Cellular Context Dictates the Suppression or Augmentation of Triple-Negative Mammary Tumor Metastasis by NLRX1.

Prior studies have defined multiple, but inconsistent, roles for the enigmatic pattern recognition receptor NLRX1 in regulating several cancer-associated biological functions. In this study, we explore the role of NLRX1 in the highly metastatic murine 4T1 mammary tumor model. We describe a functional dichotomy of NLRX1 between two different cellular contexts: expression in healthy host cells versus expression in the 4T1 tumor cells. Using Nlrx1-/- mice engrafted with 4T1 tumors, we demonstrate that NLRX1 functions as a tumor suppressor when expressed in the host cells. Specifically, NLRX1 in healthy host cells attenuates tumor growth and lung metastasis through suppressing characteristics of epithelial-mesenchymal transition and the lung metastatic niche. Conversely, we demonstrate that NLRX1 functions as a tumor promoter when expressed in 4T1 tumor cells using gain- and loss-of-function studies both in vitro and in vivo. Mechanistically, NLRX1 in the tumor cells augments 4T1 aggressiveness and metastasis through regulating epithelial-mesenchymal transition hallmarks, cell death, proliferation, migration, reactive oxygen species levels, and mitochondrial respiration. Collectively, we provide critical insight into NLRX1 function and establish a dichotomous role of NLRX1 in the 4T1 murine mammary carcinoma model that is dictated by cellular context.

Magic bubbles: utilizing histotripsy to modulate the tumor microenvironment and improve systemic anti-tumor immune responses.

Focused Ultrasound (FUS) is emerging as a promising primary and adjunct therapy for the treatment of cancer. This includes histotripsy, which is a noninvasive, non-ionizing, non-thermal ultrasound guided ablation modality. As histotripsy has progressed from bench-to-bedside, it has become evident that this therapy has benefits beyond local tumor ablation. Specifically, histotripsy has the potential to shift the local tumor microenvironment from immunologically 'cold' to 'hot'. This is associated with the production of damage associated molecular patterns, the release of a selection of proinflammatory mediators, and the induction of inflammatory forms of cell death in cells just outside of the treatment zone. In addition to the induction of this innate immune response, histotripsy can also improve engagement of the adaptive immune system and promote systemic anti-tumor immunity targeting distal tumors and metastatic lesions. These tantalizing observations suggest that, in settings of widely metastatic disease burden, selective histotripsy of a limited number of accessible tumors could be a means of maximizing responsiveness to systemic immunotherapy. More work is certainly needed to optimize treatment strategies that best synergize histotripsy parameters with innate and adaptive immune responses. Likewise, rigorous clinical studies are still necessary to verify the presence and repeatability of these phenomena in human patients. As this technology nears regulatory approval for clinical use, it is our expectation that the insights and immunomodulatory mechanisms summarized in this review will serve as directional guides for rational clinical studies to validate and optimize the potential immunotherapeutic role of histotripsy tumor ablation.

The Need for an Information Communication and Advocacy Strategy to Guide a Research Agenda to Address Burden of Invasive Nontyphoidal Salmonella Infections in Africa.

Invasive nontyphoidal salmonellosis (iNTS) is often not recognized clinically, and prevention of iNTS is largely ignored by policy planners and decision makers. During 2010, an estimated 3.4 million cases and 681,316 deaths occurred worldwide due to iNTS, with the largest estimated disease burden in resource-limited areas of sub-Saharan Africa. These figures likely underestimate global burden for several reasons, further complicating efforts to raise awareness of iNTS. To increase disease recognition and facilitate development of interventions, a communication and advocacy plan should be developed and implemented by actors in different sectors of global health, including researchers and scientists, funders, vaccine manufacturers, civil society organizations, and government officials from highly affected countries.

Pyopneumothorax of unusual aetiology.

