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Showing papers by "Manipal University published in 2014"


Journal ArticleDOI
TL;DR: This work introduces a notion of ‘core–EP inverse’ for a square matrix which is not essentially of index one, and obtained a formula to compute the core–EP generalized inverse from a particular linear combination of minors of given matrix.
Abstract: In this work, we introduce a notion of ‘core–EP inverse’ for a square matrix which is not essentially of index one. This extends the notion of ‘core inverse’, which was initially defined for the matrices of index one. The properties of matrices having ‘core–EP inverse’ and ‘core–EP generalized inverse’ are studied, and obtained a formula to compute the core–EP generalized inverse from a particular linear combination of minors of given matrix.

157 citations


Journal ArticleDOI
TL;DR: The largest identification of proteins from the synovial fluid of rheumatoid arthritis and osteoarthritis patients using a quantitative proteomics approach is reported.
Abstract: Rheumatoid arthritis and osteoarthritis are two common musculoskeletal disorders that affect the joints. Despite high prevalence rates, etiological factors involved in these disorders remain largely unknown. Dissecting the molecular aspects of these disorders will significantly contribute to improving their diagnosis and clinical management. In order to identify proteins that are differentially expressed between these two conditions, a quantitative proteomic profiling of synovial fluid obtained from rheumatoid arthritis and osteoarthritis patients was carried out by using iTRAQ labeling followed by high resolution mass spectrometry analysis. We have identified 575 proteins out of which 135 proteins were found to be differentially expressed by ≥3-fold in the synovial fluid of rheumatoid arthritis and osteoarthritis patients. Proteins not previously reported to be associated with rheumatoid arthritis including, coronin-1A (CORO1A), fibrinogen like-2 (FGL2), and macrophage capping protein (CAPG) were found to be upregulated in rheumatoid arthritis. Proteins such as CD5 molecule-like protein (CD5L), soluble scavenger receptor cysteine-rich domain-containing protein (SSC5D), and TTK protein kinase (TTK) were found to be upregulated in the synovial fluid of osteoarthritis patients. We confirmed the upregulation of CAPG in rheumatoid arthritis synovial fluid by multiple reaction monitoring assay as well as by Western blot. Pathway analysis of differentially expressed proteins revealed a significant enrichment of genes involved in glycolytic pathway in rheumatoid arthritis. We report here the largest identification of proteins from the synovial fluid of rheumatoid arthritis and osteoarthritis patients using a quantitative proteomics approach. The novel proteins identified from our study needs to be explored further for their role in the disease pathogenesis of rheumatoid arthritis and osteoarthritis. Sartaj Ahmad and Raja Sekhar Nirujogi contributed equally to this article.

156 citations


Journal ArticleDOI
TL;DR: The prevalence of CSA was found to be high in India as well as throughout the world and stringent measures should be taken for the prevention and control of this hidden public health issue.
Abstract: Child sexual abuse (CSA) is a universal problem with grave life-long outcomes. The estimates vary widely depending on the country under study, the definitions used, the type of CSA studied, the extent of coverage, and quality of data. This study intended to assess the magnitude and the issues related to CSA. We searched databases such as PubMed, Google scholar, web (newspaper reports), and government websites. The relevant data was extracted from these sources for gathering evidence on CSA and secondary data analysis was done. The prevalence of CSA was found to be high in India as well as throughout the world. CSA is an extensive problem and even the lowest prevalence includes a huge number of victims. It also has various adverse effects on the psychological, physical, behavioral, and interpersonal well-being of the victim. Hence, stringent measures should be taken for the prevention and control of this hidden public health issue.

142 citations


Journal ArticleDOI
TL;DR: The catalog of proteins generated in this study will further enhance the knowledge regarding the pathophysiology of osteoarthritis and should assist in identifying better biomarkers for early diagnosis.
Abstract: Osteoarthritis is a chronic musculoskeletal disorder characterized mainly by progressive degradation of the hyaline cartilage. Patients with osteoarthritis often postpone seeking medical help, which results in the diagnosis being made at an advanced stage of cartilage destruction. Sustained efforts are needed to identify specific markers that might help in early diagnosis, monitoring disease progression and in improving therapeutic outcomes. We employed a multipronged proteomic approach, which included multiple fractionation strategies followed by high resolution mass spectrometry analysis to explore the proteome of synovial fluid obtained from osteoarthritis patients. In addition to the total proteome, we also enriched glycoproteins from synovial fluid using lectin affinity chromatography. We identified 677 proteins from synovial fluid of patients with osteoarthritis of which 545 proteins have not been previously reported. These novel proteins included ADAM-like decysin 1 (ADAMDEC1), alanyl (membrane) aminopeptidase (ANPEP), CD84, fibulin 1 (FBLN1), matrix remodelling associated 5 (MXRA5), secreted phosphoprotein 2 (SPP2) and spondin 2 (SPON2). We identified 300 proteins using lectin affinity chromatography, including the glycoproteins afamin (AFM), attractin (ATRN), fibrillin 1 (FBN1), transferrin (TF), tissue inhibitor of metalloproteinase 1 (TIMP1) and vasorin (VSN). Gene ontology analysis confirmed that a majority of the identified proteins were extracellular and are mostly involved in cell communication and signaling. We also confirmed the expression of ANPEP, dickkopf WNT signaling pathway inhibitor 3 (DKK3) and osteoglycin (OGN) by multiple reaction monitoring (MRM) analysis of osteoarthritis synovial fluid samples. We present an in-depth analysis of the synovial fluid proteome from patients with osteoarthritis. We believe that the catalog of proteins generated in this study will further enhance our knowledge regarding the pathophysiology of osteoarthritis and should assist in identifying better biomarkers for early diagnosis.

