iTRAQ-Based Proteomic Analysis of Neonatal Kidney from Offspring of Protein Restricted Rats Reveals Abnormalities in Intraflagellar Transport Proteins.
It is well recognized that adverse events in utero can impair fetal development and lead to the development of kidney injury and hypertension in adulthood. We previously reported a lower kidney index, glomeruli number, and decreased glomerular filtration rate in intrauterine growth restriction (IUGR) offspring induced by maternal protein malnutrition. To explore the molecular mechanisms linking impaired fetal growth to renal diseases, we investigated differentially expressed proteins (DEPs) in the IUGR neonatal kidneys by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. We induced IUGR through maternal protein malnutrition. Neonatal kidneys were collected; the protein was extracted; pooled before iTRAQ labeling, and subjected to mass spectrometric analysis. Mass spectrometry results were then further confirmed by assessing five representative proteins in individual specimens with quantitative PCR (qPCR), immunohistochemical (IHC) and / or western blot analysis. A total of 367DEPs (263 up-regulated, 104 down-regulated.) with a threshold of a 1.2-fold change and a P value ≤ 0.05 between IUGR kidneys and control kidneys were identified. Further bioinformatics analysis revealed that these proteins play important roles in oxidative phosphorylation, purine metabolism, pyrimidine metabolism, RNA small body, spliceosome assembly and intraflagellar transport (IFT). IFT family proteins (IFT80, 88,144) and PKD2 were shown to be up-regulated in IUGR kidneys, confirmed by western blotting, IHC and Q-PCR. Epigenetic modulating factors SET and MYND domain containing 3 (SMYD3), a histone-lysine N-methyltransferase, and H3K4me3 level were also remarkably enhanced in IUGR neonatal kidneys. This first comprehensive analysis of the neonatal kidney proteome reveals new insights in nephridial development, and may make a valuable contribution towards the identification of the pathological mechanisms involved in the developmental origins of adult disease.


[Remote effects in plant populations from zones of radiation and chemical pollution].
A comparative research of dandelion seed progeny from the coenopopulations growing for a long time in a gradient of radioactive (zone of the East-Ural radioactive trace--EURT) or chemical (zone exposure Nizhny Tagil Metallurgical Plant--NTMP) pollution was carried out. It was revealed that the viability of seeds declined similarly in gradient of the man-caused stress regardless of its nature. Dandelion coenopopulations from the EURT zone, NTMP and the background area significantly differed in the qualitative and quantitative allozyme specifications. The analysis of clonal diversity revealed phenogenetic uniqueness of all coenopopulations. Study of F1-generation metal and radio resistance showed that the seed progeny from the impact EURT zone possessed a high viability but had hidden damage that led to a low resistance to additional man-caused influences. High viability of the seeds in the F1-generation from the NTMP zone combined with increased resistance to the provocative effects of radiation and heavy metals. Significant differences in responses to the "habitual" and "n ew" factors of influence, i.e. effect of pre-adaptation in samples from EURT and NTMP zones were not found.


A comparative study of estramustine and pregnenolone binding to prostatic binding protein: evidence for subunit cooperativity.
The binding of estramustine, a nitrogen mustard derivative of oestradiol to purified rat prostatic binding protein was studied as a test for a possible identity between this protein and the very similar estramustine-binding protein, described by Forsgren et al. In accordance with this hypothesis estramustine binds to purified prostatic binding protein with a high affinity (2.5 X 10(7)M-1). This affinity markedly exceeds the affinity of pregnenolone for this protein (0.9 X 10(6)M-1) or for a complex of prostatic binding protein, with prostatic proline-rich polypeptide, (4.7 X 10(6)M-1). In competition experiments estramustine completely suppresses the binding of [3H]pregnenolone, whereas the binding of [3H]estramustine is only partially suppressed by pregnenolone, even at high concentrations. Prostatic binding protein was separated in its F- and S-subunit by DEAE-Sepharose chromatography performed in the presence of 8 M urea. Only the S-subunit, most probably in its dimer form, displays marked estramustine and pregnenolone binding, with affinities of respectively 3.7 and 1.2 X 10(6)M-1. Recombination of both subunits results in a strong increase of estramustine binding, but not of pregnenolone binding.


Stimulation of phosphate uptake in human platelets by thrombin and collagen. Changes in specific 32P labeling of metabolic ATP and polyphosphoinositides.
The uptake of [32P]phosphate by human, gel-filtered blood platelets and its incorporation into cytoplasmic ATP and polyphosphoinositides was studied. In unstimulated platelets, uptake was Na+o-dependent and saturable at approximately 20 nmol/min/10(11) cells with a half-maximal rate at 0.5 mM extracellular phosphate. Upon stimulation with thrombin or collagen, net influx of [32P]Pi was accelerated 5- to 10-fold. With thrombin, [32P]Pi efflux was also increased. After the first 2 min, efflux exceeded influx, resulting in the net release of [32P]Pi from the platelets. Since the stimulus-induced burst in [32P]Pi uptake paralleled the secretory responses, it might be an integral part of stimulus-response coupling in platelets. The stimulus-induced burst in net [32P]Pi uptake led to an enhanced labeling of metabolic ATP, which was already detectable at 5 s after stimulation with thrombin. Concomitantly, the incorporation of [32P]Pi into phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate was accelerated. The thrombin-induced increase in specific 32P radioactivity of cytoplasmic ATP fully accounted for the simultaneous increase in specific 32P radioactivity of these phosphoinositides. In studying the extent of 32P labeling of phosphorylated compounds in response to a cellular stimulus, it is therefore essential to measure the effect of the stimulus on the specific radioactivity of cytoplasmic ATP.


Pre-trial cocaine biases choice toward cocaine through suppression of the nondrug option.
Being under the influence during choice between drug and nondrug options can have a dramatic effect on choice outcomes. When rats face a choice between cocaine and sweet water and are not under the influence, they prefer sweet water. In contrast, when they are under the influence of cocaine, this causes them to shift their choice to cocaine nearly exclusively. Here we sought to characterize the behavioral mechanisms underlying the influence of cocaine on choice. In theory, rats under the influence of cocaine should be in a mixed motivational state, at least temporarily, with both their motivation for cocaine and their motivation for the nondrug option suppressed by the drug satiating and anorexic effects of cocaine, respectively. For this mixed state to shift choice to cocaine, the satiated motivation for cocaine should recover before the suppressed motivation for the preferred nondrug option. The goal of the present study was to test this prediction in rats that expressed a preference for sweet water after extended access to cocaine self-administration. We measured their choice and response latencies to each option after pre-trial, passive administration of cocaine to estimate the duration of its drug satiating and anorexic effects. As expected, pre-trial cocaine caused most rats to shift their choice to cocaine. Though this shift was not simply due to a longer latency to respond for sweet water than for cocaine after pre-trial cocaine, it nevertheless occurred while rats' motivation for the nondrug option was still partially suppressed. Thus, cocaine seems to bias choice toward more cocaine mainly via suppression of the nondrug option.


New methods of minimally invasive brain modulation as therapies in psychiatry: TMS, MST, VNS and DBS.
Over the past 20 years, new methods have been developed that have allowed scientists to visualize the human brain in action. Initially positron emission tomography (PET) and now functional magnetic resonance imaging (fMRI) are causing a paradigm shift in psychiatry and the neurosciences. Psychiatry is abandoning the pharmacological model of 'brain as soup', used for much of the past 20 years. Instead, there is new realization that both normal and abnormal behavior arise from chemical processes that occur within parallel distributed networks in specific brain regions. Many of these pathological circuits are becoming well characterized, in disorders ranging from Parkinson's disease, to obsessive-compulsive disorder, to depression. Most recently, there has been an explosion of new techniques that allow for direct stimulation of these brain circuits, without the need for open craniotomy and neurosurgical ablation. The techniques include transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), vagus nerve stimulation (VNS), and deep brain stimulation (DBS). This review will describe these new tools, and overview their current and future potential for research and clinical neuropsychiatric use. The psychiatry of the future will be better grounded in a firm understanding of neuroanatomy and neurophysiology (as well as pharmacology). These brain stimulation tools, or their next iterations, will play an ever-larger role in clinical neuropsychiatric practice.


Homocystinuria, a possible solution of the Akhenaten's mystery.
Pharaoh Amenophis IV (Amenhotep IV), also known as Akhenaten, is the most mysterious person in Egyptian history and he still remains the object of academic argues. This revolutionary king introduced a new concept in Egyptian religion and arts. It is still unexplained if images of him and his family were just an artistic outbreak from old Egyptian canon or an excellent paleopathological study. Several pathologic conditions were proposed to explain his appearance but neither is completely acceptable. We propose a different disease that he could have suffered of homocystinuria--lack of cysthationine-synthase. Our conclusion is that in comparison with up to date most convincing theory, that he was suffering of Marfan syndrome, our theory equally well explains his physical appearance but is better in explaining affecting and unaffecting of his relatives. This is the only theory about Akhenaten's disease that could be checked in the near future.


Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules.
It is widely accepted that tissue differentiation and morphogenesis in multicellular organisms are regulated by tightly controlled concentration gradients of morphogens. How exactly these gradients are formed, however, remains unclear. Here we show that Fgf8 morphogen gradients in living zebrafish embryos are established and maintained by two essential factors: fast, free diffusion of single molecules away from the source through extracellular space, and a sink function of the receiving cells, regulated by receptor-mediated endocytosis. Evidence is provided by directly examining single molecules of Fgf8 in living tissue by fluorescence correlation spectroscopy, quantifying their local mobility and concentration with high precision. By changing the degree of uptake of Fgf8 into its target cells, we are able to alter the shape of the Fgf8 gradient. Our results demonstrate that a freely diffusing morphogen can set up concentration gradients in a complex multicellular tissue by a simple source-sink mechanism.


