Search results for: drug administration

Authors: Endang Lukitaningsih, Fathul Jannah, Arief R. Hakim, Ratna D. Puspita, Zullies Ikawati

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Rifampicin is a semisynthetic antibiotic derivative of rifamycin B produced by Streptomyces mediterranei. RIF has been used worldwide as first line drug-prescribed throughout tuberculosis therapy. This study aims to develop and to validate an HPLC method couple with a UV detection for determination of rifampicin in spiked human plasma and its application for bioequivalence study. The chromatographic separation was achieved on an RP-C18 column (LachromHitachi, 250 x 4.6 mm., 5μm), utilizing a mobile phase of phosphate buffer/acetonitrile (55:45, v/v, pH 6.8 ± 0.1) at a flow of 1.5 mL/min. Detection was carried out at 337 nm by using spectrophotometer. The developed method was statistically validated for the linearity, accuracy, limit of detection, limit of quantitation, precise and specifity. The specifity of the method was ascertained by comparing chromatograms of blank plasma and plasma containing rifampicin; the matrix and rifampicin were well separated. The limit of detection and limit of quantification were 0.7 µg/mL and 2.3 µg/mL, respectively. The regression curve of standard was linear (r > 0.999) over a range concentration of 20.0 – 100.0 µg/mL. The mean recovery of the method was 96.68 ± 8.06 %. Both intraday and interday precision data showed reproducibility (R.S.D. 2.98% and 1.13 %, respectively). Therefore, the method can be used for routine analysis of rifampicin in human plasma and in bioequivalence study. The validated method was successfully applied in pharmacokinetic and bioequivalence study of rifampicin tablet in a limited number of subjects (under an Ethical Clearance No. KE/FK/6201/EC/2015). The mean values of Cmax, Tmax, AUC(0-24) and AUC(o-∞) for the test formulation of rifampicin were 5.81 ± 0.88 µg/mL, 1.25 hour, 29.16 ± 4.05 µg/mL. h. and 29.41 ± 4.07 µg/mL. h., respectively. Meanwhile for the reference formulation, the values were 5.04 ± 0.54 µg/mL, 1.31 hour, 27.20 ± 3.98 µg/mL.h. and 27.49 ± 4.01 µg/mL.h. From bioequivalence study, the 90% CIs for the test formulation/reference formulation ratio for the logarithmic transformations of Cmax and AUC(0-24) were 97.96-129.48% and 99.13-120.02%, respectively. According to the bioequivamence test guidelines of the European Commission-European Medicines Agency, it can be concluded that the test formulation of rifampicin is bioequivalence with the reference formulation.

Keywords: validation, HPLC, plasma, bioequivalence

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Authors: Asmamaw Yehun, Tsegaye Gogie, Martin Vermeer, Addisu Hunegnaw

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The Global Positioning System (GPS) is a space-based radio positioning system, which is capable of providing continuous position, velocity, and time information to users anywhere on or near the surface of the Earth. The main objective of this work was to estimate the integrated precipitable water vapour (IPWV) using ground GPS and Low Earth Orbit (LEO) Radio Occultation (RO) to study spatial-temporal variability. For LEO-GPS RO, we used Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) datasets. We estimated the daily and monthly mean of IPWV using six selected ground-based GPS stations over a period of range from 2012 to 2016 (i.e. five-years period). The main perspective for selecting the range period from 2012 to 2016 is that, continuous data were available during these periods at all Ethiopian GPS stations. We studied temporal, seasonal, diurnal, and vertical variations of precipitable water vapour using GPS observables extracted from the precise geodetic GAMIT-GLOBK software package. Finally, we determined the cross-correlation of our GPS-derived IPWV values with those of the European Centre for Medium-Range Weather Forecasts (ECMWF) ERA-40 Interim reanalysis and of the second generation National Oceanic and Atmospheric Administration (NOAA) model ensemble Forecast System Reforecast (GEFS/R) for validation and static comparison. There are higher values of the IPWV range from 30 to 37.5 millimetres (mm) in Gambela and Southern Regions of Ethiopia. Some parts of Tigray, Amhara, and Oromia regions had low IPWV ranges from 8.62 to 15.27 mm. The correlation coefficient between GPS-derived IPWV with ECMWF and GEFS/R exceeds 90%. We conclude that there are highly temporal, seasonal, diurnal, and vertical variations of precipitable water vapour in the study area.

Keywords: GNSS, radio occultation, atmosphere, precipitable water vapour

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Authors: Kalayanee Senasu

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This research investigates the influences of different factors on the happiness of Thai people, including both general factors and sustainable ones. Additionally, this study also monitors Thai people’s happiness via Thai Happiness Index developed in 2017. Besides reflecting happiness level of Thai people, this index also identifies related important issues. The data were collected by both secondary related data and primary survey data collected by interviewed questionnaires. The research data were from stratified multi-stage sampling in region, province, district, and enumeration area, and simple random sampling in each enumeration area. The research data cover 20 provinces, including Bangkok and 4-5 provinces in each region of the North, Northeastern, Central, and South. There were 4,960 usable respondents who were at least 15 years old. Statistical analyses included both descriptive and inferential statistics, including hierarchical regression and one-way ANOVA. The Alkire and Foster method was adopted to develop and calculate the Thai happiness index. The results reveal that the quality of household economy plays the most important role in predicting happiness. The results also indicate that quality of family, quality of health, and effectiveness of public administration in the provincial level have positive effects on happiness at about similar levels. For the socio-economic factors, the results reveal that age, education level, and household revenue have significant effects on happiness. For computing Thai happiness index (THaI), the result reveals the 2018 THaI value is 0.556. When people are divided into four groups depending upon their degree of happiness, it is found that a total of 21.1% of population are happy, with 6.0% called deeply happy and 15.1% called extensively happy. A total of 78.9% of population are not-yet-happy, with 31.8% called narrowly happy, and 47.1% called unhappy. A group of happy population reflects the happiness index THaI valued of 0.789, which is much higher than the THaI valued of 0.494 of the not-yet-happy population. Overall Thai people have higher happiness compared to 2017 when the happiness index was 0.506.

