Novel multifunctional nanoliposomes inhibit a-synuclein fibrillization, attenuate microglial activation, and silence the expression of SNCA gene / Nuevos nanoliposomas multifuncionales inhiben la fibrilización de la a-sinucleína, atenúan la activación de la microglía y silencian la expresión de SNCA

Introduction: The aim of this study was to compare the effect of five types of PEGlated nanoliposomes (PNLs) on α-synuclein (α-syn) fibrillization, attenuation of microglial activation, and silence of the SNCA gene, which encodes α-syn. Methods: To evaluate the inhibition of α-syn fibrillization, we used standard in vitro assay based on Thioflavin T (ThT) fluorescence. Next, to evaluate the attenuation of microglial activation, the concentration of TNF-a and IL-6 was quantified by ELISA assay in BV2 microglia cells treated with 100 nM A53T α-syn and PNLs. In order to determine the silencing of the SNCA, real-time PCR and Western blot analysis was used. Finally, the efficacy of PNLs was confirmed in a transgenic mouse model expressing human α-syn.Results: ThT assay showed both PNL1 and PNL2 significantly inhibited a-syn fibrillization. ELISA test also showed the production of TNF-a and IL-6 was significantly attenuated when microglial cells treated with PNL1 or PNL2. We also found that SNCA gene, at both mRNA and protein levels, was significantly silenced when BV2 microglia cells were treated with PNL1 or PNL2. Importantly, the efficacy of PNL1 and PNL2 was finally confirmed in vivo in a transgenic mouse model. Conclusions: In conclusion, the novel multifunctional nanoliposomes tested in our study inhibit α-syn fibrillization, attenuate microglial activation, and silence SNCA gene. Our findings suggest the therapeutic potential of PNL1 and PNL2 for treating synucleinopathies.(AU)

Introducción: El objetivo de este estudio fue comparar el efecto de cinco tipos de nanoliposomas PEGlados (PNL) sobre la fibrilización de la α-sinucleína (α-syn), la atenuación de la activación microglial y el silencio del gen synuclein alpha (SNCA), que codifica α-syn. Métodos: Para evaluar la inhibición de la fibrilización α-syn, utilizamos un ensayo in vitro estándar basado en la fluorescencia de la tioflavina T (ThT). A continuación, para evaluar la atenuación de la activación microglial, se cuantificó la concentración de factor de necrosis tumoral alpha (TNF-a) e interleucina 6 (IL-6)mediante ensayo ELISA en células de microglía BV2 tratadas con 100 nM de α-syn de A53T y PNL. Para determinar el silenciamiento del SNCA, se utilizó reacción en cadena de la polimerasa (PCR) en tiempo real y análisis de Western blot. Finalmente, la eficacia de las PNL se confirmó en un modelo de ratón transgénico que expresa α-syn humana. Resultados: El ensayo ThT mostró que tanto PNL1 como PNL2 inhibieron significativamente la fibrilización de α-syn. La prueba enzyme-linked immunosorbent assay (ELISA) también mostró que la producción de TNF-a e IL-6 se atenuó significativamente cuando las células microgliales se trataron con PNL1 o PNL2. También encontramos que el gen SNCA, tanto a nivel de ARN mensajero (ARNm) como de proteína, se silenciaba significativamente cuando las células de microglía BV2 se trataban con PNL1 o PNL2. Es importante destacar que la eficacia de PNL1 y PNL2 finalmente se confirmó in vivo en un modelo de ratón transgénico.Conclusiones: Los nuevos nanoliposomas multifuncionales probados en nuestro estudio inhiben la fibrilización α-syn, atenúan la activación microglial y silencian el gen SNCA. Nuestros hallazgos sugieren el potencial terapéutico de PNL1 y PNL2 para el tratamiento de sinucleinopatías.(AU)

Novel multifunctional nanoliposomes inhibit α-synuclein fibrillization, attenuate microglial activation, and silence the expression of SNCA gene.

