Search results for: extremely drug- resistant

Authors: Katie E. Jennings

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The interactions between family dynamics and environmental factors with mental health vulnerability in individuals are well known and are a theme for on-going research and debate. The impact upon mental health issues and forensic issues on family dynamics, experience, and emotional wellbeing cannot be over-Emphasised. For forensic patients with diagnosed mental disorders, these relationships and environments may have also been functionally linked to the development and maintenance of those disorders; with significant adverse childhood experiences being a common feature of many Patient’s histories. Mental health hospitals remove the patient from their home environments and provide treatment outside of these relationships and often outside of the home area. There is, therefore, a major focus on Services ensuring that patients are able to build and maintain relationships with family and friends, requiring services to involve families in Patients' care and treatment wherever possible. There are standards set by Government and clinical bodies that require absolute demonstration of the inclusion of family and friends in all aspects of the care and treatment of forensic patients. For some patients and family members, this push to take on a “role” in care can be unhelpful, extremely stressful, and has constant implications for the potential delicate reparation of relationships. Based on work undertaken for over 20 years in forensic mental health settings, this paper explores the positive psychology approach to a dimensional model to family inclusion in mental health care that learns from family court work and allows for the maintenance of relationships to be at both proximal and Distil levels; to prevent the replication of abuse, decrease the need for falsehoods and assist the recovery of all. The model is based on allowing families to choose to not be involved or be involved in different ways if this is seen to be more helpful. It also allows patients to choose the level of potential involvement that they would find helpful, and for this to be reviewed at a timeframe agreed by all parties, rather than when the next survey is due or the patient has a significant care meeting. This paper is significant as there is a lack of research to support services to use a positive psychology approach to work in this area, the assumption that being asked to be involved must be positive for all seems naïve at best for this patient group. Work relating to the psychology of family can significantly contribute to the development of knowledge in this area. The development of a dimensional model will support choice within families and assist in the development of more honest and open relationships.

Keywords: family dynamics, forensic, mental disorder, positive psychology

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Authors: Ibrahim M. Labouta, Gina N. Tageldin, Salwa M. Fahmy, Hayam M. Ashour, Mounir A. Khalil, Tamer M. Ibrahim, Nefertiti A. El-Nikhely

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Bruton’s tyrosine kinase (BTK) is a critical effector molecule in B cell antigen receptor (BCR) signaling transduction. It regulates B cell proliferation, development and survival. Since BTK is widely expressed in many B cell leukaemias and lymphomas, targeting BTK by small molecules inhibitors became an attractive idea as new treatment modalities for B cell mediated hematologic malignancies. Ibrutinib is the 1st generation BTK inhibitor, approved by FDA for treatment of relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). It binds irreversibly to the unique cysteine (Cys481) within the ATP-binding pocket of BTK. Besides ibrutinib, many irreversible covalent BTK inhibitors comprising pyrimidine nucleus such as spebrutinib (phase IIb) showed high selectivity and potency when compared to it. In this study, the designed compounds were based on 5-cyano-2-methylsulfanyl pyrimidine core and decorated with electrophilic warheads which are essential for the optimal activity for targeted covalent inhibition (TCI). However, modifications at pyrimidine C4 or C6 were made by introduction of substituted amines which are provided to behave differently. The synthesized derivatives were evaluated for their anticancer activity in leukemia cell lines (e.g. THP-1). Results showed that, some derivatives exhibited antiproliferative activity with IC50 ranged from 5-50 μM, The in vitro enzymatic inhibitory assay for these compounds against BTK is still under investigation. Nevertheless, we could conclude from the initial biological screening that, the synthesized 4 or 6-subsitituted aminopyrimidines represent promising and novel antileukemic agents. Meanwhile, further studies are still needed to attribute this activity through targeting BTK enzyme and inhibition of BCR signaling pathway.

Keywords: BTK inhibitors, hematologic malignancies, structure based drug design (SBDD), targeted covalent inhibitors (TCI)

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Authors: Fitsumbrhan Tajebe, Fadil Murad, Mitikie Tigabie, Mareye Abebaw, Tadele Alemu, Sefanit Abate, Rezika Mohammedw, Arega Yeshanew, Elias Shiferaw

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Background: Visceral leshimaniasis is a parasitic disease characterized by a systemic infection of phagocytic cells. Hematological parameters of these patients may be affected by the progress of the disease or treatment. Thus, the current study aimed to assess the hematological profiles of visceral leishmaniasis patients before and after treatment. Method: An institutional based retrospective cohort study was conducted among visceral leishmaniasis patients at University of Gondar Comprehensive Specialized Referral Hospital Leishmaniasis Research and Treatment Center from 2013 to 2018. Hematological profiles before initiation and after completion of treatment were extracted from registration book. Descriptive statics was presented using frequency and percentage. Paired t-test and Wilcoxon Signed rank test were used for comparing mean difference for normally and non- normally distributed data, respectively. Spearman and Pearson correlation analysis was used to describe the correlation of hematological parameters with different variables. P value < 0.05 was considered as statistically significant. Result: Except absolute nerutrophil count, post treatment hematological parameters show a significant increment compared to pretreatment one. The prevalence of anemia, leucopenia and thrombocytopenia was 85.5%, 83.4% and 75.8% prior to treatment and it was 58.3%, 38.2% and 19.2% after treatment, respectively. Moreover, parasite load of the disease showed statistically significant negative correlation with hematological profiles mainly with white blood cell and red blood cell. Conclusion: Majority of hematological profiles of patients with active VL have been restored after treatment, which might be associated with treatment effect on parasite proliferation and concentration of parasite in visceral organ, which directly affect hematological profiles.

Keywords: visceral leshimaniasis, hematological profile, anti-leshimanial drug, Gondar

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Authors: Semra Sirin Kiris

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Nonlinear dynamic analysis is permitted to be used for structures without any restrictions. The important issue is the selection of the design earthquake to conduct the analyses since quite different response may be obtained using ground motion records at the same general area even resulting from the same earthquake. In seismic design codes, the method requires scaling earthquake records based on site response spectrum to a specified hazard level. Many researches have indicated that this limitation about selection can cause a large scatter in response and other charecteristics of ground motion obtained in different manner may demonstrate better correlation with peak seismic response. For this reason influence of eleven different ground motion parameters on the peak displacement of reinforced concrete systems is examined in this paper. From conducting 7020 nonlinear time history analyses for single degree of freedom systems, the most effective earthquake parameters are given for the range of the initial periods and strength ratios of the structures. In this study, a hysteresis model for reinforced concrete called Q-hyst is used not taken into account strength and stiffness degradation. The post-yielding to elastic stiffness ratio is considered as 0.15. The range of initial period, T is from 0.1s to 0.9s with 0.1s time interval and three different strength ratios for structures are used. The magnitude of 260 earthquake records selected is higher than earthquake magnitude, M=6. The earthquake parameters related to the energy content, duration or peak values of ground motion records are PGA(Peak Ground Acceleration), PGV (Peak Ground Velocity), PGD (Peak Ground Displacement), MIV (Maximum Increamental Velocity), EPA(Effective Peak Acceleration), EPV (Effective Peak Velocity), teff (Effective Duration), A95 (Arias Intensity-based Parameter), SPGA (Significant Peak Ground Acceleration), ID (Damage Factor) and Sa (Spectral Response Spectrum).Observing the correlation coefficients between the ground motion parameters and the peak displacement of structures, different earthquake parameters play role in peak displacement demand related to the ranges formed by the different periods and the strength ratio of a reinforced concrete systems. The influence of the Sa tends to decrease for the high values of strength ratio and T=0.3s-0.6s. The ID and PGD is not evaluated as a measure of earthquake effect since high correlation with displacement demand is not observed. The influence of the A95 is high for T=0.1 but low related to the higher values of T and strength ratio. The correlation of PGA, EPA and SPGA shows the highest correlation for T=0.1s but their effectiveness decreases with high T. Considering all range of structural parameters, the MIV is the most effective parameter.

