Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential. RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1 and TIG1 were highly methylated in PCa compared to BPH (p < 0.001), while SERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2a and SFN were not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level of SFN, SLIT2 and SERPINB5 distinguished low and high Gleason score cancers, e.g. SFN and SERPINB5 together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes including CDH1 previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001). Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes like RARB, HIN1, BCL2, APC and GSTP1 is warranted for diagnostic potential and SFN, SLIT2 and SERPINB5 for prognostic potential

Year patterns of climate impact on wheat yields

Rainfall, temperature, and solar radiation are important climate factors, which determine crop growth, development and yield from instantaneous to decadal scales. We propose to identify year patterns of climate impact on yield on the basis of rain and non-rain weather. There are inter-related impacts of climatic factors on crop production within a specific pattern. Historical wheat yield data in Queensland during 1889-2004 were used. The influence of meteorological conditions on wheat yields was derived from statistical yield data which were detrended by 9-year-smoothing averages to remove the effects of technological improvements on wheat yields over time. Climate affects crop growth and development differently over different growth stages. Therefore, we considered the climate effects at both vegetative and reproductive stages (before and after flowering date, respectively) on yield. Cluster analysis was employed to identify the year patterns of climate impact. Five patterns were significantly classified. Precipitation during the vegetative stage was the dominant and beneficial factor for wheat yields while increasing maximum temperature had a negative influence. Crop yields were strongly dependent on solar radiation under normal rainfall conditions. As the effect of rainfall on soil water is relatively long-lasting, its beneficial effect in vegetative stage was higher than its effect during the reproductive stage. The Agricultural Production Systems sIMulator (APSIM) was evaluated using long-term historical data to determine whether the model could reasonably simulate effects of climate factors for each year pattern. The model provided good estimates of wheat yield when conditions resulted in medium yield levels, however, in extremely low or high yield years, corresponding to extremely low or high precipitation in the vegetative stage, the model tended to underestimate or overestimate. Under high growing season precipitation, simulations responded more favourably to reproductive stage rainfall than measured yields. © 2013 Royal Meteorological Society

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P&lt;0.05) and macrophage (P&lt;0.05) infiltration and microvessel density (P&lt;0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P&lt;0.01), negative hormonal receptor (P&lt;0.10), lower albumin concentrations (P&lt;0.01), increased tumour proliferation (P&lt;0.05), increased tumour microvessel density (P&lt;0.05), the extent of locoregional control (P&lt;0.0001) and limited systemic treatment (Pless than or equal to0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P&lt;0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer

Zigzag-shaped nickel nanowires via organometallic template-free route

In this manuscript, the formation of nickel nanowires (average size: several tens to hundreds of μm long and 1.0-1.5 μm wide) at low temperature is found to be driven by dewetting of liquid organometallic precursors during spin coating process and by self-assembly of Ni clusters. Elaboration of metallic thin films by low temperature deposition technique makes the preparation process compatible with most of the substrates. The use of iron and cobalt precursor shows that the process could be extended to other metallic systems. In this work, AFM and SEM are used to follow the assembly of Ni clusters into straight or zigzag lines. The formation of zigzag structure is specific to the Ni precursor at appropriate preparation parameters. This template free process allows a control of anisotropic structures with homogeneous sizes and angles on standard Si/SiO2 surface

The factor structure of the Forms of Self-Criticising/Attacking & Self-Reassuring Scale in thirteen distinct populations

There is considerable evidence that self-criticism plays a major role in the vulnerability to and recovery from psychopathology. Methods to measure this process, and its change over time, are therefore important for research in psychopathology and well-being. This study examined the factor structure of a widely used measure, the Forms of Self-Criticising/Attacking & Self-Reassuring Scale in thirteen nonclinical samples (N = 7510) from twelve different countries: Australia (N = 319), Canada (N = 383), Switzerland (N = 230), Israel (N = 476), Italy (N = 389), Japan (N = 264), the Netherlands (N = 360), Portugal (N = 764), Slovakia (N = 1326), Taiwan (N = 417), the United Kingdom 1 (N = 1570), the United Kingdom 2 (N = 883), and USA (N = 331). This study used more advanced analyses than prior reports: a bifactor item-response theory model, a two-tier item-response theory model, and a non-parametric item-response theory (Mokken) scale analysis. Although the original three-factor solution for the FSCRS (distinguishing between Inadequate-Self, Hated-Self, and Reassured-Self) had an acceptable fit, two-tier models, with two general factors (Self-criticism and Self-reassurance) demonstrated the best fit across all samples. This study provides preliminary evidence suggesting that this two-factor structure can be used in a range of nonclinical contexts across countries and cultures. Inadequate-Self and Hated-Self might not by distinct factors in nonclinical samples. Future work may benefit from distinguishing between self-correction versus shame-based self-criticism.Peer reviewe

Obstructive jaundice secondary to pancreatic head adenocarcinoma in a young teenage boy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pancreatic adenocarcinoma is extremely rare in childhood. We report a case of metastatic pancreatic adenocarcinoma in a 13-year-old boy, revealed by jaundice.</p> <p>Case presentation</p> <p>A 13-year-old Moroccan boy was admitted with obstructive jaundice to the children's Hospital of Rabat, Department of Pediatric Oncology. Laboratory study results showed a high level of total and conjugated bilirubin. Computerized tomography of the abdomen showed a dilatation of the intra-hepatic and extra-hepatic bile ducts with a tissular heterogeneous tumor of the head of the pancreas and five hepatic lesions. Biopsy of a liver lesion was performed, and a histopathological examination of the sample confirmed the diagnosis of metastatic ductal adenocarcinoma of the pancreas. Our patient underwent a palliative biliary derivation. After that, chemotherapy was administered (5-fluorouracil and epirubicin), however no significant response to treatment was noted and our patient died six months after diagnosis.</p> <p>Conclusion</p> <p>Malignant pancreatic tumors, especially ductal carcinomas, are exceedingly rare in the pediatric age group and their clinical features and treatment usually go unappreciated by most pediatric oncologists and surgeons.</p

Meticulous Doxorubicin Release from pH‐responsive Nanoparticles Entrapped within an Injectable Thermoresponsive Depot.

The dual stimuli‐controlled release of doxorubicin from gel‐embedded nanoparticles is reported. Non‐cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)‐ b ‐poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH‐responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin loaded nanoparticles could be incorporated within a thermoresponsive poly(2‐hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2‐hydroxypropyl methacrylate) in DMSO solution into aqueous solution. The combination of the poly(2‐hydroxypropyl methacrylate) gel and poly(ethylene glycol)‐ b ‐poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near‐complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in non‐acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site‐specific, release of chemotherapeutics

Wigner Crystallization in a Quasi-3D Electronic System

When a strong magnetic field is applied perpendicularly (along z) to a sheet confining electrons to two dimensions (x-y), highly correlated states emerge as a result of the interplay between electron-electron interactions, confinement and disorder. These so-called fractional quantum Hall (FQH) liquids form a series of states which ultimately give way to a periodic electron solid that crystallizes at high magnetic fields. This quantum phase of electrons has been identified previously as a disorder-pinned two-dimensional Wigner crystal with broken translational symmetry in the x-y plane. Here, we report our discovery of a new insulating quantum phase of electrons when a very high magnetic field, up to 45T, is applied in a geometry parallel (y-direction) to the two-dimensional electron sheet. Our data point towards this new quantum phase being an electron solid in a "quasi-3D" configuration induced by orbital coupling with the parallel field