Abstract Background Bioabsorbable cardiac matrix (BCM) is a novel device that attenuates adverse left ventricular (LV) remodeling after large myocardial infarctions in experimental models. Objectives ...This study aimed to analyze whether BCM, compared with saline control, would result in less LV dilation and fewer adverse clinical events between baseline and 6 months. Methods In an international, randomized, double-blind, controlled trial, 303 subjects with large areas of infarction despite successful primary percutaneous coronary intervention (PCI) of ST-segment elevation myocardial infarction (STEMI) were randomized 2:1 to BCM or saline injected into the infarct-related artery 2 to 5 days after primary PCI. The primary outcome was mean change from baseline in LV end-diastolic volume index (LVEDVI) at 6 months. Secondary outcomes included change in Kansas City Cardiomyopathy Questionnaire score, 6-minute walk time, and New York Heart Association functional class at 6 months. The primary safety endpoint was a composite of cardiovascular death, recurrent MI, target-vessel revascularization, stent thrombosis, significant arrhythmia requiring therapy, or myocardial rupture through 6 months. Results In total, 201 subjects were assigned to BCM and 102 to saline control. There was no significant difference in change in LVEDVI from baseline to 6 months between the groups (mean change ± SD: BCM 14.1 ± 28.9 ml/m2 vs. saline 11.7 ± 26.9 ml/m2 ; p = 0.49). There was also no significant difference in the secondary endpoints. The rates of the primary safety outcome were similar between the 2 groups (BCM 11.6% vs. saline 9.1%; p = 0.37). Conclusions Intracoronary deployment of BCM 2 to 5 days after successful reperfusion in subjects with large myocardial infarction did not reduce adverse LV remodeling or cardiac clinical events at 6 months. (IK-5001 for the Prevention of Remodeling of the Ventricle and Congestive Heart Failure After Acute Myocardial Infarction PRESERVATION I; NCT01226563 )
Climate Change and the Integrity of Science Sills, Jennifer
Science (American Association for the Advancement of Science),
05/2010, Letnik:
328, Številka:
5979
Journal Article
Background: The objective of this systematic evaluation was to identify the sentinel standards necessary to obtain a core level of communication required of a clinical perfusionist during ...cardiopulmonary bypass (CPB). Once these sentinel standards were identified and a core level of communication was established (via four simulated case scenarios), a team of cardiac healthcare professionals was assembled to interpret both the accuracy of response and the speed of response encountered in each case scenario.
Methods: Four simulated case scenarios were utilized in order to replicate the typical patterns of verbal exchange that occur during surgeries using extracorporeal technology. The simulated case scenarios included CPB interactions associated with preparation, initiation, maintenance, termination and post CPB. For all CPB interactions, two variables were measured: accuracy of the perfusionist’s response and speed of the perfusionist’s response. The cases took place in a controlled setting within an empty operating room at The Children’s Hospital of Philadelphia. Four clinical perfusionists each represented the role of the “perfusionist” in all simulated case scenarios.
Results: When analyzing the accuracy and speed of the responses, each clinical perfusionist recorded an average score of 96.3% or higher with all case scenarios. Since the clinical perfusionists who participated in the scenarios were primarily pediatric perfusionists, the scores were best during the pediatric case scenario, 99.3% (Case Scenario #4). The lowest scores were captured during Case Scenario #3 (96.3%) which involved a more intense adult patient scenario.
Conclusion: The systematic evaluation of both response accuracy and response time (presented in various adult and pediatric patient case scenarios) can be beneficial within the realm of perfusion education. Students will be introduced to core communication concepts within the clinical realm. This study supports the idea that simulation and evaluation may ease the transition for students from the didactic to clinical realm in terms of communication. Further studies need to be developed in order to define “standard” CPB communication guidelines for perfusion students.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The West Siberian Lowland (WSL) contains the world's most extensive peatlands and a substantial fraction of the global terrestrial carbon pool. Despite its recognition as a carbon reservoir of great ...significance, the extent, thickness, and carbon content of WSL peatlands have not been analyzed in detail. This paper compiles a wide array of data into a geographic information system (GIS) to create a high‐resolution, spatially explicit digital inventory of all WSL peatlands and their associated physical properties. Detailed measurements for nearly 10,000 individual peatlands (patches) are based on compilation of previously unpublished Russian field and ancillary map data, satellite imagery, previously published depth measurements, and our own field depth and core measurements taken throughout the region during field campaigns in 1999, 2000, and 2001. At the patch level, carbon storage is estimated as the product of peatland area, depth, and carbon content. Estimates of peatland area are validated from RESURS‐01 satellite images, and the quality of the Russian peatland depth and carbon content data is independently confirmed by laboratory analysis of core samples. Through GIS‐based spatial analysis of the peat areal extent, depth, and carbon content data, we conservatively estimate the total area of WSL peatlands at 592,440 km2, the total peat mass at 147.82 Pg, and the total carbon pool at 70.21 Pg C. Our analysis concludes that WSL peatlands are more extensive and represent a substantially larger carbon pool than previously thought: Previous studies report 9,440–273,440 km2 less peatland area and 15.11–30.19 Pg less carbon than found in this analysis. The complete digital database is freely available for scientific use at http://arcss.colorado.edu/data/arcss131.html.
