The P2Y2 nucleotide receptor is an inhibitor of vascular calcification

BACKGROUND AND AIMS: Mutations in the 5'-nucleotidase ecto (NT5E) gene that encodes CD73, a nucleotidase that converts AMP to adenosine, are linked to arterial calcification. However, the role of purinergic receptor signaling in the pathology of intimal calcification is not well understood. In this study, we examined whether extracellular nucleotides acting via P2Y2 receptor (P2Y2R) modulate arterial intimal calcification, a condition highly correlated with cardiovascular morbidity. METHODS: Apolipoprotein E, P2Y2R double knockout mice (ApoE-/-P2Y2R-/-) were used to determine the effect of P2Y2R deficiency on vascular calcification in vivo. Vascular smooth muscle cells (VSMC) isolated from P2Y2R-/- mice grown in high phosphate medium were used to assess the role of P2Y2R in the conversion of VSMC into osteoblasts. Luciferase-reporter assays were used to assess the effect of P2Y2R on the transcriptional activity of Runx2. RESULTS: P2Y2R deficiency in ApoE-/- mice caused extensive intimal calcification despite a significant reduction in atherosclerosis and macrophage plaque content. The ectoenzyme apyrase that degrades nucleoside di- and triphosphates accelerated high phosphate-induced calcium deposition in cultured VSMC. Expression of P2Y2R inhibits calcification in vitro inhibited the osteoblastic trans-differentiation of VSMC. Mechanistically, expression of P2Y2R inhibited Runx2 transcriptional activation of an osteocalcin promoter driven luciferase reporter gene. CONCLUSIONS: This study reveals a role for vascular P2Y2R as an inhibitor of arterial intimal calcification and provides a new mechanistic insight into the regulation of the osteoblastic trans-differentiation of SMC through P2Y2R-mediated Runx2 antagonism. Given that calcification of atherosclerotic lesions is a significant clinical problem, activating P2Y2R may be an effective therapeutic approach for treatment or prevention of vascular calcification

Acute febrile illness and influenza disease burden in a rural cohort dedicated to malaria in Senegal, 2012-2013

Background African populations are considered to be particularly vulnerable to fever illnesses, including malaria, and acute respiratory disease, owing to limited resources and overcrowding. However, the overall burden of influenza in this context is poorly defined and incidence data for African countries are scarce. We therefore studied the fever syndrome incidence and more specifically influenza incidence in a cohort of inhabitants of Dielmo and Ndiop in Sokone district, Senegal. Methods Daily febrile-illness data were prospectively obtained from January 2012 to December 2013 from the cohort of the villages of Dielmo and Ndiop, initially dedicated to the study of malaria. Nasopharyngeal swabs were collected from, and malaria diagnosis tests (thick blood smears) carried out on, every febrile individual during clinical visits; reverse transcriptase- polymerase chain reaction was used to identify influenza viruses in the samples. Binomial negative regression analysis was used to study the relationship between the monthly incidence rate and various covariates. Results In Dielmo and Ndiop, the incidence ofmalaria has decreased, but fever syndromes remain frequent. Among the 1036 inhabitants included in the cohort, a total of 1,129 episodes of fever were reported. Influenza was present all year round with peaks in October-December 2012 and August 2013. The fever, ILI and influenza incidence density rates differed significantly between age groups. At both sites, the adjusted incidence relative risks for fever syndromes and ILI were significantly higher in the [6-24 months) than other age groups: 7.3 (95% CI: [5.7-9.3]) and 16.1 (95% CI: [11.1-23.3]) respectively. The adjusted incidence relative risk for influenza was significantly higher for the [0-6 months) than other age groups: 9.9 (95% CI: [2.9-33.6]). At both sites, incidence density rates were lowest among adults > = 50 years. Conclusions In this rural setting in Senegal, influenza was most frequent among the youngest children. Preventive strategies targeting this population should be implemented

Central factorials under the Kontorovich-Lebedev transform of polynomials

We show that slight modifications of the Kontorovich-Lebedev transform lead to an automorphism of the vector space of polynomials. This circumstance along with the Mellin transformation property of the modified Bessel functions perform the passage of monomials to central factorial polynomials. A special attention is driven to the polynomial sequences whose KL-transform is the canonical sequence, which will be fully characterized. Finally, new identities between the central factorials and the Euler polynomials are found.Comment: also available at http://cmup.fc.up.pt/cmup/ since the 2nd August 201

Synthesis, structural characterization, antimicrobial and cytotoxic effects of aziridine, 2-aminoethylaziridine and azirine complexes of copper(II) and palladium(II).

