[Update on Intensive Care Unit Management of Stroke].

In this review, we provide an update on the intensive care unit (ICU) management of ischemic stroke. Over the last decade, new evidence has led to rapid changes in the early management of patients admitted with acute ischemic stroke. Nevertheless, stroke remains a leading cause of disability.

Midbody Positioning and Distance Between Daughter Nuclei Enable Unequivocal Identification of Cardiomyocyte Cell Division in Mice.

Rationale: New strategies in the field of cardiac regeneration are directed at identifying proliferation-inducing substances to induce regrowth of myocardium. Current screening assays utilize neonatal cardiomyocytes and markers for cytokinesis, such as Aurora B-kinase. However, detection of cardiomyocyte division is complicated because of cell cycle variants, in particular, binucleation.

Neutron Scattering Reveals Water Confined in a Watertight Bilayer Vesicle.

Water molecules confined in a nanocavity possess distinctly different characteristics from those in bulk, yet the preparation of such nanocavities is still a major experimental challenge. We report here a self-assembled vesicle of an anionic perfluoroalkylated [60]fullerene, unique for its outstanding stability and water tightness, containing water not bound to the membranes. Small-angle neutron scattering revealed that a vesicle of 14 nm outer radius contains a 2 nm thick fullerene bilayer, inside of which is a 3 nm thick membrane-bound water and unbound water in the 4 nm innermost cavity.

Simple Physical Model Unravels Influences of Chemokine on Shape Deformation and Migration of Human Hematopoietic Stem Cells.

We studied the dynamic behavior of human hematopoietic stem cells (HSC) on the in vitro model of bone marrow surfaces in the absence and presence of chemokine (SDF1α). The deformation and migration of cells were investigated by varying the chemokine concentration and surface density of ligand molecules. Since HSC used in this study were primary cells extracted from the human umbilical cord blood, it is not possible to introduce molecular reporter systems before or during the live cell imaging.

Role of positive lifestyle activities on mood, cognition, well-being, and disease characteristics in multiple sclerosis.

Multiple sclerosis (MS) is a neurological condition associated with a wide variety of physical, cognitive, and mood-related symptoms. While disease-modifying treatment has been shown to reduce the severity and frequency of MS symptom relapses, engagement in certain daily activities holds promise as an adjunctive treatment to better manage disease sequelae. The present study sought to determine whether healthy nutritional choices, exercise, and social/intellectual engagement impacts functioning in individuals with MS.

Author Correction: Dynamic cellular phenotyping defines specific mobilization mechanisms of human hematopoietic stem and progenitor cells induced by SDF1α versus synthetic agents.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Neural Food Reward Processing in Successful and Unsuccessful Weight Maintenance.

Objective: Weight loss maintenance is one of the biggest challenges in behavioral weight loss programs. The present study aimed to examine metabolic influences on the mesolimbic reward system in people with successful and unsuccessful long-term weight loss maintenance.

Methods: Thirty-three women with obesity at least 6 months after the completion of a diet were recruited: seventeen women were able to maintain their weight loss, whereas sixteen showed weight regain.

Visualization of endothelial cell cycle dynamics in mouse using the Flt-1/eGFP-anillin system.

Endothelial cell proliferation is a key process during vascular growth but its kinetics could only be assessed in vitro or ex vivo so far. To enable the monitoring and quantification of cell cycle kinetics in vivo, we have generated transgenic mice expressing an eGFP-anillin construct under control of the endothelial-specific Flt-1 promoter. This construct labels the nuclei of endothelial cells in late G1, S and G2 phase and changes its localization during the different stages of M phase, thereby enabling the monitoring of EC proliferation and cytokinesis.

Dynamic cellular phynotyping defines specific mobilization mechanisms of human hematopoietic stem and progenitor cells induced by SDF1α versus synthetic agents.

