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Acute myeloid leukemia (AML) predominantly affects the elderly, and prognosis declines with age. Induction chemotherapy plus consolidation therapy is standard of care for fit patients; options for unfit patients include hypomethylating agents (HMA), low-dose cytarabine (LDAC), targeted therapies, and best supportive care (BSC). This retrospective chart review evaluated clinical outcomes in unfit patients with AML who initiated first-line treatment or BSC 01/01/2015-12/31/2018. Overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), and response rates were assessed. Of 1762 patients, 1310 received systemic therapies: 809 HMA, 199 LDAC, and 302 other therapies; 452 received BSC. Median OS was 9.9, 7.9, 5.4, and 2.5 months for HMA, LDAC, other, and BSC, respectively. Median PFS was 7.5, 5.3, 4.1, and 2.1 months for HMA, LDAC, other, and BSC, respectively; median TTF was 4.9, 2.1, 2.2, and 2.1 months, respectively. Our findings highlight the unmet need for novel therapies for unfit patients.

Some implantable medical devices contain silver. We aimed to assess at what amount implanted silver becomes toxic. Silver was elevated in bodily fluids and tissues surrounding silver-containing implants. Silver released from implants also distributes to blood and other tissues; there is evidence to suggest silver can pass the blood-brain-barrier. Silver can be deposited as nano-sized particles in various tissues. Such particles, in addition to silver, often contain other elements too, e.g., selenium and sulfur. Silver released from implants seems to stay in the body for long periods (years). Reported excretion pathways following implantation are urinary and fecal ones. Reported toxicological effects were virtually all local reactions surrounding the implants. Argyria is a blue-gray discoloration of the skin due to deposited silver granules. Localized argyria has been described after the implantation of acupuncture needles and silver-coated prostheses, although the presence of silver was tested only for and shown in the former. Other toxicological effects include local tissue reactivity and examples of neurotoxic and vascular effects. We did not include genotoxicity studies in the present publication as we recently evaluated silver to be genotoxic. Carcinogenicity studies were absent. We conclude that local toxicity of implanted silver can be foreseen in some situations.

A rapid and green approach for the synthesis of xanthenediones. This approach has many advantages such as environmentally friendly procedure, excellent yields, and short duration. The products were...

Nicotinamide phosphoribosyltransferase (NAMPT) is a bottleneck enzyme that plays a key role in recycling nicotinamide to maintain the adequate NAD + level inside the cell. It involves maintaining the cellular bioenergetics and providing a necessary substrate for functions essential to rapidly proliferating the cancer cells. Therefore, inhibition of NAMPT appears as a therapeutic potential for cancer treatment. Here, the vast virtual screening followed by focused docking and in-vitro analysis was carried out to identify the promising hits of NAMPT. We have identified two potential hits from the filtered molecules, which are chemically diverse and have shown comparable quantitative values with reported co-crystal '1QS' as their binding pattern matched nicely. These two compounds are further explored through molecular dynamics simulations (MD) combined with pharmacokinetics profiling and thermodynamic analysis demonstrating their suitability as novel NAMPT inhibitors that can be used as starting points for a hit-to-lead campaign.Communicated by Ramaswamy H. Sarma.

The essence of this paper is to propose some efficient combined and separate classes of estimators for estimating population mean Y¯ under stratified simple random sampling. The bias and mean squar...

The global pandemic due to the novel Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has taken more than a million lives. Lack of definitive vaccine/drugs against this highly contagious virus has accelerated exploratory research on novel natural and synthetic inhibitors. Tea is a rich source of bioactives and known to have antiviral properties. In this study, an in silico strategy involving ADMET property screening, receptor–ligand docking and molecular dynamic (MD) simulation was employed to screen potential tea bio-active inhibitors against three selected targets (RdRp, 3CLpro and PLpro) of SARS-CoV-2. Among the 70 tea bioactives screened, theaflavin 3,3’-di-gallate (TF3), Procyanidin B2 and Theaflavin 3-gallate (TF2a) exhibited highest binding affinities towards RdRp, 3CLpro/Mpro and PLpro targets of SARS-CoV-2 with low docking scores of −14.92, −11.68 and −10.90 kcal/mol, respectively. All of them showed a substantial number of hydrogen bonds along with other interactions in and around the active sites. Interestingly, the top bioactives in our study showed higher binding affinities compared with known antiviral drugs. Further, the top protein–ligand complexes showed less conformational changes during binding when subjected to MD simulation for 100 nanoseconds. The MMPBSA results revealed that RdRp-TF3, 3CLpro-Procyanidin B2 and PLpro-TF2a complexes were stable with binding free energies of −93.59 ± 43.97, −139.78 ± 16.51 and −96.88 ± 25.39 kJ/mol, respectively. Our results suggest that theaflavin 3,3’-digallate, Theaflavin 3-gallate and Procyanidin B2 found in black tea have the potential to act as inhibitors for selected targets of SARS-CoV-2 and can be considered as drug candidates in future studies against COVID-19. Communicated by Ramaswamy H. Sarma

