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Sökning: WFRF:(Siddique M.)

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1.
  • Khatri, C, et al. (författare)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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4.
  • Gruen, E., et al. (författare)
  • Ulysses Dust Detection System V3.1
  • 2010
  • Ingår i: NASA Planetary Data System. ; 140
  • Tidskriftsartikel (refereegranskat)abstract
    • This data set contains the data from the Ulysses dust detector system (UDDS) from start of mission through the end of mission, 1990-2007. (As the dust detector was turned off after Nov. 30, 2007, this is the last date for which UDDS data is recorded.) Included are the dust impact data, noise data, laboratory calibration data, and location and orientation of the spacecraft and instrument.
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5.
  • Fakhar-e-Alam, M, et al. (författare)
  • Role of ALA sensitivity in HepG2 cell in the presence of diode laser
  • 2011
  • Ingår i: LASER PHYSICS. - : Springer Science Business Media. - 1054-660X. ; 21:5, s. 972-980
  • Tidskriftsartikel (refereegranskat)abstract
    • 5-aminolevulinic acid (ALA) being an amazing second generation photosensitizer was studied as photodamaging drug on hepatocellular carcinoma (HepG2) cells. The mentioned photosensitizer is converted to PpIX in HepG2 cells in vitro, inducing haem in the cell causing generation of singlet oxygen leading to cell apoptosis. Cell uptake of 5-ALA was evaluated with different concentrations (ranging from 0-800 mu g/ml) for 0-49 h incubation period. ALA administered in HepG2 cells is converted into Protoporphyrin IX (PpIX) which has a short half life and constitute a good hematoporphyrin derivative (HPD). Cytotoxicity of ALA in dark and cellular viability without ALA in the presence of light was studied, showing minimal toxic effects in dark with no photodamaging effect on mentioned cells in absence of ALA were observed. The optimal uptake of photosensitizer (5-ALA) in HepG2 cells was investigated by means of spectrophotometeric measurements, cellular viability was determined by means of neutral red assay (NRA). It was observed that with different concentrations (0-800 mu g/ml) of ALA or light doses (0-160 J/cm(2)), there were no significant effect on cellular viability when studied independently. The novel of photocytotoxic study indicates that light dose of 120 J/cm(2) produces convincing Photodynamic therapy (PDT) results for HepG2 cells incubated with 262 mu g/ml of 5-ALA deducting that HepG2 cell line is sensitive to ALA mediated PDT. Finally morphological changes in HePG2 cells were determined before and after ALA-mediated PDT by confocal microscopy.
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6.
  • Krueger, H., et al. (författare)
  • Galileo Dust Detection System V4.1
  • 2010
  • Ingår i: NASA Planetary Data System. ; 139
  • Tidskriftsartikel (refereegranskat)abstract
    • This data set contains the data from the Galileo dust detector system (GDDS) from start of mission through the end of mission. Included are the dust impact data, noise data, laboratory calibration data, and location and orientation of the spacecraft and instrument.
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11.
  • Fakhar-e-Alam, M., et al. (författare)
  • Tumoricidal Effects of Nanomaterials in HeLa Cell Line
  • 2011
  • Ingår i: Laser physics. - : MAIK Nauka/Interperiodica. - 1054-660X .- 1555-6611. ; 21:11, s. 1978-1988
  • Tidskriftsartikel (refereegranskat)abstract
    • The current study exhibits the cellular response of HeLa (cervical cancer) cells to metal oxides ultrafine nanomaterials e.g. manganese dioxide nanowires (MnO(2) NRs), iron oxide nanoparticles (Fe(2)O(3) NPs) and zinc oxide nanorods (ZnO NRs) as bare and as conjugated with photosensitizers. For cytotoxic evaluations, the cellular morphology, (MTT) assay, reactive oxygen species (ROS) production were used for cases with and without photo sensitizer as well illuminated with UV-visible laser exposed conditions. Three different photosensitizers were tested. These are 5-aminolevulinic acid (5-ALA), Photofrin (R), and protoporphyrin dimethyl ester (PPDME). Significant loss in cell viability was noted with 100-500 mu g/ml in bare and conjugated forms of the metal oxides used. The effect was insignificant with lower concentrations (0.05-50 mu g/ml). While notable anticancer effect of 5-ALA under 30 J/cm(2) of diode laser irradiation was noted as compared to other photo sensitizer. By increasing the UV irradiation time of labeled cells, generation of ROS was observed, indicating the possibility of achieving efficient photodynamic therapy (PDT).
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12.
  • Paul, Sudip Kumar, et al. (författare)
  • Higher risk of hyperglycemia with greater susceptibility in females in chronic arsenic-exposed individuals in Bangladesh
  • 2019
  • Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 668, s. 1004-1012
  • Tidskriftsartikel (refereegranskat)abstract
    • Arsenic (As) toxicity and diabetes mellitus (DM) are emerging public health concerns worldwide. Although exposure to high levels of As has been associated with DM, whether there is also an association between low and moderate As exposure and DM remains unclear. We explored the dose-dependent association between As exposure levels and hyperglycemia, with special consideration of the impact of demographic variables, in 641 subjects from rural Bangladesh. The total study participants were divided into three groups depending on their levels of exposure to As in drinking water (low, moderate and high exposure groups). Prevalence of hyperglycemia, including impaired glucose tolerance (IGT) and DM was significantly associated with the subjects’ drinking water arsenic levels. Almost all exposure metrics (As levels in the subjects’ drinking water, hair and nails) showed dose-dependent associations with the risk of hyperglycemia, IGT and DM. Among the variables considered, sex, age, and BMI were found to be associated with higher risk of hyperglycemia, IGT and DM. In sex-stratified analyses, As exposure showed a clearer pattern of dose-dependent risk for hyperglycemia in females than males. Finally, drinking water containing low-to-moderate levels of As (50.01–150 μg/L) was found to confer a greater risk of hyperglycemia than safe drinking water (As ≤10 μg/L). Thus the results suggested that As exposure was dose-dependently associated with hyperglycemia, especially in females. © 2019 Elsevier B.V.
