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The reduction of substrates catalyzed by nitrogenase normally requires nucleotide-dependent Fe protein delivery of electrons to the MoFe protein, which contains the active site FeMo cofactor. Here, it is reported that independent substitution of three amino acids (β-98(Tyr→His), α-64(Tyr→His), and β-99(Phe→His)) located between the P cluster and FeMo cofactor within the MoFe protein endows it with the ability to reduce protons to H2, azide to ammonia, and hydrazine to ammonia without the need for Fe protein or ATP. Instead, electrons can be provided by the low-potential reductant polyaminocarboxylate-ligated Eu(II) (Em values of -1.1 to -0.84 V vs the normal hydrogen electrode). The crystal structure of the β-98(Tyr→His) variant MoFe protein was determined, revealing only small changes near the amino acid substitution that affect the solvent structure and the immediate vicinity between the P cluster and the FeMo cofactor, with no global conformational changes observed. Computational normal-mode analysis of the nitrogenase complex reveals coupling in the motions of the Fe protein and the region of the MoFe protein with these three amino acids, which suggests a possible mechanism for how Fe protein might communicate subtle changes deep within the MoFe protein that profoundly affect intramolecular electron transfer and substrate reduction.

The objective was to evaluate whether long-term addition of 3-nitrooxypropanol (NOP) to a beef cattle diet results in a sustained reduction in enteric CH4 emissions in beef cattle. Eight ruminally cannulated heifers (637 ± 16.2 kg BW) were used in a completely randomized design with 2 treatments: Control (0 g/d of NOP) and NOP (2 g/d of NOP). Treatments were mixed by hand into the total mixed ration (60% forage, DM basis) at feeding time. Feed offered was restricted to 65% of ad libitum DMI (slightly over maintenance energy intake) and provided once per day. The duration of the experiment was 146 d, including an initial 18-d covariate period without NOP use; a 112-d treatment period with NOP addition to the diet, divided into four 28-d time intervals (d 1 to 28, 29 to 56, 57 to 84, and 85 to 112); and a final 16-d recovery period without NOP use. During the covariate period and at the end of each interval and the end of the recovery period, CH4 was measured for 3 d using whole animal metabolic chambers. The concentration of VFA was measured in rumen fluid samples collected 0, 3, and 6 h after feeding, and the microbial population was evaluated using rumen samples collected 3 h after feeding on d 12 of the covariate period, d 22 of each interval within the treatment period, and d 8 of the recovery period. Average DMI for the experiment was 7.04 ± 0.27 kg. Methane emissions were reduced by 59.2% when NOP was used (9.16 vs. 22.46 g/kg DMI; P < 0.01). Total VFA concentrations were not affected (P = 0.12); however, molar proportion of acetate was reduced and that for propionate increased when NOP was added (P < 0.01), which reduced the acetate to propionate ratio (3.0 vs. 4.0; P < 0.01). The total copy number of the 16S rRNA gene of total bacteria was not affected (P = 0.50) by NOP, but the copy number of the 16S rRNA gene of methanogens was reduced (P < 0.01) and the copy number of the 18S rRNA gene of protozoa was increased (P = 0.03). The residual effect of NOP for most of the variables studied was not observed or was minimal during the recovery period. These results demonstrated that the addition of NOP to a diet for beef cattle caused a sustained decrease of methanogenesis, with no sign of adaptation, and that these effects were reversed once NOP addition was discontinued

Introduction: The care of premature infants requires specific, suitable parenteral nutrition, in which the dosage must be frequently adjusted., Method: A comparative analysis of four industrial standard parenteral nutrition formulations NP 100®, Pediaven AP-HP Nouveau-né 1®, Pediaven AP-HP Nouveau-né 2® and Numetah G13% E® and of two hospital preparations made specifically in hospital pharmacies produced by two separate university hospitals (Nutrine® HCL and Formule standardisée début de nutrition) was conducted. The comparison between the formulations focused on electrolytic compositions and protein/energy ratio., Results: Formule standardisée début de nutrition and Pediaven AP-HP Nouveau-né 1® are free from (i) sodium and potassium, (ii) potassium respectively. Almost equivalent sodium concentration (19-27 mM) and more variable potassium concentration (∼9-26 mM) characterize the other formulations. Protein/energy ratio of Numetah G13% E®, Nutrine® HCL and Formule standardisée début de nutrition is 58% higher than that of NP 100®, Pediaven AP-HP Nouveau-né 1® and Pediaven AP-HP Nouveau-né 2®., Discussion: Formule standardisée début de nutrition and Pediaven AP-HP Nouveau-né 1® are in accordance with the recommendations about hydro-electrolytic supplies during transition phase. Nutrine® HCL complies best to the recommendations about hydro-electrolytic account during stabilization phase., Conclusion: Hydro-electrolytic composition and protein/energy ratio of standard hospital parenteral nutrition formulations comply best to nutritional needs of premature infants., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Administrative data have been used to identify patients with various diseases, yet no prior study has determined the utility of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based codes to identify CLI patients. CLI cases (n=126), adjudicated by a vascular specialist, were carefully defined and enrolled in a hospital registry. Controls were frequency matched to cases on age, sex and admission date in a 2:1 ratio. ICD-9-CM codes for all patients were extracted. Algorithms were developed using frequency distributions of these codes, risk factors and procedures prevalent in CLI. The sensitivity for each algorithm was calculated and applied within the hospital system to identify CLI patients not included in the registry. Sensitivity ranged from 0.29 to 0.92. An algorithm based on diagnosis and procedure codes exhibited the best overall performance (sensitivity of 0.92). Each algorithm had differing CLI identification characteristics based on patient location. Administrative data can be used to identify CLI patients within a health system. The algorithms, developed from these data, can serve as a tool to facilitate clinical care, research, quality improvement, and population surveillance., (© The Author(s) 2014.)

Background: The safety of β-blockers in patients with isolated right ventricular failure because of pulmonary arterial hypertension (PAH) is unclear., Methods and Results: We studied 564 PAH patients (total cohort) referred to our center from 1982 to 2013. Propensity score-matching was used to match pairs of PAH patients with and without β-blocker use (matched cohort). We compared all-cause mortality between the groups in the total cohort and the matched cohort using bootstrap validation, Kaplan-Meier, and Cox proportional hazard analyses. Seventy-one of the 564 patients in the total cohort were on β-blockers. They were older, had higher prevalence of comorbidities, and were more often on diuretics, digoxin, and angiotensin converting enzyme inhibitors. The severity of PAH and right ventricular failure was similar between those with and without β-blocker use. After propensity matching, 63 patients with β-blocker use were compared with 51 patients without β-blocker use. During a median follow-up time of 4.8 years, there were 339 (60%) deaths in the total cohort and 70 deaths (61%) in the matched cohort. There was no difference in absolute mortality between those with and without β-blockers (P=0.71). β-Blocker use was not associated with increased all-cause mortality in the total cohort after adjusting for propensity score (adjusted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5) and in the matched cohort (hazard ratio, 1.2; 95% confidence interval, 0.8-2.0)., Conclusions: There was no statistically significant difference in long-term mortality between propensity score-matched pairs of PAH patients with and without β-blocker use. These findings need further validation in prospective clinical trials., (© 2014 American Heart Association, Inc.)

