New Media, Technology and Neurology Education.

The use of technology in neurology education has revolutionized many aspects of medical teaching, addressing some important challenges of modern education such as information overload and the unique needs of millennial learners. However, it also has inherent problems, such as depersonalization and high development costs. Due to the heterogeneity of different applications, it is difficult to establish general principles to guide front line educators, but it may be possible to describe "minimum" best practice elements. In this article, we examine commonalities of some of the most successful uses of technology in neurology education. We suggest the following for effective application of technology: (1) match technology to predetermined educational objectives, (2) characterize learners in relationship to technology, (3) optimize how technological components fit into the learning environment, (4) monitor and manage learner engagement with technology, (5) perform cost analyses, and (6) explore opportunities for educational scholarship and research.

Curriculum mapping as a tool to facilitate curriculum development: a new School of Medicine experience.

BACKGROUND: Every curriculum needs to be reviewed, implemented and evaluated; it must also comply with the regulatory standards. This report demonstrates the value of curriculum mapping (CM), which shows the spatial relationships of a curriculum, in developing and managing an integrated medical curriculum. METHODS: A new medical school developed a clinical presentation driven integrated curriculum that incorporates the active-learning pedagogical practices of many educational institutions worldwide while adhering to the mandated requirements of the accreditation bodies. A centralized CM process was run in parallel as the curriculum was being developed. A searchable database, created after the CM data was uploaded into an electronic curriculum management system, was used to ensure placing, integrating, evaluating and revising the curricular content appropriately. RESULTS: CM facilitated in a) appraising the content integration, b) identifying gaps and redundancies, c) linking learning outcomes across all educational levels (i.e. session to course to program), c) organizing the teaching schedules, instruction methods, and assessment tools and d) documenting compliance with accreditation standards. CONCLUSIONS: CM is an essential tool to develop, review, improve and refine any integrated curriculum however complex. Our experience, with appropriate modifications, should help other medical schools efficiently manage their curricula and fulfill the accreditation requirements at the same time.

Development and validation of an instrument to assess the prescribing readiness of medical students in Malaysia.

BACKGROUND: Prescribing incompetence is an important factor that contributes to prescribing error, and this is often due to inadequate training during medical schools. We therefore aimed to develop and validate an instrument to assess the prescribing readiness of medical students (PROMS) in Malaysia. METHODS: The PROMS comprised of 26 items with four domains: undergraduate learning opportunities; hands-on clinical skills practice; information gathering behaviour; and factors affecting the learning of prescribing skills. The first three domains were adapted from an existing questionnaire, while items from the last domain were formulated based on findings from a nominal group discussion. Face and content validity was determined by an expert panel, pilot tested in a class of final year (Year 5) medical students, and assessed using the Flesch reading ease. To assess the reliability of the PROMS, the internal consistency and test-retest (at baseline and 2 weeks later) were assessed using the Wilcoxon Signed Ranks test and Spearman's rho. The discriminative validity of the PROMS was assessed using the Mann-Whitney U-test (to assess if the PROMS could discriminate between final year medical students from a public and a private university). RESULTS: A total of 119 medical students were recruited. Flesch reading ease was 46.9, indicating that the instrument was suitable for use in participants undergoing tertiary education. The overall Cronbach alpha value of the PROMS was 0.695, which was satisfactory. Test-retest showed no difference for 25/26 items, indicating that our instrument was reliable. Responses from the public and private university final year medical students were significantly different in 10/26 items, indicating that the PROMS was able to discriminate between these two groups. Medical students from the private university reported fewer learning opportunities and hands-on practice compared to those from the public university. On the other hand, medical students from the private university reported more frequent use of both web based and non-web-based resources compared to their public university counterparts. CONCLUSIONS: The PROMS instrument was found to be a reliable and valid tool for assessing medical students' readiness to prescribe in Malaysia. It may also inform on the adequacy of medical programmes in training prescribing skills.

Demise of the USMLE Step-2 CS exam: Rationalizing a way forward.

