Search

There is a need for anti-seizure medications (ASMs) that are well tolerated and effective as monotherapy or first adjunctive therapy to reduce the need for adjunctive ASMs to treat newly diagnosed epilepsy, and to reduce the number of concomitant ASMs in patients with refractory epilepsy. Although the pivotal trials of perampanel evaluated its adjunctive use in patients with refractory seizures, open-label/real-world studies support its use in first/second-line settings.This paper reviews the pharmacology, efficacy, and safety/tolerability of perampanel, focusing on its use as monotherapy or first adjunctive therapy. The safety of perampanel in special populations and its safety/tolerability compared with that of other ASMs is also discussed.Perampanel is a favorable candidate for initial or first adjunctive therapy due to its favorable efficacy and safety/tolerability as monotherapy and adjunctive therapy, its long half-life and ease of use, and its limited drug-drug interactions. The proposed mitigation strategies for managing the risk of serious psychiatric adverse events are appropriate patient selection, use of low doses, and slow titration. The growing body of evidence might shift current treatment strategies toward the early use of perampanel and its use at a low dose (4 mg/day).

Betacoronaviruses (β-CoVs) have caused major viral outbreaks in the last two decades in the world. The mutation and recombination abilities in β-CoVs resulted in zoonotic diseases in humans. Proteins responsible for viral attachment and replication are highly conserved in β-CoVs. These conserved proteins have been extensively studied as targets for preventing infection and the spread of β-CoVs. Peptides are among the most promising candidates for developing vaccines and therapeutics against viral pathogens. The immunostimulatory and viral inhibitory potential of natural and synthetic peptides has been extensively studied since the SARS-CoV outbreak. Food-derived peptides demonstrating high antiviral activity can be used to develop effective therapeutics against β-CoVs. Specificity, tolerability, and customizability of peptides can be explored to develop potent drugs against β-CoVs. However, the proteolytic susceptibility and low bioavailability of peptides pose challenges for the development of therapeutics. This review illustrates the potential role of peptides in eliciting an adaptive immune response and inhibiting different stages of the β-CoV life cycle. Further, the challenges and future directions associated with developing peptide-based therapeutics and vaccines against existing and future β-CoV pathogens have been discussed.

The present investigation was envisaged to develop liposomal formulation for efficacious and targeted delivery of epidermal growth factor receptor (EGFR) inhibitor (erlotinib) against pancreatic cancer. The marketed formulations bearing current EGFR inhibitors exhibit serious adverse effects including severe skin, hemolytic and gastrointestinal toxicity. To address the obstacles, we have developed the liposomal formulation, by ether injection method, comprising erlotinib, a tyrosine kinase EGFR inhibitor, proposed to be targeted through enhanced permeability and retention effect (EPR) effect against pancreatic cancer. On succeeding, the liposomes were characterized for various pharmaceutical attributes. The developed liposomes found to sustain a particle size of 121 ± 10.7 nm, whereas PDI of 0.22 ± 0.01 with the surface charge value of -33.7 ± 2.30 mV. The entrapment efficiency and drug loading were found to be 82.60 and 15.89 (%w/w), respectively. The hemolysis study suggested that the developed formulation was safer compared with native drug solution. The proof of concept for enhanced efficacy and decreased toxicity has been established through

Different codes provide a range of values for structural behaviour factor for various masonry building systems. High variation in structural behaviour factors in different codes arises mainly due t...

Paclitaxel (PTX) in its commercial products exhibits adverse effects owing to excipients and also has poor oral bioavailability. Present work is directed towards development of tocopheryl polyethylene glycol succinate-assisted self-nanoemulsifying system (SEDDS) for oral delivery of PTX. Box-Behnken design of experiment was employed to optimize PTX-SEDDS and was characterized for droplet size (29.76 ± 2.64 nm), zeta potential (-21.46 ± 2.52 mV), PDI (0.177 ± 0.012), drug content (4.97 ± 0.98 mg), entrapment efficiency (98.33 ± 0.54%) and in vitro drug release (51.03 ± 2.23% PTX at 72 h). PTX-SEDDS exhibited IC50; 1.58 ± 0.12 µM and a 52.46-folds higher cell uptake in MDA-MB-231 cells along with cellular and nuclear morphology changes. Significantly higher G2M cell cycle arrest, apoptosis, mitochondrial membrane potential disruption and ROS production was exhibited by PTX-SEDDS in comparison to Taxol. Up-regulation of Bax, p21, cleaved-caspase 3, -caspase 9 and down-regulation of Bcl2 and survivin suggested apoptosis via intrinsic pathways. Pharmacokinetic study showed approximately 4-folds higher oral bioavailability of PTX-SEDDS than Taxol. Significant reduction in tumour volume and weight was observed in syngeneic mammary tumour in SD rats. Tumour histopathology and TUNEL assay showed apoptosis in tumour tissue. PTX-SEDDS caused low lung metastasis, and was safe and stable. Conclusively, PTX-SEDDS could be suitable option for oral delivery of PTX.