Background: Atrial fibrillation (AF) is associated with increased risk of hospitalization. Little is known about the impact of AF on utilization of noninpatient health care or about sex or race differences in AF-related utilization. We examined rates of inpatient and outpatient utilization by AF status in the Atherosclerosis Risk in Communities study., Methods and Results: Participants with incident AF enrolled in fee-for-service Medicare for at least 12 continuous months between 1991 and 2009 (n=932) were matched on age, sex, race and field center with up to 3 participants without AF (n=2729). Healthcare utilization was ascertained from Medicare claims and classified by primary International Classification of Diseases, ninth revision code. The average annual numbers of days hospitalized were 13.2 (95% CI 11.6 to 15.0) and 2.8 (95% CI 2.5 to 3.1) for those with and without AF, respectively. The corresponding numbers of annual outpatient claims were 53.3 (95% CI 50.5 to 56.3) and 22.9 (95% CI 22.1 to 23.8) for those with and without AF, respectively. Most utilization among AF patients was attributable to non-AF conditions. The adjusted rate ratio for annual days hospitalized for other cardiovascular disease-related reasons was 4.58 (95% CI: 3.41 to 6.16) for those with AF versus those without AF. The association between AF and healthcare utilization was similar among men and women and among white and black participants., Conclusions: Participants with AF had considerably greater healthcare utilization, and the difference in utilization for other cardiovascular disease-related reasons was substantial. In addition to rate or rhythm treatment, AF management should focus on the accompanying cardiovascular comorbidities., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Introduction: Severe pre-transplant pulmonary hypertension (PH) has been associated with adverse short-term clinical outcomes after heart transplantation in relatively small single-center studies. The impact of pre-transplant PH on long-term survival after heart transplantation has not been examined in a large, multi-center cohort., Methods: Adults (≥18 years) who underwent first time heart transplantation in the United States between 1987 and 2012 were retrospectively identified from the United Network for Organ Sharing registry. Pre-transplant PH was classified as mild, moderate, or severe based on pulmonary vascular resistance (PVR), trans-pulmonary gradient (TPG), and pulmonary artery (PA) mean pressure. Primary outcome was all-cause mortality., Results: Data from 26,649 heart transplant recipients (mean age 52±12 years; 76% male; 76% Caucasian) were analyzed. During a mean follow-up of 5.7±4.8 years, there were 10,334 (39%) deaths. Pre-transplant PH (PVR≥2.5 WU) was a significant predictor of mortality (hazard ratio 1.10, 95% confidence interval 1.05-1.14, p<0.0001) in multivariable analysis. However, the severity of pre-transplant PH (mild/moderate vs. severe) did not affect short or long-term survival. Similarly, even in patients who were supported with either a left ventricular assist device or a total artificial heart prior to transplant, severe pre-transplant PH was not associated with worse survival when compared to patients with mild/moderate pre-transplant PH., Conclusion: Pre-transplant PH (PVR≥2.5 WU) is associated with a modest increase in mortality when compared to patients without pre-transplant PH. However, the severity of pre-transplant PH, assessed by PVR, TPG, or mean PA pressure, is not a discriminating factor for poor survival in patients listed for heart transplantation., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Advanced heart failure teams are often faced with the decision of whether or not to offer a left ventricular assist device (LVAD) to patients who have end-stage heart failure and recent or ongoing substance abuse. The outcomes of these patients after LVAD implantation are unknown., Methods: Baseline predictors and outcomes were collected and analyzed from patients with active substance abuse and a cohort of patients without active substance abuse matched for age, INTERMACS profile and year of implantation. The primary outcome was all-cause mortality. Secondary outcomes included rates of listing for cardiac transplantation, transplantation and chronic drive-line infection., Results: The cohort consisted of 20 consecutive LVAD recipients with active substance abuse and 40 recipients without active substance abuse. During a median follow-up period of 2.3 years (IQR 1.4 to 3.6), the substance abuse group had 3.2 times the rate (hazard) of death compared with a matched cohort (HR 3.2, 95% CI 1.2 to 8.0, p < 0.05). Furthermore, the rate of listing for transplant was 69% lower (rate ratio 0.31, p < 0.0005), rate of cardiac transplant was 89% lower (rate ratio 0.11, p < 0.0005), and risk of chronic drive-line infection was 5.4 times higher (rate ratio 5.4, p < 0.0005) in the substance abuse group., Conclusions: Active substance abuse in patients who received an LVAD was associated with increased mortality and overall poor outcomes. Larger scale data will be needed to confirm these findings and to inform decision-making in this population., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Peripheral artery disease (PAD) is a major cause of cardiovascular ischemic events and amputation. Knowledge gaps exist in defining and measuring key factors that predict these events. The objective of this study was to assess whether duration of limb ischemia would serve as a major predictor of limb and patient survival., Methods: The FReedom from Ischemic Events: New Dimensions for Survival (FRIENDS) registry enrolled consecutive patients with limb-threatening peripheral artery disease at a single tertiary care hospital. Demographic information, key clinical care time segments, functional status and use of revascularization, and pharmacotherapy data were collected at baseline, and vascular ischemic events, cardiovascular mortality, and all-cause mortality were recorded at 30 days and 1 year., Results: A total of 200 patients with median (interquartile range) age of 76 years (65-84 years) were enrolled in the registry. Median duration of limb ischemia was 0.75 days for acute limb ischemia (ALI) and 61 days for chronic critical limb ischemia (CLI). Duration of limb ischemia of <12, 12 to 24, and >24 hours in patients with ALI was associated with much higher rates of first amputation (P = .0002) and worse amputation-free survival (P = .037). No such associations were observed in patients with CLI., Conclusions: For individuals with ischemic symptoms <14 days, prolonged limb ischemia is associated with higher 30-day and 1-year amputation, systemic ischemic event rates, and worse amputation-free survival. No such associations are evident for individuals with chronic CLI. These data imply that prompt diagnosis and revascularization might improve outcomes for patients with ALI., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Critical limb ischemia (CLI) represents the most severe clinical manifestation of peripheral arterial disease (PAD) and is the major cause of ischemic amputation in the United States. Risk factors and the associated incidence and prevalence of CLI have not been well described in the general population. This study describes the risk factors for PAD progression to CLI and estimates the annual incidence and prevalence of CLI in a representative United States patient cohort., Methods: This was a retrospective cohort analysis of adults with commercial, Medicare supplemental, or Medicaid health insurance who had at least one PAD or CLI health care claim from January 1, 2003, through December 31, 2008, and 12 months of continuous coverage. Two subgroups of CLI presentation were identified: primary CLI (patients without any prior PAD or subsequent PAD diagnostic code >30 days after CLI diagnostic code) and secondary CLI (patients with prior PAD or subsequent PAD diagnostic codes ≤30 days of a CLI diagnostic code). Patterns of presentation, annual incidence, and prevalence of CLI were stratified by health care plan. Risk factors for progression to CLI were compared by presentation type., Results: From 2003 to 2008, the mean annual incidence of PAD was 2.35% (95% confidence interval [CI], 2.34%-2.36%) and the incidence of CLI was 0.35% (95% CI, 0.34%-0.35%) of the eligible study population, with primary and secondary presentations occurring at similar rates. The mean annualized prevalence of PAD was 10.69% (95% CI, 10.67%10.70%) and the mean annualized prevalence of CLI was 1.33% (95% CI, 1.32%-1.34%) of the eligible study population, and two-thirds of the cases presented as secondary CLI. CLI developed in 11.08% (95% CI, 11.30%-11.13%) of patients with PAD. A multivariable model demonstrated that diabetes, heart failure, stroke, and renal failure were stronger predictors of primary rather than secondary CLI presentation., Conclusions: These data establish new national estimates of the incidence and prevalence of CLI and define key risk factors that contribute to primary or secondary presentations of CLI within a very large contemporary insured population cohort in the United States., (Published by Mosby, Inc.)