The COVID-19 pandemic has compelled rethinking and changes in medical education, the most controversial perhaps being the cancelation of USMLE Step-2 Clinical Skills exam (Step-2 CS). What started in March of 2020 as suspension of this professional licensure exam, because of concerns about infection risk for examinees, standardized patients (SPs), and administrators, soon became permanent cancelation in January 2021. Expectedly, it triggered debate in medical education circles. Positively, however, the USMLE regulatory agencies (NBME and FSMB) saw an opportunity to innovate an exam tainted with perceptions of validity deficits, cost, examinee inconvenience, and worries about future pandemics; they therefore called for a public debate to fashion a way forward. We have approached the issue by defining Clinical Skills (CS), exploring its epistemology and historic evolution, including assessment modalities from Hippocratic times to the modern era. We defined CS as the art of medicine manifest in the physician-patient encounter as history taking (driven by communication skills and cultural competence) and physical examination. We classified CS components into knowledge and psychomotor skill domains, established their relative importance in the physician process (clinical reasoning) of diagnosis, thus establishing a theoretical framework for developing valid, reliable, feasible, fair, and verifiable CS assessment. Given the concerns for COVID-19 and future pandemics, we established that CS can largely be assessed remotely, and what could not, can be assessed locally (school/regional consortia level) as part of a USMLE-regulated/supervised assessment regimen with established national standards, thus maintaining USMLE's fiduciary responsibilities. We have suggested a national/regional program for faculty development in CS curriculum development, and assessment, including standard setting skills. This pool of expert faculty will form the nucleus of our proposed USMLE-regulated External Peer Review Initiative (EPRI). Finally, we suggest that CS evolves into an academic discipline/department of its own, rooted in scholarship.

Obesity, metabolic syndrome, adipocytes and vascular function: A holistic viewpoint.

1. Obesity is a metabolic disease of pandemic proportions largely arising from positive energy balance, a consequence of sedentary lifestyle, conditioned by environmental and genetic factors. Several central and peripheral neurohumoral factors (the major ones being the anorectic adipokines leptin and adiponecin and the orexigenic gut hormone ghrelin) acting on the anorectic (pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript) and orexigenic (neuropeptide Y and agouti gene-related protein) neurons regulate energy balance. These neurons, mainly in the arcuate nucleus of the hypothalamus, project to parts of the brain modulating functions such as wakefulness, autonomic function and learning. A tilt in the anorectic-orexigenic balance, perhaps determined genetically, leads to obesity. 2. Excess fat deposition requires space, created by adipocyte (hypertrophy and hyperplasia) and extracellular matrix (ECM) remodelling. This process is regulated by several factors, including several adipocyte-derived Matrix metalloproteinases and the adipokine cathepsin, which degrades fibronectin, a key ECM protein. Excess fat, also deposited in visceral organs, generates chronic low-grade inflammation that eventually triggers insulin resistance and the associated comorbidities of metabolic syndrome (hypertension, atherosclerosis, dyslipidaemia and diabetes mellitus). 3. The perivascular adipose tissue (PVAT) has conventionally been considered non-physiological structural tissue, but has recently been shown to serve a paracrine function, including the release of adipose-derived relaxant and contractile factors, akin to the role of the vascular endothelium. Thus, PVAT regulates vascular function in vivo and in vitro, contributing to the cardiovascular pathophysiology of the metabolic syndrome. Defining the mechanism of PVAT regulation of vascular reactivity requires more and better controlled investigations than currently seen in the literature.

Characterizing the mechanisms of insulin vasodilatation of normal and streptozotocin-induced diabetic rat aorta.

