Accuracy of Intraoperative Frozen Section Diagnosis of Borderline Ovarian Tumors by Hospital Type

Study Objective

To compare the accuracy of frozen section diagnosis of borderline ovarian tumors among 3 distinct types of hospital—academic hospital with gynecologic pathologists, academic hospital with nongynecologic pathologists, and community hospital with nongynecologic pathologists—and to determine if surgical staging alters patient care or outcomes for women with a frozen section diagnosis of borderline ovarian tumor.

Lipid-like materials for low-dose,in vivo gene silencing

Significant effort has been applied to discover and develop vehicles which can guide small interfering RNAs (siRNA) through the many barriers guarding the interior of target cells. While studies have demonstrated the potential of gene silencing in vivo, improvements in delivery efficacy are required to fulfill the broadest potential of RNA interference therapeutics. Through the combinatorial synthesis and screening of a different class of materials, a formulation has been identified that enables siRNA-directed liver gene silencing in mice at doses below 0.01 mg/kg. This formulation was also shown to specifically inhibit expression of five hepatic genes simultaneously, after a single injection. The potential of this formulation was further validated in nonhuman primates, where high levels of knockdown of the clinically relevant gene transthyretin was observed at doses as low as 0.03 mg/kg. To our knowledge, this formulation facilitates gene silencing at orders-of-magnitude lower doses than required by any previously described siRNA liver delivery system.     

Effect of Intravascular Iodinated Contrast Media on Natural Course of End-Stage Renal Disease Progression in Hemodialysis Patients: A Prospective Study

We evaluated the impact of intravascular iodinated contrast medium on residual diuresis in hemodialyzed patients. Two groups of clinically stable hemodialyzed patients with residual diuresis minimally 500 ml of urine per day were studied. The patients from the first group were given iso-osmolal contrast agent iodixanol (Visipaque, GE Healthcare, United Kingdom) in concentration of iodine 320 mg/ml with osmolality 290 mOsm/kg of water during the endovascular procedure. The second control group was followed without contrast medium administered. Residual diuresis and residual renal excretory capacity expressed as 24-h calculated creatinine clearance were evaluated in the both groups after 6 months. The evaluated group included 42 patients who were given 99.3 ml of iodixanol in average (range, 60–180 ml). The control group included 45 patients. There was no statistically significant difference found between both groups in daily volume of urine (P = 0.855) and calculated clearance of creatinine (P = 0.573). We can conclude that residual diuresis is not significantly influenced by intravascular administration of iso-osmolal iodinated contrast agent (iodixanol) in range of volume from 60 to 180 ml in comparison to natural course of urinary output and residual renal function during end-stage renal disease. This result can help the nephrologist to decide which imaging method/contrast medium to use in dialyzed patients in current practice.     

Functional proteomics mapping of a human signaling pathway

Access to the human genome facilitates extensive functional proteomics studies. Here, we present an integrated approach combining large-scale protein interaction mapping, exploration of the interaction network, and cellular functional assays performed on newly identified proteins involved in a human signaling pathway. As a proof of principle, we studied the Smad signaling system, which is regulated by members of the transforming growth factor beta (TGFbeta) superfamily. We used two-hybrid screening to map Smad signaling protein-protein interactions and to establish a network of 755 interactions, involving 591 proteins, 179 of which were poorly or not annotated. The exploration of such complex interaction databases is improved by the use of PIMRider, a dedicated navigation tool accessible through the Web. The biological meaning of this network is illustrated by the presence of 18 known Smad-associated proteins. Functional assays performed in mammalian cells including siRNA knock-down experiments identified eight novel proteins involved in Smad signaling, thus validating this integrated functional proteomics approach.     

The nicotinic acetylcholine receptor gene family of the honey bee, Apis mellifera

Nicotinic acetylcholine receptors (nAChRs) mediate fast cholinergic synaptic transmission and play roles in many cognitive processes. They are under intense research as potential targets of drugs used to treat neurodegenerative diseases and neurological disorders such as Alzheimer's disease and schizophrenia. Invertebrate nAChRs are targets of anthelmintics as well as a major group of insecticides, the neonicotinoids. The honey bee, Apis mellifera, is one of the most beneficial insects worldwide, playing an important role in crop pollination, and is also a valuable model system for studies on social interaction, sensory processing, learning, and memory. We have used the A. mellifera genome information to characterize the complete honey bee nAChR gene family. Comparison with the fruit fly Drosophila melanogaster and the malaria mosquito Anopheles gambiae shows that the honey bee possesses the largest family of insect nAChR subunits to date (11 members). As with Drosophila and Anopheles, alternative splicing of conserved exons increases receptor diversity. Also, we show that in one honey bee nAChR subunit, six adenosine residues are targeted for RNA A-to-I editing, two of which are evolutionarily conserved in Drosophila melanogaster and Heliothis virescens orthologs, and that the extent of editing increases as the honey bee lifecycle progresses, serving to maximize receptor diversity at the adult stage. These findings on Apis mellifera enhance our understanding of nAChR functional genomics and provide a useful basis for the development of improved insecticides that spare a major beneficial insect species.     

Initiation of pre-B cell receptor signaling: common and distinctive features in human and mouse

B cell development in the bone marrow is a highly regulated process and expression of a functional pre-BCR represents a crucial checkpoint, common to human and mouse. In this review, we discuss pre-BCR analogies and differences between the two species leading to pre-B cell differentiation and proliferation. In addition, the mechanisms triggering pre-BCR activation are reviewed, taking into account the recent report of heparan sulfates and galectin 1 as stromal cell-derived pre-BCR ligands. Finally, ligand-induced pre-BCR activation models are proposed on the bases of the differences reported for pre-BCR and IL7 dependencies in the two species.     

