Inclusive Approaches for Measuring Demographics of Underrepresented Populations in STEM and Biomedical Research Training Programs.

As federal strategic plans prioritize increasing diversity within the biomedical workforce, and STEM training and outreach programs seek to recruit and retain students from historically underrepresented populations, there is a need for interrogation of traditional demographic descriptors and careful consideration of best practices for obtaining demographic data. To accelerate this work, equity-focused researchers and leaders from STEM programs convened to examine approaches for measuring demographic variables. Gender, race/ethnicity, disability, and disadvantaged background were prioritized given their focus by federal funding agencies. Categories of sex minority, sexual (orientation) minority, and gender minority (SSGM) should be included in demographic measures collected by STEM programs, consistent with recommendations from White House Executive Orders and federal reports. Our manuscript offers operationalized phrasing for demographic questions and recommendations for use across student-serving programs. Inclusive demographics permit the identification of individuals who are being excluded, marginalized, or improperly aggregated, increasing capacity to address inequities in biomedical research training. As trainees do not enter training programs with equal access, accommodations, or preparation, inclusive demographic measures can welcome trainees and inform a nuanced set of program outcomes that facilitate research on intersectionality to support the recruitment and retention of underrepresented students in biomedical research.

An Assessment of the Potential Economic Impacts of the Invasive Polyphagous Shot Hole Borer (Coleoptera: Curculionidae) in South Africa.

Studies addressing the economic impacts of invasive alien species are biased towards ex-post assessments of the costs and benefits of control options, but ex-ante assessments are also required to deal with potentially damaging invaders. The polyphagous shot hole borer Euwallacea fornicatus (Coleoptera: Curculionidae) is a recent and potentially damaging introduction to South Africa. We assessed the potential impact of this beetle by working across economic and biological disciplines and developing a simulation model that included dynamic mutualistic relations between the beetle and its symbiotic fungus. We modeled the potential growth in beetle populations and their effect on the net present cost of damage to natural forests, urban trees, commercial forestry, and the avocado industry over 10 yr. We modeled high, baseline, and low scenarios using discount rates of 8, 6, and 4%, and a plausible range of costs and mortality rates. Models predicted steady growth in the beetle and fungus populations, leading to average declines in tree populations of between 3.5 and 15.5% over 10 yr. The predicted net present cost was 18.45 billion international dollars (Int. $), or about 0.66% of the country's GDP for our baseline scenario ($2.7 billion to $164 billion for low and high scenarios). Most of the costs are for the removal of urban trees that die as a result of the beetle and its fungal symbiont, as has been found in other regions. We conclude that an ex-ante economic assessment system dynamics model can be useful for informing national strategies on invasive alien species management.

Fungal Planet description sheets: 400-468.