Molecular cloning and sequence analysis of the Anticarsia gemmatalis multicapsid nuclear polyhedrosis virus GP64 glycoprotein.
The gp64 locus of Anticarsia gemmatalis multicapsid nucleopolyhedrovirus isolate Santa Fe (AgMNPV-SF) was characterised molecularly in our laboratory. To this end, we have located and cloned a AgMNPV-SF genomic DNA fragment containing the gp64 gene and sequenced the complete gp64 locus. Nucleotide sequence analysis indicated that the AgMNPV gp64 gene consists of a 1500 nucleotide open reading frame (ORF), encoding a protein of 499 amino acids. Of the seven gp64 homologues identified to date, the AgMNPV gp64 ORF shared most sequence similarity with the gp64 gene of Orgyia pseudotsugata MNPV. The GP64 from AgMNPV is the smallest baculoviral envelope glycoprotein found to date, differing in 10 or more residues from the other group I nucleopolyhedroviruses. The biological activity of AgMNPV GP64 protein was assessed by cell fusion assays in UFL-AG-286 cells using the obtained recombinant plasmids. In the upstream and downstream regions, relative to the gp64 ORF, we found different conserved transcriptional and post-transcriptional regulatory elements, respectively.


Melamine impairs spatial cognition and hippocampal synaptic plasticity by presynaptic inhibition of glutamatergic transmission in infant rats.
The scandal of melamine-contamination has not been quite blown out, since the toxicity of melamine continues to raise concerns for public health. It has been well known that fetus and infant periods play the most important roles in brain development, whereas little has been done on the harmful effects of melamine on the center nervous system (CNS) of children. In the present study, we investigated the effects of melamine on behavioral and electrophysiology alternations in rats, and the effects of melamine on synaptic transmission were examined using whole-cell patch-clamp technique in the hippocampal CA1 neurons of infant rats. Morris water maze (MWM) test showed that learning and memory abilities were impaired significantly by melamine. The long-time potentiation (LTP) test exhibited that the field excitatory postsynaptic potential (fEPSP) slopes were significantly lower in melamine group compared to that in control group. Furthermore, the data of whole-cell patch-clamp experiments showed that melamine decreased the frequencies of both spontaneous EPSCs (sEPSCs) and minitura EPSCs (mEPSCs) to the same extent (about 76% and 78% respectively). However, there were no significant changes in sEPSC or mEPSC amplitude or kinetics after melamine addition, indicating that the effect of melamine on glutamatergic transmission was probably presynaptic. In conclusion, melamine reduced the release of glutamate in presynaptic transmission of hippocampus, which partly resulted in diminished LTP and further damaged the function of learning and memory.


[The effect of Tween-80 on the differentiation of Trichophyton mentagrophytes and Trichophyton rubrum strains with FT-IR spectroscopy].
Trichophyton mentagrophytes and Trichophyton rubrum, are two of the frequently identified dermatophyte species in routine microbiology laboratories. Although newer technologies may assist in species-level identification, direct application of these methods usually require improvement in order to obtain reliable identification of these species. Earlier data have shown that dermatophytes may be identified with FT-IR spectroscopy although there are some limitations. In particular, the organic bond ranges in FT-IR spectra showed more irregularity because of the eucaryotic complexity of the molds. In this study, Tween-80 which is an inorganic molecule, was added to the dermatophyte growth medium in order to investigate its effect on FT-IR spectroscopy analysis of dermatophytes. Nine reference dermatophyte strains [5 T.mentagrophytes complex (T.asteroides CBS 424.63, T.erinacei CBS 344.79, CBS 511.73, CBS 677.86, T.mentagrophytes CBS 110.65) and 4 T.rubrum complex strains with different morphotypes (T.fluviomuniense CBS 592.68, T.kuryangei CBS 422.67, T.raubitschekii CBS 102856, T.rubrum CBS 392.58)] were included in the study. All strains were cultured on Sabouraud glucose agar either with or without 1% Tween-80 for three weeks. After the incubation period, superficial scrapings from each dermatophyte colony were analyzed using FT-IR spectroscopy. All measurements were performed in transmission mode between 4400 and 400 cm-1. Numerous spectral window data were analyzed by principal component analysis and hierarchical clustering was performed. The second derivations of spectral ranges revealed clear grouping of T.mentagrophytes complex and T.rubrum complex in association over five separate spectral ranges. The findings also showed that while all of the T.mentagrophytes strains contained lipid compounds in their mold structure after Tween-80 incubation (p< 0.025), T.rubrum strains did not. Based on these results, it was concluded that culture medium containing Tween-80 was sufficient to enable differentiation of T.mentagrophytes complex from T.rubrum complex by FT-IR spectroscopy. This effect might be attributed to the possible transfer of lipid compounds from culture to cell structure during growth. Further studies with the use of large number of reference strains and clinical isolates exposed to different environmental factors, such as antifungal agents and inorganic ions, are needed to support these data indicating favorable effect of Tween-80 on the differentiation of T.mentagrophytes and T.rubrum complexes by FT-IR spectroscopy.


Colocalization of the genes for the alpha 3(IV) and alpha 4(IV) chains of type IV collagen to chromosome 2 bands q35-q37.
Each type of basement membrane in man contains between two and five genetically distinct type IV collagens: alpha 1(IV)-alpha 5(IV). Genes for alpha 1(IV), alpha 2(IV), alpha 3(IV), and alpha 5(IV) have been isolated. We have recently isolated partial cDNAs for the fifth member of the family, designated alpha 4(IV). On the basis of comparison of the deduced peptide sequences of all five chains, the type IV collagens can be divided into two families: alpha 1-like, comprising alpha 1(IV), alpha 3(IV), and alpha 5(IV); and alpha 2-like, comprising alpha 2(IV) and alpha 4(IV). Genes encoding the alpha 1(IV) and alpha 2(IV) chains (COL4A1 and COL4A2) both map to human chromosome 13q34 and have been shown to be transcribed from opposite DNA strands using a common bidirectional promoter that allows coordinate regulation of the two chains. Indeed, these two chains are commonly found together in basement membrane and form [alpha 1]2.[alpha 2] heterotrimers. Whereas alpha 1(IV) and alpha 2(IV) have been found in all basement membranes studied hitherto, it has been shown that alpha 3(IV) and alpha 4(IV) are found in only a subset of basement membranes. In basement membranes where either of these molecules is present, however, they are found together. In view of this relationship and the structural similarities between alpha 1(IV) and alpha 3(IV) and between alpha 2(IV) and alpha 4(IV), we hypothesized that COL4A3 and COL4A4, the genes encoding alpha 3(IV) and alpha 4(IV), respectively, have a genomic organization similar to that of COL4A1 and COL4A2.(ABSTRACT TRUNCATED AT 250 WORDS)


Single-arm double-mode double-order planar waveguide interferometric sensor.
A sensor is described for which interference measurements of the phase delay between two propagating modes of different orders in a slab thin-film waveguide are used as the sensing technique. The basic building block of the sensor is a polymer film doped with an indicator dye such as Bromocresol Purple. The modes of two orders such as TM(0) and TM(1) are simultaneously excited in the light-guiding film with a focusing optics and a prism coupler. The modes are decoupled from the film and recombined to produce an interference pattern in the face of an output optical fiber. The sensitivity of the sensor to the ambient temperature change is 1.5 degrees C, and the sensitivity to NH(3) is 200 parts in 10(6) for one full oscillation of the signal.


Enhanced tumor growth of both primary and established human and murine tumor cells in athymic mice after coinjection with Matrigel.
Previously we found that the reconstituted basement membrane matrix Matrigel, when premixed with human small-cell lung carcinoma cells and injected subcutaneously into athymic mice, permitted tumor growth, whereas cells injected in the absence of Matrigel did not form tumors. In the present study, we examined additional cell types and determined some of the underlying mechanisms involved in the promotion of tumor formation by Matrigel. The tumor cell lines that we studied included transformed mouse Englebreth-Holm-Swarm tumor cells (T-EHS), human submandibular carcinoma A253 cells, mouse melanoma B16F10 cells, human epidermoid carcinoma KB cells, and human primary renal cell carcinoma cells. When coinjected subcutaneously with Matrigel, these cell lines formed rapidly proliferating tumors. Primary biopsy specimens of human colon carcinoma, when dispersed and coinjected with Matrigel, also formed tumors. Only A253, KB, and B16F10 cells formed small tumors in the absence of Martrigel, but a fivefold to tenfold increase in tumor size was observed in the presence of Matrigel. These data demonstrate a useful method for improving the growth of human tumors in athymic mice.


Phosphoinositide 3-kinase signalling in the vascular system.
Phosphoinositide 3-kinases (PI3Ks) are protein and lipid kinases activated by different classes of membrane receptors, including G-protein coupled and tyrosine kinase receptors. Several lines of evidence have uncovered specific roles for distinct PI3K isoforms in the vascular system in both physiology and disease. The present review will summarize and discuss the most recent advances regarding PI3K-Akt signalling in endothelial cells, vascular smooth muscle cells, platelets, and inflammatory cells involved in the atherosclerotic process. Of interest, the development of novel isoform-selective PI3K inhibitor drugs offers a unique opportunity to selectively and differentially target PI3K-driven pathways in the vascular system and may give rise to new strategies for the treatment of cardiovascular diseases.


Multiple pilomatrixomas affecting the eyelid and face.
A 3-year-old girl presented with a right upper eyelid mass. The lesion had a reddish appearance, was firm to palpation, and was fixed to underlying tissues. Fourteen months after the lesion was excised, a similar lesion was discovered on the left side of the nose and was also excised. Histopathologic examination of the excised tumors revealed variable basophilic hair matrix cells and sheets of nonviable eosinophilic shadow cells. Foci of dystrophic calcification were also seen in the necrotic tumor areas. The histopathologic findings were found to be consistent with pilomatrixoma. Results of limited clinical work-up of the child for Gardner's syndrome, sarcoidosis, and myotonic dystrophy were negative. Multiple periocular and facial pilomatrixomas can occur in children in the clinical absence of myotonic dystrophy, Gardner's syndrome, and sarcoidosis.


Recommendations for the concepts and form of Healthy People 2020.
Since 1980, Healthy People, a comprehensive set of ten-year national public health objectives, has been used by the public health and healthcare communities to guide health planning and motivate action. The USDHHS began developing Healthy People 2020 in 2007. In 2008, USDHHS convened an external advisory committee composed of 13 experts in the fields of public health, healthcare delivery, and other health-related disciplines to advise the USDHHS Secretary on the development of Healthy People 2020, including its vision, mission, goals, objectives, and implementation strategies. In 2008, the committee considered how to improve the Healthy People initiative by building on past efforts. Its members reflected on the purpose of Healthy People and discussed questions such as: What is and is not working well in the initiative, and what else should Healthy People provide to its users? These discussions were informed by public testimony and written comments, as well as expert presentations. The end product of the committee's 2008 work is a report to the USDHHS Secretary that recommends the underlying ideas, concrete form, and implementation of Healthy People 2020. These include a mission statement, vision statement, overarching goals, and an action model for achieving the goals. It was concluded that Healthy People should no longer be known primarily as a print-based reference book. It should also be a user-friendly, Internet-accessible database that is searchable, interactive, and updatable.


