Transcranial 3D ultrasound localization microscopy using a large element matrix array with a multi-lens diffracting layer: anstudy.

. Early diagnosis and acute knowledge of cerebral disease require to map the microflows of the whole brain. Recently, ultrasound localization microscopy (ULM) was applied to map and quantify blood microflows in 2D in the brain of adult patients down to the micron scale.

Boosting transducer matrix sensitivity for 3D large field ultrasound localization microscopy using a multi-lens diffracting layer: a simulation study.

Mapping blood microflows of the whole brain is crucial for early diagnosis of cerebral diseases. Ultrasound localization microscopy (ULM) was recently applied to map and quantify blood microflows in 2D in the brain of adult patients down to the micron scale. Whole brain 3D clinical ULM remains challenging due to the transcranial energy loss which significantly reduces the imaging sensitivity.

Implementation of an in situ simulation-based training adapted from Morbidity and Mortality conference cases: effect on the occurrence of adverse events-study protocol of a cluster randomised controlled trial.

Background: Morbidity and Mortality conference provides the necessary improvement measures for patient safety. However, they are an underused resource mainly because the conclusions to be drawn from the discussion and their implications for practice are not always well integrated by inpatient care teams. We therefore propose in this study two interventions to optimise their effectiveness: a passive feedback with wide dissemination by e-mail and/or on paper of the results of the Morbidity and Mortality conference to inpatient care teams and an active feedback with in situ inter-professional simulation-training programme in which scenarios will be based on cases studied in Morbidity and Mortality conference.

Mapping Biological Current Densities With Ultrafast Acoustoelectric Imaging: Application to the Beating Rat Heart.

Ultrafast acoustoelectric imaging (UAI) is a novel method for the mapping of biological current densities, which may improve the diagnosis and monitoring of cardiac activation diseases such as arrhythmias. This paper evaluates the feasibility of performing UAI in beating rat hearts. A previously described system based on a 256-channel ultrasound research platform fitted with a 5-MHz linear array was used for simultaneous UAI, ultrafast B-mode, and electrocardiogram (ECG) recordings.

Patient-derived induced pluripotent stem cells recapitulate hematopoietic abnormalities of juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm of young children initiated by mutations that deregulate cytokine receptor signaling. Studies of JMML are constrained by limited access to patient tissues. We generated induced pluripotent stem cells (iPSCs) from malignant cells of two JMML patients with somatic heterozygous p.

Inhibition of SRC corrects GM-CSF hypersensitivity that underlies juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm in children characterized by the overproduction of monocytic cells that infiltrate the spleen, lung, and liver. JMML remains a disease for which few curative therapies are available other than myeloablative hematopoietic stem cell transplant (HSCT); however, relapse remains a major cause of treatment failure and the long-term morbidities of HSCT for survivors are substantial. A hallmark feature of JMML is acquired hypersensitivity by clonal myeloid progenitor cells to granulocyte macrophage-colony stimulating factor (GM-CSF) via a largely unknown mechanism.

Molecular characteristics of a pancreatic adenocarcinoma associated with Shwachman-Diamond syndrome.

Background: Shwachman-Diamond syndrome (SDS) is characterized by hypoplasia of the bone marrow and exocrine pancreas and a high risk of leukemia. It is unknown whether solid tumors are part of the disease phenotype.

Procedure: We performed copy number alterations using Affymetrix human SNP 6.

[How to assess the impact of morbimortality conferences on healthcare quality and safety in ICU ?].

Objective: To estimate the morbidity and mortality conferences (MMC) impact in intensive care unit (ICU) setting on quality of care and patients' safety.

Data Sources: A review of English and French articles in Medline database (1990-2011) related to MMC in the ICU. Keywords used: "morbidity (and) mortality conference(s)", "intensive care unit", "intensive/critical care medicine".

Risk factors for chronic pain after open ventral hernia repair by underlay mesh placement.

Background: Incisional hernia is a frequent complication following abdominal surgery. Repairs that include the use of mesh have been associated with decreased recurrence. The aim of the present study was to determine the outcomes and risk factors for chronic pain after ventral hernia repair with underlay placement of a composite polypropylene mesh.

Use of a collaborative database for epidemiological analyses and professional practice evaluation.