125 citations


Journal ArticleDOI
TL;DR: This review comprehensively covers all the available information on the role of SFRP molecules in various human cancers and identifies potential tools in combating Wnt-driven tumorigenesis.

105 citations


Journal ArticleDOI
TL;DR: The study demonstrated significant increase in the dissolution rate as well as increased in the total amount of drug dissolved for amorphous RTV, however it failed to demonstrate any significant improvement in the dissolve behavior of IND.

104 citations


Journal ArticleDOI
TL;DR: In rats subjected to chronic immobilization stress, long-term potentiation and NMDA receptor-mediated synaptic responses are enhanced in principal neurons of the lateral amygdala, a brain area involved in fear memory formation, thereby creating an ideal neuronal substrate for affective disorders.
Abstract: Prolonged and severe stress leads to cognitive deficits, but facilitates emotional behaviour. Little is known about the synaptic basis for this contrast. Here, we report that in rats subjected to chronic immobilization stress, long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated synaptic responses are enhanced in principal neurons of the lateral amygdala, a brain area involved in fear memory formation. This is accompanied by electrophysiological and morphological changes consistent with the formation of ‘silent synapses’, containing only NMDARs. In parallel, chronic stress also reduces synaptic inhibition. Together, these synaptic changes would enable amygdalar neurons to undergo further experience-dependent modifications, leading to stronger fear memories. Consistent with this prediction, stressed animals exhibit enhanced conditioned fear. Hence, stress may leave its mark in the amygdala by generating new synapses with greater capacity for plasticity, thereby creating an ideal neuronal substrate for affective disorders. These findings also highlight the unique features of stress-induced plasticity in the amygdala that are strikingly different from the stress-induced impairment of structure and function in the hippocampus.

101 citations


Journal ArticleDOI
TL;DR: Moderate intensity aerobic exercises can play a valuable role to disrupt the normal progression of DPN in type 2 diabetes.
Abstract: Objective To evaluate the effect of moderate intensity aerobic exercise (40%–60% of Heart Rate Reserve (HRR)) on diabetic peripheral neuropathy. Methods A parallel-group, randomized controlled trial was carried out in a tertiary health care setting, India. The study comprised of experimental (moderate intensity aerobic exercise and standard care) and control groups (standard care). Population with type 2 diabetes with clinical neuropathy, defined as a minimum score of seven on the Michigan Diabetic Neuropathy Score (MDNS), was randomly assigned to experimental and control groups by computer generated random number tables. RANOVA was used for data analysis ( p Results A total of 87 patients with DPN were evaluated in the study. After randomization there were 47 patients in the control group and 40 patients in the experimental group. A comparison of two groups using RANOVA for anthropometric measures showed an insignificant change at eight weeks. For distal peroneal nerve's conduction velocity there was a significant difference in two groups at eight weeks (p p =0.03. Sural sensory nerve at eight weeks showed a significant difference in two groups for conduction velocity, Df=1, 60, F=10.16, and p =0.00. Significant differences in mean scores of MDNS were also observed in the two groups at eight weeks ( p value significant Conclusion Moderate intensity aerobic exercises can play a valuable role to disrupt the normal progression of DPN in type 2 diabetes.

89 citations


Journal ArticleDOI
TL;DR: Fasting serum homocysteine levels in CAD patients were significantly higher than patients without coronary artery disease (p < 0.001), and Homocyseine levels correlated significantly with increasing severity of CAD.
Abstract: Coronary artery disease (CAD) has become the most common cause of mortality in the entire world. Homocysteine is implicated as an early atherosclerotic promoter. We studied the relationship between levels of serum homocysteine with severity of coronary artery disease. Total of 70 subjects who scheduled for coronary angiogram consented to participate in this study. In all the patients Gensini scoring system was used to assess the severity of CAD. Venous samples were taken from the patients in fasting state before angiography. Homocysteine levels in patients were measured by enzyme linked immunosorbant method and were compared with respective Genseni scores of participants. Fasting serum homocysteine levels in CAD patients were significantly higher than patients without coronary artery disease (p < 0.001). Also Homocyseine levels correlated significantly with increasing severity of CAD (p < 0.001). Serum homocysteine levels correlated well with the severity of CAD.