Atrial fibrillation (AF) frequently coexists in the setting of myocardial infarction (MI), being associated with increased mortality. Nonetheless, temporal trends in the occurrence of AF complicating MI and in the prognosis of these patients are not well described. We examined temporal trends in prevalence of AF in the setting of MI and the effect of AF on prognosis in the community. We studied a population-based sample of 20,049 validated first-incident nonfatal hospitalized MIs among 35- to 74-year old residents of 4 communities in the Atherosclerosis Risk in Communities (ARIC) Study from 1987 through 2009. Prevalence of AF in the setting of MI increased from 11% to 15% during the 23-year study period. The multivariable adjusted odds ratio for prevalent AF, per 5-year increment, was 1.11 (95% confidence interval 1.04 to 1.19). Overall, in patients with MI, AF was associated with increased 1-year case fatality (odds ratio 1.47, 95% confidence interval 1.07 to 2.01) compared with those without AF. However, there was no evidence that the impact of AF on MI survival changed over time or differed over time by sex, race, or MI classification (all p values >0.10). In conclusion, co-occurrence of AF in MI slightly increased between 1987 and 2009. The adverse impact of AF on survival in the setting of MI was consistent throughout. In the setting of MI, co-occurrence of AF should be viewed as a critical clinical event, and treatment needs unique to this population should be explored further., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Superoxide reductase (SOR), a non-heme mononuclear iron protein that is involved in superoxide detoxification in microorganisms, can be used as an unprecedented model to study the mechanisms of O2 activation and of the formation of high-valent iron-oxo species in metalloenzymes. By using resonance Raman spectroscopy, it was shown that the mutation of two residues in the second coordination sphere of the SOR iron active site, K48 and I118, led to the formation of a high-valent iron-oxo species when the mutant proteins were reacted with H2O2. These data demonstrate that these residues in the second coordination sphere tightly control the evolution and the cleavage of the O-O bond of the ferric iron hydroperoxide intermediate that is formed in the SOR active site., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Cardiovascular diseases are the leading causes of disability and death in the United States. Primary prevention of these events may be achieved through aspirin use. The ability of a community-based intervention to increase aspirin use has not been evaluated. The objective of this study was to evaluate an educational intervention implemented to increase aspirin use for primary prevention of cardiovascular disease in a small city in Minnesota., Methods: A community-based intervention was implemented during 16 months in a medium-sized community in Minnesota. Messages for aspirin use were disseminated to individuals, health care professionals, and the general population. Independent cross-sectional samples of residents (men aged 45-79, women aged 55-79) were surveyed by telephone to identify candidates for primary prevention aspirin use, examine their characteristics, and determine regular aspirin use at baseline and after the campaign at 4 months and 16 months., Results: In primary prevention candidates, regular aspirin use rates increased from 36% at baseline to 54% at 4 months (odds ratio = 2.05; 95% confidence interval, 1.09-3.88); the increase was sustained at 52% at 16 months (odds ratio = 1.89; 95% confidence interval, 1.02-3.49). The difference in aspirin use rates at 4 months and 16 months was not significant (P = .77)., Conclusion: Aspirin use rates for primary prevention remain low. A combined public health and primary care approach can increase and sustain primary prevention aspirin use in a community setting.

Aspirin (ASA) is recommended for the prevention of cardiovascular disease; however, the compliance is low. Reported use may not reflect actual use. Serum thromboxane B2 (STxB2) measurement was evaluated to validate reported ASA use. Males aged 45 to 79 years and females aged 55 to 79 years completed a survey and STxB2 measurement (Thromboxane B2 EIA Kit; Cayman Chemical, Ann Arbor, Michigan). The 107 patients were grouped by use of ASA (56 ASA+ and 51 ASA-) and possible interfering medications (INT) such as nonsteroidal anti-inflammatory drugs. The STxB2 levels (ng/mL) were significantly lower in ASA users: ASA+ INT- 3.0 (0.7, 8.4), ASA+ INT+ 2.0 (0.8, 4.9), ASA- INT+ 176 (75, 390), and ASA- INT- 271 (199, 366). The INT use did not cause a significant difference in STxB2 levels. A STxB2 cut point of 25 ng/mL had high sensitivity (94.1%) and specificity (91.1%) for ASA use. The STxB2 was a reliable marker of ASA use and could be used to confirm ASA exposure in population-based health studies.

Objective: Increasingly, epidemiologic studies use administrative data to identify atrial fibrillation (AF). Capture of incident AF is not well documented. We examined incidence rates and concordance of AF diagnosis based on active cohort follow-up versus surveillance of Centers for Medicare and Medicaid Services data in the Atherosclerosis Risk in Communities study., Methods: Atherosclerosis Risk in Communities cohort participants without prevalent AF enrolled in fee-for-service Medicare, with inpatient and outpatient coverage, for at least 12 continuous months between 1991 and 2009 were included. In active Atherosclerosis Risk in Communities study follow-up, annual telephone calls captured hospitalizations and deaths with incident AF diagnosis codes. For Centers for Medicare and Medicaid Services data, incident AF was defined by billed inpatient and outpatient diagnoses., Results: Of 10,134 eligible cohort participants, 738 developed AF according to both Atherosclerosis Risk in Communities and Centers for Medicare and Medicaid Services data; an additional 93 and 288 incident cases were identified using only Atherosclerosis Risk in Communities and Centers for Medicare and Medicaid Services data, respectively. Incidence rates per 1,000 person-years were 10.8 (95% confidence interval: 10.1-11.6) and 13.6 (95% confidence interval: 12.8-14.4) in Atherosclerosis Risk in Communities and Centers for Medicare and Medicaid Services, respectively; agreement was 96%; kappa was 0.77 (95% confidence interval: 0.75-0.80). Earlier AF ascertainment by one system versus the other was not associated with any cardiovascular disease risk factors, after accounting for sociodemographic factors. Additional Centers for Medicare and Medicaid Services events did not alter observed associations between risk factors and AF., Conclusion: Among fee-for-service enrollees, AF incidence rates were slightly lower for active cohort follow-up than for Centers for Medicare and Medicaid Services surveillance, because the latter included outpatient atrial fibrillation. Concordance was high and combining the two approaches could provide a more complete picture of newly-diagnosed AF.

