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Vasodilatory Actions of Glucagon-Like Peptide 1 Are Preserved in Skeletal and Cardiac Muscle Microvasculature but Not in Conduit Artery in Obese Humans With Vascular Insulin Resistance

OBJECTIVE

Obesity is associated with microvascular insulin resistance, which is characterized by impaired insulin-mediated microvascular recruitment. Glucagon-like peptide 1 (GLP-1) recruits skeletal and cardiac muscle microvasculature, and this action is preserved in insulin-resistant rodents. We aimed to examine whether GLP-1 recruits microvasculature and improves the action of insulin in obese humans.

RESEARCH DESIGN AND METHODS

Fifteen obese adults received intravenous infusion of either saline or GLP-1 (1.2 pmol/kg/min) for 150 min with or without a euglycemic insulin clamp (1 mU/kg/min) superimposed over the last 120 min. Skeletal and cardiac muscle microvascular blood volume (MBV), flow velocity and blood flow, brachial artery diameter and blood flow, and pulse wave velocity (PWV) were determined.

RESULTS

Insulin failed to change MBV or flow in either skeletal or cardiac muscle, confirming the presence of microvascular insulin resistance. GLP-1 infusion alone increased MBV by ~30% and ~40% in skeletal and cardiac muscle, respectively, with no change in flow velocity, leading to a significant increase in microvascular blood flow in both skeletal and cardiac muscle. Superimposition of insulin to GLP-1 infusion did not further increase MBV or flow in either skeletal or cardiac muscle but raised the steady-state glucose infusion rate by ~20%. Insulin, GLP-1, and GLP-1 + insulin infusion did not alter brachial artery diameter and blood flow or PWV. The vasodilatory actions of GLP-1 are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes.

CONCLUSIONS

In obese humans with microvascular insulin resistance, GLP-1’s vasodilatory actions are preserved in both skeletal and cardiac muscle microvasculature, which may contribute to improving metabolic insulin responses and cardiovascular outcomes.




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Una nueva política migratoria para una nueva era: Una conversación con la Secretaria de Gobernación Olga Sánchez Cordero

Durante su primera visita oficial a Washington, DC, la Secretaria de Gobierno Olga Sánchez Cordero presento un discurso público sobre la nueva política migratoria de México en el Instituto de Políticas Migratorias.




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Soluciones estratégicas para afrontar la crisis migratoria en Estados Unidos y México

Dado el incremento de los flujos migratorios provenientes de Centroamérica, el pasado mes de junio de 2019, los Estados Unidos y México acordaron tomar una serie de medidas para reducir los flujos irregulares. Sin embargo, será muy difícil mantener estos esfuerzos de corto plazo, debido a una debilidad institucional crónica y a estructuras de política pública poco planificadas en ambos países. Este comentario ofrece cinco recomendaciones a ambos países considerando soluciones de mediano y largo plazo para disuadir la migración irregular y, al mismo tiempo, garantizar que aquellos que busquen protección tengan un proceso justo.




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Florida oral surgeon stays atop branding as practice expands

There is an art to conveying just who you are at every stage of your dental practice. One minute you could be a single-dentist practice with a hygienist and a receptionist, and then, the next thing you know, you could have a group practice and maybe even several locations.




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ADA Accelerator Series seeks to speed up dentists’ success

The Association is launching in March a new online, on-demand program specifically designed to provide information — from parental leave to financial support — that is tailored to the early-career dentist’s unique work-life balance needs.




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ADA offers free e-book resources on management, regulatory issues

Beginning March 25, the ADA is offering members two free e-books a week. Until March 31, members can access “Managing the Regulatory Environment: Best Practices” and “A Dentist’s Guide to the Law: 228 Things Every Dentist Should Know” free of charge.




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OCR warns of imposter posing as investigator

Washington — The Office for Civil Rights released a statement April 3 warning of an individual posing as an OCR investigator. The imposter has been calling entities covered by the Health Insurance Portability and Accountability Act of 1996 in an attempt to get patient information.




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Amalgam separator deadline remains intact

The deadline for dental offices to install amalgam separators remains intact but the Environmental Protection Agency announced March 26 that it will be initiating “a new temporary enforcement discretion policy” during the COVID-19 pandemic.




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ADA streams webinar April 27 on respiratory protection

A recorded webinar will stream April 27 outlining the Association’s interim recommendation for personal protective equipment in dental settings as some states consider loosening social distancing mandates.




