bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnesium Carbonate‐Containing Phosphate Binder Prevents Connective Tissue Mineralization in Abcc6−/− Mice–Potential for Treatment of Pseudoxanthoma Elasticum
Authors: Li Qiaoli , LaRusso Jennifer , Grand‐Pierre Alix E. , Uitto Jouni 
Published: December 2009

AbstractPseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic mineralization of connective tissues primarily in the skin, eyes, and the cardiovascular system. PXE is caused by mutations in the ABCC6 gene. While PXE is associated with considerable morbidity and mortality, there is currently no effective or specific treatment. In this study, we tested oral phosphate binders for treatment of a mouse model of PXE which we have developed by targeted ablation of the corresponding mouse gene (Abcc6−/−). This “knock‐out” (KO) mouse model recapitulates features of PXE and demonstrates mineralization of a number of tissues, including the connective tissue capsule surrounding vibrissae in the muzzle skin which serves as an early biomarker of the mineralization process. Treatment of these mice with a magnesium carbonate‐enriched diet (magnesium concentration being 5‐fold higher than in the control diet) completely prevented mineralization of the vibrissae up to 6 months of age, as demonstrated by computerized morphometric analysis of histopathology as well as by calcium and phosphate chemical assays. The magnesium carbonate‐enriched diet also prevented the progression of mineralization when the mice were placed on that experimental diet at 3 months of age and followed up to 6 months of age. Treatment with magnesium carbonate was associated with a slight increase in the serum concentration of magnesium, with no effect on serum calcium and phosphorus levels. In contrast, concentration of calcium in the urine was increased over 10‐fold while the concentration of phosphorus was markedly decreased, being essentially undetectable after long‐term (>4 month) treatment. No significant changes were noted in the serum parathyroid hormone levels. Computerized axial tomography scan of bones in mice placed on magnesium carbonate‐enriched diet showed no differences in the bone density compared to mice on the control diet, and chemical assays showed a small increase in the calcium and phosphate content of the femurs by chemical assay, in comparison to mice on control diet. Similar experiments with another experimental diet supplemented with lanthanum carbonate did not interfere with the mineralization process in Abcc6−/− mice. These results suggest that magnesium carbonate may offer a potential treatment modality for PXE, a currently intractable disease, as well as for other conditions characterized by ectopic mineralization of connective tissues.
Correlates of Valvular Ossification in Patients with Aortic Valve Stenosis
Authors: Ing Steven W. , Mohler III Emile R. , Putt Mary E. , Torigian Drew , Leonard Mary B. 
Published: December 2009

AbstractValvular calcification may include a regulated process of active ossification; however, the determinants of ossification are unclear. The aim of this study was to identify subject and disease characteristics associated with valvular ossification among patients with calcified aortic valves. Medical records were reviewed for variables associated with aortic stenosis and skeletal bone in a series of 195 patients requiring aortic valve excision. Thirty patients had valvular bone on histopathology. Univariate analyses suggested that warfarin therapy (p= 0.004), African American race (p= 0.006), height (p= 0.03), and male sex (p= 0.07) were associated with greater odds of valvular ossification while diabetes was associated with lower odds (p= 0.07). Multivariate analysis demonstrated that warfarin use (OR 5.7; 95% CI: 1.5–21.3; p= 0.009) and African American race (OR 8.3; 95% CI: 1.8–39.0; p= 0.007) were strongly and independently associated with increased odds of valvular ossification. Valvular ossification was not associated with greater ossification of costochondral cartilage on chest radiography. Warfarin therapy and African American race were associated with increased risk of valvular ossification in patients with aortic stenosis. Future studies are needed to confirm this finding and determine if inhibition of matrix GLA protein by warfarin mediates this effect.
Assessment of functional vision and its rehabilitation
Authors: Colenbrander August 
Published: December 2009