Keywords: happiness, quality of life, sustainability, Thai Happiness Index

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Authors: Mona Hassan Aburahma, Alaa Hamed Salama

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Ufasomes “unsaturated fatty acids liposomes” are unique nano-sized self-assembled bilayered vesicles that can be easily created from the readily available unsaturated fatty acid. Ufasomes are formed due to weak associative interaction of the fully ionized and unionized fatty acids into bilayers structures. In the ufasomes constructs, the fatty acid molecules are oriented with their hydrocarbon tails directed toward the membrane interior and the carboxyl groups are in contact with water. Although ufasomes can be employed as a safe vesicular carrier for drugs, the extreme instability of their aqueous dispersions hinders their effective use in drug delivery field. Accordingly, in our study, lyophilized gels containing ufasomes were prepared using a simple assembling technique form the readily available oleic acid to overcome the colloidal instability of the ufasomes dispersions and convert them into accurate unit dosage forms. The influence of changing cholesterol percentage relative to oleic acid on the ufasomes vesicles were investigated using factorial design. The optimized oleic acid ufasomes comprised nanoscaled spherical vesicles. Scanning electron micrographs of the lyophilized gels revealed that the included ufasomes were intact, non-aggregating, and preserved their spherical morphology. Rheological characterization (viscosity and shear stress versus shear rate) of reconstituted ufasomal lyophilized gel ensured the ease of application. The capability of the ufasomes, included in the gel, to penetrate deep through the mucosa layers was illustrated using ex-vivo confocal laser imaging, thereby, highlighting the feasibility of stabilizing ufasomes using lyophilized gel platforms.

Keywords: ufasomes, lyophilized gel, confocal scanning microscopy, rheological characterization, oleic acid

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Authors: Ekaterina Sánchez Romero, Emily Gabriela Aguirre Herrera, Sandra Luz Espinoza Esquerra, Jorge García Campos

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Female, 7 months old, daughter of a mother with anemia during pregnancy, with no history of atopy in the family, since birth she presents with recurrent dermatological and gastrointestinal infections, chronically treated for recurrent diaper dermatitis. At 6 months of age, she begins with generalized pallor, hyperpigmentation in hands and feet, smooth tongue, psychomotor retardation with lack of head support, sedation, and hypoactivity. She was referred to our hospital for a fever of 38°C, severe diaper rash, and pancytopenia with HB 9.3, platelets 38000, neutrophils 0.39 MCV: 86.80 high for her age. The approach was initiated to rule out myeloproliferative syndrome, with negative immunohistochemical results of bone marrow aspirate; during her stay, she presented neurological regression, lack of sucking, and focal seizures. CT scan showed cortical atrophy. The patient was diagnosed with primary immunodeficiency due to history; gamma globulin was administered without improvement with normal results of immunoglobulins and metabolic screening. When dermatological and neurological diagnoses were ruled out as the primary cause, a nutritional factor was evaluated, and a therapeutic trial was started with the administration of vitamin B12 and zinc, presenting clinical neurological improvement and resolution of pancytopenia in 2 months. It was decided to continue outpatient management. Discussion: We present a patient with neurological, dermatological involvement, and pancytopenia, so the most common differential diagnoses in this population were ruled out. Vitamin B12 deficiency is an uncommon entity. Due to maternal and clinical history, a therapeutic trial was started resulting in an improvement. Conclusion: VitaminB12 deficiency should be considered one of the differential diagnoses in the approach to pancytopenia with megaloblastic anemia associated with dermatologic and neurologic manifestations. Early treatment can reduce irreversible damage in these patients.

Keywords: vitamin B12 deficiency, pediatrics, pancytopenia, diaper dermatitis

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Authors: Pravin Mishra, Ajeet K. Jha, Pankaj K. Jha

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This technical note is aimed at providing a brief information on goat breeds, its breeding seasonality and different methods of oestrous synchronization for Nepalese goat farmers. It was observed that, these goats are seasonal breeder and showed oestrous during mainly two season; December- February and March-May. This leads to an irregular supply of goat to market and a wide variations in market price. Oestrus synchronization is only an alternative reproductive tool to overcome this scarcity by enhancing production and productivity. This technique enables goat producers breed their animals within a short pre-determined period and permits breeding round the year. The principle of oestrus synchronisation is based on controlling of the luteal phase of the oestrous cycle. There are two basic mechanisms; one by shortening the luteal life (premature luteolysis) using prostaglandins or its analogues and the other by prolonging the luteal life (simulating the activity of natural progesterone produced by the corpus luteum) using exogenous progesterone source. The former is easy to apply and only effective during breeding season, whereas the latter is advantageous when the reproductive status of the goat flock is unknown. The common hormonal products easily available in Nepal includes; prostaglandins or its analogues (Oviprost® Dinoprost® Lutalyse® and Estrumate®), exogenous progesterone (Fluorogestone acetate® and Controlled Internal Drug Release®, CIDR) devices). However, before practicing the oestrous synchronization protocol, it needs to be validated for oestrous response rate, time to onset of oestrous, duration of oestrous and pregnancy rates at farmer’s field. In conclusion, application of oestrus synchronisation practice enhanced goat production and surplus the goat meat demand in Nepal.

Keywords: goat, Nepal, oestrous, synchronization

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Authors: Mohamed A. Morsy, Azza A. El-Sheikh, Abdulla Y. Al-Taher

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Resveratrol (RES) is a well-known polyphenol antioxidant. We have previously shown that testicular protective effect of RES against the anticancer drug methotrexate (MTX)-induced toxicity involves transporter-mediated mechanisms. Here, we investigated the effect of RES on MTX-induced nephrotoxicity. Rats were administered RES (10 mg/kg/day) for 8 days, with or without a single MTX dose (20 mg/kg i.p.) at day 4 of the experiment. MTX induced nephrotoxicity evident by significantly increase in serum blood urea nitrogen and creatinine compared to control, as well as distortion of kidney microscopic structure. MTX also significantly increased renal nitric oxide level, with induction of inducible nitric oxide synthase expression. MTX also significantly up-regulated fas ligand and caspase 3. Administering RES prior to MTX significantly improved kidney function and microscopic picture, as well as significantly decreased nitrosative and apoptotic markers compared to MTX alone. RES, but not MTX, caused significant increase in expression of breast cancer resistance protein (BCRP), an apical efflux renal transporter that participates in urinary elimination of both MTX and RES. Interestingly, concomitant MTX and RES caused further up-regulation of renal Bcrp compared to RES alone. Using Human BCRP ATPase assay, both RES and MTX exhibited dose-dependent increase in ATPase activity, with Km values of 0.52 ± 0.03 and 30.9 ± 4.2 µM, respectively. Furthermore, combined RES and MTX caused ATPase activity which was significantly less than maximum ATPase activity attained by the positive control; sulfasalazine (12.5 µM). In conclusion, RES exerted nephro-protection against MTX-induced toxicity through anti-nitrosative and anti-apoptotic effects, as well as via up-regulation of renal Bcrp.