A 50-year old diabetic male presented with cough, breathlessness, fever, and chest pain. Clinical and radiological evaluation revealed a right-sided pyopneumothorax. Surgical drainage with tube thoracostomy was performed. Pleural fluid cultures grew Enterococcus fecium as a sole organism. Our patient was treated with vancomycin and amikacin with an excellent clinical response. Enterococci are rarely implicated in the lower respiratory tract and pleural infections and are not usually considered if initiating empirical treatment. Their intrinsic resistance to empirically used antibiotics may complicate the course of the disease. Hence initial Gram staining and expeditious microbiological isolation with susceptibility testing is warranted in all cases. Gram-positive aerobes, notably staphylococcus followed by streptococcus and pneumococcus, are the commonly encountered organisms in pleural infections.

Cattaneo-Christov heat flux (CC model) in mixed convective stagnation point flow towards a Riga plate.

This research article proposes an improved Fourier law of heat conduction (Cattaneo-Christov) in presence of heat source/sink. The heat transport characteristics are modeled for mixed convective stagnation point flow by a Riga plate. Flow is generated due to linear stretching velocity. The partial differential system is changed to ordinary differential system through implementing appropriate transformations. Series solutions are developed through semi-analytical method called as homotopy analysis method. Present research article is related to the improved Fourier law of heat conduction (Cattaneo-Christov) over a linear stretchable surface of Riga plate when fluid saturates porous space. The main outcomes of present communication are summarized as: (i) velocity of material particles decreases subject to larger inverse Darcy-number while it enhances via velocity ratio and magnetic parameters (ii) temperature distribution as well as layer thickness enhance for higher estimations of Eckert number and heat source parameter while it decays against Prandtl number (iii) skin friction coefficient decreases through higher values of inverse Darcy number and mixed convection parameter.

Transportation of heat generation/absorption and radiative heat flux in homogeneous-heterogeneous catalytic reactions of non-Newtonian fluid (Oldroyd-B model).

BACKGROUND: This study addresses the three-dimensional (3D) stagnation point flow of non-Newtonian material (Oldroyd-B) with magnetohydrodynamics. Furthermore, Ohmic heating and radiative flux are used in the modeling of energy expression. The surface is convectively heated. Equal strengths of diffusions for homogeneous and heterogeneous reactions are counted. Results are computed and presented graphically. Heat transfer rate is numerically discussed through table. METHOD: Here the nonlinear differential system first converted into ordinary differential equation through implementation of appropriate similarity variables. The obtained ordinary system is tackled through homotopy technique for convergent solutions. The outcomes are presented through different graphs and discussed in section six. OUTCOMES: The remarkable results of the present communication which is obtained from the semi analytical method i.e., "homotopy method" is summarized as (i) Opposite impact is noticed for velocity components i.e., (f'(ξ), g(ξ)) for rising fluid parameter and rotation parameter. (ii) The temperature is direct relation with Biot number and radiative variable. (iii) Heat transfer rate is more versus Biot number and radiation variable. (iv) The concentration field shows opposite impact versus homogeneous and heterogeneous parameters.

Electro-magneto flow of nanomaterial with irreversibility.

Here we discuss the analysis of irreversibility in electrical magnetohydrodynamic convective flow of nanomaterials over a stretchable surface. Energy equation deliberated through Joule heating, dissipation and heat source/sink. Furthermore features chemical reaction is also considered. Total entropy optimization is calculated. Salient features of thermophoresis effect and random motion of particles are studied. Nonlinear couple equations are converted to ordinary system by using the transformation. The obtained system are elucidated through ND solve technique. Salient features of pertinent variables on entropy optimization, velocity, Bejan number, concentration and temperature are discussed. Nusselt number, gradient of concentration and surface drag force are computationally calculated. Velocity and temperature show opposite behaviors via magnetic parameter. Electric and magnetic field parameters on entropy optimization have opposite results.

Entropy optimization analysis in MHD nanomaterials (TiO2-GO) flow with homogeneous and heterogeneous reactions.

