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This paper reports the effect of a magnetic field on plasma parameters and surface structuring of the Mg alloy after laser irradiation. Femtosecond pulses of a Ti:sapphire laser system (800 nm, 35 fs, 1 KHz) are employed as the source of irradiation at various irradiances ranging from 0.011P W/c m 2 to 0.117P W/c m 2 to generate ablated Mg-alloy plasma. A transvers magnetic field (TMF) of strength 1.1 Tesla is employed to confine laser generated Mg plasma. All the measurements are performed with and without TMF. The two plasma parameters, i.e., excitation temperature (T e x c ) and electron number density (n e) of Mg plasma, have been evaluated by laser-induced breakdown spectroscopy (LIBS) analysis. It is observed that the values of T e x c and n e of laser produced plasma (LPP) of the Mg alloy are higher in the presence of a magnetic field as compared to the field free case. Both show initially an increasing trend with increasing laser irradiance and after attaining their respective maxima a decreasing trend is observed with the further increase of irradiance. The magnetic confinement validity is confirmed by analytically evaluating thermal beta (ß t), directional beta (ß d), confinement radius (R b), and diffusion time (t d) for LPP of the Mg alloy. To correlate the LPP parameters of the Mg alloy with surface modifications a field emission scanning electron microscope (FE-SEM) analysis is performed. It was revealed that structures like laser-induced periodic surface structures (LIPSSs), agglomerates, islands, large sized bumps, along with channels and multiple ablative layers are observed. Distinct and well-defined surface structuring is observed in the presence of TMF as compared to the field free case. It is concluded that by applying an external magnetic field during laser irradiation, controlled material surface structuring is possible for fabrication of nanogratings and field emitters where spatial uniformity is critically important.
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Rapid emergence of resistance in Salmonella enterica serovar Typhi (Salmonella Typhi) against most of the available therapeutic options for typhoid has rendered its treatment more difficult. This study sought to determine the current scenario of antimicrobial resistance in local isolates of Faisalabad following several treatment failure reports. Out of 300 clinical specimens collected in 2018, 45 isolates were identified as Salmonella Typhi. To assess changes, we compared their antibiogram profile with 31 Salmonella Typhi strains isolated in 2005. The isolates collected during 2018 showed a significant rise in antimicrobial drug resistance as compared with isolates revived from the cultures of 2005, including 15 multidrug-resistant (MDR), 20 extensively drug-resistant, and 14 pan drug-resistant isolates compared with only 8 MDRs from 2005. Notably, in 2018 isolates, resistance to azithromycin was seen in 75% of the isolates. Extended-spectrum beta-lactamase production was detected in 47% of Salmonella Typhi isolates and 18% isolates showed resistance against carbapenems. The sequences of two carbapenemase genes, VIM and GES, found in Salmonella Typhi were submitted in NCBI. The carbapenem resistance is rare in Enterobacteriaceae and probably first time reported in Salmonella Typhi. H58 haplotype was identified in the 2018 Salmonella Typhi isolates and PCR-restriction fragment length polymorphism method identified 16.7% of H58 strains that belonged to lineage I, 19.4% of H58 strains that belonged to lineage II, and the remaining 63.9% that belonged to the node. The regional difference in the antimicrobial resistance trend needs effective epidemiological studies.
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Salmonella typhi , Febre Tifoide , Humanos , Salmonella typhi/genética , Antibacterianos/farmacologia , Paquistão , Testes de Sensibilidade Microbiana , Febre Tifoide/tratamento farmacológico , Carbapenêmicos/farmacologia , Farmacorresistência BacterianaRESUMO
BACKGROUND: Outer membrane proteins (OMPs) of Gram-negative bacteria have been known as potential vaccine targets due to their antigenic properties and host specificity. Here, we focused on the exploration of the immunogenic potential and protective efficacy of total OMPs of Salmonella enterica serovar Typhi due to their multi epitope properties, adjuvanted with nanoporous chitosan particles (NPCPs). The study was designed to extrapolate an effective, low cost prophylactic approach for typhoid fever being getting uncontrolled in Pakistan due to emergence of extensively drug resistant (XDR) strains. METHODS & RESULTS: The OMPs of two S. Typhi variants (with and without Vi capsule) alone and with nanoporous chitosan particles as adjuvant were comparatively analyzed for immunogenic potential in mice. Adaptive immunity was evaluated by ELISA and relative quantification of cytokine gene expression (IL4, IL6, IL9, IL17, IL10, TNF, INF and PPIA as house keeping gene) using RT-qPCR. Statistical analysis was done using Welch's test. The protection was recorded by challenging the immunized mice with 50% ×LD50 of S. Typhi. The Vi + ve-OMPs of S. Typhi showed the most promising results by ELISA and significantly high expression of IL-6, IL-10 and IL-17 and 92.5% protective efficacy with no detectable side effects. CONCLUSION: We can conclude that the OMPs of Vi + ve S. Typhi are the most promising candidates for future typhoid vaccines because of cost effective preparation without expensive purification steps and multi-epitope properties. Chitosan adjuvant may have applications for oral protein based vaccines but found less effective in injectable preparations.