Congenital heart defects (CHD) are one of the utmost birth defects present in the neonatal after birth and a big challenge for the researchers to identify the structural abnormality during the antepartum period. An algorithm is presented here to identify the presence of CHD through foetal phonocardiographic (fPCG) signals. The recorded fPCG is decomposed using Daubechies4 wavelet with sub-level threshold to remove the noise in the signal. The Shannon energy is used to identify the different peaks of signals and then S1 and S2 according to the intervals between adjacent peaks. The signal is segmented into four important parts: S1, S1S2, S2 and S2S1. The FFT is used to identify the frequency component present in four segments which in turn indicates the presence of pathological murmur that may turn into CHD. The algorithm is tested on 25 samples with accuracy rate 88% in identifying the presence of a murmur.

An experimental study was performed on the attrition of the bed materials in a recirculating fluidized bed (RCFB) using Indian standard (IS) grade I sand (size between 2.0 and 1.0 mm) at ambient conditions. Experiments were performed with superficial air velocity ranging from 7.13 to 9.16 m/s, bed inventory of 7–10 kg, and a spacing of 0.085 m between the jet top and draft tube bottom. The main objective of the study was to investigate the effects of operation time on the attrition and size distribution of sand particles in a RCFB. It was noticed that the prime mode of attrition of bed materials was abrasion, not fragmentation. Reduction in the downcomer bed height was observed with increasing operation time. It indicates that attrition was significant and fines were elutriated out with the fluidizing air. Furthermore, variations in the shape, size, and harmonic diameter of particles were studied with increasing operation time. It has been observed that the coefficient of uniformity and coefficien...

Effects of attrition of bed material on the solid circulation rate in a recirculating fluidized bed (RCFB) were studied in detail. Effects of different operating and design parameters such as opera...

Metaphors could be used to help older adults build mental models of Information and Communication Technology (ICT) applications and services and thereby reduce the number of interaction problems, but currently, metaphors generally are not tailored to these older adults, and their construction remains vague. Inspired by concrete icons, this study proposes concrete metaphors to help novice older adults understand ICT applications and services and retains their knowledge over time. A new communication application based on concrete metaphors was designed, developed, and comparatively tested against another application based on abstract metaphors over a period of 9 days. The results indicated that the application with concrete metaphors contributed to fewer perception and cognition errors, higher usage intention, higher satisfaction, and higher preference compared to the application with abstract metaphors. In addition, the advantage of concrete metaphors was lasting, unlike concrete icons. These findi...

This paper presents a system based on Seismocardiography (SCG) to monitor the heart sound signal for the long-term. It uses an accelerometer, which is of small size and low weight and, thus, convenient to wear. Such a system should also be robust to various noises which occur in real life scenarios. Therefore, a detailed analysis is provided of the proposed system and its performance is compared to the performance of the Phoncardiography (PCG) system. For this purpose, both signals of five subjects were simultaneously recorded in clinical and different real life noisy scenarios. For the quantitative analysis, the detection rate of fundamental heart sound components, S1 and S2, is obtained. Furthermore, a quality index based on the energy of fundamental components is also proposed and obtained for the same. Results show that both the techniques are able to acquire the S1 and S2, in clinical set-up. However, in real life scenarios, we observed many favourable features in the proposed system as compared to PCG, for its use for long-term monitoring.

This work demonstrates Box-Behnken design (BBD)'s capability in exploring scientific principles governing a process, different from its use in process optimisation. We have investigated nanoprecipitation (NP) of temozolomide with polycaprolactone. Five factors, surfactant, stirring speed (SS), dropping rate (DR), phase-volume ratio (PVR) and drug-polymer ratio (DPR) were varied over three levels. Corresponding particle size (238.9 ± 42.24 nm), zeta potential (ZP, -5.92 ± 3.15 mV), poly dispersity index (PDI, 0.176 ± 0.06) and entrapment efficiency (EE, 65.74 ± 9.83%) were put into different polynomial equations. Analysis of variance, lack of fit tests and regression analysis was applied on these equations to determine the one with best fit. This selected equation was subsequently adapted as the model to describe influence of factors on NP. 3D response surface plots corresponding to models and diagnostic plots relatable to normality of residuals were also constructed. In conclusion, application of BBD efficiently strategised experimental foray conducted to elucidate NP.