The mechanism by which insulin causes vasodilatation remains unclear, so we explored this in aortic rings from normal Wistar Kyoto and streptozotocin-induced diabetic rats. Insulin-induced relaxation of phenylephrine-contracted [endothelium (ED) intact or denuded] aortic rings was recorded in the presence or absence of various drug probes. Insulin relaxant effect was more in ED-intact than in-denuded tissues from normal or diabetic rats. l-NAME or methylene blue partially inhibited insulin effect in ED-intact but not the ED-denuded tissues, whereas indomethacin (cyclooxygenase inhibitor) had no effect on any of the tissues, indicating that insulin induces relaxation by ED-dependent and -independent mechanisms, the former via the NOS-cyclic guanosine monophosphate but not the cyclooxygenase pathway. The voltage-dependent K channel (KV) blocker (4-aminopyridine) inhibited insulin action in all the tissues (normal or diabetic, with or without ED), whereas the selective BKCa blocker, tetraethylammonium, inhibited it in normal (ED intact or denuded) but not in diabetic tissues, indicating that KV mediates insulin action in normal and diabetic tissues, whereas the BKCa mediates it only in normal tissues, with possible pathophysiologic absence in diabetic tissues. The inward rectifier K channel (Kir) blocker (barium chloride) significantly inhibited insulin effect only in ED-intact or -denuded diabetic tissues, whereas the KATP channel blocker, glibenclamide, inhibited it only in the ED-denuded diabetic tissues, suggesting that Kir channels mediate insulin-induced relaxation in ED-intact or -denuded diabetic tissues, whereas the KATP channel mediates it in ED-denuded diabetic tissues. All the agents combined did not abolish insulin action, suggestive of a direct vasodilatory effect. In conclusion, insulin causes vasodilatation in normal and diabetic tissues via ED-dependent and -independent mechanisms differentially modulated by K channels, some of which functions are altered in diabetes and thus are potential therapeutic targets.

Approaches to Teaching the Physical Exam to Preclerkship Medical Students: Results of a National Survey.

PURPOSE: To assess current approaches to teaching the physical exam to preclerkship students at U.S. medical schools. METHOD: The Directors of Clinical Skills Courses developed a 49-question survey addressing the approach, pedagogical methods, and assessment methods of preclerkship physical exam curricula. The survey was administered to all 141 Liaison Committee on Medical Education-accredited U.S. medical schools in October 2015. Results were aggregated across schools, and survey weights were used to adjust for response rate and school size. RESULTS: One hundred six medical schools (75%) responded. Seventy-nine percent of schools (84) began teaching the physical exam within the first two months of medical school. Fifty-six percent of schools (59) employed both a "head-to-toe" comprehensive approach and a clinical reasoning approach. Twenty-three percent (24) taught a portion of the physical exam interprofessionally. Videos, online modules, and simulators were used widely, and 39% of schools (41) used bedside ultrasonography. Schools reported a median of 4 formative assessments and 3 summative assessments, with 16% of schools (17) using criterion-based standard-setting methods for physical exam assessments. Results did not vary significantly by school size. CONCLUSIONS: There was wide variation in how medical schools taught the physical exam to preclerkship students. Common pedagogical approaches included early initiation of physical exam instruction, use of technology, and methods that support clinical reasoning and competency-based medical education. Approaches used by a minority of schools included interprofessional education, ultrasound, and criterion-based standard-setting methods for assessments. Opportunities abound for research into the optimal methods for teaching the physical exam.

Resources Used to Teach the Physical Exam to Preclerkship Medical Students: Results of a National Survey.

PURPOSE: To examine resources used in teaching the physical exam to preclerkship students at U.S. medical schools. METHOD: The Directors of Clinical Skills Courses developed a 49-question survey addressing resources and pedagogical methods employed in preclerkship physical exam curricula. The survey was sent to all 141 Liaison Committee on Medical Education-accredited medical schools in October 2015. Results were averaged across schools, and data were weighted by class size. RESULTS: Results from 106 medical schools (75% response rate) identified a median of 59 hours devoted to teaching the physical exam. Thirty-eight percent of time spent teaching the physical exam involved the use of standardized patients, 30% used peer-to-peer practice, and 25% involved examining actual patients. Approximately half of practice time with actual patients was observed by faculty. At 48% of schools (51), less than 15% of practice time was with actual patients, and at 20% of schools (21) faculty never observed students practicing with actual patients. Forty-eight percent of schools (51) did not provide compensation for their outpatient clinical preceptors. CONCLUSIONS: There is wide variation in the resources used to teach the physical examination to preclerkship medical students. At some schools, the amount of faculty observation of students examining actual patients may not be enough for students to achieve competency. A significant percentage of faculty teaching the physical exam remain uncompensated for their effort. Improving faculty compensation and increasing use of senior students as teachers might allow for greater observation and feedback and improved physical exam skills among students.

