Relationship among expression of basic-fibroblast growth factor, MTDH/Astrocyte elevated gene-1, adenomatous polyposis coli, matrix metalloproteinase 9,and COX-2 markers with prognostic factors in prostate carcinomas

Background: The etiopathogenesis of prostate cancer (PC) is still not clear, but hormonal, genetic, and environmental factors are thought to play a role in the tumor pathogenesis. Astrocyte elevated gene-1(AEG-1) as a novel transmembrane protein is predominantly located in the perinuclear region and endoplasmic reticulum. It has been found that AEG-1 upregulation increases the invasive ability of glioma and prostate cancer. Basic fibroblast growth factor (bFGF), matrix metalloproteinase-9 (MMP-9), cyclooxygenases-2 (COX-2), and adenomatous polyposis coli (APC) are very important in tumor progression as well. Materials and Methods: This study included 97 radical prostatectomy specimens. IHC stains for bFGF, MMP-9, COX-2, APC, and AEG-1 were performed on the tissue microarray using standard procedures. For each patient, the age, Gleason score, tumor volume, lymphovascular invasion, lymph node metastasis, surgical margin, and the invasion of vesiculoseminalis areas were assessed. Analyses were performed using the statistical PASW (ver. 18). Results: Statistically significant positive relationships were found MMP-9 and COX-2 (r = 0.242 and P = 0.017), between MMP-9 and APC (r = 0.207 and P = 0.043), and between bFGF and AEG-1 (r = 0.295 and P = 0.004). However, the relationships between age and staining results and tumor volume and staining results were not found to be significant. Although a positive correlation was found between the Gleason score and tumor volume and the Gleason score and age (r = 0.415 and P = 0.0001; r = 0.246 and P = 0.015, respectively), we did not find a statistically significant relationship between other stains and other prognostic parameters (lymphovascular invasion, lymph node metastasis, surgical margin, or vesiculoseminalis invasion). Conclusion:The relationships we found between MMP-9 and COX-2, between MMP-9, and APC and between bFGF and AEG-1 as independent prognostic parameters could be helpful in the development of new therapeutic procedures.Keywords: Adenomatous polyposis coli, astrocyte elevated gene‑1, basic fibroblast growth factor, cyclooxygenases‑2, matrix metalloproteinase‑9, prognostic parameters, prostate adenocarcinomasNigerian Journal of Clinical Practice • Oct-Dec 2013 • Vol 16 • Issue

The gradient flow running coupling with twisted boundary conditions

We study the gradient flow for Yang-Mills theories with twisted boundary conditions. The perturbative behavior of the energy density $\langle E(t)\rangle$ is used to define a running coupling at a scale given by the linear size of the finite volume box. We compute the non-perturbative running of the pure gauge $SU(2)$ coupling constant and conclude that the technique is well suited for further applications due to the relatively mild cutoff effects of the step scaling function and the high numerical precision that can be achieved in lattice simulations. We also comment on the inclusion of matter fields.Comment: 27 pages. LaTe

Variable expressivity of FGF3 mutations associated with deafness and LAMM syndrome

<p>Abstract</p> <p>Background</p> <p>Recessive mutations of fibroblast growth factor 3 (FGF3) can cause LAMM syndrome (OMIM 610706), characterized by fully penetrant complete labyrinthine aplasia, microtia and microdontia.</p> <p>Methods</p> <p>We performed a prospective molecular genetic and clinical study of families segregating hearing loss linked to <it>FGF3 </it>mutations. Ten affected individuals from three large Pakistani families segregating <it>FGF3 </it>mutations were imaged with CT, MRI, or both to detect inner ear abnormalities. We also modeled the three dimensional structure of FGF3 to better understand the structural consequences of the three missense mutations.</p> <p>Results</p> <p>Two families segregated reported mutations (p.R104X and p.R95W) and one family segregated a novel mutation (p.R132GfsX26) of <it>FGF3</it>. All individuals homozygous for p.R104X or p.R132GfsX26 had fully penetrant features of LAMM syndrome. However, recessive p.R95W mutations were associated with nearly normal looking auricles and variable inner ear structural phenotypes, similar to that reported for a Somali family also segregating p.R95W. This suggests that the mild phenotype is not entirely due to genetic background. Molecular modeling result suggests a less drastic effect of p.R95W on FGF3 function compared with known missense mutations detected in fully penetrant LAMM syndrome. Since we detected significant intrafamilial variability of the inner ear structural phenotype in the family segregating p.R95W, we also sequenced <it>FGF10 </it>as a likely candidate for a modifier. However, we did not find any sequence variation, pointing out that a larger sample size will be needed to map and identify a modifier. We also observed a mild to moderate bilateral conductive hearing loss in three carriers of p.R95W, suggesting either a semi-dominant effect of this mutant allele of <it>FGF3</it>, otitis media, or a consequence of genetic background in these three family members.</p> <p>Conclusions</p> <p>We noted a less prominent dental and external ear phenotype in association with the homozygous p.R95W. Therefore, we conclude that the manifestations of recessive <it>FGF3 </it>mutations range from fully penetrant LAMM syndrome to deafness with residual inner ear structures and, by extension, with minimal syndromic features, an observation with implications for cochlear implantation candidacy.</p