INTRODUCTION: The aim of this study was to compare the effect of five types of PEGlated nanoliposomes (PNLs) on α-synuclein (α-syn) fibrillization, attenuation of microglial activation, and silence of the SNCA gene, which encodes α-syn. METHODS: To evaluate the inhibition of α-syn fibrillization, we used standard in vitro assay based on Thioflavin T (ThT) fluorescence. Next, to evaluate the attenuation of microglial activation, the concentration of TNF-a and IL-6 was quantified by ELISA assay in BV2 microglia cells treated with 100nM A53T α-syn and PNLs. In order to determine the silencing of the SNCA, real-time PCR and Western blot analysis was used. Finally, the efficacy of PNLs was confirmed in a transgenic mouse model expressing human α-syn. RESULTS: ThT assay showed both PNL1 and PNL2 significantly inhibited a-syn fibrillization. ELISA test also showed the production of TNF-a and IL-6 was significantly attenuated when microglial cells treated with PNL1 or PNL2. We also found that SNCA gene, at both mRNA and protein levels, was significantly silenced when BV2 microglia cells were treated with PNL1 or PNL2. Importantly, the efficacy of PNL1 and PNL2 was finally confirmed in vivo in a transgenic mouse model. CONCLUSIONS: In conclusion, the novel multifunctional nanoliposomes tested in our study inhibit α-syn fibrillization, attenuate microglial activation, and silence SNCA gene. Our findings suggest the therapeutic potential of PNL1 and PNL2 for treating synucleinopathies.

Alcohol Dependence Modulates Amygdalar mTORC2 and PKCε Expression in a Rodent Model.

Multiple alcohol use disorder (AUD)-related behavioral alterations are governed by protein kinase C epsilon (PKCε), particularly in the amygdala. Protein kinase C (PKC) is readily phosphorylated at Ser729 before activation by the mTORC2 protein complex. In keeping with this, the current study was conducted to assess the variations in mTORC2 and PKCε during different ethanol exposure stages. The following groups of rats were employed: control, acute, chronic, ethanol withdrawal (EW), and EW + ethanol (EtOH). Ethanol-containing and non-ethanol-containing modified liquid diets (MLDs) were administered for 27 days. On day 28, either saline or ethanol (2.5 g/kg, 20% v/v) was intraperitoneally administered, followed by bilateral amygdala extraction. PKCε mRNA levels were noticeably increased in the amygdala of the EW + EtOH and EW groups. Following chronic ethanol consumption, the stress-activated map kinase-interacting protein 1 (Sin1) gene expression was markedly decreased. In the EW, EW + EtOH, and chronic ethanol groups, there was a profound increase in the protein expression of mTOR, Sin1, PKCε, and phosphorylated PKCε (Ser729). The PKCε gene and protein expressions showed a statistically significant moderate association, according to a correlation analysis. Our results suggest that an elevated PKCε protein expression in the amygdala during EW and EW + EtOH occurred at the transcriptional level. However, an elevation in the PKCε protein expression, but not its mRNA, after chronic ethanol intake warrants further investigation to fully understand the signaling pathways during different episodes of AUD.

Numerical Simulation of Hybrid Nanofluid Mixed Convection in a Lid-Driven Square Cavity with Magnetic Field Using High-Order Compact Scheme.

In this study, the energy transference of a hybrid Al2O3-Cu-H2O nanosuspension within a lid-driven heated square chamber is simulated. The domain is affected by a horizontal magnetic field. The vertical sidewalls are insulated and the horizontal borders of the chamber are held at different fixed temperatures. A fourth-order accuracy compact method is applied to work out the vorticity-stream function view of incompressible Oberbeck-Boussinesq equations. The method used is validated against previous numerical and experimental works and good agreement is shown. The flow patterns, Nusselt numbers, and velocity profiles are studied for different Richardson numbers, Hartmann numbers, and the solid volume fraction of hybrid nanoparticles. Flow field and heat convection are highly affected by the magnetic field and volume fraction of each type of nanoparticles in a hybrid nanofluid. The results show an improvement of heat transfer using nanoparticles. To achieve a higher heat transmission rate by using the hybrid nanofluid, flow parameters like Richardson number and Hartmann number should be considered.

Alcohol Use Disorder, Neurodegeneration, Alzheimer's and Parkinson's Disease: Interplay Between Oxidative Stress, Neuroimmune Response and Excitotoxicity.

