34 research outputs found

    Clinical significance of altered nm23-H1, EGFR, RB and p53 expression in bilharzial bladder cancer

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Clinical characterization of bladder carcinomas is still inadequate using the standard clinico-pathological prognostic markers. We assessed the correlation between <it>nm23-H1</it>, <it>Rb, EGFR </it>and <it>p53 </it>in relation to the clinical outcome of patients with muscle invasive bilharzial bladder cancer (MI-BBC).</p> <p>Methods</p> <p><it>nm23-H1</it>, <it>Rb, EGFR and p53 </it>expression was assessed in 59 MI-BBC patients using immunohistochemistry and reverse transcription (RT-PCR) and was correlated to the standard clinico-pathological prognostic factors, patient's outcome and the overall survival (OS) rate.</p> <p>Results</p> <p>Overexpression of <it>EGFR </it>and <it>p53 </it>proteins was detected in 66.1% and 35.6%; respectively. Loss of <it>nm23-H1</it>and <it>Rb </it>proteins was detected in 42.4% and 57.6%; respectively. Increased <it>EGFR and </it>loss of <it>nm23-H1 </it>RNA were detected in 61.5% and 36.5%; respectively. There was a statistically significant correlation between <it>p53 </it>and <it>EGFR </it>overexpression (<it>p </it>< 0.0001), <it>nm23 </it>loss (protein and RNA), lymph node status (<it>p </it>< 0.0001); between the incidence of local recurrence and <it>EGFR </it>RNA overexpression (p= 0.003) as well as between the incidence of metastasis and altered <it>Rb </it>expression (<it>p </it>= 0.026), <it>p53 </it>overexpression (<it>p </it>< 0.0001) and mutation (<it>p </it>= 0.04). Advanced disease stage correlated significantly with increased <it>EGFR </it>(protein and RNA) (<it>p </it>= 0.003 & 0.01), reduced <it>nm23-H1 </it>RNA (<it>p </it>= 0.02), altered <it>Rb </it>(<it>p </it>= 0.023), and <it>p53 </it>overexpression (<it>p </it>= 0.004). OS rates correlated significantly, in univariate analysis, with <it>p53 </it>overexpression (<it>p </it>= 0.011), increased <it>EGFR </it>(protein and RNA, <it>p </it>= 0.034&0.031), <it>nm23-H1 RNA </it>loss (<it>p </it>= 0.021) and aberrations of ≄ 2 genes. However, multivariate analysis showed that only high <it>EGFR </it>overexpression, metastatic recurrence, high tumor grade and the combination of ≄ 2 affected markers were independent prognostic factors.</p> <p>Conclusion</p> <p><it>nm23-H1, EGFR </it>and <it>p53 </it>could be used as prognostic biomarkers in MI-BBC patients. In addition to the standard pathological prognostic factors, a combination of these markers (≄ 2) has synergistic effects in stratifying patients into variable risk groups. The higher is the number of altered biomarkers, the higher will be the risk of disease progression and death.</p

    The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

    Get PDF
    INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

    Use of One and Two Horizontal Plates to Reduce the Drag Force on the Rigid Cylinder Located Inside the Channel: Approach of the Immersed Interface Method

    No full text
    Immersed interface method is a non-matching boundary approach that has been taken into consideration in recent years. In this method, there is no need to coincide between the fluid and the solid grids. Eulerian grid is used for fluid domain and Lagrangian grid is used for solid domain. Using the Dirac Delta function, the connection between these two grids is established. Separation of the flow from the cylinder surface causes a high pressure drop in some parts of the cylinder, resulting in a dramatic increase in drag force. Drag force reduction is very important in some engineering issues, and several methods have been proposed to achieve this goal. In this study, the flow around a rigid cylinder is simulated. The goal is to reduce the drag force on the cylinder through one and two horizontal plates. The results are in good agreement with prior numerical results

    Existence and Uniqueness Theorem of Fractional Mixed Volterra-Fredholm Integrodifferential Equation with Integral Boundary Conditions

    Get PDF
    We study the existence and uniqueness of the solutions of mixed Volterra-Fredholm type integral equations with integral boundary condition in Banach space. Our analysis is based on an application of the Krasnosel'skii fixed-point theorem