Effects of angiotensin 1-7 on the actions of angiotensin II in the renal and mesenteric vasculature of hypertensive and streptozotocin-induced diabetic rats.

Angiotensin 1-7, a heptapeptide derived from metabolism of either angiotensin I or angiotensin II, is a biologically active peptide of the renin-angiotensin system. The present study investigated the effect of angiotensin 1-7 on the vasopressor action of angiotensin II in the renal and mesenteric vasculature of Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and streptozotocin-induced diabetic rats. Angiotensin II-induced dose-dependent vasoconstrictions in the renal vasculature. The pressor response was enhanced in the SHR and reduced in the streptozotocin-diabetic rat compared to WKY rats. Angiotensin 1-7 attenuated the angiotensin II pressor responses in the renal vasculature of WKY and SHR rats. However, the ability to reduce angiotensin II response was diminished in diabetic-induced rat kidneys. The effect of angiotensin 1-7 was not inhibited by 1-[(4-(Dimethylamino)-3-methylphenyl] methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate (PD123319), an angiotensin AT(2) receptor antagonist. (D-ALA(7))-Angiotensin I/II (1-7) (D-ALA) (an angiotensin 1-7 receptor antagonist), indomethacin (a cyclo-oxygenase inhibitor), and N(omega)-Nitro-L-Arginine Methyl Ester (L-NAME)(a nitric oxide synthetase inhibitor) abolished the attenuation by angiotensin 1-7 in both WKY rats and SHR, indicating that its action is mediated by angiotensin 1-7 receptor that is either coupled to the release of prostaglandins and/or nitric oxide. The vasopressor responses to angiotensin II in mesenteric vasculature bed was also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses to angiotensin II were relatively smaller in SHR but no significant difference was observed between WKY and streptozotocin-induced diabetic rats. Angiotensin 1-7 attenuated the angiotensin II pressor responses in WKY, SHR and diabetic-induced mesenteric bed. The attenuation was observed at the lower concentrations of angiotensin II in WKY and diabetic-induced rats but at higher concentrations in SHR. Similar observation as in the renal vasculature was seen with PD123319, D-ALA, and L-NAME. Indomethacin reversed the attenuation by angiotensin 1-7 only in the SHR mesenteric vascular bed. The present findings support the regulatory role of angiotensin 1-7 in the renal and mesenteric vasculature, which is differentially altered in hypertension and diabetes.

Baicalein impairs vascular tone in normal rat aortas: role of superoxide anions.