88 citations


Journal ArticleDOI
TL;DR: In this paper, the secreted frizzled-related protein 4 (sFRP4) was shown to inhibit the growth of CSCs from two HNSCC cell lines, Hep2 and KB.
Abstract: Cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC) are defined by high self-renewal and drug refractory potential. Involvement of Wnt/β-catenin signaling has been implicated in rapidly cycling cells such as CSCs, and inhibition of the Wnt/β-catenin pathway is a novel approach to target CSCs from HNSCC. In this study, we found that an antagonist of FrzB/Wnt, the secreted frizzled-related protein 4 (sFRP4), inhibited the growth of CSCs from two HNSCC cell lines, Hep2 and KB. We enriched the CD44(+) CSC population, and grew them in spheroid cultures. sFRP4 decreased the proliferation and increased the sensitivity of spheroids to a commonly used drug in HNSCC, namely cisplatin. Self-renewal in sphere formation assays decreased upon sFRP4 treatment, and the effect was reverted by the addition of Wnt3a. sFRP4 treatment of spheroids also decreased β-catenin, confirming its action through the Wnt/β-catenin signaling pathway. Quantitative PCR demonstrated a clear decrease of the stemness markers CD44 and ALDH, and an increase in CD24 and drug-resistance markers ABCG2 and ABCC4. Furthermore, we found that after sFRP4 treatment, there was a reversal in the expression of epithelial to mesenchymal (EMT) markers with the restoration of the epithelial marker E-cadherin, and depletion of EMT-specific markers twist, snail and N-cadherin. This is the first report demonstrating that the naturally occurring Wnt inhibitor, sFRP4, can be a potential drug to destroy CSC-enriched spheroids from HNSCCs. The repression of EMT and the decrease in stemness profile further strengthen the use of sFRP4 as a potent therapeutic against CSCs.

86 citations


Journal ArticleDOI
TL;DR: The presence of myofibroblasts was significantly higher in oral squamous cell carcinomas as compared to that in OSMF with dysplasia and OSMF, and may help in providing therapeutic regimens in fibrosis, dys Plasia and cancer.
Abstract: Objective: Evaluation of Myofibroblasts by studying expression of Alpha smooth muscle actin: A marker of Fibrosis, Dysplasia and Carcinoma. Background: Myofibroblasts are cells that have contractile properties and are involved in inflammation, wound healing, fibrosis and oncogenesis in most of the organs and tissues. They are involved in healing and granulation tissue formation which occur after tissue injuries, also produce inflammatory mediators, growth factors and help in extracellular matrix reorganization by secretion of proteins like collagen, fibronectin, etc. Because of their component, Alpha smooth muscle actin ([alpha]-SMA), they are involved in the contraction of extracellular matrix and aid in tissue contraction. The myofibroblasts disappear by apoptosis after completion of repair, but their persistence causes a dysfunction in the repair mechanism, leading to excessive contraction and extracellular matrix (ECM) secretion and thus, fibrosis. The purpose of this study was to evaluate the presence of myofibroblasts in cases of Oral Submucous fibrosis (OSMF), which consisted of very early, early and moderately advanced OSMF, OSMF with dysplasia and oral squamous cell carcinoma (OSCC), by detecting (alpha)-SMA, which is a specific marker for myofibroblasts. Materials and Methods: The study sample consisted of three groups which comprised of 41 cases of OSMF, 10 cases of OSMF with dysplasia and 11 cases of OSCC. All the cases were subjected to immunohistochemistry by using (alpha)-SMA antibody for detection of myofibroblasts. Results: The presence of myofibroblasts was significantly higher in oral squamous cell carcinomas as compared to that in OSMF with dysplasia and OSMF. A statistical significance was also noted between the staining index and age of the individuals and the staining index and duration of the habit. Conclusion: Myofibroblasts play a role in fibrosis, as was seen in OSMF. Activated myofibroblasts secrete proteolytic enzymes and cause matrix degradation, which is instrumental in cancer cell invasion and metastasis. Further studies in which the myofibroblasts are targetted, may help in providing therapeutic regimens in fibrosis, dysplasia and cancer.

Journal ArticleDOI
01 Jan 2014-Database
TL;DR: The TSLP signaling pathway map is presented, expecting that it will provide a rich resource to study the biology of this important cytokine as well as to identify novel therapeutic targets for diseases associated with dysregulated T SLP/TSLPR signaling.
Abstract: Thymic stromal lymphopoietin (TSLP) is a four-helix bundle cytokine that plays a critical role in the regulation of immune responses and in the differentiation of hematopoietic cells. TSLP signals through a heterodimeric receptor complex consisting of an interleukin-7 receptor α chain and a unique TSLP receptor (TSLPR) [also known as cytokine receptor-like factor 2 (CRLF2)]. Cellular targets of TSLP include dendritic cells, B cells, mast cells, regulatory T (Treg) cells and CD4+ and CD8+ T cells. The TSLP/TSLPR axis can activate multiple signaling transduction pathways including the JAK/STAT pathway and the PI-3 kinase pathway. Aberrant TSLP/TSLPR signaling has been associated with a variety of human diseases including asthma, atopic dermatitis, nasal polyposis, inflammatory bowel disease, eosinophilic eosophagitis and, most recently, acute lymphoblastic leukemia. A centralized resource of the TSLP signaling pathway cataloging signaling events is not yet available. In this study, we present a literature-annotated resource of reactions in the TSLP signaling pathway. This pathway map is publicly available through NetPath (http://www.netpath.org/), an open access signal transduction pathway resource developed previously by our group. This map includes 236 molecules and 252 reactions that are involved in TSLP/TSLPR signaling pathway. We expect that the TSLP signaling pathway map will provide a rich resource to study the biology of this important cytokine as well as to identify novel therapeutic targets for diseases associated with dysregulated TSLP/TSLPR signaling. Database URL: http://www.netpath.org/pathways?path_id=NetPath_24.

