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Aiming at confirming the chemical structure, herein, we report the crystal structure of Arbortristoside-A, isolated from the seeds of Nyctanthes arbor-tristis Linn. and investigated by single crystal X-ray crystallographic analysis. The unambiguously established structure of Arbortristoside-A not only addresses previously reported structural flaws but also encourages its chemical, computational, and physiological studies as a lead drug candidate of pharmaceutical significance. [ABSTRACT FROM AUTHOR]

With the growing demand for functional foods having better nutraceutical properties, lactic acid bacteria (LAB) has become an important industrial microorganism. LAB play a significant role in the functional food industry by exhibiting probiotic properties and has the ability to produce various biologically active metabolites such as γ-aminobutyric acid (GABA), exopolysaccharides (EPSs), conjugated linoleic acid (CLA), bacteriocins, reuterin and reutericyclin, which provides enhanced nutraceutical properties to the final food products. LAB are also known to produce several specific enzymes essential for producing substrate-derived bioactive compounds, such as polyphenols, bioactive peptides, inulin-type fructans and β-glucans, fatty acids, and polyols. These compounds exhibit many health benefits, including better mineral absorption, oxidative stress protection, blood glucose and cholesterol-lowering properties, prevention of gastrointestinal tract infections and improved cardiovascular function. Further, metabolically engineered LAB have been widely used for the nutritive enhancement of different food products and the application of CRISPR–Cas9 holds tremendous potential for the engineering of food cultures. This review provides an overview of the use of LAB as probiotics, its application in producing fermented foods and nutraceutical products, and its health benefits on the host. [ABSTRACT FROM AUTHOR]

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 in vitro assays. The IC50 for free erlotinib and formulation was found to be 2.0 ± 0.3 µg/ml and 1.1 ± 0.1 µg/ml, respectively. The effectivity was evident by cellular uptake study and apoptosis, whereas cell cycle arrest study indicated that erlotinib arrests the G0/G1 phase of cell cycle. Further the erlotinib-asolectin liposomal formulation enhanced cytotoxicity in PANC-1 cells at relatively low dose, proving to be an alternative for current chemotherapeutics against pancreatic cancer. [ABSTRACT FROM AUTHOR]

Mitophagy formed the basis of the original description of autophagy by Christian de Duve when he demonstrated that GCG (glucagon) induced macroautophagic/autophagic turnover of mitochondria in the liver. However, the molecular basis of liver-specific activation of mitophagy by GCG, or its significance for metabolic stress responses in the liver is not understood. Here we show that BNIP3 is required for GCG-induced mitophagy in the liver through interaction with processed LC3B; an interaction that is also necessary to localize LC3B out of the nucleus to cytosolic mitophagosomes in response to nutrient deprivation. Loss of BNIP3-dependent mitophagy caused excess mitochondria to accumulate in the liver, disrupting metabolic zonation within the liver parenchyma, with expansion of zone 1 metabolism at the expense of zone 3 metabolism. These results identify BNIP3 as a regulator of metabolic homeostasis in the liver through its effect on mitophagy and mitochondrial mass distribution. Abbreviations: ASS1, arginosuccinate synthetase; BNIP3, BCL2/adenovirus E1B interacting protein 3; CV, central vein; GCG – glucagon; GLUL, glutamate- ammonia ligase (glutamine synthetase); HCQ, hydroxychloroquine; LIR, LC3-interacting region; MAP1LC3B/LC3B, microtubule-associated protein 1 light chain 3 beta; mtDNA:nucDNA, ratio of mitochondrial DNA to nuclear DNA; PV, periportal vein; TOMM20, translocase of outer mitochondrial membrane protein 20. [ABSTRACT FROM AUTHOR]