BACKGROUND: Nanomaterials have higher inspiration in the growth of pioneering heat transportation fluids and good efforts were made in this field during the recent year. Nowadays numerous scientists and researchers have focused their struggle on nanomaterials study. Nanoliquids have advanced properties which make them efficient in various applications including engine cooling, hybrid-power engine, pharmaceutical processes, refrigerator and vehicle thermal management etc. Therefore such implication in mind the entropy optimization in magnetohydrodynamic nanomaterials (TiO2 - GO) flow between two stretchable rotating disks is discussed here. Energy expression subject to Joule heating, thermal radiation and viscous dissipation is modeled. Entropy optimization rate is based upon thermodynamic second law. Here titanium dioxide (TiO2) and graphene oxide (GO) and water (H2O) are used as nanoliquids. Homogeneous and heterogeneous reactions have been accounted. METHODS: Transformation process reduced nonlinear PDE's to ordinary differential systems. Formulated systems are solved due to implementation of Newton built in shooting method. RESULTS: Salient behavior of influential variables on velocity, entropy optimization, temperature, Bejan number and concentration graphically illustrated for (TiO2 and GO). Surface drag force and gradient of temperature ((Cf1, Cf2) and (Nux1, Nux2)) are numerically computed for various interesting parameters at lower and upper disks respectively. Axial and radial velocities components boost up for larger (Re) but opposite is hold for tangential velocity. Entropy optimization and temperature are increased for higher Brinkman number (Br). CONCLUSIONS: A significant augmentation occurs in radial and axial velocities (f'(ξ) and f(ξ)) versus stretching parameter, while opposite is hold for tangential velocity (g(ξ)). For larger values of Reynold and Brinkman numbers the temperature increases. Temperature and entropy optimization have opposite effect for radiation parameter. Concentration has similar results for Reynold and Schmidt numbers. Entropy optimization and Bejan number for radiation parameter have similar outcome. Bejan number decays for Brinkman number.

Theoretical and numerical investigation of Carreau-Yasuda fluid flow subject to Soret and Dufour effects.

BACKGROUND: Newtonian fluids can be categorized by a single coefficient of viscosity for specific temperature. This viscosity will change with temperature; it doesn't change with strain rate. Just a small group of liquids show such steady consistency. A fluid whose viscosity changes subject to relative flow velocity is called non-Newtonian liquids. Here we have summarized a result for the flow of Carreau-Yasuda fluid over a porous stretchable surface. Mixed convection is considered. Modeling of energy expression is performed subject to Soret and Dufour effects. METHOD: The nonlinear PDE's are changed to ODE's through suitable transformations and then solved for numerical solutions via Built-in shooting method (bvp4c). RESULTS: Variation of important variables is studied on the concentration, temperature and velocity fields. Tabular representation for study of skin friction and heat transfer rate is presented for important variables. Our results show that velocity decreases versus higher estimations of Weissenberg number, porosity parameter, buoyancy ratio and mixed convection parameter. Temperature decays via Weissenberg number and porosity parameter. Increase in concentration is noticed through higher Soret number and porosity parameter. Skin friction and heat transfer rate (Nusselt number) boosts versus larger porosity parameter and Prandtl number respectively while it decays against Weissenberg number and Dufour and Eckert number.

Magneto rotating flow of hybrid nanofluid with entropy generation.

BACKGROUND: Study of nanofluids has been enormously increased for the last couple of years. Regardless of some irregularity in the revealed outcomes and lacking consistency, yet the mechanisms of heat transport have been emerged as highly efficient. In the continuation of nanomaterials research, the investigators and analyst have also attempted to utilize hybrid nanomaterial recently, which is designed by suspending unique nanomaterials (nanoparticles) either in mixture or composite structure. The theory of hybrid nanofluids can be further modified for heat transport and pressure drop attributes by trade-off between disadvantages and advantages of individual suspension, ascribed to great aspect ratio, better thermal system and synergistic impact of nanomaterials. Therefore, we have conducted a theoretical attempt on MHD entropy optimized viscous hybrid nanomaterial flow between two parallel plates. The boundaries of plates are fixed with velocity and thermal slip aspects. Chemical reaction with novel aspect of activation energy is accounted. Furthermore, thermal radiation, heat generation and Joule heating are examined. METHOD: The modeled system is numerically simulated through bvp4c technique. RESULTS: Behaviors of pertinent variables on the velocity, skin friction, temperature, Nusselt number, entropy generation rate and concentration are presented and discussed through different graphs. Temperature field decays against higher values of Eckert number and thermal slip variable. CONCLUSIONS: It is noticed that velocity of material particles increase against larger estimations of rotation parameter. Temperature declines versus larger Prandtl and Eckert numbers. Concentration decays when an enhancement is occurred in the Lewis number. Magnitude of surface drag force upsurges for rising values of Prandtl number and radiation parameter. Furthermore, magnitude of Nusselt number enhances through larger Eckert number, magnetic number and Prandtl number.