OCCUPATIONAL APPLICATIONS Sitting in a parallel orientation in front of a touch screen (requiring twisting of the torso) was found to cause a decrement in touchscreen performance (36%–48%). However, the adverse effect of sitting orientation on performance could be ameliorated by interface design, most notably by using button sizes greater than 20×20 mm. Larger button sizes also benefit individuals with upper extremity motor control disabilities, and this information could be used to incorporate universal design in touchscreen interfaces. Larger button sizes also help in reducing the force-time integral during button activation. Touchscreens are widely used in occupational settings, such as retail, restaurants, and health care. The touchscreen performance findings from this study are applicable to touchscreen interface design for users with and without upper extremity motor control disabilities, and the touch characteristics findings are useful for ergonomists quantifying forces involved in touchscreen ope...

A microbial consortium-based sustainable and economic bionutrient package for rice has been developed to reduce reliance on chemical fertilizer. The components of the package include Pseudomonas-enriched mycostraw, Azospirillum, and cyanobacteria for different niches. Enriched mycostraw had thrice the amount of nitrogen and sulfur, twice the amount of phosphorus and 1.3–1.9 times potash and micronutrients (Zn, Fe, Mn) than rice straw and showed a 17.3 C:N ratio. Such bionutrient package application for four consecutive years resulted in an increase in fertilizer use efficiency (5–10%), ARA activity, Azospirillum preponderance, and soil nutrients like total nitrogen (4–5%), total phosphorus (0.7–1%), organic carbon (14–16%) compared to the initial value. Improvement in all the above parameters was reflected in augmentation of grain yield (17%) and straw yield (14.1%). The bionutreint package, when tested at farmers’ sites, showed an increase of 6–20% and 10–35% rice grain yield in resource rich and resourc...

Pathan AAK, Panthi B, Khan Z, et al. OncoTargets and Therapy. 2016;9:2575–2584. On page 2582, panel A, B, C of Figure 5 had typographical and color issues.Read the original article

Soil nailing is one of the in-situ soil reinforcement techniques that have been used for the past four decades. The stability of a soil-nailed slope is closely related to slope geometry and nail pa...

The potential of chitosan microparticles as a carrier of doxorubicin for the treatment of visceral leishmaniasis was evaluated by macrophage-mediated drug targeting approach. Cationic charge of doxorubicin was masked by complexing it with dextran sulphate (a poly anion) in order to facilitate its incorporation into cationic chitosan microparticles. Prior to in vitro and in vivo studies, characterization studies were carried out systematically: particle size (∼1.049 µm), surface morphology (fluorescence microscopy - spherical structured microparticles), Fourier transform infrared spectroscopy (to characterize effective cross-linking) and differential scanning calorimetry. In vitro studies were carried out in J774.1 in order to check the effective endocytotic uptake of microparticles by macrophages. In vivo studies were conducted in Syrian golden hamsters as per well-established protocols and the results drawn from in vivo studies displayed substantial reduction in leishmanial parasite load for doxorubicin-encapsulated chitosan microparticles: ∼78.2 ± 10.4%, when compared to the control (free doxorubicin): 33.3 ± 2.4%.

This study investigated in-vivo changes in upper limb dynamic mechanical properties and magnetic resonance imaging (MRI) parameters following short-term power hand tool operation. Previous studies have found reduction in mechanical properties following short-term power tool usage at long build-up times. This study advances that work by having participants operate a simulated pistol grip power hand tool and evaluating changes in mechanical properties, strength, discomfort level and MRI prior to tool operation and daily for 3 d after tool operation. Twenty-four participants were randomly assigned to operate a simulated power hand tool for either a high peak reaction force of 123 N (peak torque=8 Nm, build-up time=250 ms) or at a low peak reaction force of 5 N (peak torque=2 Nm, build-up time=50 ms). Subjects operated the tool for 60 min at the rate of six times per min. A reduction in stiffness (27%, p0.05) was observed 24 h after tool operation for the high force group and this change persisted (26%, p0.05) up to 72 h after tool operation. Similar changes were not observed for the low force group. No changes were observed in mass moment of inertia, damping, isometric strength and damping for either group (p0.05). There was a signal intensity increase (12%, CI 19%, 5.06%) in the supinator muscle MRI for both groups 24 h after tool operation but only the high force group remained elevated (10%, CI 13.7%, 0.06%) 72 h after tool operation. Persistent short-term changes in mechanical and MRI parameters at high force levels could indicate increased strain on the upper limb and may negatively affect ability to react during rapid forceful loading of the upper limb. This research can ultimately lead to better ergonomic interventions through quantitative power hand tool design guidelines and work practices based on understanding the damaging effects of exposure to specific levels of reaction force, build-up time and repetition, as well as providing new outcome measures for epidemiological studies.