The present study is aimed to formulate baicalein-loaded mixed micelles to enhance the solubility and oral bioavailability. Baicalein encapsulated D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and pluronic F127 (F127) combined micelles were prepared and investigated for anticancer effect. The optimized formulation contains 25.04 ± 0.24 nm mean particle size of micelles with a zeta potential value of −4.01 ± 0.5 mV. The calculated entrapment efficiency percentage of baicalein within the micellar structure was 83.43 ± 0.13% and the in vitro release of baicalein from micelles displayed a sustained release profile at pH 7.4. The incorporation of baicalein within micelles core was also confirmed by FTIR analysis of formulation, which hardly represents the characteristic peak of baicalein, indicating successful entrapment of the drug. In vitro cell culture experiments revealed baicalein-loaded micelles significantly enhanced cellular uptake and cytotoxicity against MDAMB-231 cell lines in comparison to free baicalein. Additionally, as compared to free baicalein, baicalein micelles demonstrated greater apoptosis-inducing potential while the results of the cell cycle study exhibited arrest of cells at the G0/G1 phase of the cell cycle. Results of ROS (reactive oxygen species) and MMP (mitochondrial membrane potential) assay revealed the ROS-dependent mitochondrial-mediated apoptosis pathway utilized by developed formulation to inhibit cell proliferation. Thus, the developed nano micelles can serve as a potent carrier system for baicalein against breast cancer. [ABSTRACT FROM AUTHOR]

This paper presents experimental investigation of the axial behaviour of built-up (BU) (I-section) cold-formed steel doubly-symmetric channel with single-/double-layer sheathing on both sides configuration. Fifteen (15) monotonic concentric axial compression tests were performed on 7-BU sections with single-layer sheathing, 7-BU sections with double-layer sheathing, 1-BU section stud without sheathing. The experiments aim to enumerate ultimate axial strength, buckling interactions, failure pattern and strength enhancement due to sheathing for BU section stud members. The novelty of the study is that, for the first time an attempt is made to investigate the axial behaviour of single-/double-layer sheathed BU section panels using seven different sheathing boards.        Results indicate large range of deformation behaviour, with local-global and distortional-global interaction buckling phenomena. Failure is also observed due to failing of screws in specimens with sheathing of thickness ≥ 9 mm and modulus of elasticity > 6400MPa. Also, for the first time, efficacies of four semi-analytical methods based on rational extension of direct strength method (DSM) are presented. Results suggest the insufficiency of current AISI design specifications, whereas predicted results obtained using the new modified DSM methodology are within the adequate variation range as the adopted methodology considers desired buckling interaction. The efficacy of the recommended design methodology is verified through reliability analysis. [ABSTRACT FROM AUTHOR]

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 to the lack of information from experimental studies. Thus, the present paper highlights investigation of behaviour of different masonry construction systems through full-scale tests on masonry buildings subjected to cyclic displacement. Six tests, out of which three on virgin masonry building systems, employing unreinforced masonry (URM), reinforced masonry (RM) and confined masonry (CM) having similar geometrical, material, constructional features and test procedures were conducted. The remaining three building models tested included repaired unreinforced masonry (URM-REP), retrofitted unreinforced masonry (URM-RET) and retrofitted reinforced masonry (RM-RET). Observations and data from the experiments have been co-related between damage index, grade of damage and displacement capacity, thereby estimation of structural behaviour factor for different masonry building typologies. The analysis shows that the ranges of structural behaviour factor mentioned in codes are adequate for URM and RM, while the same for CM is conservative, which can be relaxed. Also, it has been noticed that there is a substantial increase in structural behaviour factor for repaired and retrofitted masonry structures, thus proving the structural adequacy of retrofitting measures. [ABSTRACT FROM AUTHOR]

