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Objective: To gain insight into the current management of patients with type 2 diabetes mellitus by Canadian primary care physicians., Method: A total of 479 primary care physicians from across Canada submitted data on 5123 type 2 diabetes patients whom they had seen on a single day on or around World Diabetes Day, November 14, 2012., Results: Mean glycated hemoglobin (A1C) was 7.4%, low-density lipoprotein (LDL-C) was 2.1 mmol/L and blood pressure (BP) was 128/75 mm Hg. A1C ≤7.0% was met by 50%, LDL-C ≤2.0 mmol/L by 57%, BP <130/80 mm Hg by 36% and the composite triple target by 13% of patients. Diet counselling had been offered to 38% of patients. Of the 87% prescribed antihyperglycemic agents, 18% were on 1 non-insulin antihyperglycemic agent (NIAHA) (85% of which was metformin), 15% were on 2 NIAHAs, 6% were on ≥3 NIAHAs, 19% were on insulin only and 42% were on insulin + ≥1 NIAHA(s). Amongst the 81% prescribed lipid-lowering therapy, 88% were on monotherapy (97% of which was a statin). Among the 83% prescribed antihypertensive agents, 39%, 34%, 21% and 6% received 1, 2, 3 and >3 drugs, respectively, with 59% prescribed angiotensin-converting enzyme inhibitors and 35% angiotensin II receptor blockers., Conclusions: The Diabetes Mellitus Status in Canada survey highlights the persistent treatment gap associated with the treatment of type 2 diabetes and the challenges faced by primary care physicians to gain glycemic control and global vascular protection in these patients. It also reveals a higher use of insulin therapy in primary care practices relative to previous surveys. Practical strategies aimed at more effectively managing type 2 diabetes patients are urgently needed., (Copyright © 2013 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Surface micro- and nanostructural modifications of dental and orthopedic implants have shown promising in vitro, in vivo and clinical results. Surface wettability has also been suggested to play an important role in osteoblast differentiation and osseointegration. However, the available techniques to measure surface wettability are not reliable on clinically relevant, rough surfaces. Furthermore, how the differentiation state of osteoblast lineage cells impacts their response to micro/nanostructured surfaces, and the role of wettability on this response, remain unclear. In the current study, surface wettability analyses (optical sessile drop analysis, environmental scanning electron microscopic analysis and the Wilhelmy technique) indicated hydrophobic static responses for deposited water droplets on microrough and micro/nanostructured specimens, while hydrophilic responses were observed with dynamic analyses of micro/nanostructured specimens. The maturation and local factor production of human immature osteoblast-like MG63 cells was synergistically influenced by nanostructures superimposed onto microrough titanium (Ti) surfaces. In contrast, human mesenchymal stem cells cultured on micro/nanostructured surfaces in the absence of exogenous soluble factors exhibited less robust osteoblastic differentiation and local factor production compared to cultures on unmodified microroughened Ti. Our results support previous observations using Ti6Al4V surfaces showing that recognition of surface nanostructures and subsequent cell response is dependent on the differentiation state of osteoblast lineage cells. The results also indicate that this effect may be partly modulated by surface wettability. These findings support the conclusion that the successful osseointegration of an implant depends on contributions from osteoblast lineage cells at different stages of osteoblast commitment., (Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Telemedicine has become an increasingly popular option for long-distance/virtual medical care and education, but many telemedicine ventures fail to grow beyond the initial pilot stage. Studying the business models of successful telemedicine ventures can help develop business strategies for upcoming ventures. This article describes business models of eight telemedicine ventures from different regions of the world using Osterwalder's "Business Model Canvas." The ventures are chosen on the basis of their apparent success and their diverse value chains. The business models are compared to draw inferences and lessons regarding their business strategy and contextual factors that influenced it. Key differences between telemedicine business practices in developing and developed countries are also discussed. The purpose of this article is to inform and inspire the business strategy of the next generation of telemedicine ventures to be economically sustainable and to successfully address local healthcare challenges.