The submarine Amsterdam‐St. Paul (ASP) Plateau, bisected by the Southeast Indian Ridge (SEIR), is a bathymetric high rising ∼2 km above the surrounding seafloor that includes the islands of Amsterdam ...and St. Paul; this excess volcanism is attributed to a mantle hot spot. We obtained new Sr, Nd, and Pb (n = 37) and He isotopic (n = 10) ratios for basalt glasses from 11 SEIR segments on and adjacent to the plateau and from three seamounts on the plateau. The results show systematic spatial variations in these isotopic ratios that correlate with physical segmentation of the ridge. Specifically, lavas from the four ridge segments on the ASP Plateau have higher 208Pb/204Pb at a given 206Pb/204Pb than SEIR basalts distant from ASP Plateau. Surprisingly, lavas from the ridge segment 100 km north of the ASP Plateau are distinguished by the most radiogenic 206Pb/204Pb (up to 19.4) and highest 3He/4He ratios (up to 14.1 RA). These are characteristics of lavas erupted at Amsterdam and St Paul Islands. The isotopic data for SEIR basalts erupted on or adjacent to the ASP Plateau provide equivocal evidence for a mantle component derived from the distant Kerguelen hot spot. Overall, the Pb‐Nd‐Sr‐He isotope variations within this data set are explained well by three mantle end‐members: (1) depleted mantle having relatively low 206Pb/204Pb and 87Sr/86Sr and high 143Nd/144Nd, which has been variably mixed with (2) material having relatively high 208Pb/204Pb and 87Sr/86Sr and low 143Nd/144Nd, a signature commonly ascribed to detached or eroded metasomatized continental lithosphere, and (3) hot spot–related mantle having elevated 3He/4He and 206Pb/204Pb but intermediate 87Sr/86Sr and 143Nd/144Nd, similar to the common or C material observed in hot spots globally. These results suggest either that the ASP hot spot is isotopically heterogeneous or that the shallow mantle or lithosphere beneath the ASP Plateau contains more continentally derived material than the SEIR mantle ≥500 km away. Perhaps, like the 39°–41°E section of the Southwest Indian Ridge, beneath the ASP Plateau there are rafts of continental material stranded within a local “tectonic corridor,” possibly present since the opening of the Indian Ocean basin.
Women are often reported to be generally more resistant to fatigue than men for relative-intensity tasks. This has been observed repeatedly for elbow flexors, whereas at the ankle, sex differences ...appear less robust, suggesting localized rather than systemic influences. Thus, the purpose of this study was to examine sex differences in fatigue resistance at muscle groups in a single cohort and which factors, if any, predict endurance time.
Thirty-two young adults (age = 19-44 yr, 16 women) performed sustained isometric contractions at 50% maximum voluntary isometric contraction to failure for elbow flexion and ankle dorsiflexion. Pain, exertion, and muscle EMG were assessed throughout. Self-reported baseline activity was measured using the International Physical Activity Questionnaire.
Women were significantly more resistant to fatigue than men at the elbow (112.3 ± 6.2 vs 80.3 ± 5.8 s, P = 0.001) but not at the ankle (140.6 ± 10.7 vs 129.2 ± 10.5 s, P = 0.45). Peak torque was greater in men than that in women (P < 0.0001) at the ankle (45.0 ± 1.7 vs 30.1 ± 1.0 N·m) and at the elbow (75.7 ± 3.1 vs 34.4 ± 2.2 N·m). Peak torque was significantly related to endurance time at the elbow (R2= 0.30) but not at the ankle (R2 = 0.03). Peak pain, rate of pain increase, peak exertion, EMG, and baseline physical activity did not differ between sexes.
