Detection of human telomerase reverse transcriptase messenger RNA in urine of high risk patients as a non invasive molecular diagnostic tool for urinary bladder cancer in Egyptians

Introduction and Objectives: Bladder cancer is an important national healthproblem as it is the leading cancer in men in Egypt. Cystoscopy and biopsy, currently remains the gold standard procedure for diagnosis, yet, it is invasive and costly. Urinary cytopathology remains to be the only non-invasive alternative method for diagnosis. Although it is tumour specifi c, yet it has a poor sensitivity, especially for low grade tumours. Detection of Telomerase enzyme in exfoliated urinary cells is a potentially good molecular diagnostic marker in bladder cancer, since the catalytic subunit of this enzyme (hTERT) proved to be essential for cellular immortality and oncogenesis.Subjects and Methods: The study comprised 39 patients (36 with urothelialcarcinomas and 3 cases were squamous cell carcinoma) with bladder cancerand 22 non cancer control (including 14 patients with benign urological disorders and 8 healthy volunteers). The urine sample was split into two aliquots one was used to undertake RNA extraction and hTERT/GAPDH RT-PCR semiquantitative assay and the second for cytological examination. Cystoscopy was considered the reference standard for the identifi cation of bladder cancer.Results: The hTERT/GAPDH RT-PCR test showed signifi cantly higher diagnostic sensitivity than cytology (84% Vs. 75%

Serum clusterin as a marker for diagnosing hepatocellular carcinoma

Background: Approximately 80% of patients with hepatocellular carcinoma (HCC) areuntreatable because of advanced tumor stages at presentation. Therefore, finding newer markers for screening and diagnosing HCC is of utmost importance. Clusterin (CLU) is a 449 amino acid, heterodimeric glycoprotein with a plausible role in the regeneration, migration, and anti-apoptosis of tumor cells. It has been implicated in many malignancies such as prostate and pancreatic adenocarcinomas, but its role in HCC is not well defined.Objective: We aimed to evaluate the diagnostic performance of serum CLU level in diagnosing HCC on top of hepatitis C virus-related liver cirrhosis, and comparing it to that of alpha fetoprotein (AFP).Methods: Twenty cases of apparently healthy subjects, 27 cases of hepatitis C virus-related liver cirrhosis (CHC cases), and 44 HCC cases on top of hepatitis C virus-related liver cirrhosis were included in this study. Serum CLU concentration was determined using a quantitative sandwich enzyme immunoassay technique.Results: Serum clusterin level showed a significant increase in the HCC group compared to the control group (151.96 ± 32.74 vs. 111.40 ±27.46) and to the CHC group (151.96 ± 32.74 vs. 89.12 ±31.62), while a significant decrease in serum clusterin level was found in the CHC group compared to the control group (89.12± 31.62 vs. 111.40± 27.46). Based on receiver operator characteristic curve analysis, serum AFP still surpassed serum CLU in diagnostic sensitivity (77.3% vs. 70.5%), specificity (100% vs. 90%), and positive and negative predictive values (100% vs. 86.1% and 83.3% vs. 77.6% respectively). The use of a combined parallel approach improved the diagnostic sensitivity (95.5%) and negative predictive value (95.7%) over the single use of AFP.Conclusions: Although the diagnostic performance of serum AFP outperformed that of serum CLU, their combined parallel approach improved the sensitivity which is required in screening high risk populations such as CHC patients. KEYWORDS Clusterin; Alpha fetoprotein; Tumor marker; Hepatitis C virus related liver cirrhosis; Hepatocellular carcinom

Rovibronic spectroscopy of PN from first principles

We report an ab initio study on the rovibronic spectroscopy of the closed-shell diatomic molecule phosphorous mononitride, PN. The study considers the nine lowest electronic states, X 1Σ+, A 1Π, C 1Σ-, D 1Δ, E 1Σ-, a 3Σ+, b 3Π, d 3Δ and e 3Σ- using high level electronic structure theory and accurate nuclear motion calculations. The ab initio data cover 9 potential energy, 14 spin-orbit coupling, 7 electronic angular momentum coupling, 9 electric dipole moment and 8 transition dipole moment curves. The Duo nuclear motion program is used to solve the coupled nuclear motion Schrödinger equations for these nine electronic states and to simulate rovibronic absorption spectra of 31P14N for different temperatures, which are compared to available spectroscopic studies. Lifetimes for all states are calculated and compared to previous results from the literature. The calculated lifetime of the A1Π state shows good agreement with an experimental value from the literature, which is an important quality indicator for the ab initio A-X transition dipole moment

Empirical likelihood estimation of the spatial quantile regression

The spatial quantile regression model is a useful and flexible model for analysis of empirical problems with spatial dimension. This paper introduces an alternative estimator for this model. The properties of the proposed estimator are discussed in a comparative perspective with regard to the other available estimators. Simulation evidence on the small sample properties of the proposed estimator is provided. The proposed estimator is feasible and preferable when the model contains multiple spatial weighting matrices. Furthermore, a version of the proposed estimator based on the exponentially tilted empirical likelihood could be beneficial if model misspecification is suspect