    Gravity effect on water entry during an early stage

    No full text
    We consider the effects of gravity on the two-dimensional flow caused by a symmetric body vertically entering into initially calm water at constant speed. Surface tension, viscosity and the compressibility of the liquid are neglected. The flow is potential. The region of contact of the water with the body surface starts from a single point and grows monotonically in time. The effects of gravity on the size of the contact region, the hydrodynamic force on the body, the hydrodynamic pressure distribution on the wetted part of the body surface, and the free-surface elevation are analysed for the initial stage of impact, using asymptotic methods with a small-valued gravity-related parameter. It has been well accepted that the effects of gravity on water impact characteristics are small. The analysis reveals that the effects of gravity are relatively small even for impact conditions, where formally these effects should be included in the model. It is found that gravity: slows down the contact points, reduces the hydrodynamic pressure at the periphery of the contact region, but increases the pressure in the central part of the wetted region, and hence increases the total fluid force on the body. The asymptotic contributions are sensitive to the gravity correction to the size of the contact region, even though it is relatively small. The effects of gravity become more important with time for the later stages

    Rebound increase in microRNA levels at the end of 5-FU-based therapy in colorectal cancer patients

    No full text
    Abstract Treatment with 5-fluorouracil (5-FU) based therapy is still used for colorectal cancer (CRC). Epigenetics has become a focus of study in cancer because of its reversibility besides its known regulatory functions. In this study, we will monitor the change in microRNAs (miRNAs) levels with 5-FU-based therapy at baseline and after 3 and 6 months of treatment to be correlated with their prognostic potential. The expression levels of 5 miRNAs, namely miRNA223-3p, miRNA20a-5p, miRNA17-5p, miRNA19a-3p, and miRNA7-5p, were measured in the peripheral blood of 77 CRC patients, along with the expression of 3 proteins PTEN, ERK, and EGFR. At baseline, CRC patients had significantly higher levels of circulating miRNAs than healthy controls. This level was reduced after 3 months of 5-FU-based therapy, then increased after 6 months significantly in responder patients compared to non-responders. MiRNA19a-3p showed that significant pattern of change in the subgroups of patients with high ERK, EGFR, and PTEN protein levels, and its 6 months level after 5-FU-based therapy showed significance for the hazard of increased risk of disease recurrence and progression

    Numerical investigation of the effect of the turbulator geometry (disturber) on heat transfer in a channel with a square section

    No full text
    The principal moot point in this investigation is heat removal from surfaces with high heat flux, which is the use of tabulators and parts with a particular geometry, it has been chosen as a solution to this moot point. The primary hypothesis in this investigation is to increase fluid heat transfer by increasing turbulence and heat transfer by increasing the plane of heat transfer and establishing a vortex flow. The fundamental idea and novelty of this investigation is the simultaneous use of a turbulator (to improve turbulence and provide more effective heat transmission) and increasing the contact surface (through the installation of parts with unique geometry), which can be obtained from different turbulator used in other geometries. In this research, the limited volume method to solve governing equations in three-dimensional space and Cartesian coordinates has been used on the network using Ansys Fluent software. In order of comparison, turbulators SLT and then TRT is compared to other turbulators (TRT, SHT, RET) It has the highest Nusselt number, and in the Reynolds numbers in the turbulent flow regime, they have the most significant reduction in the friction coefficient

    Experimental study of thermal conductivity coefficient of GNSs-WO3/LP107160 hybrid nanofluid and development of a practical ANN modeling for estimating thermal conductivity

    No full text
    In the present study, the effects of nanoparticles, mass fraction percentage and temperature on the conductive heat transfer coefficient of Graphene nanosheets- Tungsten oxide/Liquid paraffin 107160 hybrid nanofluid was investigated. For this purpose, four different mass fractions were used in the range of 0.005%–5% in a number of examinations. The results illustrated that the thermal conductivity coefficient was increased with the increment of the mass fraction percentage and the temperature of Graphene nanosheets- Tungsten oxide nanomaterials in the base fluid. Then, a feed-forward artificial neural network was used to model the thermal conductivity coefficient. In general, with the increase in temperature and concentration of nanofluid, the value of thermal conductivity increases. The optimum value of thermal conductivity for this experiment was observed in the volume fraction of 5% and at the temperature of 70 °C. The results of this modeling indicated that the fault of the data estimated for the coefficient of thermal conductivity in the Graphene nanosheets- Tungsten oxide/Liquid paraffin 107160 nanofluid, as a function of mass fraction percentage and temperature, was less than 3%, as compared to the experimental data
    corecore