University of Conakry and Centre National de Formation et Recherche de Maferinyah (Guinea).

The drugs lenalidomide and pomalidomide bind to the protein cereblon, directing the CRL4-CRBN E3 ligase toward the transcription factors Ikaros and Aiolos to cause their ubiquitination and degradation. Here we describe CC-220 (compound 6), a cereblon modulator in clinical development for systemic lupus erythematosis and relapsed/refractory multiple myeloma. Compound 6 binds cereblon with a higher affinity than lenalidomide or pomalidomide. Consistent with this, the cellular degradation of Ikaros and Aiolos is more potent and the extent of substrate depletion is greater. The crystal structure of cereblon in complex with DDB1 and compound 6 reveals that the increase in potency correlates with increased contacts between compound 6 and cereblon away from the modeled binding site for Ikaros/Aiolos. These results describe a new cereblon modulator which achieves greater substrate degradation via tighter binding to the cereblon E3 ligase and provides an example of the effect of E3 ligase binding affinity with relevance to other drug discovery efforts in targeted protein degradation.

Background  The EUropean Project on obstetric Haemorrhage Reduction: Attitudes, Trial, and Early warning System (EUPHRATES) is a set of five linked projects, the first component of which was a survey of policies for management of the third stage of labour and immediate management of postpartum haemorrhage following vaginal birth in Europe. Objectives  The objectives were to ascertain and compare policies for management of the third stage of labour and immediate management of postpartum haemorrhage in maternity units in Europe following vaginal birth. Design  Survey of policies. Setting  The project was a European collaboration, with participants in 14 European countries. Sample  All maternity units in 12 countries and in selected regions of two countries in Europe. Methods  A postal questionnaire was sent to all or a defined sample of maternity units in each participating country. Main outcome measures  Stated policies for management of the third stage of labour and the immediate management of postpartum haemorrhage. Results  Policies of using uterotonics for the management of the third stage were widespread, but policies about agents, timing, clamping and cutting the umbilical cord and the use of controlled cord traction differed widely. For immediate management of postpartum haemorrhage, policies of massaging the uterus were widespread. Policies of catheterising the bladder, bimanual compression and in the choice of drugs administered were much more variable. Conclusions  Considerable variations were observed between and within countries in policies for management of the third stage of labour. Variations were observed, but to a lesser extent, in policies for the immediate management of postpartum haemorrhage after vaginal birth. In both cases, policies about the pharmacological agents to be used varied widely.

The large variations in severe tears and episiotomies and the negative association between these indicators in 2010 show the importance of improving the assessment and reporting of tears in each country, and evaluating the impact of low episiotomy rates on the perineum.

The members of MOMS-B Group are listed on page 94Objective To describe the incidence of three conditions of acute severe maternal morbidity in selected regions in nine European countries. Design A population-based questionnaire survey.Setting Eleven regions in nine countries of Europe.Population All the pregnant women in each region who had delivered during the period covered by the study.Methods Standard definitions of three severe obstetric conditions, pre-eclampsia, postpartum haemorrhage and sepsis were established by a steering committee. A common questionnaire was used in each participating country. The incidence of the three obstetric conditions and characteristics of the study women were compared. Main outcome measures Incidence of three severe obstetric conditions: pre-eclampsia, postpartum haemorrhage and sepsis. Results The study identified 1734 women with at least one of the three conditions, with 847 experiencing severe haemorrhage, 793 experiencing severe pre-eclampsia and 142 experiencing severe sepsis. There were wide variations in incidence of three conditions combined, ranging from 14.7 per thousand deliveries in Brussels, Belgium to 6.0 per thousand deliveries in Upper Austria. Conclusions This study sets a simple and straightforward approach to the definition of three severe obstetric conditions and allows population-based comparisons between developed countries in Europe, even though difficulties may have been present with applying the definition across countries. The reported incidence of these severe obstetric conditions in general and severe haemorrhage varied significantly between countries. Overall, severe haemorrhage in particular was the most common of the three conditions, followed closely by severe pre-eclampsia.