The synthesis, spectroscopic and X-ray structural characterization of copper(II) and palladium(II) complexes with aziridine ligands as 2-dimethylaziridine HNCH2CMe2 (a), the bidentate N-(2-aminoethyl)aziridines C2H4NC2H4NH2 (b) or CH2CMe2NCH2CMe2NH2 (c) as well as the unsaturated azirine NCH2CPh (d) are reported. Cleavage of the cyclometallated Pd(II) dimer [μ-Cl(C6H4CHMeNMe2-C,N)Pd]2 with ligand a yielded compound [Cl(NHCH2CMe2)(C6H4CHMe2NMe2-C,N)Pd] (1a). The reaction of the aziridine complex trans-[Cl2Pd(HNC2H4)2] with an excess of aziridine in the presence of AgOTf gave the ionic chelate complex trans-[(C2H4NC2H4NH2-N,N′)2Pd](OTf)2 (2b) which contains the new ligand b formed by an unexpected insertion and ring opening reaction of two aziridines (“aziridine dimerization”). CuCl2 reacted in pure HNC2H4 or HNCH2CMe2 (b) again by “dimerization” to give the tris-chelated ionic complex [Cu(C2H4NC2H4NH2-N,N′)3]Cl2 (3b) or the bis-chelated complex [CuCl(C2H2Me2NC2H2Me2NH2-N,N′)2]Cl (4c). By addition of 2H-3-phenylazirine (d) to PdCl2, trans-[Cl2Pd(NCH2CPh)2] (5d) was formed. All new compounds were characterized by NMR, IR and mass spectra and also by X-ray structure analyses (except 3b). Additionally the cytotoxic effects of these complexes were examined on HL-60 and NALM-6 human leukemia cells and melanoma WM-115 cells. The antimicrobial activity was also determined. The growth of Gram-positive bacterial strains (S. aureus, S. epidermidis, E. faecalis) was inhibited by almost all tested complexes at the concentrations of 37.5–300.0 μg mL−1. However, MIC values of complexes obtained for Gram-negative E. coli and P. aeruginosa, as well as for C. albicans yeast, mostly exceeded 300 μg mL−1. The highest antibacterial activity was achieved by complexes 1a and 2b. Complex 2b also inhibited the growth of Gram-negative bacteria. Graphical abstract: Synthesis, structural characterization, antimicrobial and cytotoxic effects of aziridine, 2-aminoethylaziridine and azirine complexes of copper(ii) and palladium(ii

Unintended pregnancy: magnitude and correlates in six urban sites in Senegal

BACKGROUND: In Senegal, unintended pregnancy has become a growing concern in public health circles. It has often been described through the press as a sensational subject with emphasis on the multiple infanticide cases as a main consequence, especially among young unmarried girls. Less scientific evidence is known on this topic, as fertility issues are rarely discussed within couples. In a context where urbanization is strong, economic insecurity is persistent and the population is globalizing, it is important to assess the magnitude of unintended pregnancy among urban women and to identify its main determinants. METHODS: Data were collected in 2011 from a representative sample of 9614 women aged 15–49 years in six urban sites in Senegal. For this analysis, we include 5769 women who have ever been pregnant or were pregnant at the time of the survey. These women were asked if their last pregnancy in the last two years was ‘wanted ’then’, ‘wanted later’ or ‘not wanted’. Pregnancy was considered as unintended if the woman responded ‘wanted later’ or ‘not wanted’. Descriptive analyses were performed to measure the magnitude of unintended pregnancies, while multinomial logistic regression models were used to identify factors associated with the occurrence of unintended pregnancy. The analyses were performed using Stata version 12. All results were weighted. RESULTS: The results show that 14.3% of ever pregnant women reported having a recent unintended pregnancy. The study demonstrates important distinctions between women whose last pregnancy was intended and those whose last pregnancy was unintended. Indeed, this last group is more likely to be poor, from a young age (< 25 years) and multiparous. In addition, it appears that low participation of married women in decision-making within the couple (management of financial resources) and the lack of discussion on family planning issues are associated with greater experience of unintended pregnancy. CONCLUSION: This study suggests a need to implement more targeted programs that guarantee access to family planning for all women in need. In urban areas that are characterized by economic insecurity, as in Senegal, it is important to consider strategies for promoting communication within couples on fertility issues