Multiple characterization of some glassy-alloys as photon and neutron shields: In-silico Monte Carlo investigation

In the present work, the nuclear radiation shielding proficiency of eight glassy alloys (Gd25RE25Co25Al25 (RE = Tb, Dy and Ho)) containing different amounts of rare earth elements was investigated with MCNPX simulation codes. Mass attenuation coefficients (μ/ρ) of the glassy alloys were simulated in the energy interval of 0.2-20 MeV by exploiting MCNPX codes, and the generated data were found to match with theoretical WinXCOM results. Next, other crucial photon attenuation parameters, effective atomic number (Zeff), Half Value Layer (HVL), and Mean Free Path (MFP), were gotten out using μ/ρ values. It was seen that Er20Tm20 and Er20Tb20 samples replaced with Er by Gd had the highest Zeff and μ/ρ values, whereas HVL and MFP values were the smallest among the other glassy alloys. Geometric progression (GP) procedure was enjoyed to achieve the exposure and energy absorption buildup factors (EBF and EABF) for the glassy alloys proposed. EABFs and EBFs took the largest and lowest values for Gd25Tb25 and Er20Tm20, respectively, to the other samples. Furthermore, the glassy alloys' neutron reduction abilities were estimated by acquiring fast neutron removal cross-sections (∑R). It was noticed that the ∑R values of the glassy alloys are increased with the rising sample density and seen to be comparable to ∑R values of water and ordinary concrete. The results obtained from this study are important in that they show that glassy alloys can be used as radiation shielding. © 2021 The Author(s). Published by IOP Publishing Ltd

Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome

BACKGROUND: Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue. METHODS: Using magnetic resonance imaging, we conducted voxel-based morphometry of 16 patients and 49 age-matched healthy control subjects. RESULTS: We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects. CONCLUSION: These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue

Looking for timing variations in the transits of 16 exoplanets

We update the ephemerides of 16 transiting exoplanets using our ground-based observations, new Transiting Exoplanet Survey Satellite data, and previously published observations including those of amateur astronomers. All these light curves were modelled by making use of a set of quantitative criteria with the exofast code to obtain mid-transit times. We searched for statistically significant secular and/or periodic trends in the mid-transit times. We found that the timing data are well modelled by a linear ephemeris for all systems except for XO-2 b, for which we detect an orbital decay with the rate of -12.95 +/- 1.85 ms yr(-1) that can be confirmed with future observations. We also detect a hint of potential periodic variations in the transit timing variation data of HAT-P-13 b, which also requires confirmation with further precise observations

An international collaborative evaluation of central serous chorioretinopathy: different therapeutic approaches and review of literature. The European Vitreoretinal Society central serous chorioretinopathy study