Keywords: methotrexate, resveratrol, nephrotoxicity, breast cancer resistance protein

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Authors: Baburao Ganpat Apte, Gajodhar

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Introduction: diopathic Parkinson’s disease (PD) is the most common neurodegenerative disorder. Early PD may present a diagnostic challenge with broad differential diagnoses that are not associated with striatal dopamine deficiency. This test was performed by using special type of radioactive precursor which was made available through our logistics. 131I-TOPA L-6-[131I] Iodo-3,4-Trihydroxyphenylalnine (131I -TOPA) is a positron emission tomography (PET) agent that measures the uptake of dopamine precursors for assessment of presynaptic dopaminergic integrity and has been shown to accurately reflect the sign of nervous mind going in patients suffers from monoaminergic disturbances in PD. Both qualitative and quantitative analyses of the scans were performed. Therefore, the early clinical diagnosis alone may be accurate and this reinforces the importance of functional imaging targeting the patholigically of the disease process. The patient’s medical records were then assessed for length of follow-up, response to levotopa, clinical course of sickness, and usually though of symptoms at time of 131I -TOPA PET. A respective analysis was carried out for all patients that gone through 131I -TOPA PET brain scan for motor symptoms suspicious for PD between 2000 - 2006. The eventual diagnosis by the referring neurologist, movement therapist, physiotherapist, was used as the accurate measurements in standard for further analysis. In this study, our goal to illustrate our local experience to determine the accuracy of 131I -TOPA PET for diagnosis of PD. We studied a total of 48 patients. Of the 25 scans, it found that one was a false negative, 40 were true positives, and 7 were true negatives. The resultant values are Sensitivity 90.4% (95% CI: 100%-71.3%), Specificity 100% (92% CI: 100%-58.0%), PPV 100% (91% CI 100%-75.7%), and NPV 80.5% (95% CI: 92.5%-48.5%). Result: Twenty-three patients were found in the initial query, and 1 were excluded (2 uncertain diagnosis, 2 inadequate follow-up). Twenty-eight patients (28 scans) remained with 15 males (62%) and 8 females (30%). All the patients had a clinical follow-up of at least 3 years, however the median length of follow-up was 5.5 years (range: 2-8 years). The median age at scan time was 51.2 years (range: 35-75)

Keywords: 18F-TOPA, petct, parkinson’s disease, cardiac

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Authors: Junaid Jibran Jawed, Prasanta Saini, Subrata Majumdar

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Background: Leishmania donovani infection causes severe host immune-suppression through the modulation of pathogen recognition receptors. Apart from TLRs (Toll Like Receptor), recent studies focus on the important contribution of NLR (NOD-Like Receptor) family member NOD1 and NOD2 as these receptors are capable of triggering host innate immunity. The aim of this study was to decipher the role of NOD1/NOD2 receptors during experimental visceral leishmaniasis (VL) and the important link between host failure and parasite evasion strategy. Method: The status of NOD1 and NOD2 receptors were analysed in uninfected and infected cells through western blotting and RT-PCR. The active contributions of these receptors in reducing parasite burden were confirmed by siRNA mediated silencing, and over-expression studies and the parasite numbers were calculated through microscopic examination of the Giemsa-stained slides. In-vivo studies were done by using non-toxic dose of Mw (Mycobacterium indicus pranii), Ara-LAM(Arabinoasylated lipoarabinomannan) along with MDP (Muramyl dipeptide) administration. Result: Leishmania donovani infection of the macrophages reduced the expression of NOD2 receptors whereas NOD1 remain unaffected. MDP, a NOD2-ligand, treatment during over-expression of NOD2, reduced the parasite burden effectively which was associated with increased pro-inflammatory cytokine generation and NO production. In experimental mouse model, Ara-LAM treatment increased the expression of NOD2 and in combination with MDP it showed active therapeutic potential against VL and found to be more effective than Mw which was already reported to be involved in NOD2 modulation. Conclusion: This work explores the essential contribution of NOD2 during experimental VL and mechanistic understanding of Ara-LAM + MDP combination therapy to work against this disease and highlighted NOD2 as an essential therapeutic target.

Keywords: Ara-LAM (Arabinoacylated Lipoarabinomannan), NOD2 (nucleotide binding oligomerization receptor 2), MDP (muramyl di peptide), visceral Leishmaniasis

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Authors: Kabiru Adamu

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The Nigerian electricity industry was deregulated and privatized in 2005 and 2014 in line with global trend and practice. International and multilateral lending institutions advised developing countries, Nigeria inclusive, to adopt deregulation and privatization as part of reforms in their electricity sectors. The ideological basis of these reforms are traceable to neoliberalism. Neoliberalism is an ideology that believes in the supremacy of free market and strong non-interventionist competition law as against government ownership of the electricity market. This ideology became a state practice and a blue print for the deregulation and privatization of the electricity markets in many parts of the world. The blue print was used as a template for the privatization of the Nigerian electricity industry. In this wise, this paper, using documentary analysis and review of academic literatures, examines neoliberalism as an ideology and model of economic governance for the electricity supply industry in Nigeria. The paper examines the origin of the ideology, it features and principles and how it was used as the blue print in designing policies for electricity reforms in both developed and developing countries. The paper found out that there is gap between the ideology in theory and in practice because although the theory is rational in thinking it is difficult to be implemented in practice. The paper argues that the ideology has a mismatched effect and this has made its application in the electricity industry in many developing countries problematic and unsuccessful. In the case of Nigeria, the article argues that the template is also not working. The article concludes that the electricity sectors in Nigeria have failed to develop into competitive market for the benefit of consumers in line with the assumptions and promises of the ideology. The paper therefore recommends the democratization of the electricity sectors in Nigeria through a new system of public ownership as the solution to the failure of the neoliberal policies; but this requires the design of a more democratic and participatory system of ownership with communities and state governments in charge of the administration, running and operation of the sector.

