Grief Symptoms in Relatives Who Experienced Organ Donation Requests in the ICU.

Rationale: Studies show that the quality of end-of-life communication and care have a significant impact on the living long after the death of a relative and have been implicated in the burden of psychological symptoms after the ICU experience. In the case of organ donation, the patient's relatives are centrally involved in the decision-making process; yet, few studies have examined the impact of the quality of communication on the burden of psychological symptoms after death.

Objectives: To assess the experience of the organ donation process and grief symptoms in relatives of brain-dead patients who discussed organ donation in the ICU.

A molecular atlas of cell types and zonation in the brain vasculature.

Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells.

Mapping Interactions between p27 and RhoA that Stimulate Cell Migration.

p27 mediates cell cycle arrest by binding to and inhibiting cyclin-dependent kinase/cyclin complexes, but p27 can also contribute to pro-oncogenic signaling upon mislocalization to the cytoplasm. Cytoplasmic p27 stimulates cell migration by associating with RhoA and interfering with the exchange of GDP from RhoA stimulated by guanine nucleotide exchange factors. We used biophysical methods to show that the N-terminus of p27 directly interacts with RhoA in vitro.

Cellular pharmacology studies of anticancer agents: recommendations from the EORTC-PAMM group.

An increasing number of manuscripts focus on the in vitro evaluation of established and novel anti-tumor agents in experimental models. Whilst the design of such in vitro assays is inherently flexible, some of these studies lack the minimum information necessary to critically evaluate their relevance or have been carried out under unsuitable conditions. The use of appropriate and robust methods and experimental design has important implications for generating results that are reliable, relevant, and reproducible.

A Novel Translational Model of Spinal Cord Injury in Nonhuman Primate.

Spinal cord injuries (SCI) lead to major disabilities affecting > 2.5 million people worldwide. Major shortcomings in clinical translation result from multiple factors, including species differences, development of moderately predictive animal models, and differences in methodologies between preclinical and clinical studies.

Extremely long-term memory and familiarity after 12 years.

In 2006 Mitchell demonstrated that implicit memory was robust to decay. He showed that the ability to identify fragments of pictures seen 17 years before was significantly higher than for new stimuli. Is this true only for implicit memory? In this study, we tested whether explicit memory was still possible for drawings (n = 144) that had been presented once or three times, two seconds each time on average, approximately 12 years earlier.

Familial Aggregation and Heritability of Loa loa Microfilaremia.

Background: For a given prevalence of Loa loa microfilaremia, the proportion of people with high densities varies significantly between communities. We hypothesized that this variation is related to the existence of familial clusters of hypermicrofilaremic individuals that would be the consequence of a genetic predisposition to present high L. loa microfilarial densities.

Association of light-to-moderate alcohol drinking in pregnancy with preterm birth and birth weight: elucidating bias by pooling data from nine European cohorts.

Women who drink light-to-moderately during pregnancy have been observed to have lower risk of unfavourable pregnancy outcomes than abstainers. This has been suggested to be a result of bias. In a pooled sample, including 193 747 live-born singletons from nine European cohorts, we examined the associations between light-to-moderate drinking and preterm birth, birth weight, and small-for-gestational age in term born children (term SGA).

Gamma Knife radiosurgery for glossopharyngeal neuralgia: A study of 21 patients with long-term follow-up.

Objective Glossopharyngeal neuralgia (GPN) is a very rare condition, affecting the patient's quality of life. We report our experience in drug-resistant, idiopathic GPN, treated with Gamma Knife radiosurgery (GKRS), in terms of safety and efficiency, on a very long-term basis. Methods The study was opened, self-controlled, non-comparative and bicentric (Marseille and Lausanne University Hospitals).

Timing of Angiography and Outcomes in High-Risk Patients With Non-ST-Segment-Elevation Myocardial Infarction Managed Invasively: Insights From the TAO Trial (Treatment of Acute Coronary Syndrome With Otamixaban).

Background: In patients with non-ST-segment-elevation myocardial infarction (NSTEMI) and GRACE (Global Registry of Acute Coronary Events) score >140, coronary angiography (CAG) is recommended by European and American guidelines within 24 hours. We sought to study the association of very early (ie, ≤12 hours), early (12-24 hours), and delayed (>24 hours) CAG in patients with NSTEMI with GRACE score >140 with ischemic outcomes.

Methods: The TAO trial (Treatment of Acute Coronary Syndrome With Otamixaban) randomized patients with NSTEMI and CAG scheduled within 72 hours to heparin plus eptifibatide versus otamixaban.