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Arthritis drug shows promise against respiratory distress caused by COVID-19

Anakinra, a drug developed to treat rheumatoid arthritis might help patients who have developed acute respiratory distress syndrome caused by COVID-19, a small study published by The Lancet Rheumatology has found.




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Cardiovascular Risk Reduction With Liraglutide: An Exploratory Mediation Analysis of the LEADER Trial

OBJECTIVE

The LEADER trial (ClinicalTrials.gov reg. no. NCT01179048) demonstrated a reduced risk of cardiovascular (CV) events for patients with type 2 diabetes who received the glucagon-like peptide 1 receptor agonist liraglutide versus placebo. The mechanisms behind this CV benefit remain unclear. We aimed to identify potential mediators for the CV benefit observed with liraglutide in the LEADER trial.

RESEARCH DESIGN AND METHODS

We performed exploratory analyses to identify potential mediators of the effect of liraglutide on major adverse CV events (MACE; composite of CV death, nonfatal myocardial infarction, or nonfatal stroke) from the following candidates: glycated hemoglobin (HbA1c), body weight, urinary albumin-to-creatinine ratio (UACR), confirmed hypoglycemia, sulfonylurea use, insulin use, systolic blood pressure, and LDL cholesterol. These candidates were selected as CV risk factors on which liraglutide had an effect in LEADER such that a reduction in CV risk might result. We used two methods based on a Cox proportional hazards model and the new Vansteelandt method designed to use all available information from the mediator and to control for confounding factors.

RESULTS

Analyses using the Cox methods and Vansteelandt method indicated potential mediation by HbA1c (up to 41% and 83% mediation, respectively) and UACR (up to 29% and 33% mediation, respectively) on the effect of liraglutide on MACE. Mediation effects were small for other candidates.

CONCLUSIONS

These analyses identify HbA1c and, to a lesser extent, UACR as potential mediators of the CV effects of liraglutide. Whether either is a marker of an unmeasured factor or a true mediator remains a key question that invites further investigation.




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Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes

OBJECTIVE

To determine the effect of tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptors, on biomarkers of nonalcoholic steatohepatitis (NASH) and fibrosis in patients with type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS

Patients with T2DM received either once weekly tirzepatide (1, 5, 10, or 15 mg), dulaglutide (1.5 mg), or placebo for 26 weeks. Changes from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), keratin-18 (K-18), procollagen III (Pro-C3), and adiponectin were analyzed in a modified intention-to-treat population.

RESULTS

Significant (P < 0.05) reductions from baseline in ALT (all groups), AST (all groups except tirzepatide 10 mg), K-18 (tirzepatide 5, 10, 15 mg), and Pro-C3 (tirzepatide 15 mg) were observed at 26 weeks. Decreases with tirzepatide were significant compared with placebo for K-18 (10 mg) and Pro-C3 (15 mg) and with dulaglutide for ALT (10, 15 mg). Adiponectin significantly increased from baseline with tirzepatide compared with placebo (10, 15 mg).

CONCLUSIONS

In post hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in patients with T2DM.




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[ Politics ] Open Question : When will the democrats be arrested for being trators to SAmerica by conspiring with chine to make trump looik bad?




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Moroccan chicken skewers with feta, pea and tomato tabbouleh

1 onion, grated 1 cup Greek yoghurt 1/2 cup olive oil 1/2 lemon, juiced 2 cloves of garlic, crushed 1 tsp. smoked paprika 1/2 tsps. ground coriander 1/2 tsps. ground cumin 500g chicken thighs, cut in to 3 cm pieces 2 tbsps. sesame seeds, toasted tabbouleh 100g burghul 2 1/2 cups frozen peas 1 handful of flat leaf parsley, chopped 1 punnit of cherry tomatoes, halved 1 handful of mint leaves, lightly chopped 3 shallots, thinly sliced 200g Greek feta, crumbled 1/3 cup olive oil 1/2 lemon, juiced 1/2 tsp. ground cinnamon Good pinch of sea salt flakes and black pepper




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Potato mushroom walnut sesame salad

A new take on that old favourite, potato salad. The sesame and miso adds interest, while the walnuts add taste and crunch. So substantial it could be a meal in itself.