Abstract.This article, based on a report prepared for the International Council of Ophthalmology (ICO) and the International Society for Low Vision Research and Rehabilitation (ISLRR), explores the assessment of various aspects of visual functioning as needed to document the outcomes of vision rehabilitation. Documenting patient abilities and functional vision (how the person functions) is distinct from the measurement of visual functions (how the eye functions) and also from the assessment of quality of life. All three areas are important, but their assessment should not be mixed. Observation of task performance offers the most objective measure of functional vision, but it is time‐consuming and not feasible for many tasks. Where possible, timing and error rates provide an easy score. Patient response questionnaires provide an alternative. They may save time and can cover a wider area, but the responses are subjective and proper scoring presents problems. Simple Likert scoring still predominates but Rasch analysis, needed to provide better result scales, is gaining ground. Selection of questions is another problem. If the range of difficulties does not match the range of patient abilities, and if the difficulties are not distributed evenly, the results are not optimal. This may be an argument to use different outcome questions for different conditions. Generic questionnaires are appropriate for the assessment of generic quality of life, but not for specific rehabilitation outcomes. Different questionnaires are also needed for screening, intake and outcomes. Intake questions must be relevant to actual needs to allow prioritization of rehabilitation goals; the activity inventory presents a prototype. Outcome questions should be targeted at predefined rehabilitation goals. The Appendix cites some promising examples. The Low Vision Intervention Trial (LOVIT) is an example of a properly designed randomized control study, and has demonstrated the remarkable effectiveness of vision rehabilitation. It is hoped that further similar studies will follow.
Effect of water temperature, timing, physiological condition, and lake thermal refugia on migrating adult Weaver Creek sockeye salmon (Oncorhynchus nerka)
Authors: Mathes M. Todd , Hinch Scott G. , Cooke Steven J. , Crossin Glenn T. , Patterson David A. , Lotto Andrew G. , Farrell Anthony P. 
Published: December 2009

We coupled physiological biopsy and positional telemetry to examine survival to reach spawning grounds in relation to water temperature, timing, physiological condition, and holding location (river or lake) in adult migrating sockeye salmon ( Oncorhynchus nerka ). We tracked 83 fish across a large temperature range (13.5–21.5 °C), which included record highs. Only early-timed migrants that held in Harrison Lake survived to reach spawning grounds (16%, or n = 4). Normal-timed fish, those that migrated at historically observed times, survived at higher levels if they held in Harrison River (72%, or n = 18). Mortalities were identified on the bottoms of both the lake and river. Hypothetical degree-day (DD) accumulation revealed that early-timed river fish would have greatly surpassed (~800 °C DD) a critical disease threshold value (~500 °C DD). There was no difference in hypothetical DD accumulation between normal-timed river fish and early-timed lake fish. Early-timed sockeye had elevated physiological stress (e.g., plasma lactate, glucose, and hematocrit), which may have contributed to high levels of mortality. By using lakes as thermal refugia, early-timed fish likely reduce rates of disease development and may better recover from physiological stress associated with high encountered temperatures.
The opportunity cost of information: an economic framework for understanding the balance between assessment and control in sea lamprey (Petromyzon marinus) management
Authors: Fenichel Eli P. , Hansen Gretchen J.A. 
Published: December 2009

Fisheries managers must make trade-offs between competing management actions; however, the inherent trade-offs associated with information gathering are seldom explicitly considered. Incorporating economics into management decisions at the outset can aid managers in explicitly considering the trade-off between collecting more information to guide management and taking management actions. We use control of the invasive sea lamprey ( Petromyzon marinus ) in the Laurentian Great Lakes to illustrate how budget constraints shape this trade-off. Economic theory is used to frame previous empirical work showing that reducing the allocation of resources to conducting assessment, and thereby freeing resources for treatment, would result in a greater reduction of sea lamprey populations — the overarching management objective. The optimal allocation of resources between assessment and control depends on the total budget, the relative cost of each management activity, the marginal reduction in uncertainty associated with increased assessment, and the marginal effectiveness of increased treatment. Formal incorporation of prior information can change the optimal allocation of resources. The approach presented here is generally applicable to a wide range of fishery management and research questions.
A production estimate approach to analyze habitat and weather effects on recruitment of two endangered freshwater fish
Authors: Cooperman Michael S. , Markle Douglas F. , Terwilliger Mark , Simon David C. 
Published: December 2009