Alcohol use disorder (AUD) has been associated with neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Prolonged excessive alcohol intake contributes to increased production of reactive oxygen species that triggers neuroimmune response and cellular apoptosis and necrosis via lipid peroxidation, mitochondrial, protein or DNA damage. Long term binge alcohol consumption also upregulates glutamate receptors, glucocorticoids and reduces reuptake of glutamate in the central nervous system, resulting in glutamate excitotoxicity, and eventually mitochondrial injury and cell death. In this review, we delineate the following principles in alcohol-induced neurodegeneration: (1) alcohol-induced oxidative stress, (2) neuroimmune response toward increased oxidants and lipopolysaccharide, (3) glutamate excitotoxicity and cell injury, and (4) interplay between oxidative stress, neuroimmune response and excitotoxicity leading to neurodegeneration and (5) potential chronic alcohol intake-induced development of neurodegenerative diseases, including Alzheimer's and Parkinson's disease.

mTORC and PKCε in Regulation of Alcohol Use Disorder.

Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.

Ethanol-Induced Changes in PKCε: From Cell to Behavior.

The long-term binge intake of ethanol causes neuroadaptive changes that lead to drinkers requiring higher amounts of ethanol to experience its effects. This neuroadaptation can be partly attributed to the modulation of numerous neurotransmitter receptors by the various protein kinases C (PKCs). PKCs are enzymes that control cellular activities by regulating other proteins via phosphorylation. Among the various isoforms of PKC, PKCε is the most implicated in ethanol-induced biochemical and behavioral changes. Ethanol exposure causes changes to PKCε expression and localization in various brain regions that mediate addiction-favoring plasticity. Ethanol works in conjunction with numerous upstream kinases and second messenger activators to affect cellular PKCε expression. Chauffeur proteins, such as receptors for activated C kinase (RACKs), cause the translocation of PKCε to aberrant sites and mediate ethanol-induced changes. In this article, we aim to review the following: the general structure and function of PKCε, ethanol-induced changes in PKCε expression, the regulation of ethanol-induced PKCε activities in DAG-dependent and DAG-independent environments, the mechanisms underlying PKCε-RACKε translocation in the presence of ethanol, and the existing literature on the role of PKCε in ethanol-induced neurobehavioral changes, with the goal of creating a working model upon which further research can build.

Addressing tuberculosis control in fragile states: Urban DOTS experience in Kabul, Afghanistan, 2009-2015.

Tuberculosis (TB) is a major public health problem in Afghanistan, but experience in implementing effective strategies to prevent and control TB in urban areas and conflict zones is limited. This study shares programmatic experience in implementing DOTS in the large city of Kabul. We analyzed data from the 2009-2015 reports of the National TB Program (NTP) for Kabul City and calculated treatment outcomes and progress in case notification using rates, ratios, and confidence interval. Urban DOTS was implemented by the NTP in partnership with United States Agency for International Development (USAID)-funded TB projects, the World Health Organization (WHO), and the private sector. Between 2009 and 2015, the number of DOTS-providing centers in Kabul increased from 22 to 85. In total, 24,619 TB patients were enrolled in TB treatment during this period. The case notification rate for all forms of TB increased from 59 per 100,000 population to 125 per 100,000. The case notification rate per 100,000 population for sputum-smear-positive TB increased from 25 to 33. The treatment success rate for all forms of TB increased from 31% to 67% and from 47% to 77% for sputum-smear-positive TB cases. The treatment success rate for private health facilities increased from 52% in 2010 to 80% in 2015. In 2013, contact screening was introduced, and the TB yield was 723 per 100,000-more than two times higher than the estimated national prevalence of 340 per 100,000. Contact screening contributed to identifying 2,509 child contacts of people with TB, and 76% of those children received isoniazid preventive therapy. The comprehensive urban DOTS program significantly improved service accessibility, TB case finding, and treatment outcomes in Kabul. Public- and private-sector involvement also improved treatment outcomes; however, the treatment success rate remains higher in private health facilities. While the treatment success rate increased significantly, it remains lower than the national average, and more efforts are needed to improve treatment outcomes in Kabul. We recommend that the urban DOTS approach be replicated in other countries and cities in Afghanistan with settings similar to Kabul.

Generalized Magnetic Field Effects in Burgers' Nanofluid Model.