Keywords: earthquake parameters, earthquake resistant design, nonlinear analysis, reinforced concrete

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Authors: Vladimir Zobov, Nail Nazarov, Alexandra Vyshtakalyuk, Vyacheslav Semenov, Irina Galyametdinova, Vladimir Reznik

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The aim of this study was to investigate hepatoprotective properties of the Xymedon derivative L-ascorbate 1- (2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one (XD), which exhibits high efficiency as actoprotector. The study was carried out on 68 male albino rats weighing 250-400 g using preventive exposure to the test preparation. Effectiveness of XD win comparison with effectiveness of Xymedon (original substance) after administration of the compounds in identical doses. Maximum dose was 20 mg/kg. The animals orally received Xymedon or its derivative in doses of 10 and 20 mg/kg over 4 days. In 1-1.5 h after drug administration, CCl4 in vegetable oil (1:1) in a dose of 2 ml/kg. Controls received CCl4 but without hepatoprotectors. Intact control group consisted of rats, not receiving CCl4 or other compounds. The next day after the last administration of CCl4 and compounds under study animals were dehematized under ether anesthesia, blood and liver samples were taken for biochemical and histological analysis. Xymedon and XD administered according to the preventice scheme, exerted hepatoprotective effects: Xymedon — in the dose of 20 mg/kg, XD — in doses of 10 and 20 mg/kg. The drugs under study had different effects on liver condition, affected by induction with CCl4. Xymedon had a more pronounced effect both on the ALT level, which can be elevated not only due to destructive changes in hepatocytes, but also as a cholestasis manifestation, and on the serum total protein level, which reflects protein synthesis in liver. XD had a more pronounced effect on AST level, which is one of the markers of hepatocyte damage. Lower effective dose of XD — 10 mg/kg, compared to Xymedon effective according to, and its pronounced effect on AST, the hepatocyte cytolysis marker, is indicative of its higher preventive effectiveness, compared to Xymedon. This work was performed with the financial support of Russian Science Foundation (grant No: 14-50-00014).

Keywords: hepatoprotectors, pyrimidine derivatives, toxic liver damage, xymedon

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Authors: Jason Hoellwarth, Atiya Oomatia, Anuj Chavan, Kevin Tetsworth, Munjed Al Muderis

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Introduction: Percutaneous EndoProsthetic Osseointegration for Limbs (PEPOL) facilitates improved quality of life (QOL) and objective mobility for most amputees discontent with their traditional socket prosthesis (TSP) experience. Some amputees desiring PEPOL have residual bone much shorter than the currently marketed press-fit implant lengths of 14-16 cm, potentially a risk for failure to integrate. We report on the techniques used, complications experienced, the management of those complications, and the overall mobility outcomes of seven patients who had femur distraction osteogenesis (DO) with a Freedom nail followed by PEPOL. Method: Retrospective evaluation of a prospectively maintained database identified nine patients (5 females) who had transfemoral DO in preparation for PEPOL with two years of follow-up after PEPOL. Six patients had traumatic causes of amputation, one had perinatal complications, one was performed to manage necrotizing fasciitis and one was performed as a result of osteosarcoma. Result: The average age at which DO commenced was 39.4±15.9 years, and seven patients had their amputation more than ten years prior (average 25.5±18.8 years). The residual femurs, on average, started at 102.2±39.7 mm and were lengthened 58.1±20.7 mm, 98±45% of the goal (99±161% of the original bone length). Five patients (56%) had a complication requiring additional surgery: four events of inadequate regeneration were managed with continued lengthening to the desired goal followed by autograft placement harvested from contralateral femur reaming; one patient had the cerclage wires break, which required operative replacement. All patients had osseointegration performed at 355±123 days after the initial lengthening nail surgery. One patient had K-level >2 before DO, at a mean of 3.4±0.6 (2.6-4.4) years following osseointegration. Six patients had K-level >2. The 6-Minute Walk Test remained unchanged (267±56 vs. 308 ± 117 meters). Patient self-rating of prosthesis function, problems, and amputee situation did not significantly change from before DO to after osseointegration. Six patients required additional surgery following osseointegration: six to remove fixation plates placed to maintain distraction osteogenesis length at osseointegration; two required irritation and debridement for infection. Conclusion: Extremely short residual femurs, which make TSP use troublesome, can be lengthened with externally controlled telescoping nails and successfully achieve osseointegration. However, it is imperative to counsel patients that additional surgery to address inadequate regeneration or to remove painful hardware used to maintain fixation may be necessary. This may improve the amputee’s expectations before beginning a potentially arduous process.

Keywords: osseointegration, limb lengthening, quality of life, amputation

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Authors: Josephine Muchiri, Makena Muriithi

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Adverse mental health consequences are experienced by those that have been touched by Intimate Partner Violence (IPV), whether directly or indirectly. These negative effects are felt not only in the short term but in years to come. It is important to examine the prevalence and co-occurrence of mental disorders in order to provide strategic interventions for women who have experienced IPV. The aim of this study was to examine the prevalence and comorbidity of post-traumatic stress disorder (PTSD), Depression, and Anxiety among women who had experienced intimate Partner violence in two selected informal settlements in Nairobi County, Kenya. Participants were 116 women (15-60 years) selected through purposive and snowball sampling from the low social, economic settlements (Kawangware and Kibera) in Nairobi, Kenya. A social demographic questionnaire and the Woman Abuse Screening Tool (WAST) were used to collect data on intimate partner violence experiences. The PTSD Checklist for DSM-5 (PCL-5), Beck’s Depression Inventory, and the Beck’s Anxiety Inventory assessed for post-traumatic stress disorder, depression, and anxiety, respectively. Data analysis was conducted using the Statistical Package for Social Sciences (SPSS) version 29, utilizing descriptive and correlation analyses. Findings indicated that the women had undergone various forms of abuse from their intimate partners, which were physical abuse 111(92.5%), sexual abuse 70(88.6%), and verbal abuse 92(93.9%). The prevalence of the mental disorders was PTSD 47(32.4%); M= 44.11, S.D =14.67, depression was the highest at n=131(90.3%; M=33.37±9.98) with the levels of depression having varying prevalence rates where severe depression had the highest representation [moderate: n= 35; 24.1%, severe: n=69 (47.6%) and extremely severe: n=27(18.6%)]. Anxiety had the second highest prevalence of n=99 (68.8%; M= 28.55±13.63) with differing prevalence rates in the levels of anxiety which were normal anxiety: 45(31.3%), moderate anxiety n=62(43.1%) and severe anxiety: n=37(25.7%). Regarding comorbidities, the Pearson correlation test showed that there was a significant (p=0.000) positive relationship between PTSD and depression (r=0.379; p=.000), PTSD and anxiety (r=0.624; p=.000), and depression and anxiety (r=0.386; p=.000) such that increase in one disorder concomitantly led to increase of the other two disorders; hence comorbidity of the three disorders was ascertained. Conclusion: The study asserted the adverse impacts of IPV on women’s mental well-being, where the prevalence of PTSD, depression, and anxiety was established. Almost all the women had depressive symptoms; whereas more than half had anxiety and slightly more than a third had PTSD. Regarding the severity levels of anxiety and depression, almost half of the women with depression had severe depression whereas moderate anxiety was more prevalent for those with anxiety. The three disorders were found to co-occur where comorbidities of PTSD and anxiety had the highest probability of co-occurrence. It is thus recommended that mental health interventions with a focus on the three disorders be offered for women undergoing IPV.