We have advanced a mechanism for nitrogenase catalysis that rests on the identification of a low-spin EPR signal (S = 1/2) trapped during turnover of a MoFe protein as the E4 state, which has accumulated four reducing equivalents as two [Fe-H-Fe] bridging hydrides. Because electrons are delivered to the MoFe protein one at a time, with the rate-limiting step being the off-rate of oxidized Fe protein, it is difficult to directly control, or know, the degree of reduction, n, of a trapped intermediate, denoted En, n = 1-8. To overcome this previously intractable problem, we introduced a quench-cryoannealing relaxation protocol for determining n of an EPR-active trapped En turnover state. The trapped "hydride" state was allowed to relax to the resting E0 state in frozen medium, which prevents additional accumulation of reducing equivalents; binding of reduced Fe protein and release of oxidized protein from the MoFe protein both are abolished in a frozen solid. Relaxation of En was monitored by periodic EPR analysis at cryogenic temperature. The protocol rests on the hypothesis that an intermediate trapped in the frozen solid can relax toward the resting state only by the release of a stable reduction product from FeMo-co. In turnover under Ar, the only product that can be released is H2, which carries two reducing equivalents. This hypothesis implicitly predicts that states that have accumulated an odd number of electrons/protons (n = 1, 3) during turnover under Ar cannot relax to E0: E3 can relax to E1, but E1 cannot relax to E0 in the frozen state. The present experiments confirm this prediction and, thus, the quench-cryoannealing protocol and our assignment of E4, the foundation of the proposed mechanism for nitrogenase catalysis. This study further gives insights into the identity of the En intermediates with high-spin EPR signals, 1b and 1c, trapped under high electron flux.

Two new ligands N,N,N',N'-tetrakis(2-methylbenzoic acid)-1,4-diaminomethylbenzene, 5H4, and N,N,N',N'-tetrakis(2-methylbenzoic acid)-4,4'-diaminomethyldiphenyl, 6H4, carrying four carboxylate groups suitable for bridging dinuclear centers have been prepared and their paddlewheel complexes with copper(II) prepared. The phenyl-bridged ligand 5H4 gives a cyclic octanuclear species [(Cu2)4(5)4], while the diphenyl-bridged ligand 6H4 gives a lantern-like tetranuclear species [(Cu2)2(6)2]; both were characterized by X-ray crystallography. If the amine functions of 5 are protonated, intramolecular hydrogen bonds position the four carboxylates in such a way as to allow formation of the unusual compound [Cu4(5H2)2Cl](3+) in which a Cu4 square centered by a chloro ligand is sandwiched between two (5H2)(2-) ligands. The magnetic properties of this compound have been studied and show antiferromagnetic coupling between adjacent coppers (J = -33.7 cm(-1)).

Background: Long-term marathon running improves many cardiovascular risk factors, and is presumed to protect against coronary artery plaque formation. This hypothesis, that long-term marathon running is protective against coronary atherosclerosis, was tested by quantitatively assessing coronary artery plaque using high resolution coronary computed tomographic angiography (CCTA) in veteran marathon runners compared to sedentary control subjects., Methods: Men in the study completed at least one marathon yearly for 25 consecutive years. All study subjects underwent CCTA, 12-lead electrocardiogram, measurement of blood pressure, heart rate, and lipid panel. A sedentary matched group was derived from a contemporaneous CCTA database of asymptomatic healthy individuals. CCTAs were analyzed using validated plaque characterization software., Results: Male marathon runners (n = 50) as compared with sedentary male controls (n = 23) had increased total plaque volume (200 vs. 126 mm3, p < 0.01), calcified plaque volume (84 vs. 44 mm3, p < 0.0001), and non-calcified plaque volume (116 vs. 82 mm3, p = 0.04). Lesion area and length, number of lesions per subject, and diameter stenosis did not reach statistical significance., Conclusion: Long-term male marathon runners may have paradoxically increased coronary artery plaque volume.

By incorporating two linearly chirped ultrabroadband fiber Bragg gratings of opposite dispersion in an all-fiber ring laser, we demonstrate a mode-locking regime in which a femtosecond pulse evolving in the normal dispersion gain segment is locally transformed into a highly chirped picosecond pulse that propagates in the remaining section of the cavity. By minimizing nonlinear effects and avoiding soliton pulse shaping in this anomalous-dispersion section, low repetition rate fiber lasers can be made to produce high-energy ultrashort pulses. Using this approach, 98 fs pulses with 0.96 nJ of energy are obtained from an erbium-doped fiber laser operated in the highly anomalous dispersion regime at a repetition rate of 9.4 MHz.

Background: In the era of increasing percutaneous treatment options for heart disease, the estimation of surgical risk has become a key factor in selecting optimal treatment strategies. Surgical risk has historically been estimated by physician's subjective assessment and more recently by statistical risk estimates., Methods and Results: We studied 5099 consecutive patients who underwent cardiac surgery at Minneapolis Veterans Affairs Medical Center between 1993 and 2010. Operative mortality risk was estimated statistically by the Veterans Affairs mortality risk estimate and subjectively by cardiac surgeons before surgery. Observed mortality rate was 3.3% (168 deaths) at 1 month, 7.1% (360 deaths) at 1 year, and 18.5% (942 deaths) at 5 years after surgery. Physician's risk estimate (mean [SD], 5.6% [4.4]) and statistical risk estimate (4.3% [5.1]) had modest correlation (c-index, 0.56; P<0.001). Both methods modestly overestimated operative mortality risk. Statistical risk estimate was significantly better than physician's risk estimate in separating patients who died from those who survived at 30 days (c-index, 0.78 versus 0.73; P=0.003), at 1 year (c-index, 0.72 versus 0.61; P<0.001), and at 5 years (c-index, 0.72 versus 0.64; P<0.001) after surgery. Physician's risk estimate was higher than statistical risk estimate in all subgroups except high-risk patients., Conclusions: In patients undergoing cardiac surgery, statistical risk estimate is a better method to predict operative and long-term mortality compared with physician's subjective risk estimate. However, both methods modestly overestimate actual operative mortality risk.