Acute exposure to the flavonoid baicalein inhibited endothelium-dependent relaxation in physiological arteries, although the mechanisms are not fully understood. We investigated the effect of baicalein on vascular tone in Wistar-Kyoto (WKY) rat isolated aortic rings in the presence and absence of oxidative stress to further determine the underlying mechanisms. Exposure to baicalein (10 microM) completely abolished endothelium-dependent relaxation induced by acetylcholine and attenuated significantly the endothelium-independent relaxation induced by sodium nitroprusside. Baicalein, similar to Nomega-nitro-L-arginine methyl ester (L-NAME, 10 microM), potentiated significantly the contractile response of aortic rings to alpha1-adrenoceptor agonist phenylephrine. In the presence of L-NAME the baicalein effect on phenylphrine contraction or acetylcholine relaxation was unaltered, suggesting that these effects of baicalein are (like L-NAME effect) endothelial nitric oxide synthase (eNOS)/endothelium-derived nitric oxide-dependent. Inhibition of cyclooxygenase activity with indomethacin (10 microM) or scavenging of superoxide anions with superoxide dismutase (150 units/ml), but not scavenging of hydrogen peroxide with catalase (800 units/ml), enhanced significantly by an essentially similar extent the relaxation to acetylcholine in baicalein-pretreated aortic rings. Relaxant effect to acetylcholine was significantly attenuated in control aortic rings, but was completely abolished in baicalein-pretreated aortic rings in the presence of reduced form of beta-nicotinamide adenine di-nucleotide (beta-NADH, 300 microM). Baicalein blocked beta-NADH (300 microM)-induced transient contractions, suggesting that baicalein may have inhibited activity of NADH/NADPH-oxidase. Baicalein did not alter the failure of acetylcholine to induce relaxation in the presence of pyrogallol (300 microM). In summary, acute exposure to baicalein impairs eNOS/endothelium-derived nitric oxide-mediated vascular tone in rat aortas through the inhibition of endothelium-derived nitric oxide bioavailability coupled to reduced bioactivity of endothelium-derived nitric oxide and to cyclooxygenase-mediated release of superoxide anions.

Quercetin and pioglitazone synergistically reverse endothelial dysfunction in isolated aorta from fructose-streptozotocin (F-STZ)-induced diabetic rats.

Pioglitazone is an anti-diabetic drug with potential to cause adverse effects following prolonged use. This study, therefore, investigated the effects of combination treatment of a subliminal concentration of pioglitazone and quercetin, a potent antioxidant, on vascular reactivity of aorta isolated from fructose-streptozotocin (F-STZ)-induced diabetic rats. Relaxation to acetylcholine and sodium nitroprusside, and contraction to phenylephrine were tested in organ bath chambers following pre-incubation with vehicle (DMSO; 0.05%), quercetin (10-7 M), pioglitazone (10-7 M), or their combination (P+Q; 10-7 M each drug). Subliminal concentration of quercetin or pioglitazone did not alter the acetylcholine- induced relaxation nor the phenylephrine-induced contraction in both normal rat and diabetic F-STZ induced tissues. However, P+Q combination synergistically improved the impaired acetylcholine-induced relaxation and decreased the elevated phenylephrine-induced contraction in aortic rings from diabetic, but not in the normal rats. Neither mono nor combination treatment altered sodium nitroprusside-induced relaxation. The combination also synergistically decreased superoxide anion and increased nitric oxide production compared to the individual treatments in aorta from diabetic rats. Overall, these data demonstrated a synergistic effect, in which, a combination (P+Q; 10-7 M each drug) caused a significantly greater effect than 10-6 M of either agent in improving endothelial function of isolated diabetic aorta. In conclusion, a combination of subliminal concentrations of pioglitazone and quercetin is able to decrease oxidative stress and provide synergistic vascular protection in type 2 diabetes mellitus and thus the possibility of using quercetin as a supplement to pioglitazone in the treatment of diabetes with the goal of reducing pioglitazone toxicity.

Effect of quercetin on altered vascular reactivity in aortas isolated from streptozotocin-induced diabetic rats.

The present work examined ex vivo the acute effect of quercetin on diabetic rat aortic ring reactivity in response to endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) relaxants, and to the alpha(1)-adrenergic agonist phenylephrine (PE). Responses were compared to those of aortic rings from age- and sex-matched euglycemic rats. Compared to euglycemic rat aortic rings, diabetic rings showed less relaxation in response to ACh and SNP, and greater contraction in response to PE. Pretreatment with quercetin (10microM, 20min) increased ACh-induced relaxation and decreased PE-induced contraction in diabetic, but did not affect euglycemic rat aortic ring responses. Following pretreatment with the nitric oxide synthase inhibitor Nomega-nitro-l-arginine methyl ester (l-NAME, 10microM), quercetin reduced PE-induced contractions in both aortic ring types, although l-NAME attenuated the reduction in the diabetic rings. Quercetin did not alter SNP vasodilatory effects in either ring type compared to their respective controls. These findings indicate that quercetin acutely improved vascular responsiveness in blood vessels from diabetic rats, and that these effects were mediated, at least in part, by enhanced endothelial nitric oxide bioavailability. These effects of quercetin suggest the possible beneficial effects of quercetin in vivo in experimental diabetes and possibly in other cardiovascular diseases.