Forecasting Player Behavioral Data and Simulating in-Game Events

Understanding player behavior is fundamental in game data science. Video games evolve as players interact with the game, so being able to foresee player experience would help to ensure a successful game development. In particular, game developers need to evaluate beforehand the impact of in-game events. Simulation optimization of these events is crucial to increase player engagement and maximize monetization. We present an experimental analysis of several methods to forecast game-related variables, with two main aims: to obtain accurate predictions of in-app purchases and playtime in an operational production environment, and to perform simulations of in-game events in order to maximize sales and playtime. Our ultimate purpose is to take a step towards the data-driven development of games. The results suggest that, even though the performance of traditional approaches such as ARIMA is still better, the outcomes of state-of-the-art techniques like deep learning are promising. Deep learning comes up as a well-suited general model that could be used to forecast a variety of time series with different dynamic behaviors

In the beginning: Role of autonomy support on the motivation, mental health and intentions of participants entering an exercise referral scheme

Self-determination theory (Deci & Ryan, 2000, Intrinsic motivation and self-determination in human behaviour. New York: Plenum Publishing) highlights the impact autonomy supportive environments can have on exercise motivation and positive health outcomes. Yet little is known about whether differential effects occur as a function of which significant other is providing this support. Further, no research has examined the relationship between motivation and the social environment with participants’ mental health and intentions to be physically active before entering an exercise intervention. Study participants were 347 British adults who were about to start an exercise referral scheme. Regression analyses revealed that the effects of autonomy support on mental health and physical activity intentions differed as a function of who provided the support (offspring, partner or physician), with the offspring having the weakest effects. A structural model was supported, indicating that autonomy support and more autonomous regulations led to more positive mental health outcomes and stronger intentions to be physically active. Knowledge of the social environmental and personal motivation of those about to commence an exercise programme can provide important insights for professionals supporting such efforts

Clinical, anthropometric, radiological and molecular characteristics of Egyptian achondroplasia patients

Background: Achondroplasia is the most common form of non lethal skeletal dysplasia. It is a fully penetrant autosomal dominant disorder and the majority of cases are sporadic resulting from de novo mutations associated with advanced paternal age. The phenotype of achondroplasia is related to disturbance in endochondral bone formation due to mutations in the fi broblast growth factor receptor-3 (FGFR3) gene. Aim of the Work: Evaluation of the cardinal phenotypic features in achondroplasia, the body physique using anthropometric measurements, the characteristic radiological signs in the patients as a main tool for diagnosis and detection of the most common mutations in achondroplasia patients in the studied sample.Subjects and Methods: From 42 cases referred to us as achondroplasia, we selected 20 cases where clinical manifestations were consistent with achondroplasia. Cases were subjected to full clinical examination, detailed anthropometric measurements, whole body skeletal survey and molecular studies of the most common mutations of the FGFR3 gene using PCR amplifi cation technique. Results: Nineteen cases were sporadic (95%) and one case had an affected father (5%). A paternal age above 35 years at the time of child’s birth was present in 7 cases (35%). Paternal exposure to occupational heat was noted in 6 cases (30%) and parental exposure to chemicals in 3 cases (15%). All cases showed typical clinical and radiological manifestations of achondroplasia. Anthropometricmeasurements quantitatively confi rmed the body physique in thestudied cases. G380R common mutations of the FGFR3 gene were detected in 15/18 cases (83%) with the G to A transition at nucleotide 1138 in 14 cases (77%). Agenesis of corpus callosum, not previously reported in association with achondroplasia, was present in the only case with the G-C transversio nmutation at nucleotide 1138 (5%).Conclusions: Awareness of the cardinal features of achondroplasia, properanthropometric measurements and detailed skeletal survey are the key foraccurate diagnosis, genetic counseling and avoidance of over diagnosis. The majority of studied Egyptian achondroplasia patients have the same common mutation that has been most often defi ned in patients with achondroplasia from other countries.Keywords: Achondroplasia, fi broblast growth factor receptor3,skeletal dysplasia, paternal heat exposure

Genetic Reconstruction of Protozoan rRNA Decoding Sites Provides a Rationale for Paromomycin Activity against Leishmania and Trypanosoma

Aminoglycoside antibiotics target the ribosomal decoding A-site and are active against a broad spectrum of bacteria. These compounds bind to a highly conserved stem-loop-stem structure in helix 44 of bacterial 16S rRNA. One particular aminoglycoside, paromomycin, also shows potent antiprotozoal activity and is used for the treatment of parasitic infections, e.g. by Leishmania spp. The precise drug target is, however, unclear; in particular whether aminoglycoside antibiotics target the cytosolic and/or the mitochondrial protozoan ribosome. To establish an experimental model for the study of protozoan decoding-site function, we constructed bacterial chimeric ribosomes where the central part of bacterial 16S rRNA helix 44 has been replaced by the corresponding Leishmania and Trypanosoma rRNA sequences. Relating the results from in-vitro ribosomal assays to that of in-vivo aminoglycoside activity against Trypanosoma brucei, as assessed in cell cultures and in a mouse model of infection, we conclude that aminoglycosides affect cytosolic translation while the mitochondrial ribosome of trypanosomes is not a target for aminoglycoside antibiotics

Simple models of the chemical field around swimming plankton

Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism