Complement factor H serum levels determine resistance to pneumococcal invasive disease

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A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients

An analytical assay has been developed and validated for ultrafast and high-throughput mass spectrometric determination of pemetrexed concentrations in plasma using matrix assisted laser desorption/ionization–triple quadrupole–tandem mass spectrometry. Patient plasma samples spiked with the internal standard methotrexate were measured by multiple reaction monitoring. The detection limit was 0.4 fmol/μL, lower limit of quantification was 0.9 fmol/μL, and upper limit of quantification was 60 fmol/μL, respectively. Overall observed pemetrexed concentrations in patient samples ranged between 8.7 (1.4) and 142.7 (20.3) pmol/μL (SD). The newly developed mass spectrometric assay is applicable for (routine) therapeutic drug monitoring of pemetrexed concentrations in plasma from non-small cell lung cancer patients

The Knight of Malta

BACKGROUND: For most women, participation in decision-making during maternity care has a positive impact on their childbirth experiences. Shared decision-making (SDM) is widely advocated as a way to support people in their healthcare choices. The aim of this study was to identify quality criteria and professional competencies for applying shared decision-making in maternity care. We focused on decision-making in everyday maternity care practice for healthy women. METHODS: An international three-round web-based Delphi study was conducted. The Delphi panel included international experts in SDM and in maternity care: mostly midwives, and additionally obstetricians, educators, researchers, policy makers and representatives of care users. Round 1 contained open-ended questions to explore relevant ingredients for SDM in maternity care and to identify the competencies needed for this. In rounds 2 and 3, experts rated statements on quality criteria and competencies on a 1 to 7 Likert-scale. A priori, positive consensus was defined as 70% or more of the experts scoring >/=6 (70% panel agreement). RESULTS: Consensus was reached on 45 quality criteria statements and 4 competency statements. SDM in maternity care is a dynamic process that starts in antenatal care and ends after birth. Experts agreed that the regular visits during pregnancy offer opportunities to build a relationship, anticipate situations and revisit complex decisions. Professionals need to prepare women antenatally for unexpected, urgent decisions in birth and revisit these decisions postnatally. Open and respectful communication between women and care professionals is essential; information needs to be accurate, evidence-based and understandable to women. Experts were divided about the contribution of professional advice in shared decision-making and about the partner's role. CONCLUSIONS: SDM in maternity care is a dynamic process that takes into consideration women's individual needs and the context of the pregnancy or birth. The identified ingredients for good quality SDM will help practitioners to apply SDM in practice and educators to prepare (future) professionals for SDM, contributing to women's positive birth experience and satisfaction with care

Current European Labyrinthula zosterae Are Not Virulent and Modulate Seagrass (Zostera marina) Defense Gene Expression

Pro- and eukaryotic microbes associated with multi-cellular organisms are receiving increasing attention as a driving factor in ecosystems. Endophytes in plants can change host performance by altering nutrient uptake, secondary metabolite production or defense mechanisms. Recent studies detected widespread prevalence of Labyrinthula zosterae in European Zostera marina meadows, a protist that allegedly caused a massive amphi-Atlantic seagrass die-off event in the 1930's, while showing only limited virulence today. As a limiting factor for pathogenicity, we investigated genotype×genotype interactions of host and pathogen from different regions (10–100 km-scale) through reciprocal infection. Although the endophyte rapidly infected Z. marina, we found little evidence that Z. marina was negatively impacted by L. zosterae. Instead Z. marina showed enhanced leaf growth and kept endophyte abundance low. Moreover, we found almost no interaction of protist×eelgrass-origin on different parameters of L. zosterae virulence/Z. marina performance, and also no increase in mortality after experimental infection. In a target gene approach, we identified a significant down-regulation in the expression of 6/11 genes from the defense cascade of Z. marina after real-time quantitative PCR, revealing strong immune modulation of the host's defense by a potential parasite for the first time in a marine plant. Nevertheless, one gene involved in phenol synthesis was strongly up-regulated, indicating that Z. marina plants were probably able to control the level of infection. There was no change in expression in a general stress indicator gene (HSP70). Mean L. zosterae abundances decreased below 10% after 16 days of experimental runtime. We conclude that under non-stress conditions L. zosterae infection in the study region is not associated with substantial virulence

Requirement of argininosuccinate lyase for systemic nitric oxide production

Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to use extracellular arginine for NO production. Administration of nitrite, which can be converted into NO in vivo, rescued the manifestations of NO deficiency in hypomorphic Asl mice, and a nitric oxide synthase (NOS)-independent NO donor restored NO-dependent vascular reactivity in humans with ASL deficiency. Mechanistic studies showed that ASL has a structural function in addition to its catalytic activity, by which it contributes to the formation of a multiprotein complex required for NO production. Our data demonstrate a previously unappreciated role for ASL in NOS function and NO homeostasis. Hence, ASL may serve as a target for manipulating NO production in experimental models, as well as for the treatment of NO-related diseases