Analysis has been conducted to present the generalized magnetic field effects on the flow of a Burgers' nanofluid over an inclined wall. Mathematical modelling for hydro-magnetics reveals that the term "[Formula: see text]" is for the Newtonian model whereas the generalized magnetic field term (as mentioned in Eq 4) is for the Burgers' model which is incorporated in the current analysis to get the real insight of the problem for hydro-magnetics. Brownian motion and thermophoresis phenomenon are presented to analyze the nanofluidics for the non-Newtonian fluid. Mathematical analysis is completed in the presence of non-uniform heat generation/absorption. The constructed set of partial differential system is converted into coupled nonlinear ordinary differential system by employing the suitable transformations. Homotopy approach is employed to construct the analytical solutions which are shown graphically for sundr5y parameters including Deborah numbers, magnetic field, thermophoresis, Brownian motion and non-uniform heat generation/absorption. A comparative study is also presented showing the comparison of present results with an already published data.

Synthesis and characterization of Fe3O4-PEG-LAC-chitosan-PEI nanoparticle as a survivin siRNA delivery system.

The limited effectiveness of the conventional methods for cancer treatment makes the researchers to find novel safe and effective therapeutic strategies. One of these strategies is to use small interfering RNAs (siRNAs). A major challenge here is the siRNA delivery into the cells. The purpose of this study was to design and prepare a biocompatible, biodegradable, and safe nanosized particle for siRNA delivery into human breast cancer MCF-7 and leukemia K562 cells. Chemically synthesized magnetic nanoparticles containing polyethyleneglycol-lactate polymer (PEG-LAC), chitosan, and polyethyleneimine (PEI) were successfully prepared and used as a gene delivery vehicle. The nanoparticles were characterized by Fourier transform infrared spectroscopy and zeta potential. The Fe3O4-PEG-LAC-chitosan-PEI nanoparticle showed efficient and stable survivin siRNA loading in gel retardation assay. The cytotoxicity of the prepared nanoparticle was studied using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and was compared with that of mitoxantrone (MTX) in combination with the prepared siRNA delivery system to evaluate the possible synergic effect of MTX and survivin siRNA. The nanoparticles with and without noncomplementary siRNA showed low toxicity against both cell lines; however, a twofold decrease was observed in cell survival percent after MTX addition to MCF-7 cells treated with either nanoparticle itself or complexed with noncomplementary siRNA. While survivin siRNA nanoplex caused threefold decrease in the cell survival percent, its combination with MTX did not result in a significant increase in the cytotoxic effect. Therefore, Fe3O4-PEG-LAC-chitosan-PEI nanoparticle should be considered as a potential carrier for enhanced survivin siRNA delivery into MCF-7 and K562 cells.

Speed-up hyperspheres homotopic path tracking algorithm for PWL circuits simulations.

In the present work, we introduce an improved version of the hyperspheres path tracking method adapted for piecewise linear (PWL) circuits. This enhanced version takes advantage of the PWL characteristics from the homotopic curve, achieving faster path tracking and improving the performance of the homotopy continuation method (HCM). Faster computing time allows the study of complex circuits with higher complexity; the proposed method also decrease, significantly, the probability of having a diverging problem when using the Newton-Raphson method because it is applied just twice per linear region on the homotopic path. Equilibrium equations of the studied circuits are obtained applying the modified nodal analysis; this method allows to propose an algorithm for nonlinear circuit analysis. Besides, a starting point criteria is proposed to obtain better performance of the HCM and a technique for avoiding the reversion phenomenon is also proposed. To prove the efficiency of the path tracking method, several cases study with bipolar (BJT) and CMOS transistors are provided. Simulation results show that the proposed approach can be up to twelve times faster than the original path tracking method and also helps to avoid several reversion cases that appears when original hyperspheres path tracking scheme was employed.

Laplace transform homotopy perturbation method for the approximation of variational problems.

This article proposes the application of Laplace Transform-Homotopy Perturbation Method and some of its modifications in order to find analytical approximate solutions for the linear and nonlinear differential equations which arise from some variational problems. As case study we will solve four ordinary differential equations, and we will show that the proposed solutions have good accuracy, even we will obtain an exact solution. In the sequel, we will see that the square residual error for the approximate solutions, belongs to the interval [0.001918936920, 0.06334882582], which confirms the accuracy of the proposed methods, taking into account the complexity and difficulty of variational problems.

