Sleep: the sound of a local alarm clock.

Besides the master clock located in the suprachiasmatic nucleus (SCN) of the brain, additional clocks are distributed across the central nervous system and the body. The role of these 'secondary' clocks remains unclear. A new study shows that the lack of an internal clock in histamine neurons profoundly perturbs sleep.

Transdiaphragmatic Resuscitative Open Cardiac Massage: Description of the Technique and a First Case-Series of an Alternative Approach to the Heart

Abstract BACKGROUND: The purpose of this paper is to describe the transdiaphragmatic approach to the heart for open CPR in patients that arrest at laparotomy and to present a first case series of patients that have undergone this procedure. METHODS: All patients who had undergone intraperitoneal transdiaphragmatic open CPR between January 1, 2002 and December 31, 2012 were retrieved from the operation registry at Bern University Hospital, Switzerland. Transdiaphragmatic access to the heart is initiated with a 10-cm-long anterocaudal incision in the central tendon of the diaphragm--approximately at 2 o'clock. Internal cardiac compression through the diaphragmatic incision can be performed from both sides of the patient. From the right side of the patient, cardiac massage is performed with the right hand and vice versa. RESULTS: A total of six patients were identified that suffered cardiac arrest during laparotomy with open CPR performed through the transdiaphragmatic approach. Four patients suffered cardiac arrest during orthotopic liver transplantation and two trauma patients suffered cardiac arrest during damage control laparotomy. In three patients, cardiac activity was never reestablished. However, three patients regained a perfusion heart rhythm and two of these survived to the ICU. One patient ultimately survived to discharge. CONCLUSIONS: In patients suffering cardiac arrest during laparotomy, the transdiaphragmatic approach allows for a rapid, technically easy, and almost atraumatic access to the heart, with excellent CPR performance. After this potentially life-saving procedure, pulmonary or surgical site complications are expected to occur much less compared with the conventionally performed emergency department left-sided thoracotomy.

Larger visual stimuli are perceived to last longer from time to time: The internal clock is not affected by nontemporal visual stimulus size

Performance on interval timing is often explained by the assumption of an internal clock based on neural counting. According to this account, a neural pacemaker generates pulses, and the number of pulses relating to a physical time interval is recorded by a counter. Thus, the number of accumulated pulses is the internal representation of this interval. Several studies demonstrated that large visual stimuli are perceived to last longer than smaller ones presented for the same duration. The present study was designed to investigate whether nontemporal visual stimulus size directly affects the internal clock. For this purpose, a temporal reproduction task was applied. Sixty participants were randomly assigned to one of two experimental conditions with stimulus size being experimentally varied within either the target or the reproduction interval. A direct effect of nontemporal stimulus size on the pacemaker-counter system should become evident irrespective of whether stimulus size was experimentally varied within the target or the reproduction interval. An effect of nontemporal stimulus size on reproduced duration only occurred when stimulus size was varied during the target interval. This finding clearly argues against the notion that nontemporal visual stimulus size directly affects the internal clock. Furthermore, our findings ruled out a decisional bias as a possible cause of the observed differential effect of stimulus size on reproduced duration. Rather the effect of stimulus size appeared to originate from the memory stage of temporal information processing at which the timing signal from the pacemaker-counter component is encoded in reference memory.

The CODE MGEX orbit and clock solution

The Center for Orbit Determination in Europe (CODE) is contributing as a global Analysis center to the International GNSS Service (IGS) since many years. The processing of GPS and GLONASS data is well established in CODE’s ultra-rapid, rapid, and final product lines. With the introduction of new signals for the established and new GNSS, new challenges and opportunities are arising for the GNSS data management and processing. The IGS started the Multi-GNSS-EXperiment (MGEX) in 2012 in order to gain first experience with the new data formats and to develop new strategies for making optimal use of these additional measurements. CODE has started to contribute to IGS MGEX with a consistent, rigorously combined triple-system orbit solution (GPS, GLONASS, and Galileo). SLR residuals for the computed Galileo satellite orbits are of the order of 10 cm. Furthermore CODE established a GPS and Galileo clock solution. A quality assessment shows that these experimental orbit and clock products allow even a Galileo-only precise point positioning (PPP) with accuracies on the decimeter- (static PPP) to meter-level (kinematic PPP) for selected stations.

Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm

Fgfrl1 (also known as Fgfr5; OMIM 605830) homozygous null mice have thin, amuscular diaphragms and die at birth because of diaphragm hypoplasia. FGFRL1 is located at 4p16.3, and this chromosome region can be deleted in patients with congenital diaphragmatic hernia (CDH). We examined FGFRL1 as a candidate gene for the diaphragmatic defects associated with 4p16.3 deletions and re-sequenced this gene in 54 patients with CDH. We confirmed six known coding single nucleotide polymorphisms (SNPs): c.209G > A (p.Pro20Pro), c.977G > A (p.Pro276Pro), c.1040T > C (p.Asp297Asp), c.1234C > A (p.Pro362Gln), c.1420G > T (p.Arg424Leu), and c.1540C > T (p.Pro464Leu), but we did not identify any gene mutations. We genotyped additional CDH patients for four of these six SNPs, including the three non-synonymous SNPs, to make a total of 200 chromosomes, and found that the allele frequency for the four SNPs, did not differ significantly between patients and normal controls (p > or = 0.05). We then used Affymetrix Genechip Mouse Gene 1.0 ST arrays and found eight genes with significantly reduced expression levels in the diaphragms of Fgfrl1 homozygous null mice when compared with wildtype mice-Tpm3, Fgfrl1 (p = 0.004), Myl2, Lrtm1, Myh4, Myl3, Myh7 and Hephl1. Lrtm1 is closely related to Slit3, a protein associated with herniation of the central tendon of the diaphragm in mice. The Slit proteins are known to regulate axon branching and cell migration, and inhibition of Slit3 reduces cell motility and decreases the expression of Rac and Cdc42, two genes that are essential for myoblast fusion. Further studies to determine if Lrtm1 has a similar function to Slit3 and if reduced Fgfrl1 expression can cause diaphragm hypoplasia through a mechanism involving decreased myoblast motility and/or myoblast fusion, seem indicated.

The FGFRL1 receptor is shed from cell membranes, binds fibroblast growth factors (FGFs), and antagonizes FGF signaling in Xenopus embryos

FGFRL1 (fibroblast growth factor receptor like 1) is the fifth and most recently discovered member of the fibroblast growth factor receptor (FGFR) family. With up to 50% amino acid similarity, its extracellular domain closely resembles that of the four conventional FGFRs. Its intracellular domain, however, lacks the split tyrosine kinase domain needed for FGF-mediated signal transduction. During embryogenesis of the mouse, FGFRL1 is essential for the development of parts of the skeleton, the diaphragm muscle, the heart, and the metanephric kidney. Since its discovery, it has been hypothesized that FGFRL1 might act as a decoy receptor for FGF ligands. Here we present several lines of evidence that support this notion. We demonstrate that the FGFRL1 ectodomain is shed from the cell membrane of differentiating C2C12 myoblasts and from HEK293 cells by an as yet unidentified protease, which cuts the receptor in the membrane-proximal region. As determined by ligand dot blot analysis, cell-based binding assays, and surface plasmon resonance analysis, the soluble FGFRL1 ectodomain as well as the membrane-bound receptor are capable of binding to some FGF ligands with high affinity, including FGF2, FGF3, FGF4, FGF8, FGF10, and FGF22. We furthermore show that ectopic expression of FGFRL1 in Xenopus embryos antagonizes FGFR signaling during early development. Taken together, our data provide strong evidence that FGFRL1 is indeed a decoy receptor for FGFs.

A new multimodality technique accurately maps the primary lymphatic landing sites of the bladder

Pathoanatomic studies have failed to map accurately the primary lymphatic landing sites of the urinary bladder.

Differences in the quality of interpersonal care in complementary and conventional medicine

The study was part of a nationwide evaluation of complementary and alternative medicine (CAM) in Swiss primary care. The aim of the study was to compare patient-physician relationships and the respective patient-reported relief of symptoms between CAM and conventional primary care (COM).

Identification of a fibronectin interaction site in the extracellular matrix protein ameloblastin

Mammalian teeth are composed of hydroxyapatite crystals that are embedded in a rich extracellular matrix. This matrix is produced by only two cell types, the mesenchymal odontoblasts and the ectodermal ameloblasts. Ameloblasts secrete the enamel proteins amelogenin, ameloblastin, enamelin and amelotin. Odontoblasts secrete collagen type I and several calcium-binding phosphoproteins including dentin sialophosphoprotein, dentin matrix protein, bone sialoprotein and osteopontin. The latter four proteins have recently been grouped in the family of the SIBLINGs (small integrin-binding ligand, N-linked glycoproteins) because they display similar gene structures and because they contain an RGD tripeptide sequence that binds to integrin receptors and thus mediates cell adhesion. We have prepared all the other tooth-specific proteins in recombinant form and examined whether they might also promote cell adhesion similar to the SIBLINGs. We found that only ameloblastin consistently mediated adhesion of osteoblastic and fibroblastic cells to plastic or titanium surfaces. The activity was dependent on the intact three-dimensional structure of ameloblastin and required de novo protein synthesis of the adhering cells. By deletion analysis and in vitro mutagenesis, the active site could be narrowed down to a sequence of 13 amino acid residues (VPIMDFADPQFPT) derived from exon 7 of the rat ameloblastin gene or exons 7-9 of the human gene. Kinetic studies and RNA interference experiments further demonstrated that this sequence does not directly bind to a cell surface receptor but that it interacts with cellular fibronectin, which in turn binds to integrin receptors. The identification of a fibronectin-binding domain in ameloblastin might permit interesting applications for dental implantology. Implants could be coated with peptides containing the active sequence, which in turn would recruit fibronectin from the patient's blood. The recruited fibronectin should then promote cell adhesion on the implant surface, thereby accelerating osseointegration of the implant.

Readaptation of the peritoneum following extended pelvic lymphadenectomy and cystectomy has a significant beneficial impact on early postoperative recovery and complications: results of a prospective randomized trial

Prolonged postoperative pain and delayed intestinal transit are frequent problems following extended pelvic lymph-node dissection (PLND) and cystectomy.