Acute myopathy secondary to oral steroid therapy in a 49-year-old man: a case report

<p>Abstract</p> <p>Introduction</p> <p>Acute myopathy caused by oral corticosteroids is rare. We present a case of myopathy occurring after two doses of methylprednisolone. Typically, acute steroid myopathy occurs with therapy using intravenous corticosteroids at high doses. Acute myopathy developing very early in the course of treatment with oral corticosteroids has been reported only once in the literature. Corticosteroid therapy may be complicated by myopathy, usually chronic, after prolonged high-dose therapy. Acute myopathy caused by exogenous corticosteroids is rare, usually with intravenous corticosteroids at high doses.</p> <p>Case presentation</p> <p>A 49-year-old Caucasian man developed acute myopathy after taking oral methylprednisolone for only two days, 24 mg on day 1 and 20 mg on day 2. He discontinued the medication because of new-onset myalgias and lethargy on day 3 and was seen in our clinic four days after beginning therapy. He completely recovered in four weeks by discontinuing the corticosteroids.</p> <p>Conclusion</p> <p>Among the many complications of corticosteroid therapy, acute myopathy is very rare. It requires prompt recognition and adjustment of therapy.</p

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Fate of Allochthonous Dissolved Organic Carbon in Lakes: A Quantitative Approach

Inputs of dissolved organic carbon (DOC) to lakes derived from the surrounding landscape can be stored, mineralized or passed to downstream ecosystems. The balance among these OC fates depends on a suite of physical, chemical, and biological processes within the lake, as well as the degree of recalcintrance of the allochthonous DOC load. The relative importance of these processes has not been well quantified due to the complex nature of lakes, as well as challenges in scaling DOC degradation experiments under controlled conditions to the whole lake scale. We used a coupled hydrodynamic-water quality model to simulate broad ranges in lake area and DOC, two characteristics important to processing allochthonous carbon through their influences on lake temperature, mixing depth and hydrology. We calibrated the model to four lakes from the North Temperate Lakes Long Term Ecological Research site, and simulated an additional 12 ‘hypothetical’ lakes to fill the gradients in lake size and DOC concentration. For each lake, we tested several mineralization rates (range: 0.001 d−1 to 0.010 d−1) representative of the range found in the literature. We found that mineralization rates at the ecosystem scale were roughly half the values from laboratory experiments, due to relatively cool water temperatures and other lake-specific factors that influence water temperature and hydrologic residence time. Results from simulations indicated that the fate of allochthonous DOC was controlled primarily by the mineralization rate and the hydrologic residence time. Lakes with residence times <1 year exported approximately 60% of the DOC, whereas lakes with residence times >6 years mineralized approximately 60% of the DOC. DOC fate in lakes can be determined with a few relatively easily measured factors, such as lake morphometry, residence time, and temperature, assuming we know the recalcitrance of the DOC

The Development of a Content Analysis Model for Assessing Students’ Cognitive Learning in Asynchronous Online Discussions

The purpose of this study was to develop and validate a content analysis model for assessing students\u27 cognitive learning in asynchronous online discussions. It adopted a fully mixed methods design, in which qualitative and quantitative methods were employed sequentially for data analysis and interpretation. Specifically, the design was a sequential exploratory (QUAL→ quan) design with priority given to qualitative data and methods. Qualitative data were 800 online postings collected in two online courses. Quantitative data were 803 online postings from the same two courses but from different discussion topics and different weeks. During the qualitative process, a grounded theory approach was adopted to construct a content analysis model based on qualitative data. During the quantitative process, chi-square tests and confirmative factor analysis (CFA) which used online postings as cases or observations and was the first of its kind were performed to test if the new model fit the quantitative data

A comparative-advantage approach to government debt maturity’,

Abstract We study optimal government debt maturity in a model where investors derive monetary services from holding riskless short-term securities. In a setting where the government is the only issuer of such riskless paper, it trades off the monetary premium associated with short-term debt against the refinancing risk implied by the need to roll over its debt more often. We then extend the model to allow private financial intermediaries to compete with the government in the provision of short-term, money-like claims. We argue that if there are negative externalities associated with private money creation, the government should tilt its issuance more towards short maturities. The idea is that the government may have a comparative advantage relative to the private sector in bearing refinancing risk, and hence should aim to partially crowd out the private sector&apos;s use of short-term debt