Factors affecting the early life survival of fishes are often difficult to demonstrate because variable immigration and mortality rates coupled with noncontinuous sampling may confound estimates of mortality and bias inference to more numerous smaller individuals. The larval production estimate (LPE) method eliminates these problems by compensating catch data for size- or age-specific mortality and growth and back-calculating abundance at a predetermined size or age. Despite its utility, LPE has not been widely applied in studies of freshwater fish recruitment. We executed an LPE analysis using 10–14 mm and 15–19 mm size classes of Upper Klamath Lake’s (UKL) endangered Lost River suckers ( Deltistes luxatus ) and shortnose suckers ( Chasmistes brevirostris ) for five cohorts per year for 1995–2001. Larval survival peaked when habitat conditions included high availability of emergent macrophytes as habitat (>15 000 m3), air temperatures between 14 and 22 °C, and a low frequency of wind speeds >16 km·h–1. Age-0 juvenile suckers collected later in each year corroborated results of the LPE analysis, as most (88%) juveniles had otolith-estimated swim-up dates corresponding to early life rearing under the specified habitat conditions. Our results support the management practice of maintaining higher than natural UKL water surface elevations through the larval rearing period.
The effect of climate change on the western rock lobster (Panulirus cygnus) fishery of Western Australia
Authors: Caputi Nick , Melville-Smith Roy , de Lestang Simon , Pearce Alan , Feng Ming 
Published: December 2009

Environmental factors such as the Leeuwin Current (influenced by the El Niño – Southern Oscillation cycle) and westerly winds in late winter – spring significantly affect puerulus settlement of the western rock lobster ( Panulirus cygnus ) fishery. Climate change is causing an increase in water temperature that is seasonally variable, a weakening of westerly winds in winter, and an increase in the frequency of El Niño events. Rising water temperatures over 35 years may have resulted in a decrease in size at maturity and size of migrating lobsters from shallow to deep water, increases in abundance of undersized and legal-sized lobsters in deep water relative to shallow water, and shifts in catch to deep water. The size of migrating lobsters is related to the water temperature about the time of puerulus settlement (four years previously). Climate change effects on puerulus settlement, catchability, females moulting from setose to non-setose, timing of moults, and peak catch rates are assessed. As climate change models project that the warming trend will continue, these biological trends are likely to continue. The changes may have negative (increasing frequency of El Niño events) or positive (increasing water temperature) implications for the fishery, which need to be taken into account in stock assessments and management.
Human solCD39 inhibits injury-induced development of neointimal hyperplasia
Authors: Kraemer Rosemary , Shen Hao , Upmacis Rita , Marcus Aaron , Musi Elgilda , Drosopoulos Joan 
Published: December 2009

SummaryBlood platelets provide the initial response to vascular endothelial injury, becoming activated as they adhere to the injured site. Activated platelets recruit leukocytes, and initiate proliferation and migration of vascular smooth muscle cells (SMC) within the injured vessel wall, leading to development of neointimal hyperplasia. Endothelial CD39/NTPDase1 and recombinant solCD39 rapidly metabolise nucleotides, including stimulatory ADP released from activated platelets, thereby suppressing additional platelet reactivity. Using a murine model of vascular endothelial injury, we investigated whether circulating human solCD39 could reduce platelet activation and accumulation, thus abating leukocyte infiltration and neointimal formation following vascular damage. Intraperitoneally-administered solCD39 ADP -ase activity in plasma peaked 1 hour (h) post-injection, with an elimination half-life of 43 h. Accordingly, mice were administered solCD39 or saline 1 h prior to vessel injury, then either sacrificed 24 h post-injury or treated with solCD39 or saline (three times weekly) for an additional 18 days. Twenty-four hours post-injury, solCD39-treated mice displayed a reduction in platelet activation and recruitment, P-selectin expression, and leukocyte accumulation in the arterial lumen. Furthermore, repeated administration of solCD39 modulated the late stage of vascular injury by suppressing leukocyte deposition, macrophage infiltration and smooth muscle cell (SMC) proliferation/migration, resulting in abrogation of neointimal thickening. In contrast, injured femoral arteries of saline-injected mice exhibited massive platelet thrombus formation, marked P-selectin expression, and leukocyte infiltration. Pronounced neointimal growth with macrophage and SMC accretion was also observed (intimal-to-medial area ratio 1.56 ± 0.34 at 19 days). Thus, systemic administration of solCD39 profoundly affects injury-induced cellular responses, minimising platelet deposition and leukocyte recruitment, and suppressing neointimal hyperplasia.
Frequency, demographics and risk (according to tumour type or site) of cancer-associated thrombosis among patients seen at outpatient DVT clinics
Authors: Paneesha Shankaranarayana , McManus Aidan , Arya Roopen , Scriven Nicholas , Farren Timothy , Nokes Tim , Bacon Sue , Nieland Anthea , Cooper Derek , Smith Harry , O‘Shaughnessy Denise , Rose Peter ,   for the VERITY Investigators
Published: December 2009