Sex differences in fatigue resistance are muscle group specific. Women were more fatigue resistant at the elbow but not at the ankle during a sustained isometric contraction. Further, factors that may contribute to fatigue resistance for one muscle group (e.g., sex, peak torque) may not be critical at another.
Lysine 2,3-aminomutase (LAM) catalyzes the interconversion of l-lysine and l-β-lysine, by a radical mechanism initiated by the reversible, reductive homolytic scission of the C5‘−S bond in ...S-adenosylmethionine (SAM) to form methionine and the 5‘-deoxyadenosyl radical at the active site. LAM is a member of a superfamily of enzymes in which a 4Fe-4S+ cluster with a unique, noncysteinyl coordinated Fe provides the electron required in the cleavage of SAM. Little is known of the mechanism by which the electron is inserted into SAM, and it is not known whether all enzymes of the family employ the same mechanism. Selenium X-ray absorption spectroscopy (XAS) in the reaction of Se-adenosyl-l-selenomethionine (SeSAM) in place of SAM shows that electron transfer occurs by an inner sphere mechanism culminating in direct ligation of selenomethionine to iron upon cleavage of SeSAM. Here, we report an electron nuclear double resonance (ENDOR) spectroscopic investigation of LAM to which has been bound 14N, 17O, 2H, or 13C labeled SAM. It is found that LAM exhibits the same motif for SAM binding to the 4Fe-4S+,2+ clusters as does pyruvate formate lyase: chelation by the unique iron of the amino and carboxylato groups of SAM; close proximity of the methionine methyl group to the cluster. However, there appear to be significant, and possibly mechanistically important, differences in the details of the binding geometry of SAM. On the basis of the correlation of the ENDOR and XAS spectroscopic results, we postulate a mechanism by which LAM cleaves SAM to generate an intermediate where N, O, and S of the methionine product are bound to the octahedrally coordinated unique Fe of the 4Fe-4S cluster.
Abstract Objective In men with prolactinomas, an impaired bone density is the principle consequence of hyperprolactinemia-induced hypogonadism. While dopamine (DA-) agonists are the first-line ...approach in prolactinomas, surgery can be considered in selected cases. In the present study, we aimed to investigate on the long-term control of hyperprolactinemia, hypogonadism and bone health comparing primary medical and surgical therapy in men who had not had prior DA-agonist treatment. Methods Retrospective case-note study of 44 consecutive men with prolactinomas and no prior DA-agonists managed in a single tertiary referral center. Clinical, biochemical and radiological response to the first-line approach were analyzed in the two cohorts. Results Mean age at diagnosis was 47 years (range 22-78). The prevalence of hypogonadism was 86%, and 27% of patients had pathological bone density at baseline. The primary therapeutic strategy was surgery for 34% and DA-agonists for 66% of patients. Median long-term follow-up was 63 months (range 17-238). Long-term control of hyperprolactinemia required DA-agonists in 53% of patients with primary surgical therapy, versus 90% of patients with primary medical therapy (p=.02). Hypogonadism was controlled in 73% of patients. The prevalence of patients with pathological bone density was 37% at last follow-up, with no differences between the two therapeutic cohorts (p=.48). Conclusions Despite control of hyperprolactinemia and hypogonadism in the majority of patients independent of the primary treatment modality, the prevalence of an impaired bone health status remains high, and osteodensitometry should be recommended.
A powerful and potentially general approach to the targeting and crystallization of proteins on lipid interfaces through coordination of surface histidine residues to lipid-chelated divalent metal ...ions is presented. This approach, which should be applicable to the crystallization of a wide range of naturally occurring or engineered proteins, is illustrated here by the crystallization of streptavidin on a monolayer of an iminodiacetate-Cu(II) lipid spread at the air-water interface. This method allows control of the protein orientation at interfaces, which is significant for the facile production of highly ordered protein arrays and for electron density mapping in structural analysis of two-dimensional crystals. Binding of native streptavidin to the iminodiacetate-Cu lipids occurs via His-87, located on the protein surface near the biotin binding pocket. The two-dimensional streptavidin crystals show a previously undescribed microscopic shape that differs from that of crystals formed beneath biotinylated lipids.