N-ftaloil-glicin-hidroksamska kiselina kao kelator željeza u serumu štakora

The aim of this study was to investigate the activity of N-phthaloyl-glycine-hydroxamic acid (Phth-Gly-HA) as a new iron chelator in vivo to be used in iron overload diseases. After intraperitoneal application of Phth-Gly-HA to male rats (1 mg kg1 body mass) once a day for seven days, iron serum level decreased by 21%, whereas the iron value dropped by 32% in female rats (1.5 mg kg1 body mass). The results indicate that the tested substance has the ability to bind serum iron by complexation. Besides transferrin iron release, mobilization of ferritin iron is also possibleU cilju pronalaženja novog efikasnog kelatora koji bi mogao poslužiti u liječenju bolesti izazvanih viškom željeza, u ovom je radu ispitano djelovanje N-ftaloil-glicin-hidroksamske kiseline (Phth-Gly-HA) in vivo. Istraživan je utjecaj kelatora na razinu željeza u serumu štakora nakon intraperitonealne primjene vodene otopine Phth-Gly-HA (0,1 mg mL1) jednom dnevno tijekom 7 dana. Kontrolne su životinje primale fiziološku otopinu. Kod mužjaka injektiranje test supstancije (1 mg kg1) uzrokovalo je pad serumskog željeza za 21%. Kod ženki je nakon tretmana (1,5 mg kg1) izmjereno sniženje razine željeza za 35%. Rezultati pokazuju da ispitivana supstanca ima sposobnost kompleksiranja serumskog željeza, pretežno transferinskog, ali da postoji mogućnost mobilizacije željeza i iz feritinskih zaliha

Early Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia

An elevated neutrophil–lymphocyte ratio negatively predicts the outcome of patients with cancer and is associated with cachexia, the terminal wasting syndrome. Here, using murine model systems of colorectal and pancreatic cancer we show that neutrophilia in the circulation and multiple organs, accompanied by extramedullary hematopoiesis, is an early event during cancer progression. Transcriptomic and metabolic assessment reveals that neutrophils in tumor-bearing animals utilize aerobic glycolysis, similar to cancer cells. Although pharmacological inhibition of aerobic glycolysis slows down tumor growth in C26 tumor-bearing mice, it precipitates cachexia, thereby shortening the overall survival. This negative effect may be explained by our observation that acute depletion of neutrophils in pre-cachectic mice impairs systemic glucose homeostasis secondary to altered hepatic lipid processing. Thus, changes in neutrophil number, distribution, and metabolism play an adaptive role in host metabolic homeostasis during cancer progression. Our findings provide insight into early events during cancer progression to cachexia, with implications for therapy

Children and Virtual Reality: Emerging Possibilities and Challenges

Virtual Reality is fast becoming a reality, with estimates that over 200m headsets will have been sold by 2020, and the market value for VR hardware and software reaching well over $20bn by then. Key players in the market currently include PlayStation with PSVR, Facebook with Oculus Rift, Google Cardboard and Daydream, Mattel with Viewmaster, and many other brands investing in content production for various audiences. One of those audiences is young people and children. “Children and Virtual Reality” is a collaboration between Dubit, Turner, WEARVR and the COST (European Cooperation in Science and Technology) Action DigiLitEY. Dubit, Turner and WEARVR are companies that specialise in digital, TV and VR content, with an interest in developing best practices around VR and children. DigiLitEY is a five year (2013-2017) academic network that focuses on existing and emerging communicative technologies for young children. This includes wearable technologies, 3D printers, robots, augmented reality, toys and games and relevant aspects of the Internet of Things. This report brings together industry research into the effects of VR on 8 to 12 year olds, and ideas that arose from a COST funded Think Tank to explore what the research findings might mean for the use of VR by under 8s

A coupled method for initializing El Niño Southern Oscillation forecasts using sea surface temperature