Core-shell noble metal nanostructures templated by gold nanorods.
The main research progress in core-shell noble metal nanostructures templated by gold nanorods (Au NRs) is summarized regarding synthesis, optical, and catalytic properties. Design and fabrication of core-shell hybrid nanostructures are demonstrated to be effective not only for optimizing and expanding intrinsic properties but also for creating novel localized surface plasmon enhanced optical and catalytic functionalities, thus providing great prospects in both fundamental research and potential applications.


Effects of adenosine and adenosine 5'-triphosphate on ventricular escape rhythm in the canine heart.
The effects of adenosine and adenosine 5'-triphosphate (ATP) on ventricular escape rhythms were studied in 16 closed chest dogs after electroablation of the His bundle region. All dogs exhibited complete atrioventricular (AV) block and stable ventricular escape rhythm with a mean cycle length of 1,210 +/- 80 ms and a QRS width of 91 +/- 5 ms. Physiologic AV sequential pacing was operative during experiments and was interrupted for rapid (less than or equal to 1 second) administration of either adenosine or ATP (3 mumol/kg) into the right atrium. Adenosine and ATP effectively depressed ventricular escape rhythms in a similar manner both qualitatively and quantitatively (cycle length from 1,210 +/- 80 to 1,764 +/- 132 ms and from 1,274 +/- 84 to 2,000 +/- 150 ms, respectively; each p less than 0.01). These effects were not significantly altered by either physostigmine (an acetylcholinesterase inhibitor) or atropine (a muscarinic cholinergic blocker), but were slightly attenuated by propranolol (a beta-adrenoceptor blocker). In the presence of autonomic blockade, the adenosine transport blocker dipyridamole markedly enhanced the depressant effects of adenosine and ATP. The adenosine competitive antagonist aminophylline reversed the action of dipyridamole. Thus, both adenosine and ATP depress ventricular escape rhythms in vivo, independent of the autonomic nervous system. Moreover, the effects of ATP can be accounted for in large part by its rapid breakdown to adenosine.


[MRI study of the tissue volume progression of lower limbs in hemiplegic subjects].
The aim of this paper was to present the first results of a study about lower limbs' soft tissues (fat and muscle) evolution using magnetic resonance images. Magnetic resonance images method (MRI) was chosen instead of X-ray scanner for its non-invasive and non-radiating properties. Three hemiplegics volunteers were followed during the first 6 months of their therapy. Lower limbs' MRI captures were made at the beginning and in the end of this period. Computerized processing of the data allows automatic recognition of the main lower limb's tissues. Volumes were determined from images and classified in 4 categories (i.e. muscle, fat, spongy bone, cortical bone). Data analysing showed a different evolution of soft tissues in healthy lower limb compared to pathological lower limb. This results should lead us to a better understanding of therapeutic efficiency.


[Explicit and implicit memory for emotional stimuli in depressed elderly and Alzheimer's disease].
It is well known that emotional events are better recalled than neutral events. It indicates that memory is affected by the emotional content of stimuli. Since psychiatric and neurodegenerative diseases produce qualitatively and quantitively different memory and emotional disorders, a better understanding of their relations should improve our knowledge about memory and emotion interaction. We present here a review of recent studies that examined the effects of emotions on episodic (explicit) memory and on perceptual and conceptual priming (implicit memory) in depression and in Alzheimer's disease. Several studies of memory in depressed patients reported a tendency toward recall of negatively toned material indicating the existence of a bias toward processing of mood-congruent information. On the other hand, an enhancement of memory performance is observed in Alzheimer's disease when positive and negative stimuli are used.


Allergy immunotherapy for allergic rhinitis effectively prevents asthma: Results from a large retrospective cohort study.
Allergic rhinitis (AR) is a main risk factor for the development of asthma. Two randomized open-label trials indicated that allergy immunotherapy (AIT) prevents the onset of asthma in patients with AR. However, these trials have methodological limitations, and it is unclear to what extent this experimental efficacy translates into clinical effectiveness. We sought to investigate the effectiveness of AIT to prevent asthma in patients with AR. Using routine health care data from German National Health Insurance beneficiaries, we identified a consecutive cohort of 118,754 patients with AR but without asthma who had not received AIT in 2005. These patients were stratified into one group starting AIT in 2006 and one group receiving no AIT in 2006. Both groups were observed regarding the risk of incident asthma in 2007 to 2012. Risk ratios (RRs) were calculated with generalized linear models by using a Poisson link function with robust error variance and adjustment for age, sex, health care use because of AR, and use of antihistamines. In a total of 2431 (2.0%) patients, AIT was started in 2006. Asthma was newly diagnosed from 2007-2012 in 1646 (1.4%) patients. The risk of incident asthma was significantly lower in patients exposed to AIT (RR, 0.60; 95% CI, 0.42-0.84) compared with patients receiving no AIT in 2006. Sensitivity analyses suggested significant preventive effects of subcutaneous immunotherapy (RR, 0.54; 95% CI, 0.38-0.84) and AIT including native (nonallergoid) allergens (RR, 0.22; 95% CI, 0.02-0.68). AIT for 3 or more years tended to have stronger preventive effects than AIT for less than 3 years. AIT effectively prevents asthma in patients with AR in a real-world setting. Confounding by indication cannot be excluded but would lead to an underestimation of the true preventive effects of AIT.


The use of Robertsonian translocations in the mouse for studies on non-disjunction.
In the mouse, gametes with gross chromosome duplications and deficiencies can complement each other to give viable zygotes (with some notable exceptions involving particular chromosomes). These complementation-type offspring can be recognised in intercrosses between translocation heterozygotes in which one parent is homozygous for a recessive genetic marker not carried by the other. This system has beeN used by Lyon and colleagues (1976) to study non-disjunction in heterozygotes for tobacco mouse and laboratory-derived Robertsonian translocations. Although non-disjunction is frequent in the former group, still higher frequencies are needed for a workable test system in which wild type mice are treated and mated to a tester stock generating many aneuploid gametes. Possible approaches include (1) use of semidominant markers, (2) marking both arms, (3) combining two or three independent Robertsonians in the tester stock, (4) use of compounds of Robertsonians wih monobrachial homology, since these give very high frequencies of non-disjunction, (5) generation of a compound of three Robertsonians with tribrachial homology, which should produce aneuploid gametes only. This last seems the most promising approach, if the compound proves fertile, and would be analogous to the isochromosome system of Drosophila.


Towards High-Performance Electrocatalysts for Oxygen Reduction: Inducing Atomic-Level Reconstruction of Fe-Nx Site for Atomically Dispersed Fe/N-Doped Hierarchically Porous Carbon.
A rational and effective strategy for the synthesis of a high-performance non-precious metal electrocatalyst for oxygen reduction reaction (ORR) was developed by inducing reconstruction of Fe-Nx site on pig-bone-derived nitrogen-doped hierarchically porous carbon. The resultant Fe/N-doped carbon electrocatalyst possessed abundant atomically dispersed non-planar Fe-N4 ORR active sites, with absolute presence of active D1 (FeII -N4 ) and D3 (N-FeII -N2+2 ) sites, as well as large specific surface area and three-dimensional porous structure with hierarchical micro-/meso-/macro-pore distribution, which increased the utilization of active sites and promoted mass transport of ORR reactants. This resulted in a remarkably superior ORR activity with half-wave potential of 0.87 V (20 mV higher than Pt/C) and kinetic current density of 10.9 mA cm-2 at 0.85 V (2.3-fold of Pt/C) in alkaline electrolyte. This methodology provides a route for atomic-level design of high-performance ORR electrocatalyst.


Experiences with surgically treated primary or secondary hepatic sarcoma.
Liver resection in hepatic sarcoma is rare, but other alternative treatment options are scarce. Surgery offers the only aggressive approach to achieve a tumour-free state. The aim of this investigation was to evaluate the outcome and survival of these patients at a single hepato-biliary university hospital. Between January 2004 and July 2013, 896 anatomical liver resections were performed. Eleven liver resections (1.2%) were performed due to primary hepatic sarcoma or hepatic sarcoma metastases. The demographic and clinical parameters were collected from the institutional patients' records. In eight patients (83%), liver resection was performed due to hepatic sarcoma metastases. The surgical procedures were as follows: two patients (18%) had segmentectomy, six patients (55%) had hemihepatectomy or extended hemihepatectomy and three patients (27%) had multivisceral resections. In nine patients (82%), the resection margins were tumour free. In 55% (n = 6) of the patients, the maximal tumour diameter was greater than 10 cm. The postoperative morbidity was low with a Clavien-Dindo score of 2 (range 0-5). One patient died on postoperative day 2 after multivisceral resection. During the follow-up of 932 days (range 2-2.220 days) the 1-, 2- and 3-year survival rates were 91, 63 and 45%, respectively. Tumour recurrence was detected in seven patients (63%). Liver resections in patients with primary or secondary hepatic sarcoma are rare. The main goal in these patients is to achieve complete tumour resection because chemotherapy offers no suitable alternative, but the long-term survival rates are limited because of high a recurrence rate even after aggressive surgical approaches.


Vital tooth esthetics in Captek restorations.
Captek crowns and bridges employ optical effects that simulate vital tooth esthetics. The intensive red color of the blood in the vital pulp plays an important role in natural tooth appearance. This role is often ignored in restoration construction and results in a dead-looking restored tooth. To achieve optimal tooth esthetics, it is essential to mimic these often overlooked esthetic qualities.


Characterization of signal-sequence-coding regions selected from the Bacillus subtilis chromosome.
Signal-sequence-coding regions for protein export were selected from chromosomal Bacillus subtilis DNA. The number of different signals obtained was higher than expected on the basis of known exported proteins in B. subtilis. Most of the selected regions showed the characteristics of typical signal sequences, including a basic N-terminal region followed by a hydrophobic core and a potential signal-peptidase cleavage site. The signal-coding regions were functionally interchangeable between the B. licheniformis alpha-amylase and Escherichia coli TEM beta-lactamase genes. In addition to the signal-sequence-coding regions, the nature of the host cells, and the mature parts of the reporter proteins contributed to the amounts of protein secreted.