Purpose: The therapeutic benefit of the cytokine-induced killer (CIK) cells was unknown in the renal cell carcinoma (RCC). This prospectively randomized study was conducted to evaluate the effects of autologous CIK cell immunotherapy in patients with metastatic clear cell RCCs.Experimental Design: From June 2005 to June 2008, 148 patients with metastatic clear cell RCC were randomized to autologous CIK cell immunotherapy (arm 1, n ¼ 74), or interleukin-2 treatment combination with IFN-a-2a (arm 2, n ¼ 74). The primary endpoint was overall survival (OS) and secondary endpoint was progression-free survival (PFS) evaluated by Kaplan-Meier analyses and treatment HRs with the Cox proportional hazards model.Results: The 3-year PFS and OS in arm 1 were 18% and 61%, as compared with 12% and 23% in arm 2 (P ¼ 0.031 and <0.001, respectively). The median PFS and OS in arm 1 were significantly longer than those in arm 2 (PFS, 12 vs. 8 months, P ¼ 0.024; OS, 46 vs. 19 months, P < 0.001). Multivariate analyses indicated that the cycle count of CIK cell immunotherapy as a continuous variable was significantly associated with prolonged PFS [HR ¼ 0.88; 95% confidence interval (CI), 0.84-0.93; P < 0.001] and OS (HR ¼ 0.58; 95% CI, 0.48-0.69; P < 0.001) in arm 1.Conclusion: The data suggested that CIK cell immunotherapy could improve the prognosis of metastatic clear cell RCC, and increased cycle count of CIK cell treatment could further enhance the beneficial effects.

Purpose To estimate the prevalence of myopia among primary and middle schoolaged students in Guangzhou and to explore the potentially contributing factors to myopia. Methods This cross-sectional study was based on a sample of students in grades 1-6 and grades 7-9. Data were collected from refractive error measurements and a structured questionnaire. Results A total of 3055 participants were involved in this analysis, and the overall prevalence of myopia was 47.4% (95% confidence interval (CI) = 45.6-49.2%). The prevalence of myopia in students increased along with the growth of grade level; the prevalence of myopia in students in grade 1 was only 0.2%, as it increased to 38.8% in students in grade 3, and the rate was the highest (68.4%) in students in grade 9. Girls were at a higher risk of myopia than boys (adjusted odds ratio = 1.22, 95% CI = 1.04-1.44). Both male and female students whose distance of reading was longer than 25 cm were less likely to have myopia and who have one or two myopic parents were at a higher risk of myopia. In addition, reading for pleasure more than 2 h per day (adjusted odds ratio = 1.84, 95% CI = 1.09-3.12) was only positively associated with myopia in boys and spending time watching television per week was only positively associated with myopia in girls. Conclusion Myopia in students is a significant public health problem in Guangzhou. Female gender, higher grade, longer time spent for near work, shorter distance of near work, and parental myopia were shown to be associated with the increasing risk of myopia in children.

Abstractobjectives To measure pre-intervention quality of routine antenatal and childbirth care in rural districts of Burkina Faso, Ghana and Tanzania and to identify shortcomings.methods In each country, we selected two adjoining rural districts. Within each district, we randomly sampled 6 primary healthcare facilities. Quality of care was assessed through health facility surveys, direct observation of antenatal and childbirth care, exit interviews and review of patient records.results By and large, quality of antenatal and childbirth care in the six districts was satisfactory, but we did identify some critical gaps common to the study sites in all three countries. Counselling and health education practices are poor; laboratory investigations are often not performed; examination and monitoring of mother and newborn during childbirth are inadequate; partographs are not used. Equipment required to provide assisted vaginal deliveries (vacuum extractor or forceps) was absent in all surveyed facilities.conclusion Quality of care in the three study sites can be improved with the available human resources and without major investments. This improvement could reduce maternal and neonatal mortality and morbidity.keywords quality of care, maternal and newborn health, childbirth, antenatal care, sub-Saharan Africa, emergency obstetric care, haemorrhage, pre-eclampsia /eclampsia, obstructed labour