High Efficacy of Two Artemisinin-Based Combinations (Artesunate + Amodiaquine and Artemether + Lumefantrine) in Caala, Central Angola.

In April 2004, 137 children 6-59 months of age with uncomplicated Plasmodium falciparum (Pf) malaria (Caala, Central Angola) were randomized to receive either artemether-lumefantrine (Coartem) or artesunate + amodiaquine (ASAQ). After 28 days of follow-up, there were 2/61 (3.2%) recurrent parasitemias in the Coartem group and 4/64 (6.2%) in the ASAQ group (P = 0.72), all classified as re-infections after PCR genotyping (cure rate = 100% [95%CI: 94-100] in both groups). Only one patient (ASAQ group) had gametocytes on day 28 versus five (Coartem) and three (ASAQ) at baseline. Compared with baseline, anemia was significantly improved after 28 days of follow-up in both groups (Coartem: from 54.1% to 13.4%; ASAQ: from 53.1% to 15.9%). Our findings are in favor of a high efficacy of both combinations in Caala. Now that Coartem has been chosen as the new first-line anti-malarial, the challenge is to insure that this drug is available and adequately used

Micro-RNA-215 and -375 regulate thymidylate synthase protein expression in pleural mesothelioma and mediate epithelial to mesenchymal transition

The standard front-line treatment for pleural mesothelioma (PM) is pemetrexed-based chemotherapy, whose major target is thymidylate synthase (TS). In several cancer models, miR-215 and miR-375 have been shown to target TS, while information on these miRNAs in PM are still limited although suggest their role in epithelial to mesenchymal transition. Seventy-one consecutive PM tissues (4 biphasic, 7 sarcomatoid, and 60 epithelioid types) and 16 commercial and patient-derived PM cell lines were screened for TS, miR-215, and miR-375 expression. REN and 570B cells were selected for miR-215 and miR-375 transient transfections to test TS modulation. ZEB1 protein expression in tumor samples was also tested. Moreover, genetic profile was investigated by means of BAP1 and p53 immunohistochemistry. Expression of both miR-215 and miR-375 was significantly higher in epithelioid histotype. Furthermore, inverse correlation between TS protein and both miR-215 and miR-375 expression was found. Efficiently transfected REN and 570B cell lines overexpressing miR-215 and miR-375 showed decreased TS protein levels. Epithelioid PM with a mesenchymal component highlighted by reticulin stain showed significantly higher TS and ZEB1 protein and lower miRNA expression. A better survival was recorded for BAP1 lost/TS low cases. Our data indicate that miR-215 and miR-375 are involved in TS regulation as well as in epithelial-to-mesenchymal transition in PM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00428-022-03321-8

Vitamin D status of pregnant women with obesity in the United Kingdom and its association with pregnancy outcomes: a secondary analysis of the UPBEAT study

Prenatal vitamin D deficiency is widely reported and may affect perinatal outcomes. In this secondary analysis of the UK Pregnancies Better Eating and Activity Trial (UPBEAT), we examined vitamin D status and its relationship with selected pregnancy outcomes in women with obesity (BMI≥30kg/m2) from multi-ethnic inner-city settings in the UK. Determinants of vitamin D status at a mean of 17±1 weeks' gestation were assessed using multivariable linear regression and reported as percent differences in serum hydroxyvitamin D (25(OH)D). Associations between 25(OH)D and clinical outcomes were examined using logistic regression. Among 1089 participants, 67% had 25(OH)D &lt;50nmol/L and 26% had concentrations &lt;25nmol/L. In fully adjusted models accounting for socio-demographic and anthropometric characteristics, 25(OH)D was lower among women of Black (% difference = -33; 95%CI: -39 to -27), Asian (% difference= -43; 95%CI: -51 to -35) and other non-White (% difference= -26; 95%CI: -35 to -14) ethnicity compared to women of White ethnicity (n=1086; P&lt;0.001 for all). In unadjusted analysis, risk of gestational diabetes was greater in women with 25(OH)D &lt;25nmol/L compared to ≥50nmol/L (OR=1.58; 95%CI: 1.09 to 2.31), but the magnitude of effect estimates was attenuated in the multivariable model (OR=1.33; 95%CI: 0.88 to 2.00). There were no associations between 25(OH)D and risk of preeclampsia, preterm birth, or SGA or LGA delivery. These findings demonstrate low 25(OH)D among pregnant women with obesity and highlight ethnic disparities in vitamin D status in the UK. However, evidence for a greater risk of adverse perinatal outcomes among women with vitamin D deficiency was limited.</p

Metal-Substituted Microporous Aluminophosphates

This chapter aims to present the zeotypes aluminophosphates (AlPOs) as a complementary alternative to zeolites in the isomorphic incorporation of metal ions within all-inorganic microporous frameworks as well as to discuss didactically the catalytic consequences derived from the distinctive features of both frameworks. It does not intend to be a compilation of either all or the most significant publications involving metal-substituted microporous aluminophosphates. Families of AlPOs and zeolites, which include metal ion-substituted variants, are the dominant microporous materials. Both these systems are widely used as catalysts, in particular through aliovalent metal ions substitution. Here, some general description of the synthesis procedures and characterization techniques of the MeAPOs (metal-contained aluminophosphates) is given along with catalytic properties. Next, some illustrative examples of the catalytic possibilities of MeAPOs as catalysts in the transformation of the organic molecules are given. The oxidation of the hardly activated hydrocarbons has probably been the most successful use of AlPOs doped with the divalent transition metal ions Co2+, Mn2+, and Fe2+, whose incorporation in zeolites is disfavoured. The catalytic role of these MeAPOs is rationalized based on the knowledge acquired from a combination of the most advanced characterization techniques. Finally, the importance of the high specificity of the structure-directing agents employed in the preparation of MeAPOs is discussed taking N,N-methyldicyclohexylamine in the synthesis of AFI-structured materials as a driving force. It is shown how such a high specificity could be predicted and how it can open great possibilities in the control of parameters as critical in catalysis as crystal size, inter-and intracrystalline mesoporosity, acidity, redox properties, incorporation of a great variety of heteroatom ions or final environment of the metal site (surrounding it by either P or Al)

Computation of the heat and entropy of adsorption in proximity of inflection points

The adsorption of different heptane isomers in MFI- and MEL-type Zeolites is studied to investigate the performance of molecular simulation for computing the heat and entropy of adsorption as a function of loading. It is :shown that none of the conventional methods are capable of computing the heat or entropy of adsorption of bulky molecules such as 2,4-dimethylpentane around the inflection point of the adsorption isotherm. The "Energy Slope" method, is introduced which outperforms the present techniques at loadings near and above the inflection point. There is a quantitative agreement between the heats of adsorption computed with the energy slope method for a butane/isobutarie mixture and the ones computed by the method based on energy/particle fluctuations in the grand-canonical ensemble. This verifies that the energy slope method is a valuable and robust tool for computing the heat and entropy of adsorption for a wide range of hydrocarbon lengths and loadings