Background: Advanced lower extremity peripheral artery disease (PAD), whether presenting as acute limb ischemia (ALI) or chronic critical limb ischemia (CLI), is associated with high rates of cardiovascular ischemic events, amputation, and death. Past research has focused on strategies of revascularization, but few data are available that prospectively evaluate the impact of key process of care factors (spanning pre-admission, acute hospitalization, and post-discharge) that might contribute to improving short and long-term health outcomes., Methods/design: The FRIENDS registry is designed to prospectively evaluate a range of patient and health system care delivery factors that might serve as future targets for efforts to improve limb and systemic outcomes for patients with ALI or CLI. This hypothesis-driven registry was designed to evaluate the contributions of: (i) pre-hospital limb ischemia symptom duration, (ii) use of leg revascularization strategies, and (iii) use of risk-reduction pharmacotherapies, as pre-specified factors that may affect amputation-free survival. Sequential patients would be included at an index "vascular specialist-defined" ALI or CLI episode, and patients excluded only for non-vascular etiologies of limb threat. Data including baseline demographics, functional status, co-morbidities, pre-hospital time segments, and use of medical therapies; hospital-based use of revascularization strategies, time segments, and pharmacotherapies; and rates of systemic ischemic events (e.g., myocardial infarction, stroke, hospitalization, and death) and limb ischemic events (e.g., hospitalization for revascularization or amputation) will be recorded during a minimum of one year follow-up., Discussion: The FRIENDS registry is designed to evaluate the potential impact of key factors that may contribute to adverse outcomes for patients with ALI or CLI. Definition of new "health system-based" therapeutic targets could then become the focus of future interventional clinical trials for individuals with advanced PAD.

The biological reduction of N2 to NH3 catalyzed by Mo-dependent nitrogenase requires at least eight rounds of a complex cycle of events associated with ATP-driven electron transfer (ET) from the Fe protein to the catalytic MoFe protein, with each ET coupled to the hydrolysis of two ATP molecules. Although steps within this cycle have been studied for decades, the nature of the coupling between ATP hydrolysis and ET, in particular the order of ET and ATP hydrolysis, has been elusive. Here, we have measured first-order rate constants for each key step in the reaction sequence, including direct measurement of the ATP hydrolysis rate constant: kATP = 70 s(-1), 25 °C. Comparison of the rate constants establishes that the reaction sequence involves four sequential steps: (i) conformationally gated ET (kET = 140 s(-1), 25 °C), (ii) ATP hydrolysis (kATP = 70 s(-1), 25 °C), (iii) Phosphate release (kPi = 16 s(-1), 25 °C), and (iv) Fe protein dissociation from the MoFe protein (kdiss = 6 s(-1), 25 °C). These findings allow completion of the thermodynamic cycle undergone by the Fe protein, showing that the energy of ATP binding and protein-protein association drive ET, with subsequent ATP hydrolysis and Pi release causing dissociation of the complex between the Fe(ox)(ADP)2 protein and the reduced MoFe protein.

Background: Thymosin β4 (Tβ4) has been shown to enhance the survival of cultured cardiomyocytes. Here, we investigated whether the cytoprotective effects of Tβ4 can increase the effectiveness of transplanted swine mesenchymal stem cells (sMSCs) for cardiac repair in a rat model of myocardial infarction (MI)., Methods and Results: Under hypoxic conditions, cellular damage (lactate dehydrogenase leakage), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelingc cells), and caspase-8 activity were significantly lower, whereas B-cell lymphoma-extra large protein expression was significantly higher, in sMSCs cultured with Tβ4 (1 μg/mL) than in sMSCs cultured without Tβ4, and Tβ4 also increased sMSC proliferation. For in vivo experiments, animals were treated with basal medium (MI: n=6), a fibrin patch (Patch: n=6), a patch containing sMSCs (sMSC: n=9), or a patch containing sMSCs and Tβ4 (sMSC/Tβ4: n=11); Tβ4 was encapsulated in gelatin microspheres to extend Tβ4 delivery. Four weeks after treatment, echocardiographic assessments of left-ventricular ejection fraction and fractional shortening were significantly better (P<0.05) in sMSC/Tβ4 animals (left-ventricular ejection fraction=51.7 ± 1.1%; fractional shortening=26.7 ± 0.7%) than in animals from MI (39 ± 3%; 19.5 ± 1.7%) and Patch (43 ± 1.4%; 21.6 ± 0.9%) groups. Histological assessment of infarct wall thickness was significantly higher (P<0.05) in sMSC/Tβ4 animals (50%, [45%, 80%]) than in animals from MI (25%, [20%, 25%]) group. Measurements in sMSC (left-ventricular ejection fraction=45 ± 2.6%; fractional shortening=22.9 ± 1.6%; TH = 43% [25%, 45%]), Patch, and MI animals were similar. Tβ4 administration also significantly increased vascular growth, the retention/survival of the transplanted sMSCs, and the recruitment of endogenous c-Kit(+) progenitor cells to the infarcted region., Conclusions: Extended-release Tβ4 administration improves the retention, survival, and regenerative potency of transplanted sMSCs after myocardial injury.

Nitrogenase is an enzyme found in many bacteria and archaea that catalyzes biological dinitrogen fixation, the reduction of N2 to NH3, accounting for the major input of fixed nitrogen into the biogeochemical N cycle. In addition to reducing N2 and protons, nitrogenase can reduce a number of small, non-physiological substrates. Among these alternative substrates are included a wide array of carbon-containing compounds. These compounds have provided unique insights into aspects of the nitrogenase mechanism. Recently, it was shown that carbon monoxide (CO) and carbon dioxide (CO2) can also be reduced by nitrogenase to yield hydrocarbons, opening new insights into the mechanism of small molecule activation and reduction by this complex enzyme as well as providing clues for the design of novel molecular catalysts. This article is part of a Special Issue entitled: Metals in Bioenergetics and Biomimetics Systems., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: There is increasing awareness of adult degenerative or de novo scoliosis, and its surgical treatment when indicated can be challenging and resource intense. Surgical randomized controlled trials are rare, and observational studies pose limitations because of the heterogeneity of surgical practices, techniques, and patient populations. Pooled analysis of current literature may identify effective treatment strategies and guide future efforts at prospective clinical research. This study aimed to synthesize existing data on the outcomes of surgical intervention for adult degenerative scoliosis., Methods: PubMed, Medline, Cochrane, and Web of Science databases were searched using key words and were limited to the English language. Spine surgeons reviewed abstracts and evaluated whether they contained surgically treated cohorts of adults (more than 18 years of age) with degenerative scoliosis. Full-text articles were reviewed in detail and data were abstracted. All meta-analyses were conducted using random effects models and heterogeneity was estimated with I 2 . Random-effects meta-regression models were used to investigate the association of treatment effects with baseline levels of each outcome., Results: Of 482 articles, 24 (n = 805) met inclusion criteria Available outcomes included Cobb angle correction, coronal and sagittal balance, visual analog scale for pain (VAS), and Oswestry Disability Index. Despite significant heterogeneity among studies, random-effects meta-analysis showed significant improvements in Cobb angle (-11.1°; 95% confidence interval [CI], -13.86° to -8.40°), coronal balance (7.674 mm; 95% CI, -10.5 to -4.9), VAS (-3.24; 95% CI, -4.5 to -1.98), and Oswestry Disability Index (-27.18%; 95% CI, -34.22 to -20.15) postoperative treatment (p < .001). Meta-regression models showed that preoperative values for Cobb angle, coronal balance, and VAS were significantly associated with surgical treatment effect (p < .05). Changes in sagittal balance did not reach statistical significance although only 6 articles were included., Conclusions: Exhaustive literature review yielded 24 studies reporting preoperative and postoperative data regarding the surgical treatment of adult degenerative scoliosis. No randomized clinical trials (RCTs) were identified. Despite heterogeneity, a limited meta-analysis showed significant improvement in Cobb angle, coronal balance, and VAS after surgical treatment of adult degenerative scoliosis., (Copyright © 2013 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.)