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13.
  • Saeed, M, et al. (författare)
  • Age and founder effect of SOD1 A4V mutation causing ALS.
  • 2009
  • Ingår i: Neurology. - : American Academy of Neurology. - 0028-3878 .- 1526-632X. ; 72:19, s. 1634-1639
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The alanine to valine mutation at codon 4 (A4V) of SOD1 causes a rapidly progressive dominant form of amyotrophic lateral sclerosis (ALS) with exclusively lower motor neuron disease and is responsible for 50% of SOD1 mutations associated with familial ALS in North America. This mutation is rare in Europe. The authors investigated the origin (geographic and time) of the A4V mutation. METHODS: Several cohorts were genotyped: North American patients with confirmed A4V mutation (n = 54), Swedish (n = 3) and Italian (n = 6) A4V patients, patients with ALS with SOD1 non-A4V mutations (n = 66) and patients with sporadic ALS (n = 96), healthy white (n = 96), African American (n = 17), Chinese (n = 53), Amerindian (n = 11), and Hispanic (n = 12) subjects. High-throughput SNP genotyping was performed using Taqman assay in 384-well format. A novel biallelic CA repeat in exon 5 of SOD1, tightly linked to A4V, was genotyped on sequencing gels. Association statistics were estimated using Haploview. p Values less than 0.05 were considered significant. Age of A4V was estimated using a novel method based on r(2) degeneration with genetic distance and a Bayesian method incorporated in DMLE+. RESULTS: A single haplotype of 10 polymorphisms across a 5.86-cM region was associated with A4V (p = 3.0e-11) when white controls were used, suggesting a founder effect. The strength of association of this haplotype progressively decreased when African American, Chinese, Hispanic, and Amerindian subjects were used as controls. The associated European haplotype was different from the North American haplotype, indicating two founder effects for A4V (Amerindian and European). The estimated age of A4V with the r(2) degeneration method was 458 +/- 59 years (range 398-569) and in agreement with the Bayesian method (554-734 years with 80-90% posterior probability). CONCLUSIONS: North American SOD1 alanine to valine mutation at codon 4 descended from two founders (Amerindian and European) 400-500 years ago.
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  • Silva, M., et al. (författare)
  • EMB3Rs: A game-changer tool to support waste heat recovery and reuse
  • 2024
  • Ingår i: Energy Conversion and Management. - : Elsevier BV. - 0196-8904 .- 1879-2227. ; 309
  • Tidskriftsartikel (refereegranskat)abstract
    • At a time when European countries try to cope with escalating energy prices while decarbonizing their economies, waste heat recovery and reuse arises as part of the solution for sustainable energy transitions. The lack of appropriate assessment tools has been pointed out as one of the main barriers to the wider deployment of waste heat recovery projects and as a reason why its potential remains largely untapped. The EMB3Rs platform emerges as an online, open-source, comprehensive and novel tool that provides an integrated assessment of different types of waste heat recovery solutions, (e.g. internal or external) and comprises several analysis dimensions (e.g. physical, geographical, technical, market, and business models). It has been developed together with stakeholders, and tested in a number of representative contexts, covering both industrial and heat network applications. This has demonstrated the enormous potential of the tool in dealing with complex simulations, while delivering accurate results within a significantly lower time-frame than traditional analysis. The EMB3Rs tool removes important barriers such as analysis costs, time and complexity for the user, and aims at supporting a wider investment in waste heat recovery and reuse by providing an integrated estimation of the costs and benefits of such projects. This paper describes the tool and illustrates how it can be applied to help unlock the potential of waste heat recovery across European countries.
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  • Ejaz, Syeda Abida, et al. (författare)
  • New Insight into the Pharmacological Importance of Atropine as the Potential Inhibitor of AKR1B1 via Detailed Computational Investigations: DFTs, ADMET, Molecular Docking, and Molecular Dynamics Studies
  • 2023
  • Ingår i: Applied Biochemistry and Biotechnology. - : SPRINGER. - 0273-2289 .- 1559-0291. ; 195:8, s. 5136-5157
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this research is to investigate the quantum geometric properties and chemical reactivity of atropine, a pharmaceutically active tropane alkaloid. Using density functional theory (DFT) computations with the B3LYP/SVP functional theory basis set, the most stable geometry of atropine was determined. Additionally, a variety of energetic molecular parameters were calculated, such as the optimized energy, atomic charges, dipole moment, frontier molecular orbital energies, HOMO-LUMO energy gap, molecular electrostatic potential, chemical reactivity descriptors, and molecular polarizability. To determine atropines inhibitory potential, molecular docking was used to analyze ligand interactions within the active pockets of aldo-keto reductase (AKR1B1 and AKR1B10). The results of these studies showed that atropine has greater inhibitory action against AKR1B1 than AKR1B10, which was further validated through molecular dynamic simulations by analyzing root mean square deviation (RMSD) and root mean square fluctuations (RMSF). The results of the molecular docking simulation were supplemented with simulation data, and the ADMET characteristics were also determined to predict the drug likeness of a potential compound. In conclusion, the research suggests that atropine has potential as an inhibitor of AKR1B1 and could be used as a parent compound for the synthesis of more potent leads for the treatment of colon cancer associated with the sudden expression of AKR1B1.