Keywords: anxiety, comorbidity, depression, intimate partner violence, post-traumatic stress disorder

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Authors: Nitin Kumar

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Purpose: The current research work focuses mainly on evolving a delivery system for ginseng extract (GE), which in turn will ameliorate the neuroprotective potential by means of enhancing the ginsenoside (Rb1) bio-availability (BA). For more noteworthy enhancement in oral bioavailability (OBA) along with pharmacological properties, the drug carriers’ performance can be strengthened by utilizing phytosomes-loaded microspheres (PM) delivery system. Methods: For preparing the disparate phytosome complexes (F1, F2, and F3), an aqueous extract of ginseng roots (GR) along with phospholipids were reacted in disparate ratio. Considering the outcomes, F3 formulation (spray-dried) was chosen for preparing the phytosomes powder (PP), PM, and extract microspheres (EM). PM was made by means of loading of F3 into Gum Arabic (GA) in addition to maltodextrin polymer mixture, whereas EM was prepared by means of the addition of extract directly into the same polymer mixture. For investigating the neuroprotective effect (NPE) in addition to their pharmacokinetic (PK) properties, PP, PM, and EM formulations were assessed. Results: F3 formulation gave enhanced entrapment efficiency (EE) (i.e., 50.61%) along with good homogeneity of spherical shaped particle size (PS) (42.58 ± 1.4 nm) with least polydispersity index (PDI) (i.e., 0.193 ± 0.01). The sustained release (up to 24 h) of ginsenoside Rb1 (GRb1) is revealed by the dissolution study of PM. A significantly (p < 0.05) greater anti-oxidant (AO) potential of PM can well be perceived as of the diminution in the lipid peroxidase level in addition to the rise in the glutathione superoxide dismutase (SOD) in addition to catalase levels. It also showed a greater neuroprotective potential exhibiting significant (p < 0.05) augmentation in the nociceptive threshold together with the diminution in damage to nerves. A noteworthy enhancement in the relative BA (157.94%) of GRb1 through the PM formulation can well be seen in the PK studies. Conclusion: It is exhibited that the PM system is an optimistic and feasible strategy to enhance the delivery of GE for the effectual treatment of neuropathic pain.

Keywords: ginseng, neuropathic, phytosome, pain

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Authors: Abdorrasoul Malekpour, Mohammad Ghorbani Mojtaba Mortazavi, Mohammadreza Fattahi, Mohammad Hassan Meshkibaf, Ali Fakhrzad, Saeid Salehi, Saeideh Zahedi, Amir Ahmadimoghaddam, Parviz Farzadnia Dr., Mohammadreza Hajyani Asl Bs

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Hepatitis B as an infectious disease has eight main genotypes (A–H). The aim of this study is to Bioinformatically identify Rare Codon Clusters (RCC) in proteins structure of HBV. For detection of protein family accession numbers (Pfam) of HBV proteins; used of uni-prot database and Pfam search tool were used. Obtained Pfam IDs were analyzed in Sherlocc program and RCCs in HBV proteins were detected. In further, the structures of TrEMBL entries proteins studied in PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software. Pfam search tool have found nine significant hits and 0 insignificant hits in 3 frames. Results of Pfams studied in the Sherlocc program show this program not identified RCCs in the external core antigen (PF08290) and truncated HBeAg protein (PF08290). By contrast the RCCs become identified in Hepatitis core antigen (PF00906) Large envelope protein S (PF00695), X protein (PF00739), DNA polymerase (viral) N-terminal domain (PF00242) and Protein P (Pf00336). In HBV genome, seven RCC identified that found in hepatitis core antigen, large envelope protein S and DNA polymerase proteins and proteins structures of TrEMBL entries sequences that reported in Sherlocc program outputs are not complete. Based on situation of RCC in structure of HBV proteins, it suggested those RCCs are important in HBV life cycle. We hoped that this study provide a new and deep perspective in protein research and drug design for treatment of HBV.

Keywords: rare codon clusters, hepatitis B virus, bioinformatic study, infectious disease

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Authors: Christine Ysabelle G. Roman, Pauline Torres

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Background: Hypertrophic cardiomyopathy is a disease of marked heterogeneity. It is a genetically determined heart disease characterized by significant myocardium hypertrophy that results in diastolic dysfunction, left ventricular outflow tract obstruction, and an increased risk of arrhythmias. The primary treatment in patients with such conditions is negative inotropic drugs, such as beta-blockers, calcium channel antagonists, and disopyramide. However, for those who remain symptomatic and need septal reduction therapy, surgical septal myectomy or alcohol septal ablation are options. Case Summary: A 19 – year old female presented in the authors’ institution with easy fatigability. The consult was done a year prior, and 2D echocardiography was requested which showed concentric left ventricular hypertrophy, asymmetrically hypertrophied interventricular septum (IVS) with the largest diameter of 3.3cm & subaortic dynamic obstruction with a maximum gradient of 47 mmHg. A repeat echo a year later showed asymmetric septal hypertrophy (IVS measuring at 3cm) with the systolic anterior motion of anterior mitral valve leaflet and left ventricular outflow tract obstruction (peak gradient of 50mmHg). The patient then underwent alcohol septal ablation and was discharged stable after four days of admission. Conclusion: Hypertrophic obstructive cardiomyopathy, a cardiovascular genetic disease, results in various patterns of left ventricular hypertrophy and abnormality of mitral valve apparatus. The patient is managed medically initially. However, despite optimal drug therapy and significant left ventricular outflow tract obstruction, significant heart failure symptoms or syncope require invasive treatment.

Keywords: hypertrophic obstructive cardiomyopathy, left ventricular outflow tract obstruction, alcohol septal ablation, alcohol

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Authors: Nicole Virgili, Marco Utili

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The design of the Breeding Blanket in Tokamak fusion energy systems has to guarantee sufficient availability in addition to its functions, that are, tritium breeding self-sufficiency, power extraction and shielding (the magnets and the VV). All these function in the presence of extremely harsh operating conditions in terms of heat flux and neutron dose as well as chemical environment of the coolant and breeder that challenge structural materials (structural resistance and corrosion resistance). The movement and activation of fluids from the BB to the Ex-vessel components in a fusion power plant have an important radiological consideration because flowing material can carry radioactivity to safety-critical areas. This includes gamma-ray emission from activated fluid and activated corrosion products, and secondary activation resulting from neutron emission, with implication for the safety of maintenance personnel and damage to electrical and electronic equipment. In addition to the PbLi breeder activation, it is important to evaluate the contribution due to the activated corrosion products (ACPs) dissolved in the lead-lithium eutectic alloy, at different concentration levels. Therefore, the purpose of the study project is to evaluate the PbLi activity utilizing the FISPACT II inventory code. Emphasis is given on how the design of the EU-DEMO WCLL, and potential recycling of the breeder material will be impacted by the activation of PbLi and the associated active corrosion products (ACPs). For this scope the following Computational Tools, Data and Geometry have been considered: • Neutron source: EU-DEMO neutron flux < 1014/cm2/s • Neutron flux distribution in equatorial breeding blanket module (BBM) #13 in the WCLL BB outboard central zone, which is the most activated zone, with the aim to introduce a conservative component utilizing MNCP6. • The recommended geometry model: 2017 EU DEMO CAD model. • Blanket Module Material Specifications (Composition) • Activation calculations for different ACP concentration levels in the PbLi breeder, with a given chemistry in stationary equilibrium conditions, using FISPACT II code. Results suggest that there should be a waiting time of about 10 years from the shut-down (SD) to be able to safely manipulate the PbLi for recycling operations with simple shielding requirements. The dose rate is mainly given by the PbLi and the ACP concentration (x1 or x 100) does not shift the result. In conclusion, the results show that there is no impact on PbLi activation due to ACPs levels.