Despite estimated high prevalence of inherited hemoglobin (Hb) disorders among tribal populations in Madhya Pradesh State, India, the burden of disease is unknown, leading to high morbidity and associated mortality. Our aim was to screen tribal populations in designated tribal districts of Madhya Pradesh State for various hemoglobinopathies and to estimate the prevalence and plausible cause of anemia. The present study screened a total of 3992 tribal individuals comprised of students of Tribal schools, ashrams of Dindori, Mandla, and Chhindwara districts of Madhya Pradesh State. Screening of hemoglobinopathies was done using Hb electrophoresis and or high performance liquid chromatography (HPLC), α-thalassemia (α-thal) was detected using polymerase chain reaction (PCR). The median age of the studied cohort was 15 years (interquartile range 13–16 years). High prevalence (76.7%) of anemia was observed among the studied cohort. The prevalence of sickle cell trait and sickle cell disease varies from 10.7 to 15.6% and 0.4 to 0.8%, respectively. The allele frequency of sickle cell gene was highest in the Pradhan tribe followed by the Panika tribe. Dindori district had the highest prevalence of sickle cell trait. β-Thalassemia (β-thal) trait was observed in only 1.4% of the screened population. α Gene deletions were observed in 84.7% individuals. Significant association of α gene deletion mutations with mean Hb, mean corpuscular volume (MCV), and mean corpuscular Hb (MCH) was observed. The Bharia tribe showed the highest prevalence for α-thal. For comprehensive health care, effective intervention programs are needed to reduce the high prevalence of anemia and hemoglobinopathies among tribes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 operation time, superficial velocity, bed inventory, particle size, and spacing between jet top and draft tube bottom on the solid circulation rate in terms of attrition were studied. A mathematical model was developed on the basis of experimental results to identify the effects of attrition of bed particles on the solid circulation rate incorporating the effects of the various operating and design parameters. To develop the model, dimensional analysis and nonlinear regression were used. The model equation was a nonlinear equation, which implies a relationship between the solid circulation rate and other operating and design parameters. The model equation can estimate the solid circulation rate over a range of operation time and other parameters. Decrease in solid circulation rate can be predicted with increasing operation time, using the model equation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 coefficient of curvature showed increasing patterns. It specifies that particles of different size ranges and fines were formed due to attrition of particles. At the end of the operation, it was found that a significant amount of fines was elutriated with fluidizing air from the reactor. [ABSTRACT FROM PUBLISHER]

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 findings indicated that concrete metaphors could be an icebreaker or stepping stone to draw novice older adults into the information society. To further increase the impact of concrete metaphors, representing real-world operations is an essential challenge. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Context:Nanoemulsions (NE) are one of the robust delivery tools for drugs due to their higher stability and efficacy. Objectives:The purpose of present investigation is to develop stable, effective and safe NE of docetaxel (DTX). Methods:Soybean oil, lecithin, Pluronic F68, PEG 4000 and ethanol were employed as excipients and NEs were prepared by hot homogenization followed by ultra-sonication. NEs were optimized and investigated for differentin vitroandin vivoparametersviz.droplet size, poly dispersity index, charge; zeta potential, drug content andin vitrodrug release,in vitrocytotoxicity,in vitrocell uptake and acute toxicity. Transmission electron microscopy was performed to study morphology and structure of NEs. Stability studies of the optimized formulation were performed. Results:Droplet size, poly dispersity index, zeta potential, drug content andin vitrodrug release were found to be 233.23 ± 4.3 nm, 0.24 ± 0.010, −43.66 ± 1.9 mV, 96.76 ± 1.5%, 96.25 ± 2.1%, respectively. NE F11 exhibited higher cell uptake (2.83 times than control) and strong cytotoxic activity against MCF-7 cancer cells (IC50; 13.55 ± 0.21 µg/mL at 72 h) whereas no toxicity or necrosis was observed with liver and kidney tissues of mice at a dose of 20 mg/kg. Transmission electron microscopy ensured formation of poly-dispersed and spherical droplets in nanometer range. NE F11 (values indicated above) was selected as the optimized formulation based on the aforesaid parameters. Conclusion:Conclusively, stable, effective and safe NE was developed which might be used as an alternative DTX therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 resource poor farmers, respectively, over the farmers' conventional practice. Varietal difference did not have any influence on benefit derived from the bionutrient package. A novel approach for the conversion of rice straw into mycostraw (organic manure) and its enrichment with plant growth promoting rhizobacteria (PGPR) is also proposed. [ABSTRACT FROM AUTHOR]

Foetal phonocardiography (fPCG) is a non-invasive, cost-effective and simple technique for antenatal care. The fPCG signals contain vital information of diagnostic importance regarding the foetal health. However, the fPCG signal is usually contaminated by various noises and thus requires robust signal processing to denoise the signal. The main aim of this paper is to develop a methodology for removal of unwanted noise from the fPCG signal. The proposed methodology utilizes the non-negative matrix factorization (NMF) algorithm. The developed methodology is tested on both simulated and real-time fPCG signals. The performance of the developed methodology has been evaluated in terms of the gain in signal-to-noise ratio (SNR) achieved through the process of denoising. In particular, using the NMF algorithm, a substantial improvement in SNR of the fPCG signals in the range of 12-30 dB has been achieved, providing a high quality assessment of foetal well-being. [ABSTRACT FROM AUTHOR]