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Italian tomato, saffron and mozzarella arancini

1/2 cup chicken stock 1 pinch of saffron olive oil, for cooking 1 small brown onion, diced 1 tbsp. tomato paste 150 g Carnaroli rice or Arborio rice Himalayan salt and freshly ground black pepper 100 ml white wine 60 g grated parmesan finely grated zest of 1 lemon 100 g grated mozzarella 3 eggs 125 ml (1/2 cup) milk 50 g plain flour 160 g panko breadcrumbs (see Note) vegetable oil, for deep-frying




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Sad Vegetable Ratatouille

This recipe features on Foodie Tuesday, a weekly segment on 774 Drive with Raf Epstein, 3.30PM, courtesy of Cassie Duncan from Sustainable Table.




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Galatopita

This recipe features on Foodie Tuesday, a weekly segment on 774 Drive with Raf Epstein, 3.30PM, courtesy of Kathy Tsaples.




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Potatoes with Lemon and Oregano

This recipe features on Foodie Tuesday, a weekly segment on 774 Drive with Raf Epstein, 3.30PM, courtesy of Kathy Tsaples.




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Spinach and Sweet Potato Frittata

The frittata has almost overtaken the classic quiche. It is a healthier option as it doesn't have the extra kilojoules of a pastry case. It's Italian in origin and a versatile dish as you can serve it hot or at room temperature for lunch or dinner, alone or with a salad or vegetables, as part of an Antipasto selection or cut in bite-size pieces to serve as a nibble with drinks.







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Medallions of Beef, with pan juice sauce, wilted cherry tomatoes, wine and basil

Medallions of Beef, with pan juice sauce, wilted cherry tomatoes, any old wine and basil. Really nice with a potato salad, with fresh spring peas and crispy bacon pieces. Something I do very often is knock up quick tasty dinner utilising your favourite heavy-based frying pan.




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MACADAMIA PESTO POTATO SALAD WITH CRISPY PROSCIUTTO AND MARKET CHERRY TOMATOES

Love this time of year where our makers are abundant with the sweet aroma of fresh basil . Here is my take on a fancy potato salad of macadamia pesto , crispy prosciutto, sweet cherry tomatoes




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Bush food native tomato seasoned chicken with plum and chilli dip

chicken thigh fillets, skinless and cut in to finger length strips 100g melted butter 1 tbsp. native tomato spice mix plum and chilli bottled sauce




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Upside down local tomato, goats cheese and onion tart

Always a winner taking advantage of the local summer tomatoes . Who doesn't like flaky puff pastry?





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Greek Santorini tomato fritters with yogurt and dill dip

400g ripe roma (plum) or pomodorino (baby plum) tomatoes 1 1/2 tablespoons chopped mint 1 teaspoon dried oregano 90g plain flour 1 teaspoon baking powder 1 teaspoon salt Light olive oil, or sunflower oil for pan-frying 250g Greek-style yogurt 1 tablespoon finely chopped dill Lemon wedges, to serve




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Indian 5 spiced potatoes

3 tbsps. coconut oil oil 2 tbsps. panch phoran spice mix 1 large onion, finely chopped 2 long green chillies, sliced lengthways 6 curry leaves 2 garlic cloves, crushed 1 tbsps. grated ginger 1 tsp. ground turmeric 4 large potatoes, peeled and diced Panch phoran spice mix: 3 tbsp. brown mustard seeds 3 tbsp. fennel seeds 3 tbsp. Nigella seeds 3 tbsp. cumin seeds salt, to taste chopped coriander leaves, to serve




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Respuestas latinoamericanas a las crisis migratorias venezolanas y nicaragüenses

Responsables de políticos principales y partes interesadas de América Latina, así como representantes de instituciones internacionales claves, ofrecen sus puntos de vista sobre los desafíos futuros mientras gobiernos latinoamericanos buscan establecer las estrategias para responder a flujos migratorios forzados a gran escala, como los de Venezuela y Nicaragua.




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    Inoreader mobile apps updated to support Automatic Night Mode, Microblogs, Sort by Magic and popularity indicators.

    Hey, it’s been quite some time without updates on this front, but our latest updates to our Android and iOS…




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    Effects of MK-0941, a Novel Glucokinase Activator, on Glycemic Control in Insulin-Treated Patients With Type 2 Diabetes

    OBJECTIVE

    To assess the efficacy and safety of MK-0941, a glucokinase activator (GKA), when added to stable-dose insulin glargine in patients with type 2 diabetes.