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  • Islam, M. Shahidul, et al. (författare)
  • Is road-side fishpond water in Bangladesh safe for human use? An assessment using water quality indices
  • 2022
  • Ingår i: Environmental Challenges. - : Elsevier BV. - 2667-0100. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Pond water is used in everyday life by many people in Bangladesh, however, without sufficient and reliable information regarding water quality and pollution status. For this reason, geospatial analysis and mapping of water quality indices such as metal (MI), contamination (Cd), and physicochemical water quality index (WQI) were assessed to improve the understanding of potential pollution sources. Samples were collected from twenty randomly selected ponds situated in Jashore Sadar Upazila, Bangladesh. Nineteen (19) water quality parameters were measured, including pH, temperature, EC, TDS, total suspended solids (TSS), chloride, alkalinity, total hardness, salinity, Fe, Mn, Pb, Cr, Cd, Co, Zn, Ag, Ni, and Cu. The average concentration of Fe, Mn, Pb, Cd, and Ag was much higher than recommended standards. The WQI ranged from 1.59-5.27, Cd from -0.19-18.28, and MI from 7.81-26.28. The spatial distribution of MI indicates that the south-western and south-eastern region of the study area are stands out with a very high pollution pressure. The spatial distribution of Cd, follows the same trend as for MI. A multitude of different types of pollution sources contributes to the high pollution load such as, municipal wastewater, leachate from landfills, small industry wastewater and stormwater, and agricultural runoff. The studied pond water is highly polluted and not suitable for household use and fish consumption.
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  • Islam, M. Shahidul, et al. (författare)
  • Toxicity and source identification of pollutants in an urban river in Bangladesh
  • 2023
  • Ingår i: Environmental Earth Sciences. - : Springer Science and Business Media LLC. - 1866-6280 .- 1866-6299. ; 82:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Urban rivers in Asian developing countries are becoming increasingly polluted due to industrialization and lacking treatment of wastewater. We investigated toxicity and likely sources of pollutants for the urban Shitalakshaya River, Bangladesh. Physiochemical variables and heavy metals were examined in water and sediment of an urban river section in Narayanganj City. The spatial distribution of quality indices and cluster groups indicates that the river’s downstream urban-affected areas are the most contaminated. Water and sediment quality guidelines indicate that COD, TSS, Fe, Pb, Zn in water, and Pb, Co, Ni, Cu, Zn, and particularly Pb and Cu in sediment, pose a serious threat to the aquatic ecosystem and human health in the area. Correlation, principal component (PCA), and cluster analysis (CA) indicate that the sources of Mn and Cd are geogenic, COD, TSS, Pb, Zn, Cu anthropogenic, and Fe, Ni, Co both geogenic and anthropogenic. The main anthropogenic pollution sources of the study area are municipal and industrial wastewater, boat and car traffic, runoff from agricultural areas, and stormwater runoff.
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  • Kanwal, Ansa, et al. (författare)
  • Polyethersulfone (PES) nanofiltration membrane for treatment of toxic metal contaminated water
  • 2022
  • Ingår i: Emerging Techniques for Treatment of Toxic Metals from Wastewater. - 9780128228807 ; , s. 319-341
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Polyethersulfone is most extensively utilized material in waste treatment application via membranes technology since it offers high thermal, chemical, and mechanical properties. The world now has problems with drinking water and the present situation seems to be very complex to meet clean water requirements. The treatment of water supplies by clean-up techniques is urgently considered by increased daily demand, which leads to dangerous conditions unless this problem is controlled. Most important contributors to ecological pollution with metal ions are mining, metal shining, power generation houses, galvanization, tannery industries, metallurgical, and electroplating. There are many techniques to remove the metal ions such as adsorption, microbial fuel cells, oxidation/reductions, ion exchange etc. Among all the technologies nanofiltration membranes attract more attention to remove the toxic metal ions from water even at lower concentration. It is very simple, feasible and economically affordable technology. Several types of nanofiltration techniques are used before but most attractive is polyethersulfone (PES) nanofiltration membrane. It minimizes several issues which are present in the nanofiltration process. In this chapter we briefly discussed the modification strategies and removal efficiency of metal ions via polyethersulfone (PES) nanofiltration membrane.
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  • Kishwar, Sultana, et al. (författare)
  • Biotoxicity of nanometallic oxides and their ligands with photosensitizers in osteosarcom a cells
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • The cytotoxic effects in osteosarcoma (U2OS) cells to different nanosized metallic oxides e.g. zinc oxide nanowires (ZnO-NWs), manganese di-oxide nanowires (MnO2 NWs), ferric oxide nanoparticles (Fe2O3 NPs) individually and their complex forms with photosensitizers photofrin®, 5-Aminolevulinic acid (5-ALA), and protoporphyrin IX (Pp IX) were studied. The cellular effects were assayed by analyzing the cellular morphology. The reactive oxygen species (ROS) were detected using 2', 7'-Dichlorofluorescein diacetate, and cell viability were assessed using MTT assay under ultraviolet (UV), visible light and laser exposed conditions. Prominent cell death with above cited nanomaterials in their complex forms with photosensitizer was observed in labeled U2OS cells. This cell death might be due to their synergetic effect via the release of singlet oxygen species in osteosarcoma cells showing their anticancer-cell effects.