Novel species of fungi described in the present study include the following from Australia: Vermiculariopsiella eucalypti, Mulderomyces natalis (incl. Mulderomyces gen. nov.), Fusicladium paraamoenum, Neotrimmatostroma paraexcentricum, and Pseudophloeospora eucalyptorum on leaves of Eucalyptus spp., Anungitea grevilleae (on leaves of Grevillea sp.), Pyrenochaeta acaciae (on leaves of Acacia sp.), and Brunneocarpos banksiae (incl. Brunneocarpos gen. nov.) on cones of Banksia attenuata. Novel foliicolous taxa from South Africa include Neosulcatispora strelitziae (on Strelitzia nicolai), Colletotrichum ledebouriae (on Ledebouria floridunda), Cylindrosympodioides brabejum (incl. Cylindrosympodioides gen. nov.) on Brabejum stellatifolium, Sclerostagonospora ericae (on Erica sp.), Setophoma cyperi (on Cyperus sphaerocephala), and Phaeosphaeria breonadiae (on Breonadia microcephala). Novelties described from Robben Island (South Africa) include Wojnowiciella cissampeli and Diaporthe cissampeli (both on Cissampelos capensis), Phaeotheca salicorniae (on Salicornia meyeriana), Paracylindrocarpon aloicola (incl. Paracylindrocarpon gen. nov.) on Aloe sp., and Libertasomyces myopori (incl. Libertasomyces gen. nov.) on Myoporum serratum. Several novelties are recorded from La Réunion (France), namely Phaeosphaeriopsis agapanthi (on Agapanthus sp.), Roussoella solani (on Solanum mauritianum), Vermiculariopsiella acaciae (on Acacia heterophylla), Dothiorella acacicola (on Acacia mearnsii), Chalara clidemiae (on Clidemia hirta), Cytospora tibouchinae (on Tibouchina semidecandra), Diaporthe ocoteae (on Ocotea obtusata), Castanediella eucalypticola, Phaeophleospora eucalypticola and Fusicladium eucalypticola (on Eucalyptus robusta), Lareunionomyces syzygii (incl. Lareunionomyces gen. nov.) and Parawiesneriomyces syzygii (incl. Parawiesneriomyces gen. nov.) on leaves of Syzygium jambos. Novel taxa from the USA include Meristemomyces arctostaphylos (on Arctostaphylos patula), Ochroconis dracaenae (on Dracaena reflexa), Rasamsonia columbiensis (air of a hotel conference room), Paecilomyces tabacinus (on Nicotiana tabacum), Toxicocladosporium hominis (from human broncoalveolar lavage fluid), Nothophoma macrospora (from respiratory secretion of a patient with pneumonia), and Penidiellopsis radicularis (incl. Penidiellopsis gen. nov.) from a human nail. Novel taxa described from Malaysia include Prosopidicola albizziae (on Albizzia falcataria), Proxipyricularia asari (on Asarum sp.), Diaporthe passifloricola (on Passiflora foetida), Paramycoleptodiscus albizziae (incl. Paramycoleptodiscus gen. nov.) on Albizzia falcataria, and Malaysiasca phaii (incl. Malaysiasca gen. nov.) on Phaius reflexipetalus. Two species are newly described from human patients in the Czech Republic, namely Microascus longicollis (from toenails of patient with suspected onychomycosis), and Chrysosporium echinulatum (from sole skin of patient). Furthermore, Alternaria quercicola is described on leaves of Quercus brantii (Iran), Stemphylium beticola on leaves of Beta vulgaris (The Netherlands), Scleroderma capeverdeanum on soil (Cape Verde Islands), Scleroderma dunensis on soil, and Blastobotrys meliponae from bee honey (Brazil), Ganoderma mbrekobenum on angiosperms (Ghana), Geoglossum raitviirii and Entoloma kruticianum on soil (Russia), Priceomyces vitoshaensis on Pterostichus melas (Carabidae) (Bulgaria) is the only one for which the family is listed, Ganoderma ecuadoriense on decaying wood (Ecuador), Thyrostroma cornicola on Cornus officinalis (Korea), Cercophora vinosa on decorticated branch of Salix sp. (France), Coprinus pinetorum, Coprinus littoralis and Xerocomellus poederi on soil (Spain). Two new genera from Colombia include Helminthosporiella and Uwemyces on leaves of Elaeis oleifera. Two species are described from India, namely Russula intervenosa (ectomycorrhizal with Shorea robusta), and Crinipellis odorata (on bark of Mytragyna parviflora). Novelties from Thailand include Cyphellophora gamsii (on leaf litter), Pisolithus aureosericeus and Corynascus citrinus (on soil). Two species are newly described from Citrus in Italy, namely Dendryphiella paravinosa on Citrus sinensis, and Ramularia citricola on Citrus floridana. Morphological and culture characteristics along with ITS nrDNA barcodes are provided for all taxa.

The importance of pollinators and autonomous self-fertilisation in the early stages of plant invasions: Banksia and Hakea (Proteaceae) as case studies.

Reproduction is a crucial stage in the naturalisation of introduced plant species. Here, using breeding system experiments and observations of floral visitors, we investigate whether a lack of pollinators or an inability to autonomously self-fertilise limits naturalisation in five Australian Banksia species and the co-familial Hakea salicifolia in South Africa. Banksia species were heavily utilised by native insects and nectar-feeding birds. Although Banksia produced fruit when pollinators were excluded, pollinators significantly increased seed set in four of the five species. H. salicifolia flowers were visited by 11 insect species; honeybees (Apis mellifera) were the main visitors. Flowers in naturalised H. salicifolia populations received almost four times the number of visits as flowers in non-naturalised populations; the latter showed both pollen limitation (PLI 0.40) and partial self-incompatibility. This should not prevent invasion, since H. salicifolia produces fruits via autonomous selfing in the absence of pollinators. The results suggest a limited role of breeding systems in mediating naturalisation of introduced Proteaceae species. Other factors, such as features of the recipient environments, appear to be more important. Spatial variation in rates of reproduction might, however, explain variation in the extent and rate of naturalisation of different populations.

Fungal Planet description sheets: 371-399.

