Peptide hormones and lipopeptides: from self-assembly to therapeutic applications

This review describes the properties and activities of lipopeptides and peptide hormones and how the lipidation of peptide hormones could potentially produce therapeutic agents combating some of the most prevalent diseases and conditions. The self-assembly of these types of molecules is outlined, and how this can impact on bioactivity. Peptide hormones specific to the uptake of food and produced in the gastrointestinal tract are discussed in detail. The advantages of lipidated peptide hormones over natural peptide hormones are summarised, in terms of stability and renal clearance, with potential application as therapeutic agent

Removing user fees to improve access to caesarean delivery: a quasi-experimental evaluation in western Africa

International audienceIntroduction Mali and Benin introduced a user feeexemption policy focused on caesarean sections in 2005and 2009, respectively. The objective of this study is toassess the impact of this policy on service utilisation andneonatal outcomes. We focus specifically on whether thepolicy differentially impacts women by education level,zone of residence and wealth quintile of the household.Methods We use a difference-in-differences approachusing two other western African countries with no feeexemption policies as the comparison group (Cameroonand Nigeria). Data were extracted from Demographic andHealth Surveys over four periods between the early 1990sand the early 2000s. We assess the impact of the policy onthree outcomes: caesarean delivery, facility-based deliveryand neonatal mortality.Results We analyse 99 800 childbirths. The freecaesarean policy had a positive impact on caesareansection rates (adjusted OR=1.36 (95% CI 1.11 to 1.66;P≤0.01), particularly in non-educated women (adjustedOR=2.71; 95% CI 1.70 to 4.32; P≤0.001), those livingin rural areas (adjusted OR=2.02; 95% CI 1.48 to 2.76;P≤0.001) and women in the middle-class wealth index(adjusted OR=3.88; 95% CI 1.77 to 4.72; P≤0.001). Thepolicy contributes to the increase in the proportion offacility-based delivery (adjusted OR=1.68; 95% CI 1.48 to1.89; P≤0.001) and may also contribute to the decreaseof neonatal mortality (adjusted OR=0.70; 95% CI 0.58 to0.85; P≤0.001).Conclusion This study is the first to evaluate the impactof a user fee exemption policy focused on caesareansections on maternal and child health outcomes withrobust methods. It provides evidence that eliminating feesfor caesareans benefits both women and neonates in sub-Saharan countries

DECIDE : a cluster-randomized controlled trial to reduce unnecessary caesarean deliveries in Burkina Faso

International audienceBACKGROUND:In Burkina Faso, facility-based caesarean delivery rates have markedly increased since the national subsidy policy for deliveries and emergency obstetric care was implemented in 2006. Effective and safe strategies are needed to prevent unnecessary caesarean deliveries.METHODS:We conducted a cluster-randomized controlled trial of a multifaceted intervention at 22 referral hospitals in Burkina Faso. The evidence-based intervention was designed to promote the use of clinical algorithms for caesarean decision-making using in-site training, audits and feedback of caesarean indications and SMS reminders. The primary outcome was the change in the percentage of unnecessary caesarean deliveries. Unnecessary caesareans were defined on the basis of the literature review and expert consensus. Data were collected daily using a standardized questionnaire, in the same way at both the intervention and control hospitals. Caesareans were classified as necessary or unnecessary in the same way, in both arms of the trial using a standardized computer algorithm.RESULTS:A total of 2138 and 2036 women who delivered by caesarean section were analysed in the pre and post-intervention periods, respectively. A significant reduction in the percentage of unnecessary caesarean deliveries was evident from the pre- to post-intervention period in the intervention group compared with the control group (18.96 to 6.56% and 18.27 to 23.30% in the intervention and control groups, respectively; odds ratio [OR] for incremental change over time, adjusted for hospital and patient characteristics, 0.22; 95% confidence interval [CI], 0.14 to 0.34; P < 0.001; adjusted risk difference, - 17.02%; 95% CI, - 19.20 to - 13.20%). The intervention did not significantly affect the rate of maternal death (0.75 to 0.19% and 0.92 to 0.40% in the intervention and control groups, respectively; adjusted OR 0.32; 95% CI 0.04 to 2.23; P = 0.253) or intrapartum-related neonatal death (4.95 to 6.32% and 5.80 to 4.29% in the intervention and control groups, respectively, adjusted OR 1.73; 95% CI 0.82 to 3.66; P = 0.149). The overall perinatal mortality data were not available.CONCLUSION:Promotion and training on clinical algorithms for decision-making, audit and feedback and SMS reminders reduced unnecessary caesarean deliveries, compared with usual care in a low-resource setting.TRIAL REGISTRATION:The DECIDE trial is registered on the Current Controlled Trials website: ISRCTN48510263

Do free caesarean section policies increase inequalities in Benin and Mali?