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  • Shahid, Ahosanul H., et al. (författare)
  • Molecular detection of vancomycin and methicillin resistance in Staphylococcus aureus isolated from food processing environments
  • 2021
  • Ingår i: One Health. - : Elsevier. - 2352-7714. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Staphylococcus aureus is a well-known foodborne pathogen. The aim of this study was to investigate the presence of S. aureus isolated from serving utensils in food processing environments in Mymensingh city, Bangladesh and to determine their antibiogram and resistance determinants. A total of 120 environmental samples were collected from different food settings. Isolation and identification were conducted using conventional biochemical tests. Molecular identification of isolates and detection of methicillin and vancomycin resistance were done using primer-specific polymerase chain reaction (PCR) targeting Tuf, nuc, mecA, and mecC genes. Antibiotic sensitivity tests were performed, and resistance genes were also detected by amplifying blaTEM, vanA, vanB, and vanC genes. Among the 120 samples, 81 (67.5%) were positive for Staphylococcus spp. and 41 (50.62%) were positive for the nuc-gene. Among the 41 isolates, 5 (12.20%) were positive for mecA, but none were positive for the mecC gene. A total of 12.2% of the isolates were vanC-positive, of which 4 isolates (9.76%) were also positive for the mecA gene. Antibiotic sensitivity testing revealed that all S. aureus isolates (100%) from hotel samples were sensitive to ciprofloxacin and chloramphenicol, 90.32% were sensitive to doxycycline, and 80.65% were sensitive to streptomycin. Conversely, all isolates (100%) were resistant to ampicillin, and 29.03% were resistant to vancomycin. All S. aureus isolates obtained from non-hotel samples were susceptible to chloramphenicol, ceftriaxone, ciprofloxacin, doxycycline, meropenem, and vancomycin; however, 40% of isolates were resistant to novobiocin. Among the hotel isolates, 29 (93.55%) of the ampicillin-resistant isolates harbored the blaTEM gene while 5 (55.55%) of the vancomycin-resistant isolates harbored the vanC gene. Four of the five vanC positive isolates were also positive for the mecA gene. The presence of methicillin-resistant S. aureus (MRSA) which is also vancomycin-resistant in food processing environments is a threat to public health. This is the first report on the molecular detection of methicillin and vancomycin-resistant S. aureus isolated from food processing environments in Bangladesh.
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  • Siddique, Waqar, et al. (författare)
  • The Development of Eletriptan Hydrobromide Immediate Release Buccal Films Using Central Composite Rotatable Design : An In Vivo and In Vitro Approach
  • 2022
  • Ingår i: Polymers. - : MDPI. - 2073-4360. ; 14:19
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective is to develop immediate release buccal films of Eletriptan Hydrobromide (EHBR) using hydroxypropyl methylcellulose (HPMC) E5. The buccal films have the ability to disintegrate rapidly and provide both systemic and local effects. The solvent casting method was employed to prepare the films and the central composite rotatable design (CCRD) model was used for film optimization. All the formulated films were characterized for physicochemical evaluation (Fourier transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), differential scanning calorimetry (DSC), and Scanning electron microscopy (SEM), in in-vitro, ex-vivo, and in-vivo drug release. The fabricated films were transparent, colorless, and evenly distributed. The FTIR spectra showed no chemical interaction between the drug and excipients. In in-vitro analysis, the film has the highest% drug release (102.61 +/- 1.13), while a maximum of 92.87 +/- 0.87% drug was diffused across the cellulose membrane having a pore size of 0.45 mu m. In the ex-vivo study, drug diffusion across the goat mucosa was performed and 80.9% of the drug was released in 30 min. In-vivo results depict a mean half-life (t1/2) of 4.54 +/- 0.18 h and a C-max of 128 +/- 0.87 (ng/mL); T-max was achieved in 1 h. Furthermore, instability and histopathological studies buccal films were proven to be safe and act as an effective dosage form. In a nutshell, optimized and safe instant release EHBR buccal films were prepared that have the tendency to provide effect effectively.
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  • Ahsan, Hajra, et al. (författare)
  • Photocatalysis and adsorption kinetics of azo dyes by nanoparticles of nickel oxide and copper oxide and their nanocomposite in an aqueous medium
  • 2022
  • Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Azo dyes are recalcitrant organic pollutants present in textile industry effluents. Conventional treatment methods to remove them come with a range of disadvantages. Nanoparticles and their nanocomposites offer more efficient, less expensive and easy to handle wastewater treatment alternative. Methods. In this study, nanoparticles of nickel oxide (NiO-NPs), copper oxide (CuO-NPs) and their nanocomposite (NiO/CuO-NC) were synthesized using co- precipitation method. The functional groups present on the surface of synthesized nanomaterials were verified using Fourier-transform infrared spectroscopy (FTIR). Surface morphology was assessed using scanning electron microscopy (SEM) whereas purity, shape and size of the crystallite were determined using X-ray diffraction (XRD) technique. The potential of these nanomaterials to degrade three dyes i.e., Reactive Red-2 (RR-2), Reactive Black-5 (RB-5) and Orange II sodium salt (OII) azo dyes, was determined in an aqueous medium under visible light (photocatalysis). The photodegradation effectiveness of all nanomaterials was evaluated under different factors like nanomaterial dose (0.02-0.1 g 10 mL-1), concentration of dyes (20-100 mg L-1), and irradiation time (60-120 min). They were also assessed for their potential to adsorb RR-2 and OII dyes. Results. Results revealed that at optimum concentration (60 mgL-1) of RR-2, RB-5, and OII dyes, NiO-NPs degraded 90, 82 and 83%, CuO-NPs degraded 49, 34, and 44%, whereas the nanocomposite NiO/CuO-NC degraded 92, 93, and 96% of the said dyes respectively. The nanomaterials were categorized as the efficient degraders of the dyes in the order: NiO/CuO-NC > NiO-NPs > CuO-NPs. The highest degradation potential shown by the nanocomposite was attributed to its large surface area, small particles size, and quick reactions which were proved by advance analytical techniques. The equilibrium and kinetic adsorption of RR-2 and OII on NiO-NPs, CuO-NPs, and NiO/CuO-NC were well explained with Langmuir and Pseudo second order model, respectively (R2 ≥0.96). The maximum RR-2 adsorption (103 mg/g) was obtained with NiO/CuO-NC. It is concluded that nanocomposites are more efficient and promising for the dyes degradation from industrial wastewater as compared with dyes adsorption onto individual NPs. Thus, the nanocomposite NiO/CuO-NC can be an excellent candidate for photodegradation as well as the adsorption of the dyes in aqueous media.