Novel species of fungi described in the present study include the following from Australia: Neoseptorioides eucalypti gen. & sp. nov. from Eucalyptus radiata leaves, Phytophthora gondwanensis from soil, Diaporthe tulliensis from rotted stem ends of Theobroma cacao fruit, Diaporthe vawdreyi from fruit rot of Psidium guajava, Magnaporthiopsis agrostidis from rotted roots of Agrostis stolonifera and Semifissispora natalis from Eucalyptus leaf litter. Furthermore, Neopestalotiopsis egyptiaca is described from Mangifera indica leaves (Egypt), Roussoella mexicana from Coffea arabica leaves (Mexico), Calonectria monticola from soil (Thailand), Hygrocybe jackmanii from littoral sand dunes (Canada), Lindgomyces madisonensis from submerged decorticated wood (USA), Neofabraea brasiliensis from Malus domestica (Brazil), Geastrum diosiae from litter (Argentina), Ganoderma wiiroense on angiosperms (Ghana), Arthrinium gutiae from the gut of a grasshopper (India), Pyrenochaeta telephoni from the screen of a mobile phone (India) and Xenoleptographium phialoconidium gen. & sp. nov. on exposed xylem tissues of Gmelina arborea (Indonesia). Several novelties are introduced from Spain, namely Psathyrella complutensis on loamy soil, Chlorophyllum lusitanicum on nitrified grasslands (incl. Chlorophyllum arizonicum comb. nov.), Aspergillus citocrescens from cave sediment and Lotinia verna gen. & sp. nov. from muddy soil. Novel foliicolous taxa from South Africa include Phyllosticta carissicola from Carissa macrocarpa, Pseudopyricularia hagahagae from Cyperaceae and Zeloasperisporium searsiae from Searsia chirindensis. Furthermore, Neophaeococcomyces is introduced as a novel genus, with two new combinations, N. aloes and N. catenatus. Several foliicolous novelties are recorded from La Réunion, France, namely Ochroconis pandanicola from Pandanus utilis, Neosulcatispora agaves gen. & sp. nov. from Agave vera-cruz, Pilidium eucalyptorum from Eucalyptus robusta, Strelitziana syzygii from Syzygium jambos (incl. Strelitzianaceae fam. nov.) and Pseudobeltrania ocoteae from Ocotea obtusata (Beltraniaceae emend.). Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa.

Assessment of the impact on crop protection by the "cut-off criteria" in a new regulation for authorisation of plant protection products.

In January 2009, European Parliament agreed a draft Regulation to replace Council Directive 91/414/EEC. This Regulation, originally proposed in July 2006, maintained risk assessment but also introduced the concept of hazard assessment or 'cut-off criteria' for the approval of active substances. Pesticides Safety Directorate (PSD) conducted a series of three impact assessments of the potential effects on active substance availability and agronomy of the initial proposals for the Regulation and of the text agreed in January 2009. Since publication of the first assessment (May 2008) and through the second reading, therehas been a substantive amelioration of many of the proposals. An assessment by PSD of the agreed (but not yet adopted) Regulation (PSD, 2009) indicated that between 26 and 50 active substances are considered most likely to be lost as a result. This paper briefly identifies the potential impact of the original proposals for a new Regulation and of the final Regulation as agreed in January 2009.

A biome-scale assessment of the impact of invasive alien plants on ecosystem services in South Africa.

This paper reports an assessment of the current and potential impacts of invasive alien plants on selected ecosystem services in South Africa. We used data on the current and potential future distribution of 56 invasive alien plant species to estimate their impact on four services (surface water runoff, groundwater recharge, livestock production and biodiversity) in five terrestrial biomes. The estimated reductions in surface water runoff as a result of current invasions were >3000 million m(3) (about 7% of the national total), most of which is from the fynbos (shrubland) and grassland biomes; the potential reductions would be more than eight times greater if invasive alien plants were to occupy the full extent of their potential range. Impacts on groundwater recharge would be less severe, potentially amounting to approximately 1.5% of the estimated maximum reductions in surface water runoff. Reductions in grazing capacity as a result of current levels of invasion amounted to just over 1% of the potential number of livestock that could be supported. However, future impacts could increase to 71%. A 'biodiversity intactness index' (the remaining proportion of pre-modern populations) ranged from 89% to 71% for the five biomes. With the exception of the fynbos biome, current invasions have almost no impact on biodiversity intactness. Under future levels of invasion, however, these intactness values decrease to around 30% for the savanna, fynbos and grassland biomes, but to even lower values (13% and 4%) for the two karoo biomes. Thus, while the current impacts of invasive alien plants are relatively low (with the exception of those on surface water runoff), the future impacts could be very high. While the errors in these estimates are likely to be substantial, the predicted impacts are sufficiently large to suggest that there is serious cause for concern.

Coronary vasa vasorum neovascularization precedes epicardial endothelial dysfunction in experimental hypercholesterolemia.