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Quitosana , Vacinas Tíficas-Paratíficas , Adjuvantes Imunológicos/farmacologia , Animais , Proteínas da Membrana Bacteriana Externa , Quitosana/farmacologia , Epitopos , Camundongos , Salmonella typhi/genética , Vacinas Tíficas-Paratíficas/farmacologiaRESUMO
The dengue virus (DENV) genome encodes 10 different genes including the NS3 gene, which has a protease and helicase domain used in virus replication. This domain is a potential target for antiviral agents against dengue. Due to a high mutation rate, DENV is classified into four major serotypes (DENV1-DENV4). This study was designed to perform conservancy analysis of all four serotypes by drawing a consensus sequence for each serotype and then drawing a global consensus sequence to study conserved residues in all four serotypes. A total of 127 NS3 sequences belonging to all four serotypes were retrieved and aligned using multiple alignment feature of CLC Workbench and were subjected to phylogenetic tree construction. Conservancy analysis of NS3 revealed conserved peptides with active site residues that can be important in developing antiviral agents against dengue virus. Among conserved residues, residues G142, Ser144, and G145 (catalytic pocket residues), A219, D220, and D221 (divalent cations binding residues), and His56, Asp79, Ser144, 146 were highly conserved among all the serotypes. Residues from L138 to L149 and from L226 to L245 were also considerably conserved in all serotypes, while lysine141 mutated to serine in serotype 3. A total of 14 peptides from the conserved regions of DENV NS3 protein were identified, which may be helpful to develop peptide inhibitors. The DENV NS3 phylogenetic tree showed the evolutionary relationship among all four serotypes, and all serotypes of dengue were found to have evolved from the dengue 4 serotype. Because of its high variability, DENV has become a global health concern. It is important to study residues that are present in protease, helicase, the catalytic pocket Mg(2+) binding site, and the AAA domain. This study revealed peptides with active site residues that are highly conserved among all four serotypes. These regions of the NS3 sequence may be helpful in developing antiviral agents.
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Hepatocellular carcinoma (HCC) is a deadly and emerging disease leading to death in Asian countries. High hepatitis B virus (HBV) load and chronic hepatitis B (CHB) infection increase the risk of developing HCC. HBV is a DNA virus that can integrate DNA into host genome thereby increase the yield of transactivator protein HBxAg that may deregulate many pathways involving in metabolism of cells. Several monogenic and polygenic risk factors are also involved in HCC development. This review summarizes the mechanism involved in HCC development and discusses some promising therapies to make HCC curative.
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Carcinoma Hepatocelular , Predisposição Genética para Doença/genética , Vírus da Hepatite B/fisiologia , Hepatite B , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/virologia , Predisposição Genética para Doença/epidemiologia , Hepatite B/epidemiologia , Hepatite B/fisiopatologia , Hepatite B/virologia , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/virologia , Prevalência , Fatores de RiscoRESUMO
OBJECTIVES: To study the pattern of chromosomal abnormalities in adult patients with acute lymphoblastic leukemia. STUDY DESIGN: A retrospective study. PLACE AND DURATION OF STUDY: January 1998 to June 2005 at the Cytogenetics department, Aga Khan University Hospital, Karachi. PATIENTS AND METHODS: A retrospective analysis of cytogenetic studies was carried out in patients who were diagnosed as ALL and were more than 15 years of age. Cytogenetic analysis was performed using a trypsin-Giemsa banding technique. Karyotypes were interpreted using International System for Cytogenetics Nomenclature (1995) criteria. RESULTS: The requests were received for cytogenetic analysis of bone marrow specimens in 69 patients who were diagnosed as ALL. Cytogenetic results were available in 62 patients; out of which 51 were males and 11 were females. 44 patients (70%) were found to have a normal karyotype. In 18 patients (29%), abnormal karyotype was found. CONCLUSION: Cytogenetic studies should be part of the initial work up of every patient with ALL. Larger scale studies will help refine our understanding of the less common chromosomal patterns and conduct multivariate analysis to define the relative prognostic value of karyotypic results.