Development of thixotropic nanomaterial in fluid flow with gyrotactic microorganisms, activation energy, mixed convection.

BACKGROUND: In this article, impact of gyrotactic microorganisms on nonlinear mixed convective MHD flow of thixotropic nanoliquids is addressed. Effects of Brownian motion and thermophoresis diffusion are considered. Characteristics of heat and mass transfer are analyzed with activation energy, Joule heating and binary chemical reaction. Nonlinear PDE's are reduced to ordinary equation by using suitable transformations. METHOD: For convergent series solution the given system is solved by the implementation of the homotopic analysis technique (HAM). RESULTS: Influences of different flow controlling variables on the velocity, microorganisms, concentration and temperature are examined through graphs. Surface drag force, density number, Sherwood number and gradient of temperature are examined versus different flow parameters through graphs. For larger thixotropic fluid parameters the velocity field boosts up. For rising values of Hartmann number the velocity and temperature have opposite behaviors.

Evaluation of entropy generation in cubic autocatalytic unsteady squeezing flow of nanofluid between two parallel plates.

BACKGROUND: Nanomaterials have advanced behaviors that make them possibly beneficial in various applications in mass and heat transports such as engine cooling, pharmaceutical processes, fuel cells, engine cooling and domestic refrigerator etc. Therefore here we deliberated the entropy generation in unsteady magnetohydrodynamic squeezing flow of viscous nanomaterials between two parallel plates. The upper plate is squeezing towards lower plate. The lower plate exhibits porous character. Energy attributes are discussed through heat flux, dissipation and Joule heating. Furthermore the irreversibility analysis with cubic autocatalysis chemical reaction is also accounted. METHODS: Nonlinear differential systems are converted to ordinary differential system by transformations. For convergent series solution the given system are solved by homotopy analysis method (HAM). RESULTS: Characteristics of various interesting variables on velocity, Bejan number, concentration, entropy optimization and temperature are deliberated through graphs. Gradient of velocity (Cfx) and Nusselt number (Nux) are numerically computed against various physical variables. Entropy generation and Bejan number both quantitatively enhance versus radiation parameter. For larger squeezing parameter the velocity and temperature field are increased. CONCLUSIONS: The obtained results show that for larger squeezing parameter the velocity field boosts up. Velocity have opposite impact For larger magnetic and porosity parameters. Temperature is decreased for higher values of radiation parameter and Prandtl number. Temperature and concentration have same outcome for thermophoresis parameter. Entropy generation and Bejan number both quantitatively enhance versus radiation parameter, while reverse is hold for Brinkman number.

MHD peristaltic motion of Johnson-Segalman fluid in an inclined channel subject to radiative flux and convective boundary conditions.

BACKGROUND: In abundant of a digestive tract like smooth muscle tissue, human gastrointestinal tract contracts in sequence to generate a peristaltic wave, which pushes a food along the tract. The peristaltic motion contains circular relaxation smooth muscles, then their shrinkage (contraction) behind the chewed material to keep it from moving backward, then longitudinal contraction to shove it ahead. Therefore, we have conducted a theoretical investigation on peristaltic transport in flow of Johnson-Segalman liquid subject to inclined magnetic field. The energy equation is developed with extra heat transport assumptions like thermal radiative flux and dissipation. The channel walls are heated convectively. METHODS: Dimensionless problems subject to small Reynolds number and long wavelength are tackled. Perturbation technique is implemented for small Weissenberg number. RESULTS: The physical importance of involved parameters that directly affect the heat transfer rate temperature and velocity. The pertinent variables are amplitude ratio, wave number, Reynolds number, Hartman number, Prandtl number, Weissenberg number, thermal radiative heat flux, Biot number, elasticity variables and Froude number are graphically discussed. The obtained outcome shows that the velocity field increases against higher values of elasticity variables but velocity the material decays through higher fluid parameter. Temperature field declines through higher Hartman number. Furthermore, it is also examined that the heat transfer rate decays against rising Hartman number. CONCLUSIONS: The impact of complaint walls on radiative peristaltic transport of Johnson-Segalman liquid in symmetric channel subject to inclined angle. The influence of Johnson-Segalman variable on the velocity field shows decreasing behavior. Velocity also declines against larger Hartman number. Temperature and heat transfer rate boosts through rising values of E1 E2 while decays versus larger E3. Furthermore, reduction in heat transfer coefficient is observed when the values of α and Br are increased.