The bioflavonoid quercetin synergises with PPAR-γ agonist pioglitazone in reducing angiotensin-II contractile effect in fructose-streptozotocin induced diabetic rats.

This study investigated the effects of combined minimal concentrations of quercetin and pioglitazone on angiotensin II-induced contraction of the aorta from fructose-streptozotocin (F-STZ)-induced type 2 diabetic rats and the possible role of superoxide anions (O2(-)) and nitric oxide (NO) in their potential therapeutic interaction. Contractile responses to Ang II of aortic rings from Sprague-Dawley (SD) and F-STZ rats were tested following pre-incubation of the tissues in the vehicle (DMSO; 0.05%), quercetin (Q, 0.1 µM), pioglitazone (P, 0.1 µM) or their combination (P + Q; 0.1 µM each). The amount of superoxide anion was evaluated by lucigenin-enhanced chemiluminescence and dihydroethidium fluorescence, and NO by assay of total nitrate/nitrite, and 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate. The synergistic reduction of Ang II-induced contraction of diabetic but not normal aorta with minimally effective concentrations of P + Q occurs through inhibiting O2(-) and increasing NO bioavailability. This finding opens the possibility of maximal vascular protective/antidiabetic effects with low dose pioglitazone combined with quercetin, thus minimizing the risk of adverse effects.

Des-aspartate angiotensin I (DAA-I) reduces endothelial dysfunction in the aorta of the spontaneously hypertensive rat through inhibition of angiotensin II-induced oxidative stress.

Des-aspartate angiotensin I (DAA-I), an endogenous nonapeptide, counteracts several effects of angiotensin II on vascular tone. The aim of this study was to investigate the acute protective effect of DAA-I on endothelial function in the spontaneously hypertensive rat (SHR) as well as its effect on angiotensin II-induced contractions and oxidative stress. Aortic rings were incubated with DAA-I (0.1µM) for 30min prior to the assessment of angiotensin II-induced contractions (0.1nM-10µM) in WKY and SHR aortas. Total nitrate and nitrite levels were assessed using a colorimetric method and reactive oxygen species (ROS) were measured by dihydroethidium (DHE) fluorescence and lucigenin-enhanced chemiluminescence. The effect of DAA-I was also assessed against endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside, respectively. Angiotensin II-induced contractions were significantly reduced by DAA-I, losartan and tempol. Incubation with ODQ (soluble guanylyl cyclase inhibitor) and removal of the endothelium prevented the reduction of angiotensin II-induced contractions by DAA-I. Total nitrate and nitrite levels were increased in DAA-I, losartan and tempol treated-SHR tissues while ROS level was reduced by DAA-I and the latter inhibitors. In addition, DAA-I significantly improved the impaired acetylcholine-induced relaxation in SHR aortas whilst sodium nitroprusside-induced endothelium-independent relaxation remained unaffected. The present findings indicate that improvement of endothelial function by DAA-I in the SHR aorta is mediated through endothelium-dependent release of nitric oxide and inhibition of angiotensin II-induced oxidative stress.

A preliminary evaluation of the efficacy and safety of Cogent db (an ayurvedic drug) in the glycemic control of patients with type 2-diabetes.