Keywords: activation, corrosion products, recycling, WCLL BB., PbLi

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Authors: M. Ardelean, F. Manea, A. Pop, J. Schoonman

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The presence of pharmaceuticals in the environment and especially in water has gained increasing attention. They are included in emerging class of pollutants, and for most of them, legal limits have not been set-up due to their impact on human health and ecosystem was not determined and/or there is not the advanced analytical method for their quantification. In this context, the development of various advanced analytical methods for the quantification of pharmaceuticals in water is required. The electrochemical methods are known to exhibit the great potential for high-performance analytical methods but their performance is in direct relation to the electrode material and the operating techniques. In this study, two types of carbon-based electrodes materials, i.e., boron-doped diamond (BDD) and carbon nanofiber (CNF)-epoxy composite electrodes have been investigated through voltammetric techniques for the detection of naproxen in water. The comparative electrochemical behavior of naproxen (NPX) on both BDD and CNF electrodes was studied by cyclic voltammetry, and the well-defined peak corresponding to NPX oxidation was found for each electrode. NPX oxidation occurred on BDD electrode at the potential value of about +1.4 V/SCE (saturated calomel electrode) and at about +1.2 V/SCE for CNF electrode. The sensitivities for NPX detection were similar for both carbon-based electrode and thus, CNF electrode exhibited superiority in relation to the detection potential. Differential-pulsed voltammetry (DPV) and square-wave voltammetry (SWV) techniques were exploited to improve the electroanalytical performance for the NPX detection, and the best results related to the sensitivity of 9.959 µA·µM^-1 were achieved using DPV. In addition, the simultaneous detection of NPX and fluoxetine -a very common antidepressive drug, also present in water, was studied using CNF electrode and very good results were obtained. The detection potential values that allowed a good separation of the detection signals together with the good sensitivities were appropriate for the simultaneous detection of both tested pharmaceuticals. These results reclaim CNF electrode as a valuable tool for the individual/simultaneous detection of pharmaceuticals in water.

Keywords: boron-doped diamond electrode, carbon nanofiber-epoxy composite electrode, emerging pollutans, pharmaceuticals

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Authors: Suchhanda Ghosh, A. K. Paul

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Nickel, an industrially important metal is not mined in India, due to the lack of its primary mining resources. But, the chromite deposits occurring in the Sukinda and Baula-Nuasahi region of Odhisa, India, is reported to contain around 0.99% of nickel entrapped in the goethite matrix of the lateritic iron rich ore. Weathering of the dumped chromite mining overburden often leads to the contamination of the ground as well as the surface water with toxic nickel. Microbes inherent to this metal contaminated environment are reported to be capable of removal as well as detoxification of various metals including nickel. Nickel resistant fungal isolates obtained in pure form from the metal rich overburden were evaluated for their potential to biosorb nickel by using their dried biomass. Penicillium simplicissimum SAU203 was the best nickel biosorbant among the 20 fungi tested and was capable to sorbing 16.85 mg Ni/g biomass from a solution containing 50 mg/l of Ni. The identity of the isolate was confirmed using 18S rRNA gene analysis. The sorption capacity of the isolate was further standardized following Langmuir and Freundlich adsorption isotherm models and the results reflected energy efficient sorption. Fourier-transform infrared spectroscopy studies of the nickel loaded and control biomass in a comparative basis revealed the involvement of hydroxyl, amine and carboxylic groups in Ni binding. The sorption process was also optimized for several standard parameters like initial metal ion concentration, initial sorbet concentration, incubation temperature and pH, presence of additional cations and pre-treatment of the biomass by different chemicals. Optimisation leads to significant improvements in the process of nickel biosorption on to the fungal biomass. P. simplicissimum SAU203 could sorb 54.73 mg Ni/g biomass with an initial Ni concentration of 200 mg/l in solution and 21.8 mg Ni/g biomass with an initial biomass concentration of 1g/l solution. Optimum temperature and pH for biosorption was recorded to be 30°C and pH 6.5 respectively. Presence of Zn and Fe ions improved the sorption of Ni(II), whereas, cobalt had a negative impact. Pre-treatment of biomass with various chemical and physical agents has affected the proficiency of Ni sorption by P. simplicissimum SAU203 biomass, autoclaving as well as treatment of biomass with 0.5 M sulfuric acid and acetic acid reduced the sorption as compared to the untreated biomass, whereas, NaOH and Na₂CO₃ and Twin 80 (0.5 M) treated biomass resulted in augmented metal sorption. Hence, on the basis of the present study, it can be concluded that P. simplicissimum SAU203 has the potential for the removal as well as detoxification of nickel from contaminated environments in general and particularly from the chromite mining areas of Odhisa, India.

Keywords: nickel, fungal biosorption, Penicillium simplicissimum SAU203, Indian chromite mines, mining overburden

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Authors: Zinhle Cindi, Collet Dandara, Mpiko Ntsekhe, Edson Makambwa, Miguel Larceda

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Background: Warfarin is the most commonly used drug in the management of thromboembolic disease. However, there is a huge variability in the time, number of doses or starting doses for patients to achieve the required international normalised ratio (INR) which is compounded by a narrow therapeutic index. Many genetic-association studies have reported on European and Asian populations which have led to the designing of specific algorithms that are now being used to assist in warfarin dosing. However, very few or no studies have looked at the pharmacogenetics of warfarin in African populations, yet, huge differences in dosage requirements to reach the same INR have been observed. Objective: We set out to investigate the distribution of 3 SNPs CYP4F2 c.1347C > T, VKORC1 g.-1639G > A and VKORC1 c.1173C > T among South African Mixed Ancestry (MA) and Black African patients. Methods: DNA was extracted from 383 participants and subsequently genotyped using PCR/RFLP for the CYP4F2 c.1347 (V433M) (rs2108622), VKORC1 g.-1639 (rs9923231) and VKORC1 c.1173 (rs9934438) SNPs. Results: Comparing the Black and MA groups, significant differences were observed in the distribution of the following genotypes; CYP4F2 c.1347C/T (23% vs. 39% p=0.03). All VKORC1 g.-1639G > A genotypes (p < 0.006) and all VKORC1 c.1173C > T genotypes (p < 0.007). Conclusion: CYP4F2 c.1347T (V433M) reduces CYP4F2 protein levels and therefore expected to affect the amount of warfarin needed to block vitamin k recycling. The VKORC1 g-1639A variant alters transcriptional regulation therefore affecting the function of vitamin k epoxide reductase in vitamin k production. The VKORC1 c.1173T variant reduces the enzyme activity of VKORC1 consequently enhancing the effectiveness of warfarin. These are preliminary results; more genetic characterization is required to understand all the genetic determinants affecting how patients respond to warfarin.

Keywords: algorithms, pharmacogenetics, thromboembolic disease, warfarin

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Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

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Authors: Tamer M. Shehata

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Objective: Currently, mucoadhesive microparticles acquired a high interest in both research and pharmaceutical technology fields. Recently, BÜCHI lunched its latest fourth generation nano spray dryer B-90 used for nanoparticle production. B-90 offers an elegant technology combined particle engineering and drying in one step. In our laboratory, we successfully developed a new formulation for metformin hydrochloride, mucoadhesive microparticles utilizing B-90 technology for treatment of type 2-diabetis. Method: Gelatin or sodium alginate, natural occurring polymers with mucoadhesive properties, solely or in combination was used in our formulation trials. Preformulation studies (atomization head mesh size, flow rate, head temperature, polymer solution viscosity and surface tension) and postformulation characters (particle size, flowability, surface scan and dissolution profile) were evaluated. Finally, hypoglycemic effect of the selected formula was evaluated in streptozotocin-induced diabetic rats. Spray head with 7 µm hole, flow rate of 3.5 mL/min and head temperature 120 ºC were selected. Polymer viscosity was less than 11.5 cP with surface tension less than 70.1 dyne/cm. Result: Discrete, non aggregated particles and free flowing powders with particle size was less than 2000 nm were obtained. Gelatin and sodium alginate combination in ratio 1:3 were successfully sustained the in vitro release profile of the drug. Hypoglycemic evaluation of the previous formula, showed a significant reduction of blood glucose level over 24 h. Conclusion: B-90 technology can open a new era of , mucoadhesive microparticles preparation offering convenient dosage form that can enhance compliance of type 2 diabetic patients.