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26.
  • Albrectsen, Benedicte Riber, 1960-, et al. (författare)
  • Both plant genotype and herbivory shape aspen endophyte communities
  • 2018
  • Ingår i: Oecologia. - : Springer. - 0029-8549 .- 1432-1939. ; 187:2, s. 535-545
  • Tidskriftsartikel (refereegranskat)abstract
    • Salicinoid phenolic glycosides are common defence substances in salicaceous trees and specialist leaf beetles use these compounds for their own defence against predators. Salicinoids vary qualitatively and qualitatively in aspen (Populus tremula) and this variation has a genetic basis. The foliar endophyte mycobiome is plentiful and we hypothesised that it is related to plant genotype, potentially mediated by salicinoid composition, and that interactions with the leaf beetle Chrysomela tremula may alter this relationship. We studied these three-way interactions in controlled greenhouse experiments. Endophytic fungi were isolated from sterilised leaf tissues with and without beetle damage, and from beetles. We confirmed that endophyte composition was influenced by host genotype. Beetle activity added generalist morphs to the mycobiome that overrode the initial host association. Yeast-like genera (Cryptococcus and Rhodotorula) were isolated only from beetle-damaged tissues and from beetles, whereas fast-growing filamentous fungi dominated beetle-free control plants. Competition experiments between filamentous fungi of plant origin and beetle-related yeasts suggested interaction of both stimulating and inhibiting modes of action amongst the fungi. As a result, we detected examples of amensalism, commensalism, parasitism and competition between the morphs tested, but we found no evidence of mutualism, and consequently no co-evolutionary relationship could be demonstrated, between yeasts carried by beetles, host genotype and associated filamentous morphs. Endophyte studies are method-dependent and high-throughput sequencing technology best define the fungal mycobiome, culturing however continues to be a cheap way to provide fundamental ecological insights and it is also required for experimental studies.
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  • Aziz, Mubashir, et al. (författare)
  • Identification of NEK7 inhibitors: structure based virtual screening, molecular docking, density functional theory calculations and molecular dynamics simulations
  • 2023
  • Ingår i: Journal of Biomolecular Structure and Dynamics. - : TAYLOR & FRANCIS INC. - 0739-1102 .- 1538-0254. ; 41:14, s. 6894-6908
  • Tidskriftsartikel (refereegranskat)abstract
    • NEK7 is a NIMA related-protein kinase that plays a crucial role in spindle assembly and cell division. Dysregulation of NEK7 protein leads to development and progression of different types of malignancies including colon and breast cancers. Therefore, NEK7 could be considered as an attractive target for anti-cancer drug discovery. However, few efforts have been made for the development of selective inhibitors of NIMA-related kinase but still no FDA approved drug is known to selectively inhibit the NEK7 protein. Dacomitinib and Neratinib are two Enamide derivatives that were approved for treatment against non-small cell lung cancer and breast cancer respectively. Drug repurposing is a time and cost-efficient method for re-evaluating the activities of previously authorized medications. Thus, the present research involves the repurposing of two FDA-approved medications via comprehensive in silico approach including Density functional theory (DFTs) studies which were conducted to determine the electronic properties of the Dacomitinib and Neratinib. Afterward, binding orientation of selected drugs inside NEK7 activation loop was evaluated through molecular docking approach. Selected drugs exhibited potential molecular interactions engaging important amino acid residues of active site. The docking score of Dacomitinib and Neratinib was -30.77 and -26.78 kJ/mol, respectively. The top ranked pose obtained from molecular docking was subjected to Molecular Dynamics (MD) Simulations for investigating the stability of protein-ligand complex. The RMSD pattern revealed the stability of protein-ligand complex throughout simulated trajectory. In conclusion, both drugs displayed inhibitory efficacy against NEK7 protein and provide a prospective therapy option for malignant malignancies linked with NEK7. Communicated by Ramaswamy H. Sarma
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30.
  • Bashir, J., et al. (författare)
  • The influence of Cr doping on the structural and magnetic properties of Sr2Fe1-xCrxMoO6 double perovskite
  • 2006
  • Ingår i: Physica. B, Condensed matter. - : Elsevier BV. - 0921-4526 .- 1873-2135. ; 385, s. 126-129
  • Tidskriftsartikel (refereegranskat)abstract
    • We have studied the effect of Cr substitution for Fe in Sr2Fe1-xCr,MoO6 (x <= 0.3) double perovskites. X-ray diffraction, neutron powder diffraction (NPD), magnetisation measurements as well as Mossbauer spectroscopy have been used to determine the structural and magnetic properties of these compounds. All these materials were found to crystallise with tetragonal symmetry. The main observed effect is a decrease with respect to the undoped composition, of the cationic order with Cr doping levels. Mossbauer spectroscopy measurement revealed that iron exists in high spin + 3 oxidation state.
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31.