Two-year recombinant human growth hormone (rhGH) treatment is more effective in pre-pubertal compared to pubertal short children with X-linked hypophosphatemic rickets (XLHR).

Context: Twenty-five to 40% of patients with well-controlled X-linked hypophosphatemic rickets (XLHR) have a final height under -2 SDS. Previous studies have shown that recombinant human growth hormone (rhGH) treatment improves linear growth in short children with XLHR.

Objective: We studied the effectiveness of rhGH treatment in children with XLHR in a larger cohort.

Synthesis and Identification of AceDoxyPC, a Protectin-Containing Structured Phospholipid, Using Liquid Chromatography/Mass Spectrometry.

Fatty acids have many health benefits in a great variety of diseases ranging from cardiovascular to cerebral diseases. For instance, docosahexaenoic acid (DHA), which is highly enriched in brain phospholipids, plays a major role in anti-inflammatory or neuroprotective pathways. Its effects are thought to be due, in part, to its conversion into derived mediators such as protectins.

Trajectories of Emergent Central Sleep Apnea During CPAP Therapy.

Background: The emergence of central sleep apnea (CSA) during positive airway pressure (PAP) therapy has been observed clinically in approximately 10% of obstructive sleep apnea titration studies. This study assessed a PAP database to investigate trajectories of treatment-emergent CSA during continuous PAP (CPAP) therapy.

Methods: U.

Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4).

Benefits of rituximab as a second-line treatment for autoimmune haemolytic anaemia in children: a prospective French cohort study.

Childhood autoimmune haemolytic anaemia (AIHA) requires second-line immunosuppressive therapy in 30-50% of cases. It appears that rituximab is indicated in such circumstances. This prospective national study reports the practice, efficacy and tolerance of rituximab in children with isolated AIHA and AIHA in the setting of Evans syndrome (ES).

Screening for Protein-Protein Interaction Inhibitors Using a Bioluminescence Resonance Energy Transfer (BRET)-Based Assay in Yeast.

The bioluminescence resonance energy transfer (BRET) technology is a widely used live cell-based method for monitoring protein-protein interactions as well as conformational changes within proteins or molecular complexes. Considering the emergence of protein-protein interactions as a new promising class of therapeutic targets, we have adapted the BRET method in budding yeast. In this technical note, we describe the advantages of using this simple eukaryotic model rather than mammalian cells to perform high-throughput screening of chemical compound collections: genetic tractability, tolerance to solvent, rapidity, and no need of expensive robotic systems.

Socioeconomic status and the 25 × 25 risk factors as determinants of premature mortality: a multicohort study and meta-analysis of 1·7 million men and women.

Background: In 2011, WHO member states signed up to the 25 × 25 initiative, a plan to cut mortality due to non-communicable diseases by 25% by 2025. However, socioeconomic factors influencing non-communicable diseases have not been included in the plan. In this study, we aimed to compare the contribution of socioeconomic status to mortality and years-of-life-lost with that of the 25 × 25 conventional risk factors.

Rare and low-frequency coding variants alter human adult height.

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.

High-throughput discovery of novel developmental phenotypes.

Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts.

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus.

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-negative BC (P=1.

Lysophosphatidylcholine acyltransferase 1 is downregulated by hepatitis C virus: impact on production of lipo-viro-particles.

Objective: HCV is intimately linked with the liver lipid metabolism, devoted to the efflux of triacylglycerols stored in lipid droplets (LDs) in the form of triacylglycerol-rich very-low-density lipoproteins (VLDLs): (i) the most infectious HCV particles are those of lowest density due to association with triacylglycerol-rich lipoproteins and (ii) HCV-infected patients frequently develop hepatic steatosis (increased triacylglycerol storage). The recent identification of lysophosphatidylcholine acyltransferase 1 (LPCAT1) as an LD phospholipid-remodelling enzyme prompted us to investigate its role in liver lipid metabolism and HCV infectious cycle.

Design: Huh-7.

Concordance between HER-2 status determined by qPCR in Fine Needle Aspiration Cytology (FNAC) samples compared with IHC and FISH in Core Needle Biopsy (CNB) or surgical specimens in breast cancer patients.

Determining the status of HER2-neu amplification and overexpression in breast cancer is crucial for prognosis but mostly for treatment purposes. Standard techniques include the determination of IHC in combination with in situ hybridization techniques to confirm a HER2-neu amplification in case of IHC2+ using either a core-needle biopsy or a surgical specimen. qPCR has been also demonstrated to be able to determine HER2 status, mostly in core biopsies or in surgical specimens.