Keywords: electricity, energy governance, neo-liberalism, regulation

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Authors: S. A. El-Marasy, S. A. El Awdan, R. M. Abd-Elsalam

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This study aimed to investigate the possible neuroprotective effect of chrysin on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also, the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. Male Wistar rats were randomly allocated into five groups. The first group received the vehicle (distilled water) for 21 days and is considered as normal group. While the second one received intraperitoneal dose of TAA (200 mg/kg) at three alternative days during the third week of the experiment to induce HE and is considered as control group. The other three groups were orally administered chrysin for 21 days (25, 50, 100 mg/kg) and starting from day 17; rats received intraperitoneal dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Chrysin reversed TAA-induced motor coordination in rotarod test, cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonemia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.

Keywords: chrysin, hepatic encephalopathy, oxidative stress, rats, thioacetamide, TLR4/NF-κB pathway

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Authors: Farah Ali, Tehreem Fayyaz, Musadiq Idris

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The present work was undertaken to investigate effects of various extracts of W. somniferafor anti-diabetic activity in alloxan induced diabetic rabbits. Rabbits were acclimatized for a week to standard laboratory temperature. Animals were fed according to a strict schedule (8 am, 3 pm and 10 pm) with green fodder (Medicago sativa) and tap water ad libitum. Animals were divided into nine groups of six rabbits each in a random manner. Body weights and physical activities of all rabbits were recorded before start of experiments. The animals of group 1 and 2 were given lactose (250 mg/kg,p.o) and Withaniasomniferaroot powder (100 mg/kg, p.o) respectively daily from day 1-20. Animals of group 3 were given alloxan (100 mg/kg,i.v) as a single dose on day 1. Powdered root of Withaniasomnifera in the doses of 100, 150, 200 mg/kg and its aqueous and ethanol extracts (equivalent to 200 mg/kg of crude drug) were given to the treated animals (groups 4-8), respectively by oral route for three weeks (day 1-20o.d), along with alloxan (100 mg/kg, i.v) as a single dose on day 1. Group 9 was treated with metformin (200 mg/kg, p.o) daily from day 1-20, along with a single dose of alloxan (100 mg/ kg, i.v) on day 1. Fasting serum glucose concentration in groups 3-9 was increased significantly (p<0.05) on day 3, with a maximum increase (215.3 mg/dl) in animals of toxic control (TC) group (3) on day 21 of the experiment as compared to normal control (NC) group (1). Effects of different doses (100, 150, 200 mg/kg, p.o) of W. somnifera root powder (WS) decreased the fasting serum glucose concentration as compared to toxic control group, with a maximum decrease (88.3 mg/dl) in group 2 (treated control) on day 21 of the experiment. Metformin (200 mg/kg, p.o) (reference control), aqueous extract (AWS) and ethanol extract (EWS) of W. somnifera (equivalent to 100 mg/kg W.somnifera root, p.o) antagonized the effects of alloxan as compared to toxic control group. These results indicate that the W. somnifera possess significant anti –diabetic activity.

Keywords: diabetes, serum, glucose, blood, sugar, rabbits

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Authors: Miroslava Rysová, Zdena Syrová, Tomáš Zajíc, Petr Exnar

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Currently, attention of tissue engineers has been attracted to novel nanofibrous materials having advanced properties and ability to mimic extracellular matrix (ECM) by structure which makes them interesting candidates for application in regenerative medicine as scaffolding and/or drug delivering material. Throughout the last decade, more than 200 synthetic and natural polymers have been successfully electrospun leading to the formation of nanofibres with a wide range of chemical, mechanical and degradation properties. In this family, inorganic nanofibres represent very specific group offering an opportunity to manufacture inert to body, well degradable and in properties tunable material. Aim of this work, was to reveal unique properties of silica (SiO2, CAS 7631-86-9) nanofibres and their potential in field of regenerative medicine. Silica nanofibres were prepared by sol-gel method from tetraethyl orthosilicate (TEOS, CAS 78-10-4) as a precursor and subsequently manufactured by needleless electrospinning on NanospiderTM device. Silica nanofibres thermally stabilized under 200°C were confirmed to be fully biodegradable and soluble in several simulated body fluids. In vitro cytotoxicity tests of eluate (ES ISO 10993-5:1999) and in direct contact (ES ISO 10993-5:2009) showed no toxicity - e.g. cell viabilities reached values exceeding 80%. Those results were obtained equally from two different cell lines (Vero, 3T3). Non-toxicity of silaca nanofibres´ eluate was additionally confirmed in real time by testing on xCelligence (ACEA Biosciences, Inc.) device. Both cell types also showed good adhesion to material. To conclude, all mentioned results lead to resumption that silica nanofibres have a potential as material for regenerative medicine which opens door to further research.

Keywords: cytotoxicity, electrospinning, nanofibres, silica, tissue engineering

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Authors: Chamilani Nikapitiya, Mahanama De Zoysa, Jehee Lee

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Most of the bacterial diseases are associated with high mortalities in aquaculture species and causing huge economic losses. Different approaches have been taken to prevent or control of bacterial diseases including use of vaccines, probiotics, chemotherapy, water quality management, etc. Antibiotics are widely applying as chemotherapy to control bacterial diseases, however, it has been shown that frequent use of antibiotics is favored to develop multi-drug resistance bacteria. Therefore, phages and phage encoded lytic proteins are known to be one of the most promising alternatives for antibiotics to avoid the emergence of antibiotic-resistant bacteria. We isolated and characterized the two lytic phages, namely pAh-1 and pAs-1 against pathogenic Aeromonas hydrophila and Aeromonas salmonicida, respectively. Morphological characteristics were analyzed by Transmission electron microscopy (TEM) and host strain specificities were tested with Aeromonas and other closely related bacterial strains. TEM analysis revealed that both pAh-1 and pAsm-1 are composed of an icosahedral head and a segmented tail, and we suggest that, they are new members of Myoviridae family. Genome sizes of isolated phages were estimated by restriction enzyme digestion of genomic DNA using selected endonucleases followed by agarose gel electrophoresis. Estimated genome size of pAh-1 and pAs-1 were approximately 64 Kbp and 120 Kbp, respectively. Both pAh-1 and pAs-1 have shown narrow host specificity. Moreover, protective effects of phage therapy against fish pathogenic A. hydrophila were investigated in zebrafish model. The survival rate was 40% higher when zebrafish received intra-peritoneal injection (i.p.) of pAh-1 were simultaneously challenge A. hydrophila (2 x 106 CFU/fish) compared to that without phage treatment. Overall results suggest that both pAh-1 and pAs-1 can be used as a potential phage therapy to control Aeromonas infections in aquaculture.