Effects of dietary supplementation of mannan-oligosaccharide on virus shedding in avian influenza (H9N2) challenged broilers.

Avian influenza (AI) is a highly contagious disease causing significant economic losses worldwide. The aim of this study is to evaluate the effect of mannan-oligosaccharide (MOS) on tracheal and cloacal virus shedding in AI challenged broilers and contamination of environment with H9N2. A total of 300 1-day-old-broiler chicks were randomly divided into 3 groups (A, B and C) and supplemented 0.2, 0.5 and 0.0% MOS, respectively in NRC recommended diet for 36 days. On day 21 the groups were further split into two sub groups A+ve, A-ve, B+ve, B-ve, C+ve and C-ve with 5 replicates each. The positive groups were shifted to remote sheds and were challenged intranasally with 0.1 ml of reference virus (AIV; Pk-UDL/01/08 H9N2) with EID50 = 10-6.66. Treatment reduces (P<0.05) cloacal virus shedding from day 24 to 26 and 28 to 32. Tracheal virus shedding was lower (P<0.05) on days 25-26 and 28-30 in treatment groups. Day 27 showed highest (P>0.05) virus shedding in all groups. However the reduction of viral shedding is faster in treatment groups and showed no virus shedding on day 32. Maternal antibody titer against AI showed a declining pattern but MOS influenced (P<0.05) the titer in treated groups. Hence the use of MOS may constitute a novel and effective plausible alternative that reduces the spread of disease by decreasing virus shedding and contamination of environment from AIV (H9N2) infection in poultry.

Does knowledge about bloodborne pathogens influence the reuse of medical injection syringes among women in Pakistan?

Injections with re-used syringes have been identified as a major risk factor for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in Pakistan. We analyzed data from the 2006-2007 Pakistan Demographic Health Survey (PDHS) to describe the distribution of injections administered with newly opened syringes and assessed the association of knowledge about bloodborne pathogens with syringe reuse in Pakistan. In the PDHS, women aged 12-49 years were enrolled through a multistage stratified cluster-sampling strategy across Pakistan. Approximately 10,000 women were interviewed to collect information regarding receiving injections, the use of syringes taken out of new unopened packages for their last injections, and knowledge regarding the transmission of Human Immunodeficiency Virus (HIV), HBV and HCV through the re-use of syringes and transfusion of unscreened blood. Of the 5126/10,023 women who provided information concerning their last injection, 4342 (86%) received this injection with a new syringe taken out of an unopened package. The proportion of injections received with a new syringe increased with the education level, wealth, HIV knowledge and knowledge about HCV/HBV transmission through the re-use of syringes. In the multivariable model, respondents in the 4th (adjusted odds ratio (AOR): 2.1, 95%CI: 1.4-3.0) and 5th (AOR: 2.4, 95%CI: 1.6-3.5) wealth quintiles, with some education (AOR: 1.4, 95%CI: 1.1-1.9), those in the 4th quartile of the HIV knowledge score (AOR: 1.5, 95%CI: 1.1-2.0), and those with the knowledge that a new syringe protects against HCV/HBV and HIV (AOR: 2.3, 95%CI: 1.5-3.5) were more likely to receive injections with a newly opened syringe. The patients' knowledge regarding the transmission of bloodborne pathogens is an important factor in receiving injections with a new syringe.