International audienceBackground: Benin and Mali introduced user fee exemption policies focused on caesarean sections (C-sections) in2005 and 2009, respectively. These policies had a positive impact on access to C-sections and facility based deliveriesamong all women, but the impact on socioeconomic inequality is still highly uncertain. The objective of this study wasto observe whether there was an increase or a decrease in urban/rural and socioeconomic inequalities in access toC-sections and facility based deliveries after the free C-section policy was introduced.Methods: We used data from three consecutive Demographic and Health Surveys (DHS): 2001, 2006 and 2011–2012 inBenin and 2001, 2006 and 2012–13 in Mali. We evaluated trends in inequality in terms of two outcomes: C-sections andfacility based deliveries. Adjusted odds ratios were used to estimate whether the distributions of C-sections and facilitybased deliveries favoured the least advantaged categories (rural, non-educated and poorest women) or the mostadvantaged categories (urban, educated and richest women). Concentration curves were used to observe the degreeof wealth-related inequality in access to C-sections and facility based deliveries.Results: We analysed 47,302 childbirths (23,266 in Benin and 24,036 in Mali). In Benin, we found no significantdifference in access to C-sections between urban and rural women or between educated and non-educated women.However, the richest women had greater access to C-sections than the poorest women. There was no significantchange in these inequalities in terms of access to C-sections and facility based deliveries after introduction of the freeC-section policy.In Mali, we found a reduction in education-related inequalities in access to C-sections after implementation of thepolicy (p-value = 0.043). Inequalities between urban and rural areas had already decreased prior to implementation ofthe policy, but wealth-related inequalities were still present.Conclusions: Urban/rural and socioeconomic inequalities in C-section access did not change substantially after thecountries implemented free C-section policies. User fee exemption is not enough. We recommend switching tomechanisms that combine both a universal approach and targeted action for vulnerable populations to address thisissue and ensure equal health care access for all individuals

Regulation of hypoxia-inducible factor-1alpha protein level during hypoxic conditions by the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3beta pathway in HepG2 cells.

Hypoxia initiates an intracellular signaling pathway leading to the activation of the transcription factor hypoxia-inducible factor-1 (HIF-1). HIF-1 activity is regulated through different mechanisms involving stabilization of HIF-1alpha, phosphorylations, modifications of redox conditions, and interactions with coactivators. However, it appears that some of these steps can be cell type-specific. Among them, the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in the regulation of HIF-1 by hypoxia remains controversial. Here, we investigated the activation state of PI3K/Akt/glycogen synthase kinase 3beta (GSK3beta) in HepG2 cells. Increasing incubation times in hypoxia dramatically decreased both the phosphorylation of Akt and the inhibiting phosphorylation of GSK3beta. The PI3K/Akt pathway was necessary for HIF-1alpha stabilization early during hypoxia. Indeed, its inhibition was sufficient to decrease HIF-1alpha protein level after 5-h incubation in hypoxia. However, longer exposure (16 h) in hypoxia resulted in a decreased HIF-1alpha protein level compared with early exposure (5 h). At that time, Akt was no longer present or active, which resulted in a decrease in the inhibiting phosphorylation of GSK3beta on Ser-9 and hence in an increased GSK3beta activity. GSK3 inhibition reverted the effect of prolonged hypoxia on HIF-1alpha protein level; more stabilized HIF-1alpha was observed as well as increased HIF-1 transcriptional activity. Thus, a prolonged hypoxia activates GSK3beta, which results in decreased HIF-1alpha accumulation. In conclusion, hypoxia induced a biphasic effect on HIF-1alpha stabilization with accumulation in early hypoxia, which depends on an active PI3K/Akt pathway and an inactive GSK3beta, whereas prolonged hypoxia results in the inactivation of Akt and activation of GSK3beta, which then down-regulates the HIF-1 activity through down-regulation of HIF-1alpha accumulation