Mammalian cell-adhesion kinetics is measured by counting the number of cells lost from suspension due to adhesion to planar or particulate substrata as a function of time rather than by the counting of adherent cells that is widely applied in the literature. A simple statistical model shows that this "suspension-depletion" method is most accurate at low cell counts in the critical early stage of cell adhesion that is diagnostic of forces in close proximity between cell and substratum responsible for cell adhesion. Furthermore, suspension depletion avoids experimental artifacts associated with substratum rinsing and the removal of cells from the substratum using enzymatic and/or mechanical methods. Experimental method is demonstrated for three different cell types (MDCK, epithelioid; MC3T3-E1, pre-osteoblast; MDA-MB-231, human breast tumor) adhering to seven different substrata incrementally sampling the observable water-wettability range in Petri-dish format, as well as MDCK adhesion to particulate carriers in stirred suspension. Suspension depletion is ideal for biocompatibility and fouling studies where quantification of "low-and-slow" cell adhesion is important. In particular, it is shown that a typical method of counting adherent cells does not correctly measure adhesion kinetics to hydrophobic surfaces that are generally resistant to mammalian cell adhesion., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The severity of heavy drinking among Asian Americans has often been dismissed because of relatively low rates compared to other racial/ethnic groups. However, higher depression and suicide rates among Asian Americans and their association to alcohol use suggest serious detrimental effects of heavy alcohol use among Asian Americans. Gender differences in heavy drinking have been documented among other immigrant based ethnic minorities, little is known of this pattern for Asian Americans. The purpose of the present study was to examine gender differences in heavy drinking, poor mental health, and substance use among a national sample of Asian Americans ( N = 581) in the National Latino and Asian American Study (NLAAS). Using National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines, heavy drinkers were categorized as those who exceeded the recommended weekly number of drinks (≥14 drinks/week for male and ≥7 drinks/week for female). Accordingly, six comparison groups were created (male non, light, and heavy drinkers, and female non, light, and heavy drinkers). Pearson's chi-square test was conducted to examine percentage distribution for the six groups for mental health disorders (i.e., suicidality, DSM-IV mental health endorsement for past 12-month and lifetime). Logistic regression was followed to determined predictors for heavy drinking behavior for men and for women. Female heavy drinkers reported significantly poorer mental health than non drinkers, light drinkers and male heavy drinkers, as indicated by higher rates of lifetime generalized anxiety, and depressive disorders. In contrast, male heavy drinkers were more likely to have lifetime substance use disorders. Findings suggest the need to develop gender-specific drinking interventions for Asian Americans that focus on improving mental health among women and substance treatment among men.

Staphylococcus aureus is an important human pathogen that causes skin and soft tissue abscesses. Abscess formation is not unique to staphylococcal infection and purulent discharge has been widely considered a physiological feature of healing and tissue repair. Here we present a different view, whereby S. aureus deploys specific virulence factors to promote abscess lesions that are distinctive for this pathogen. In support of this model, only live S. aureus is able to form abscesses, requiring genes that act at one or more of four discrete stages during the development of these infectious lesions. Protein A and coagulases are distinctive virulence attributes for S. aureus, and humoral immune responses specific for these polypeptides provide protection against abscess formation in animal models of staphylococcal disease., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is an age-related dementia, with the pathological hallmarks of neuritic plaques and neurofibrillary tangles, brain atrophy and loss of synaptic terminals. Dysfunctional mitochondrial bioenergetics is implicated as a contributing factor to the cognitive decline observed in AD. We hypothesized that, in the presence of the AD neurotoxic peptide beta-amyloid, mitochondrial respiration is impaired early in synaptic terminals, which are vital to cognitive performance, preferentially in cognitive centers of the brain. We compared oxygen consumption in synaptosomal and perikaryal mitochondria prepared from the cerebral cortex and cerebellum of wild type (WT) and AD transgenic Tg2576 mice. Compared to WT mice, Tg2576 mice showed decreased mitochondrial respiration in the cerebral cortex specifically in synaptosomal fraction, while the perikaryal mitochondria were unaffected. Neither mitochondrial fraction was affected in the cerebellum of Tg2576 mice as compared to WT. The occurrence of a bioenergetic defect in synaptic terminals of mice overexpressing mutant beta-amyloid, in particular in an area of the brain important to cognition, points to an early role of mitochondrial defects in the onset of cognitive deficits in AD.

