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Imeglimin is a novel agent currently in development to treat type 2 diabetes. Laboratory studies have demonstrated that it has the potential to impact the three main pathophysiologic components of type 2 diabetes: impaired glucose uptake by muscle tissue, excess hepatic gluconeogenesis, and increased beta-cell apoptosis. Preliminary human studies that have been published within the last 2 years demonstrate that imeglimin improves hemoglobin A1c and fasting plasma glucose similarly when compared with metformin and with sitagliptin. There has also been a low incidence of adverse effects, especially hypoglycemia, reported in these early human studies. Currently, imeglimin is lacking long-term evidence to demonstrate any effects on its cardiovascular safety, and data on morbidity and mortality, though some studies are currently in progress. There is great potential for imeglimin, if FDA approved, to play a significant role in the type 2 diabetes management algorithm.  相似文献   
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Competency-based assessments (CBAs) have gained traction in graduate medical education and inform important learner outcomes through the continuum of medical training. Active participation in new CBAs presents challenges to faculty working in a busy clinical environment. As such, the implementation of new CBAs can be approached with intention to foster acceptance and engagement with new evaluations. This paper describes strategies utilized to implement CBAs among clinician educators during a national assessment pilot. Our methods are grounded in educational, psychological, business, ecological, communication, and information technology theory. Our primary interventions included creating a multilevel vision, engaging a dedicated work group, incorporating quality improvement methodology, and integrating technology to successfully implement the assessments. These practical and effective interventions may also be applied to the implementation of other educational innovations.  相似文献   
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Background  

Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis.  相似文献   
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Background

Cardiovagal baroreflex gain (cBRG) reflects an individual's ability to buffer swings in blood pressure. It is not well understood how this mechanism is influenced by physical activity in pregnancy. Because pregnant women tend to engage in low levels of moderate-to-vigorous physical activity (MVPA) and high levels of sedentary behaviour, we sought to determine the influence of MVPA and sedentary behaviour on cBRG and mean arterial pressure (MAP) in pregnancy.

Methods

Fifty-eight third trimester (31.9 ± 3.0 weeks) normotensive pregnant women (31.2 ± 2.8 years) were tested. Heart rate (electrocardiogram) and blood pressure (systolic blood pressure and MAP; finger photoplethysmography) were collected on a beat-by-beat basis, and averaged over 3 minutes of rest. Spontaneous cBRG was calculated as the slope of the relationship between fluctuations in systolic blood pressure and heart rate. Objective measures of MVPA and sedentary behaviour were collected over a 7-day period using an ActiGraph accelerometer (model wGTX3-BT; ActiGraph LLC, Pensacola, FL).

Results

Participants spent 67.5 ± 7.9% of waking hours engaged in sedentary behaviour, and performed 68.6 ± 91.9 minutes of MVPA per week. Sedentary behaviour was not related to cBRG (r = ?0.035; P = 0.793) or MAP (r = ?0.033; P = 0.803). However, MVPA was positively associated with cBRG (r = 0.315; P = 0.016), but not MAP (r = ?0.115; P = 0.389). The association between MVPA and cBRG remained significant after controlling for age, pre-pregnancy body mass index, gestational age, and wear time (r = 0.338; P = 0.013), indicating that women who engaged in greater amounts of MVPA showed increased cBRG.

Conclusions

Our data suggest that increased MVPA, but not necessarily reduced sedentary behaviour, might be beneficial for reflex control of blood pressure during pregnancy.  相似文献   
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PURPOSEImage-guided adaptive brachytherapy (IGABT) recently has shown excellent clinical outcomes with superior local control and less toxicity. For IGABT, T2W (T2-weighted) MRI is the gold standard. However, studies have shown that target delineation with the same results in uncertainties, poor interobserver variabilities, and low conformity indices for high-risk clinical target volume contours. In this study, we investigate the role of diffusion-weighted imaging–derived apparent diffusion coefficient (ADC) maps to aid in IGABT. We also evaluated ADC from the baseline to brachytherapy.Methods and MaterialsThirty selected patients were enrolled for this study, and two MRIs were taken at diagnosis and before brachytherapy. Patients were divided into two groups, Group 1 being patients with parametrial involvement before external beam radiotherapy and no parametrial involvement before brachytherapy. Group 2 included patients with parametrial involvement before external beam radiotherapy and persistent parametrial involvement before brachytherapy. ADC was measured at the center, edge, and 1 cm from the edge.ResultsThe measured ADC increased from diagnosis to brachytherapy, and this increase was more for the patients in Group 1 than in Group 2. The mean TDadc (diagnosis ADC, center), TEadc (tumor edge ADC diagnosis), and T1cmDadc (1 cm from edge at diagnosis) were 0.884, 1.45, and 1.9 × 10?3 mm2/s, respectively. The TBadc (ADC at brachytherapy, center), TEBadc (tumor edge ADC at brachytherapy), and TE1cmBadc (1 cm from edge brachytherapy) were 1.2, 1.8, and 2.3 × 10?3 mm2/s, respectively, p-value <0.00001. No abnormal ADC was present outside the high-risk clinical target volume contours.ConclusionMRI-based IGABT using T2W imaging essentially covers all functionally abnormal zones at brachytherapy. Diffusion-weighted imaging, along with ADC maps, should only be used as a supplement for target delineation.  相似文献   
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