Targeted Drug Delivery of Magnetic Nano-Particle in the Specific Lung Region

Aerosolized drug inhalation plays an important role in the treatment of respiratory diseases. All of the published in silico, in vivo, and in vitro studies have improved the knowledge of aerosol delivery in the human respiratory system. However, aerosolized magnetic nano-particle (MNP) transport and deposition (TD) for the specific position of the human lung are still unavailable in the literature. Therefore, this study is aimed to provide an understanding of the magnetic nano-particle TD in the targeted region by imposing an external magnetic field for the development of future therapeutics. Uniform aerosolized nano-particle TD in the specific position of the lung airways will be modelled by adopting turbulence k–ω low Reynolds number simulation. The Euler–Lagrange (E–L) approach and the magneto hydrodynamics (MHD) model are incorporated in the ANSYS fluent (18.0) solver to investigate the targeted nano-particle TD. The human physical activity conditions of sleeping, resting, light activity and fast breathing are considered in this study. The aerosolized drug particles are navigated to the targeted position under the influence of external magnetic force (EMF), which is applied in two different positions of the two-generation lung airways. A numerical particle tracing model is also developed to predict the magnetic drug targeting behavior in the lung. The numerical results reveal that nano-particle deposition efficiency (DE) in two different magnetic field position is different for various physical activities, which could be helpful for targeted drug delivery to a specific region of the lung after extensive clinical trials. This process will also be cost-effective and will minimize unwanted side effects due to systemic drug distribution in the lung.</jats:p

Transcriptional analysis of temporal gene expression in germinating Clostridium difficile 630 endospores.

Clostridium difficile is the leading cause of hospital acquired diarrhoea in industrialised countries. Under conditions that are not favourable for growth, the pathogen produces metabolically dormant endospores via asymmetric cell division. These are extremely resistant to both chemical and physical stress and provide the mechanism by which C. difficile can evade the potentially fatal consequences of exposure to heat, oxygen, alcohol, and certain disinfectants. Spores are the primary infective agent and must germinate to allow for vegetative cell growth and toxin production. While spore germination in Bacillus is well understood, little is known about C. difficile germination and outgrowth. Here we use genome-wide transcriptional analysis to elucidate the temporal gene expression patterns in C. difficile 630 endospore germination. We have optimized methods for large scale production and purification of spores. The germination characteristics of purified spores have been characterized and RNA extraction protocols have been optimized. Gene expression was highly dynamic during germination and outgrowth, and was found to involve a large number of genes. Using this genome-wide, microarray approach we have identified 511 genes that are significantly up- or down-regulated during C. difficile germination (p≤0.01). A number of functional groups of genes appeared to be co-regulated. These included transport, protein synthesis and secretion, motility and chemotaxis as well as cell wall biogenesis. These data give insight into how C. difficile re-establishes its metabolism, re-builds the basic structures of the vegetative cell and resumes growth

Opportunities for improved cardiovascular disease prevention in oncology patients

PURPOSE OF REVIEW: Cancer patients often have cardiovascular risk factors at the time of cancer diagnosis, which are known to increase the risk of cardiotoxicity. Cancer survivors have significantly higher cardiovascular risk. Current cardiovascular disease prevention guidelines are based on studies that largely excluded these patients. We reviewed recent data regarding cardiovascular disease prevention in this population. RECENT FINDINGS: Nonpharmacologic therapies aiming to reduce 'lifestyle toxicity' produced by cancer treatments have demonstrated potential to decrease the incidence of adverse outcomes. Exercise before, during and after cancer treatment not only promotes higher quality of life and cardiorespiratory fitness but also reduces adverse cardiovascular outcomes. Lipid and cardiometabolic disease management is paramount but predominantly based on data that excludes these populations of cancer patients and survivors. SUMMARY: A comprehensive approach including medical evaluation, prescriptive exercise, cardiac risk factor modification, education, counseling, pharmacologic and behavioral interventions are needed in cancer patients. These interventions constitute the core of cardio-oncology rehabilitation programs, which if implemented appropriately may help reduce cardiovascular events in this population. Knowledge gaps in these areas are starting to be addressed by ongoing clinical trials