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

Hsp90 Inhibition Decreases Mitochondrial Protein Turnover

Cells treated with hsp90 inhibitors exhibit pleiotropic changes, including an expansion of the mitochondrial compartment, accompanied by mitochondrial fragmentation and condensed mitochondrial morphology, with ultimate compromise of mitochondrial integrity and apoptosis.We identified several mitochondrial oxidative phosphorylation complex subunits, including several encoded by mtDNA, that are upregulated by hsp90 inhibitors, without corresponding changes in mRNA abundance. Post-transcriptional accumulation of mitochondrial proteins observed with hsp90 inhibitors is also seen in cells treated with proteasome inhibitors. Detailed studies of the OSCP subunit of mitochondrial F1F0-ATPase revealed the presence of mono- and polyubiquitinated OSCP in mitochondrial fractions. We demonstrate that processed OSCP undergoes retrotranslocation to a trypsin-sensitive form associated with the outer mitochondrial membrane. Inhibition of proteasome or hsp90 function results in accumulation of both correctly targeted and retrotranslocated mitochondrial OSCP.Cytosolic turnover of mitochondrial proteins demonstrates a novel connection between mitochondrial and cytosolic compartments through the ubiquitin-proteasome system. Analogous to defective protein folding in the endoplasmic reticulum, a mitochondrial unfolded protein response may play a role in the apoptotic effects of hsp90 and proteasome inhibitors

Interprofessional collaborative practice within cancer teams: Translating evidence into action. A mixed methods study protocol

<p>Abstract</p> <p>Background</p> <p>A regional integrated cancer network has implemented a program (educational workshops, reflective and mentoring activities) designed to support the uptake of evidence-informed interprofessional collaborative practices (referred to in this text as EIPCP) within cancer teams. This research project, which relates to the Registered Nurses' Association of Ontario (RNAO) Best Practice Guidelines and other sources of research evidence, represents a unique opportunity to learn more about the factors and processes involved in the translation of evidence-based recommendations into professional practices. The planned study seeks to address context-specific challenges and the concerns of nurses and other stakeholders regarding the uptake of evidence-based recommendations to effectively promote and support interprofessional collaborative practices.</p> <p>Aim</p> <p>This study aims to examine the uptake of evidence-based recommendations from best practice guidelines intended to enhance interprofessional collaborative practices within cancer teams.</p> <p>Design</p> <p>The planned study constitutes a practical trial, defined as a trial designed to provide comprehensive information that is grounded in real-world healthcare dynamics. An exploratory mixed methods study design will be used. It will involve collecting quantitative data to assess professionals' knowledge and attitudes, as well as practice environment factors associated with effective uptake of evidence-based recommendations. Semi-structured interviews will be conducted concurrently with care providers to gather qualitative data for describing the processes involved in the translation of evidence into action from both the users' (n = 12) and providers' (n = 24) perspectives. The Graham <it>et al. </it>Ottawa Model of Research Use will serve to construct operational definitions of concepts, and to establish the initial coding labels to be used in the thematic analysis of the qualitative data. Quantitative and qualitative results will be merged during interpretation to provide complementary perspectives of interrelated contextual factors that enhance the uptake of EIPCP and changes in professional practices.</p> <p>Discussion</p> <p>The information obtained from the study will produce new knowledge on the interventions and sources of support most conducive to the uptake of evidence and building of capacity to sustain new interprofessional collaborative practice patterns. It will provide new information on strategies for overcoming barriers to evidence-informed interventions. The findings will also pinpoint critical determinants of 'what works and why' taking into account the interplay between evidence, operational, relational micro-processes of care, uniqueness of patients' needs and preferences, and the local context.</p

A multi-factorial analysis of response to warfarin in a UK prospective cohort

Background Warfarin is the most widely used oral anticoagulant worldwide, but it has a narrow therapeutic index which necessitates constant monitoring of anticoagulation response. Previous genome-wide studies have focused on identifying factors explaining variance in stable dose, but have not explored the initial patient response to warfarin, and a wider range of clinical and biochemical factors affecting both initial and stable dosing with warfarin. Methods A prospective cohort of 711 patients starting warfarin was followed up for 6 months with analyses focusing on both non-genetic and genetic factors. The outcome measures used were mean weekly warfarin dose (MWD), stable mean weekly dose (SMWD) and international normalised ratio (INR) > 4 during the first week. Samples were genotyped on the Illumina Human610-Quad chip. Statistical analyses were performed using Plink and R. Results VKORC1 and CYP2C9 were the major genetic determinants of warfarin MWD and SMWD, with CYP4F2 having a smaller effect. Age, height, weight, cigarette smoking and interacting medications accounted for less than 20 % of the variance. Our multifactorial analysis explained 57.89 % and 56.97 % of the variation for MWD and SMWD, respectively. Genotypes for VKORC1 and CYP2C9*3, age, height and weight, as well as other clinical factors such as alcohol consumption, loading dose and concomitant drugs were important for the initial INR response to warfarin. In a small subset of patients for whom data were available, levels of the coagulation factors VII and IX (highly correlated) also played a role. Conclusion Our multifactorial analysis in a prospectively recruited cohort has shown that multiple factors, genetic and clinical, are important in determining the response to warfarin. VKORC1 and CYP2C9 genetic polymorphisms are the most important determinants of warfarin dosing, and it is highly unlikely that other common variants of clinical importance influencing warfarin dosage will be found. Both VKORC1 and CYP2C9*3 are important determinants of the initial INR response to warfarin. Other novel variants, which did not reach genome-wide significance, were identified for the different outcome measures, but need replication