Purpose: To study and compare the efficacy of different therapeutic options for the treatment of central serous chorioretinopathy (CSCR). Methods: This is a nonrandomized, international multicentre study on 1719 patients (1861 eyes) diagnosed with CSCR, from 63 centres (24 countries). Reported data included different methods of treatment and both results of diagnostic examinations [fluorescein angiography and/or optical coherent tomography (OCT)] and best-corrected visual acuity (BCVA) before and after therapy. The duration of observation had a mean of 11&nbsp;months but was extended in a minority of cases up to 7&nbsp;years. The aim of this study is to evaluate the efficacy of the different therapeutic options of CSCR in terms of both visual (BCVA) and anatomic (OCT) improvement. Results: One thousand seven hundred nineteen patients (1861 eyes) diagnosed with CSCR were included. Treatments performed were nonsteroidal anti-inflammatory eye drops, laser photocoagulation, micropulse diode laser photocoagulation, photodynamic therapy (PDT; Standard PDT, Reduced-dose PDT, Reduced-fluence PDT), intravitreal (IVT) antivascular endothelial growth factor injection (VEGF), observation and other treatments. The list of the OTHERS included both combinations of the main proposed treatments or a variety of other treatments such as eplerenone, spironolactone, acetazolamide, beta-blockers, anti-anxiety drugs, aspirin, folic acid, methotrexate, statins, vitis vinifera extract medication and pars plana vitrectomy. The majority of the patients were men with a prevalence of 77%. The odds ratio (OR) showed a partial or complete resolution of fluid on OCT with any treatment as compared with observation. In univariate analysis, the anatomical result (improvement in subretinal fluid using OCT at 1&nbsp;month) was favoured by age &lt;60&nbsp;years (p&nbsp;&lt;&nbsp;0.005), no previous observation (p&nbsp;&lt;&nbsp;0.0002), duration less than 3&nbsp;months (p&nbsp;&lt;&nbsp;0.0001), absence of CSCR in the fellow eye (p&nbsp;=&nbsp;0.04), leakage outside of the arcade (p&nbsp;=&nbsp;0.05) and fluid height &gt;500&nbsp;\u3bcm (p&nbsp;=&nbsp;0.03). The OR for obtaining partial or complete resolution showed that anti-VEGF and eyedrops were not statistically significant; whereas PDT (8.5), thermal laser (11.3) and micropulse laser (8.9) lead to better anatomical results with less variability. In univariate analysis, the functional result at 1&nbsp;month was favoured by first episode (p&nbsp;=&nbsp;0.04), height of subretinal fluid &gt;500&nbsp;\u3bcm (p&nbsp;&lt;&nbsp;0.0001) and short duration of observation (p&nbsp;=&nbsp;0.02). Finally, there was no statistically significant difference among the treatments at 12&nbsp;months. Conclusion: Spontaneous resolution has been described in a high percentage of patients. Laser (micropulse and thermal) and PDT seem to lead to significant early anatomical improvement; however, there is little change beyond the first month of treatment. The real visual benefit needs further clarification

Magnetic Particle-Scanning for Ultrasensitive Immunodetection On-Chip

We describe the concept of magnetic particle-scanning for on-chip detection of biomolecules: a magnetic particle, carrying a low number of antigens (Ag's) (down to a single molecule), is transported by hydrodynamic forces and is subjected to successive stochastic reorientations in an engineered magnetic energy landscape. The latter consists of a pattern of substrate-bound small magnetic particles that are functionalized with antibodies (Ab's). Subsequationuent counting of the captured Ag-carrying particles provides the detection signal. The magnetic particle-scanning principle is investigated in a custom-built magneto-microfluidic chip and theoretically described by a random walk-based model, in which the trajectory of the contact point between an Ag-carrying particle and the small magnetic particle pattern is described by stochastic moves over the surface of the mobile particle, until this point coincides with the position of an Ag, resulting in the binding of the particle. This model explains the particular behavior of previously reported experimental dose-response curves obtained for two different ligand-receptor systems (biotin/streptavidin and TNF-alpha) over a wide range of concentrations. Our model shows that magnetic particle-scanning results in a very high probability of irrununocomplex formation for very low Ag concentrations, leading to an extremely low limit of detection, down to the single molecule-per-particle level. When compared to other types of magnetic particle-based surface coverage assays, our strategy was found to offer a wider dynamic range (>8 orders of magnitude), as the system does not saturate for concentrations as high as 10(11) Ag molecules in a 5 mu L drop. Furthermore, by emphasizing the importance of maximizing the encounter probability between the Ag and the Ab to improve sensitivity, our model also contributes to explaining the behavior of other particle-based heterogeneous immunoassays