A simple method for initializing coupled general circulation models (CGCMs) using only sea surface temperature (SST) data is comprehensively tested in an extended set of ensemble hindcasts with the Max-Planck-Institute (MPI) climate model, MPI-OM/ECHAM5. In the scheme, initial conditions for both atmosphere and ocean are generated by running the coupled model with SST nudged strongly to observations. Air–sea interaction provides the mechanism through which SST influences the subsurface. Comparison with observations indicates that the scheme is performing well in the tropical Pacific. Results from a 500-yr control run show that the model's El Niño Southern Oscillation (ENSO) variability is quite realistic, in terms of strength, structure and period. The hindcasts performed were six months long, initiated four times per year, consisted of nine ensemble members, and covered the period 1969–2001. The ensemble was generated by only varying atmospheric initial conditions, which were sampled from the initialization run to capture intraseasonal variability. At six-month lead, the model is able to capture all the major ENSO extremes of the period. However, because of poor sampling of ocean initial conditions and model deficiencies, the ensemble-mean anomaly correlation skill for Niño3 SST is only 0.6 at six-month lead. None the less, the results presented here demonstrate the potential of such a simple scheme, and provide a simple method by which SST information may be better used in more complex initialization schemes

Anterior colporrhaphy does not induce bladder outlet obstruction

We aimed to evaluate if anterior colporrhaphy causes incomplete voiding due to bladder outlet obstruction. Women scheduled for anterior colporrhaphy were asked to undergo multichannel urodynamic investigation before surgery and the first postoperative day. Bladder outlet obstruction was assessed using the Blaivas-Groutz voiding nomogram. Maximum flow rate, detrusor pressure and residual volume were compared between pre- and postoperative measurements and between women with and without an abnormal post-void residual volume (PVR; volume exceeding 150 ml). Seventeen women participated. One woman who was unobstructed before surgery was obstructed after surgery. Overall, detrusor pressure and maximum flow rate before and after surgery did not differ. After surgery, six women had an abnormal PVR, one was unable to void, four were mildly obstructed and one moderately obstructed. Urodynamic investigation the first day after anterior colporrhaphy did not show that anterior colporrhaphy induces bladder outlet obstruction. The explanation for postoperative urinary retention can therefore also lie in non-anatomical causes such as postoperative pain and psychological factor

Exploiting differential Wnt target gene expression to generate a molecular biomarker for colorectal cancer stratification

OBJECTIVE Pathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins (, β-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affecting the synergistic R-Spondin axis (, -fusions) acting through amplification of endogenous Wnt signal transmembrane transduction. Our aim was to exploit differential Wnt target gene expression to generate a mutation-agnostic biomarker for LD tumours. DESIGN We undertook harmonised multi-omic analysis of discovery (n=684) and validation cohorts (n=578) of colorectal tumours collated from publicly available data and the Stratification in Colorectal Cancer Consortium. We used mutation data to establish molecular ground truth and subdivide lesions into LI/LD tumour subsets. We contrasted transcriptional, methylation, morphological and clinical characteristics between groups. RESULTS Wnt disrupting mutations were mutually exclusive. Desmoplastic stromal upregulation of may compensate for absence of epithelial mutation in a subset of stromal-rich tumours. Key Wnt negative regulator genes were differentially expressed between LD/LI tumours, with targeted hypermethylation of some genes (, ) occurring even in CIMP-negative LD cancers. mRNA expression was used as a discriminatory molecular biomarker to distinguish LD/LI tumours (area under the curve >0.93). CONCLUSIONS Epigenetic suppression of appropriate Wnt negative feedback loops is selectively advantageous in LD tumours and differential expression in LD/LI lesions can be exploited as a molecular biomarker. Distinguishing between LD/LI tumour types is important; patients with LD tumours retain sensitivity to Wnt ligand inhibition and may be stratified at diagnosis to clinical trials of Porcupine inhibitors

Midline fascial plication under continuous digital transrectal control: which factors determine anatomic outcome?

Contains fulltext : 88897.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: The aim of the study was to report anatomic and functional outcome of midline fascial plication under continuous digital transrectal control and to identify predictors of anatomic failure. METHODS: Prospective observational cohort. Anatomic success defined as POP-Q stage or= II underwent midline fascial plication under continuous digital transrectal control. Median follow-up was 14 months (12-35 months), and anatomic success was 80.3% (95% CI 75-86). Independent predictors of failure were posterior compartment POP stage >or= III [OR 8.7 (95% CI 2.7-28.1)] and prior colposuspension [OR 5.6 (95% CI 1.1-27.8)]. Sixty-three percent of patients bothered by obstructed defaecation experienced relief after surgery. CONCLUSIONS: Anatomic and functional outcomes were good. Risk factors for anatomic failure were initial size of posterior POP (stage >or= III) and prior colposuspension.1 juni 201