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 parameters. This paper presents a parametric study on various factors influencing the overall stability of soil-nailed slopes. Stability analysis was performed to study the effect of slope geometry, nail parameters and effect of rising water surface within the slope on the overall stability of soil-nailed slopes. The stability of soil-nailed slopes is considered in terms of a factor of safety. The slope geometry varied for the present study includes slope inclination and back slope inclination while the nail parameters include nail inclination, nail length, nail length pattern, and nail layout (horizontal spacing). The study shows that with horizontal back slopes, the optimal nail inclination (αopt) increases with the decrease in slope inclination but it increases with an increase in back slope inclination. Two nail length patterns: Pattern 1, nail length decreasing with depth of the slope and Pattern 2, nail length increasing with depth of the slope have been studied. Pattern 1 is found to be effective for a 10.2 m high slope whereas Pattern 2 is found to be effective for 7.2 m high slope. Rising water surface within the slope, increase in horizontal spacing and decrease in length of the nail reduce the overall stability of a soil-nailed slope. Contribution of nails to the overall stability of soil-nailed slopes is different and found to be dependent on their location and inclination with respect to the slip surface. [ABSTRACT FROM AUTHOR]

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 µµm), 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%%. [ABSTRACT FROM AUTHOR]

This paper is aimed at the selection of suitable mother wavelet and denoising algorithm for the analysis of foetal phonocardiographic (fPCG) signals. Fourier based analysing tools have some limitations concerning frequency and time resolutions. Although wavelet transform (WT) overcomes these limitations, it requires proper selection of a mother wavelet and denoising algorithm. In this study a suitable mother wavelet is selected on the basis of properties of different wavelet families and characteristics of the fPCG signals. The universal threshold, minimax threshold and rigorous SURE threshold algorithms along with soft or hard thresholding rule have been compared to denoise these signals. The mean squared error (MSE) is used to evaluate the performance of these algorithms. The results show that the fourth order Coiflets wavelet has a better performance for the analysis of fPCG signals when using the rigorous SURE threshold denoising algorithm with soft thresholding rule. The proposed approach is simple and proves to be effective when applied to the selection of suitable mother wavelet and denoising algorithm for the fPCG signals. These denoised signals can be used for the accurate determination of foetal heart rate (FHR) and further diagnostic applications of the foetus. [ABSTRACT FROM AUTHOR]

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%, p < 0.05) was observed 24 h after tool operation for the high force group and this change persisted (26%, p < 0.05) 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 (p > 0.05). 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. [ABSTRACT FROM AUTHOR]

Objective. In patients with gastroesophageal reflux disease (GERD), refluxed gastric juice can damage the esophagus, and hence the more acidic the juice, the more the expected damage. Nocturnal acid breakthrough (NAB) is known to occur in GERD patients on treatment with proton-pump inhibitors (PPIs); however, whether this causes esophageal acidification and symptoms is controversial. The aims of this study were to investigate the relationship between gastric acid and the severity of GERD and the esophageal acidification and symptoms during NAB. Material and methods. Patients with GERD were evaluated using endoscopy (graded according to the Los Angeles (LA) classification), manometry and 24-h dual-channel pH-metry for esophageal and gastric acid profile and follow-up pH-metry while on PPIs for NAB. Results. In 61 patients (39.2±12.8 years, 40 M) the endoscopic grading was endoscopy negative (ENRD) in 19 (32%), endoscopic (ERD) in 40 (68%), (LA-A in 25, 42.4%, LA-B in12, 20.3%, peptic stricture in 2, 3.4%, and Barrett's esophagus in 1, 1.7%) and 2 patients were unclassified. Patients in the different groups had comparable gastric acid profiles, though esophageal acid exposure was different (LA-B and above versus ENRD, p=0.007; LA-B and above versus LA-A, p=0.003). Patients with NAB (7/18, 39%) had lower gastric pH than patients without NAB (p=0.003) though average esophageal pH and esophageal acid exposure were comparable. Frequency of nocturnal symptoms was comparable in patients with or without NAB (2/7 versus 3/11, p=NS). Lower esophageal sphincter (LES) pressure was negatively correlated with average gastric pH. Conclusions. Although severity of GERD is related to esophageal acid exposure, it does not correlate to gastric acid. No difference was found in esophageal acid exposure and nocturnal symptoms in patients with or without NAB. [ABSTRACT FROM AUTHOR]