Journal ArticleDOI
TL;DR: A novel series of 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1-3,4-oxadiazoles were designed and synthesized for selective COX-2 inhibition with potent anti-inflammatory activity and showed suppression of acetic acid-induced writhes comparable to that of aspirin and gastro-sparing profile superior to the aspirin.

Journal ArticleDOI
TL;DR: Glycosaminoglycans of extracellular matrix played a significant role in regulating osteoblast differentiation and could be exploited in the biomimetic approach of fabricating or functionalizing scaffolds for stem cell based bone tissue engineering.
Abstract: Extracellular matrix plays an important role in regulating cell growth and differentiation. The biomimetic approach of cell-based tissue engineering is based on mirroring this in vivo micro environment for developing a functional tissue engineered construct. In this study, we treated normal tissue culture plates with selected extracellular matrix components consisting of glycosaminoglycans such as chondroitin-4-sulphate, dermatan sulphate, chondroitin-6-sulphate, heparin and hyaluronic acid. Mesenchymal stem cells isolated from adult human bone marrow were cultured on the glycosaminoglycan treated culture plates to evaluate their regulatory role in cell growth and osteoblast differentiation. Although no significant improvement on human mesenchymal stem cell adhesion and proliferation was observed on the glycosaminoglycan-treated tissue culture plates, there was selective osteoblast differentiation, indicating its potential role in differentiation rather than proliferation. Osteoblast differentiation studies showed high osteogenic potential for all tested glycosaminoglycans except chondroitin-4-sulphate. Osteoblast differentiation-associated genes such as osterix, osteocalcin, integrin binding sialoprotein, osteonectin and collagen, type 1, alpha 1 showed significant upregulation. We identified osterix as the key transcription factor responsible for the enhanced bone matrix deposition observed on hyaluronic acid, heparin and chondroitin-6-sulphate. Hyaluronic acid provided the most favourable condition for osteoblast differentiation and bone matrix synthesis. Our results confirm and emphasise the significant role of extracellular matrix in regulating cell differentiation. To summarise, glycosaminoglycans of extracellular matrix played a significant role in regulating osteoblast differentiation and could be exploited in the biomimetic approach of fabricating or functionalizing scaffolds for stem cell based bone tissue engineering.

Journal ArticleDOI
TL;DR: The present study revealed that all the groups of students perceived their learning environment positively, however, a few problematic areas of learning environment were perceived such as: students were stressed more often; they felt that the course organizers were authoritarian and emphasized factual learning.
Abstract: Background: Students’ perception of the environment within which they study has shown to have a significant impact on their behavior, academic progress and sense of well-being. This study was undertaken to evaluate the students’ perception of their learning environment in an Indian medical school following traditional curricula and to study differences, if any, between the students according to the stages of medical education, i.e., the pre-clinical and clinical stages. Methodology: In the present study, the Dundee Ready Education Environment Measure (DREEM) inventory was administered to undergraduate medical students of first (n = 227), third (n = 175), fifth (n = 171) and seventh (n = 123) semesters. Scores obtained were expressed as mean ± Standard Deviation (SD) and analyzed using one-way ANOVA and Dunnett’s test. P-value < 0.05 was considered as significant. Results: The mean DREEM score for our medical school was 123/200.The first-year students were found to be more satisfied with learning environment (indicated by their higher DREEM score) compared to other semester students. Progressive decline in scores with each successive semester was observed. Evaluating the sub-domains of perception, the registrars in all semesters had a more positive perception of learning (Average mean score: 29.44), their perception of course organizers moved in the right direction (Average mean score: 26.86), their academic self-perception was more on the positive side (Average mean score: 20.14), they had a more positive perception of atmosphere (Average mean score: 29.07) and their social self-perception could be graded as not too bad (Average mean score: 17.02). Conclusion: The present study revealed that all the groups of students perceived their learning environment positively. However, a few problematic areas of learning environment were perceived such as: students were stressed more often; they felt that the course organizers were authoritarian and emphasized factual learning. Implementing more problem-based learning, student counseling and workshops on teaching-learning for educators might enable us to remedy and enrich our learning environment.

Journal ArticleDOI
TL;DR: The lecithin-based carrier system of silymarin is developed by incorporating phytosomal-liposomal approach to increase its oral bioavailability and to make it target-specific to the liver for enhanced hepatoprotection and better anti-inflammatory effects.