Background: Hepatic artery stenosis (HAS) is a serious complication of liver transplantation but data on the most effective endovascular management are lacking. We aimed to compare percutaneous balloon angioplasty (PBA) with stent placement., Methods: We searched MEDLINE, Cochrane, Web of Science, EMBASE, SCOPUS, and Biosis Previews between 1970 and December 2011 and performed meta-analysis of short-term (procedural success, complications) and long-term outcomes (liver function, arterial patency, survival, re-intervention, re-transplantation). Random effects models were used for the analysis and meta-regression performed for the year of study., Results: A total of 263 liver transplants in 257 patients [age 43 (±8) years] underwent 147 PBAs and 116 stents. Transplanted livers were from deceased donors in 240 (91 %). Follow-up was 1 month to 4.5 years (median 17 months). PBA and stent had similar procedural success (89 % vs. 98 %), complications (16 % vs. 19 %), normal liver function tests (80 % vs. 68 %), arterial patency (76 % vs. 68 %), survival (80 % vs. 82 %), and requirement for re-intervention (22 % vs. 25 %) or re-transplantation (20 % vs. 24 %) (P non-significant). In the most recent studies re-transplantation was reported less compared to older series (P = 0.04)., Conclusion: Both PBA and stent offer comparable results for HAS. These techniques have contributed to a recent decline in re-transplantation., Key Points: • Interventional radiological procedures are often used to treat post-transplant hepatic artery stenosis. • Meta-analysis shows that percutaneous balloon angioplasty and stent placement are both efficacious. • Percutaneous balloon angioplasty and stent placement appear to have similar complication rates. • Re-transplantation rates have declined, partly due to interventional management for arterial stenosis.

Although at low concentrations, arsenic commonly occurs naturally as a local geological constituent. Whereas both arsenate and arsenite are strongly toxic to life, a number of prokaryotes use these compounds as electron acceptors or donors, respectively, for bioenergetic purposes via respiratory arsenate reductase, arsenite oxidase and alternative arsenite oxidase. The recent burst in discovered arsenite oxidizing and arsenate respiring microbes suggests the arsenic bioenergetic metabolisms to be anything but exotic. The first goal of the present review is to bring to light the widespread distribution and diversity of these metabolizing pathways. The second goal is to present an evolutionary analysis of these diverse energetic pathways. Taking into account not only the available data on the arsenic metabolizing enzymes and their phylogenetical relatives but also the palaeogeochemical records, we propose a crucial role of arsenite oxidation via arsenite oxidase in primordial life. This article is part of a Special Issue entitled: The evolutionary aspects of bioenergetic systems., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Living cells are able to harvest energy by coupling exergonic electron transfer between reducing and oxidising substrates to the generation of chemiosmotic potential. Whereas a wide variety of redox substrates is exploited by prokaryotes resulting in very diverse layouts of electron transfer chains, the ensemble of molecular architectures of enzymes and redox cofactors employed to construct these systems is stunningly small and uniform. An overview of prominent types of electron transfer chains and of their characteristic electrochemical parameters is presented. We propose that basic thermodynamic considerations are able to rationalise the global molecular make-up and functioning of these chemiosmotic systems. Arguments from palaeogeochemistry and molecular phylogeny are employed to discuss the evolutionary history leading from putative energy metabolisms in early life to the chemiosmotic diversity of extant organisms. Following the Occam's razor principle, we only considered for this purpose origin of life scenarios which are contiguous with extant life. This article is part of a Special Issue entitled: The evolutionary aspects of bioenergetic systems., (Copyright © 2012 Elsevier B.V. All rights reserved.)

New oral anticoagulants constitute an important breakthrough for cardiologists and their patients. After reviewing their mechanism of action, their role in the context of interventional cardiology, particularly for patients with acute coronary syndromes, is discussed., (Copyright © 2012. Published by Elsevier SAS.)

Background: This study examined risk factors for extended-spectrum β-lactamase (ESBL) infection in patients at the University of Minnesota Medical Center, Fairview., Methods: Laboratory-confirmed cases of ESBL infection between January 2005 and June 2008 were evaluated in a case-control study. Risk factors were assessed based on source of infection, either health facility-acquired (HFA) or community-acquired (CA). Cases were identified through hospital infection control department ESBL surveillance records. Controls were selected from the patient population present within the same facility as the cases., Results: Our evaluation revealed that 60.6% of the health facility-acquired ESBL infections were due to Escherichia coli. Risk factors included previous antibiotic use (odds ratio [OR], 23.7; P < .0001), recurrent urinary tract infection (OR, 7.0; P < .022), venous or arterial catheter use (OR, 12.5; P < .0001), and long-term care facility residence (OR, 7.7; P = .043). For each day of antibiotic use, the risk of infection increased by 2%. Similarly, 76.5% of the community-acquired ESBL infections were due to E coli. Risk factors included previous antibiotic use (OR, 5.1; P = .0005) and recurrent urinary tract infection (OR, 9.1; P = .0098). For each day of antibiotic use, the risk of infection increased by 1%., Conclusions: Developing policies and methods to promote good antibiotic stewardship and reduce the incidence of urinary tract infections will decrease the risk of ESBL infection., (Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Square self-assemblies are obtained from dirhodium(II) tetracarboxylate complexes using an isonicotinate-type ligand to act as an equatorial ligand to one dirhodium unit and an axial ligand to another. It is shown that the supramolecular squares are formed selectively out of a number of possible compounds in the dynamic carboxylate exchange library.

Detection of peripheral artery disease (PAD) typically entails collection of medical history, physical examination, and noninvasive imaging, but whether a risk factor-based model has clinical utility in population screening is unclear. Our objective was to derive and validate a new score for estimating PAD probability in individuals or populations. PAD presence was determined by a history of previous or current intermittent claudication associated with an ankle-brachial index (ABI) of < 0.9 or previous lower extremity arterial intervention. Multivariable stepwise logistic regression identified cross-sectional correlates of PAD from demographic, clinical, and laboratory variables. Analyses were derived from 18,049 US REACH (REduction of Atherothrombosis for Continued Health) Registry outpatients with a complete baseline risk factor profile (enrolled from December 2003 to June 2004). Model performance was assessed internally using 10-fold cross validation, and effect estimates were used to generate the score. The model was externally validated using the Framingham Offspring Study. Age, sex, smoking, diabetes mellitus, body mass index, hypertension stage, and history of heart failure, coronary artery disease, and cerebrovascular disease were predictive of PAD prevalence. The model had reasonable discrimination on derivation and internal validation (c-statistic = 0.61 and 0.60, respectively) and external validation (c-statistic = 0.63 [ABI < 0.9] or 0.64 [clinical PAD]). The model-estimated PAD prevalence varied more than threefold from lowest to highest decile (range, 4.5-16.7) and corresponded closely with actual PAD prevalence in each population. In conclusion, this new tool uses clinical variables to estimate PAD prevalence. While predictive power may be limited, it may improve PAD detection in vulnerable, at-risk populations.

