incapable of activating FX without the exogenous addition of FX and had a marked increase in FX activation following the addition of both FX and FVII. We conclude that human ECs produce their own coagulation factors that can activate cell surface FX without the addition of exogenous proteins or phospholipids.

Teleneurology Network to Improve Access to Neurologists for Patients in Rural Areas: A Real-World Experience.

Background: The need for neurologists has been steadily increasing over the past few years. The implementation of teleneurology networks could serve as a potential solution to this need. Methods: A retrospective review of the Medical University of South Carolina (MUSC) Teleneurology records for all consults performed between August 2014 and July 2018 was conducted. Collected data included number of consults, baseline characteristics, final diagnosis, and number of providers and hospitals over the study period. Results: A total of 4,542 Teleneurology consults were performed during the study period. The most common diagnosis was cerebrovascular disease, followed by seizure disorders. The number of consults per month increased throughout the study period from three in August 2014 to 257 in July 2018. The number of community hospitals covered has increased from 3 hospitals in August 2014 to 14 hospitals throughout the state of South Carolina in July 2018. Conclusion: Over 4 years, the MUSC teleneurology program has evolved into a robust partnership with 14 partner hospitals, and is now delivering more than 250 expert neurology consultations monthly to patients throughout the state of South Carolina.

Functional Outcomes of Intravenous Thrombolysis in Octogenarians and Nonagenarians Through Telestroke: Single-Center Experience.

Background: Patients aged ≥80 years are often underrepresented in stroke trials. Observational studies have shown that older patients have worse outcomes compared with younger patients, but outcomes in patients aged ≥80 years treated with intravenous (IV)-alteplase specifically through telestroke (TS) have not been studied. Aim: To compare clinical and safety outcomes in stroke patients aged ≥80 and 60-79 years treated with IV-alteplase via TS. Methods: The Medical University of South Carolina TS database was analyzed to identify IV-alteplase-treated patients aged 60-79 and ≥80 years between January 2015 and March 2018. Baseline demographics and TS-specific variables were compared. Clinical outcomes were assessed using the 90-day modified Rankin Scale (mRS). Safety outcomes were evaluated by comparing symptomatic intracranial hemorrhage (sICH). Multivariate logistic regression analysis was performed to determine odds ratio (OR) for good outcome (mRS 0-2) in the older age group at 90 days. Results: IV-alteplase was used in 151 patients in ≥80 years age group and 273 patients in 60-79 years age group. The older age group had more women and a higher National Institutes of Health Stroke Scale. The mean "ED-door-to-TS-consultant-login" time was shorter (21.6 min vs. 25.6 min; p = 0.048), but "TS-consultant-login-to-alteplase" time was longer (22.1 min vs. 19.3 min; p = 0.01) in the older age group. No difference was noted in eventual "door-to-needle" time. The older age group had fewer good outcomes (39.1% vs. 74%; p = 0.001) and more deaths (38% vs. 14%; p = 0.001) at 90 days. The sICH rates were similar in the two groups. The OR for good outcome in ≥80 years age group was 0.20 (95% CI: 0.12-0.34) after controlling for baseline variables. Conclusions: Stroke patients aged ≥80 years treated via TS have similar post-thrombolysis hemorrhage rates but worse clinical outcomes compared with patients aged 60-79 years.