Development of milk and egg incurred reference materials

Abstract Background Effective allergenic risk assessment and management are important to limit the use of precautionary statements such as &apos;may contain&apos; and to be able to protect allergic consumers. However, such approaches require reliable analytical tools for the detection of allergens in food. Very few validation data are available for the comparison of results obtained with different allergen detection methods. This is certainly due to the lack of harmonized validation protocols and of recognized reference materials. Aims The Monitoring and Quality Assurance Working Group on Food Allergens will provide incurred reference materials with egg and milk proteins at various concentrations. Materials and Methods The development of an incurred reference material for the analysis of milk and egg allergens in a baked cookie food matrix is described. Results and Discussion We present the results of the development of the incurred reference material and a prering trial with two incurred reference materials for milk detection methods: cookies and soy-based infant formula. Conclusions The material produced seems to be suitable as reference material as well as for testing the performance of test kits. The forthcoming validation study according to the harmonized validation protocol will significantly and positively impact on future validation procedures

Forfait obstétrical en Mauritanie: évaluation d'impact

Texte publié dans la rubrique "Zoom sur la recherche" du site Internet du CERDISince 2002, Mauritania has gradually introduced an original prepayment scheme, the obstetrical risk insurance scheme, based on voluntary enrolment with the aim of covering care related to pregnancy and childbirth. The impact evaluation of this package shows that a voluntary prepayment system targeting pregnant women can improve the use of health services during pregnancy and childbirth.Depuis 2002, l’État mauritanien a progressivement mis en place un dispositif de prépaiement original, le forfait obstétrical, reposant sur une adhésion volontaire dans le but de couvrir les soins liés à la grossesse et l’accouchement. L’évaluation d’impact de ce forfait montre qu’un système de prépaiement volontaire ciblant les femmes enceintes peut améliorer l'utilisation des services de santé pendant la grossesse et l'accouchement

Forfait obstétrical en Mauritanie: évaluation d'impact

Texte publié dans la rubrique "Zoom sur la recherche" du site Internet du CERDISince 2002, Mauritania has gradually introduced an original prepayment scheme, the obstetrical risk insurance scheme, based on voluntary enrolment with the aim of covering care related to pregnancy and childbirth. The impact evaluation of this package shows that a voluntary prepayment system targeting pregnant women can improve the use of health services during pregnancy and childbirth.Depuis 2002, l’État mauritanien a progressivement mis en place un dispositif de prépaiement original, le forfait obstétrical, reposant sur une adhésion volontaire dans le but de couvrir les soins liés à la grossesse et l’accouchement. L’évaluation d’impact de ce forfait montre qu’un système de prépaiement volontaire ciblant les femmes enceintes peut améliorer l'utilisation des services de santé pendant la grossesse et l'accouchement

The impact of the obstetrical risk insurance scheme in Mauritania on maternal healthcare utilization: a propensity score matching analysis

International audienceIn Mauritania, obstetrical risk insurance (ORI) has been progressively implemented at the health district level since 2002 and was available in 25% of public healthcare facilities in 2015. The ORI scheme is based on pre-payment scheme principles and focuses on increasing the quality of and access to both maternal and perinatal healthcare. Compared with many community-based health insurance schemes, the ORI scheme is original because it is not based on risk pooling. For a pre-payment of 16–18 USD, women are covered during their pregnancy for antenatal care, skilled delivery, emergency obstetrical care [including caesarean section (C-section) and transfer] and a postnatal visit. The objective of this study is to evaluate the impact of ORI enrolment on maternal and child health services using data from the Multiple Indicator Cluster Survey (MICS) conducted in 2015. A total of 4172 women who delivered within the last 2 years before the interview were analysed. The effect of ORI enrolment on the outcomes was estimated using a propensity score matching estimation method. Fifty-eight per cent of the studied women were aware of ORI, and among these women, more than two-thirds were enrolled. ORI had a beneficial effect among the enrolled women by increasing the probability of having at least one prenatal visit by 13%, the probability of having four or more visits by 11% and the probability of giving birth at a healthcare facility by 15%. However, we found no effect on postnatal care (PNC), C-section rates or neonatal mortality. This study provides evidence that a voluntary pre-payment scheme focusing on pregnant women improves healthcare services utilization during pregnancy and delivery. However, no effect was found on PNC or neonatal mortality. Some efforts should be exerted to improve communication and accessibility to ORI