Efficient mobilization of hematopoietic stem and progenitor cells (HSPC) is one of the most crucial issues for harvesting an adequate amount of peripheral HSPC for successful clinical transplantation. Applying well-defined surrogate models for the bone marrow niche, live cell imaging techniques, and novel tools in statistical physics, we have quantified the functionality of two mobilization agents that have been applied in the clinic, NOX-A12 and AMD3100 (plerixafor), as compared to a naturally occurring chemokine in the bone marrow, SDF1α. We found that NOX-A12, an L-enantiomeric RNA oligonucleotide to SDF1, significantly reduced the adhesion of HSPC to the niche surface mediated via the CXCR4-SDF1α axis, and stretched the migration trajectories of the HSPC.

Lensless Tomographic Imaging of Near Surface Structures of Frozen Hydrated Malaria-Infected Human Erythrocytes by Coherent X-Ray Diffraction Microscopy.

Lensless, coherent X-ray diffraction microscopy has been drawing considerable attentions for tomographic imaging of whole human cells. In this study, we performed cryogenic coherent X-ray diffraction imaging of human erythrocytes with and without malaria infection. To shed light on structural features near the surface, "ghost cells" were prepared by the removal of cytoplasm.

Reward-related decision making and long-term weight loss maintenance.

Background: Heightened sensitivity towards reward and insensitivity towards disadvantageous consequences may constitute a driving factor underlying unrestricted food intake and consequent weight gain in people with overweight and obesity. Therefore, the present study applied a behavioral economics approach to investigate the potential contribution of poor reward-related decision making to unsuccessful long-term weight loss maintenance (i.e.

Combined genetic and splicing analysis of BRCA1 c.[594-2A>C; 641A>G] highlights the relevance of naturally occurring in-frame transcripts for developing disease gene variant classification algorithms.

A recent analysis using family history weighting and co-observation classification modeling indicated that BRCA1 c.594-2A > C (IVS9-2A > C), previously described to cause exon 10 skipping (a truncating alteration), displays characteristics inconsistent with those of a high risk pathogenic BRCA1 variant. We used large-scale genetic and clinical resources from the ENIGMA, CIMBA and BCAC consortia to assess pathogenicity of c.

The RAD51C exonic splice-site mutations c.404G>C and c.404G>T are associated with familial breast and ovarian cancer.

Whereas RAD51C mutations increase the relative risk for ovarian cancer (OC) to 5.88 (95% confidence interval=2.91-11.

Naturally occurring BRCA2 alternative mRNA splicing events in clinically relevant samples.

Background: BRCA1 and BRCA2 are the two principal tumour suppressor genes associated with inherited high risk of breast and ovarian cancer. Genetic testing of BRCA1/2 will often reveal one or more sequence variants of uncertain clinical significance, some of which may affect normal splicing patterns and thereby disrupt gene function. mRNA analyses are therefore among the tests used to interpret the clinical significance of some genetic variants.

Neuroticism and vigilance revisited: A transcranial doppler investigation.

Selecting for vigilance assignments remains an important factor in human performance research. The current study revisits the potential relationship between vigilance performance and trait neuroticism, in light of two possible theories. The first theory suggests that neuroticism impairs vigilance performance by competing for available resources.

The effects of self-control on cognitive resource allocation during sustained attention: a transcranial Doppler investigation.

Vigilance, or sustained attention, is a required ability in many operational professions. While past research has consistently indicated that vigilance performance declines over time, referred to as the vigilance decrement, the theoretical mechanisms underlying the decrement continue to be explored. In the current study, trait self-control was examined to determine how this individual differences measure may contribute to the theoretical explanation of vigilance decrement.

Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer.

Importance: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists.

Objective: To identify mutation-specific cancer risks for carriers of BRCA1/2.

Design, Setting, And Participants: Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations.

Comprehensive annotation of splice junctions supports pervasive alternative splicing at the BRCA1 locus: a report from the ENIGMA consortium.