    RESEARCH DESIGN AND METHODS

    In this double-blind study, 587 patients taking stable-dose insulin glargine (±metformin ≥1,500 mg/day) were randomized (1:1:1:1:1) to MK-0941 10, 20, 30, or 40 mg or matching placebo t.i.d. before meals (a.c.). This study included an initial 14-week, dose-ranging phase followed by a 40-week treatment phase during which patients were to be uptitrated as tolerated to 40 mg (or placebo) t.i.d. a.c. The primary efficacy end point was change from baseline in A1C at Week 14.

    RESULTS

    At Week 14, A1C and 2-h postmeal glucose (PMG) improved significantly versus placebo with all MK-0941 doses. Maximal placebo-adjusted least squares mean changes from baseline in A1C (baseline A1C 9.0%) and 2-h PMG were –0.8% and –37 mg/dL (–2 mmol/L), respectively. No significant effects on fasting plasma glucose were observed at any dose versus placebo. By 30 weeks, the initial glycemic responses noted at 14 weeks were not sustained. MK-0941 at one or more doses was associated with significant increases in the incidence of hypoglycemia, triglycerides, systolic blood pressure, and proportion of patients meeting criteria for predefined limits of change for increased diastolic blood pressure.

    CONCLUSIONS

    In patients receiving stable-dose insulin glargine, the GKA MK-0941 led to improvements in glycemic control that were not sustained. MK-0941 was associated with an increased incidence of hypoglycemia and elevations in triglycerides and blood pressure.




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    Respuestas latinoamericanas a las crisis migratorias venezolanas y nicaragüenses

    Responsables de políticos principales y partes interesadas de América Latina, así como representantes de instituciones internacionales claves, ofrecen sus puntos de vista sobre los desafíos futuros mientras gobiernos latinoamericanos buscan establecer las estrategias para responder a flujos migratorios forzados a gran escala, como los de Venezuela y Nicaragua.




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    Diabetes Self-management Education and Support in Type 2 Diabetes: A Joint Position Statement of the American Diabetes Association, the American Association of Diabetes Educators, and the Academy of Nutrition and Dietetics

    Margaret A. Powers
    Apr 1, 2016; 34:70-80
    Position Statements




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    Here’s How The Online Status Indicators In Apps Influence Our Behaviour

    By Emily Reynolds. People are often required to adjust their behaviour to meet demands of apps, rather than technology being designed to meet our needs, researchers say.




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    How Massachusetts Is Building Capacity of Educator-Preparation Programs

    Research findings on the implementation of a new teacher candidate performance assessment in Massachusetts inform the development of additional supports for educator preparation programs.




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    Educators Who Ran for Office Share Their Lessons Learned (Video)

    Watch a discussion between three educators who ran for their state legislatures about their experiences on the campaign trail.




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    Educators, Advocates Chase Political Office in Several States

    In Arkansas, Ohio, and Wisconsin, educators and advocates will be on this year's ballot for governor, a position that will inevitably have an outsized role in shaping education policy.




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    ECOT Looms Over Ohio Gubernatorial Candidates' Education Plans

    Any discussion in politics of the future of education in Ohio inevitably turns to the Electronic Classroom of Tomorrow.




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    Educators Who Ran for Office Share Their Lessons Learned (Video)

    Watch a discussion between three educators who ran for their state legislatures about their experiences on the campaign trail.




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    Who Shows Up for Teachers? Coalition-Building in the Era of Educator Activism

    "Teaching is a political act," argues teacher-turned-politician John Waldron. And it's going to take more organizing to rescue public education.




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    Rural educator enters race for state schools superintendent




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    Educators, This Is Our Moment to Defend the Teaching Profession

    In this moment of loss, the coronavirus pandemic offers four opportunities to demand the rebirth of public education, writes Amy Stuart Wells.




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    In Texas, Administrators Arrested for Cheating

    Five El Paso educators have been charged with scheming to defraud the federal accountability system and, in some cases, retaliating against co-workers who cooperated with the FBI's 5½-year investigation of the Texas school district.




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    Texas' Educators Tally the Steep Costs of Harvey

    Houston education officials estimate it will cost $700 million to repair and replace schools damaged by Hurricane Harvey.




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    State Legislators Revamp Funding in Texas, Nevada

    Several states this year sought to replace their funding formulas, a monumental fiscal and political feat, but only a handful of legislatures have been able to get proposals to their governors' desks.




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    State Legislators Revamp Funding in Texas, Nevada

    Several states this year sought to replace their funding formulas, a monumental fiscal and political feat, but only a handful of legislatures have been able to get proposals to their governors' desks.




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    Maryland educators, students aim to adapt to closures




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    Rural educator enters race for state schools superintendent