Quantifying the role of online news in linking conservation research to Facebook and Twitter.
Conservation science needs to engage the general public to ensure successful conservation interventions. Although online technologies such as Twitter and Facebook offer new opportunities to accelerate communication between conservation scientists and the online public, factors influencing the spread of conservation news in online media are not well understood. We explored transmission of conservation research through online news articles with generalized linear mixed-effects models and an information theoretic approach. In particular, we assessed differences in the frequency conservation research is featured on online news sites and the impact of online conservation news content and delivery on Facebook likes and shares and Twitter tweets. Five percent of articles in conservation journals are reported in online news, and the probability of reporting depended on the journal. There was weak evidence that articles on climate change and mammals were more likely to be featured. Online news articles about charismatic mammals with illustrations were more likely to be shared or liked on Facebook and Twitter, but the effect of news sites was much larger. These results suggest journals have the greatest impact on which conservation research is featured and that news site has the greatest impact on how popular an online article will be on Facebook and Twitter.


[Small cell lung cancer (CPC). Small cell bronchial carcinoma: therapeutic management].
Small cell bronchial carcinoma holds a prominent position among malignant tumours on account of its high incidence and the problems of its treatment. The diagnostic approach is dictated by the concern not to overlook any metastatic sites. Small cell bronchial carcinoma is often metastatic at the time of diagnosis and should be considered an actual or potential systemic disease. Chemotherapy is therefore the basis of treatment. It should consist of at least a two drug regime combining cisplatin and etoposide. In extensive disease, that is when all the disease cannot be contained within one irradiation field, chemotherapy alone is recommended. In limited disease combined simultaneous radiotherapy and chemotherapy is recommended. Prophylactic cranial irradiation is indicated in patients in complete remission after chemotherapy. The therapeutic armamentarium has recently been enlarged by the development of new antineoplastic drugs and the development of non-toxic targeted agents including those influencing angiogenesis. The understanding of the specific mechanisms of drug resistance and the study of the tumour phenotypes and genotypes will allow, in the future, the development of treatments adapted for each patient.


Composite resin microhardness: the influence of light curing method, composite shade, and depth of cure.
The aim of this study was to investigate the influence of light curing method, composite shade, and depth of cure on composite microhardness. Forty-eight specimens with 4 mm of depth were prepared with a hybrid composite (Filtek Z-100, 3M ESPE); 24 with shade A1 and the remaining with shade C2. For each shade, two light curing units (LCUs) were used: a quartz-tungsten-halogen (QTH) LCU (Optilight Plus - Gnatus) and a light emitting diode (LED) LCU (LEC 470 II - MM Optics). The LED LCU was tested using two exposure times (LED 40 seconds and LED 60 seconds). After 24-hour storage, three indentations were made at mm depth intervals using a Knoop indenter. Data were submitted to three-way analysis of variance (ANOVA) and Tukey's test (p<0.05). The three factors tested (light curing method, shade, and depth) had a significant influence on the composite microhardness (p<0.05). All groups presented similar hardness values in the first mm, except for composite shade C2 cured with LED for 40 seconds. The hardness decreased with depth, especially for shade C2 for 40 seconds. Increasing light-curing time with LED produced hardness values similar to the QTH. The light curing method including variations of time, the depth of cure, and the composite shade influence the composite microhardness. Clinicians should avoid thicker increments when working with composite restorations. Extended light-curing time might be indicated depending on the composite shade and on the light-curing device.


Increased cancer antigen 27.29 (CA27.29) level in patients with mycosis fungoides.
Mycosis fungoides, also called cutaneous T-cell lymphoma, comprise a group of extranodal, indolent non-Hodgkin's lymphomas of T-cell origin with primary involvement of the skin. There are few data available on tumor markers in these patients. Cancer antigen 27.29 (CA27.29), which is expressed on most carcinoma cells, is a soluble form of the glycoprotein MUC1. Measuring CA27.29 has been approved by the US Food and Drug Administration for monitoring disease activity in patients with breast cancer. We sought to assess whether CA27.29 levels were increased in patients with cutaneous T-cell lymphoma and whether there was a correlation of this marker with tumor response. We evaluated the CA27.29 blood levels from 6 patients with advanced mycosis fungoides (who had no evidence of breast cancer) and reviewed their charts for information about history and physical examinations, laboratory data, pathology findings, and radiologic examinations. We demonstrated that 3 of 6 patients with advanced mycosis fungoides had markedly elevated CA27.29 blood levels. In the two patients who had serial blood levels drawn, CA27.29 increased or decreased during treatment as the disease progressed or responded, respectively. This study reflects pilot data on a limited number of patients. Our observations suggest that CA27.29 merits further investigation as a tumor marker in patients who have cutaneous T-cell lymphoma.


Associations of cardiorespiratory fitness in children and adolescents with physical activity, active commuting to school, and screen time.
The objective of this study was to analyze associations of cardiorespiratory fitness (CRF) with physical activity, time spent watching television and using computer, mode of commuting to school (CS), and adiposity, by gender. Participants were 1708 students (53.8% girls), aged 11 to 19 years. CRF was evaluated with a 20-meter shuttle-run test using VO2max by previously published equation. Maturation stages determined by Tanner's criteria, body mass index, and skinfolds were measured, and a questionnaire used to assess socioeconomic status, PA, television and computer time, and mode of CS. We conducted a regression analysis using CRF as the dependent variable. CRF was independent and positively associated with physical activity [β = 0.338 (95% CI = 0.119; 0.188); P < .001] and with maturation [β = -0.876 (95% CI = 0.666; 1.087); P < .001]; independent and negatively associated with television time [β = -0.003 (95% CI = -0.005; -0.002); P < .001] and adiposity [β = -0.068 (95% CI = -0.076; -0.060); P < .001]. CRF was positively associated with CS [β = 0.337; (95% CI = 0.014; 0.741); P = .014]. No associations were found for computer time. These findings suggest that increasing overall physical activity levels through interventions in different domains such as active CS, reducing sedentary activities, such as television time, might be effective strategies for improving CRF in youth.


Discovery of novel inhibitors of signal transducer and activator of transcription 3 (STAT3) signaling pathway by virtual screening.
Inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling pathway has been considered a novel therapeutic strategy to treat human cancers that harbor aberrantly-active STAT3. In this study, nearly 204,000 compounds in Specs database were screened by virtual screening, and samples of top 100 compounds identified as candidate small-molecule inhibitors of STAT3 were evaluated by STAT3-dependent luciferase reporter assay as well as other cell-based assays. A benzothiazole core scaffold containing compound, 9, was identified as an inhibitor of IL-6/STAT3 signaling with an IC50 of 3.567 μM. It is the first time to discover benzothiazole scaffold as a potent STAT3 signaling inhibitor. We further investigated the (structure-activity relationship) SAR of the benzothiazole analogues, and discovered compound 16w as a better small-molecule inhibitor. Both compounds inhibited the phosphorylation of STAT3 and had no obvious effect on upstream JAK2 kinase.


The microbiome of otitis media with effusion.
The adenoid pad has been considered a reservoir for bacteria in the pathogenesis of otitis media with effusion. This study aimed to characterize the middle ear microbiota in children with otitis media with effusion and establish whether a correlation exists between the middle ear and adenoid microbiota. Prospective, controlled study. Middle ear aspirates adenoid pad swabs were collected from 23 children undergoing ventilation tube insertion. Adenoid swabs from patients without ear disease were controls. Samples were analyzed using 16S rRNA sequencing on the Illumina MiSeq platform. Thirty-five middle ear samples were collected. The middle ear effusion microbiota was dominated by Alloiococcus otitidis (23% mean relative abundance), Haemophilus (22%), Moraxella (5%), and Streptococcus (5%). Alloiococcus shared an inverse correlation with Haemophilus (P = .049) and was found in greater relative abundance in unilateral effusion (P = .004). The microbiota of bilateral effusions from the same patient were similar (P < .001). However, the otitis media with effusion microbiota were found to be dissimilar to that of the adenoid (P = .01), whereas the adenoid microbiota of otitis media with effusion and control patients were similar (P > .05) (permutational multivariate analysis of the variance). Dissimilarities between the local microbiota of the adenoid and the middle ear question the theory that the adenoid pad is a significant reservoir to the middle ear in children with otitis media with effusion. A otitidis had the greatest cumulative relative abundance, particularly in unilateral effusions, and shares an inverse correlation with the relative abundance of Haemophilus. NA Laryngoscope, 126:2844-2851, 2016.


Preimplantation diagnosis of inherited disease by embryo biopsy: an update of the world figures.
Cleavage stage embryo biopsy and preimplantation diagnosis was first reported five years ago. The annual collation of the world figures for centres offering this procedure is important to continually assess the efficiency and success of the biopsy, diagnosis and pregnancies obtained. Data was collected from 14 centres worldwide. The largest series of diagnosis has been performed for those patients carrying X-linked disease where the embryos have been sexed either by PCR or FISH. PCR has also been used for the specific diagnosis of a number of single gene defects, mainly for cystic fibrosis but also for the diagnosis of Lesch Nyhan syndrome, Fragile X, Duchenne muscular dystrophy, Tay Sachs, haemophilia and RhD blood typing. For PCR sexing, a total of 62 cycles have been performed with 14 pregnancies, 8 deliveries and 11 babies born. For FISH sexing, 70 cycles have resulted in 15 pregnancies, 8 deliveries and 11 babies born. For the specific diagnosis of single genes defects, a total of 65 cycles resulted in 21 pregnancies, 12 deliveries and 12 babies born. Overall, 197 cycles were performed, with 171 embryo transfers (86%), 50 pregnancies (25% per cycle, 29% per transfer), 28 deliveries and 34 babies born. New methods are being developed to increase the scope of preimplantation diagnoses that can be offered. From next year, the biochemical and miscarriage rates will also be recorded.