OBJECTIVE: Experimental hypercholesterolemia is associated with vasa vasorum neovascularization, unknown to occur before or after initial lesion formation. Thus, this study was performed to determine the temporal course of neovascularization of coronary vasa vasorum in relation to endothelial dysfunction, a hallmark of early atherosclerosis. METHODS: Female domestic pigs were fed a normal diet (Group 1), a hypercholesterolemic diet for 2 and 4 weeks (Group 2), or a hypercholesterolemic diet for 6 and 12 weeks (Group 3). In vitro analysis of relaxation response to bradykinin served as an index for epicardial endothelial function. Spatial pattern and density of coronary vasa vasorum were assessed by three-dimensional microscopic computed tomography. RESULTS: Relaxation response of coronary arteries to bradykinin was normal in both Group 1 (93+/-6%) and Group 2 (89+/-7%) but impaired in Group 3 (71+/-11%; P<0.05 vs. Group 1 and 2). In contrast, density of coronary vasa vasorum was significantly higher in both Group 2 (4.88+/-2.45 per-mm(2)) and Group 3 (4.50+/-1.37 per-mm(2)) compared to Group 1 (2.97+/-1.37 per-mm(2); P<0.05 vs. Group 2 and 3). CONCLUSION: This study demonstrates that coronary vasa vasorum neovascularization occurs within the first weeks of experimental hypercholesterolemia and prior to the development of endothelial dysfunction of the host vessel, suggesting a role for vasa vasorum neovascularization in the initial stage of atherosclerotic vascular disease.

Analysis of the TGF beta functional pathway in epithelial ovarian carcinoma.

Epithelial ovarian carcinoma is often diagnosed at an advanced stage of disease and is the leading cause of death from gynaecological neoplasia. The genetic changes that occur during the development of this carcinoma are poorly understood. It has been proposed that IGFIIR, TGFbeta1 and TGFbetaRII act as a functional unit in the TGFbeta growth inhibitory pathway, and that somatic loss-of-function mutations in any one of these genes could lead to disruption of the pathway and subsequent loss of cell cycle control. We have examined these 3 genes in 25 epithelial ovarian carcinomas using single-stranded conformational polymorphism analysis and DNA sequence analysis. A total of 3 somatic missense mutations were found in the TGFbetaRII gene, but none in IGFRII or TGFbeta1. An association was found between TGFbetaRII mutations and histology, with 2 out of 3 clear cell carcinomas having TGFbetaRII mutations. This data supports other evidence from mutational analysis of the PTEN and beta-catenin genes that there are distinct developmental pathways responsible for the progression of different epithelial ovarian cancer histologic subtypes.

Biliary PAH metabolites and EROD activity in flounder (Platichthys flesus) from a contaminated estuarine environment.

The present study in the Firth of Forth, Scotland, emphasises the usefulness of biliary metabolite measurements in estuarine monitoring using the flounder (Platichthys flesus). The short time scale (a few hours) of response to polycyclic aromatic hydrocarbon (PAH) exposure, allowed clearer interpretation of trends and differences between sites. Such differences and trends in the metabolite data were not as apparent from 7-ethoxyresorufin O-deethlyation (EROD) activity measurements, which were likely to have been blurred by the movements of flounder between sites. Statistical differences were not observed in EROD activity in flounder from the Firth of Forth (ANOVA, P = 0.065). The biliary metabolites showed statistical differences between the uppermost site of Longannet and Port Edgar, in the outer Firth, for both the 1-OH pyrene and 2-OH naphthalene metabolites (ANOVA, Tukeys, P = 0.012 and 0.022 respectively). There was also a significant correlation between the concentrations of all three individual metabolites (1-OH pyrene, 2-OH naphthalene, I-OH phenanthrene) and the log of the distance downstream from the major PAH input sources of Longannet power station and Grangemouth. Biliary PAH metabolites were shown to better reflect local contamination gradients than EROD activity. This is explained by the relative response times of the two biomarkers and local movements of the flounder in the estuary.

Plant invasions--the role of mutualisms.