Over the past decade, clinical practice guidelines have lowered their glycemic targets for people with type 2 diabetes. However, recent randomized controlled trials (ACCORD, ADVANCE, and VADT) demonstrate that intensive glycemic targets do not reduce cardiovascular risk among higher-risk individuals over a period of 3.5 to 5 years. Thus, targeting a hemoglobin A(1c) below 6% among high-risk patients should not be recommended. However, the 10-year post-trial monitoring of the UKPDS demonstrated cardiovascular benefit of intensive glycemic control among those with newly diagnosed type 2 diabetes over a median follow-up of 17 years. This raises the possibility that cardiovascular benefits of glycemic control require many years to manifest and early intervention may carry greater benefit. Therefore, these recent trials continue to support the recommended hemoglobin A(1c) target of below 7% to reduce microvascular complications in type 2 diabetes and perhaps macrovascular complications in those with newly diagnosed diabetes.

Among individuals with diabetes mellitus, cardiovascular disease remains the leading cause of death, despite the many treatment modalities that have been developed over time. The PPAR family, including PPAR-alpha, play important roles in glucose and lipid metabolism and atherosclerosis and thus are potential therapeutic targets. Fibrates act upon PPAR-alpha and appear to target the typical dyslipidaemia of diabetes. Several large prospective clinical trials have shown both primary prevention and secondary prevention benefit with fibrates, although they only had small subgroups of patients with diabetes. The first large outcome study to exclusively study those with diabetes was the FIELD study, which showed no reduction in the primary cardiovascular end-point and only some benefit in the secondary end-point. There are many potential explanations for these results; however, it would appear that at present, there is no role for fibrates as monotherapy for the reduction of cardiovascular risk among those with diabetes. However, their potential role in combination with statin therapy remains to be further elucidated with ongoing studies.

Diabetes mellitus is a chronic disease that is growing in prevalence worldwide. Pharmacologic therapy is often necessary to achieve optimal glycemic control in the management of diabetes. Orally administered antihyperglycemic agents (OHAs) can be used either alone or in combination with other OHAs or insulin. The number of available OHAs has increased significantly in the last decade, which translates into more therapeutic options and complex decision-making for physicians. This review article is designed to help with these decisions. We review the mechanism of action, efficacy and side effects of the different classes of OHAs (alpha-glucosidase inhibitors, biguanides, insulin secretagogues, insulin sensitizers and intestinal lipase inhibitor) and discuss the current recommendations for their use.

Despite advances in pharmacological therapies to treat and prevent cardiovascular disease, it remains the leading cause of death in Canada. There now exists a large body of evidence demonstrating that reduction of low-density lipoprotein cholesterol (LDL-C) effectively reduces cardiovascular morbidity and mortality. Despite this, a large proportion of patients who would benefit from this intervention are still not achieving the recommended LDL-C levels. The currently available pharmacological agents, especially statins, are very effective but have rare, yet potentially significant, side effects. The likelihood of these side effects is small but does increase with increasing drug dose. As a result, dosages are often not titrated upward because they cannot be tolerated or their side effects are feared by either physicians or patients. Ezetimibe is a new cholesterol absorption inhibitor that is safe and effective in total cholesterol and LDL-C reduction. When used as monotherapy or in combination with a statin, ezetimibe has been shown to reduce LDL-C by an additional 15% to 20% and improve high-density lipoprotein cholesterol and triglycerides slightly. The addition of ezetimibe to a statin produces an LDL-C reduction of similar magnitude to a three-fold increase in statin dose. The combination of ezetimibe and either atorvastatin or simvastatin has also been found to be beneficial in patients with homozygous familial hypercholesterolemia. The safety profile is similar to placebo and no significant drug interactions have been observed. There is no clinical trial outcome evidence associated with the use of ezetimibe at this time. Thus, ezetimibe is a safe and effective addition to the current LDL-C lowering regimen and is most useful in those patients who cannot achieve sufficient LDL-C reduction with an adequate dose of statin alone, cannot tolerate a statin or are fearful of a statin.