The Darkening Cloud of Diabetes: Do trends in cardiovascular risk management provide a silver lining?

OBJECTIVE—We aimed to evaluate the changes in cardiovascular-related health care utilization (drug therapies, hospitalizations) and mortality for the diabetic population during a 9-year period in Saskatchewan, Canada

Dynamics of Simple Balancing Models with State Dependent Switching Control

Time-delayed control in a balancing problem may be a nonsmooth function for a variety of reasons. In this paper we study a simple model of the control of an inverted pendulum by either a connected movable cart or an applied torque for which the control is turned off when the pendulum is located within certain regions of phase space. Without applying a small angle approximation for deviations about the vertical position, we see structurally stable periodic orbits which may be attracting or repelling. Due to the nonsmooth nature of the control, these periodic orbits are born in various discontinuity-induced bifurcations. Also we show that a coincidence of switching events can produce complicated periodic and aperiodic solutions.Comment: 36 pages, 12 figure

Desenvolvimento de geleia light de abacaxi com hortelã.

A geleia desenvolvida é um produto com potencial funcional ? contem abacaxi e hortelã ? que tem ação benéfica para a saúde. O objetivo da pesquisa foi sugerir ao consumidor brasileiro uma ?geleia light? ? menos açúcar e calorias ? contendo alta proporção de polpa de abacaxi e a hortelã como ingredientes saudáveis. O Processo4 se caracterizou por ter uma representação, por 100g de geleia, dos ingredientes alimentícios seguintes: 160g de abacaxi Pérola, 4g de hortelã, 2g de pectina cítrica e 30g de açúcar. A geleia do Processo4, por apresentar textura própria de geleia, agradável sabor e aparência de hortelã, bem como sabor característico de polpa de abacaxi, foi avaliada quanto à aceitação sensorial (aparência, textura, sabor, percepção da fruta) e intenção de compra. Um total de 83,7% dos avaliadores declararam que gostaram da geleia light, e, dos 81,9% que consomem geleia, 75,3% comprariam esse produto. A geleia light de abacaxi com hortelã apresentou redução de 50% de açúcar e 50% de calorias atribuídas ao açúcar. Assim, uma porção de 20g dessa geleia light (30ºbrix) possui 6g de carboidrato e 24kcal, enquanto que, da geleia convencional de 60ºbrix, 12g de carboidrato e 48kcal. Também, por ter uma alta representação de polpa de abacaxi Pérola (160g.100g-1) possui um teor mais alto de vitamina C (2,6mg.100g-1). Assim, a pesquisa atual disponibiliza ao mercado uma ?geleia light de abacaxi com hortelã? que tem relevância para a saúde do consumidor, visto que possui reduzido índice de carboidrato e calorias e seus ingredientes apresentam ação positiva para a saúde

Macromolecular theory of solvation and structure in mixtures of colloids and polymers

The structural and thermodynamic properties of mixtures of colloidal spheres and non-adsorbing polymer chains are studied within a novel general two-component macromolecular liquid state approach applicable for all size asymmetry ratios. The dilute limits, when one of the components is at infinite dilution but the other concentrated, are presented and compared to field theory and models which replace polymer coils with spheres. Whereas the derived analytical results compare well, qualitatively and quantitatively, with mean-field scaling laws where available, important differences from ``effective sphere'' approaches are found for large polymer sizes or semi-dilute concentrations.Comment: 23 pages, 10 figure

Treatment of Type 2 Diabetes and Outcomes in Patients With Heart Failure: A Nested Case–Control Study From the U.K. General Practice Research Database

OBJECTIVE - Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with met formin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents. RESEARCH DESIGN AND METHODS - We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI. RESULTS - The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48-0.87]) or metformin with or without other agents (0.72 [0.59-0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45-0.68]) and beta-blockers (0.76 [0.61-0.95]) were associated with reduced mortality. CONCLUSIONS - Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose

Emergent complex neural dynamics

A large repertoire of spatiotemporal activity patterns in the brain is the basis for adaptive behaviour. Understanding the mechanism by which the brain's hundred billion neurons and hundred trillion synapses manage to produce such a range of cortical configurations in a flexible manner remains a fundamental problem in neuroscience. One plausible solution is the involvement of universal mechanisms of emergent complex phenomena evident in dynamical systems poised near a critical point of a second-order phase transition. We review recent theoretical and empirical results supporting the notion that the brain is naturally poised near criticality, as well as its implications for better understanding of the brain

How spiking neurons give rise to a temporal-feature map

A temporal-feature map is a topographic neuronal representation of temporal attributes of phenomena or objects that occur in the outside world. We explain the evolution of such maps by means of a spike-based Hebbian learning rule in conjunction with a presynaptically unspecific contribution in that, if a synapse changes, then all other synapses connected to the same axon change by a small fraction as well. The learning equation is solved for the case of an array of Poisson neurons. We discuss the evolution of a temporal-feature map and the synchronization of the single cells’ synaptic structures, in dependence upon the strength of presynaptic unspecific learning. We also give an upper bound for the magnitude of the presynaptic interaction by estimating its impact on the noise level of synaptic growth. Finally, we compare the results with those obtained from a learning equation for nonlinear neurons and show that synaptic structure formation may profit from the nonlinearity