Colon targeted drug delivery has the potential to deliver bioactive agents for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. Various strategies, currently available to target the release of drugs to colon, include formation of prodrug, coating of pH-sensitive polymers, use of colon-specific biodegradable polymers, timed released systems, osmotic systems, and pressure controlled drug delivery systems. Among the different approaches to achieve targeted drug release to the colon, the use of polymers especially biodegradable by colonic bacteria holds great promise. Polysaccharidases are bacterial enzymes that are available in sufficient quantity to be exploited in colon targeting of drugs. Based on this approach, various polysaccharides have been investigated for colon-specific drug release. These polysaccharides include pectin, guar gum, amylose, inulin, dextran, chitosan, and chondroitin sulphate. This family of natural polymers has an appeal to drug delivery as it is comprised of polymers with a large number of derivatizable groups, a wide range of molecular weights, varying chemical compositions, and, for the most part, low toxicity and biodegradability yet high stability. The most favorable property of these materials is their approval as pharmaceutical excipients.

Transdermal drug delivery system of diltiazem hydrochloride was developed to obtain a prolonged controlled drug delivery. Both the matrix diffusion controlled (MDC) and membrane permeation controlled (MPC) systems were developed. The matrix diffusion controlled systems used various combinations of hydrophilic and lipophillic polymers, whereas membrane permeation controlled systems were developed using the natural polymer chitosan. The MDC systems were prepared using the cast film method and the MPC systems by an adhesive sealing technique. Both the systems were characterized for in vitro and in vivo performance. The MDC systems were characterized for physicochemical properties such as tensile strength, moisture content, and water vapor transmission. The in vitro release studies showed that the release from the matrix diffusion controlled transdermal drug delivery systems follows a nonfickian pattern and that from the membrane permeation controlled transdermal drug delivery systems follow zero-order kinetics. The release from the matrix systems increased on increasing the hydrophilic polymer concentration, but the release from the membrane systems decrease on cross-linking of the rate controlling membrane and also on addition of citric acid to the chitosan drug reservoir gel. The in vivo studies of the selected systems showed that both systems are capable of achieving the effective plasma concentration for a prolonged period of time. The MPC system achieved effective plasma concentration a little more slowly than the MDC system, but it exhibited a more steady state plasma level for 24 hr.

There is a growing realization that tumor cells rely on healthy mitochondria to promote their growth under changing microenvironmental stresses and do so by dynamically modulating both their mitochondrial mass and state of mitochondrial fusion. Our recent work adds to this appreciation by showing that the mitophagy receptor BNIP3 functions as a tumor suppressor in mammary tumorigenesis and also as a prognostic indicator of progression to metastasis in certain sub-types of human breast cancer.