Keywords: Aeromonas infections, antibiotic resistance, bacteriophage, bio-control, lytic phage

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Authors: Benjamin Newman

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The picture of an adverse contest between two parties has often been used as an archetypal description of the Anglo-American adversarial criminal trial. However, in actuality, guilty pleas and plea-bargains have been dominating the procedure for over the last half-a-century. Characterised by two adverse parties, the court adjudicative system in the Anglo-American world adhere to the adversarial procedure, and while further features have been attributed and the values that are embedded within the procedure vary, it is a system that we have no adequate theory. Damaska had argued that the adversarial conflict-resolution mode of administration of justice stems from a liberal laissez-faire concept of a value neutral liberal state. Having said that, the court’s neutrality has been additionally rationalised in light of its liberal end as a safeguard from the state’s coercive force. Both conceptions of the court’s neutrality conflict in cases where the by-standing role disposes of its liberal duty in safeguarding the individual. Such is noticeable in plea bargains, where the defendant has the liberty to plead guilty, despite concerns over wrongful convictions and deprivation of liberty. It is an inner liberal tension within the notion of criminal adversarialism, between the laissez-faire mode which grants autonomy to the parties and the safeguarding liberal end of the trial. Langbein had asserted that the adversarial system is a criminal procedure for which we have no adequate theory, and it is by reference to political and moral theories that the research aims to articulate a normative account. The paper contemplates on the above liberal-tension, and by reference to Duff’s ‘calling-to-account’ theory, argues that autonomy is of inherent value to the criminal process, being considered a constitutive element in the process of being called to account. While the aspiration is that the defendant’s guilty plea should be genuine, the guilty-plea decision must be voluntary if it is to be considered a performative act of accountability. Thus, by valuing procedural autonomy as a necessary element within the criminal adjudicative process, it assimilates a liberal procedure, whilst maintaining the liberal end by holding the defendant to account.

Keywords: liberal theory, adversarial criminal procedure, criminal law theory, liberal perfectionism, political liberalism

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Authors: Karolina Siejka, Monika Piekarska, Monika Zbroja, Weronika Cyranka, Maryla Kuczynska, Magdalena Grzegorczyk, Malgorzata Nowakowska, Agnieszka Brodzisz, Magdalena Maria Wozniak

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Crohn’s disease is one of chronic inflammatory bowel diseases. It is increasing in prevalence worldwide, especially with young people. The disease usually occurs in the second to the fourth decade of life. Traditionally is diagnosed by clinical indicates, endoscopic, and histological findings. Magnetic Resonance Enterography (MRE) can demonstrate mural and extramural inflammatory signs and complications, which make it a valuable diagnostic modality. The study included 76 adults and 36 children diagnosed with Crohn’s disease. Each patient underwent MRE with intravenous administration of a contrast agent. All the studies were performed using Siemens Aera 1.5T scanner according to a local study protocol. Whenever applicable, MR Enterography findings were verified with endoscopy. Forty adults and all 36 children had an active phase of Crohn’s disease; five adults had a chronic phase of the disease; one adult had both chronic and active inflammatory features. Thirty adults have no sings of pathology. In both adult and pediatric groups the most commonly observed manifestation of active disease was thickened edematous ileum wall (26 adults and 36 children). Adults had Bauhin’s valve edema in 58% cases (n=23) and mesenteric changes in 34% cases (n=9). To compare, 32 children had Bauhin’s valve edema (89%) and, in 23 cases, was found inflammatory infiltration of the peri-intestinal fat (64%). The involvement of the large intestine was more common among children (100%). Complications of Crohn’s disease were found commonly in adults (40% of adults, 22% of children). There were observed 18 fistulas (14 adults, four children) and six abscesses (2 adults, four children). MRE is a reliable method in the evaluation of Crohn’s disease activity, especially of its complications. The lack of radiations makes MRE well-tolerated modality, which can be often repeated, particularly in young patients. The disease had different medical sings depending on age – children often had a more active inflammatory process, but there were more complications in the adult group.

Keywords: Crohn's disease, diagnostics, inflammatory bowel disease, magnetic resonance enterography, MRE

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Authors: Chante J. De Klerk

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The potential of music to facilitate superior performance during high to elite level gymnastics conditioning instigated this research. A team of seven gymnasts completed a fixed conditioning programme eight times, alternating the two variable conditions. Four sessions of each condition were conducted: without music (session 1), with music (session 2), without music (3), with music (4), without music (5), and so forth. Quantitative data were collected in both conditions through physiological monitoring of the gymnasts, and administration of the Situational Motivation Scale (SIMS). Statistical analysis of the physiological data made it possible to quantify the presence as well as the magnitude of the musical intervention’s impact on various aspects of the gymnasts' physiological functioning during conditioning. The SIMS questionnaire results were used to evaluate if their motivation towards conditioning was altered by the intervention. Thematic analysis of qualitative data collected through semi-structured interviews revealed themes reflecting the gymnasts’ sentiments towards the data collection process. Gymnast-specific descriptions and experiences of the team as a whole were integrated with the quantitative data to facilitate greater dimension in establishing the impact of the intervention. The results showed positive physiological, motivational, and emotional effects. In the presence of music, superior sympathetic nervous activation, and energy efficiency, with more economic breathing, dominated the physiological data. Fatigue and arousal levels (emotional and physiological) were also conducive to improved conditioning outcomes compared to conventional conditioning (without music). Greater levels of positive affect and motivation emerged in analysis of both the SIMS and interview data sets. Overall, the intervention was found to promote psychophysiological coherence during the physical activity. In conclusion, a strategically constructed musical intervention, designed to accompany a gymnastics conditioning session for high to elite level gymnasts, has ergogenic potential.