Journal ArticleDOI
TL;DR: The results show that scaling up from the individual to higher levels of social organization can highlight important factors that influence attitudes of people toward wildlife and toward formal conservation efforts in general.
Abstract: The threat posed by large carnivores to livestock and humans makes peaceful coexistence between them difficult. Effective implementation of conservation laws and policies depends on the attitudes of local residents toward the target species. There are many known correlates of human attitudes toward carnivores, but they have only been assessed at the scale of the individual. Because human societies are organized hierar- chically, attitudes are presumably influenced by different factors at different scales of social organization, but this scale dependence has not been examined. We used structured interview surveys to quantitatively assess the attitudes of a Buddhist pastoral community toward snow leopards (Panthera uncia) and wolves (Canis lupus). We interviewed 381 individuals from 24 villages within 6 study sites across the high-elevation Spiti Valley in the Indian Trans-Himalaya. We gathered information on key explanatory variables that together captured variation in individual and village-level socioeconomic factors. We used hierarchical linear models to examine how the effect of these factors on human attitudes changed with the scale of analysis from the individual to the community. Factors significant at the individual level were gender, education, and age of the respondent (for wolves and snow leopards), number of income sources in the family (wolves), agricultural production, and large-bodied livestock holdings (snow leopards). At the community level, the significant factors included the number of smaller-bodied herded livestock killed by wolves and mean agricultural production (wolves) and village size and large livestock holdings (snow leopards). Our results show that scaling up from the individual to higher levels of social organization can highlight important factors that influence attitudes of people toward wildlife and toward formal conservation efforts in general. Such scale-specific information can help managers apply conservation measures at appropriate scales. Our results reiterate the need for conflict management programs to be multipronged.

Journal ArticleDOI
TL;DR: It is noticed that DOX-Gel nanocarriers are especially effective when injected during the early stage of tumor progression, and achieve a substantial decrease in tumor load in the long term.
Abstract: The majority of the localized drug delivery systems are based on polymeric or polypeptide scaffolds, as weak intermolecular interactions of low molecular weight hydrogelators (LMHGs, Mw <500 Da) are significantly perturbed in the presence of anticancer drugs. Here, we present l-alanine derived low molecular weight hydrogelators (LMHGs) that remain injectable even after entrapping the anticancer drug doxorubicin (DOX). These DOX containing nanoassemblies (DOX-Gel) showed promising anticancer activity in mice models. Subcutaneous injection of DOX-Gel near the tumor achieved a greater decrease in tumour load than by intravenous injection of DOX (DOX-IV), and local injection of DOX alone (DOX-Local) at the tumor site. We noticed that DOX-Gel nanocarriers are especially effective when injected during the early stage of tumor progression, and achieve a substantial decrease in tumor load in the long term.

Journal ArticleDOI
TL;DR: The pace of wound healing was enhanced by BNCPs compared with copper in native form when evaluated for its wound healing activity by excision wound model in rat.
Abstract: Nanotechnologies reinvented the utilities of various substances in healthcare. Copper in its native form (copper ion) has been well studied for its antimicrobial and anti-inflammatory activities. Copper in its nano form could have better biological profile and finds many applications in healthcare. There were reports on synthesis of copper nanoparticles by physical and chemical methods and their biological activities, although these methods have limitations. Biosynthesis of nanoparticles using microbes is an ecofriendly approach helping in the synthesis of biocompatible and stable nanoparticles. With this background in mind, the present study was designed to synthesise copper nanoparticles by Pseudomonas aeruginosa and testing their efficacy in enhancing the pace of wound healing. Culture supernatant was used to synthesise copper nanoparticles. Optimum conditions were selected to maximise the biosynthesis of nanoparticles. Biosynthesised copper nanoparticles (BNCPs) were characterised by Malvern zeta sizer and scanning electron microscopy. Average particle size, polydispersivity index and zeta potential of BNCPs were found to be 110.9 nm, 0.312 and (-) 18.3 mV, respectively. BNCPs was evaluated for its wound healing activity by excision wound model in rat. The pace of wound healing was enhanced by BNCPs compared with copper in native form.

Journal ArticleDOI
TL;DR: This review focuses on neural differentiation potential of MSCs isolated from different sources and how certain growth factors/small molecules can be used to derive neuronal phenotypes from M SCs.
Abstract: Regenerative medicine is an evolving interdisciplinary topic of research involving numerous technological methods that utilize stem cells to repair damaged tissues. Particularly, mesenchymal stem cells (MSCs) are a great tool in regenerative medicine because of their lack of tumorogenicity, immunogenicity and ability to perform immunomodulatory as well as anti-inflammatory functions. Numerous studies have investigated the role of MSCs in tissue repair and modulation of allogeneic immune responses. MSCs derived from different sources hold unique regenerative potential as they are self-renewing and can differentiate into chondrocytes, osteoblasts, adipocytes, cardiomyocytes, hepatocytes, endothelial and neuronal cells, among which neuronal-like cells have gained special interest. MSCs also have the ability to secrete multiple bioactive molecules capable of stimulating recovery of injured cells and inhibiting inflammation. In this review we focus on neural differentiation potential of MSCs isolated from different sources and how certain growth factors/small molecules can be used to derive neuronal phenotypes from MSCs. We also discuss the efficacy of MSCs when transplanted in vivo and how they can generate certain neurons and lead to relief or recovery of the diseased condition. Furthermore, we have tried to evaluate the appropriatemerits of different sources ofMSCs with respect to their propensity towards neurological differentiation as well as their effectiveness in preclinical studies.