SummaryVenous thromboembolism (VTE) is a clinically important complication for both hospitalised and ambulatory cancer patients. In the current study, the frequency, demographics and risk (according to tumour site) of VTE were examined among patients seen at outpatient DVT (deep-vein thrombosis) clinics. Of 10,015 VTE cases, 1,361 were diagnosed with cancer, for an overall rate of cancer-associated VTE of 13.6% in this outpatient population. Patients with cancer-associated VTE were significantly older than cancer-free VTE cases (66.4 ± 12.7 vs. 58.8 ± 18.5 years; p<0.0001). The frequency of cancer-associated VTE peaked earlier among females than males, occurring in the sixth (137/639, 21.4% vs. 98/851, 11.3%; p<0.001) and seventh decades (213/980, 21.7% vs. 197/1096, 18%; p=0.036). VTE was described most frequently in common cancers – breast, prostate, colorectal and lung (56.1% of cases). The risk of VTE varied widely across 17 cancer types. Calculating odds ratios (OR) to assess the effect size of cancer type on VTE risk, the highest odds were observed for patients with pancreatic cancer (OR 9.65, 95% confidence interval [CI] (5.51–16.91). Tumours of the head and neck had higher odds than previously reported (OR 8.24, 95% CI 5.06–13.42). Reduced risk estimates were observed for skin cancers (melanoma and non-melanoma: OR 0.89, 95% CI 0.42–1.87; OR 0.74, 95% CI, 0.32–1.69, respectively). We conclude that outpatients have a similar rate of cancer-associated VTE as VTE patient populations previously reported, that cancer-associated VTE occurs in an older age group and earlier in females and that outpatients exhibit distinct tumour site-specific risk from that described among hospitalised cancer patients.
Proteolytic resistance conferred to fibrinogen by von Willebrand factor
Authors: Tanka-Salamon Anna , Machovich Raymund , Komorowicz Erzsebet , Kolev Krasimir 
Published: December 2009

SummaryThe formation of platelet-rich thrombi under high shear rates requires both fibrinogen and von Willebrand factor (VWF) as molecular adhesives between platelets. We attempted to describe the role of VWF as a potential substrate and modulator of the fibrinolytic system using binding assays, as well as kinetic measurements on the cleavage of fibrin(ogen) and a synthetic plasmin substrate (Spectrozyme-PL). The similar dissociation constants for the binding of plasminogen, plasmin, and active site-blocked plasmin onto immobilised VWF suggest that the primary binding site in plasmin(ogen) is not the active site. The progressive loss of clottability and generation of degradation products during fibrinogen digestion with plasmin were delayed in the presence of VWF at physiological concentrations, while VWF cleavage was not detectable. Determination of kinetic parameters for fibrinogen degradation by plasmin, miniplasmin and microplasmin showed that VWF did not modify the Km, whereas kcat values decreased with increasing VWF concentrations following the kinetic model of non-competitive inhibition. Inhibitory constants calculated for VWF were in the range of its physiological plasma concentration (5.4 μg/ml, 5.7 μg/ml and 10.0 μg/ ml for plasmin, miniplasmin and microplasmin, respectively) and their values suggested a modulating role of the kringle 5 domain in the interaction between VWF and (mini)plasmin. VWF had no effect on the amidolytic activity of plasmin on Spectrozyme-PL, or on fibrin dissolution by (mini)plasmin. Our data suggest that VWF, while a poor plasmin substrate relative to fibrinogen, protects fibrinogen against degradation by plasmin preserving its clottability in plasma and its adhesive role in platelet-rich thrombi.
Toll-like receptor 2 stimulation of platelets is mediated by purinergic P2X1-dependent Ca2+ mobilisation, cyclooxygenase and purinergic P2Y1 and P2Y12 receptor activation
Authors: Skoglund Caroline , Helldahl Christian , Lerm Maria , Grenegård Magnus , Bengtsson Torbjörn , Kälvegren Hanna 
Published: December 2009

