Search

The propagation of linear and nonlinear electrostatic waves is investigated in magnetized dusty plasma with stationary negatively or positively charged dust, cold mobile ions and non-extensive electrons. Two normal modes are predicted in the linear regime, whose characteristics are investigated parametrically, focusing on the effect of electrons non-extensivity, dust charge polarity, concentration of dust and magnetic field strength. Using the reductive perturbation technique, a Zakharov-Kuznetsov (ZK) type equation is derived which governs the dynamics of small-amplitude solitary waves in magnetized dusty plasma. The properties of the solitary wave structures are analyzed numerically with the system parameters i.e. electrons non-extensivity, concentration of dust, polarity of dust and magnetic field strength. Following Allen and Rowlands (J. Plasma Phys. 53:63, 1995), we have shown that the pulse soliton solution of the ZK equation is unstable, and have analytically traced the dependence of the instability growth rate on the nonextensive parameter $q$ for electrons, dust charge polarity and magnetic field strength. The results should be useful for understanding the nonlinear propagation of DIA solitary waves in laboratory and space plasmas.

BackgroundLong-term peritoneal dialysis (PD) is associated with distinct peritoneal structural changes characterized by thickening of the sub-mesothelial cell layer, fibrosis and angiogenesis. These changes were assumed to be the cause for peritoneal membrane dysfunction and technique failure that was observed in some long-term PD patients. However, this assumption was refuted by the findings from animal models of chronic PD that showed the exact structural phenotype of the long-term PD, and yet a normal peritoneal function. This study was set to determine that the peritoneal microvascular and interstitial changes associated with long-term PD in rats produce peritoneal dysfunction by uremia related mechanisms. Our studies have demonstrated that acute exposure of the peritoneum to glucose-based PD solutions produces rapid and sustained visceral peritoneal microvascular vasodilation via the nitric oxide (NO) pathway. At present, there is no literature data on the reactivity of these peritoneal microvessels after long-term exposure of the peritoneum to PD solutions. NO as the mediator of the peritoneal microvascular reactivity to PD solutions is also involved in angiogenesis. Angiogenesis is initiated by proliferation of endothelial cells, which penetrate into the surrounding tissue, and is tightly regulated by growth factors and inhibitors. Matrix metalloproteinases (MMPs) regulate angiogenesis, on the one hand by facilitating extracellular matrix (ECM) degradation to allow new vessel expansion, and on the other hand, by interfering with angiogenesis through the production of angiostatin. Angiostatin is generated by the proteolytic cleavage of plasminogen by MMP-2, -7, -9, and -12. Angiogenesis was observed in patient undergoing PD as proven by peritoneal biopsy studies and in animal models of chronic PD. As a possible mechanistic explanation, angiogenesis and vasodilation increase the peritoneal surface area available for exchange, for rapid dissipation of the osmotic gradient, and hence, peritoneal membrane dysfunction.MethodologyRat studies were done on old animals as typical in chronic PD models because of the time required to develop the animal model. Three animal groups were used: Group - I: Chronic PD solution infusion: Interventions included indwelling peritoneal catheter placement and daily infusion of a glucose-based clinical PD solution for one month. Group – II: Interventions included renal injury and indwelling peritoneal catheter placement: Renal injury was induced by unilateral nephrectomy and ipsilateral kidney injury by cryosurgery. Group – III: Interventions included induction of uremia and indwelling peritoneal catheter placement: Uremia was induced by 5/6 nephrectomy. In all groups, procedures for animal model development including surgery were conducted under anesthesia and according to standard aseptic techniques. Studies on each animal were conducted after complete healing of the surgical incisions. These include: 1) Peritoneal equilibration test (PET-test) to assess the peritoneal transport properties; 2) Intravital microscopy to assess the visceral peritoneal microvascular reactivity to a clinical glucose-based PD solution, and endothelial functions of these visceral peritoneal micro vessels; 3) Assess the NO pathway via immunoblotting. Endothelial nitric oxide synthase (eNOS) which releases NO was measured via western blot. eNOS is activated by serine/threonine protein kinase Akt protein and itself activates matrix metalloprotease 2 (MMP2). Akt is activated by shear stress through activation of PI3K. Protein expression of eNOS, MMP-2 and Akt was assessed.ResultsUremia caused a remarkable increase in the reactivity of the visceral peritoneal microvasculature to the dialysis solution as compared with the renal injury and the chronic infusion groups. Inversely, Uremia markedly decreased the sensitivity and reactivity of the visceral peritoneal microvasculature to the exogenous endothelium-dependent receptor-dependent Acetylcholine to indicate marked endothelial cell dysfunction. A subset of uremic animals exhibited very high net ultrafiltration which seems to correlate with a phenotype of extensive angiogenesis and uremia-induced hypertension. However, this high net ultrafiltration was not seen in any of our normotensive non-uremic animals that were subjected to indwelling peritoneal catheter placement and daily infusion of a dialysis solution for one month. Arterioles from the renal injury group reacted similarly to the arterioles from the chronic infusion animals. On the animals that showed prolific angiogenesis, expression of Akt and eNOS was elevated as compared with the animals that had kidney injury or control animals. MMP-2 showed elevated expression in animals with angiogenesis compared to animals with kidney injury. That is confirmation in molecular level that angiogenesis occurs in animals that display uremic phenotype. Control animals exhibited a significantly reduced MMP levels, indicating impaired angiogenesis process. Unlike in the naïve control animals, experimental groups demonstrated significant activation of MMP-2. In addition, Enos was found to be upregulated in the experimental groups, as compared with the naïve controls.ConclusionsFour major conclusions were drawn from this study. 1) Aging is an independent risk factor for peritoneal microvascular endothelial cell dysfunction; 2) indwelling peritoneal catheter placement compounds a pre-existing age-related endothelial cell dysfunction; 3) Uremia unlike reduction in renal mass and injury causes marked peritoneal microvascular endothelial cell dysfunction as proven by the measurement of proteins involved in the vasodilation and angiogenesis pathways; 4) Uremia unlike aging or indwelling peritoneal catheter enhances the basic permeably of the peritoneal membrane for small solute transport.