Rationale: In nephrology, the NEOERICA project assessed the feasibility of the diagnosis scheme based on a general practice database. This approach opened a new area where routinely collected data could be used for purposes other than patient management, such as epidemiological analysis and professional practice evaluation. In Lyon, the TIRCEL network is made up of a coordination team and an online database.

Replication and extension of association between common genetic variants in SIM1 and human adiposity.

Haplo-insufficiency of the bHLH (basic helix-loop-helix) transcription factor single-minded 1 (SIM1) causes severe obesity in mice and humans. We hypothesized that common genetic variations in/near SIM1 could exert more subtle effects on its function and associate with human adiposity. First, SIM1 coding regions were sequenced in severely obese subjects, and two common nonsynonymous single-nucleotide polymorphisms (nsSNPs) in complete linkage disequilibrium (LD) were identified: Pro352Thr (rs3734354) and Ala371Val (rs3734355).

Identification, characterization and rescue of a novel vasopressin-2 receptor mutation causing nephrogenic diabetes insipidus.

Objective: X-linked nephrogenic diabetes insipidus (XNDI), caused by mutations in the V2 vasopressin receptor (V2R), is clinically distinguished from central diabetes insipidus (CDI) by elevated serum vasopressin (AVP) levels and unresponsiveness to 1-desamino-8-d-arginine vasopressin (DDAVP). We report two infants with XNDI, and present the characterization and functional rescue of a novel V2R mutation.

Patients: Two male infants presented with poor growth and hypernatraemia.

Lichen striatus: description of 89 cases in children.

Lichen striatus (LS) is a benign, self-limited, linear, inflammatory dermatosis of unknown etiology that usually affects children. We analyzed 89 cases in regard to age of appearance, sex, race, symptoms, seasonal incidence, localization of lesions and affected side of the body, and presence of atopy. Lesions predominated on the inferior limbs, with no preponderance of any age, and were asymptomatic in the majority of the instances.

A conserved lysine in the estrogen receptor DNA binding domain regulates ligand activation profiles at AP-1 sites, possibly by controlling interactions with a modulating repressor.

BACKGROUND: Estrogen receptors alpha and beta (ERalpha and ERbeta) differentially activate genes with AP-1 elements. ERalpha activates AP-1 targets via activation functions with estrogens (the AF-dependent pathway), whereas ERbeta, and a short version of ERalpha (ERalpha DBD-LBD) activate only with anti-estrogens (AF-independent pathway). The DNA binding domain (DBD) plays an important role in both pathways, even though neither pathway requires ERE recognition.

Identification of plasma proteins adsorbed on hemodialysis tubing that promote Staphylococcus aureus adhesion.

Risk factors for Staphylococcus aureus infections in patients undergoing hemodialysis include underlying disease, material-induced host defects, and the presence of vascular access catheters. To determine the specific contribution of various potentially adsorbed plasma components in promoting S aureus adhesion to shunt tubing during chronic hemodialysis, we quantified their respective amounts by Western immunoblotting and densitometry and estimated their individual adhesion-promoting activities with specific adhesion-modified bacterial mutants. Fibrinogen, which was the only component consistently present in tubing protein extracts from all patients, was adsorbed in significantly higher amounts on predialyzer than on postdialyzer tubing segments.

Is phosphorylation of the alpha1 subunit at Ser-16 involved in the control of Na,K-ATPase activity by phorbol ester-activated protein kinase C?

The alpha1 subunit of Na,K-ATPase is phosphorylated at Ser-16 by phorbol ester-sensitive protein kinase(s) C (PKC). The role of Ser-16 phosphorylation was analyzed in COS-7 cells stably expressing wild-type or mutant (T15A/S16A and S16D-E) ouabain-resistant Bufo alpha1 subunits. In cells incubated at 37 degrees C, phorbol 12, 13-dibutyrate (PDBu) inhibited the transport activity and decreased the cell surface expression of wild-type and mutant Na,K-pumps equally ( approximately 20-30%).

From the molecular biology of prolactin and its receptor to the lessons learned from knockout mice models.

Prolactin (PRL), a polypeptide hormone secreted mainly by the pituitary and, to a lesser extent, by peripheral tissues, affects more physiological processes than all other pituitary hormones combined since it is involved in > 300 separate functions in vertebrates. Its main actions are related to lactation and reproduction. The initial step of PRL action is the binding to a specific membrane receptor, the PRLR, which belongs to the class 1 cytokine receptor superfamily.