Keywords: mucoadhesive, microparticles, technology, diabetis

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Authors: Shahnaz Haque, Anand Shukla, Sunita Singh, Anil Kem

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Introduction: Diabetes Mellitus is a chronic metabolic disease affecting millions worldwide. Metformin is the most commonly prescribed first line oral hypoglycemic drug for type 2 diabetes mellitus, but due to progressive worsening of blood glucose control during the natural history of type 2 diabetes, combination therapy usually becomes necessary. Objective: This study was designed to assess the treatment satisfaction between Sitagliptin versus Pioglitazone added to Metformin in patients with type 2 diabetes mellitus (T2DM). Methods: We conducted a prospective, open label, randomized, parallel group study in SIMS, Hapur, U.P. Eligible patients fulfilling inclusion criteria were randomized into two groups having 25 patients in each group using tab Sitagliptin 100mg, tab Pioglitazone 30mg added to ongoing tab Metformin (500mg) therapy for 16 weeks. The follow-up visits were on weeks 4,12 and 16. Result: 16 weeks later, addition of Sitagliptin 100mg compared to that of Pioglitazone 30 mg to ongoing Metformin therapy provided similar glycosylated hemoglobin (HbA1c) lowering efficacy in patients with T2DM with inadequate glycemic control on metformin monotherapy. Change in HbA1c in group1 was -0.656±0.21%(p<0.0001) whereas in group2 was -0.748±0.35%(p<0.0001). Hence decrease in HbA1c from baseline was more in group2. Both treatments were well tolerated with negligible risk of hypoglycaemia. Weight loss was observed with Sitagliptin in contrast to weight gain seen in Pioglitazone. Conclusion: In this study, Sitagliptin 100 mg along with metformin therapy in comparison to pioglitazone 30 mg plus metformin therapy was both effective, well-tolerated and improved glycemic control in both the groups. Addition of pioglitazone had cause oedema and weight gain to the patients whereas sitagliptin caused weight loss in its patients.

Keywords: sitagliptin, pioglitazone, metformin, type 2 diabetes mellitus

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Authors: Ke Zhang, Yongli Zhu

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Due to rapid load growths in today’s highly electrified societies and the requirement for green energy sources, large-scale wind farm power transmission system is constantly developing. This system is a typical multi-terminal power supply system, whose structure of the network topology of transmission lines is complex. What’s more, it locates in the complex terrain of mountains and grasslands, thus increasing the possibility of transmission line faults and finding the fault location with difficulty after the faults and resulting in an extremely serious phenomenon of abandoning the wind. In order to solve these problems, a fault location method for multi-terminal transmission line based on wind farm characteristics and improved single-ended traveling wave positioning method is proposed. Through studying the zero sequence current characteristics by using the characteristics of the grounding transformer(GT) in the existing large-scale wind farms, it is obtained that the criterion for judging the fault interval of the multi-terminal transmission line. When a ground short-circuit fault occurs, there is only zero sequence current on the path between GT and the fault point. Therefore, the interval where the fault point exists is obtained by determining the path of the zero sequence current. After determining the fault interval, The location of the short-circuit fault point is calculated by the traveling wave method. However, this article uses an improved traveling wave method. It makes the positioning accuracy more accurate by combining the single-ended traveling wave method with double-ended electrical data. What’s more, a method of calculating the traveling wave velocity is deduced according to the above improvements (it is the actual wave velocity in theory). The improvement of the traveling wave velocity calculation method further improves the positioning accuracy. Compared with the traditional positioning method, the average positioning error of this method is reduced by 30%.This method overcomes the shortcomings of the traditional method in poor fault location of wind farm transmission lines. In addition, it is more accurate than the traditional fixed wave velocity method in the calculation of the traveling wave velocity. It can calculate the wave velocity in real time according to the scene and solve the traveling wave velocity can’t be updated with the environment and real-time update. The method is verified in PSCAD/EMTDC.

Keywords: grounding transformer, multi-terminal transmission line, short circuit fault location, traveling wave velocity, wind farm

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Authors: Luis Fernando Calvo Prieto, Raul Herrero Martínez, Mónica Santamarta Llorente, Sergio Paniagua Bermejo

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The project that is presented starts from the questioning about the compartmentalization of knowledge that occurs in university higher education. There are several authors who describe the problems associated with this reality (Rodamillans, M) indicating a lack of integration of the knowledge acquired by students throughout the subjects taken in their university degree. Furthermore, this disintegration is accentuated by the enrollment system of some Faculties and/or Schools of Engineering, which allows the student to take subjects outside the recommended curricular path. This problem is accentuated in an ostentatious way when trying to find an integration between humanistic subjects and the world of experimental sciences or engineering. This abrupt separation between humanities and sciences can be observed in any study plan of Spanish degrees. Except for subjects such as economics or English, in the Faculties of Sciences and the Schools of Engineering, the absence of any humanistic content is striking. At some point it was decided that the only value to take into account when designing their study plans was “usefulness”, considering the humanities systematically useless for their training, and therefore banishing them from the study plans. forgetting the role they have on the capacity of both Leadership and Civic Humanism in our professionals of tomorrow. The teaching guides for the different subjects in the branch of science or engineering do not include any competency, not even transversal, related to leadership capacity or the need, in today's world, for social, civic and humanitarian knowledge part of the people who will offer medical, pharmaceutical, environmental, biotechnological or engineering solutions to a society that is generated thanks to more or less complex relationships based on human relationships and historical events that have occurred so far. If we want professionals who know how to deal effectively and rationally with their leadership tasks and who, in addition, find and develop an ethically civic sense and a humanistic profile in their functions and scientific tasks, we must not leave aside the importance that it has, for the themselves, know the causes, facts and consequences of key events in the history of humanity. The words of the humanist Paul Preston are well known: “he who does not know his history is condemned to repeat the mistakes of the past.” The idea, therefore, that today there can be men of science in the way that the scientists of the Renaissance were, becomes, at the very least, difficult to conceive. To think that a Leonardo da Vinci can be repeated in current times is a more than crazy idea; and although at first it may seem that the specialization of a professional is inevitable but beneficial, there are authors who consider (Sánchez Inarejos) that it has an extremely serious negative side effect: the entrenchment behind the different postulates of each area of knowledge, disdaining everything. what is foreign to it.