Despite the availability of sufficient data on the effects of individual metal exposure on living organisms, a critical knowledge gap still exists in predicting effects of multi-metals particularly on the pituitary-testicular axis. Thus, the aim of the present study was to check the effects of individual or combined (binary and ternary) exposure to aluminum, copper, and zinc on (i) sperm and testosterone levels (ii) oxidative stress and (iii) structural changes in testis of male Wistar rats. Animals were exposed to aluminum, copper, and zinc either individually (20

The present work deals with a practically efficient protocol designed for the synthesis of tetraketones using ultrasound in the presence of boric acid as the catalyst. One of the tetraketone, (3a) ...

Small hydropower is a mature and cost-competitive energy technology. The maintenance cost of small hydropower plant is one of the critical factors to analyse the net benefits of the plant. In this ...

For the treatment of cerebral ischaemia, vitamin-D3 loaded nanoemulsions were developed. Tween 20 and polyethylene glycol were chosen as surfactant/co-surfactant, while oleic acid as the oil phase....

This paper proposes some optimal classes of estimators under ranked set sampling. We have acquainted some modifications of the difference and ratio type estimators under ranked set sampling, consid...

Primary Objective The primary objective of this study was to explore the pharmacological potential of tocopherol and doxycycline against traumatic brain injury-induced cognitive/motor impairment in rats. Research Design Weight drop model of traumatic brain injury. Methods and Procedures After TBI, the animals were treated with doxycycline (50 and 100 mg/kg; p.o), tocopherol (5 and 10 mg/kg; p.o) alone and in combination as doxycycline and tocopherol (50 and 10 mg/kg; p.o) from 1st day to 28th day. The behavioral parameters were performed on a weekly basis from 1st day to 28th day. On 29th day, animals were sacrificed and striatum and cortex were homogenized for the estimation of biochemical (LPO, nitrite, and GSH), neuroinflammatory (IL-6, IL-1β, and TNF-α), and neurotransmitters (dopamine, norepinephrine, serotonin, GABA, and glutamate) analysis. Main Outcomes and Results Induction of TBI had significantly reduced locomotor activity, recognition memory, increased neuroinflammatory markers, and imbalance neurotransmitter levels. The treatment with doxycycline and tocopherol alone and in combination significantly attenuated locomotor activity, memory recognition, reduced neuroinflammation, preserved oxidative balance, and restored the level of neurotransmitters. Conclusions The neuroprotective effect of doxycycline and tocopherol might be due to its anti-inflammatory and free radical scavenging mechanisms. Abbreviations TBI: Traumatic brain injury; Doxy: Doxycycline; Toco: Tocopherol; LPO: Lipid peroxidation; MDA: Malondialdehyde; TNF-α: Tumor necrosis factor-alpha; IL-1b: Interleukin-1 beta; GSH: Glutathione; GABA: gamma-Aminobutyric acid.

The purpose of this paper is to predict the maximum pressure of journal bearing using ANN. The maximum pressure values are analysed using FEM and predicted using ANN. The FEM analysis is performed ...

Cloudburst over Tehri district of Uttarakhand resulted in flash flood on 8 August 2019. This catastrophic event killed four persons and damaged few bridges. Results presented in this short communic...

The lubricant properties have a significant influence on the static and dynamic performance characteristics of journal bearing such as load-carrying capability, minimum fluid film thickness, maximu...

