Monitoring Inequalities in the Health Workforce: The Case Study of Brazil 1991–2005

Introduction: Both the quantity and the distribution of health workers in a country are fundamental for assuring equitable access to health services. Using the case of Brazil, we measure changes in inequalities in the distribution of the health workforce and account for the sources of inequalities at sub-national level to identify whether policies have been effectiv

Progress and setbacks in socioeconomic inequalities in adolescent health-related behaviours in Brazil: results from three cross-sectional surveys 2009-2015.

OBJECTIVES: Despite some progress, Brazil is still one of the most unequal countries, and the extent of socioeconomic inequalities in adolescent health is unclear. We assessed trends in socioeconomic inequalities in adolescent's health-related behaviours in Brazil between 2009 and 2015. DESIGN: We used cross-sectional data from the Brazilian National Survey of School Health carried out in 2009, 2012 and 2015. SETTING: Brazilian state capitals. PARTICIPANTS: Students attending ninth grade from public and private schools in Brazilian state capitals in 2009 (60 973 students), 2012 (61 145 students) and 2015 (51 192 students). MAIN OUTCOME MEASURE: We assessed 12 health-related behaviours (irregular fruit, vegetables and bean consumption; regular soft drink consumption; irregular physical activity; alcohol, drug and tobacco use; unsafe sex; involvement in gun fights; bullying victimisation and domestic violence victimisation), under the broad domains of lifestyle risk behaviours, engagement in risky activities and exposure to violence. Socioeconomic status was assessed through an asset-based wealth index derived from principal component analysis. Absolute and relative inequalities in these health behaviours and inequalities trends were investigated. RESULTS: From 2009 to 2015, prevalence of certain harmful health-related behaviours increased, such as unsafe sex (21.5% to 33.9%), domestic violence (9.5% to 16.2%), bullying victimisation (14.2% to 21.7%) and irregular consumption of beans (37.5% to 43.7%). Other indicators decreased: alcohol use (27.1% to 23.2%), irregular physical activity (83.0% to 75.6%) and consumption of soft drinks (37.2% to 28.8%). Over the period, we found consistent evidence of decreasing health inequalities for lifestyle behaviours (fruit, bean and soft drink consumption) and alcohol use, set against increasing inequalities in violence (domestic violence, fights using guns and bullying victimisation). CONCLUSION: Socioeconomic inequality increased in the violence domain and decreased for lifestyle behaviours among Brazilian adolescents. Widening gaps in violence domain urge immediately policy measures in Brazil

Functional Characterization of MODY2 Mutations Highlights the Importance of the Fine-Tuning of Glucokinase and Its Role in Glucose Sensing

Glucokinase (GK) acts as a glucose sensor in the pancreatic beta-cell and regulates insulin secretion. Heterozygous mutations in the human GK-encoding GCK gene that reduce the activity index increase the glucose-stimulated insulin secretion threshold and cause familial, mild fasting hyperglycaemia, also known as Maturity Onset Diabetes of the Young type 2 (MODY2). Here we describe the biochemical characterization of five missense GK mutations: p.Ile130Thr, p.Asp205His, p.Gly223Ser, p.His416Arg and p.Ala449Thr. The enzymatic analysis of the corresponding bacterially expressed GST-GK mutant proteins show that all of them impair the kinetic characteristics of the enzyme. In keeping with their position within the protein, mutations p.Ile130Thr, p.Asp205His, p.Gly223Ser, and p.His416Arg strongly decrease the activity index of GK, affecting to one or more kinetic parameters. In contrast, the p.Ala449Thr mutation, which is located in the allosteric activator site, does not affect significantly the activity index of GK, but dramatically modifies the main kinetic parameters responsible for the function of this enzyme as a glucose sensor. The reduced Kcat of the mutant (3.21±0.28 s−1 vs 47.86±2.78 s−1) is balanced by an increased glucose affinity (S0.5 = 1.33±0.08 mM vs 7.86±0.09 mM) and loss of cooperativity for this substrate. We further studied the mechanism by which this mutation impaired GK kinetics by measuring the differential effects of several competitive inhibitors and one allosteric activator on the mutant protein. Our results suggest that this mutation alters the equilibrium between the conformational states of glucokinase and highlights the importance of the fine-tuning of GK and its role in glucose sensing

Serum from Calorie-Restricted Rats Activates Vascular Cell eNOS through Enhanced Insulin Signaling Mediated by Adiponectin

eNOS activation resulting in mitochondrial biogenesis is believed to play a central role in life span extension promoted by calorie restriction (CR). We investigated the mechanism of this activation by treating vascular cells with serum from CR rats and found increased Akt and eNOS phosphorylation, in addition to enhanced nitrite release. Inhibiting Akt phosphorylation or immunoprecipitating adiponectin (found in high quantities in CR serum) completely prevented the increment in nitrite release and eNOS activation. Overall, we demonstrate that adiponectin in the serum from CR animals increases NO• signaling by activating the insulin pathway. These results suggest this hormone may be a determinant regulator of the beneficial effects of CR

Influence of Ecto-Nucleoside Triphosphate Diphosphohydrolase Activity on Trypanosoma cruzi Infectivity and Virulence

The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, an endemic zoonosis present in some countries of South and Central Americas. The World Health Organization estimates that 100 million people are at risk of acquiring this disease. The infection affects mainly muscle tissues in the heart and digestive tract. There are no vaccines or effective treatment, especially in the chronic phase when most patients are diagnosed, which makes a strong case for the development of new drugs to treat the disease. In this work we evaluate a family of proteins called Ecto-Nucleoside-Triphosphate-Diphosphohydrolase (Ecto-NTPDase) as new chemotherapy target to block T. cruzi infection in mammalian cells and in mice. We have used inhibitors and antibodies against this protein and demonstrated that T. cruzi Ecto-NTPDases act as facilitators of infection in mammalian cells and virulence factors in mice model. Two of the drugs used in this study (Suramin and Gadolinium) are currently used for other diseases in humans, supporting the possibility of their use in the treatment of Chagas disease