Proceedings ArticleDOI
06 Nov 2014
TL;DR: Algorithms that determine PR from videoplethysmographic signals extracted from multiple regions of interest (ROI) simultaneously available within the field of view of the camera where cardiac signal is registered are described.
Abstract: We describe a novel method to monitor pulse rate (PR) on a continuous basis of patients in a neonatal intensive care unit (NICU) using videos taken from a high definition (HD) webcam. We describe algorithms that determine PR from videoplethysmographic (VPG) signals extracted from multiple regions of interest (ROI) simultaneously available within the field of view of the camera where cardiac signal is registered. We detect motion from video images and compensate for motion artifacts from each ROI. Preliminary clinical results are presented on 8 neonates each with 30 minutes of uninterrupted video. Comparisons to hospital equipment indicate that the proposed technology can meet medical industry standards and give improved patient comfort and ease of use for practitioners when instrumented with proper hardware.

Journal ArticleDOI
TL;DR: It is demonstrated that phosphorylation of cortactin by AKT1 is important for mutant PI3K enhanced cell migration and invasion through mutagenesis studies, and a quantitative and global approach is described for identifying mutation-specific signaling events and for discovering novel signaling molecules as readouts of pathway activation or potential therapeutic targets.
Abstract: The PIK3CA gene is frequently mutated in human cancers. Here we carry out a SILAC-based quantitative phosphoproteomic analysis using isogenic knockin cell lines containing 'driver' oncogenic mutations of PIK3CA to dissect the signalling mechanisms responsible for oncogenic phenotypes induced by mutant PIK3CA. From 8,075 unique phosphopeptides identified, we observe that aberrant activation of PI3K pathway leads to increased phosphorylation of a surprisingly wide variety of kinases and downstream signalling networks. Here, by integrating phosphoproteomic data with human protein microarray-based AKT1 kinase assays, we discover and validate six novel AKT1 substrates, including cortactin. Through mutagenesis studies, we demonstrate that phosphorylation of cortactin by AKT1 is important for mutant PI3K-enhanced cell migration and invasion. Our study describes a quantitative and global approach for identifying mutation-specific signalling events and for discovering novel signalling molecules as readouts of pathway activation or potential therapeutic targets.

Journal ArticleDOI
TL;DR: The weakened immune response in diabetic individuals and synergism among pathogenic micro-organisms may be the critical factors that determine the delicate balance of the wound healing process.
Abstract: While virulence factors and the biofilm-forming capabilities of microbes are the key regulators of the wound healing process, the host immune response may also contribute in the events following wound closure or exacerbation of non-closure. We examined samples from diabetic and non-diabetic foot ulcers/wounds for microbial association and tested the microbes for their antibiotic susceptibility and ability to produce biofilms. A total of 1074 bacterial strains were obtained with staphylococci, Pseudomonas, Citrobacter and enterococci as major colonizers in diabetic samples. Though non-diabetic samples had a similar assemblage, the frequency of occurrence of different groups of bacteria was different. Gram-negative bacteria were found to be more prevalent in the diabetic wound environment while Gram-positive bacteria were predominant in non-diabetic ulcers. A higher frequency of monomicrobial infection was observed in samples from non-diabetic individuals when compared to samples from diabetic patients. The prevalence of different groups of bacteria varied when the samples were stratified according to age and sex of the individuals. Several multidrug-resistant strains were observed among the samples tested and most of these strains produced moderate to high levels of biofilms. The weakened immune response in diabetic individuals and synergism among pathogenic micro-organisms may be the critical factors that determine the delicate balance of the wound healing process.

Journal ArticleDOI
TL;DR: Moderate intensity aerobic exercise is cornerstone in improving the quality of life of individuals with peripheral neuropathy in type 2 diabetes.
Abstract: To evaluate the effect of 8-week moderate intensity aerobic (heart-rate reserve 40–60 %) exercise on neuropathy quality of life in type 2 diabetes. A single blind, parallel-group, randomized controlled trial was carried out in a tertiary setting. People with type 2 diabetes were eligible for the study if they had clinical neuropathy which was defined by a minimum score of seven on the Michigan diabetic neuropathy score. Following which, the patients were randomly assigned to an 8-week program by a computer-generated random number tables to intervention or control group. Repeated measure analysis of variance was used for data analysis (p < 0.05 was considered significant). There were 47 participants in the control group and 40 participants in the study group after randomization but 37 from the control group and 29 from the intervention group completed the final analysis. The two groups had a significant difference, pre–post intervention in scores of pain (F = 7, p = 0.01), sensory symptoms (F = 4.60, p = 0.04), restricted activities of daily living (F = 4.97, p = 0.03), disruptions in social relationships (F = 5.43, p = 0.02), specific impact on quality of life (F = 9.28, p < 0.001) overall quality of life (F = 28.72, p < 0.001), and total score (F = 31.10, p < 0.001). Degrees of freedom for all the components were 1, 62. Moderate intensity aerobic exercise is cornerstone in improving the quality of life of individuals with peripheral neuropathy in type 2 diabetes.