  • Bilal, Muhammad Sajjad, et al. (författare)
  • Computational Investigation of 1, 3, 4 Oxadiazole Derivatives as Lead Inhibitors of VEGFR 2 in Comparison with EGFR : Density Functional Theory, Molecular Docking and Molecular Dynamics Simulation Studies
  • 2022
  • Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular endothelial growth factor (VEGF) is an angiogenic factor involved in tumor growth and metastasis. Gremlin has been proposed as a novel therapeutic pathway for the treatment of renal inflammatory diseases, acting via VEGFR 2 receptor. To date, most FDA-approved tyrosine kinase (TK) inhibitors have been reported as dual inhibitors of EGFR and VEGFR 2. The aim of the present study was to find the potent and selective inhibitor of VEGFR 2 specifically for the treatment of renal cancer. Fourteen previously identified anti-inflammatory compounds i.e., 1, 3, 4 oxadiazoles derivatives by our own group were selected for their anti-cancer potential, targeting the tyrosine kinase (TK) domain of VEGFR2 and EGFR. A detailed virtual screening-based study was designed viz density functional theory (DFT) study to find the compounds stability and reactivity, molecular docking for estimating binding affinity, SeeSAR analysis and molecular dynamic simulations to confirm protein ligand complex stability and ADMET properties to find the pharmacokinetic profile of all compounds. The DFT results suggested that among all the derivatives, the 7g, 7j, and 7l were chemically reactive and stable derivatives. The optimized structures obtained from the DFTs were further selected for molecular docking, and the results suggested that 7g, 7j and 7l derivatives as the best inhibitors of VEGFR 2 with binding energy values -46.32, -48.89 and -45.01 kJ/mol. The Estimated inhibition constant (IC50) of hit compound 7j (0.009 mu M) and simulation studies of its complexes confirms its high potency and best inhibitor of VEGFR2. All the derivatives were also docked with EGFR, where they showed weak binding energies and poor interactions, important compound 7g, 7j and 7i exhibited binding energy of -31.01, -33.23 and -34.19 kJ/mol respectively. Furthermore, the anticancer potential of the derivatives was confirmed by cell viability (MTT) assay using breast cancer and cervical cancer cell lines. At the end, the results of ADMET studies confirmed these derivatives as drug like candidates. Conclusively, the current study suggested substituted oxadiazoles as the potential anticancer compounds which exhibited more selectivity towards VEGFR2 in comparison to EGFR. Therefore, the identified lead molecules can be used for the synthesis of more potent derivatives of VEGFR2, along with extensive in vitro and in vivo experiments, that can be used to treat various cancers, especially renal cancers, and to prevent angiogenesis due to aberrant expression of VEGFR2.
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32.
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33.
  • Ejaz, Syeda Abida, et al. (författare)
  • In-silico Investigations of quinine and quinidine as potential Inhibitors of AKR1B1 and AKR1B10: Functional and structural characterization
  • 2022
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 17:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The aberrant expression of aldo keto reductases (AKR1B1 & AKR1B10) has been extensively studied in different types of cancer especially the colon cancer but a very few studies have yet been reported regarding the discovery of inhibitors for the treatment of colon cancer by targeting these isozymes. Therefore, there is a need of selective inhibitors of both targets for the eradication of colon cancer. Currently, the study is focused on the exploration of two quinolone compounds i.e., (S)-(6-Methoxyquinolin-4-yl)[(1S,2R,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinidine) and (R)-(6-Methoxyquinolin-4-yl)[(1S,2S,4S,5R)-5-vinylquinuclidin-2-yl]methanol (Quinine) as the potential inhibitors of AKR1B1 and AKR1B10 via detailed in-silico approach. The structural properties including vibrational frequencies, dipole moment, polarizability and the optimization energies were estimated using density functional theory (DFT) calculations; where both compounds were found chemically reactive. After that, the optimized structures were used for the molecular docking studies and here quinidine was found more selective towards AKR1B1 and quinine exhibited maximum inhibition of AKR1B10. The results of molecular docking studies were validated by molecular dynamics simulations which provided the deep insight of stability of protein ligand complex. At the end, the ADMET properties were determined to demonstrate the druglikeness properties of both selected compounds. These findings suggested further exploration of both compounds at molecular level using different in-vivo and in-vitro approaches that will lead to the designing of potential inhibitor of AKR1B1/AKR1B10 for curing colon cancer and related malignancies.
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34.
  • Hossain, Md. Alamgir, et al. (författare)
  • Understanding the socio-demographic and programmatic factors associated with adolescent motherhood and its association with child undernutrition in Bangladesh
  • 2024
  • Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 24
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Worldwide, a significant number of girls become mothers during adolescence. In Bangladesh, adolescent childbirth is highly prevalent and has adverse effects on children's health and undernutrition. We aimed to identify the relationship between the undernutrition of children and adolescent motherhood, the factors associated with adolescent mothers' age at first birth, and to examine the programmatic factors and gaps influencing children's undernutrition in Bangladesh.Methods: We analysed the 'Bangladesh Demographic and Health Survey' BDHS-17-18 data and desk review. To examine the factors associated with adolescent motherhood and its impact on child undernutrition, data from 7,643 mother-child pairs were selected. Child stunting, wasting, and underweight were measured according to the World Health Organisation (WHO) median growth guidelines based on z-scores - 2. Univariate, bivariate, simple, and multiple logistic regressions were used for analyse. We followed the systematic procedures for the literature review.Results: Approximately, 89% of adolescents aged ≤ 19 years were married and 71% of them gave their first childbirth. Children of adolescent mothers (≤ 19 years) were significantly 1.68 times more wasted (aOR: 1.68; 95% CI: 1.08 to 2.64), 1.37 times more underweight (aOR: 1.37; 95% CI: 1.01 to 1.86) and either form 1.32 times more stunting, wasting or underweight (aOR:1.32; 95% Cl: 1.05 to 1.66) compared to the children of adult mothers (> 19 years) after adjusting potential confounders. The factors associated with mothers' first childbirth during adolescence were the age gap between husband and wife 5-10 years (aOR: 1.81; 95% Cl: 1.57-2.10) and age gap > 10 years (aOR: 2.41; 95% Cl: 1.96-2.97) compared with the age group < 5 years, and husbands' education (aOR: 1.29; 95% Cl: 1.04-1.61) compared with the uneducated husbands. In the literature review, we found potential gaps in focusing on the Adolescent Sexual and Reproductive Health (ASRH) program in Bangladesh, from thirty-two programmes only half of them focused on adolescents aged 10-19 years, and eleven programmes focused only on girls.Conclusion: Children of adolescent mothers are at risk of wasting, underweight, and any form of undernutrition. For effective policies and interventions in Bangladesh, it is important to emphasise delaying adolescent pregnancy and prioritising child undernutrition.