UCx_x target design for the SPIRAL 2 project and the ALTO project

ACC NESTERInternational audienceTwo ways of production of radioactive beams using uranium carbide targets are taken into consideration: fission induced by fast neutrons and by bremsstrahlung radiation. For the SPIRAL 2 project, the fission of 238U in uranium carbide target will be induced by a neutron flow created by bombarding a carbon converter with a 40 MeV high intensity deuteron beam. Calculations and design of the target in order to reach 1013 fissions/s with good release time have been done. The second way is the photofission using an electron beam. In 2005 the ALTO project (Accélérateur Linéaire Auprès du Tandem d'Orsay) will give a 50 MeV/10$\mu$A electron beam. This facility will allow more than 1011 fissions/s. In this case, the electron beam hits the target without converter. Calculations realised in order to estimate the production are used to choose the best target shape. For the two cases some R & D on targets to improve release is described

Ectopia cordis about a case at Ourossogui regional hospital center

We report in this work, an extremely rare and major case of anterior body wall defects included ectopia cordis define by abnormal location of heart outside of the thorax. This case was diagnosed at the maternity of Ourossogui regional hospital center, in Senegal. Any scan was performed during the pregnancy. Newborn died 10 minutes after birth. Ectopia cordis is related to a possible ventral midline developmental abnormality. It’s associated to other midline abnormalities and is a part of pentalogy of Cantrell. An X-linked genetic abnormality

Allogeneic hematopoietic cell transplantation for multiple myeloma in Europe: trends and outcomes over 25 years. A study by the EBMT Chronic Malignancies Working Party

We describe the use and outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for multiple myeloma (MM) in Europe between January 1990 and December 2012. We identified 7333 patients, median age at allo-HSCT was 51 years (range: 18-78), of whom 4539 (62%) were males. We distinguished three groups: (1) allo-HSCT upfront (n=1924), (2) tandem auto-allo-HSCT (n=2004) and (3) allo-HSCT as a second line treatment and beyond (n=3405). Overall, there is a steady increase in numbers of allo-HSCT over the years. Upfront allo-HSCT use increased up to year 2000, followed by a decrease thereafter and represented 12% of allo-HSCTs performed in 2012. Tandem auto-allo-HSCT peaked around year 2004 and contributed to 19% of allo-HSCTs in 2012. Allo-HSCT as salvage after one or two or three autografts was steadily increasing over the last years and represented 69% of allo-HSCTs in 2012. Remarkable heterogeneity in using allo-HSCT was observed among the different European countries. The 5-year survival probabilities from time of allo-HSCT for the three groups after year 2004 were 42%, 54% and 32%, respectively. These results show that the use of allo-HSCT is increasing in Europe, especially as second line treatment and beyond. There is an unmet need for well-designed prospective studies investigating allo-HSCT as salvage therapy for MM

Exchange Rate Pass-Through into German Import Prices – A Disaggregated Perspective

This study analyzes the exchange rate pass-through into German import prices based on disaggregated data taken on a monthly basis between 1995 and 2012. Our main contribution is twofold: firstly, we employ various time-series techniques to analyze data for different product categories, and also cointegration techniques to carefully distinguish between short-run and long-run pass-through coefficients. Secondly, in a panel data approach we estimate time-varying pass-through coefficients and explain their development with regard to various macroeconomic factors. Our results show that long-run pass-through is only partly observable and incomplete, while short-run pass-through shows a more unique character, although heterogeneity across product groups does exist. We are also able to identify several macroeconomic factors which determine changes in the degree of pass-through, which is especially relevant for policymakers

Neurodevelopmental milestones and associated behaviours are similar among healthy children across diverse geographical locations

It is unclear whether early child development is, like skeletal growth, similar across diverse regions with adequate health and nutrition. We prospectively assessed 1307 healthy, well-nourished 2-year-old children of educated mothers, enrolled in early pregnancy from urban areas without major socioeconomic or environmental constraints, in Brazil, India, Italy, Kenya and UK. We used a specially developed psychometric tool, WHO motor milestones and visual tests. Similarities across sites were measured using variance components analysis and standardised site differences (SSD). In 14 of the 16 domains, the percentage of total variance explained by between-site differences ranged from 1.3% (cognitive score) to 9.2% (behaviour score). Of the 80 SSD comparisons, only six were >±0.50 units of the pooled SD for the corresponding item. The sequence and timing of attainment of neurodevelopmental milestones and associated behaviours in early childhood are, therefore, likely innate and universal, as long as nutritional and health needs are met