Keywords: arousal, fatigue, gymnastics conditioning, motivation, musical intervention, psychophysiological coherence

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Authors: Amaraporn Puraya, Roongtiva Boonpracom, Somsak Thojampa, Sirikanok Klankhajhon, Kittisak Kumpeera

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The objective of this qualitative research was to study the elderly health care process by community participation. Data were collected by quality research methods, including secondary data study, observation, in-depth interviews, and focus group discussions and analyzed by content analysis, reflection and review of information. The research results pointed out that the important elderly health care process by community participation consisted of 2 parts, namely the community participation development process in elderly health care and the outcomes from the participation development process. The community participation development process consisted of 4 steps as follows: 1) Building the leadership team, an important social capital of the community, which started from searching for both formal and informal leaders by giving the opportunity for public participation and creating clear agreements defining roles, duties and responsibilities; 2) investigating the problems and the needs of the community, 3) designing the elderly health care activities under the concept of self-care potential development of the elderly through participation in community forums and meetings to exchange knowledge with common goals, plans and operation and 4) the development process of sustainable health care agreement at the local level, starting from opening communication channels to create awareness and participation in various activities at both individual and group levels as well as pushing activities/projects into the community development plan consistent with the local administration policy. The outcomes from the participation development process were as follows. 1) There was the integration of the elderly for doing the elderly health care activities/projects in the community managed by the elderly themselves. 2) The service system was changed from the passive to the proactive one, focusing on health promotion rather than treating diseases or illnesses. 3) The registered nurses / the public health officers can provide care for the elderly with chronic illnesses through the implementation of activities/projects of elderly health care so that the elderly can access the services more. 4) The local government organization became the main mechanism in driving the elderly health care process by community participation.

Keywords: elderly health care process, community participation, elderly, Thailand

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Authors: Gordon James Knowles

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Historically the Chinatown district in Sandwich Islands has been plagued with the traditional vice crimes of illegal drugs, gambling, and prostitution since the early 1800s. However, a new form of psychologically addictive arcade style table gambling machines has become the dominant form of illegal revenue made in Honolulu, Hawaii. This study attempts to document the drive, desire, or will to play and wager with arcade style video gaming and understand the role of illegal game rooms in facilitating pathological gambling addiction. Indicators of police corruption by Chinese organized crime syndicates related to protection rackets, bribery, and pay-offs were revealed. Information fusion from a police science and sociological intelligence perspective indicates insurgent warfare is being waged on the streets of Honolulu by the People’s Republic of China. This state-sponsored communist terrorism in the Hawaiian Islands used “contactless” irregular warfare entailing: (1) the deployment of psychologically addictive gambling machines, (2) the distribution of the physically addictive fentanyl drug as a lethal chemical weapon, and (3) psychological warfare by circulating pro-China anti-American propaganda newspapers targeted at the small island populace.

Keywords: Chinese and Polynesian organized crime, china daily newspaper, electronic arcade style table games, gaming technology addiction, illegal compulsive gambling, and police intelligence

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Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra

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Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.

Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed

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Authors: Howaida I. Abd-Alla, Amal Z. Hassan, Maha Soltan, Atef G. Hanna, Mounir M. El-Safty

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Acokanthera oblongifolia (Apocynaceae) is used for treatment of several infection diseases and is a well-known cardiac glycoside-containing plant. The infusion of their leaves is gargled to treat tonsillitis and is used medicinally to treat snakebites. The total cardiac glycosides content in the leaves was determined by referring to gitoxigenin as a reference compound. Two triterpenes, lup-20(29)-en-3β-ol (1) and oleanolic acid (2); two cardenolides, acovenoside A (3) and acobioside A (4) were isolated from the ethyl acetate extract. Their structures were determined on the basis of spectral analysis. Major constituents isolated from this species were evaluated for cytotoxicity against normal lung cell line (Wi38) and antimicrobial activities against Gram-positive (two strains) and Gram-negative bacteria (four strains), yeast-like fungi (two strains) and fungi (five strains). The minimum inhibitory concentration (MIC) of the compounds was determined using broth microdilution method. Their viral inhibitory effects against avian influenza virus type A (AI-H5N1) and Newcastle disease virus (NDV) in specific pathogen free (SPF) embryonated chicken eggs (ECE), chicken embryo fibroblasts (CEF) and Vero cells were evaluated. The cardenolide (3) showed viral inhibitory effects against AI-H5N1 and NDV in SPF ECE. The two cardenolides isolated have shown potent cytotoxicity against Vero cells. Compound (3) showed potent anti-Gram-negative bacteria activity. These results suggested that acovenoside A might be promising for future antiviral and antimicrobial drug design.

Keywords: Acokanthera, AI-H5N1, Cardenolides, NDV, SPF-ECE, VERO, Wi38 , Microbe

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Authors: Hiba T. Allah ALtieb Gusm ALsied, Amna Beshir Medani Ahmed, Ikram Mohamed ELtayeb, Saad Mohamed Hussein Ayoub

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This study was carried out to determine the hepatoactivity and the antioxidant activity of Coiradrum sativum L. aerial part and fruit extracts against CCL4 induced acute liver damages in Wistar rats. The aerial parts and fruits part of the plant were extracted 96% ethanol with soxhlet apparatus. Hepatic injury was achieved by subcutaneous injection of 3 ml/kg of CCL4 diluted with olive oil with ratio 1:1. The extracts were mixed together 1:1 ratio and given in different doses 100,200,400 mg/kg/day for 5 days under CCL4 induction at 3rd day. The significance of differences between means by using T-test was compared among the groups. The mixture of the two extracts didn’t show any significant result in protecting liver injury (antagonistic effects), it shows high level of liver enzyme like alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (SGOT) and glutamate pyruvate transaminase (SGPT). Serological studies further confirmed the results. The results obtained were compared with silymarin (70 mg/kg/day) orally, the standard drug for hepatoprotection which show recovery close to normalization almost like that of silymarin; therefore, further studies on this plant with different ratios especially in isolated tissue to spot more light on antagonistic effects of the two extracts. Antioxidant activity of the extracts was determined by the DPPH method. The results obtained show high anti-oxidant activity for fruits extract while slight or moderate antioxidant activity to aerial extracts.