Cell shrinkage triggers the activation of mitogen-activated protein kinases by hypertonicity in the rat kidney medullary thick ascending limb of the Henle's loop. Requirement of p38 kinase for the regulatory volume increase response.

The kidney medulla is exposed to very high interstitial osmolarity leading to the activation of mitogen-activated protein kinases (MAPK). However, the respective roles of increased intracellular osmolality and of cell shrinkage in MAPK activation are not known. Similarly, the participation of MAPK in the regulatory volume increase (RVI) following cell shrinkage remains to be investigated.

Glomerulonephritis and sodium retention: enhancement of Na+/K+-ATPase activity in the collecting duct is shared by rats with puromycin induced nephrotic syndrome and mice with spontaneous lupus-like glomerulonephritis.

Background: In rats with puromycin aminoglucoside-induced (PAN) nephrotic syndrome, micropuncture studies have localized the site of sodium retention to the collecting duct. We have confirmed this finding by demonstrating a two-fold increase in Na+/K+-ATPase activity specifically limited to the cortical collecting duct in PAN rats. To further define whether this phenomenon was dependent on the chemical induction of the nephrotic syndrome or was a general phenomenon observed in glomerulonephritis, we measured Na+/K+-ATPase activity in nephron segments from mice with spontaneous lupus-like nephritis.

Insulin-induced stimulation of Na+,K(+)-ATPase activity in kidney proximal tubule cells depends on phosphorylation of the alpha-subunit at Tyr-10.

Phosphorylation of the alpha-subunit of Na+,K(+)-ATPase plays an important role in the regulation of this pump. Recent studies suggest that insulin, known to increase solute and fluid reabsorption in mammalian proximal convoluted tubule (PCT), is stimulating Na+,K(+)-ATPase activity through the tyrosine phosphorylation process. This study was therefore undertaken to evaluate the role of tyrosine phosphorylation of the Na+,K(+)-ATPase alpha-subunit in the action of insulin.

Inhibition and restoration of prolactin signal transduction by suppressors of cytokine signaling.

Prolactin (PRL) has been shown to activate the cytoplasmic tyrosine kinase Janus kinase 2 (Jak2) and the subsequent recruitment of various signaling molecules including members of the signal transducer and activator of transcription family of transcription factors. Recently, an expanding family of cytokine-inducible inhibitors of signaling has been identified that initially included four members: suppressor of cytokine signaling (SOCS)-1, SOCS-2, SOCS-3, and cytokine-inducible src homology domain 2 (SH-2) proteins. The present study analyzes the role of these members in PRL signaling.

Improvement of drug-induced chronic renal failure in lung transplantation.

Background: Nephrotoxicity is a frequently encountered adverse effect of calcineurin inhibitors (cyclosporine and tacrolimus)-combined immunosuppressive regimens.

Methods: We have compared the glomerular filtration rate in 14 patients who underwent lung transplantation, before and after replacement of azathioprine by mycophenolate mofetil and reduction of associated calcineurin inhibitors doses.

Results: After a mean follow-up of 16+/-4 months with the modified immunosuppressive regimen, the mean glomerular filtration rate increased by 20% with no change in lung function.

Dual effects of suppressor of cytokine signaling (SOCS-2) on growth hormone signal transduction.

A family of suppressors of cytokine signaling (SOCS) has recently been identified of which two members have been shown to block growth hormone (GH) signaling. Dose-response experiments were conducted in 293 cells and SOCS-1 and SOCS-3 were shown to inhibit the transcriptional activation of a GH-responsive element and suppressed Jak2 tyrosine kinase activity. SOCS-2 had two opposite effects: at low concentrations it inhibited GH-induced STAT5-dependent gene transcription, but restoration of GH signaling was observed at higher concentrations.

Effect of cAMP on the activity and the phosphorylation of Na+,K(+)-ATPase in rat thick ascending limb of Henle.

Background: In rat kidney medullary thick ascending limb of Henle's loop (MTAL), activation of protein kinase A (PKA) was previously reported to inhibit Na+,K(+)-ATPase activity. This is paradoxical with the known stimulatory effect of cAMP on sodium reabsorption. Because this inhibition was mediated by phospholipase A2 (PLA2) activation, a pathway stimulated by hypoxia, we evaluated the influence of oxygen supply on cAMP action on Na+,K(+)-ATPase in MTAL.