Many introduced plant species rely on mutualisms in their new habitats to overcome barriers to establishment and to become naturalized and, in some cases, invasive. Mutualisms involving animal-mediated pollination and seed dispersal, and symbioses between plant roots and microbiota often facilitate invasions. The spread of many alien plants, particularly woody ones, depends on pollinator mutualisms. Most alien plants are well served by generalist pollinators (insects and birds), and pollinator limitation does not appear to be a major barrier for the spread of introduced plants (special conditions relating to Ficus and orchids are described). Seeds of many of the most notorious plant invaders are dispersed by animals, mainly birds and mammals. Our review supports the view that tightly coevolved, plant-vertebrate seed dispersal systems are extremely rare. Vertebrate-dispersed plants are generally not limited reproductively by the lack of dispersers. Most mycorrhizal plants form associations with arbuscular mycorrhizal fungi which, because of their low specificity, do not seem to play a major role in facilitating or hindering plant invasions (except possibly on remote islands such as the Galapagos which are poor in arbuscular mycorrhizal fungi). The lack of symbionts has, however, been a major barrier for many ectomycorrhizal plants, notably for Pinus spp. in parts of the southern hemisphere. The roles of nitrogen-fixing associations between legumes and rhizobia and between actinorhizal plants and Frankia spp. in promoting or hindering invasions have been virtually ignored in the invasions literature. Symbionts required to induce nitrogen fixation in many plants are extremely widespread, but intentional introductions of symbionts have altered the invasibility of many, if not most, systems. Some of the world's worst invasive alien species only invaded after the introduction of symbionts. Mutualisms in the new environment sometimes re-unite the same species that form partnerships in the native range of the plant. Very often, however, different species are involved, emphasizing the diffuse nature of many (most) mutualisms. Mutualisms in new habitats usually duplicate functions or strategies that exist in the natural range of the plant. Occasionally, mutualisms forge totally novel combinations, with profound implications for the behaviour of the introduced plant in the new environment (examples are seed dispersal mutualisms involving wind-dispersed pines and cockatoos in Australia; and mycorrhizal associations involving plant roots and fungi). Many ecosystems are becoming more susceptible to invasion by introduced plants because: (a) they contain an increasing array of potential mutualistic partners (e.g. generalist frugivores and pollinators, mycorrhizal fungi with wide host ranges, rhizobia strains with infectivity across genera); and (b) conditions conductive for the establishment of various alien/alien synergisms are becoming more abundant. Incorporating perspectives on mutualisms in screening protocols will improve (but not perfect) our ability to predict whether a given plant species could invade a particular habitat.

Insulin and insulin-like growth factor-I cause vasorelaxation in human vessels in vitro.

BACKGROUND: Insulin and insulin-like growth factor-I (IGF-I) are endogenous peptides with vasoactive activities. OBJECTIVE: To evaluate the vasodilatory effects of insulin and IGF-I on human vessels taken from patients with and without noninsulin-dependent diabetes mellitus (NIDDM) and to elucidate their mechanisms of action. METHODS: Vascular rings of human internal mammary artery (IMA) and saphenous vein harvested from 54 patients with and without NIDDM undergoing coronary bypass surgery were studied in vitro. RESULTS: For samples from patients without NIDDM both insulin and IGF-I (10(-12)-10(-7) mol/l) evoked greater relaxation in IMA rings (30 +/- 4 and 29 +/- 6%, maximal relaxation +/- SEM, respectively) than they did in saphenous-vein rings (43 +/- 4 and 42 +/- 5%, respectively, P < 0.05 both for insulin and for IGF-I). Similar results were obtained with vessels from patients with NIDDM. Relaxation was not affected by the removal of the endothelium and by inhibition of the production of nitric oxide. However, the vascular relaxation caused by insulin and IGF-I was completely abolished by KCI, and was attenuated by the nonspecific potassium-channel blocker tetraethylammonium (for IMA rings, to 77 +/- 8 and 66 +/- 4% with insulin and IGF-I, respectively; for saphenous vein rings, 73 +/- 2 and 77 +/- 1% for insulin and IGF-I, respectively, P < 0.001). CONCLUSIONS: Both insulin and IGF-I induced endothelial-independent, nitric oxide-independent vasorelaxation of rings from human IMA and saphenous veins, through a mechanism involving activation of potassium channels. This response remained intact in vessels from patients with NIDDM. This result supports the hypothesis that insulin and IGF-I play roles in the regulation of vascular tone in human vessels.

Attenuated in vitro coronary arteriolar vasorelaxation to insulin-like growth factor I in experimental hypercholesterolemia.