Keywords: antioxidant, aerial part, Coriadrum sativum L., fruity, hepatoprotection, Silymarin, phytochemical screening

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Authors: Yan Ding, Fei Yan, Ji Liang, Hong Jiang, Xiaoguang Yang, Xu Qian

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The health status of GonjiKolela District, Amhara Region, Ethiopia is below its national average, and a sub-project of China UK Global Health Support Programme (GHSP) is expected to increase the uptake of a suite of reproductive, maternal, newborn and child health (RMNCH) interventions there. To explore what is on the ground and what could be helpful for the uptake of RMNCH services in GonjiKolela, a qualitative study was performed as part of the baseline assessment before the implementation of the project. Nine key informants from GonjiKolela were interviewed with self-designed interview guides and they were from the district Health Office, health centers, health posts, women health development army (community volunteer groups), mothers of newborns, and also a gynecologist from the maternal and child health center which is the referral center for pregnant women for this project. The interview were transcribed into words and sorted with qualitative analysis software MAXqda. Content analysis was mainly used to analyze the data. The district health office, the health centers and the health posts all had focal persons taking care of the management and provision of RMNCH services, and RMNCH related indicators were recorded and reported at each level routinely. In addition, district government and administration at community/administrative village level kept a close eye on the reduction of maternal, neonatal and child mortality. Women Health Development Amy at household level supported health workers at community/administrative village level (called health extension workers) in tracing, recording and reporting pregnant women, newborn and under-five children,organizing events for health education, demonstrating and leading health promotion activities, and stimulating the utilization of RMNCH.

Keywords: Reproductive Maternal Newborn and Child Health, Health Care Utilization, Qualitative Study, Ethiopia

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Authors: Alexandra P. Alexandropoulou, Andreas Fousteris, Eleni Didaskalou, Dimitrios A. Georgakellos

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As urbanization is becoming a major stress factor not only for the urban environment but also for the wellbeing of city dwellers, incorporating the issues of urban health in strategic city planning and policy-making has never been more relevant. The impact of urbanization can vary from low to severe and relates to all non-communicable diseases caused by the different functions of cities. Air pollution, noise pollution, water and soil pollution, availability of open green spaces, and urban heat island are the major factors that can compromise citizens' health. Urban health describes the effects of the social environment, the physical environment, and the availability and accessibility to health and social services. To assess the quality of urban wellbeing, all urban characteristics that might have an effect on citizens' health must be considered, evaluated, and introduced in integrated local planning. A series of indices and indicators can be used to better describe these effects and set the target values in policy making. Local strategic planning is one of the most valuable development tools a local city administration can possess; thus, it has become mandatory under Greek law for all municipalities. It involves a two-stage procedure; the first aims to collect, analyse and evaluate data on the current situation of the city (administrative data, population data, environmental data, social data, swot analysis), while the second aims to introduce a policy vision described and supported by distinct (nevertheless integrated) actions, plans and measures to be implemented with the aim of city development and citizen wellbeing. In this procedure, the element of health is often neglected or under-evaluated. A relative survey was conducted among all Greek local authorities in order to shed light on the current situation. Evidence shows that the rate of incorporation of health in strategic planning is lacking behind. The survey also highlights key hindrances and concerns raised by local officials and suggests a path for the way forward.

Keywords: urban health, strategic planning, local authorities, integrated development

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Authors: Tasneem Imam, Justine S. Gibson, Mohammad Foysal, Shetu B. Das, Rashed Mahmud, Suman D. Gupta, Ahasanul Hoque, Guillaume Fournie, Joerg Henning

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Commercial chicken production is an import livestock industry in Bangladesh. Antimicrobials are commonly used to control and prevent infectious diseases. It was hypothesized that inadequate biosecurity practices might promote antimicrobial usage on commercial chicken farms. A cross-sectional study was carried out to evaluate antimicrobial usage and farm biosecurity practices implemented on 57 layer and 83 broiler farms in eight sub-districts of the Chattogram district in Bangladesh. A questionnaire was used to collect data on antimicrobial usage and biosecurity practices on these farms. A causal framework was used to guide the development of a multi-level mixed-effects logistic regression analysis to evaluate the total and direct effects of practiced biosecurity management on prophylactic and therapeutic administration of antimicrobials. A total of 24 antimicrobials were administered in the current production cycle at the time of the survey. The most administered antimicrobials on layer farms were ciprofloxacin (37.0% of farms), amoxicillin (33.3%), and tiamulin (31.5%); however, on broiler farms, colistin (56.6% of farms), doxycycline (50.6%), and neomycin (38.6%) were most used. Only 15.3% of commercial farmers used antimicrobials entirely for therapeutic purposes, whereas 84.7% administered antimicrobials prophylactically. Inadequate biosecurity practices were more common among commercial broiler farmers compared to layer farmers. For example, only 2.4% of broiler farmers used footbaths before entering sheds compared to 22.2% of the layer farmers (p < 0.001). Farms that used antimicrobials only for therapeutic purposes (vs prophylactic) implemented more frequently adequate disease control measures, such as separating sick birds from healthy birds. This research highlighted that the prophylactic application of antimicrobials is often conducted to substitute poor biosecurity practices on commercial chicken farms. Awareness programs for farmers are crucial to inform them about the risk associated with antimicrobial usage and to highlight the economic benefits of implementing cost-effective biosecurity measures to control infectious poultry diseases.