Control of ammonia and urea emissions from urea manufacturing facilities of Petrochemical Industries Company (PIC), Kuwait.

UNLABELLED: Petrochemical Industries Company (PIC) in Kuwait has mitigated the pollution problem of ammonia and urea dust by replacing the melting and prilling units of finished-product urea prills with an environmentally friendly granulation process. PIC has financed a research project conducted by the Coastal and Air Pollution Program's research staff at the Kuwait Institute for Scientific Research to assess the impact of pollution control strategies implemented to maintain a healthy productive environment in and around the manufacturing premises. The project was completed in three phases: the first phase included the pollution monitoring of the melting and prilling units in full operation, the second phase covered the complete shutdown period where production was halted completely and granulation units were installed, and the last phase encompassed the current modified status with granulation units in full operation. There was substantial decrease in ammonia emissions, about 72%, and a 52.7% decrease in urea emissions with the present upgrading of old melting and prilling units to a state-of-the-art technology "granulation process" for a final finished product. The other pollutants, sulfur dioxide (SO2), nitrogen oxides (NOx), and volatile organic compounds (VOCs), have not shown any significant change, as the present modification has not affected the sources of these pollutants. IMPLICATIONS: Petrochemical Industries Company (PIC) in Kuwait has ammonia urea industries, and there were complaints about ammonia and urea dust pollution. PIC has resolved this problem by replacing "melting and prilling unit" of final product urea prills by more environmentally friendly "granulation unit." Environmental Pollution and Climate Program has been assigned the duty of assessing the outcome of this change and how that influenced ammonia and urea dust emissions from the urea manufacturing plant.

An ultra-sensitive impedimetric immunosensor for detection of the serum oncomarker CA-125 in ovarian cancer patients.

Effective treatment of ovarian cancer depends upon the early detection of the malignancy. Here, we report on the development of a new nanostructured immunosensor for early detection of cancer antigen 125 (CA-125). A gold electrode was modified with mercaptopropionic acid (MPA), and then consecutively conjugated with silica coated gold nanoparticles (AuNP@SiO2), CdSe quantum dots (QDs) and anti-CA-125 monoclonal antibody (mAb). The engineered MPA|AuNP@SiO2|QD|mAb immunosensor was characterised using transmission electron microscopy (TEM), atomic force microscopy (AFM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Successive conjugation of AuNP@SiO2, CdSe QD and anti-CA-125 mAb onto the gold electrode resulted in sensitive detection of CA-125 with a limit of detection (LOD) of 0.0016 U mL(-1) and a linear detection range (LDR) of 0-0.1 U mL(-1). Based on the high sensitivity and specificity of the immunosensor, we propose this highly stable and reproducible biosensor for the early detection of CA-125.

Decreasing global transcript levels over time suggest that phytoplasma cells enter stationary phase during plant and insect colonization.

To highlight different transcriptional behaviors of the phytoplasma in the plant and animal host, expression of 14 genes of "Candidatus Phytoplasma asteris," chrysanthemum yellows strain, was investigated at different times following the infection of a plant host (Arabidopsis thaliana) and two insect vector species (Macrosteles quadripunctulatus and Euscelidius variegatus). Target genes were selected among those encoding antigenic membrane proteins, membrane transporters, secreted proteins, and general enzymes. Transcripts were detected for all analyzed genes in the three hosts; in particular, those encoding the antigenic membrane protein Amp, elements of the mechanosensitive channel, and two of the four secreted proteins (SAP54 and TENGU) were highly accumulated, suggesting that they play important roles in phytoplasma physiology during the infection cycle. Most transcripts were present at higher abundance in the plant host than in the insect hosts. Generally, transcript levels of the selected genes decreased significantly during infection of A. thaliana and M. quadripunctulatus but were more constant in E. variegatus. Such decreases may be explained by the fact that only a fraction of the phytoplasma population was transcribing, while the remaining part was aging to a stationary phase. This strategy might improve long-term survival, thereby increasing the likelihood that the pathogen may be acquired by a vector and/or inoculated to a healthy plant.