Keywords: STEM, higher education, social sciences, history

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Authors: Valeria Velasco, Ana M. Bonilla, José L. Vergara, Alcides Lofa, Jorge Campos, Pedro Rojas-García

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Staphylococcus aureus is both commensal bacterium and opportunistic pathogen that can cause different diseases in humans and can rapidly develop antimicrobial resistance. Since this bacterium has the ability to colonize the nares and skin of humans and animals, there is a risk of contamination of food in different steps of the food chain supply. Emerging strains have been detected in food-producing animals and meat, such as methicillin-resistant S. aureus (MRSA). The aim of this study was to determine the prevalence and oxacillin susceptibility of S. aureus in the pork chain supply in Chile and to suggest some natural antimicrobials for control. A total of 487 samples were collected from pigs (n=332), carcasses (n=85), and retail pork meat (n=70). Presumptive S. aureus colonies were isolated by selective enrichment and culture media. The confirmation was carried out by biochemical testing (Api® Staph) and molecular technique PCR (detection of nuc and mecA genes, associated with S. aureus and methicillin resistance, respectively). The oxacillin (β-lactam antibiotic that replaced methicillin) susceptibility was assessed by minimum inhibitory concentration (MIC) using the Epsilometer test (Etest). A preliminary assay was carried out to test thymol, carvacrol, oregano essential oil (Origanum vulgare L.), Maqui or Chilean wineberry extract (Aristotelia chilensis (Mol.) Stuntz) as anti-staphylococcal agents using the disc diffusion method at different concentrations. The overall prevalence of S. aureus in the pork chain supply reached 33.9%. A higher prevalence of S. aureus was determined in carcasses (56.5%) than in pigs (28.3%) and pork meat (32.9%) (P ≤ 0.05). The prevalence of S. aureus in pigs sampled at farms (40.6%) was higher than in pigs sampled at slaughterhouses (23.3%) (P ≤ 0.05). The contamination of no packaged meat with S. aureus (43.1%) was higher than in packaged meat (5.3%) (P ≤ 0.05). The mecA gene was not detected in S. aureus strains isolated in this study. Two S. aureus strains exhibited oxacillin resistance (MIC ≥ 4µg/mL). Anti-staphylococcal activity was detected in solutions of thymol, carvacrol, and oregano essential oil at all concentrations tested. No anti-staphylococcal activity was detected in Maqui extract. Finally, S. aureus is present in the pork chain supply in Chile. Although the mecA gene was not detected, oxacillin resistance was found in S. aureus and could be attributed to another resistance mechanism. Thymol, carvacrol, and oregano essential oil could be used as anti-staphylococcal agents at low concentrations. Research project Fondecyt No. 11140379.

Keywords: antimicrobials, mecA gen, nuc gen, oxacillin susceptibility, pork meat

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Authors: Kar Yue Chan

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Cantonese opera is a valuable heritage originated from South China, and started to span its influence across the area to Hong Kong, and became extremely popular back in the 1950s to the 1970s. It has also been honoured and recognized as one treasurable item on the Intangible Cultural Heritage of Humanity on the Representative List of UNESCO since 2009. A certain level of difficulty is encountered when one identifies the gender roles and representations from a usual performance of Cantonese opera, as conventional practices of Cantonese opera display to the audience that many of the male hero roles are played by female upon the prior knowledge of all audience, and it is understandable for them as well because in the past there were insufficient male actors and performers on the market. Female actresses, in some senses, are more capable to sing near-male voices, and their appearances in heroic operatic attires are more appreciated by general audience. Therefore, perspectives of 'feminine representation' and the 'Reception Theory' in literature are conducive to analyzing such phenomenon. In spite of some 'normal' performances with romantic love stories or historical accounts involving often a talented intellectual and a beautiful wise lady (in Chinese caizi jiaren 才子佳人), in which the male role is actually male and the female role is actually female, there have still been some opera titles specifically manifesting these extreme gender associations by putting together displacement of gender roles in the same performance in view of such chaotic complication. On top of all other factors, translators dealing with any operatic texts face plenty of challenges upon transferring Cantonese operatic performances into English. It is found that translators need to deal with cultural elements embedded in the lyrics; the form (which is as delicate as those deriving from classical Chinese poetry); the gender misplacements that affect the mood and tone of the lyrics that much when they are in the process of translating. Some lyrics and tunes are specifically designed for a particular gender role to perform, while some others are more generic; both of which require different and specific translation strategies. After scrutinizing the various sources of reference, readers of this paper should be well informed of a significance which lies in the refined nature of the poetic form and content that signifies in the way the distinguished gender voice segregation of the discourse from which the lyrics are derived, and definitely also through the on-stage performability aspect of the task. In order to produce a relatively short and concise translated version which fits performance needs, all of the above factors will be looked at in this paper with relevant examples and analysis.

Keywords: Cantonese opera, translation, chaotic gender, performance

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Authors: S. B. Otieno1, F. Were, A. Afullo, K. Waza

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Background: Multi drug resistance HIV has emerged rendering the current conventional treatment of HIV ineffective. There is a need for new treatment regime which is cheap, effective and not prone to resistance development by HIV. Methods: In randomized clinical study of 68 HIV positive children 3 – 15 years to asses the efficacy of yeast selenium in HIV/AIDS patients, 50μ yeast selenium was administered to 34 children while in matched control of 34 were put on placebo. Blood samples and weight of the both groups which were taken every 3 months intervals up to 6 months, were analyzed by ELIZA for CD4T cells, the data was analyzed by SPSS version 16, WAZ scores were analyzed by Epi Info version 6. Results: No significant difference in age { χ2 (1, 62) =0.03, p =0.853}, cause of morbidity between test and controls {χ2 (1, 65) = 5.87, p= 0.015} and on condition of foster parents {χ2 ( 1,63) = 5.57, p= 0.0172} was observed. Children on selenium showed progressive improvement of WAZ and significant difference at six months {F (5,12) = =5.758, P=0.006}, and weight gain of up to 4.1 kilograms in six months, and significant CD4 T cell count increase t= -2.943, p<0.05 compared to matched controls t = -1.258 p> 0.05. CD4 T cell count increased among all age groups on test 3-5 years (+ 267.1),5-8 years (+200.3) 9-15 years (+71.2) cells/mm3 and in matched controls a decrease 3-5 years (-71), 5-8 years (-125) and 9-13 years (-10.1) cells/mm3 . No significant difference inCD4 T cell count between boys {F (2, 32) = 1.531 p= 0.232} and between boys {F (2, 49) = 1.040, p= 0.361} on test and between boys and girls {F (5, 81) = 1.379, p= 0.241} on test. Similarly no significant difference between boys and girls were observed {F (5, 86) = 1.168, p= 0.332}.In the test group there was significant positive correlation β =252.23 between weight for age (WAZ), and CD4 T Cell Count p=0.007, R2= 0.252, F< 0.05. In matched controls no significant correlation between weight gain and CD4 T cell count change was observed at six months p > 0.05. No positive correlation β =-138.23 was observed between CD4T Cell count, WAZ, p=0.934, R2 =0.0337 F >0.05. Majority (96.78%) of children on test either remained or progressed to WHO immunological stage I. Conclusion: From this study it can be concluded that yeast Selenium is effective in slowing the progress of HIV 1 in children from WHO clinical stage I by improving CD4 T cell count and hence the immunity.

Keywords: selenium, HIV, AIDS, WAZ

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Authors: Praveen Adusumilli, Meher Lakshmi Konatam, Sadashivudu Gundeti, Stalin Bala

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The invention of trastuzumab has changed the treatment of breast cancer and lives of many patients all over the world. Despite many patients getting benefitted from the drug, it is out of reach for most of the patients. There is very limited real world data regarding the epidemiology and clinical outcome of Her2neu positive breast cancer patients. Materials and Methods: This is a retrospective analysis of breast cancer patients presenting to a tertiary care cancer centre in Southern India from 2007 to2013. All early and locally advanced breast cancer patients, who were Her2neu 3+ on IHC are included in the study and evaluated in terms of epidemiology, 3-year disease free survival (DFS)and 5-year overall survival(OS). Chemotherapy regimens used were-FAC 6 cycles or AC 4 cycles followed by 12 cycles of weekly paclitaxel . Trastuzumab was given after 6 cycles of FAC or weekly with paclitaxel followed by 3weekly maintenance until 1 year. Results: Over the period of this study there were 885 newly diagnosed cases of carcinoma breast, of which 242 (27%) were Her2neu positive, 360(40%) were hormone receptor positive, and 212(24%) were triple negative. A total of 71(8%) were Her2neu equivocal of which only 10 patients got FISH test done. Of the 212 newly diagnosed patients, only 74 (29%) opted to have standard of care therapy with trastuzumab at our centre, out of which 52(24%), 8(3%), received under insurance, paying basis respectively. 14(9%) patients received the care as part of clinical trial program (ALTTO trial). 7 (9.72%) patients developed decrease of ejection fraction by greater than 10%, requiring stoppage of trastuzumab out of which 5 were restarted in 2 months. Patients receiving trastuzumab along with chemotherapy had longer 3year DFS 92% vs. 60% (p value<0.0001) when compared to chemotherapy alone. 5 year OS was 87% vs 44% (p-value <0.0001) compared to chemotherapy alone. Conclusion: Trastuzumab with chemotherapy improves the DFS and OS in Her2neu positive patients. The biggest constraint is the cost of the treatment and absence of universal health security net to treat all patients with this diagnosis.