A pragmatic cluster randomized trial evaluating the impact of a community pharmacy intervention on statin adherence: rationale and design of the Community Pharmacy Assisting in Total Cardiovascular Health (CPATCH) study

<p>Abstract</p> <p>Background</p> <p>Traditional randomized controlled trials are considered the gold standard for evaluating the efficacy of a treatment. However, in adherence research, limitations to this study design exist, especially when evaluating real-world applicability of an intervention. Although adherence interventions by community pharmacists have been tested, problems with internal and external validity have limited the usefulness of these studies, and further well-designed and well-conducted research is needed. We aimed to determine the real-world effectiveness of a community pharmacy adherence intervention using a robust study design. This novel design integrates cluster randomization and an outcome evaluation of medication adherence using a population-based administrative data source in the province of Saskatchewan, Canada.</p> <p>Methods/Design</p> <p>Community pharmacies from across the province of Saskatchewan, Canada were randomized to deliver an adherence intervention to their patients or usual care. Intervention pharmacies were trained to employ a practical adherence strategy targeted at new users of statin medications. While randomization and implementation of the intervention occurred at the community pharmacy level, the outcome analysis will occur at the level of the individual subjects. The primary outcome is the mean statin adherence among all eligible new users of statin medications. Secondary outcomes include the proportion of new statin users who exhibit adherence ≥80%, and persistence with statin use.</p> <p>Discussion</p> <p>This novel study design was developed to combine the rigor of a randomized trial with a pragmatic approach to implementing and capturing the results in a real-world fashion. We believe this approach can serve as an example for future study designs evaluating practice-based adherence interventions.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov no. NCT00971412.</p

Metformin treatment in diabetes and heart failure: when academic equipoise meets clinical reality

<p>Abstract</p> <p>Objective</p> <p>Metformin has had a 'black box' contraindication in diabetic patients with heart failure (HF), but many believe it to be the treatment of choice in this setting. Therefore, we attempted to conduct a pilot study to evaluate the feasibility of undertaking a large randomized controlled trial with clinical endpoints.</p> <p>Study Design</p> <p>The pilot study was a randomized double blinded placebo controlled trial. Patients with HF and type 2 diabetes were screened in hospitals and HF clinics in Edmonton, Alberta, Canada (population ~1 million). Major exclusion criteria included the current use of insulin or high dose metformin, decreased renal function, or a glycosylated hemoglobin <7%. Patients were to be randomized to 1500 mg of metformin daily or matching placebo and followed for 6 months for a variety of functional outcomes, as well as clinical events.</p> <p>Results</p> <p>Fifty-eight patients were screened over a six month period and all were excluded. Because of futility with respect to enrollment, the pilot study was abandoned. The mean age of screened patients was 77 (SD 9) years and 57% were male. The main reasons for exclusion were: use of insulin therapy (n = 23; 40%), glycosylated hemoglobin <7% (n = 17; 29%) and current use of high dose metformin (n = 12; 21%). Overall, contraindicated metformin therapy was the most commonly prescribed oral antihyperglycemic agent (n = 27; 51%). On average, patients were receiving 1,706 mg (SD 488 mg) of metformin daily and 12 (44%) used only metformin.</p> <p>Conclusion</p> <p>Despite uncertainty in the scientific literature, there does not appear to be clinical uncertainty with regards to the safety or effectiveness of metformin in HF making a definitive randomized trial virtually impossible.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00325910</p

Development of a Cx46 Targeting Strategy for Cancer Stem Cells

Gap-junction-mediated cell-cell communication enables tumor cells to synchronize complex processes. We previously found that glioblastoma cancer stem cells (CSCs) express higher levels of the gap junction protein Cx46 compared to non-stem tumor cells (non-CSCs) and that this was necessary and sufficient for CSC maintenance. To understand the mechanism underlying this requirement, we use point mutants to disrupt specific functions of Cx46 and find that Cx46-mediated gap-junction coupling is critical for CSCs. To develop a Cx46 targeting strategy, we screen a clinically relevant small molecule library and identify clofazimine as an inhibitor of Cx46-specific cell-cell communication. Clofazimine attenuates proliferation, self-renewal, and tumor growth and synergizes with temozolomide to induce apoptosis. Although clofazimine does not cross the blood-brain barrier, the combination of clofazimine derivatives optimized for brain penetrance with standard-of-care therapies may target glioblastoma CSCs. Furthermore, these results demonstrate the importance of targeting cell-cell communication as an anti-cancer therapy