Loss-of-function germline mutations in BRCA1 (MIM #113705) confer markedly increased risk of breast and ovarian cancer. The full-length transcript codifies for a protein involved in DNA repair pathways and cell-cycle checkpoints. Several BRCA1 splicing isoforms have been described in public domain databases, but the physiological role (if any) of BRCA1 alternative splicing remains to be established.

RAD51C deletion screening identifies a recurrent gross deletion in breast cancer and ovarian cancer families.

RAD51C is an integral part of the DNA double-strand repair through homologous recombination, and monoallelic mutations were found in ~1.3% of BRCA1/2-negative breast cancer (BC) and/or ovarian cancer (OC) families. Several studies confirmed the occurrence of RAD51C mutations predominantly in BC and/or OC families, although with varying frequencies, clearly establishing RAD51C as a cancer-predisposing gene.

Comparison of mRNA splicing assay protocols across multiple laboratories: recommendations for best practice in standardized clinical testing.

Background: Accurate evaluation of unclassified sequence variants in cancer predisposition genes is essential for clinical management and depends on a multifactorial analysis of clinical, genetic, pathologic, and bioinformatic variables and assays of transcript length and abundance. The integrity of assay data in turn relies on appropriate assay design, interpretation, and reporting.

Methods: We conducted a multicenter investigation to compare mRNA splicing assay protocols used by members of the ENIGMA (Evidence-Based Network for the Interpretation of Germline Mutant Alleles) consortium.

Effect of field size and length of plantar spur on treatment outcome in radiation therapy of plantar fasciitis: the bigger the better?

Purpose: Radiation therapy is well established in the treatment of painful plantar fasciitis or heel spur. A retrospective analysis was conducted to investigate the effect of field definition on treatment outcome and to determine the impact of factors potentially involved.

Methods And Materials: A review of treatment data of 250 patients (285 heels) with a mean follow-up time of 11 months showed that complete symptom remission occurred in 38%, partial remission in 32%, and no change in 19% (11% were lost to follow-up).

Activating somatic FGFR2 mutations in breast cancer.

It is known that FGFR2 gene variations confer a risk for breast cancer. FGFR2 and FGF10, the main ligand of FGFR2, are both overexpressed in 5-10% of breast tumors. In our study, we sequenced the most important coding regions of FGFR2 in somatic tumor tissue of 140 sporadic breast cancer patients and performed MLPA analysis to detect copy number variations in FGFR2 and FGF10.

Analysis of 30 putative BRCA1 splicing mutations in hereditary breast and ovarian cancer families identifies exonic splice site mutations that escape in silico prediction.

Screening for pathogenic mutations in breast and ovarian cancer genes such as BRCA1/2, CHEK2 and RAD51C is common practice for individuals from high-risk families. However, test results may be ambiguous due to the presence of unclassified variants (UCV) in the concurrent absence of clearly cancer-predisposing mutations. Especially the presence of intronic or exonic variants within these genes that possibly affect proper pre-mRNA processing poses a challenge as their functional implications are not immediately apparent.

A 24-color metaphase-based radiation assay discriminates heterozygous BRCA2 mutation carriers from controls by chromosomal radiosensitivity.

Numerous allelic variants identified in the familial breast cancer and DNA repair genes BRCA1 and BRCA2 are of unknown impact on protein function or clinical relevance, referred to as unclassified variants (UCV). Lymphocytes from pathogenic BRCA1/2 mutation carriers exhibit an increased level of chromosomal damage after irradiation. We established a radiation assay for the discrimination of pathogenic BRCA2 variants versus controls based on the level of chromosomal damage upon irradiation (p < 0.

Proteolytic processing of chromogranin A by the prohormone convertase PC2.

The neuroendocrine secretory protein chromogranin A (CgA) is a precursor for various biologically active peptides. Several single and paired basic residues are present within its primary amino acid sequence comprising cleavage sites for prohormone convertases. In this study, SH-SY5Y human neuroblastoma cells were stably transfected with the prohormone convertase PC2 to analyse the proteolytic processing of endogenous chromogranin A and, in particular, the formation of the chromogranin-A-derived peptide GE-25.