Keywords: breast cancer, Her 2 neu positive, real world data, Trastuzumab

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Authors: Maria Ostroukhova, Zhanneta Zalutskaya, Elena Ermilova

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The alternative oxidase (AOX) mediates cyanide-resistant respiration, which bypasses proton-pumping complexes III and IV of the cytochrome pathway to directly transfer electrons from reduced ubiquinone to molecular oxygen. In Chlamydomonas reinhardtii, AOX is a monomeric protein that is encoded by two genes of discrete subfamilies, AOX1 and AOX2. Although AOX has been proposed to play essential roles in stress tolerance of organisms, the role of subfamily AOX2 is largely unknown. In C. reinhardtii, AOX2 was initially identified as one of constitutively low expressed genes. Like other photosynthetic organisms C. reinhardtii cells frequently experience periods of hypoxia. To examine AOX2 transcriptional regulation and role of AOX2 in hypoxia adaptation, real-time PCR analysis and artificial microRNA method were employed. Two experimental approaches have been used to induce the anoxic conditions: dark-anaerobic and light-anaerobic conditions. C. reinhardtii cells exposed to the oxygen deprivation have shown increased AOX2 mRNA levels. By contrast, AOX1 was not an anoxia-responsive gene. In C. reinhardtii, a subset of genes is regulated by transcription factor CRR1 in anaerobic conditions. Notable, the AOX2 promoter region contains the potential motif for CRR1 binding. Therefore, the role of CRR1 in the control of AOX2 transcription was tested. The CRR1-underexpressing strains, that were generated and characterized in this work, exhibited low levels of AOX2 transcripts under anoxic conditions. However, the transformants still slightly induced AOX2 gene expression in the darkness. These confirmed our suggestions that darkness is a regulatory stimulus for AOX genes in C. reinhardtii. Thus, other factors must contribute to AOX2 promoter activity under dark-anoxic conditions. Moreover, knock-down of CRR1 caused a complete reduction of AOX2 expression under light-anoxic conditions. These results indicate that (1) CRR1 is required for AOX2 expression during hypoxia, and (2) AOX2 gene is regulated by CRR1 together with yet-unknown regulatory factor(s). In addition, the AOX2-underexpressing strains were generated. The analysis of amiRNA-AOX2 strains suggested a role of this alternative oxidase in hypoxia adaptation of the alga. In conclusion, the results reported here show that C. reinhardtii AOX2 gene is stress inducible. CRR1 transcriptional factor is involved in the regulation of the AOX2 gene expression in the absence of oxygen. Moreover, AOX2 but not AOX1 functions under oxygen deprivation. This work was supported by Russian Science Foundation (research grant № 16-14-10004).

Keywords: alternative oxidase 2, artificial microRNA approach, chlamydomonas reinhardtii, hypoxia

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Authors: Parastoo Parhizkar, Jaber Yaghini, Omid Fakheran

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Background: Third molar surgery is often associated with postoperative problems which cause serious impediments on daily activities and quality of life. Steroidal anti-inflammatory drugs may decrease these common post-operative complications. The purpose of this review is evaluating the available evidence regarding the efficacy of corticosteroids used as adjunctive therapy for patients undergoing third molar surgery. Methods: PubMed, Google scholar, Scopus, web of science, clinicaltrials.gov, scirus.com, Cochrane central register for controlled trials, LILACS, OpenGrey, centerwatch, isrctn, who.int and ebsco were searched without restrictions regarding the year of publication. Randomized clinical trials assessing patient-reported outcomes in patients undergoing surgical therapy, were eligible for inclusion. Study quality was assessed using the CONSORT-checklist. No meta-analysis was performed. Results: A total of twelve Randomized Clinical Trials were included in this study. Methylprednisolone and Dexamethasone may decrease postoperative side effects such as pain, trismus and edema. Based on the results both of them could improve patients’ satisfaction, and there is no significant difference between these two types of corticosteroids regarding the patient centered outcomes (p > 0.05). Intralesional and intravenous injection of Dexamethasone showed an equivalent result, with statistically significant better results (P < 0.05) in comparison with the oral treatment. Conclusion: various types of corticosteroids can enhance the patient’s satisfaction following third molar surgery. However, there is no significant difference between Dexamethasone, Prednisolone and Methylprednisolone groups in this regard. Comparing the various administration routs, local injection of Dexamethasone is quite simple, painless and cost-effective adjunctive therapy with better drug efficacy.

Keywords: third molar surgery, corticosteroids, patient-reported outcomes, health related quality of life

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Authors: Abhishek Pandey

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Ibuprofen and Acetaminophen is widely used as prescription & non-prescription medicine. Ibuprofen mainly used in the treatment of mild to moderate pain related to headache, migraine, postoperative condition and in the management of spondylitis, osteoarthritis and rheumatoid arthritis. Acetaminophen is used as an analgesic and antipyretic drug. Ibuprofen having high tendency of sticking to punches of tablet punching machine while Acetaminophen is not ordinarily compressible to tablet formulation because Acetaminophen crystals are very hard and brittle in nature and fracture very easily when compressed producing capping and laminating tablet defects therefore wet granulation method is used to make them compressible. The aim of study was to prepare Ibuprofen and Acetaminophen tablets by direct compression and top spray granulation technique. In this Investigation tablets were prepared by using directly compressible grade excipients. Dibasic calcium phosphate, lactose anhydrous (DCL21), microcrystalline cellulose (Avicel PH 101). In order to obtain best or optimized formulation, nine different formulations were generated among them batch F7, F8, F9 shows good results and within the acceptable limit. Formulation (F7) selected as optimize product on the basis of dissolution study. Furtherly, directly compressible granules of both drugs were prepared by using top spray granulation technique in fluidized bed processor equipment and compressed .In order to obtain best product process optimization was carried out by performing four trials in which various parameters like inlet air temperature, spray rate, peristaltic pump rpm, % LOD, properties of granules, blending time and hardness were optimized. Batch T3 coined as optimized batch on the basis physical & chemical evaluation. Finally formulations prepared by both techniques were compared.

Keywords: direct compression, top spray granulation, process optimization, blending time

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Authors: Dangut Maren David, Skaf Zakwan

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Adequate monitoring of vehicle component in other to obtain high uptime is the goal of predictive maintenance, the major challenge faced by businesses in industries is the significant cost associated with a delay in service delivery due to system downtime. Most of those businesses are interested in predicting those problems and proactively prevent them in advance before it occurs, which is the core advantage of Prognostic Health Management (PHM) application. The recent emergence of industry 4.0 or industrial internet of things (IIoT) has led to the need for monitoring systems activities and enhancing system-to-system or component-to- component interactions, this has resulted to a large generation of data known as big data. Analysis of big data represents an increasingly important, however, due to complexity inherently in the dataset such as imbalance classification problems, it becomes extremely difficult to build a model with accurate high precision. Data-driven predictive modeling for condition-based maintenance (CBM) has recently drowned research interest with growing attention to both academics and industries. The large data generated from industrial process inherently comes with a different degree of complexity which posed a challenge for analytics. Thus, imbalance classification problem exists perversely in industrial datasets which can affect the performance of learning algorithms yielding to poor classifier accuracy in model development. Misclassification of faults can result in unplanned breakdown leading economic loss. In this paper, an advanced approach for handling imbalance classification problem is proposed and then a prognostic model for predicting aircraft component replacement is developed to predict component replacement in advanced by exploring aircraft historical data, the approached is based on hybrid ensemble-based method which improves the prediction of the minority class during learning, we also investigate the impact of our approach on multiclass imbalance problem. We validate the feasibility and effectiveness in terms of the performance of our approach using real-world aircraft operation and maintenance datasets, which spans over 7 years. Our approach shows better performance compared to other similar approaches. We also validate our approach strength for handling multiclass imbalanced dataset, our results also show good performance compared to other based classifiers.