SummaryToll-like receptor 2 (TLR2), which recognise and respond to conserved microbial pathogen-associated molecular patterns, is expressed on the platelet surface. Furthermore, it has recently been shown that the TLR2/1 agonist Pam3CSK4 stimulates platelet activation. The aim of the present study was to clarify important signalling events in Pam3CSK4-induced platelet aggregation and secretion. Platelet interaction with Pam3CSK4 and the TLR2/6 agonist MALP-2 was studied by analysing aggregation, ATP-secretion, [Ca2+]i mobilisation and thromboxane B2 (TxB2) production. The results show that Pam3CSK4 but not MALP-2 induces [Ca2+]i increase, TxB2 production, dense granule secretion and platelet aggregation. Preincubation of platelets with MALP-2 inhibited the Pam3CSK4-induced responses. The ATP-secretion and aggregation in Pam3CSK4-stimulated platelets was impeded by the purinergic P2X1 inhibitor MRS 2159, the purinergic P2Y1 and P2Y12 antagonists MRS 2179 and cangrelor, the phospholipase C inhibitor U73122, the calcium chelator BAPT-AM and aspirin. The calcium mobilisation was lowered by MRS 2159, aspirin and U73122 whereas the TxB2 production was antagonised by MRS 2159, aspirin and BAPT-AM. When investigating the involvement of the myeloid differentiation factor-88 (MyD88) -dependent pathway, we found that platelets express MyD88 and interleukin 1 receptor-associated kinase (IRAK-1), which are proteins important in TLR signalling. However, Pam3CSK4 did not stimulate a rapid (within 10 minutes) phosphorylation of IRAK-1 in platelets. In conclusion, the results show that Pam3CSK4-induced platelet aggregation and secretion depends on a P2X1-mediated Ca2+ mobilisation, production of TxA2 and ADP receptor activation. The findings in this study further support a role for platelets in sensing bacterial components.
Anticoagulation for valvular heart disease in community-based practice
Authors: Ozonoff Al , Henault Lori , Hylek Elaine , Rose Adam 
Published: December 2009

SummaryLittle is known about patients who receive oral anticoagulation for valvular heart disease (VHD) in community-based practice. It was this study’s objective to describe the characteristics, management, and outcomes of patients anticoagulated for VHD, compared to patients anticoagulated for atrial fibrillation (AF). We used a nationally-representative cohort of community-based anticoagulation care in the United States. Data collected included indications for therapy, demographics, selected comorbid conditions, international normalised ratio (INR) target ranges, INR control, and clinical outcomes. We identified 1,057 patients anticoagulated for VHD (15.6% of the overall cohort) and 3,396 patients anticoagulated for AF (50.2%). INR variability was similar between the two groups (0.64 vs. 0.69, p = 0.80). Among patients with aortic VHD, for whom a standard (2–3) target INR range is recommended, 461 (84%) had a high target range (2.5–3.5), while 95 (16%) had a standard target range. VHD patients had a higher rate of major haemorrhage compared to AF patients (3.57 vs. 1.78 events per 100 patient-years, incidence rate ratio 2.02, 95% CI 1.33 – 3.06). The rate of stroke/systemic embolus was similar between groups (0.67 vs. 0.97 events per 100 patient-years, incidence rate ratio 0.71, 95% CI 0.32 – 1.57). In our community-based study, approximately 15.6% of patients receiving warfarin were anticoagulated for VHD. VHD patients achieved similar anticoagulation control to patients with AF, as measured by INR variability. Nevertheless, the rate of major haemorrhage was elevated among VHD patients compared to AF patients; this finding requires further investigation.Disclaimer: The opinions expressed in this manuscript do not necessarily represent the views or policies of the United States Department of Veterans Affairs.