Journal ArticleDOI
TL;DR: This review highlights the mechanism through which saturated fatty acids contribute to CV disease (CVD), how oils and fats contribute to the risk of CVD, and the existing views on VCO and how its cardioprotective effects may make this a possible dietary intervention in isolation or in combination with exercise to help reduce the burden ofCVDs.
Abstract: Emphasis on diet to improve the cardiovascular (CV) risk profile has been the focus of many studies. Recently, virgin coconut oil (VCO) has been growing in popularity due to its potential CV benefits. The chemical properties and the manufacturing process of VCO make this oil healthier than its copra-derived counterpart. This review highlights the mechanism through which saturated fatty acids contribute to CV disease (CVD), how oils and fats contribute to the risk of CVD, and the existing views on VCO and how its cardioprotective effects may make this a possible dietary intervention in isolation or in combination with exercise to help reduce the burden of CVDs.

Journal ArticleDOI
02 Jan 2014
TL;DR: The aim of this audit was to analyze indications, complications, and correlation of preoperative diagnosis with final histopathology report of all hysterectomies, performed in a premier teaching hospital in Southern India in one year.
Abstract: Objective. Aim of this audit was to analyze indications, complications, and correlation of preoperative diagnosis with final histopathology report of all hysterectomies, performed in a premier teaching hospital. Methods. Present study involved all patients who underwent hysterectomy at a premier university hospital in Southern India, in one year (from 1 January, 2012, to 31 December, 2012). Results. Most common surgical approach was abdominal (74.7%), followed by vaginal (17.8%), and laparoscopic (6.6%) hysterectomy. Most common indication for hysterectomy was symptomatic fibroid uterus (39.9%), followed by uterovaginal prolapse (16.3%). Overall complication rate was 8.5%. Around 84% had the same pathology as suspected preoperatively. Only 6 (5 with preoperative diagnosis of abnormal uterine bleeding and one with high grade premalignant cervical lesion) had no significant pathology in their hysterectomy specimen. Conclusion. Hysterectomy is used commonly to improve the quality of life; however at times it is a lifesaving procedure. As any surgical procedure is associated with a risk of complications, the indication should be carefully evaluated. With the emergence of many conservative approaches to deal with benign gynecological conditions, it is prudent to discuss available options with the patient before taking a direct decision of surgically removing her uterus.

Journal ArticleDOI
TL;DR: Dental pulp stem cells immobilized in alginate hydrogels exhibit enhanced osteogenic potential while maintaining high cell viability both of which are fundamental for bone tissue regeneration.
Abstract: Aim To immobilize dental pulp stem cells (DPSC) in alginate microspheres and to determine cell viability, proliferation, stem cell characteristics and osteogenic potential of the immobilized DPSCs. Methodology Human DPSCs isolated from the dental pulp were immobilized in 1% w/v alginate microspheres. Viability and proliferation of immobilized DPSCs were determined by trypan blue and MTT assay, respectively. Stem cell characteristics of DPSCs post immobilization were verified by labelling the cells with CD73 and CD90. Osteogenic potential of immobilized DPSCs was assessed by the presence of osteocalcin. Alizarin red staining and O-cresolphthalein complexone method confirmed and quantified calcium deposition. A final reverse transcriptase PCR evaluated the expression of osteogenic markers – ALP, Runx-2 and OCN. Results More than 80% of immobilized DPSCs were viable throughout the 3-week study. Proliferation appeared controlled and consistent unlike DPSCs in the control group. Presence of CD73 and CD90 markers confirmed the stem cell nature of immobilized DPSCs. The presence of osteocalcin, an osteoblastic marker, was confirmed in the microspheres on day 21. Mineralization assays showed high calcium deposition indicating elevated osteogenic potential of immobilized DPSCs. Osteogenic genes- ALP, Runx-2 and OCN were also upregulated in immobilized DPSCs. Surprisingly, immobilized DPSCs in the control group cultured in conventional stem cell media showed upregulation of osteogenic genes and expressed osteocalcin. Conclusion Dental pulp stem cells immobilized in alginate hydrogels exhibit enhanced osteogenic potential while maintaining high cell viability both of which are fundamental for bone tissue regeneration.