Background: When a clinical culture emphasizes cure, as in bone marrow transplantation (BMT) services, BMT nurses commonly experience enormous stress when patients are suffering or dying. In this context, it is unclear what meanings BMT nurses experience in their work and how they find meaning and sustain hope, given conflicting responsibilities to patients., Objective: This study aimed to explore BMT nurses' experiences of meaning and hope and the effects of a meaning-centered intervention (MCI) on these experiences using qualitative methodology., Methods: Fourteen BMT nurses engaged in a 5-session MCI, with 7 members each participating in 2 groups. Semistructured qualitative interviews were conducted at 1 month before and after the intervention. Interpretive phenomenology guided data analysis., Results: The BMT nurses in the Princess Margaret Hospital experienced meaning in their involvement with their patients' suffering. The MCI seemed to inspire participants to engage more with patients and their suffering. Three subthemes reflected this influence: (a) greater awareness of boundaries between their personal and professional involvement, (b) enhanced empathy from an awareness of a shared mortality, and (c) elevated hope when nurses linked patients' suffering with meaning., Conclusions: This study confirms that patients' suffering constitutes nurses' search for meaning and hope in their work. The MCI offers a way in which to actively support nurses in this process., Implications for Practice: Nurses can learn to be more responsive to patients' suffering beyond limits of cure. A minimal intervention, such as the MCI, supports BMT nurses in finding positive personal meaning and purpose in their otherwise highly stressful work culture.

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion method in patients with ST-elevation myocardial infarction (STEMI) if it can be performed in a timely manner in high-volume centers. Regional STEMI networks improve timely access to PCI but are frequently criticized for being single center. To determine if results of regional STEMI systems could be replicated and achieve similar outcomes in 2 separate geographic regions, we examined the prospective databases of 2 large regional STEMI networks that use identical standardized protocols and integrated transfer systems. The Minneapolis Heart Institute (MHI) database included 2,266 patients with STEMI from 31 hospitals (498 at the PCI hospital, 1,033 transferred from 11 hospitals <60 miles away, and 735 transferred from 19 hospitals 60 to 210 miles away). The Iowa Heart Center (IHC) database included 1,206 patients with STEMI from 24 hospitals (710 at the PCI hospital, 266 transferred from 10 hospitals <60 miles away, and 230 transferred from 13 hospitals 60 to 120 miles away). Median total door-to-balloon times for the PCI hospital, zone 1, and zone 2 patients were 64, 95, and 123 minutes for the MHI and 59, 102, and 136 for the IHC (p <0.05 for each comparison between MHI and IHC). Overall in-hospital, 30-day, and 1-year mortalities was 4.8%, 5.4%, and 8.0% respectively (p = NS for each comparison between MHI and IHC). In conclusion, the use of identical protocols in 2 large regional STEMI systems in geographically separate locations produced nearly identical outcomes, adding to evidence that regional STEMI centers expand timely access to PCI., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aims: To determine the safety and efficacy of a pharmaco-invasive reperfusion strategy utilizing half-dose fibrinolysis combined with transfer for immediate percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) patients presenting to remote rural hospitals. Primary PCI is preferred for STEMI if performed in a timely manner. However, <20% of STEMI patients transferred for PCI in the USA have door-to-balloon times <2 h., Methods and Results: Prospective data from the Level 1 MI programme were analysed. All STEMI patients presenting to the Minneapolis Heart Institute or 31 referral hospitals received aspirin, clopidogrel, and unfractionated heparin (UFH) at the presenting hospital and those presenting to hospitals ≥60 miles away also received half-dose fibrinolytic with transfer for immediate PCI. From April 2003 through December 2009, we enrolled 2634 consecutive STEMI patients in the Level 1 MI database including 660 transferred from remote hospitals utilizing pharmaco-invasive therapy and 600 patients who presented directly to the PCI centre. There were no significant differences in 30-day mortality (5.5 vs. 5.6%; P= 0.94), stroke (1.1 vs. 1.3%; P= 0.66) or major bleeding (1.5 vs. 1.8%; P= 0.65), or re-infarction/ischaemia (1.2 vs. 2.5%; P= 0.088) in patients receiving a pharmaco-invasive strategy compared with patients presenting directly to the PCI centre, despite a significantly longer door-to-balloon time., Conclusion: Within a regional STEMI system of care, half-dose fibrinolysis combined with immediate transfer for PCI may be a safe and effective option for STEMI patients with expected delays due to long-distance transfer.

Background and Aim of the Study: Chronic mitral regurgitation (MR) causes volume overload on the left ventricle and, if uncorrected, will over time lead to left ventricular remodeling and heart failure. The benefits of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) in primary MR are not well defined., Methods: MEDLINE was searched for studies in which the effects of ACE inhibitors and ARBs on chronic MR had been examined. The inclusion criteria required the patient population to have chronic MR, a normal left ventricular ejection fraction, and to report a quantitative measure of the change in MR severity. Studies in which patients had secondary MR were excluded., Results: Nineteen studies met the inclusion criteria (13 daily therapy, five single-dose, and one combined study). The pooled mean decrease in regurgitant fraction (RF) was 7.7% [95% CI 4.9, 10.6] and 9.3% [95% CI 3.4, 15.2] for studies in patients with daily therapy and single-dose therapy, respectively. Among studies which reported changes in regurgitant volume (RV), the pooled mean decrease was 7.9 ml [95% CI 1.4, 14.5]. For patients with mitral valve prolapse (MVP), the pooled mean reduction in RF was 8.1% [95% CI 4.3, 11.9] and in rheumatic disease it was 3.4% [95% CI 13.2 - 7.0]. Across the seven studies of daily therapy which reported a change in left ventricular end-diastolic volume index (LVEDVI), the mean decrease was 11.5 ml/m2 [95% CI 2.4, 20.6]., Conclusion: ACE inhibitors and ARBs each reduced the RF, RV, and left ventricular size by a modest degree in chronic primary MR.

Objectives: We examined population-based smoking trends in Minnesota between 1980 and 2009., Methods: The Minnesota Heart Survey (MHS) is a population-based, serial, cross-sectional study of cardiovascular risk factor trends among Minneapolis-Saint Paul metropolitan residents. The MHS recently completed its sixth survey (1980-1982 [n = 3799], 1985-1987 [n = 4641], 1990-1992 [n = 5159], 1995-1997 [n = 6690], 2000-2002 [n = 3281], and 2007-2009 [n = 3179]). We used MHS data to examine smoking trends among adults aged 25 to 74 years by means of age-adjusted generalized linear mixed models., Results: Between 1980 and 2009, the prevalence of current smoking decreased from 32.8% to 15.5% for men and from 32.7% to 12.2% for women (P < .001 for each). Greater decreases occurred among those with higher income and those with more education. Among currently smoking men, the number of cigarettes smoked per day decreased from 26.0 in the 1980-1982 survey to 16.0 in the 2007-2009 survey (P < .001). Similar trends were observed among women., Conclusions: Although the prevalence of smoking and cigarette consumption decreased from the 1980-1982 period to the 2007-2009 period, interventions specifically designed for those of lower socioeconomic status are needed.