Akbar Ali Khan Pathan,1,2,* Bhavana Panthi,3,* Zahid Khan,1 Purushotham Reddy Koppula,4–6 Mohammed Saud Alanazi,1 Sachchidanand,3 Narasimha Reddy Parine,1 Mukesh Chourasia3,* 1Genome Research Chair (GRC), Department of Biochemistry, College of Science, King Saud University, 2Integrated Gulf Biosystems, Riyadh, Kingdom of Saudi Arabia; 3Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, Hajipur, India; 4Department of Internal Medicine, School of Medicine, 5Harry S. Truman Memorial Veterans Affairs Hospital, 6Department of Radiology, School ofMedicine, Columbia, MO, USA *These authors contributed equally tothis work Objective: Kirsten rat sarcoma (K-Ras) protein is a member of Ras family belonging to the small guanosine triphosphatases superfamily. The members of this family share a conserved structure and biochemical properties, acting as binary molecular switches. The guanosine triphosphate-bound active K-Ras interacts with a range of effectors, resulting in the stimulation of downstream signaling pathways regulating cell proliferation, differentiation, and apoptosis. Efforts to target K-Ras have been unsuccessful until now, placing it among high-value molecules against which developing a therapy would have an enormous impact. K-Ras transduces signals when it binds to guanosine triphosphate by directly binding to downstream effector proteins, but in case of guanosine diphosphate-bound conformation, these interactions get disrupted. Methods: In the present study, we targeted the nucleotide-binding site in the “on” and “off” state conformations of the K-Ras protein to find out suitable lead compounds. A structure-based virtual screening approach has been used to screen compounds from different databases, followed by a combinatorial fragment-based approach to design the apposite lead for the K-Ras protein. Results: Interestingly, the designed compounds exhibit a binding preference for the “off” state over “on” state conformation of K-Ras protein. Moreover, the designed compounds’ interactions are similar to guanosine diphosphate and, thus, could presumably act as a potential lead for K-Ras. The predicted drug-likeness properties of these compounds suggest that these compounds follow the Lipinski’s rule of five and have tolerable absorption, distribution, metabolism, excretion and toxicity values. Conclusion: Thus, through the current study, we propose targeting only “off” state conformations as a promising strategy for the design of reversible inhibitors to pharmacologically inhibit distinct conformations of K-Ras protein. Keywords: antitumor agent, K-Ras, molecular docking, molecular modeling, virtual screening

Some di- and triorganotin(IV) derivatives of phthalanilic acid of the general formula R4-nSn[C6H5NHC(O)C6H4COO]n [where R = Me, n-Bu] have been synthesised by the reactions of di- and triorganotin(IV) chlorides with the sodium salt of phthalanilic acid (prepared in situ by the reaction of sodium isopropoxide with the phthalanilic acid) in 1:2 and 1:1 molar ratios, respectively. Alternatively, triphenyltin(IV) phthalanilate has also been prepared by refluxing triphenyltin(IV) hydroxide with phthalanilic acid in 1:1 molar ratio in toluene. These newly synthesised derivatives have been characterised by elemental analyses, melting points as well as IR and NMR (1H and 119Sn) spectral studies.

The Bundelkhand area of central India consists of weathered granitic bedrock. The aim of the present study was to identify the effects of surface water irrigation on groundwater quality in shallow ...

The Effect Of Temperature, Relative Humidity and Light On Elaboration Of Afl-Bj In Neem and Datura Seeds Was Studied. The Highest Level Of Afl-B1 Production In Case Of Both Seeds (0.55-1.12 (Jg/G In Datura Seeds and 0.47-1.15 Pg/G Inneem Seeds) Was Recorded At 30°c Temperature, 96% Rh and Total Darkness After 3 Weeks Of Incubation. The Growth Of A. Flavus and Aflatoxin Production Was Inhibited At 33-35% Rh and 10°C Temperature. Darkness Favored The Synthesis Of Afl-Bj Whereas Sunlight Inhibited It Completely.

Analytical studies on crude root drugs (roots of medicinal value) collected from a number of storehouses in India showed the molds Aspergillus flavus group, A. niger, A. ochraceus, Penicillium citrinum, Penicillium spp., Fusarium moniliforme and Fusarium spp. as dominant fungal flora. Forty-four root samples of five plants were subjected to various physico-chemical tests, and 22 were found positive for mycotoxins. Aflatoxin B1 was present in all the contaminated samples, whereas zearalenone, ochratoxin A and citrinin were of low incidence. Forty-four strains of A. flavus were isolated from different root samples, and 21 were found to produce Aflatoxin-B1 in the range of 0.08 to 0.75 μg/ml of culture filtrate.

The human jaw is an exclusive habitat for odontogenic lesions. Ghost cells associated odontogenic lesions are a diverse group with a variety of presentations in the jaws. Calcifying cystic odontogenic tumor is a benign cystic neoplasm of odontogenic origin which demonstrates ghost cells in the epithelial component. This tumor sometimes mimics the features of a cyst clinically and radiographically, but histopathologically as well as behavior-wise shows the features of a tumor. Many classification systems have been proposed and revised from time to time. Presently a dualistic concept is highlighted to classify this group of lesions. The present case highlights a case of calcifying cystic odontogenic tumor associated with a complex composite odontome, which appeared like a cyst clinically and radiographically.

The effect of temperature on aflatoxin B, (Afl-B) production was examined. The highest level of Afl-B, (1.25 μg/g) production was at 30°C after 3 weeks of incubation. At 20, 25, 35 and 40°C aflatoxin levels ranged from 0.22- 1.00 jug/g- However, at 15°C aflatoxin production (0.12 to 0.24 μg/g) was much lower.