Optimization of genetic engineering and homologous recombination of collagen type I genes in rat bone marrow mesenchymal stem cells (MSC).
Mutations in COL1A1 or COL1A2 genes lead to osteogenesis Imperfecta (OI) in humans. There are three possiblities to successfully treat OI including (1) gene therapy, (2) mesenchymal stem cell (MSC) therapy, or (3) a combination of both. The aim of this study was to develop a model for combined gene/cell OI therapy by targeting Col1a1 and Col1a2 genes with isogenic sequences from corresponding human genes in rat bone marrow (BM)-derived MSCs. The recombination efficacy was tested for five different rat-human-rat hybrid DNAs with rat fragments that were 1 to 4 kb long. For selection of transfected clones a neomycine resistance gene was cotransfected, and clones resistant to G418 (G418(+)) were recovered and screened for integration of specific gene loci in the rat genome. Over 90% of G418(+) clones correctly integrated the rat-human-rat hybrid DNAs, and both OI loci in the rat genome were targeted to a similar degree. Longer homologous sequences integrated into rat collagen genes approximately 10 times more efficiently. Based on our data the nonviral gene targeting technology could be potentially employed to repair collagen genes in OI patients.


Phase I and pharmacokinetic study of 5-fluorouracil administered by 5-day continuous infusion in patients with hepatocellular carcinoma.
In this study the maximum tolerated dose of 5-fluorouracil administered by 5-day (120-h) continuous infusion every 4 weeks was investigated and the pharmacokinetics in patients with hepatocellular carcinoma were evaluated. Patients with hepatocellular carcinoma no longer amenable to established forms of treatment were eligible for the study. The starting dose of 5-fluorouracil was 300 mg/m(2) per day and doses were escalated in 50 mg/m(2) per day increments in successive cohorts of three new patients if tolerated. Pharmacokinetic studies were performed at the time of the first course of therapy. Enrolled in the study were 20 patients. The maximum tolerated dose was 500 mg/m(2) per day and the dose-limiting toxicity was stomatitis. Other toxicities were mild and well tolerated. Age, gender and associated liver cirrhosis were significant factors influencing 5-fluorouracil clearance. With regard to biochemical parameters, serum alanine aminotransferase and cholesterol levels were correlated with 5-fluorouracil clearance. The maximum tolerated dose for 5-day continuous infusion of 5-fluorouracil in hepatocellular carcinoma patients was 500 mg/m(2) per day. The recommended dose for phase II studies using this schedule is 450 mg/m(2) per day. Furthermore, the pharmacokinetic data obtained in this study may be useful in determining chemotherapy dosage adjustments for reduction of toxicity.


Inefficient presentation of tumor-derived antigen by tumor-infiltrating dendritic cells.
Transplantable B16 melanoma is widely used as a tumor model to investigate tumor immunity. We wished to characterize the leukocyte populations infiltrating B16 melanoma tumors, and the functional properties of tumor-infiltrating dendritic cells (TIDC). We used the B16 melanoma cell line expressing ovalbumin protein (OVA) to investigate the phenotype and T cell stimulatory capacity of TIDC. The majority of leukocytes in B16 melanoma were macrophages, which colocalized with TIDCs, B and T cells to the peripheral area of the tumor. Both myeloid and plasmacytoid DC populations were present within tumors. Most of these DCs appeared immature, but about a third expressed a mature phenotype. TIDCs did not present tumor-derived antigen, as they were unable to induce the proliferation of tumor-specific CD4+ and CD8+ T cells in vitro unless in the presence of specific peptides. Some presentation of tumor-derived antigen could be demonstrated in the tumor-draining lymph node using in vivo proliferation assays. However, while proliferation of CD8+ T cells was reproducibly demonstrated, no proliferation of CD4+ T cells was observed. In summary, our data suggest that DCs in tumors have limited antigen-presenting function. Inefficient antigen presentation extends to the tumor-draining lymph node, and may affect the generation of antitumor immune responses.


Acute coordinative exercise improves attentional performance in adolescents.
Teachers complain about growing concentration deficits and reduced attention in adolescents. Exercise has been shown to positively affect cognitive performance. Due to the neuronal connection between the cerebellum and the frontal cortex, we hypothesized that cognitive performance might be influenced by bilateral coordinative exercise (CE) and that its effect on cognition might be already visible after short bouts of exercise. One hundred and fifteen healthy adolescents aged 13-16 years of an elite performance school were randomly assigned to an experimental and a control group and tested using the d2-test, a test of attention and concentration. Both groups performed the d2-test after a regular school lesson (pre-test), after 10 min of coordinative exercise and of a normal sport lesson (NSL, control group), respectively (post-test). Exercise was controlled for heart rate (HR). CE and NSL enhanced the d2-test performance from pre- to post-test significantly. ANOVA revealed a significant group (CE, NSL) by performance interaction in the d2-test indicating a higher improvement of CE as compared to NSL. HR was not significantly different between the groups. CE was more effective in completing the concentration and attention task. With the HR being the same in both groups we assume that the coordinative character of the exercise might be responsible for the significant differences. CE might lead to a pre-activation of parts of the brain which are also responsible for mediating functions like attention. Thus, our results support the request for more acute CE in schools, even in elite performance schools.


GABAB receptor agonists and antagonists: pharmacological properties and therapeutic possibilities.
Gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, is widely distributed throughout the brain and spinal cord. Two major families of GABA receptors have been identified, GABAA and GABAB. While much is known about the pharmacological and molecular properties of GABAA receptors, it is only within the last few years that potent and selective antagonists have been developed for the GABAB site, and only within the past few months that this receptor has been cloned. Thus, tools are now available to define more fully the GABAB receptor in terms of its biology and the therapeutic potential of manipulating this site. Data suggest that, in addition to their established use as muscle relaxants, GABAB receptor agonists possess analgesic and antitussive properties, and may be useful for treating bladder dysfunction. While there is less clinical data on GABAB receptor antagonists, preclinical results indicate that they may be of value in treating absence epilepsy, cognitive dysfunction and, possibly, pulmonary and intestinal disorders. However, for this potential to be fully exploited, it is necessary to identify and characterise molecularly and pharmacologically distinct GABAB receptor subtypes.


Communication: Hot-atom abstraction dynamics of hydrogen from tungsten surfaces: The role of surface structure.
Adiabatic and non-adiabatic quasiclassical molecular dynamics simulations are performed to investigate the role of the crystal face on hot-atom abstraction of H adsorbates by H scattering from covered W(100) and W(110). On both cases, hyperthermal diffusion is strongly affected by the energy dissipated into electron-hole pair excitations. As a result, the hot-atom abstraction is highly reduced in favor of adsorption at low incidence energy and low coverages, i.e., when the mean free path of the hyperthermal H is typically larger. Qualitatively, this reduction is rather similar on both surfaces, despite at such initial conditions, the abstraction process involves more subsurface penetration on W(100) than on W(110).


[Decompensated valvular disease and coarctation. One-stage repair using a median approach with an ascending aorta-abdominal aorta shunt].
The tactical decision in patients with decompensated valvular disease associated with a severe stenosis of the aortic isthmus is always difficult. One stage surgical repair using two separate approaches is a long and high risk procedure. It would seem more logical and safer to treat the lesions in two stages a few weeks apart, the severest lesion being managed first. In the two cases reported. The isthmic stenoses and valvular lesions were of the same severity and made both classical techniques impracticable. Therefore the patients underwent a single stage procedure by a median approach associating valve replacement under cardiopulmonary bypass (mitral and tricuspid in one and aortic in the other case) and an ascending aorta-abdominal aorta dacron conduit. The present postoperative survival periods are 30 and 9 months. The functional result was good (Class 1 and 0) and postoperative angiography has shown the montage to be working satisfactorily. This technique is exceptional but may be useful in borderline cases with decompensated valvular disease and severe isthmic stenosis.


A new flavin enzyme catalyzing the reduction of dihydrodipicolinate in sporulating Bacillus subtilis. II. Kinetics and regulatory function.
Dihydrodipicolinate reductase in Bacillus subtilis PCI 219 had FMN as a prosthetic group, and the hydrogen transfer pathway is considered to be NADPH yields FMN yields dihydrodipicolinate. Linewaver-Burk plots of the reciprocal of the activity against the reciprocal of the concentration of either of the two substrates, dihydrodipocolinate and NADPH, are consistent with a reaction mechanism involving interconversion of two free forms of the enzyme by the two substrates. The Km values obtained from the secondary plots are 0.77 mM for dihydrodipicolinate and 72 muM for NADPH. Inhibition by dipicolinate is competitive with NADPH and noncompetitive with dihydrodipicolinate, and shows positive cooperativity. The possible metabolic role of the reductase in sporulating Bacillus subtilis is discussed in connection with regulation of the biosyntheses of dipicolinate and diaminopimelate.


Beclomethasone for asthma in children: effects on linear growth.
Inhaled steroids play a central role in the management of childhood asthma. There is concern about their side effects, especially on growth. However asthma may also cause growth retardation. Growth rates are not stable, so randomised controlled parallel group studies are needed to assess the impact of inhaled steroids on growth. This review is confine to one inhaled steroid, beclomethasone, that is known to have significant levels of systemic absorption. To determine whether inhaled beclomethasone cause significant delay in the linear growth of children with asthma. The Cochrane Airways Group asthma register was searched. Bibliographies from included studies, and known reviews were searched for additional citations. Personal contact with colleagues and researchers working in the field of asthma were made to identify potentially relevant trials. Randomized, controlled trials comparing the effects of beclamethasone to non-steroidal medication (placebo or non-steroidal therapy) on the linear growth of children with asthma. Data related to the clinical outcome "change in growth" were extracted by two reviewers working independently One hundred and fifty-nine citations were identified by the search strategy and bibliography review. Three studies met the inclusion criteria. All used beclomethasone 200 mcg twice daily delivered by dry powder Diskhaler to treat children with mild-moderate asthma. Study duration was 7-12 months. In all three studies, a significant decrease in linear growth occurred in children treated with beclomethasone compared to those receiving placebo or non-steroidal asthma therapy. The average decrease, calculated through meta-analysis, was -1.54 cm per year (95% CI -1.15, -1.94). In children with mild-moderate asthma, beclomethasone 200 mcg twice daily caused a decrease in linear growth of -1.54 cm per year. These studies lasted a maximum of 54 weeks, so it remains unclear whether the decrease in growth is sustained or whether it reverses with 'catch up' after therapy is discontinued. We are unable to comment on growth effects of other inhaled steroids that have potentially less systemic effects. If inhaled steroids are required to control a child's asthma, we recommend using the minimum dose that effectively controls the child's asthma and closely following growth.


Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands.
Evasion of death receptor ligand-induced apoptosis represents an important contributor to cancer development and progression. Therefore, molecules that restore sensitivity to death receptor stimuli would be important tools to better understand this biological pathway and potential leads for therapeutic adjuncts. Previously, the small-molecule 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide (that we propose be named droxinostat) was identified as a chemical sensitizer to death receptor stimuli, decreasing the expression of the caspase-8 inhibitor FLIP. However, the direct targets of droxinostat were unknown. To better understand the mechanism of action of droxinostat and highlight new strategies to restore sensitivity to death receptor ligands, we analyzed changes in gene expression using the Connectivity Map after treating cells with droxinostat. Changes in gene expression after droxinostat treatment resembled changes observed after treatment with histone deacetylase (HDAC) inhibitors. Therefore, we examined the effects of droxinostat on HDAC activity and showed that it selectively inhibited HDAC3, HDAC6, and HDAC8 and that inhibition of these HDACs was functionally important for its ability to sensitize cells to death ligands. Thus, we have identified a selective HDAC inhibitor and showed that selective HDAC inhibition sensitizes cells to death ligands, thereby highlighting a new mechanism to overcome resistance to death receptor ligands.


Passive length-tensile properties of extraocular muscles under botulinum toxin type C.
Passive length-tension of the extraocular muscle was measured after injection of botulinum neurotoxin type C (BoNT-C) to evaluate its chemo-denervation effect. BoNT-C was injected unilaterally at 5.0 or 2.5 units in the superior rectus muscle of the albino rabbit. The muscle was separated several times at its original insertion between 3 days to 8 weeks after injection, and the passive length-tension produced by stretching the muscle from its physiologic length was measured. The length-tension curve was analyzed, and the passive load was determined from early components. The compliance was determined by approximating the entire ascending curve by an exponential function. In the 5.0-unit group, the passive load increased significantly 2 weeks after injection but decreased to the level of the control group after 4 weeks and remained at that level until after 8 weeks after injection. In the 2.5-unit group, also, there were changes similar to those in the 5.0-unit group, but the changes were not significant compared to the control group. No significant change was observed in the compliance in either group. Persistent chemo-denervation effect was not observed in passive length-tension at the doses of BoNT-C used in this study. The increase in the passive load soon after injection was suggested to have been caused by the same mechanism as BoNT-A.


Readability and quality assessment of websites related to microtia and aural atresia.
Many parents and children utilize the Internet for health-related information, but the quality of these websites can vary. The objective of this study was to assess the quality and readability of microtia and aural atresia related websites. The search engine Google was queried with the terms 'microtia' and 'aural atresia.' The first 30 results were evaluated, and those websites containing original information written in English were reviewed. Quality of content was assessed with the DISCERN instrument, and readability was assessed with the Flesch-Kincaid Reading Grade Level (FKGL) and the Flesch Reading Ease Score (FRES) tests. Each website was also reviewed for ownership and the date of last update. Sixteen microtia and 14 aural atresia websites were included for full review. The mean DISCERN score for microtia websites was 54.4 (SD=8.3), and for aural atresia websites it was 47.6 (SD=10.7), which indicates 'good' and 'fair' quality of content, respectively. Readability assessments showed an average reading level requiring a grade 10 education on FKGL, and only one microtia (6.3%) and one aural atresia (7.1%) websites were deemed to be at 'reasonable' reading level on FRES. High-quality websites that are considered easily comprehensible to the general public were lacking. Since parents and children may use websites when making treatment decisions, physicians should be aware of the quality of health information pertaining to their area of expertise available on the Internet.


[Results of overlapping sphincter repair in response to obstetric injury].
Obstetric trauma is one of the most common causes of faecal incontinence, and the standard therapy for clear sphincter defects is overlapping sphincter repair. We aimed to assess the short-term success rates of sphincter repair using modified V-Y plastic without covering colostomy and with primary closure of the perineum. Between November 1997 and March 2002, 21 patients were operated on for faecal incontinence due to obstetric trauma. Cleveland Clinic Incontinence Score (CCIS), patients' subjective assessment, and pathophysiological parameters were evaluated pre- and postoperatively. At follow-up, 19 patients (90%) reported improvements in continence symptoms over their preoperative situations. Three patients (14%) classified themselves subjectively as fully continent, six (28%) as highly improved, ten (48%) as improved, and two (10%) as unchanged. Our results indicate that faecal diversion is not necessary in sphincter repair and that primary perineal wound closure should be performed. Patients' subjective assessments and CCIS are suitable tools for evaluating improvements in faecal incontinence.


Photopheresis in the treatment of refractory bronchiolitis obliterans complicating lung transplantation.
Photopheresis has been successfully used to treat heart allograft rejection and has had some initial success in the treatment of bronchiolitis obliterans (BO) following lung transplantation. This report describes five patients treated with photopheresis after the failure of augmented immunosuppression for BO. Four patients had a temporary stabilization of their airflow obstruction, and minimal side effects of the procedure were noted, although there were consequences from additional augmented immunosuppression (principally sepsis). Photopheresis may provide a safe modality for the treatment of BO that is unresponsive to standard and augmented immunosuppression.


Pseudohypoparathyroidism type 1a and insulin resistance in a child.
Background. A 5-year-old white girl with a history of hypothyroidism in infancy presented to the endocrinology clinic of a tertiary hospital. Her physical examination noted a stocky physique, broad chest, short neck and short digits. Two years later, skin examination revealed subcutaneous nodules and acanthosis nigricans.Investigations. Measurement of levels of serum phosphate, parathyroid hormone, ionized calcium and insulin; measurement of peak growth hormone by the arginine-levodopa stimulation test; calculation of homeostasis model assessment of insulin resistance; assessment of bone age; DNA analysis of the GNAS gene.Diagnosis. Pseudohypoparathyroidism type 1a in a patient with Albright hereditary osteodystrophy, characterized by hypocalcemia, hypothyroidism, growth-hormone deficiency and insulin resistance.Management. The child continued to take levothyroxine 25 microg once daily, and at 5 years of age she was started on 40 mg/kg elemental calcium as calcium carbonate daily, and calcitriol (active vitamin D) 0.25 microg twice daily. Lifestyle modifications were also recommended for weight control. At 6 years and 4 months of age, treatment with growth hormone was initiated at a dose of 0.3 mg/kg weekly.


Test-Retest Reliability of Cervical and Ocular Vestibular Evoked Myogenic Potential With Simultaneous and Sequential Recording.
Purpose Simultaneous recording of cervical (cVEMP) and ocular (oVEMP) vestibular evoked myogenic potentials aids in reducing the testing time when compared to conventional sequential recordings. The purpose of this study was to examine the test-retest reliability of sequential and simultaneous acquisitions of cVEMP and oVEMP. Method cVEMP and oVEMP were recorded in 35 normal-hearing individuals. The cVEMP and oVEMP were obtained using sequential and simultaneous methods. The VEMP recordings were performed across 3 sessions. The 1st 2 recording sessions were consecutive with a gap of 5 min between sessions. The 3rd recording session was after a gap of 3-5 days. Results Both simultaneous and sequential recordings showed fair-to-good test-retest reliability for latencies and amplitude of cVEMP and oVEMP. Conclusion Simultaneous cVEMP and oVEMP recordings can be used to obtain fast VEMP recording with test-retest reliability comparable with that of sequential recording.


Guidelines for the uniform reporting of data for Medical Emergency Teams.
It is more than 15 years since the first Medical Emergency Team (MET) system was introduced to identify patients at risk and prevent serious adverse events in Liverpool Hospital, Sydney, Australia. Since then the MET system has been introduced to many other hospitals in Australia and around the world. Standardised and complete reporting of data related to MET activity is increasingly important to identify the role and benefits of the system and to facilitate quality improvement in health care in general. A uniform method for reporting data related to MET activity will aid interpretation of results, comparisons, review and changes to the MET system. The guidelines for uniform reporting of data in relation to MET activities used in our group of hospitals are presented. Future refinement and consensus agreement on the reporting of MET data internationally should enable comparisons between MET systems in several countries.


Glioma-specific antigens for immune tumor therapy.
This review describes glioma-specific antigens important in immunotherapy of glioma tumors. The structure and function of these antigens and recent immunotherapy data are summarized. Also, some important aspects of tumor formation are outlined. The roles of neuronal precursor cells and tumor stroma cells are discussed. The stroma cells of the tumor may be of interest as a target for tumor therapy, especially since they are less heterogeneous than the tumor cells. To date, the clinical benefit of immunotherapy has been very limited. Immunotherapy is, however, still an extremely promising approach to tumor therapy and it will most likely be implemented as a future treatment option for many types of tumors. The current shortcomings of immunotherapy will probably diminish as we start to understand and are able to modulate tumor-induced immunosuppression. There is also a need for a continued search for new tumor-specific antigens and to optimize protocols for vaccine administration.


The clinical outcomes of 234 spiral family implants.
Spiral family implants (SFIs) are a new type of implant fixture with a conical internal helix and a variable thread design. The aim of this retrospective study was to evaluate the clinical outcomes of a series of SFIs. A total of 234 SFIs were placed in 86 patients (55 females and 31 males, median age 53 years) during the period between May 2004 and November 2007. The mean follow-up was 13 months. Several host, surgery, and implant-related factors were investigated, and the Kaplan Meier algorithm and the Cox regression were used to detect variables associated with the clinical outcome. Only nine out of 234 implants were lost (i.e., survival rate (SVR) of 96.2%) and no differences were detected among the studied variables. SFIs have a high SVR similar to those reported in previous studies on different implant types. SFIs demonstrated a very high primary stability which offers the potential for use of a specific implant device for immediate loading. However, additional studies are necessary to verify their outcome on the medium/long period.