Insulin and insulin-like growth factor (IGF) 1 affect coronary vasoactivity. Experimental hypercholesterolemia is associated with coronary atherogenesis and altered vasomotor regulation. Because the IGF axis is altered during atherogenesis, we postulated that experimental hypercholesterolemia is associated with an altered coronary vasoactive response to IGF-1 in vitro. Coronary arteries and arterioles from pigs fed either a normal or high-cholesterol diet for 10 weeks were contracted with endothelin-1 and relaxed with cumulative concentrations of insulin or IGF-1 (10(-12) to 10(-7) mol/L). Control arterioles were also incubated with the nitric oxide synthase inhibitor 10(-4) mol/L N(G)-monomethyl-L-arginine (L-NMMA) or the potassium channel blocker 10(-2) mol/L tetraethylammonium (TEA), contracted with endothelin-1, and relaxed with insulin or IGF-1. Experimental hypercholesterolemia (1) increased serum cholesterol (9.5+/-1.0 versus 1.9+/-0.08 mmol/L; P<0.0001), (2) caused coronary arterial and arteriolar endothelial dysfunction in vitro (attenuated vasorelaxation to bradykinin), (3) did not alter the epicardial response to either insulin (P=0.80) or IGF-1 (P=0.12), and (4) significantly attenuated the arteriolar response to IGF-1 (maximal relaxation of 79+/-6% versus 42+/-8%; P=0.01) but not insulin (43+/-6% versus 53+/-7%; P=0.99). Control arteriolar vasorelaxation to IGF-1 was attenuated by both L-NMMA (P<0.001) and TEA (P=0.01), whereas only L-NMMA attenuated insulin (P<0.001). Staining for IGF-1 and IGF binding protein 2 was increased (P<0.05) in arterioles of cholesterol-fed pigs. IGF-1 and insulin are therefore coronary arteriolar vasorelaxants through different mechanisms. Experimental hypercholesterolemia is associated with resistance to the coronary arteriolar vasorelaxing effects of IGF-1 but not insulin, in conjunction with increased ligand and binding-protein expression. The IGF axis may contribute to the altered coronary vasoactivity in hypercholesterolemia.

Enhanced coronary vasoconstriction to oxidative stress product, 8-epi-prostaglandinF2 alpha, in experimental hypercholesterolemia.

OBJECTIVES: The F2-isoprostanes are a family of novel prostaglandin isomers and a stable product of in vivo oxidative stress. 8-epi-prostaglandinF2 alpha, a member of this isoprostane family, is a vasoconstrictor and its local release may contribute to the abnormal vasomotor tone associated with hypercholesterolemia. We therefore aimed to outline the role of 8-epi-prostaglandinF2 alpha as a coronary vasoconstrictor in experimental hypercholesterolemia. METHODS AND RESULTS: Pigs were randomized to two experimental groups (each n = 9): normal (N) and high cholesterol (HC) diet. To determine the vasoconstrictive effects of 8-epi-prostaglandinF2 alpha in vitro, doses from 10(-9) to 10(-5) M were used to constrict coronary epicardial rings. Plasma total and LDL cholesterol levels were significantly higher in the HC group compared with the N group (P < 0.005) as were plasma 8-epi-prostaglandinF2 alpha levels (P < 0.001). 8-epi-prostaglandinF2 alpha immunoreactivity was present in the vessel wall in both groups. Normal vessels with intact endothelium (n = 8 rings) contracted to 8-epi-prostaglandinF2 alpha (maximal contraction 15.5 +/- 8.74%). In the HC group, rings with intact endothelium had a greater contractile response to 8-epi-prostaglandinF2 alpha compared to normals (72.3 +/- 7.9%; n = 8; P < 0.0001). This was reversed by preincubation with NOR-3, a NO donor (maximal contraction 6.7 +/- 1.56%; n = 5; P < 0.0001). Enhanced contraction in normal vessels occurred with endothelial denudation (98.4 +/- 3.56%; n = 6; P < 0.0001) and with preincubation of the endothelium-intact rings with L-NMMA (N-monomethyl-L-arginine), an NO synthase inhibitor (85.5 +/- 10.3%, n = 6, P < 0.001). The enhanced contraction seen with hypercholesterolemia did not occur with other prostanoid vasoconstrictors. CONCLUSION: Experimental hypercholesterolemia leads to a significant increase in 8-epi-prostaglandinF2 alpha levels in addition to enhanced 8-epi-prostaglandinF2 alpha-induced coronary vasoconstriction, in vitro. These findings support a role for the F2-isoprostanes in the regulation of coronary vasomotor tone in pathophysiologic states.

Insulin and IGF-I attenuate the coronary vasoconstrictor effects of endothelin-1 but not of sarafotoxin 6c.