Software defined networking (SDN) over space division multiplexing (SDM) optical networks: features, benefits and experimental demonstration.

We present results from the first demonstration of a fully integrated SDN-controlled bandwidth-flexible and programmable SDM optical network utilizing sliceable self-homodyne spatial superchannels to support dynamic bandwidth and QoT provisioning, infrastructure slicing and isolation. Results show that SDN is a suitable control plane solution for the high-capacity flexible SDM network. It is able to provision end-to-end bandwidth and QoT requests according to user requirements, considering the unique characteristics of the underlying SDM infrastructure.

On the Application of Homotopy Perturbation Method for Solving Systems of Linear Equations.

The application of homotopy perturbation method (HPM) for solving systems of linear equations is further discussed and focused on a method for choosing an auxiliary matrix to improve the rate of convergence. Moreover, solving of convection-diffusion equations has been developed by HPM and the convergence properties of the proposed method have been analyzed in detail; the obtained results are compared with some other methods in the frame of HPM. Numerical experiment shows a good improvement on the convergence rate and the efficiency of this method.

Semi-computational simulation of magneto-hemodynamic flow in a semi-porous channel using optimal homotopy and differential transform methods.

In this paper, the semi-numerical techniques known as the optimal homotopy analysis method (HAM) and Differential Transform Method (DTM) are applied to study the magneto-hemodynamic laminar viscous flow of a conducting physiological fluid in a semi-porous channel under a transverse magnetic field. The two-dimensional momentum conservation partial differential equations are reduced to ordinary form incorporating Lorentizian magnetohydrodynamic body force terms. These ordinary differential equations are solved by the homotopy analysis method, the differential transform method and also a numerical method (fourth-order Runge-Kutta quadrature with a shooting method), under physically realistic boundary conditions. The homotopy analysis method contains the auxiliary parameter ℏ, which provides us with a simple way to adjust and control the convergence region of solution series. The differential transform method (DTM) does not require an auxiliary parameter and is employed to compute an approximation to the solution of the system of nonlinear differential equations governing the problem. The influence of Hartmann number (Ha) and transpiration Reynolds number (mass transfer parameter, Re) on the velocity profiles in the channel are studied in detail. Interesting fluid dynamic characteristics are revealed and addressed. The HAM and DTM solutions are shown to both correlate well with numerical quadrature solutions, testifying to the accuracy of both HAM and DTM in nonlinear magneto-hemodynamics problems. Both these semi-numerical techniques hold excellent potential in modeling nonlinear viscous flows in biological systems.

Differential transform semi-numerical analysis of biofluid-particle suspension flow and heat transfer in non-Darcian porous media.

The differential transform method (DTM) is semi-numerical method which is used to study the steady, laminar buoyancy-driven convection heat transfer of a particulate biofluid suspension in a channel containing a porous material. A two-phase continuum model is used. A set of variables is implemented to reduce the ordinary differential equations for momentum and energy conservation (for both phases) to a dimensionless system. DTM solutions are obtained for the dimensionless system under appropriate boundary conditions. We examine the influence of momentum inverse Stokes number (Skm), Darcy number (Da), Forchheimer number (Fs), particle loading parameter (pL), particle-phase wall slip parameter (Ω) and buoyancy parameter (B) on the fluid-phase velocity (U) and particle-phase velocity (Up). Padé approximants are also employed to achieve satisfaction of boundary conditions. Excellent correlation is obtained between the DTM and numerical quadrature solutions. The results indicate that there is a strong decrease in fluid-phase velocities with increasing Darcian (first-order) drag and the second-order Forchheimer drag, and a weaker reduction in particle-phase velocity field. Fluid and particle-phase velocities are also strongly affected with inverse momentum Stokes number. DTM is shown to be a powerful tool providing engineers with an alternative simulation approach to other traditional methods for multi-phase computational biofluid mechanics. The model finds applications in haemotological separation and biotechnological processing.

Morgagni hernia with Down syndrome: a rare association.

We report a case of a 22-year-old male with Down syndrome and Morgagni hernia, who presented to us with complaints of cough, regurgitation and vomiting. He was successfully treated surgically and the defect was repaired with prolene mesh.