A review of the predictability and prediction of ENSO

A hierarchy of El Niño-Southern Oscillation (ENSO) prediction schemes has been developed during the Tropical Ocean-Global Atmosphere (TOGA) program which includes statistical schemes and physical models. The statistical models are, in general, based on linear statistical techniques and can be classified into models which use atmospheric (sea level pressure or surface wind) or oceanic (sea surface temperature or a measure of upper ocean heat content) quantities or a combination of oceanic and atmospheric quantities as predictors. The physical models consist of coupled ocean-atmosphere models of varying degrees of complexity, ranging from simplified coupled models of the “shallow water” type to coupled general circulation models. All models, statistical and physical, perform considerably better than the persistence forecast in predicting typical indices of ENSO on lead times of 6 to 12 months. The TOGA program can be regarded as a success from this perspective. However, despite the demonstrated predictability, little is known about ENSO predictability limits and the predictability of phenomena outside the tropical Pacific. Furthermore, the predictability of anomalous features known to be associated with ENSO (e.g., Indian monsoon and Sahel rainfall, southern African drought, and off-equatorial sea surface temperature) needs to be addressed in more detail. As well, the relative importance of different physical mechanisms (in the ocean or atmosphere) has yet to be established. A seasonal dependence in predictability is seen in many models, but the processes responsible for it are not fully understood, and its meaning is still a matter of scientific discussion. Likewise, a marked decadal variation in skill is observed, and the reasons for this are still under investigation. Finally, the different prediction models yield similar skills, although they are initialized quite differently. The reasons for these differences are also unclear

Size and Composition Distribution of Atmospheric Particles in Southern California

Continuous measurements of single particle size and chemical composition in the atmosphere are made using aerosol time-of-flight mass spectrometers (ATOFMS) operated alongside more conventional reference air sampling instruments at a network of three urban air monitoring sites in southern California. Electrical aerosol analyzers and optical particle counters are employed to acquire continuous particle size distribution data, and inertial impactor and bulk filter samples with 4-h resolution are taken for determination of particle size and chemical composition. Filter and impactor samples also are taken upwind of the air basin at Santa Catalina Island in order to characterize background air quality. The airborne particle size and composition distribution as measured by the cascade impactors at inland sites differ from that over the ocean principally due to depletion of sea salt particles accompanied by the addition of fine carbon-containing particles and secondary aerosol nitrate. Data from the ATOFMS systems create a continuous time series of sodium-, ammonium-, nitrate-, and carbon-containing particle counts that provide a high-resolution view of differences in particle composition as a function of location in the air basin. Results show that the characteristic peak in the Los Angeles area aerosol mass distribution in the 0.2−0.3-μm size range observed during the 1987 SCAQS experiments has been reduced, consistent with reductions in diesel soot and elemental carbon emissions since that time

Size and Composition Distribution of Atmospheric Particles in Southern California

Continuous measurements of single particle size and chemical composition in the atmosphere are made using aerosol time-of-flight mass spectrometers (ATOFMS) operated alongside more conventional reference air sampling instruments at a network of three urban air monitoring sites in southern California. Electrical aerosol analyzers and optical particle counters are employed to acquire continuous particle size distribution data, and inertial impactor and bulk filter samples with 4-h resolution are taken for determination of particle size and chemical composition. Filter and impactor samples also are taken upwind of the air basin at Santa Catalina Island in order to characterize background air quality. The airborne particle size and composition distribution as measured by the cascade impactors at inland sites differ from that over the ocean principally due to depletion of sea salt particles accompanied by the addition of fine carbon-containing particles and secondary aerosol nitrate. Data from the ATOFMS systems create a continuous time series of sodium-, ammonium-, nitrate-, and carbon-containing particle counts that provide a high-resolution view of differences in particle composition as a function of location in the air basin. Results show that the characteristic peak in the Los Angeles area aerosol mass distribution in the 0.2−0.3-μm size range observed during the 1987 SCAQS experiments has been reduced, consistent with reductions in diesel soot and elemental carbon emissions since that time