Objective. Although Helicobacter pylori infection is associated with gastric cancer (GC), only 1% of patients develop a malignancy, which suggests a role of host genetic factors. The aim of this study was to investigate the role of polymorphisms of GSTM1, GSTT1, and GSTP1 genes, which encode for carcinogen-detoxifying enzymes, in gastric mutagenesis. Material and methods. Genotyping of GSTT1 and GSTM1 was done using PCR, while PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) was used for genotyping of GSTP1 in 76 patients with gastric neoplasm (GN), 67 with non-ulcer dyspepsia (NUD), 44 with peptic ulcer (PU), and 100 healthy controls (HC). Results. The study population included: GN (intestinal 40 (53%), diffuse 26 (34%), primary gastric lymphoma 8 (11%) and unclassified 2 (2%)), PU (duodenal ulcer (DU) 33 (75%), gastric ulcer (GU) 10 (23%), both PU and DU 1 (2%)). GSTT1 null genotype (GSTT1*0) was more common in patients with GN (30/76 (40%)) than in those with PU (5/44 (11%); p=0.001, odds ratio (OR) 5; 95% CI=1-4) and HC (23/100 (23%); p=0.02, OR 2; 95% CI=1-4). GSTT1*0 conferred a higher cancer risk for patients with DU (2/33 (6%), OR 10; 95% CI=2-45; p=0.00). GSTM1*0 and GSTP1 variant genotypes (ile/val and val/val) not alone but in combination with GSTT1*0 conferred a higher risk in PU patients (21 (28%) versus 5 (11%); OR 3; 95% CI=1-9; p=0.04). Both GSTM1*0 (16/26 (61%) versus 10/40 (25%); p=0.003, OR 5; 95% CI=2-14) and GSTT1*0 (12/26 (46%) versus 13/40 (33%); p=0.2, OR 2; 95% CI=0.6-5) were associated with a higher risk of diffuse tumor than of intestinal tumor. Conclusions. GSTT1*0 alone and in combination with GSTM1*0 and GSTP1 variant genotypes is a risk factor for GN in the Indian population. Low GSTT1*0 in DU patients may play a protective role against GN. GSTM1*0 and GSTT1*0 are risk factors for diffuse GC. [ABSTRACT FROM AUTHOR]

Topical application of the drugs at the pathological sites offer potential advantages of delivering the drug directly to the site of action and thus producing high tissue concentrations of the drug. The solid lipid nanoparticles (SLN) bearing flurbiprofen were prepared by microemulsion method by dispersing o/w microemulsion in a cold aqueous surfactant medium under mechanical stirring. The SLN gel was prepared by adding SLN dispersion to polyacrylamide gel prepared by using polyacrylamide (0.5%), glycerol (10%), and water (69.5%). Shape and surface morphology was determined by scanning electron microscopy that revealed fairly spherical shape of the formulation. Percent drug entrapment was higher in SLN dispersion in comparison to SLN gel formulations. In vitro drug release, determined using cellophane membrane, showed that SLN dispersion exhibited higher drug release compared with SLN gel formulations. Both the SLN dispersion and SLN-gel formulation possessed a sustained drug release over a 24-hr period, but this sustained effect was more pronounced with SLN-gel formulations. The percent inhibition of edema after 8 hr was 55.51 ± 0.26% in case of SLN-T4-gel, whereas flurbiprofen and SLN-T4 dispersion exhibited 28.81 ± 0.46 and 31.89 ± 0.82 inhibition of edema. The SLN-T4-gel not only decreased the inflammation to larger magnitude, but also sustained its effect. [ABSTRACT FROM AUTHOR]