Determining the effect of cartridge case coatings on GSR using post-fire priming cup residue.
Ammunition is typically composed of a lead-based priming mixture which contributes to the characteristics most commonly used for the identification of gunshot residue (GSR). Due to the health risks often associated with lead, the use of lead-free primers in ammunitions is becoming more popular. Thus, the presence of GSR is becoming more difficult to discern based on the traditional means, i.e. the presence of lead (Pb), barium (Ba), and antimony (Sb). While research has been conducted on the differences between lead-based and lead-free muzzle discharge residue, few have researched other components of ammunition which may lead to other means of characterizing GSR. This research, therefore, covers that gap by focusing on the priming cup present in ammunition and the residue which may originate from it, that can contribute to muzzle discharge residue. In this study, a lead-based and a lead-free ammunition from four different manufacturers were chosen. The cartridges were fired using a Glock 17, 9mm Parabellum, collected post-fire, and subsequently de-primed resulting in the removal of the anvil. The GSR present on the anvils and cups was analyzed using scanning electron microscopy coupled with energy dispersive x-ray spectrometry (SEM-EDX). The data was then processed using unit vector analysis for normalization and analyzed using principal component analysis (PCA) and linear discriminant analysis (LDA). This data was then used to determine the components of the cartridge case which contribute to GSR and develop a method of characterization between lead-free and lead-based ammunition. Such a method will improve the detection of GSR by strengthening the criteria of identification.


Protective role of trehalose during heat stress in Saccharomyces cerevisiae.
Yeast cells accumulate the disaccharide trehalose in response to certain stress conditions. In an attempt to verify the role that trehalose plays when yeast cells are faced with heat stress, yeast mutant strains with specific lesions in trehalose metabolism were used. Cultures growing exponentially on glucose were shifted from 28 to 40 degrees C for 1 h. Accumulation of trehalose was correlated with heat tolerance, measured as resistance to 50.5 degrees C. Additionally, it was observed that the trehalose carrier was not involved in the mechanism of thermotolerance acquisition. Mutants that lack the carrier were also able to acquire thermotolerance as long as synthesis of the disaccharide took place.


Tube decompression of the dilated colon.
With the technique described herein, decompression of a massively dilated colon is effectively accomplished, allowing resection to proceed safely. This method of decompression has allowed us to perform colonic resection in all patients with toxic megacolon seen in recent years. It is desirable to remove the infected and inflamed colon in such a circumstance. We have not resorted to blowhole colostomies in cases of toxic megacolon, as this leaves the colon, which is the septic source, within the abdominal cavity. This technique has also been used successfully to expedite subtotal colectomy and ileosigmoid anastomosis in patients with obstructing lesions of the left side. It allows colonic decompression and on-table bowel preparation by irrigation with antiseptics such as povidone-iodine (Betadine).


The effects of a 5-lipoxygenase inhibitor on antigen-induced mediator release, late-phase bronchoconstriction and cellular infiltrates in primates.
Inhaled BI-L-239 significantly inhibited i-LTC4 generation, late-phase bronchoconstriction and the influx of neutrophils into the lungs. We conclude that leukotriene generation and release within the lungs, following allergen exposure, in part mediate altered lung function and contribute to the development of airway inflammation. As such, treatment with a selective 5-lipoxygenase inhibitor may aid in the treatment of bronchial asthma and other allergic diseases.


Comparison of malocclusion in preschool black and white children.
Previous research confirms ethnic and gender differences among children with malocclusions. A limited amount of information is available on preschool children. With an increasing interest in the early recognition of malocclusion and a corresponding emphasis on preventive procedures, more information on preschool children may prove to be useful. This study compared ethnic and gender differences for Angle's classification, anterior crossbite, and posterior crossbite. The sample consisted of 238 children, 3 to 5 years of age; 99 of the children were black and 139 were white. The acquired data were tested with chi(2). The results indicate significant racial differences in occlusal patterns and little or no gender difference.


How to prepare a life expectancy report for an attorney in a tort case.
The purpose of this methodology article is to describe a suitable format for a legally acceptable report on the life expectancy of the principal in a tort case that is being advocated or defended by an attorney. Life insurance medical directors and underwriters are clearly skilled and experienced in mortality risk classification for life insurance. However, the judicial system is accustomed to measuring excess mortality only in terms of reduced life expectancy. The analyst preparing the report must convert the excess mortality into a figure for reduced life expectancy and compare this with the life expectancy of persons matched by age, sex and race in the latest Decennial US Life Tables. This process is different from the life insurance underwriting process. A life table projected to age 109 must be constructed as an essential part of the report, and the entire process must be presented clearly and convincingly. There are good reasons why the excess death rate (EDR) should be used as the index of excess mortality in constructing the life table, in preference to the mortality ratio (MR), which is used most of the time in life insurance risk classification. All of these considerations are discussed in this article, which is based on a sample of 40 cases handled by the author, a retired life insurance medical director.


Remittive effects of intramuscular alefacept in psoriasis.
Alefacept is the first biologic agent approved for the treatment of chronic plaque psoriasis in the United States. Alefacept, administered intravenously (i.v.) or intramuscularly (i.m.), was found to be well tolerated, safe, and efficacious in two pivotal phase 3 studies in patients with moderate to severe psoriasis. Treatment with i.v. alefacept was associated with a median duration of off-treatment response of 216 days (approximately 7 months). In a follow-up extension study to the phase 3 i.m. study, duration of therapeutic response was also examined. Patients who achieved a > or = 75% reduction in baseline Psoriasis Area and Severity Index (PASI 75) with the first course of alefacept 15 mg i.m. in the phase 3 study maintained a PASI 50 for a median duration of 209 days. In addition, the extension study demonstrated that a second course of i.m. alefacept is safe and well tolerated in patients with psoriasis.


Northern Ireland's young vets host impressive YVN event.
Laura Carleton, BVA member services and policy support officer, reports on a recent CPD event held in Northern Ireland for young graduates in the region.


Spinal cord injury: pathophysiology, treatment strategies, associated challenges, and future implications.
Axonal regeneration and formation of tripartite (axo-glial) junctions at damaged sites is a prerequisite for early repair of injured spinal cord. Transplantation of stem cells at such sites of damage which can generate both neuronal and glial population has gained impact in terms of recuperation upon infliction with spinal cord injury. In spite of the fact that a copious number of pre-clinical studies using different stem/progenitor cells have shown promising results at acute and subacute stages, at the chronic stages of injury their recovery rates have shown a drastic decline. Therefore, developing novel therapeutic strategies are the need of the hour in order to assuage secondary morbidity and effectuate improvement of the spinal cord injury (SCI)-afflicted patients' quality of life. The present review aims at providing an overview of the current treatment strategies and also gives an insight into the potential cell-based therapies for the treatment of SCI.


The role of transcranial magnetic stimulation in evaluation of motor cortex excitability in Rett syndrome.
Rett syndrome (RTT) is a frequent neurodevelopmental disorder confirmed by clinical criteria and supported by the methyl-CpG-binding protein 2 gene (MECP2) mutation. A short central motor conduction time (CMCT) was reported in transcranial magnetic stimulation (TMS) studies performed in RTT. This was attributed to hyperexcitability of the motor cortex and/or spinal motor neurons, but was not studied further. We performed TMS in RTT to evaluate motor cortex excitability by determining the cortical motor threshold (CMT) and motor cortex inhibition by the cortical silent period (CSP) besides measuring CMCT. Single-pulse TMS was performed in 17 Rett patients, diagnosed by clinical criteria and MECP2 mutation testing, and the same number of healthy controls. The outcome measures were compared between RTT groups with different antiepileptic drugs (AED) and those with and without the MECP2 mutation. CMCT was shorter, but we found elevated CMT and shorter CSP, which suggests decreased excitatory and inhibitory motor cortical function. The outcome was independent of AED and the presence or absence of the MECP2 mutation. Decreased excitatory and inhibitory motor cortical function could explain the short CMCT, with higher stimulus intensities needed to excite pyramidal neurons.


[Anaesthesia for thyroid surgery in the patient suffering from myasthenia gravis].
The preparation and perioperative treatment of patients with myasthenia gravis and hyperthyreosis constitutes a serious problem for a surgeon as well as an anaesthetist. The need of anticholinesterase therapy application makes it difficult to achieve euthyreosis in the patients. The aim of this case report is to present perioperative management and the methods used in anaesthesia in 41-year-old woman suffering from both illnesses.


Integrating legacy medical data sensors in a wireless network infrastucture.
In the process of developing a wireless networking solution to provide effective field-deployable communications and telemetry support for rescuers during major natural disasters, we are faced with the task of interfacing the multitude of medical and other legacy data collection sensors to the network grid. In this paper, we detail a number of solutions, with particular attention given to the issue of data security. The chosen implementation allows for sensor control and management from remote network locations, while the sensors can wirelessly transmit their data to nearby network nodes securely, utilizing the latest commercially available cryptography solutions. Initial testing validates the design choices, while the network-enabled sensors are being integrated in the overall wireless network security framework.


Stochastic simulation of Taylor's dispersion in the airways.
A stochastic simulation was devised in order to obtain a more correct solution of the phenomenon of convection combined with axial and radial diffusion, which is also called Taylor's dispersion, as it could occur in the pulmonary tract. The fit with Aris' moments which can be deemed as a reference since they are obtained analytically without approximation, was quite good. On the other hand, Taylor's solution usually led to large discrepancies with these moments. Taylor's stipulation that his solution be used only under certain conditions was therefore confirmed. This solution is not applicable in the lungs.


Strategic planning in competitive environments.
Private voluntary social welfare organizations (PVSOs) are operating under increasingly competitive conditions. "Strategic Planning" (SP) is a management tool designed to meet those conditions. In an exploratory study of 154 PVSOs the authors examined management's reasons for adopting strategic planning, the attention given to external analysis, and the degree of change and satisfaction achieved. PVSOs use SP because they are required/urged to do so by external agencies. External analysis received the least attention. One-half of the organizations achieved major change which was associated with high levels of satisfaction. Widespread stakeholder participation and the use of consensus strategies detracted from both major change and high satisfaction outcomes.