Objective: To evaluate systemic and limb ischemic event rates of PAD patients with prior leg amputation and determine predictors of adverse outcomes., Methods: The REduction of Atherothrombosis for Continued Health (REACH) Registry provided a prospective multinational cohort of 7996 outpatients with PAD enrolled from primary medical clinics in 44 countries in 2003-2004. 1160 patients (14.5%) had a prior leg amputation at any level. Systemic (myocardial infarction [MI], stroke, cardiovascular death) and limb (angioplasty, surgery, amputation) ischemic event rates were determined in a 3-year follow-up., Results: PAD patients with leg amputations on entry had a 5-fold higher rate of a subsequent amputation (12.4% vs. 2.4%, P<.001), lower rate of peripheral angioplasty (8.3% vs. 10.7%, P = .005), and similar rates of surgical revascularization procedures compared with PAD patients without amputation. A nearly 2-fold increase in rates of cardiovascular death (14.5% vs. 7.7%, P<.001) and all-cause mortality (21.8% vs. 12.6%, P<.001) and an increase in the composite outcome of MI, stroke, cardiovascular death, or hospitalization (48.7% vs. 40.0%, P<.001) were noted. Recent (≤ 1 year) amputation was associated with higher rates of worsening PAD, subsequent lower extremity surgical revascularization procedures, re-amputation, non-fatal MI, and the composite outcome, including hospitalization. Adverse systemic and limb ischemic outcomes were similar regardless of amputation level., Conclusions: Individuals with a history of leg amputations have markedly elevated rates of systemic and limb-related outcomes. PAD patients with recent ischemic amputation have the highest risk of adverse events. A history of "minor" ischemic amputation may confer an identical systemic risk as "major" leg amputation., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Superoxide reductase is a nonheme iron metalloenzyme that detoxifies superoxide anion radicals O(2)(•-) in some microorganisms. Its catalytic mechanism was previously proposed to involve a single ferric iron (hydro)peroxo intermediate, which is protonated to form the reaction product H(2)O(2). Here, we show by pulse radiolysis that the mutation of the well-conserved lysine 48 into isoleucine in the SOR from Desulfoarculus baarsii dramatically affects its reaction with O(2)(•-). Although the first reaction intermediate and its decay are not affected by the mutation, H(2)O(2) is no longer the reaction product. In addition, in contrast to the wild-type SOR, the lysine mutant catalyzes a two-electron oxidation of an olefin into epoxide in the presence of H(2)O(2), suggesting the formation of iron-oxo intermediate species in this mutant. In agreement with the recent X-ray structures of the peroxide intermediates trapped in a SOR crystal, these data support the involvement of lysine 48 in the specific protonation of the proximal oxygen of the peroxide intermediate to generate H(2)O(2), thus avoiding formation of iron-oxo species, as is observed in cytochrome P450. In addition, we proposed that the first reaction intermediate observed by pulse radiolysis is a ferrous-iron superoxo species, in agreement with TD-DFT calculations of the absorption spectrum of this intermediate. A new reaction scheme for the catalytical mechanism of SOR with O(2)(•-) is presented in which ferrous iron-superoxo and ferric hydroperoxide species are reaction intermediates, and the lysine 48 plays a key role in the control of the evolution of iron peroxide intermediate to form H(2)O(2).

Heterometallic cuboidal clusters [Mo(3)S(4)M(H(2)O)(9)Cl](3+) M = Pd or Ni react with the trivacant [AsW(9)O(33)](9-) anion to give tetramodular complexes [(H(2)AsW(9)O(33))(4){Mo(3)S(4)M(H(2)O)(5)}(2)](20-) (M = Pd for anion 2 and M = Ni for anion 3) in good yield. Both anions crystallized as single crystals of potassium salts to give K-2 and K-3 salts which have been characterized structurally by X-ray diffraction. Both compounds are isomorphous and the anions 2 and 3 are described as two dimeric moeties, associated by internal hydrogen bonds, electrostatic interactions involving four outer potassium ion and coordination bonds within a central {M(2)S(2)} unit containing a M-M metallic bond. Studies in solution reveal that the dimeric association is maintained in solution in the 2 × 10(-4)-2 × 10(-3) mol L(-1) range. Conversely, in the presence of exogeneous ligands, such as iodide or pyridine the UV-vis data are consistent with the dissociation of the anion 2 into monomer through a Pd-L coordination bond (L = I(-) or Py). Furthermore, (183)W NMR spectrum of 2 shows that molecular structure of 2 is retained in solution. Elemental analysis and IR are also supplied. Electrochemical behavior of 2 and 3 are given and compared with the Pd or Ni free parent anion. The CVs are dominated mainly by irreversible reduction or oxidation processes, where the peak potentials appear dependent upon the ionic charge of the complex. However, the CV of the Pd-containing anion (2) is consistent with the deposition of Pd metal at the electrode, which gives rise to an oxidation process into palladium oxide.

Trim and fill is a popular method of accounting for publication bias in meta-analysis. However, the use of trim and fill is limited to the setting in which all meta-analyzed studies represent a true common effect. In many practical settings, within-study effect estimates are a function of some covariate. Because methods of accounting for publication bias in meta-regression have received little attention, we propose here a generalization of trim and fill for application in meta-regression. The proposed algorithm preserves the computational features of trim and fill and adds only an assumption of symmetry in the hypothesized distribution of the measured covariate. By simulation, we evaluate properties (mean bias, root mean squared error, and coverage probability) of meta-regression parameter estimates and corresponding confidence intervals with application of the proposed algorithm in a range of scenarios, including violation of the aforementioned assumption of symmetry. We also evaluate the performance of common estimators of the number of suppressed studies. In general, we show that the proposed algorithm is successful in identifying suppression of studies and reducing the bias in regression parameters derived from the analysis of the augmented set of studies. We apply the proposed algorithm to an analysis of the effect of cognitive-behavioral therapy on the risk of recidivism. Copyright © 2012 John Wiley & Sons, Ltd., (Copyright © 2012 John Wiley & Sons, Ltd.)

Patent Foramen Ovale (PFO) is a normal fetal communication between right and left atria that persists after birth by about 30% in adults. It is discussed to be associated to potential clinical events, asking rational of such closure. Its correction throughout venous access can be attempted on four different indications: (1) secondary prevention of stroke or transient ischemic attack, (2) decompression illness, (3) migraine with aura, and (4) platypnea-orthodeoxia. The PFO closure procedure implies the double control of X-rays and ultrasound, and is relatively simple to perform, using various prostheses. In France, the place of percutaneous closure procedure is nowadays unclear since the Haute Autorité de santé currently suspended recommendations about the management after stroke., (Copyright © 2011. Published by Elsevier SAS.)