OBJECTIVE: To examine the hypothesis that insulin and insulin-like growth factor I (IGF-I) attenuate endothelin-induced contraction of porcine coronary epicardial arteries in vitro. BACKGROUND: Endothelin-induced coronary vasoconstriction is mediated by two types of receptors, A (ETA) and B (ETB), resulting in calcium influx. Both insulin and IGF-I attenuate endothelin-induced calcium influx into porcine coronary artery smooth muscle. METHODS: Epicardial arteries harvested from juvenile pigs were contracted with cumulative concentrations of endothelin-1 (ETA- and ETB-receptor agonist; 10(-10)-10(-6) M) or of sarafotoxin-6c (ETB-receptor agonist; 10(-11)-10(-7) M). In additional experiments, endothelin-1 or sarafotoxin-6c were added after incubation with 10(-8) M regular insulin or IGF-I. These experiments were repeated in vessels without endothelium. Contraction for each vessel was calculated relative to the response to 60 mM KCl. RESULTS: The maximal contractions to endothelin-1 in vessels with and without endothelium were 158 +/- 8 and 200 +/- 21%, respectively (p < 0.05 at 10(-8.5)-10(-6.5) M). Both insulin (at 10(-7)-10(-6) M) and IGF-I (at 10(-6.5)-10(-6) M) attenuated the contraction to endothelin-1 in vessels with intact endothelium, as well as in vessels without endothelium (at 10(-7) and 10(-6) M for insulin and 10(-7.5)-10(-6) M for IGF-I). The maximal contractions to sarafotoxin-6c in vessels with and without endothelium were 54 +/- 13 and 84 +/- 7%, respectively (p < 0.05 at 10(-9), 10(-8.5) and 10(-7) M). Insulin and IGF-I did not affect the response to sarafotoxin-6c in vessels with and without endothelium. CONCLUSION: Insulin and IGF-I attenuated ETA-receptor-mediated coronary contraction through an endothelium-independent mechanism. The IGF axis may serve as an endogenous modulator of endothelin-mediated vasoconstriction.

Insulin and insulin-like growth factor-I cause coronary vasorelaxation in vitro.

Insulin and insulin-like growth factor-I (IGF-I) may play a role in the modulation of coronary artery tone, yet there are few data regarding their vasoactive effects on the coronary vascular bed. We evaluated the vasorelaxation effects of insulin and IGF-I on porcine coronary epicardial vessels in vitro and elucidated possible mechanisms. Porcine epicardial arteries were contracted with 10(-7) mol/L endothelin-1 and relaxed with cumulative concentrations of either insulin or IGF-I (10(-12) to 10(-7) mol/L). The above experiments were repeated in vessels without endothelium. Vessels were also incubated with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 10(-4) mol/L) with and without 10(-3.5) mol/L L-arginine, the potassium channel blocker tetraethylammonium (TEA; 10(-2) mol/L), and the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ; 10(-5.5) mol/L); vessels were then contracted with endothelin-1 and relaxed with insulin or IGF-I. Insulin and IGF-I were also added after contraction with 60 mmol/L KCl. Insulin and IGF-I caused a similar decrease in coronary epicardial tension after contraction with endothelin-1 (relaxation of 28+/-4% [n=7] and 25+/-3% [n=8] with insulin and IGF-I, respectively; P<0.0001 for both peptides). Removal of the endothelium did not affect these responses. Incubation with L-NMMA, but not ODQ, attenuated the vasorelaxation response to insulin and IGF in vessels without endothelium. L-Arginine did not reverse this effect of L-NMMA. KCl and TEA attenuated the vasorelaxation effect of both insulin and IGF-I. Thus, both insulin and IGF-I caused non-endothelium-dependent coronary vasorelaxation in vitro, probably through a mechanism involving the activation of potassium channels. These findings suggest that insulin and IGF-I participate in the regulation of coronary vasomotor tone.

Technical and economic feasibility of reusing disposable perfusion cannulas.

OBJECTIVE(S): The reuse of disposable devices is a potential source of significant cost savings to hospitals. Venous and arterial perfusion cannulas under new and reused conditions were selected to identify the clinical, safety, technical, logistic, and economic issues that must be addressed to realize these savings. METHODS: Single- and dual-stage venous and arterial cannulas from two manufacturers were tested when new, after initial clinical use, and after a single clinical use plus up to nine simulated reuses. Reuse was simulated by end-to-end bending, coupling and uncoupling of the connectors, and by two 1-hour soaks in plasma at 4 degrees and 40 degrees C, respectively. Cannulas were decontaminated and then processed by a peracetic acid-based liquid chemical sterilization system after each use/reuse. Sterilization was validated by eliminating Bacillus subtilis spores from the cannulas on each of five consecutive cycles. Cannulas were tested for physical changes, functional integrity, biocompatibility, and in vivo performance in sheep. A cost analysis was also performed. RESULTS: Sterilization was successfully achieved. Mechanical changes were less than 20% on all variables studied and were undetectable by experienced cardiac surgeons in selective evaluation. No clinically important differences were found between new and reused cannulas, even after nine simulated reuses. Reusing cannulas four times would reduce the cost per procedure from $53 to $19 (64%). CONCLUSIONS: Preliminary data suggest that the perfusion cannulas tested can be safely and efficaciously used five times. Limited reuse of these disposable cannulas is technically feasible and cost-effective. Cannula reuse would result in a small incremental savings; however, with more expensive devices and higher-volume sterilization procedures, the savings could be considerably greater. This program provides a model for evaluation of other single-use medical devices for reuse.