Constraining Bosonic Supersymmetry from Higgs results and 8 TeV ATLAS multi-jets plus missing energy data

The collider phenomenology of models with Universal Extra Dimensions (UED) is surprisingly similar to that of supersymmetric (SUSY) scenarios. For each level-1 bosonic (fermionic) Kaluza-Klein (KK) state, there is a fermionic (bosonic) analog in SUSY and thus UED scenarios are often known as bosonic supersymmetry. The minimal version of UED (mUED) gives rise to a quasi-degenerate particle spectrum at each KK-level and thus, can not explain the enhanced Higgs to diphoton decay rate hinted by the ATLAS collaboration of the Large Hadron Collider (LHC) experiment. However, in the non-minimal version of the UED (nmUED) model, the enhanced Higgs to diphoton decay rate can be easily explained via the suitable choice of boundary localized kinetic (BLK) terms for higher dimensional fermions and gauge bosons. BLK terms remove the degeneracy in the KK mass spectrum and thus, pair production of level-1 quarks and gluons at the LHC gives rise to hard jets, leptons and large missing energy in the final state. These final states are studied in details by the ATLAS and CMS collaborations in the context of SUSY scenarios. We find that the absence of any significant deviation of the data from the Standard Model (SM) prediction puts a lower bound of about 2.1 TeV on equal mass excited quarks and gluons.Comment: 19 page

Mutation detection analysis of a region of 16S-like ribosomal RNA gene of Entamoeba histolytica, Entamoeba dispar and Entamoeba moshkovskii

<p>Abstract</p> <p>Background</p> <p>The level of intra-species genetic variation in <it>Entamoeba histolytica, Entamoeba dispar </it>and <it>Entamoeba moshkovskii </it>populations in a localized geographic area, like Puducherry, India, remains unknown.</p> <p>Methods</p> <p>In the present study the existence of genetic variation in the nested multiplex polymerase chain reaction (NM-PCR) amplified region of the 16S-like ribosomal RNA genes of <it>E. histolytica, E. dispar </it>and <it>E. moshkovskii </it>was investigated by riboprinting and single strand conformation polymorphism (SSCP) analysis.</p> <p>Results</p> <p>We found that 70 stool specimens were positive for <it>E. histolytica</it>, 171 stool specimens were positive for <it>E. dispar</it>, and 37 stool specimens were positive for <it>E. moshkovskii </it>by NM-PCR. Ninety liver abscess pus specimens, 21 urine specimens, and 8 saliva specimens were positive for <it>E. histolytica </it>by NM-PCR. Riboprinting analysis detected a mutation in the PCR product of only one <it>E. histolytica </it>isolate from a stool specimen. However, SSCP analysis detected mutations in the PCR products of five <it>E. histolytica </it>isolates and three <it>E. moshkovskii </it>isolates from stool specimens, and one <it>E. histolytica </it>isolate from a saliva specimen. The mutations detected by riboprinting and SSCP analysis were confirmed by sequencing. All the nucleotide sequences showing mutations in this study have already been deposited into the NCBI GenBank database under accession numbers [GenBank: <ext-link ext-link-type="gen" ext-link-id="EF682200">EF682200</ext-link> to GenBank: <ext-link ext-link-type="gen" ext-link-id="EF682208">EF682208</ext-link>].</p> <p>Conclusion</p> <p>The present study has revealed the subsistence of mutations in the ribosomal RNA genes of <it>E. histolytica </it>and <it>E. moshkovskii</it>, which points towards the existence of intra-species genetic variation in <it>E. histolytica </it>and <it>E. moshkovskii </it>isolates infecting humans.</p

Search for electromagnetic properties of the neutrinos at the LHC

Exclusive production of neutrinos via photon-photon fusion provides an excellent opportunity to probe electromagnetic properties of the neutrinos at the LHC. We explore the potential of processes pp-> p gamma gamma p -> p nu anti-nu p and pp -> p gamma gamma p -> p nu anti-nu Z p to probe neutrino-photon and neutrino-two photon couplings. We show that these reactions provide more than seven orders of magnitude improvement in neutrino-two photon couplings compared to LEP limits.Comment: 11 pages, 4 tables, New backgrounds have been adde