BackgroundThe X-linked inhibitor of apoptosis (XIAP) is a promising molecular target for the design of novel anticancer drugs aiming at overcoming apoptosis-resistance of cancer cells. Recent studies demonstrated that the BIR3 domain of XIAP where caspase-9 and Smac proteins bind is an attractive site for designing small-molecule inhibitors of XIAP. Embelin, identified primarily from the Embelica ribes plant, is one such compound shown to exhibit chemopreventive, anti-inflammatory, and apoptotic activities via inhibiting XIAP activity.Material and MethodsReagentsEmbelin was purchased from Tocris (Cambridge, MA). TRAIL was purchased from Alexis Corporation (Lausen, Switzerland). Antibodies against Caspase 3, cleaved caspase-3 were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). Polyadenosine 5’-diphosphate ribose polymerase (PARP) was purchased from Cell Signaling Technologies (Beverly, MA). BD Cytofix/Cytoperm Plus Fixation and Permeabilization Solution Kit, Propidium Iodide Staining Solution, Annexin V Binding Buffer, Mitochondrial Membrane Potential Detection (JC-1) Kit, Stain Buffer (FBS), Annexin V-FITC antibody, H2AX (pS139)-Alexa Fluor 647 antibody, Rabbit Anti- Active Caspase-3- BV605 antibody and PARP Cleaved Form-AF700 antibody were obtained from BD Biosciences (NJ, USA). CellROX Deep Red Reagent was obtained from Molecular Probes, Life Technologies (CA, USA). (3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyl tetrazolium bromide) solution (MTT) powder, DAPI, and N-Acetyl-L-Cysteine were obtained from Sigma-Aldrich (MO, USA). Apoptotic DNA ladder Kit was procured from Thermo fisher Scientific (USA).MethodologyWe used following assays and methods for this study.Cell cultureLeukemic cell lines K562 and U937 leukemic cells were cultured in RPMI 1640 medium supplemented with 10% (vol/vol) fetal bovine serum (FBS), 100 U/ml Penicillin and 100 U/ml Streptomycin at 370C in humidified atmosphere containing 5% CO2. All experiments were conducted in 5% serum.Cell viabilityExperiments were performed following treatment with various doses of embelin with and without pre-treatment with NAC for 24 hours using MTT assay.ROS ProductionCellROX Deep Red Oxidative Stress Reagent is a fluorogenic probe designed to reliably measure reactive oxygen species (ROS) in live cells. The cell-permeable reagent is non-fluorescent or very weakly fluorescent while in a reduced state and upon oxidation exhibit strong fluorogenic signal. The signals from CellROX Deep Red Reagent are localized in the cytoplasm and measured by flow cytometry (Excitation 640 nm/Emission 665 nm). K562 cells were treated with embelin for indicated time periods and finally analyzed by flow cytometry.ApoptosisApoptosis was measured using annexinV-FITC/PI staining and analyzed by flow cytometry. Cells were treated with embelin in the presence and absence of NAC for 24 hours. Following treatment, cells were harvested, washed with PBS and stained with annexin V-FITC/PI for 20 minutes at room temperature and apoptosis was measured by flow cytometry.Western blotFollowing treatment with embelin and NAC for 24 hours, cells were lysed and proteins were isolated. Equal amounts of protein were separated by SDS-PAGE, transferred to PVDF membranes and probed with specific antibodies.ResultsThe results from our study showed that Embelin causes a dose dependent inhibition of cell proliferation in K562 and U937 leukemic cells. Anti-proliferative activity of Embelin correlated with induction of apoptosis. In addition, Embelin treatment of K562 cells decreased the constitutive phosphorylation/activation of AKT followed by the upregulation of proapototic protein Bax. Embelin also induced loss of mitochondrial membrane potential, as determined by JC1 staining, with subsequent activation of caspase-3 and polyadenosin-5’-diphosphate-ribose polymerase (PARP) cleavage. Pretreatment of K562 cells with N-acetyl-L-cystein, a scavenger of reactive oxygen species (ROS) prevented Embelin mediated apoptotic effects. Embelin also suppressed K562 derived progenitor colony formation, suggesting its antileukemic effect. Finally our data also showed that co-treatment of subtoxic doses of Embelin and TRAIL potentiated anticancer activity in leukemic cells.ConclusionAltogether, these findings suggest that Embelin causes inhibition of cell proliferation and induction of apoptosis via generation of ROS in leukemic cells, which raises the possibility that Embelin alone or in combination of chemotherapeutic agents may have a future therapeutic role in leukemia and possibly other malignancies with up-regulated XIAP pathway.KeywordsApoptosis, CML, ROS

