Sphingosine-1-Phosphate-Mediated Mobilization of Hematopoietic Stem/Progenitor Cells During Intravascular Hemolysis Requires Attenuation of SDF-1-CXCR4 Retention Signaling in Bone Marrow

Sphingosine-1-phosphate (S1P) is a crucial chemotactic factor in peripheral blood (PB) involved in the mobilization process and egress of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM). Since S1P is present at high levels in erythrocytes, one might assume that, by increasing the plasma S1P level, the hemolysis of red blood cells would induce mobilization of HSPCs. To test this assumption, we induced hemolysis in mice by employing phenylhydrazine (PHZ). We observed that doubling the S1P level in PB from damaged erythrocytes induced only a marginally increased level of mobilization. However, if mice were exposed to PHZ together with the CXCR4 blocking agent, AMD3100, a robust synergistic increase in the number of mobilized HSPCs occurred. We conclude that hemolysis, even if it significantly elevates the S1P level in PB, also requires attenuation of the CXCR4-SDF-1 axis-mediated retention in BM niches for HSPC mobilization to occur. Our data also further confirm that S1P is a major chemottractant present in plasma and chemoattracts HSPCs into PB under steady-state conditions. However, to egress from BM, HSPCs first have to be released from BM niches by blocking the SDF-1-CXCR4 retention signal

Long-term spatiotemporal stability and dynamic changes in the haemoparasite community of spiny mice (Acomys dimidiatus) in four montane wadis in the St. Katherine Protectorate, Sinai, Egypt

Background: Long-term field studies of parasite communities are rare but provide a powerful insight into the ecological processes shaping host-parasite interactions. The aim of our study was to monitor long-term trends in the haemoparasite communities of spiny mice (Acomys dimidiatus) and to identify the principal factors responsible for changes over a 12 year period. Methods: To this end we sampled four semi-isolated populations of mice (n= 835) in 2000, 2004, 2008 and 2012 in four dry montane valleys (wadis) located in the Sinai Massif, Egypt. Results: Overall 76.2 % of spiny mice carried at least one of the five haemoparasite genera (Babesia, Bartonella, Haemobartonella, Hepatozoon, Trypanosoma) recorded in the study. Prevalence of haemoparasites varied significantly between the sites with the highest overall prevalence in Wadi Tlah and the lowest in W. El Arbaein, and this changed significantly with time. In the first two surveys there was little change in prevalence, but by 2008, when the first signs of a deepening drought in the region had become apparent, prevalence began to drift downwards, and by 2012 prevalence had fallen to the lowest values recorded from all four sites over the entire 12-year period. The overall mean species richness was 1.2 ± 0.03, which peaked in 2004 and then dropped by more than 50 % by 2012. Species richness was highest among mice from Wadi Tlah and peaked in age class 2 mice (young adults). Site was the most significant factor affecting the prevalence of individual parasite species, with Trypanosoma acomys and Hepatozoon sp. occurring mainly in two wadis (W. Tlah & W. Gharaba). In four of the five genera recorded in the study we observed a significant drop in prevalence or/and abundance since 2004, the exception being Hepatozoon sp. Conclusions: During the 12-year-long period of study in the Sinai, we observed dynamic changes and possibly even cycles of prevalence and abundance of infections which differed depending on parasite species. Although the exact reasons cannot be identified at this time, we hypothesize that the effects of a 15-year-long scarcity of rainfall in the local environment and a fall in host densities over the period of study may have been responsible for a drop in transmission rates, possibly by a negative impact on vector survival

Sphingosine-1-phosphate-Mediated Mobilization of Hematopoietic Stem/Progenitor Cells during Intravascular Hemolysis Requires Attenuation of SDF-1-CXCR4 Retention Signaling in Bone Marrow