Journal ArticleDOI
TL;DR: Prevalence showed Gram-negative bacteria was slightly more than Gram- positive bacteria in diabetic foot ulcers, and doxycycline should be empirical treatment of choice for Gram-positive isolates and amikacin, cefoperazone/sulbactam, and meropenem should be considered for most of the Gram-negatives aerobes.
Abstract: Background: Diabetic foot infections (DFIs) are major public health problems and knowledge of microbes that cause infections are helpful to determine proper antibiotic therapy. Aims: The aim was to investigate the antimicrobial susceptibility pattern of microbes in DFIs. Subjects and Methods: A cross‑sectional study was conducted for a period of 6 months at the Department of General Surgery, KMC hospital, Manipal University, Manipal, India. During this period, 108 patients having DFIs admitted in the general surgery wards were tracked from the hospital data management system. These patients’ pus samples were examined as Gram‑stained smear and cultured aerobically on blood agar and MacConkey agar plates. Antimicrobial susceptibility test was performed by disc diffusion techniques according to Clinical and Laboratory Standards Institute guidelines. Results: Of the 108 specimens of the diabetic foot lesions, culture showed polymicrobial growth in 44.4% (48/108). Prevalence of Gram‑negative organisms (56%, 84/150) was found to be more than Gram‑positive organisms (44%, 66/150). However, Staphylococcus aureus was the most frequent pathogen (28%, 42/150). All Gram‑positive aerobes were sensitive to doxycycline. All Gram‑negative isolates, including extended spectrum beta lactamase producing strains of Proteus mirabilis and Klebsiella oxytoca except Acinetobacter were highly sensitive to amikacin, cefoperazone/sulbactam, and meropenem. Acinetobacter was completely resistant to all the common antibiotics tested. Conclusion: Prevalence showed Gram‑negative bacteria was slightly more than Gram‑positive bacteria in diabetic foot ulcers. This study recommends doxycycline should be empirical treatment of choice for Gram‑positive isolates and amikacin, cefoperazone/sulbactam, and meropenem should be considered for most of the Gram‑negatives aerobes.

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TL;DR: The data clearly demonstrate for the first time that DPSCs in the presence of embryonic midbrain cues show efficient propensity towards functional dopaminergic cell‐type.
Abstract: Dental pulp originating from the neural crest is considered a better source of postnatal stem cells for cell-based therapies in neurodegenerative diseases. Dental Pulp Stem Cells (DPSCs) have been shown to differentiate into cell-types of cranial neural crest ontology; however, their ability to differentiate to functional neurons of the central nervous system remains to be studied. We hypothesized that midbrain cues might commit DPSCs to differentiate to functional dopaminergic cell-type. As expected, DPSCs in their naive state spontaneously expressed early and mature neuronal markers like nestin, musashi12, β tubulin III, and Map2ab. On exposure to midbrain cues (sonic hedgehog, fibroblast growth factor 8 and basic fibroblast growth factor), DPSCs showed upregulation of dopaminergic neuron-specific transcription factors Nuclear Receptor related protein 1 (Nurr1), Engrailed 1 (En1) and paired-like homeodomain transcription factor 3 (Pitx3) as revealed by real-time RT-PCR. Immunofluorescence and flow cytometry analysis showed enhanced expression of mature neuronal marker Map2ab and dopaminergic-neuronal markers [tyrosine hydroxylase (TH), En1, Nurr1, and Pitx3], with nearly 77% of the induced DPSCs positive for TH. Functional studies indicated that the induced DPSCs could secrete dopamine constitutively and upon stimulation with potassium chloride (KCl) and adenosine triphosphate (ATP), as measured by dopamine ELISA. Additionally, the induced DPSCs showed intracellular Ca(2+) influx in the presence of KCl, unlike control DPSCs. ATP-stimulated Ca(2+) influx was observed in control and induced DPSCs, but only the induced cells secreted dopamine. Our data clearly demonstrate for the first time that DPSCs in the presence of embryonic midbrain cues show efficient propensity towards functional dopaminergic cell-type.

Journal Article
TL;DR: These findings provide a basis for enhancing nursing practices, knowledge and skills and minimising barriers is crucial to increasing the use of EBP in Oman.
Abstract: Objectives: The aim of this study was to describe nurses’ practices, attitudes, knowledge/skills and perceived barriers in relation to evidence-based practice (EBP) in Oman. Methods: This descriptive cross-sectional study was conducted between February and November 2012. A self-reported 24-item questionnaire was used to measure EBP practices, attitudes and knowledge/skills among a convenience sample of 600 nurses working in four governmental hospitals in Muscat, Oman. Responses were scored on a one to seven rating scale. Barriers to EBP were measured on a five-point Likert scale using two subscales. Descriptive statistics and general linear regression were used to analyse the data. Results: A total of 414 nurses were included in the study. The greatest barriers to developing EBP among nurses were insufficient time for research (3.51 ± 0.97) and insufficient resources to change practices (3.64 ± 0.99). Nurses with more years of experience reported increased use of EBP (P <0.01), more positive attitudes towards EBP (P <0.001) and fewer barriers to research (P <0.01). Significant positive correlations were found between years of experience and practice (r = 0.16) and attitudes (r = 0.20). Nurses with a baccalaureate degree reported fewer barriers to research than those qualified at a diploma level (P <0.001). Nurses who perceived more barriers to research reported less use of EBP (P <0.001), less positive attitudes towards EBP (P <0.001) and limited EBP knowledge/skills (P <0.001). Conclusion: These findings provide a basis for enhancing nursing practices, knowledge and skills. Continuing education for nurses and minimising barriers is crucial to increasing the use of EBP in Oman.