In the wake of the 9/11 terrorist attacks on the United States, the threat of militant Islamist terrorism rooted in the Middle East and South Asia has taken center stage in U.S. foreign policy. While these violent religious extremists represent a minority view, their threat to the United States and its allies is real (Moore 2011). Since 9/11, understanding and keeping apace of the evolution of U.S. foreign policy constitutes an imperative task in understanding the international security landscape. Given recent events such as the U.S.—India nuclear treaty, the grant of $2.29 billion of U.S. aid to Pakistan, and failures in the Afghan reconstruction process and political development, South Asia has become one of the major foreign policy focal points of Barack Obama’s presidency. In this context, Bangladesh has become an important strategic partner for America because of its geostrategic location, relations with the major competing powers (China and India) in the Indian Ocean basin, and the spread of radical Islamist militancy.

The history of power compression is a series of developmental epochs that are (1) characteristically marked by a technological breakthrough and (2) generally separated by a factor of ∼1010 in power density. Based on new advances in high‐power coherent x‐ray technology, the transition to a new nuclear epoch of laser interactions is presently commencing. Chief outcomes foreseen are (1) the generation of power densities in the 1028–1030 W/cm3 realm, (2) the controlled induction of nuclear interactions, and (3) the production of new states and forms of nuclear matter.