Sphingosine-1-phosphate (S1P) is a crucial chemotactic factor in peripheral blood (PB) involved in the mobilization process and egress of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM). Since S1P is present at high levels in erythrocytes, one might assume that, by increasing the plasma S1P level, the hemolysis of red blood cells would induce mobilization of HSPCs. To test this assumption, we induced hemolysis in mice by employing phenylhydrazine (PHZ). We observed that doubling the S1P level in PB from damaged erythrocytes induced only a marginally increased level of mobilization. However, if mice were exposed to PHZ together with the CXCR4 blocking agent, AMD3100, a robust synergistic increase in the number of mobilized HSPCs occurred. We conclude that hemolysis, even if it significantly elevates the S1P level in PB, also requires attenuation of the CXCR4-SDF-1 axis-mediated retention in BM niches for HSPC mobilization to occur. Our data also further confirm that S1P is a major chemottractant present in plasma and chemoattracts HSPCs into PB under steady-state conditions. However, to egress from BM, HSPCs first have to be released from BM niches by blocking the SDF-1-CXCR4 retention signal

Strategic Transformations in the Media

Digital technologies have transformed the way many media organisations have conducted their business over the past two decades. This transformational context raises a number of important questions for media management researchers. Firstly, how have media firms adapted their strategies, resources and capabilities in response to the challenges presented by an increasingly digital environment? Secondly, how have these adaptive practices affected their corporate financial performance? This paper advances our theoretical understanding of media firm transformation by using a multi-disciplinary approach that draws on knowledge from corporate strategy, dynamic capabilities and firm performance. This integrated approach provides a more holistic view of strategic business transformation by understanding the strategic arguments that compel firm’s to reconfigure their resources and capabilities in a dynamic business environment

Low Hydrophobic Mismatch Scores Calculated for HLA-A/B/DR/DQ Loci Improve Kidney Allograft Survival

We evaluated the impact of human leukocyte antigen (HLA) disparity (immunogenicity; IM) on long-term kidney allograft survival. The IM was quantified based on physicochemical properties of the polymorphic linear donor/recipient HLA amino acids (the Cambridge algorithm) as a hydrophobic, electrostatic, amino acid mismatch scores (HMS\AMS\EMS) or eplet mismatch (EpMM) load. High-resolution HLA-A/B/DRB1/DQB1 types were imputed to calculate HMS for primary/re-transplant recipients of deceased donor transplants. The multiple Cox regression showed the association of HMS with graft survival and other confounders. The HMS integer 0-10 scale showed the most survival benefit between HMS 0 and 3. The Kaplan-Meier analysis showed that: the HMS=0 group had 18.1-year median graft survival, a 5-year benefit over HMS\u3e0 group; HMS ≤ 3.0 had 16.7-year graft survival, a 3.8-year better than HMS\u3e3.0 group; and, HMS ≤ 7.8 had 14.3-year grafts survival, a 1.8-year improvement over HMS\u3e7.8 group. Stratification based on EMS, AMS or EpMM produced similar results. Additionally, the importance of HLA-DR with/without -DQ IM for graft survival was shown. In our simulation of 1,000 random donor/recipient pairs, 75% with HMS\u3e3.0 were re-matched into HMS ≤ 3.0 and the remaining 25% into HMS≥7.8: after re-matching, the 13.5 years graft survival would increase to 16.3 years. This approach matches donors to recipients with low/medium IM donors thus preventing transplants with high IM donors

Using Robson's Ten-Group Classification System for comparing caesarean section rates in Europe: an analysis of routine data from the Euro-Peristat study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadObjective: Robson's Ten Group Classification System (TGCS) creates clinically relevant sub-groups for monitoring caesarean birth rates. This study assesses whether this classification can be derived from routine data in Europe and uses it to analyse national caesarean rates. Design: Observational study using routine data. Setting: Twenty-seven EU member states plus Iceland, Norway, Switzerland and the UK. Population: All births at ≥22 weeks of gestational age in 2015. Methods: National statistical offices and medical birth registers derived numbers of caesarean births in TGCS groups. Main outcome measures: Overall caesarean rate, prevalence and caesarean rates in each of the TGCS groups. Results: Of 31 countries, 18 were able to provide data on the TGCS groups, with UK data available only from Northern Ireland. Caesarean birth rates ranged from 16.1 to 56.9%. Countries providing TGCS data had lower caesarean rates than countries without data (25.8% versus 32.9%, P = 0.04). Countries with higher caesarean rates tended to have higher rates in all TGCS groups. Substantial heterogeneity was observed, however, especially for groups 5 (previous caesarean section), 6, 7 (nulliparous/multiparous breech) and 10 (singleton cephalic preterm). The differences in percentages of abnormal lies, group 9, illustrate potential misclassification arising from unstandardised definitions. Conclusions: Although further validation of data quality is needed, using TGCS in Europe provides valuable comparator and baseline data for benchmarking and surveillance. Higher caesarean rates in countries unable to construct the TGCS suggest that effective routine information systems may be an indicator of a country's investment in implementing evidence-based caesarean policies. Tweetable abstract: Many European countries can provide Robson's Ten-Group Classification to improve caesarean rate comparisons. Keywords: Caesarean birth; Europe; Robson classification; Ten-Group Classification System; health information systems; perinatal health indicators.InfAct Joint Action Bridge Health Project, Public Health Programme, Consumers, Health, Agriculture and Food Executive Agency (CHAFEA