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35.
  • Jonsson, Andreas P., et al. (författare)
  • CuZn-superoxide dismutase in D90A heterozygotes from recessive and dominant ALS pedigrees
  • 2002
  • Ingår i: Neurobiology of Disease. - : Academic Press. - 0969-9961 .- 1095-953X. ; 10:3, s. 327-333
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutations in CuZn-superoxide dismutase (CuZn-SOD) have been linked to ALS. In most cases ALS is inherited as a dominant trait and there is marked reduction in CuZn-SOD activity in samples from the patients. The D90A mutation, however, mostly causes ALS as a recessive trait and shows near normal CuZn-SOD activity. A few familial and sporadic ALS cases heterozygous for the D90A mutation have also been found. Haplotype analysis of both types of D90A families has suggested that all recessive cases share a common founder and may carry a protective factor located close to the D90A mutant CuZn-SOD locus. To search for effects of a putative protective factor we analysed erythrocytes from D90A heterozygous individuals for SOD activity by a direct assay, subunit composition by immunoblotting, and zymogram pattern formed by isoelectric focusing and SOD staining. Included were heterozygotes from 17 recessive families, and from 2 dominant families and 4 apparently sporadic cases. The CuZn-SOD activity in the recessive and dominant groups was found to be equal, and 95% of controls. The ratio between mutant and wildtype subunits was likewise equal and 0.8:1 in both groups. The zymograms revealed multiple bands representing homo- and heterodimers. There were, however, no differences between the groups in patterns or in ratios between the molecular forms. In conclusion we find no evidence from analyses in erythrocytes that the putative protective factor in recessive families acts by simply downregulating the synthesis or altering the molecular structure or turnover of the mutant enzyme.
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36.
  • Kishwar, Sultana, et al. (författare)
  • Investigation of the phototoxic effect of ZnO nanorods on fibroblasts and melanoma human cells
  • 2014
  • Ingår i: Laser Physics Letters. - : Institute of Physics (IOP). - 1612-2011 .- 1612-202X. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Photo-cytotoxicity of zinc oxide (ZnO) nanowires (NWs) either bare or conjugated with photosensitizers was studied in dark and after ultraviolet light exposure, in human melanoma and foreskin fibroblast cells. ZnO NWs were grown on the capillary tip and then coated with photosensitizer. This coated tip was used as pointer for intracellular insertion of ZnO NWs and photosensitizer. ZnO NWs pointer was inserted into a specific cell and then irradiated with ultraviolet (UVA), which led to loss of mitochondrial membrane potential, as estimated by loss of the Mitotracker Red staining. Dissolved ZnO NWs showed cytotoxicity as detected by MTT viability assay and morphological evaluation. UVA-irradiation enhanced the toxicity and caused the production of reactive oxygen species (ROS) resulting in cell necrosis. ZnO NWs were photo-toxic for both normal and cancer cells, questioning their bio-safety.
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37.
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38.
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39.
  • Li, Cheng, et al. (författare)
  • Response of plastic film mulched maize to soil and atmospheric water stresses in an arid irrigation area
  • 2024
  • Ingår i: European Journal of Agronomy. - 1161-0301. ; 154
  • Tidskriftsartikel (refereegranskat)abstract
    • Water stress can severely decrease crop productivity by restricting photosynthesis, while the use of plastic film mulching can mitigate these water stress effects. However, the intricacies of photosynthetic and stomatal responses to soil water stress under plastic film mulching, particularly when combined with atmospheric water stress, have not been well studied, especially in arid irrigation areas. Limited research has investigated photosynthetic chlorophyll fluorescence parameters, stomatal responses, grain filling process and crop productivity to soil and atmospheric water stress under plastic film mulching. Our study addresses this knowledge gap through a comprehensive field experiment in an arid irrigation area involving maize (Zea mays L.). Well-watered and water deficit conditions with and without plastic film mulching treatments, alone or combined with atmospheric water stress (different vapor pressure deficits) were conducted. Our findings revealed that soil water stress significantly increased stomatal limitations (by 6.4–12.4 %) and may cause non-stomatal limitations. Plastic film mulching significantly improved plant photosynthetic performance (increased net photosynthesis rate by 12.2–39.8 %), chlorophyll fluorescence parameters, and stomatal regulation. Under mulched conditions, soil water stress primarily affected photosynthetic performance through stomatal limitations. Moreover, plastic film mulching significantly improved grain filling process (increased grain-filling rate by 6.3–78.5 %) and productivity (increased grain yield by 12.1–45.8 %) in spring maize subjected to soil water stress. Atmospheric water stress, alone or combined with soil water stress, influenced plant photosynthetic performance, decreasing the net photosynthesis rate and stomatal conductance. Mulching enhanced photosynthetic performance under atmospheric water stress. Overall, the positive effect of mulching on spring maize photosynthetic performance and productivity under soil and atmospheric water stresses holds promise for alleviating water resource shortages and addressing global climate warming issues in arid irrigation areas.