DOES VISUAL SUBORDINATE-LEVEL CATEGORISATION ENGAGE THE FUNCTIONALLY DEFINED FUSIFORM FACE AREA?

Functional magnetic resonance imaging was used to compare brain activation associated with basic-level (e.g. bird) and subordinate-level (e.g. eagle) processing for both visual and semantic judgements. We localised the putative face area for 11 subjects, who also performed visual matching judgements for pictures and aurally presented words. The middle fusiform and occipital gyri were recruited for subordinate minus basic visual judgements, reflecting additional perceptual processing. When the face area was localised individually for each subject, analyses in the middle fusiform gyri revealed that subordinate-level processing activated the individuals face area. We propose that what is unique about the way faces engage this region is the focal spatial distribution of the activation rather than the recruitment of the face per se. Eight subjects also performed semantic judgements on aurally presented basic- and subordinate-level words. The parahippocampal gyri were more activated for subordinate-level than basic-level semantic judgements. Finally, the left posterior inferior temporal gyrus was activated for subordinate-level judgements, both visual and semantic, as well as during passive viewing of faces.     

Application de la spectroscopie infrarouge (NIRS) dans l’évaluation des adaptations musculaires périphériques chez l’enfant cardiaque

Objective. – The purpose of this work is to study the muscular responses in children with congenital heart disease using near infrared spectroscopy during isometric exercise.Materials and methods. – Twelve healthy children and eight children with congenital heart disease (class II and III NYHA) performed an isometric knee extension on Cybex Norm. For every subject, maximal voluntary contraction (MVC) and endurance time (TE) at 50% of MVC was assessed. The near infrared spectroscopy (NIRS) has been used to assess muscular oxygenation (SmO₂) and of blood volume (VS) during exercise and recovery. Half time recovery of the SmO₂ (1/2 Trec) has been also measured.Results. – Cardiac subjects developed MVC and TE weaker than healthy subjects (MVC: 96.1 ±5.0 vs 125.1 ±6.7 N·m; P <0.01) and (TE: 60.88 ±5.7 vs 116.5 ±8.7 secondes; P <0.001). No significant difference of the SmO₂ and the VS has been noted at rest. The SmO₂ decrease rapidly to reach a plateau at 25% of TE in the healthy subjects, whereas the cardiac subjects reach this plateau at 50% of TE. During recovery, 1/2 Trec is significantly higher in cardiac subjects compared to healthy subjects (26.6 ±1.8 secondes vs 18.9 ±1.9 secondes; respectively, P <0.05).Conclusion. – A decreased muscular performance accompanied with oxygenation and blood volume abnormalities has been found in children with congenital heart diseases. The NIRS is a valuable non-invasive technique for assessment of oxygenation and blood volume during exercise.     

Na/P(i) cotransporter ( Npt2) gene disruption increases duodenal calcium absorption and expression of epithelial calcium channels 1 and 2

Mice homozygous for the disrupted type-II Na/P(i) cotransporter gene ( Npt2(-/-)) exhibit hypophosphataemia, increased serum concentration of 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) and calcium (Ca) and elevated urinary Ca excretion. To determine whether the hypercalcaemia and hypercalciuria are secondary to 1,25-(OH)(2)D-stimulated intestinal Ca absorption, we examined the effect of Npt2 gene disruption on serum Ca and urinary Ca excretion after an overnight fast, and on duodenal Ca absorption. We also compared the duodenal expression of the epithelial Ca channels, ECaC1 and ECaC2, and calbindinD(9K) mRNAs, relative to that of beta-actin mRNA, in Npt2(+/+) and Npt2(-/-) mice. Both serum Ca and urine Ca/creatinine were significantly decreased in Npt2(-/-) mice after an overnight fast and were no longer different from that in wild-type mice. Absorption of (45)Ca from isolated duodenal segments in vivo and (45)Ca appearing in the plasma were significantly increased in Npt2(-/-) compared with Npt2(+/+) mice. In addition, the duodenal abundance of ECaC1, ECaC2 and calbindinD(9K) mRNAs was significantly elevated in mutant mice relative to that in wild-type mice. In contrast, both duodenal Ca absorption and ECaC1 and ECaC2 mRNA abundance were lower in mice with X-linked hypophosphataemia ( Hyp) than in normal littermates. In summary, we provide evidence for increased duodenal Ca absorption in Npt2(-/-) mice and suggest a role for ECaC1, ECaC2 and calbindinD(9K) in mediating this response.     

Rapid antimicrobial susceptibility testing of urinary tract isolates and samples by flow cytometry

A multiparametric flow cytometry antimicrobial susceptibility test was developed and its performance was evaluated on clinical urine isolates and samples in comparison with standard methods. Alterations in cytoplasmic membrane integrity were monitored by propidium iodide, and the anionic probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBAC4(3)) was used to measure changes in membrane potential. Microbial size and cellular content were analysed by light scattering. Twelve antibiotics were tested on 6 ATCC control strains, 22 urine isolates and 19 clinical urine samples, variously containing Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, Staphylococcus aureus, S. saprophyticus and S. epidermidis. Agreement between the flow cytometry results, broth microdilution and disk diffusion tests was 93.9% (n = 328 tests). Of the 20 discrepancies observed, 18 were for species other than E. coli. Perfect correlation was obtained with five antibiotics, whereas norfloxacin, nitrofurantoin and tetracycline were responsible for 13(65%) of the 20 discrepancies.