Technical and economic feasibility of reusing disposable perfusion cannulae.

The reuse of disposable devices is a potential source of significant cost savings to hospitals. Venous and arterial perfusion cannulae under new and reused conditions were selected to identify the clinical, safety, technical, logistic, and economic issues that must be addressed to realize these savings. Single- and dual-stage venous and arterial cannulae from two manufacturers were tested when new, after initial clinical use, and after a single clinical use plus up to nine simulated reuses. Reuse was simulated by end-to-end bending, coupling and uncoupling the connectors, and by two 1-hour soaks in plasma at 4 degrees C and 40 degrees C, respectively. Cannulae were decontaminated and then sterilized by a peracetic acid based liquid chemical sterilization system following each use/reuse. Sterilization was validated by eliminating Bacillus subtilis spores from the cannulae on each of five consecutive cycles. Cannulae were tested for physical changes, functional integrity, biocompatibility, and in vivo performance in sheep. A cost minimization analysis was also performed. No clinically important differences were found between new and reused cannulae, even after nine simulated reuses. Mechanical changes were less than 20% on all variables studied and were undetectable by experienced cardiac surgeons in selective evaluation. Sterilization was successfully achieved. Reusing cannulae for times would reduce the cost per procedure from $53 to $19 (64%). Perfusion cannulae tested can be safely and efficaciously used five times. This study suggests that reuse would result in a small incremental savings; however, with more expensive devices and higher-volume sterilization procedures, the savings could be exponentially greater. Although this study demonstrates that it may be technically feasible and cost-effective to reuse disposable cannulae, the U.S. Food and Drug Administration does not sanction the reuse of disposable cannulae.

Genetic risk factors in inflammatory abdominal aortic aneurysms: polymorphic residue 70 in the HLA-DR B1 gene as a key genetic element.

PURPOSE: Evidence of a genetic predisposition to the development of inflammatory abdominal aortic aneurysms (AAAs) exists as a positive family history in 17% of patients. Familial clustering and other similarities between inflammatory AAAs and giant cell arteritis (GCA), which possesses a genetic risk determinant mapped to the HLA-DR molecule, suggest a role of genetic risk factors in inflammatory AAAs. The purpose of this study was to explore whether patients with inflammatory AAAs express disease-relevant genes associated with the HLA-DR region on the short arm of chromosome 6. METHODS: Thirty-seven patients with histomorphologic findings of inflammatory AAA at operation were genotyped for the polymorphism of the HLA-DR B1 and HLA DQ B1 alleles and compared to ethnically matched, healthy control subjects (n = 90). RESULTS: Distribution of HLA-DR B1 alleles was nonrandom in patients with inflammatory AAAs versus control subjects. The HLA-DR B1 alleles B1*15 and B1*0404 were enriched in patients with inflammatory AAAs compared with control subjects (47% versus 27%, and 14% versus 3%; p < 0.05, respectively). Analysis of functionally relevant amino acid polymorphisms encoded by the HLA-DR B1 gene showed relevance at amino acid position 70. HLA-DR B1 alleles overrepresented in patients with inflammatory AAAs express a glutamine substitution at position 70, whereas alleles disfavored in the patient cohort express a negatively charged aspartic acid. Distribution of HLA-DQ B1 alleles were indistinguishable in patients and control subjects. CONCLUSION: These data indicate that a genetic risk determinant can be mapped to the HLA-DR B1 locus in patients with inflammatory AAAs. This association suggests a critical contribution of antigen binding in the pathogenesis of this disease.

Endemic cross-infection in an acute medical ward.

Urine samples from patients on an acute medical ward were examined each week over a three-month period in order to detect endemic cross colonization or infection. The bed positions for each patient in the ward were recorded continuously and the patients cared for by each different nurse team noted. We found an outbreak of urinary colonization/infection with a strain of Klebsiella K8 in nine patients. Two groups of two patients probably suffered cross colonization/infection with different strains of Escherichia coli. These episodes were not detected by our routine laboratory ward liaison surveillance, but by the weekly samples and molecular typing methods applied to these relatively common strains. This survey demonstrates that cross colonization/infection may occur more widely than is normally detected. The implications of these findings to surveillance audit programmes are discussed.