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40.
  • Li, Cheng, et al. (författare)
  • Ridge planting with transparent plastic mulching improves maize productivity by regulating the distribution and utilization of soil water, heat, and canopy radiation in arid irrigation area
  • 2023
  • Ingår i: Agricultural Water Management. - : Elsevier BV. - 0378-3774. ; 280
  • Tidskriftsartikel (refereegranskat)abstract
    • Ridge-furrow mulching system is widely used for improving soil hydrothermal conditions and crop productivity in semiarid and arid rainfed areas. The response of crop productivity to resource capture and utilization is crucial for agricultural field management and sustainable development. However, few have simultaneously investigated the coupling effect of plastic film mulching (PM) types and planting patterns on root and shoot growth, photosynthesis, yield, resource capture and utilization as well as their potential links in the same experiment, especially in arid irrigation areas, limiting our understanding of PM and ridge planting application. This study conducted a two-year field experiment with four treatments: 1) flat planting with transparent plastic film mulch (FT); 2) flat planting with black plastic film mulch (FB); 3) ridge–furrow planting with transparent plastic film mulch (RT); 4) ridge–furrow planting with black plastic film mulch (RB). The results showed that RT significantly increased soil water storage and root growth at the silking and grain-filling stages in both years by enhancing soil thermal time with 151.9–176.2 °C d and the intercepted photosynthetic active radiation with 22.2–57.4 MJ m–2. In addition, RT had a significantly higher net photosynthetic rate than FT and FB at the 12-leaf and silking stages, enhancing the transportation of stem and leaf to grain. The logistic equation using growing degree days as the independent variable characterized the dynamic features of maize growth under different PM types (transparent or black) coupled with ridge–furrow planting. RT accelerated dry matter accumulation by enhancing the maximum growth rate and extending the rapid growth period, resulting in 12.9–15.2 % more dry matter accumulation and 10.0–16.7 % higher grain yields than FB. Furthermore, RT significantly increased resource use efficiencies by 10.1–17.3 % for water, 3.0–5.5 % for thermal, and 4.0–9.1 % for radiation compared with FB. Ridge planting had the highest contributor rates, with >40 % for yield and resource capture. This study suggests that RT maintains high maize productivity and resource use efficiencies in arid irrigation areas with limited water resources by regulating soil water, heat, and canopy radiation distribution and utilization.
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41.
  • Shaheen, R., et al. (författare)
  • Crystal structure of ALaMnFeO(6) (A = Ca, Sr, Ba)
  • 2006
  • Ingår i: Physica. B, Condensed matter. - : Elsevier BV. - 0921-4526 .- 1873-2135. ; 385, s. 103-105
  • Tidskriftsartikel (refereegranskat)abstract
    • The crystal structures of perovskites of the formula ALaMnFeO(6) (A = Ca, Sr, Ba) have been characterised by powder X-ray, neutron powder diffraction and Mossbauer spectroscopy. Both CaLaMnFeO6 and BaLaMnFeO6 were found to crystallise in orthorhombic symmetry (space group Pbnm), whereas SrLaMnFeO6 was rhombohedral (space group R (3) over barc). No evidence of phase transformation or magnetic structure was noticed in the low-temperature (10K) neutron diffraction measurements. The Mossbauer parameters indicate that iron is present in Fe3+ high-spin (d(5) configuration) state in octahedral coordination.
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42.
  • Siddique, Abu Bakar, First research engineer, et al. (författare)
  • A cost-effective and efficient strategy for Illumina sequencing of fungal communities: A case study of beech endophytes identified elevation as main explanatory factor for diversity and community composition
  • 2016
  • Ingår i: Fungal ecology. - : Elsevier. - 1754-5048 .- 1878-0083. ; 20, s. 175-185
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe an accurate and efficient workflow for highly multiplexed paired-end Illumina sequencing of fungal full-length ITS amplicons. The impact of habitat and substratum conditions on leaf-inhabiting fungal communities was analysed. Fully vital and clearly senescent leaves of European beech (Fagus sylvatica) were sampled along an elevation gradient of about 1000 m in the Bavarian Alps, Germany, in autumn 2013. Surface-sterilised leaves were used for genomic DNA extraction, tagging-by-amplification and high-throughput sequencing. Significant correlation of community composition with elevation was observed. The mycobiome was little affected by the physiological state of the leaves, because only a partial shift of taxonomic composition was observed from vital towards clearly senescent leaves.
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43.
  • Teerlink, John R., et al. (författare)
  • Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure
  • 2021
  • Ingår i: New England Journal of Medicine. - Waltham, MA, United States : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:2, s. 105-116
  • Tidskriftsartikel (refereegranskat)abstract
    • Among patients with heart failure and a reduced ejection fraction, those who received the cardiac myosin activator omecamtiv mecarbil had a lower incidence of a composite of heart-failure events or cardiovascular death at a median of 22 months than those who received placebo. Background The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. Methods We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. Results During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P=0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. Conclusions Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, ; EudraCT number, 2016-002299-28.)
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44.
  • Teerlink, John R., et al. (författare)
  • Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction: GALACTIC-HF baseline characteristics and comparison with contemporary clinical trials
  • 2020
  • Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:11, s. 2160-2171
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials. Methods and results Adults with established HFrEF, New York Heart Association (NYHA) functional class >= II, ejection fraction <= 35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non-white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N-terminal pro-B-type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC-HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m(2) (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594). Conclusions GALACTIC-HF enrolled a well-treated, high-risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation.
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