Working Group Report: Heavy-Ion Physics and Quark-Gluon Plasma

This is the report of Heavy Ion Physics and Quark-Gluon Plasma at WHEPP-09 which was part of Working Group-4. Discussion and work on some aspects of Quark-Gluon Plasma believed to have created in heavy-ion collisions and in early universe are reported.Comment: 20 pages, 6 eps figures, Heavy-ion physics and QGP activity report in "IX Workshop on High Energy Physics Phenomenology (WHEPP-09)" held in Institute of Physics, Bhubaneswar, India, during January 3-14, 2006. To be published in PRAMANA - Journal of Physics (Indian Academy of Science

Motion and Flexibility in Human Cytochrome P450 Aromatase

The crystal structures of human placental aromatase in complex with the substrate androstenedione and exemestane have revealed an androgen-specific active site and the structural basis for higher order organization. However, X-ray structures do not provide accounts of movements due to short-range fluctuations, ligand binding and protein-protein association. In this work, we conduct normal mode analysis (NMA) revealing the intrinsic fluctuations of aromatase, deduce the internal modes in membrane-free and membrane-integrated monomers as well as the intermolecular modes in oligomers, and propose a quaternary organization for the endoplasmic reticulum (ER) membrane integration. Dynamics of the crystallographic oligomers from NMA is found to be in agreement with the isotropic thermal factors from the X-ray analysis. Calculations of the root mean square fluctuations of the C-alpha atoms from their equilibrium positions confirm that the rigid-core structure of aromatase is intrinsic regardless of the changes in steroid binding interactions, and that aromatase self-association does not deteriorate the rigidity of the catalytic cleft. Furthermore, NMA on membrane-integrated aromatase shows that the internal modes in all likelihood contribute to breathing of the active site access channel. The collective intermolecular hinge bending and twisting modes provide the flexibility in the quaternary association necessary for membrane integration of the aromatase oligomers. Taken together, fluctuations of the active site, the access channel, and the heme-proximal cavity, and a dynamic quaternary organization could all be essential components of the functional aromatase in its role as an ER membrane-embedded steroidogenic enzyme

Nanostructured 3D Constructs Based on Chitosan and Chondroitin Sulphate Multilayers for Cartilage Tissue Engineering

Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and chondroitin sulphate (CS) on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH). The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA) showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs) up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM) formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs

Epiploic appendagitis – clinical characteristics of an uncommon surgical diagnosis

<p>Abstract</p> <p>Background</p> <p>Epiploic appendagitis (EA) is a rare cause of focal abdominal pain in otherwise healthy patients with mild or absent secondary signs of abdominal pathology. It can mimick diverticulitis or appendicitis on clinical exam. The diagnosis of EA is very infrequent, due in part to low or absent awareness among general surgeons. The objective of this work was to review the authors' experience and describe the clinical presentation of EA.</p> <p>Methods</p> <p>All patients diagnosed with EA between January 2004 and December 2006 at an urban surgical emergency room were retrospectively reviewed by two authors in order to share the authors' experience with this rare diagnosis. The operations were performed by two surgeons. Pathological examinations of specimens were performed by a single pathologist. A review of clinical presentation is additionally undertaken.</p> <p>Results</p> <p>Ten patients (3 females and 7 males, average age: 44.6 years, range: 27–76 years) were diagnosed with symptomatic EA. Abdominal pain was the leading symptom, the pain being localized in the left (8 patients, 80 %) and right (2 patients, 20%) lower quadrant. All patients were afebrile, and with the exception of one patient, nausea, vomiting, and diarrhea were not present. CRP was slightly increased (mean: 1.2 mg/DL) in three patients (33%). Computed tomography findings specific for EA were present in five patients. Treatment was laparoscopic excision (n = 8), excision via conventional laparotomy (n = 1) and conservative therapy (n = 1).</p> <p>Conclusion</p> <p>In patients with localized, sharp, acute abdominal pain not associated with other symptoms such as nausea, vomiting, fever or atypical laboratory values, the diagnosis of EA should be considered. Although infrequent up to date, with the increase of primary abdominal CT scans and ultrasound EA may well be diagnosed more frequently in the future.</p