Cloning, purification and preliminary crystallographic analysis of a putative pyridoxal kinase from Bacillus subtilis

A putative pyridoxal kinase from B. subtilis has been cloned, overexpressed, purified and crystallized and data have been collected to 2.8 Å resolution

Raloxifene neutralizes bone brittleness induced by anti-remodeling treatment and increases fatigue life through non-cell mediated mechanisms

Pre-clinical data have shown that tissue level effects stemming from bisphosphonateinduced suppression of bone remodeling can result in bone that is stronger yet more brittle. Raloxifene has been shown to reduce bone brittleness through non-cellular mechanisms. The goal of this work was to test the hypothesis that raloxifene can reverse the bone brittleness resulting from bisphosphonate treatment. Dog and mouse bone from multiple bisphosphonate dosing experiments were soaked in raloxifene and then assessed for mechanical properties. Mice treated with zoledronate in vivo had lower post-yield mechanical properties compared to controls. Raloxifene soaking had significant positive effects on select mechanical properties of bones from both vehicle and zoledronate treated mice. Although the effects were blunted in zoledronate bones relative to vehicle, the soaking was sufficient to normalize properties to control levels. Additional studies showed that raloxifene-soaked bones had a significant positive effect on cycles to failure (+114%) compared to control-soaked mouse bone. Finally, raloxifene soaking significantly improved select properties of ribs from dogs treated for 3 years with alendronate. These data show that ex vivo soaking in raloxifene can act through non-cellular mechanisms to enhance mechanical properties of bone previously treated with bisphosphonate. We also document that the positive effects of raloxifene soaking extend to enhancing fatigue properties of bone

The benefits of neighborhood racial diversity: Neighborhood factors and its association with increased physical activity in ACS patients

Regular physical activity reduces the risk of adverse events after an acute coronary syndrome (ACS) [1]. Physical activity level is influenced by neighborhood factors such as racial diversity in the general population [2] and [3], but the impact of neighborhood factors on physical activity after an ACS is unknown. We therefore prospectively evaluated the relationship of post-ACS physical activity assessed by continuous activity monitors with neighborhood characteristics, including ethnic density, income, female headed households, and racial diversity, in patients enrolled in the Prescription Use, Lifestyle, and Stress Evaluation (PULSE) Study. We included 107 patients enrolled in the PULSE study from February 1, 2009 to June 30, who were monitored with an Actical® (Philips Respironics, Inc., Bend, Oregon) accelerometer device during the first 45 days following discharge from their ACS. For this analysis, physical activity level was operationalized as the mean maximum 6 min of activity during the day (M6m), which has previously been employed in studies of patients with chronic heart failure to summarize the patients' peak activity level [4] and [5]. Because the trajectory of physical activity is expected to change after hospital discharge, we calculated the M6m measure at 7, 14, 21, and 28 days post-discharge

Cost-effectiveness of secondary screening modalities for hypertension

Background: Clinic-based blood pressure (CBP) has been the default approach for the diagnosis of hypertension, but patients may be misclassified because of masked hypertension (false negative) or ‘white coat’ hypertension (false positive). The incorporation of other diagnostic modalities, such as home blood pressure monitoring (HBPM) and ambulatory blood pressure monitoring (ABPM), holds promise to improve diagnostic accuracy and subsequent treatment decisions. Materials and methods: We reviewed the literature on the costs and cost-effectiveness of adding HBPM and ABPM to routine blood pressure screening in adults. We excluded letters, editorials, and studies of pregnant and/or pre-eclamptic patients, children, and patients with specific conditions (e.g. diabetes). Results: We identified 14 original, English language studies that included cost outcomes and compared two or more modalities. ABPM was found to be cost saving for diagnostic confirmation following an elevated CBP in six studies. Three of four studies found that adding HBPM to an elevated CBP was also cost-effective. Conclusion: Existing evidence supports the cost-effectiveness of incorporating HBPM or ABPM after an initial CBP-based diagnosis of hypertension. Future research should focus on their implementation in clinical practice, long-term economic values, and potential roles in identifying masked hypertension

Relation of Patients Living Without a Partner or Spouse to Being Physically Active After Acute Coronary Syndromes (from the PULSE Accelerometry Substudy)

Living alone is associated with adverse outcomes after acute coronary syndromes (ACS). One potential mediator of the relation between partner status and outcomes after ACS is physical activity. To evaluate the association of partner status with physical activity after ACS, data from 107 participants enrolled in the Prescription Use, Lifestyle, and Stress Evaluation (PULSE) study, a prospective observational study of post-ACS patients, were analyzed. Accelerometers were used to measure physical activity after hospital discharge. The primary outcome measure was a maximum 10 hours of daytime activity 1 month after discharge. One month after discharge from ACS hospitalizations, participants without a partner or spouse exhibited 24.4% lower daytime activity than those with a partner or spouse (p = 0.003). After controlling for age, gender, body mass index, Charlson co-morbidity index, and traditional psychosocial and clinical cardiovascular correlates of post-ACS physical activity, partner status remained an independent predictor of post-ACS physical activity (20.5% lower daytime activity among those without a partner or spouse, p = 0.008). In conclusion, in this study of accelerometer-measured physical activity after an ACS hospitalization, those without a partner or spouse exhibit significantly less physical activity than those with a partner or spouse 1 month after discharge from the hospital. Low physical activity may be an important mediator of the prognosis associated with partner status after ACS

Identifying dynamical modules from genetic regulatory systems: applications to the segment polarity network