Various approaches for colon targeted drug delivery have been studied over the last decade including, pro-drugs, timed-released systems, coating of pH-dependant polymer and the use of polysaceharides. In the present work, a novel formulation consisting of cross-linked microspheres of guar gum has been investigated for colon-targeted delivery of metronidazole. An emulsification method involving the dispersion of aqueous solution of guar gum in castor oil was used to prepare spherical microspheres. Process parameters were analyzed in order to optimize the formulation. Shape and surface morphology of the microspheres were examined using scanning electron microscopy. Placebo microspheres exhibited a smooth surface while the incorporation of drug imparted a slight roughness to the surface texture. Particle size of the microspheres was determined using laser diffraction particle size analyzer. The in vitro drug release studies were performed in simulated gastric fluid for 2 h and intestinal fluid for 3 h, which revealed that the drug was retained comfortably inside the microspheres and that only 15.27 ± 0.56% of the drug was released in 5h. In vitro release rate studies were also carried out in simulated colonic fluid (SCF) in the presence of rat cecal contents, which showed improved drug release. Moreover, to induce the enzymes that specifically act on guar gum. the rats were treated with 1 ml of 1% w/v dispersion of guar gum for 2. 4 and 6 days and release rate studies were repeated in SCF in the presence of 2 and 4% w/v of cecal matter. A marked improvement in the drug release was observed in presence of cecal matter obtained after induction when compared to those without induction. In vitro release studies exhibited 31.23 ± 1.49% drug release in 24 h in dissolution medium without rat cecal matter. However, the Incorporation of 4% w/v cecal matter obtained after 6 days of enzymes induction increased the drug release to 96.24 ± 4.77%. [ABSTRACT FROM AUTHOR]

A multiparticulate system combining pH-sensitive property and specific biodegradability for colon-targeted delivery of metronidazole has been investigated. Cross-linked chitosan microspheres were prepared from an emulsion system using liquid paraffin as the external phase and solution of chitosan in acetic acid as the disperse phase. The multiparticulate system was prepared by coating cross-linked chitosan microspheres exploiting Eudragit® L-100 and S-100 as pH-sensitive polymers. Morphology and surface characteristics of the formulations were determined by scanning electron microscopy. Particle size of the chitosan microspheres was determined by optical microscopy while that of coated microspheres was determined by particle size analyzer. In vitro drug-release studies were performed in conditions simulating stomach-to-colon transit in presence and absence of rat caecal contents. The size of the microspheres was small and they were efficiently microencapsulated within Eudragit® microspheres, forming a multireservoir system. By coating the microspheres with Eudragit® pH-dependant release profiles were obtained. No release was observed at acidic pH; however, when it reached the pH where Eudragit® starts solublizing there was continuous release of drug from the formulation. Further, the release of drug was found to be higher in the presence of rat caecal contents, indicating the susceptibility of chitosan matrix to colonic enzymes released from rat caecal contents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Mucoadhesive drug delivery systems are those that provide intimate contact of the drug with the mucosa for an extended period of time. In our present work, mucoadhesive chitosan microspheres were prepared by emulsion solvent method. Formulations were characterized for various physicochemical attributes, shape, surface morphology, size, and size distribution, drug payload, swelling ability, and mucoadhesion. The effect of drug, citric acid, and permeation enhancer concentration on the physicochemical properties was studied. Crosslinked chitosan microspheres showed very good mucoadhesion, which was decreased on increasing the drug concentration and citric acid concentration, and slightly improved upon incorporation of permeation enhancer. The in vitro drug release and in vitro drug permeability through mucous membrane were performed, and slow release/permeation was noted with chitosan citrate complexed microspheres compared with noncomplexed chitosan microspheres. The in vivo performance of mucoadhesive microspheres formulations showed prolonged and controlled release of salbutamol as compared with oral administration of conventional dosage form. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of counseling on stress levels of NICU mothers. Methods: Stress levels were assessed using the Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU) questionnaire among 100 NICU mothers. After providing counseling including NICU educational support, the questionnaire was re-administered after 48 h. Coding of the responses was done and the data was analyzed using SPSS Ver.16. Results: The mean pre intervention subscale stress score was highest for parental role alteration (4.12) followed by looks and behavior of the baby (4.10) and sights and sounds (2.55). There was significant reduction in the post-counseling stress levels among NICU mothers in all three sub scales of PSS:NICU. Conclusion: Counseling of mothers whose babies are admitted to the NICU with regards to various aspects of the infant`s environment and condition was significantly effective in reducing the stress levels of mothers. [ABSTRACT FROM AUTHOR]