OBJECTIVES AND STUDY DESIGN: A nonrandomized, non-placebo-controlled clinical trial to evaluate the efficacy of Cogent db (an herbal preparation; Cybele Herbal Laboratories [PVT] Ltd. Kochi, Kerala State, India) as an adjuvant in the treatment of patients with type 2 diabetes was carried out during a 3-month period. SETTINGS/LOCATION: This study was conducted in two major peripheral clinics of Kuala Lumpur in the Klang Valley, Malaysia. SUBJECTS: A total of 39 Cogent db-treated cases and 40 age-matched controls were recruited for this preliminary study. Nineteen (19) subjects (10 and 9 from control and treatment groups, respectively) dropped out of the study leaving a total of 60 subjects (30 each for control and treatment groups) who completed the study. INTERVENTIONS: All subjects in the treatment group were given Cogent db (2 tablets three times daily after each meal) in addition to the regular allopathic drugs (Daonil, [Aventis Farma, SA Petaling Jaya, Selangor State, Malaysia] and Diamicron [Sevier, Bangkok, Thailand], with or without Metformin [Upha Corporation, Bangi, Selangor State, India]) that they took in common with the control group. OUTCOME MEASURES: Thirty-two (32) clinical variables were investigated, including liver enzymes, kidney function tests, hematologic parameters, blood glucose, insulin, and C-peptide assays. RESULTS: At the end of 3 months it was found that there was a significant decrease in the levels of fasting and postprandial blood glucose, cholesterol, triglycerides, glycated hemoglobin (Hb A(1C)) and fasting insulin in the treatment group compared to the controls. Cogent db did not alter the liver function tests, hematologic parameters, or the kidney function tests. CONCLUSIONS: These results concur with earlier animal studies that indicate that Cogent db is safe, reliable, tolerable, and efficacious in the control of type 2 diabetes mellitus.

Advancing safe drug use through interprofessional learning (IPL): a pilot study.

Interprofessional collaborative patient-centered care (IPCPC) improves healthcare quality and cost. Drug-related morbidity drives healthcare costs, thus requiring IPCPC approaches. The lack of educational preparedness for would-be IPCPC practitioners underlies the failure of historic IPCPC attempts, hence today's emphasis on pre-licensure interprofessional education (IPE). A pilot IPE class was conducted on rational drug use (RDU) through rational drug prescribing. Twenty fourth-year nursing students and 88 second-year medical students participated (8-10 medical per 2-3 nursing students) in small group activity in a lecture hall. A case study on rational drug choice and prescription writing processes from medical and nursing perspectives was used. Eighty of 108 (74%) students completed the post-activity questionnaire and were satisfied with the class, with a mean weighted score (mws) of 0.8. The learning outcomes (mws = 1.0) contributed more (P < 0.05) to students satisfaction than the organization/delivery (mws = 0.6). A majority (84-94%) agreed the class objectives were achieved and favored more classes. Interaction with other healthcare professionals and the crowded classroom were, respectively, the most- and least-liked aspects of the class. The study revealed students' appetite for IPE, highlights the challenges in developing IPE curricula, and could serve as impetus for schools developing IPE for RDU curricula.

Boldine protects endothelial function in hyperglycemia-induced oxidative stress through an antioxidant mechanism.

Increased oxidative stress is involved in the pathogenesis and progression of diabetes. Antioxidants are therapeutically beneficial for oxidative stress-associated diseases. Boldine ([s]-2,9-dihydroxy-1,10-dimethoxyaporphine) is a major alkaloid present in the leaves and bark of the boldo tree (Peumus boldus Molina), with known an antioxidant activity. This study examined the protective effects of boldine against high glucose-induced oxidative stress in rat aortic endothelial cells (RAEC) and its mechanisms of vasoprotection related to diabetic endothelial dysfunction. In RAEC exposed to high glucose (30 mM) for 48 h, pre-treatment with boldine reduced the elevated ROS and nitrotyrosine formation, and preserved nitric oxide (NO) production. Pre-incubation with ß-NAPDH reduced the acetylcholine-induced endothelium-dependent relaxation; this attenuation was reversed by boldine. Compared with control, endothelium-dependent relaxation in the aortas of streptozotocin (STZ)-treated diabetic rats was significantly improved by both acute (1 µM, 30 min) and chronic (20mg/kg/daily, i.p., 7 days) treatment with boldine. Intracellular superoxide and peroxynitrite formation measured by DHE fluorescence or chemiluminescence assay were higher in sections of aortic rings from diabetic rats compared with control. Chronic boldine treatment normalized ROS over-production in the diabetic group and this correlated with reduction of NAD(P)H oxidase subunits, NOX2 and p47(phox). The present study shows that boldine reversed the increased ROS formation in high glucose-treated endothelial cells and restored endothelial function in STZ-induced diabetes by inhibiting oxidative stress and thus increasing NO bioavailability.