BACKGROUND It is widely accepted that genetic regulatory systems are 'modular', in that the whole system is made up of smaller 'subsystems' corresponding to specific biological functions. Most attempts to identify modules in genetic regulatory systems have relied on the topology of the underlying network. However, it is the temporal activity (dynamics) of genes and proteins that corresponds to biological functions, and hence it is dynamics that we focus on here for identifying subsystems. RESULTS Using Boolean network models as an exemplar, we present a new technique to identify subsystems, based on their dynamical properties. The main part of the method depends only on the stable dynamics (attractors) of the system, thus requiring no prior knowledge of the underlying network. However, knowledge of the logical relationships between the network components can be used to describe how each subsystem is regulated. To demonstrate its applicability to genetic regulatory systems, we apply the method to a model of the Drosophila segment polarity network, providing a detailed breakdown of the system. CONCLUSION We have designed a technique for decomposing any set of discrete-state, discrete-time attractors into subsystems. Having a suitable mathematical model also allows us to describe how each subsystem is regulated and how robust each subsystem is against perturbations. However, since the subsystems are found directly from the attractors, a mathematical model or underlying network topology is not necessarily required to identify them, potentially allowing the method to be applied directly to experimental expression data

Observed Hostility and the Risk of Incident Ischemic Heart Disease: A Prospective Population Study From the 1995 Canadian Nova Scotia Health Survey

Objectives The aim of this study was to examine the relation between hostility and incident ischemic heart disease (IHD) and to determine whether observed hostility is superior to patient-reported hostility for the prediction of IHD in a large, prospective observational study. Background Some studies have found that hostile patients have an increased risk of incident IHD. However, no studies have compared methods of hostility assessment or considered important psychosocial and cardiovascular risk factors as confounders. Furthermore, it is unknown whether all expressions of hostility carry equal risk or whether certain manifestations are more cardiotoxic. Methods We assessed the independent relationship between baseline observed hostility and 10-year incident IHD in 1,749 adults of the population-based Canadian Nova Scotia Health Survey. Results There were 149 (8.5%) incident IHD events (140 nonfatal, 9 fatal) during the 15,295 person-years of observation (9.74 events/1,000 person-years). Participants with any observed hostility had a greater risk of incident IHD than those without (p = 0.02); no such relation was found for patient-reported hostility. Those with any observed hostility had a significantly greater risk of incident IHD (hazard ratio: 2.06, 95% confidence interval: 1.04 to 4.08, p = 0.04), after adjusting for cardiovascular (age, sex, Framingham Risk Score) and psychosocial (depression, positive affect, patient-reported hostility, and anger) risk factors. Conclusions The presence of any observed hostility at baseline was associated with a 2-fold increased risk of incident IHD over 10 years of follow-up. Compared with patient-reported measures, observed hostility is a superior predictor of IHD

Prevalence and Characteristics of Anergia (Lack of Energy) in Patients With Acute Coronary Syndrome

Anergia, a commonly occurring syndrome in older adults and patients with cardiovascular diseases, is associated with functional and clinical limitations. To date, the prevalence and clinical–demographic characteristics of anergia in patients with acute coronary syndrome (ACS) have not been elucidated. We examined the prevalence and clinical–demographic characteristics of anergia in a multiethnic sample of patients with ACS. Hospitalized patients with ACS (n = 472), enrolled in the Prescription Usage, Lifestyle, and Stress Evaluation (PULSE) prospective cohort study, completed assessments of demographic, behavioral, and clinical characteristics within 7 days of hospitalization for an ACS event. Current depressive disorder was ascertained using a structured psychiatric interview 3 to 7 days after discharge. Anergia was assessed at baseline and defined using patients' binary responses (yes/no) to 7 items related to energy level. At least 1 complaint of anergia was reported by 79.9% of patients (n = 377) and 32% of patients (n = 153) met criteria for anergia. In a multivariable logistic regression model, anergia was independently associated with being a woman, being white (compared to black), having bodily pain, participating in exercise, having current depressive disorder, and having higher values on the Charlson Co-morbidity Index. In conclusion, anergia is a highly prevalent syndrome in patients with ACS. It is distinct from depression and is associated with modifiable clinical factors such as participation in exercise and bodily pain that may be appropriate targets for intervention

On Global Conservation Laws at Null Infinity

The ``standard'' expressions for total energy, linear momentum and also angular momentum of asymptotically flat Bondi metrics at null infinity are also obtained from differential conservation laws on asymptotically flat backgrounds, derived from a quadratic Lagrangian density by methods currently used in classical field theory. It is thus a matter of taste and commodity to use or not to use a reference spacetime in defining these globally conserved quantities. Backgrounds lead to N\oe ther conserved currents; the use of backgrounds is in line with classical views on conservation laws. Moreover, the conserved quantities are in principle explicitly related to the sources of gravity through Einstein's equations, while standard definitions are not. The relations depend, however, on a rule for mapping spacetimes on backgrounds

Discovery-based games for learning software

ABSTRACT We propose using discovery-based learning games to teach people how to use complex software. Specifically, we developed Jigsaw, a learning game that asks players to solve virtual jigsaw puzzles using tools in Adobe Photoshop. We conducted an eleven-person lab study of the prototype, and found the game to be an effective learning medium that can complement demonstration-based tutorials. Not only did the participants learn about new tools and techniques while actively solving the puzzles in Jigsaw, but they also recalled techniques that they had learned previously but had forgotten