Use of activated recombinant human factor VII (rhFVIIa) for colonic polypectomies in patients with cirrhosis and coagulopathy.
The prevalence of colonic polyps in patients with cirrhosis appears to be higher than that of the general population. The current practice for a polypectomy in a coagulopathic cirrhotic patient involves the reversal of the coagulopathy using fresh frozen plasma (FFP) prior to the polypectomy, usually at a second colonoscopy. The use of FFP is associated with many problems, particularly that of volume overload. Here we report four cases with advanced cirrhosis and severe coagulopathy that underwent polypectomies by snare cautery after an intravenous bolus infusion of recombinant human factor VIIa (rhFVIIa). The dose used was 120 microg/kg, which provided normalization of the coagulation parameters for 10-16 hr. The immediate use of rhFVIIa reduced the utilization of resources and enabled the performance of the polypectomies at the initial colonoscopy. No postpolypectomy bleeding was noted. The high cost of the drug is the only obstacle to a wider use of rhFVIIa for this purpose. The cost of the drug, however, is offset substantially by the cost of hospitalization for the administration of FFP, the cost of a second colonoscopy, and the charges associated with a second utilization of the endoscopy suite.


Possible role of chromatin alteration in the radiosensitivity of ataxia-telangiectasia.
Cells derived from individuals with ataxia-telangiectasia (A-T) are known to exhibit increased sensitivity to ionizing radiation and certain radiomimetic chemical agents. Here we summarize our findings regarding the role of chromosome damage and repair in this radiosensitivity. Lymphoblastoid cells derived from A-T homozygotes were characterized for initial chromosome (premature chromosome condensation) and DNA (neutral filter elution) damage and repair kinetics in cells from G1 and G2 cell cycle phases. Despite initial levels of DNA damage being similar to normal controls, A-T cells exhibited nearly a two-fold higher initial amount of chromosome damage. Different A-T cell lines exhibited differing chromosome repair capacities compared with control lymphoblastoid cell lines. These results suggest that A-T cells have an altered chromatin structure whereby DNA double-strand breaks are apparently more efficiently converted into chromosome breaks. Four A-T heterozygote cell lines were examined for chromosome damage and repair in the same fashion and all exhibited increased levels of chromosome damage, although the degree of sensitivity was more prominent in G2 phase cells (two-fold higher) than in G1 phase cells (1.5-fold higher than normal controls). These results suggest that A-T heterozygotes also exhibit an altered chromatin structure which impacts on chromosome damage expression. Of interest, A-T cells also exhibited increased chromosome stickiness after irradiation, and telomere regions appeared to be frequently involved. While the molecular basis for preferential telomere involvement is not understood, these results again suggest that structural alterations in the chromatin of A-T cells may play an important role in A-T radiosensitivity.


Synthesis of metal-chelating lipids to sensitize lanthanide ions.
Sensitization of lanthanide ions is important for lanthanide ion-based assays and sensing. To the best of our knowledge, there are very few reports of lanthanide ion sensitization after it is incorporated into the liposome surface. This paper describes the syntheses of several saturated and polymerizable metal-chelating lipids based on chelidamic acid. The lipids are synthesized either from (S)-ornithine or racemic 2,3-diaminopropanoic acid. These lipids as well as polymerized liposomes incorporating these lipids sensitize lanthanide ions. Liposomes from the lipid 18-Eu(3+) provided a probe that relies not only on the emission wavelengths of Eu(3+) but also on a reproducible lifetime that can be used for protein identification.


[Functional studies on the implanted ureter].
Electronical measurements of pressure in 8 successfully implanted ureters (6 Boari-Plastics, 2 direct implantations) yielded the following results. 1. Frequency, amplitude, duration and rate of spreading of the contractions show no differences compared to the normal ureter. 2. In the Boari-plastic the peristaltic activity is transferred also to the area of the anastomosis between bladder-flap and ureter. 3. Increasing pressure of bladder by retrograde filling produced temporary impairments of peristaltic of the implanted ureter in one case only.


Care givers in the workplace: employer support for employees with elderly and chronically disabled dependents.
With increasing demands for dependent care, and more women in the work force, employees may be required to balance work and care giving responsibilities. The New York Business Group on Health survey examines the role of business and industry concerning this issue: employer awareness about problems of employees responsible for the care of elderly or chronically disabled dependent family members, and company programs and policies to deal with employee care giver problems. Findings from this exploratory study of 69 companies in the greater New York area indicate that approximately half are aware of care giver needs, and many have identified employee problems in the workplace (lateness, absenteeism, etc). Few have programs designed specifically for care givers. However, larger companies and those with a predominantly female work force have more policies and programs that can accommodate care giver needs. Various strategies currently being tried by companies to support care givers are described.


Observation of Charge Generation and Transfer during CVD Growth of Carbon Nanotubes.
Carbon nanotube (CNT) is believed to be the most promising material for next generation IC industries with the prerequisite of chirality specific growth. For various approaches to controlling the chiral indices of CNTs, the key is to deepen the understanding of the catalytic growth mechanism in chemical vapor deposition (CVD). Here we show our discovery that the as-grown CNTs are all negatively charged after Fe-catalyzed CVD process. The extra electrons come from the charge generation and transfer during the growth of CNTs, which indicates that an electrochemical process happens in the surface reaction step. We then designed an in situ measurement equipment, verifying that the CVD growth of CNTs can be regarded as a primary battery system. Furthermore, we found that the variation of the Fermi level in Fe catalysts have a significant impact on the chirality of CNTs when different external electric fields are applied. These findings not only provide a new perspective on the growth of CNTs but also open up new possibilities for controlling the growth of CNTs by electrochemical methods.


Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum.
Proplasmepsin II is the zymogen of plasmepsin II, an aspartic proteinase used by Plasmodiumfalciparum to digest hemoglobin during the blood stage of malaria. A large shift between the N-domain and the central and C-domains of proplasmepsin II opens the active site cleft, preventing the formation of a functional aspartic proteinase active site. This mode of inhibition of catalytic activity has not been observed in any other aspartic proteinase zymogen. Instead of occluding a pre-formed active site, as in the gastric aspartic proteinase zymogens, the prosegment of proplasmepsin II interacts extensively with the C-domain and serves as a 'harness' to keep the domains apart. Disruption of key salt bridges at low pH may be important in activation.


The Vulnerability of Occupational Health and Safety to Deregulation: The Weakening of Information Regulations during the Economic Crisis in Korea.
This study was conducted to investigate the causes and consequences of the vulnerability of occupational health and safety (OHS) regulations to deregulation during a period of economic crisis in the Republic of Korea. Analysis of Korea's national regulation database revealed that the vulnerability of OHS regulations to deregulation was related to the fact that OHS policy included many regulations without direct deregulatory impacts on workers. The most affected victim of this characteristic was information regulation that provided a legal basis for government's monitoring and inspection of OHS activities. The massive relaxation of information regulation has the potential to weaken government oversight and to tempt businesses to hide industrial accidents. Since changes in regulations without direct deregulatory impacts are not easily identifiable by workers, careful monitoring of deregulation is necessary to prevent policy impacts harmful to workers' health and safety.


Maternal mortality in America: lessons from the developing world.
In separate but related articles, Drs. Tsu and Goodburn outline strategies for confronting the staggering number of maternal deaths in the developing world: monitoring process indicators and elucidating technologically feasible interventions. American providers face a maternal mortality rate that is only a fraction of that seen in the developing world, but they are challenged by large disparities in perinatal outcomes between African Americans and whites. Strategies similar to those advanced by Tsu and Goodburn might be applicable in the United States. American perinatal health care providers need to look beyond the details of individual adverse events to the structure of care in settings where adverse outcomes are common. Inadequate staffing levels, overcrowded neonatal intensive care units, and provider fatigue are examples of structural problems that have been linked to poor outcomes. Ultimately, improved quality may be achieved only after the relationship between poor-quality health care (medical errors) and inequality is recognized and acted on. Providers should take an active role in identifying and reporting near misses and in developing the skills and technologies with which to implement systems that prevent recurrences.


Characterization of Two New Endo-β-1,4-xylanases from Eupenicillium parvum 4-14 and Their Applications for Production of Feruloylated Oligosaccharides.
Two new endo-1,4-beta-xylanases encoding genes EpXyn1 and EpXyn3 were isolated from mesophilic fungus Eupenicillium parvum 4-14. Based on analysis of catalytic domain and phylogenetic trees, the xylanases EpXYN1 (404 aa) and EpXYN3 (220 aa) belong to glycoside hydrolase (GH) family 10 and 11, respectively. Both EpXYN1 and EpXYN3 were successfully expressed in Pichia pastoris and the recombinant enzymes were characterized using beechwood xylan, birchwood xylan, or oat spelt xylan as substrates, respectively. The optimum temperatures and pH values were 75 °C and 5.5 for EpXYN1, and 55 °C and 5.0 for EpXYN3. EpXYN1 exhibited a high stability at high temperature (65 °C) or at pH values from 8 to 10. EpXYN3 kept over 80% enzymatic activity after treatment at pH values from 3 to 10. The specific activities of EpXYN1 and EpXYN3 were 384.42 and 214.20 U/mg using beechwood xylan as substrate, respectively. EpXYN1 showed lower Km values and higher specific activities toward different xylans compared to EpXYN3. Thin-layer chromatography analysis indicated that the hydrolysis profiles of xylans or xylo-oligosacharides were different by EpXYN1and EpXYN3. EpXYN3 had a higher efficiency than EpXYN1 in production of feruloylated oligosaccharides (FOs) from de-starched wheat bran. The maximum levels of FOs released by EpXYN1 and EpXYN3 were 11.1 and 14.4 μmol/g, respectively. In conclusion, the two xylanases are potential candidates for various industrial applications.


Organocatalytic Enantioselective Synthesis of Tetrahydrofluoren-9-ones via Vinylogous Michael Addition/Henry Reaction Cascade of 1,3-Indandione-Derived Pronucleophiles.
An unprecedented organocatalytic enantioselective vinylogous Michael addition/Henry cyclization cascade is presented for the synthesis of highly substituted tetrahydrofluoren-9-ones 3 employing novel 1,3-indandione-derived pronucleophiles 1a-g and nitroalkenes 2. Following a very simple protocol, a wide range of products were obtained in good to excellent yields and with excellent enantioinduction (43-98% yield, up to 98% ee). The reaction proceeded with excellent diastereocontrol despite the simultaneous generation of four stereogenic centers. Surprisingly, when 2-(1-phenylethylidene)-1H-indandione (1h) was used as a pronucleophile, no cyclization was observed, and only Michael addition adducts 4a-x were furnished in very good yields and excellent enantioselectivities.