This study evaluates the biosynthesis of gold nanoparticle (GNP) using Antarctic bacteria and assesses its potential antibacterial activity on sulfate-reducing bacteria (SRB). The GNPs were biosynthesized at distinct temperatures (4°, 10°, 25°, 30° and 37° C) using bacterial isolate GL1.3, obtained from Antarctic lake water. Biochemical and phylogenetic analysis concluded that the isolate GL1.3 belongs to

Molecular Docking and complete quantum chemical studies of 1-{[(Z)-Cyclopentylidene] amino}-3-phenylthiourea have been done by using DFT/ B3LYP method and 6-311 G (d, p) as the basis set. We have compared optimized geometry of title molecule with experimental data. A detailed interpretation of the vibrational assignments of title molecule is reported. Molecular Electrostatic Potential (MESP) generated by a chemical species is widely used as a tool for exploring its properties and locating potential sites for interaction with other moieties. Nonlinear optics (NLO) is the branch of optics that describes the behavior of materials in nonlinear media. In quantum chemistry, a natural bond orbital or NBO is a calculated bonding orbital with maximum electron density. Time-dependent density functional theory (TDDFT) is a quantum mechanical theory used in physics and chemistry to investigate the properties and dynamics of many-body systems in the presence of time-dependent potentials, such as electric or magnetic fields.The electronic properties of title molecule are discussed with help of molecular FHOMO, FLUMO composition, band gap, and MESP plots. The NLO, NBO, UV spectra of title molecule also calculated with same level of theory. Some biological parameter Log P and Log S are also calculated which suggests that the title molecule have good ability to deliver drugs in various diseases.

This study attempts to understand online retail format choice behavior of Indians through cultural dimension of individualism-collectivism. Extended reasoned action model of Fishbein and Aj...

Drawing on the theories of new media and Domingo’s typology of interactivity, this paper examines the presence of interactive and participatory features on the websites of six Indian national daili...

In this paper a complete quantum chemical study of [1,2,4]-triazolo [3,4-b][1,3,4] thiadiazole has been done with the combination of DFT/B3LYP method and 6-311G(d, p) basis set. The vibrational assignments are calculated with the help of PED. By using quantum theory of atoms in the molecule (QTAIM) we have calculated topological parameters at BCP point by which the nature of several intermolecular hydrogen bondings are studied. Electronic properties are calculated with the help of HOMO-LUMO plot. Chemical active sites of title molecule are described by FF, chemical hardness, chemical softness etc. UV spectra are calculated with the help of TDDFT using optimized parameters. NBO analysis gives idea about transfer of charge between bonding and antibonding electrons. Biological activity analysis suggests that the molecule can be used in anti- inflammatory drugs to explore new drugs. The molecule is docked with MBNL1 receptor with the help of Swiss-Dock online server with Full fitness score of −541.58 a.u. Keywords: QTAIM, DFT, TDDFT, HOMO, LUMO, MESP, UV, MBNL1, NBO

The present work deals with the thermodynamic analysis of a solar-powered triple combined power cycle to generate emission-free power. The triple combined cycle comprises one topping cycle as Brayt...

We have examined the land surface changes in the Lidder Valley of Kashmir in the context of socio-economy, climate and environmental aspect using geoscience technology. It was found that there are ...

Here we report for the first time the time-dependent mechanisms of self assembly and growth of Mg(OH)2 nanoparticles. For this purpose, the nanopowders are obtained by a simple chemical precipitation route. To understand the route map of the growth process; the nanopowders are subsequently characterized by XRD, FTIR, BET, pore size distribution, FESEM and TEM analysis techniques. Based on the results obtained from aforesaid characterizations the mechanisms of self-assembly and nanoplatelets growth process as a function of reaction time are explained.

Methylene blue (MB) dye present in industrial wastewater is a well-known carcinogenic source. By utilizing phase pure three dimensional self assembly of magnesium hydroxide nanoparticle (3DSAMHNPs)...

The present work aims at improving the design of an energy conversion system operating on solar radiation harvesting and converting it into electricity with the help of thermopiles. Here, the major...

The in vivo genotoxic potential of bisphenol A using the comet assay in mice and in human sperm cells in vitro without metabolizing enzymes was studied. Male mice were exposed by oral gavage to the following doses of bisphenol A (0,125, 250 and 500 mg/kg body weight). DNA damage was investigated in liver, kidney, testes, urinary bladder, colon and lungs cells. In testicular cells, a significant increase in DNA strand breaks was observed in the lowest, but not in the medium or highest dose groups. Histopathological investigation of the testicular samples did not show any treatment dose-related effects. No DNA strand breaks were observed in any of the other investigated tissues. In human sperm cells in vitro, bisphenol A did not induce DNA strand breaks.