Keywords: antimicrobial, biosecurity, broiler, layer

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Authors: Tabassum Yasmin, Hamid Pahlevan

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HIV/Hepatitis C co-infection treatments have evolved substantially and they have similar sustained virologic response rates as those of Hepatitis C monoinfected population. There are a few studies on therapy of patients with dual genotypes, especially in HIV/Hepatic C coinfected group. Most studies portrayed case reports of dual genotype chronic Hepatitis C coinfection treatment with Sofosbuvir/Ledipasvir and Ribavirin. A 79-year-old male with a history of HIV on Truvada and Isentress had chronic Hepatitis C with 1a and 2 genotypes. The patient has a history of alcohol intake for 40 years but recently stopped drinking alcohol. He has a history of intravenous drug use in the past and currently is not using any recreational drugs. Patient has Fibro score of 0.7 with Metavir score F2 to F4. AFP is 3.2. The HCV RNA is 493,034 IU/ML. The HBV viral DNA is < 1.30 (not detected). The CD4 is 687CU/MM. The FIB 4 is 3.34 with APRI index 0.717. The HIV viral load is 101 copies/ML. MRI abdomen did not show any liver abnormality. Fixed dose Sofosbuvir/Ledipasvir was used for therapy without Ribavirin. He tolerated medication except for some minor gastrointestinal side effects like abdominal bloating. He demonstrated 100% adherence rate. Patient completed 12 weeks of therapy. HCV RNA was undetectable at 4 and 12 weeks. He achieved SVR at week 12 and subsequently had undetectable RNA for 2 years. Dual genotype prevalence in chronic hepatitis C population is rare, especially in HIV/hepatic coinfection. Our case demonstrates that dual genotypic cases can still be successfully treated with Direct Acting Antiviral agents. The newer agents for therapy for pan genotypes were not available at the time the patient was being treated. We demonstrated that dual agent therapy was still able to maintain SVR in our patient.

Keywords: HIV/Hepatitis C, SVR (sustained virologic response), DAA (direct active antiviral agents, dual genotype

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Authors: A. Pascual Ramsay

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Accounts of the management of the economic and euro crisis in Spain have been dominated by an emphasis on external constraints. However, this approach leaves unanswered important questions about the role of domestic political factors. Using systematic qualitative primary research and employing elite interviewing and process tracing, this paper aims to fill this gap for the period of the Partido Socialista Obrero Español (PSOE) administration. The paper shows that domestic politics played a crucial role in the management of the crisis, most importantly by determining the shape of the measures undertaken. In its three distinct stages – downplaying/inaction, reaction/stimulus, and austerity/reform – the PSOE's response was certainly constrained by external factors, most notably EMU membership and the actions of sovereign-bond investors, the ECB and Germany. Yet while these external constraints forced the government to act, domestic political factors fundamentally shaped the content of key measures: the fiscal stimulus, the labour, financial and pension reforms, the refusal to accept a bailout or the reform of the Constitution. Seven factors were particularly influential: i) electoral and political cost, ii) party and partisanship, iii) organised interests, iv) domestic institutions, v) ideological preferences, vi) ineffective decision-making, and vii) judgement and personal characteristics of decision-makers. In conclusion, domestic politics played an important role in the management of the crisis, a role that has been underestimated by dominant approaches focusing on external constraints and weak domestic policy autonomy. The findings provide empirical evidence to support research agendas that identify significant state discretion in the face of international economic integration and an important role for domestic political factors such as institutions, material interests, partisanship and ideology in shaping economic outcomes.

Keywords: economic crisis, Euro, PSOE, Spain

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Authors: Irene Alevizos, Jessica Lewis, Marina Harper, John Boyce

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Acinetobacter baumannii causes a range of severe nosocomial-acquired infections, and many strains are multi-drug resistant. A. baumannii possesses survival mechanisms allowing it to thrive in competitive polymicrobial environments, including a Type VI Secretion System (T6SS) that injects effector proteins into other bacteria to give a competitive advantage. The effects of T6SS firing are broad and depend entirely on the effector that is delivered. Effects can include toxicity against prokaryotic or eukaryotic cells and the acquisition of essential nutrients. The T6SS of some species can deliver ‘specialised effectors’ that are fused directly to T6SS components, such as PAAR proteins. PAAR proteins are predicted to form the piercing tip of the T6SS and are essential for T6SS function. Although no specialised effectors have been identified in A. baumannii, many strains encode multiple PAAR proteins. Analysis of PAAR proteins across the species identified 12 families of PAAR proteins with distinct C-terminal extensions. A. baumannii AB307-0294 encodes two PAAR proteins, one of which has a C-terminal extension. Mutation of one or both of the PAAR-encoding genes in this strain showed that expression of either PAAR protein was sufficient for T6SS function. We employed a heterologous expression approach and determined that PAAR proteins from different A. baumannii strains, as well as the closely related A. baylyi species, could complement the A. baumannii ∆paar mutant and restore T6SS function. Furthermore, we showed that PAAR fusions could be used to deliver artificially cloned protein fragments by generating Histidine- and Streptavidin- tagged PAAR specialised effectors, which restored T6SS activity. This provides evidence that the fusion of protein fragments onto PAAR proteins in A. baumannii is compatible with a functional T6SS. Successful delivery by this mechanism extends the scope of what the T6SS can deliver, including user designed proteins.

Keywords: A. baumannii, effectors, PAAR, T6SS

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Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi

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Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.

Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration

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Authors: Mandeep Kaur, Jitendra K. Bera

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The search for atom-economical and green synthetic methods for the synthesis of functionalized molecules has attracted much attention. Metal ligand cooperation (MLC) plays a pivotal role in organometallic catalysis to activate C−H, H−H, O−H, N−H and B−H bonds through reversible bond breaking and bond making process. Towards this goal, a bifunctional N─heterocyclic carbene (NHC) based pyridyl-functionalized amide ligand precursor, and corresponding dearomatized iridium complex was synthesized. The NMR and UV/Vis acid titration study have been done to prove the proton response nature of the iridium complex. Further, the dearomatized iridium complex explored as a catalyst on the platform of MLC via dearomatzation/aromatization mode of action towards atom economical α and β─alkylation of ketones and secondary alcohols by using primary alcohols through hydrogen borrowing methodology. The key features of the catalysis are high turnover frequency (TOF) values, low catalyst loading, low base loading and no waste product. The greener syntheses of quinoline, lactone derivatives and selective alkylation of drug molecules like pregnenolone and testosterone were also achieved successfully. Another structurally similar iridium complex was also synthesized with modified ligand precursor where a pendant amide unit was absent. The inactivity of this analogue iridium complex towards catalysis authenticated the participation of proton responsive imido sidearm of the ligand to accelerate the catalytic reaction. The mechanistic investigation through control experiments, NMR and deuterated labeling study, authenticate the borrowing hydrogen strategy.

Keywords: C-C bond formation, hydrogen borrowing, metal ligand cooperation (MLC), n-heterocyclic carbene

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