Long-term spatiotemporal stability and dynamic changes in helminth infracommunities of spiny mice (Acomys dimidiatus) in St. Katherine’s Protectorate, Sinai, Egypt

The importance of parasites as a selective force in host evolution is a topic of current interest. However, short-term ecological studies of host-parasite systems, on which such studies are usually based, provide only snap-shots of what may be dynamic systems. We report here on four surveys, carried out over a period of 12 years, of helminths of spiny mice (Acomys dimidiatus), the numerically dominant rodents inhabiting the dry montane wadis in the Sinai Peninsula. With host age (age-dependent effects on prevalence and abundance were prominent) and sex (female bias in abundance in helminth diversity and in several taxa including Cestoda) taken into consideration, we focus on the relative importance of temporal and spatial effects on helminth infracommunities. We show that site of capture is the major determinant of prevalence and abundance of species (and higher taxa) contributing to helminth community structure, the only exceptions being Streptopharaus spp. and Dentostomella kuntzi. We provide evidence that most (notably the Spiruroidea, Protospirura muricola, Mastophorus muris and Gongylonema aegypti, but with exceptions among the Oxyuroidae e.g. Syphacia minuta), show elements of temporal-site stability, with rank order of measures among sites remaining similar over successive surveys and hence some elements of predictability in these systems

Variations in Multiple Birth Rates and Impact on Perinatal Outcomes in Europe

Objective Infants from multiple pregnancies have higher rates of preterm birth, stillbirth and neonatal death and differences in multiple birth rates (MBR) exist between countries. We aimed to describe differences in MBR in Europe and to investigate the impact of these differences on adverse perinatal outcomes at a population level. Methods We used national aggregate birth data on multiple pregnancies, maternal age, gestational age (GA), stillbirth and neonatal death collected in the Euro-Peristat project (29 countries in 2010, N = 5 074 643 births). We also used European Society of Human Reproduction and Embryology (ESHRE) data on assisted conception and single embryo transfer (SET). The impact of MBR on outcomes was studied using meta-analysis techniques with random-effects models to derive pooled risk ratios (pRR) overall and for four groups of country defined by their MBR. We computed population attributable risks (PAR) for these groups. Results In 2010, the average MBR was 16.8 per 1000 women giving birth, ranging from 9.1 (Romania) to 26.5 (Cyprus). Compared to singletons, multiples had a nine-fold increased risk (pRR 9.4, 95% Cl 9.1–9.8) of preterm birth (<37 weeks GA), an almost 12-fold increased risk (pRR 11.7, 95% CI 11.0–12.4) of very preterm birth (<32 weeks GA). Pooled RR were 2.4 (95% Cl 1.5–3.6) for fetal mortality at or after 28 weeks GA and 7.0 (95% Cl 6.1–8.0) for neonatal mortality. PAR of neonatal death and very preterm birth were higher in countries with high MBR compared to low MBR (17.1% (95% CI 13.8–20.2) versus 9.8% (95% Cl 9.6–11.0) for neonatal death and 29.6% (96% CI 28.5–30.6) versus 17.5% (95% CI 15.7–18.3) for very preterm births, respectively). Conclusions Wide variations in MBR and their impact on population outcomes imply that efforts by countries to reduce MBR could improve perinatal outcomes, enabling better long-term child health