48 Background: Electrochemotherapy (ECT) combines the administration of poorly permeable chemotherapeutic agents with electroporation. It has been shown to be effective when compared with other treatments. This study assessed how breast cancer patients were benefited and identified potential problems at a designated treatment centre. Methods: This was a single centre prospective study of patients with cutaneous metastases from breast cancer. Patients who fulfilled NICE UK (National Institute Of Clinical Excellence) and local guidelines were treated. Gabapentin was given prior to general anaesthesia. Intravenous Bleomycin 15,000IU/m2 was given as a bolus. Treatment was commenced 8 minutes later with Cliniporator. Electrical pulses were delivered via an electrode inserted through the skin surface. Treatment response, disease progression free duration, post-operative pain and length of in-patient stay (LOS) were recorded. Patients recorded a symptom diary post treatment. Results: 20 treatments were performed in 16 patients from 2011-2015 with 53 separate areas treated. 8 patients had diffuse lesions, 5 had discrete lesions and 3 had both diffuse and discrete areas. 16 patients were being treated with ECT for the first time and 4 patients required 2 treatments. Median LOS was 3 days. Median follow up was 6 months (range 3-12).12 patients had complete response (75%) and 4 patients partial response. There was no disease progression for 6 months or more in 9 patients (56%) and 2 further patients had disease stabilised for 3 months with systemic or cutaneous progression in the remaining patients in 3 months or less. There were no deaths or immediate adverse events from ECT. 5 Patients (31%) with extensive diffuse chest wall disease reported persistent discomfort post treatment requiring extended period of post treatment analgesia. Conclusions: Electrochemotherapy is safe and effective treatment for cutaneous metastases. Appropriate patient selection for treatment, pre-emptive analgesia, post treatment support and follow up is essential in order to maximise the benefits and minimise potential side-effects particularly in extensive chest wall disease.

Background: The different types of hazards to which doctors are exposed in the hospitals need to be identified and eradicated.Objective: To study the awareness among doctors about the occupational hazards and the preventive measures that are taken.Materials and Methods: The sample size was 200, selected by convenient non-probability technique. The study was conducted inAyub Teaching Hospital, Abbottabad from 2nd March 2019 to 3rd June 2020. Data was collected via questionnaires and thenanalyzed by using Statistical Package for Social Sciences 21. House Officers, Post graduate residents, and Trainee Registrarswere included in the study.Results: Most frequent hazard recorded was needle prick injury (52.5%), followed by workload/stress/exhaustion (42.5%). Studyalso showed that only half of doctors (52.3%) were using preventive measures of different kinds like gloves, masks, standardoperating procedures etc., rest (47.7%) didn't use them. Almost half (48.1%) of the doctors didn't report the hazards to theadministration and even if they did, proper response was not given to address their problem.Conclusion: Most common occupational hazards were found to be needle prick injury and exhaustion, and they were moreprevalent among the doctors of surgery department. Consequently, doctors aren't able to perform their duties properly. Moreover,the hazards remained unreported both from doctors' and hospital administration's side.Keywords: Hazards, Injuries, Awareness

Background and study aims Despite advances in curative treatments for esophageal cancer, many patients often present with advanced disease. Dysphagia resulting in significant weight loss and malnutrition leads to poor quality of life. Palliative esophageal stenting with self-expanding metal stents (SEMS) helps alleviate symptoms and prolongs survival. However, access to fluoroscopy may be limited at certain centers causing delay in patient care. Methods We searched multiple databases from inception to November 2019 to identify studies evaluating the efficacy and safety of endoscopic palliative esophageal stenting and selected only those studies where fluoroscopic guidance was not used. Our primary aim was to calculate the overall technical as well as clinical success. Using meta-regression analysis, we also evaluated the effect of tumor location and obstruction length on overall technical and clinical success. Results A total of 1778 patients from 17 studies were analyzed. A total of 2036 stents were placed without the aid of fluoroscopy. The pooled rate of technical success was 94.7 % (CI 89.9–97.3, PI 55–99; I2 = 85) and clinical success was 82.1 % (CI 67.1–91.2, PI 24–99; I2 = 87). Based on meta-regression analysis both the length of obstruction and tumor location did not have any statistically significant effect on technical and clinical success. The pooled rate of adverse events was 4.1 % (CI 2.4–7.2; I2 = 72) for stent migration, 8.1 % (CI 4.1–15.4; I2 = 89) for tumor overgrowth and 1.2 % (CI 0.7–2; I2 = 0) for perforation. The most frequent clinical adverse event was retro-sternal chest pain. Conclusion Palliative esophageal stenting without fluoroscopy using SEMS is both safe and effective in patients with advanced esophageal cancer.