Keywords: prognostics, data-driven, imbalance classification, deep learning

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Authors: Luminita Marin, Dalila Belei, Carmen Dumea

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Aggregation induced emission (AIE) is an intriguing optical phenomenon recently evidenced by Tang and his co-workers, for which aggregation works constructively in the improving of light emission. The AIE challenging phenomenon is quite opposite to the notorious aggregation caused quenching (ACQ) of light emission in the condensed phase, and comes in line with requirements of photonic and optoelectronic devices which need solid state emissive substrates. This paper reports a series of ten new aggregation induced emission (AIE) low molecular weight compounds based on triazole and pyridine-N-oxide heterocyclic units bonded by short flexible chains, obtained by a „click” chemistry reaction. The compounds present extremely weak luminescence in solution but strong light emission in solid state. To distinguish the influence of the crystallinity degree on the emission efficiency, the photophysical properties were explored by UV-vis and photoluminescence spectroscopy in solution, water suspension, amorphous and crystalline films. On the other hand, the compound morphology of the up mentioned states was monitored by dynamic light scattering, scanning electron microscopy, atomic force microscopy and polarized light microscopy methods. To further understand the structural design – photophysical properties relationship, single crystal X-ray diffraction on some understudy compounds was performed too. The UV-vis absorption spectra of the triazole water suspensions indicated a typical behaviour for nanoparticle formation, while the photoluminescence spectra revealed an emission intensity enhancement up to 921-fold higher of the crystalline films compared to solutions, clearly indicating an AIE behaviour. The compounds have the tendency to aggregate forming nano- and micro- crystals in shape of rose-like and fibres. The crystals integrity is kept due to the strong lateral intermolecular forces, while the absence of face-to-face forces explains the enhanced luminescence in crystalline state, in which the intramolecular rotations are restricted. The studied flexible triazoles draw attention to a new structural design in which small biologically friendly luminophore units are linked together by small flexible chains. This design enlarges the variety of the AIE luminogens to the flexible molecules, guiding further efforts in development of new AIE structures for appropriate applications, the biological ones being especially envisaged.

Keywords: aggregation induced emission, pyridine-N-oxide, triazole

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Authors: Debalina Ghoshal

Abstract:

Nuclear security is the ‘prevention and detection of, and response to unauthorised removal, sabotage, unauthorised access, illegal transfer or other malicious acts involving nuclear or radiological material or their associated facilities.’ Ever since the end of Cold War, nuclear materials security has remained a concern for global security. However, with the increase in terrorist attacks not just in India especially, security of nuclear materials remains a priority. Therefore, India has made continued efforts to tighten its security on nuclear materials to prevent nuclear theft and radiological terrorism. Nuclear security is different from nuclear safety. Physical security is also a serious concern and India had been careful of the physical security of its nuclear materials. This is more so important since India is expanding its nuclear power capability to generate electricity for economic development. As India targets 60,000 MW of electricity production by 2030, it has a range of reactors to help it achieve its goal. These include indigenous Pressurised Heavy Water Reactors, now standardized at 700 MW per reactor Light Water Reactors, and the indigenous Fast Breeder Reactors that can generate more fuel for the future and enable the country to utilise its abundant thorium resource. Nuclear materials security can be enhanced through two important ways. One is through proliferation resistant technologies and diplomatic efforts to take non proliferation initiatives. The other is by developing technical means to prevent any leakage in nuclear materials in the hands of asymmetric organisations. New Delhi has already implemented IAEA Safeguards on their civilian nuclear installations. Moreover, the IAEA Additional Protocol has also been ratified by India in order to enhance its transparency of nuclear material and strengthen nuclear security. India is a party to the IAEA Conventions on Nuclear Safety and Security, and in particular the 1980 Convention on the Physical Protection of Nuclear Material and its amendment in 2005, Code of Conduct in Safety and Security of Radioactive Sources, 2006 which enables the country to provide for the highest international standards on nuclear and radiological safety and security. India's nuclear security approach is driven by five key components: Governance, Nuclear Security Practice and Culture, Institutions, Technology and International Cooperation. However, there is still scope for further improvements to strengthen nuclear materials and nuclear security. The NTI Report, ‘India’s improvement reflects its first contribution to the IAEA Nuclear Security Fund etc. in the future, India’s nuclear materials security conditions could be further improved by strengthening its laws and regulations for security and control of materials, particularly for control and accounting of materials, mitigating the insider threat, and for the physical security of materials during transport. India’s nuclear materials security conditions also remain adversely affected due to its continued increase in its quantities of nuclear material, and high levels of corruption among public officials.’ This paper would study briefly the progress made by India in nuclear and nuclear material security and the step ahead for India to further strengthen this.

Keywords: India, nuclear security, nuclear materials, non proliferation

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Authors: Isabella Lima Leite de Freitas

Abstract:

The importance of astronomy for humanity is unquestionable. Despite being a robust science, capable of bringing new discoveries every day and quickly increasing the ability of researchers to understand the universe more deeply, scientific research in this area can also help in various applications outside the domain of astronomy. The objective of this study was to review and conduct a descriptive analysis of published studies that presented the importance of astronomy in the area of education. A narrative review of the literature has been performed, considering the articles published in the last five years. As astronomy involves the study of physics, chemistry, biology, mathematics and technology, one of the studies evaluated presented astronomy as the gateway to science, demonstrating the presence of astronomy in 52 school curricula in 37 countries, with celestial movement the dominant content area. Another intervention study, evaluating individuals aged 4-5 years, demonstrated that the attribution of personal characteristics to cosmic bodies, in addition to the use of comprehensive astronomy concepts, favored the learning of science in preschool-age children, considering the use of practical activities of accompaniment and free drawing. Aiming to measure scientific literacy, another study developed in Turkey, motivated the authorities of this country to change the teaching materials and curriculum of secondary schools after the term “astronomy” appeared as one of the most attractive subjects for young people aged 15 to 24. There are also reports in the literature of the use of pedagogical tools, such as the representation of the Solar System on a human scale, where students can walk along the orbits of the planets while studying the laws of dynamics. The use of this tool favored the teaching of the relationship between distance, duration and speed over the period of the planets, in addition to improving the motivation and well-being of students aged 14-16. An important impact of astronomy on education was demonstrated in the study that evaluated the participation of high school students in the Astronomical Olympiads and the International Astronomy Olympiad. The study concluded that these Olympics have considerable influence on students who pursue a career in teaching or research later on, many of whom are in the area of astronomy itself. In addition, the literature indicates that the teaching of astronomy in the digital age has facilitated the availability of data for researchers, but also for the general population. This fact can increase even more the curiosity that the astronomy area has always instilled in people and promote the dissemination of knowledge on an expanded scale. Currently, astronomy has been considered an important ally in strengthening the school curricula of children, adolescents and young adults. This has been used as teaching tools, in addition to being extremely useful for scientific literacy, being increasingly used in the area of education.

Keywords: astronomy, education area, teaching, review

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