The aporphine alkaloid boldine improves endothelial function in spontaneously hypertensive rats.

Boldine, a major aporphine alkaloid found in Chilean boldo tree, is a potent antioxidant. Oxidative stress plays a detrimental role in the pathogenesis of endothelial dysfunction in hypertension. In the present study, we investigated the effects of boldine on endothelial dysfunction in hypertension using spontaneously hypertensive rats (SHR), the most studied animal model of hypertension. SHR and their age-matched normotensive Wistar-Kyoto (WKY) rats were treated with boldine (20 mg/kg per day) or its vehicle, which served as control, for seven days. Control SHR displayed higher systolic blood pressure (SBP), reduced endothelium-dependent aortic relaxation to acetylcholine (ACh), marginally attenuated endothelium-independent aortic relaxation to sodium nitroprusside (SNP), increased aortic superoxide and peroxynitrite production, and enhanced p47(phox) protein expression as compared with control WKY rats. Boldine treatment significantly lowered SBP in SHR but not in WKY. Boldine treatment enhanced the maximal relaxation to ACh in SHR, but had no effect in WKY, whereas the sensitivity to ACh was increased in both SHR and WKY aortas. Boldine treatment enhanced sensitivity, but was without effect on maximal aortic relaxation responses, to SNP in both WKY and SHR aortas. In addition, boldine treatment lowered aortic superoxide and peroxynitrite production and downregulated p47(phox) protein expression in SHR aortas, but had no effect in the WKY control. These results show that boldine treatment exerts endothelial protective effects in hypertension, achieved, at least in part, through the inhibition of NADPH-mediated superoxide production.

Gender discrimination in the influence of hyperglycemia and hyperosmolarity on rat aortic tissue responses to insulin.

Hyperglycaemia initiates endothelial dysfunction causing diabetic macro- and micro-vasculopathy, the main causes of morbidity and mortality in diabetes mellitus. The vasculopathy exhibits gender peculiarities. We therefore explored gender differences in comparing the effects of hyperglycaemia (50 mM) per se with its hyperosmolar (50 mM) effects on vascular tissue responses to insulin. Endothelium-intact or denuded thoracic aortic rings from age-matched male and female Sprague-Dawley rats were incubated for 10 min or 6 h (acute versus chronic exposure) in normal, hyperglycaemic or hyperosmolar Krebs solution. Relaxant responses to insulin (6.9x10(-7)-6.9x10(-5) M) of the phenylephrine-contracted tissues were recorded. Endothelium denudation in both genders inhibited relaxation to insulin in all conditions, more significantly in female than in male tissues, suggesting the female response to insulin is more endothelium-dependent than the male. Acutely and chronically exposed normoglycemic endothelium-intact or -denuded tissues responded similarly to insulin. Chronic hyperglycemic or hyperosmolar exposure did not alter the endothelium-denuded tissue responses to insulin, whereas the responses of the endothelium-intact male and female hyperosmolar, and male hyperglycemic tissues were enhanced. The results show that insulin exerts an endothelium-dependent and independent relaxation with the female tissue responses more endothelium-dependent than the male. The data also suggest that hyperosmolarity per se enhances aortic tissue relaxant responses to insulin whereas hyperglycemia per se inhibits the same and more so in female than male tissues. These effects are endothelium-dependent.