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Τρίτη, 14 Μαρτίου 2017

Fatty Acid Synthesis Intermediates Represent Novel Noninvasive Biomarkers of Prostate Cancer Chemoprevention by Phenethyl Isothiocyanate

Increased de novo synthesis of fatty acids is a distinctive feature of prostate cancer, which continues to be a leading cause of cancer-related deaths among American men. Therefore, inhibition of de novo fatty acid synthesis represents an attractive strategy for chemoprevention of prostate cancer. We have shown previously that dietary feeding of phenethyl isothiocyanate (PEITC), a phytochemical derived from edible cruciferous vegetables such as watercress, inhibits incidence and burden of poorly-differentiated prostate cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model. The present study was designed to test the hypothesis of whether fatty acid intermediate(s) can serve as noninvasive biomarker(s) of prostate cancer chemoprevention by PEITC using archived plasma and tumor specimens from the TRAMP study as well as cellular models of prostate cancer. Exposure of prostate cancer cells (LNCaP and 22Rv1) to pharmacological concentrations of PEITC resulted in downregulation of key fatty acid metabolism proteins, including acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A). The mRNA expression of FASN and CPT1A as well as acetyl-CoA levels were decreased by PEITC treatment in both cell lines. PEITC administration to TRAMP mice also resulted in a significant decrease in tumor expression of FASN protein. Consistent with these findings, the levels of total free fatty acids, total phospholipids, triglyceride, and ATP were significantly lower in the plasma and/or prostate tumors of PEITC-treated TRAMP mice compared with controls. The present study is the first to implicate inhibition of fatty acid synthesis in prostate cancer chemoprevention by PEITC.



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Controlled delivery of platelet-derived proteins enhances porcine wound healing

Publication date: Available online 14 March 2017
Source:Journal of Controlled Release
Author(s): Daniel W. Long, Noah R. Johnson, Eric M. Jeffries, Hidetaka Hara, Yadong Wang
Platelet-rich plasma (PRP) is widely used for many clinical indications including wound healing due to the high concentrations of growth factors. However, the short half-life of these therapeutic proteins requires multiple large doses, and their efficacy is highly debated among clinicians. Here we report a method of protecting these proteins and releasing them in a controlled manner via a heparin-based coacervate delivery vehicle to improve wound healing in a porcine model. Platelet-derived proteins incorporated into the coacervate were protected and slowly released over 3weeks in vitro. In a porcine model, PRP coacervate significantly accelerated the healing response over 10days, in part by increasing the rate of wound reepithelialization by 35% compared to control. Additionally, PRP coacervate doubled the rate of wound contraction compared to all other treatments, including that of free PRP proteins. Wounds treated with PRP coacervate exhibited increased collagen alignment and an advanced state of vascularity compared to control treatments. These results suggest that this preparation of PRP accelerates healing of cutaneous wounds only as a controlled release formulation. The coacervate delivery vehicle is a simple and effective tool to improve the therapeutic efficacy of platelet-derived proteins for wound healing.

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Targeting ETS1 with RNAi-based supramolecular nanoassemblies for multidrug-resistant breast cancer therapy

Publication date: Available online 14 March 2017
Source:Journal of Controlled Release
Author(s): Min Wu, Xingang Liu, Weihong Jin, Yongbing Li, Yang Li, Qinglian Hu, Paul K. Chu, Guping Tang, Yuan Ping
Overexpression of erythroblastosis virus E26 oncogene homolog 1 (ETS1) gene is correlated with both tumor progression and poor response to chemotherapy in cancer treatment, and the exploitation of RNA interference (RNAi) technology to downregulate ETS1 seems to be a promising approach to reverse multidrug-resistant cancer cells to chemotherapy. Hence, the RNAi-based nanomedicine which is able to simultaneously downregulate ETS1 expression and to deliver chemotherapeutic agents may improve multidrug-resistant cancer therapy synergistically. In this study, we developed a supramolecular nanoassembly that could deliver siRNA targeting ETS1 (siETS1) and doxorubicin (DOX) as an effective nanomedicine to achieve successful chemotherapy towards multidrug-resistant breast cancer. The nanotherapeutic system was prepared by loading adamantane-conjugated doxorubicin (AD) into polyethyleneimine-modified (2-hydroxypropyl)-γ-cyclodextrin (HP) through the supramolecular assembly to form AD-loaded HP (HPAD), followed by electrostatically-driven self-assembly between siETS1 and HPAD. When the HPAD/siETS1 nanoassemblies were delivered into drug-resistant MCF-7/ADR cells, the drug efflux was significantly reduced as a result of simultaneous silencing of ETS1 and MDR1 genes. Importantly, the HPAD/siETS1 nanoassembly could enhance drug residence time at tumor site, and effectively inhibit drug-resistant tumor growth due to the inhibition of angiogenesis and necrosis in tumor tissues. Western blot analysis indicated that the gene expression of both ETS1 and MDR1 in vivo was considerably downregulated after the drug-resistant tumor-bearing mouse was treated with HPAD/siETS1 nanoassemblies. This study offers a new therapeutic delivery strategy targeting ETS1 for the effective multidrug-resistant chemotherapy.

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Editorial Board

Publication date: 28 March 2017
Source:Journal of Controlled Release, Volume 250





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Attenuating the immunogenicity of PEGylated liposomes by gangliosides

Publication date: 28 March 2017
Source:Journal of Controlled Release, Volume 250
Author(s): Kinam Park




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Calendar

Publication date: 28 March 2017
Source:Journal of Controlled Release, Volume 250





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Characterization of pegylated and non-pegylated liposomal formulation for the delivery of hypoxia activated vinblastine-N-oxide for the treatment of solid tumors

Publication date: Available online 14 March 2017
Source:Journal of Controlled Release
Author(s): Vidhi M. Shah, Duc X. Nguyen, Adel Alfatease, Shay Bracha, Adam WG. Alani
Solid tumors often contain hypoxic regions which are resistant to standard chemotherapy and radiotherapy. We have developed a liposomal delivery system for a prodrug of vinblastine (CPD100) which converts to the parent compound only in the presence of lower oxygen levels. As a part of this work we have developed and optimized two formulations of CPD100: one composed of sphingomyelin/cholesterol (55/45; mol/mol) (CPD100Li) and the other composed of sphingomyelin/cholesterol/PEG (55/40/5; mol/mol) (CPD100 PEGLi). We evaluated the antiproliferative effect of CPD100 and the two formulations against A549 non-small lung cancer cell. A549 cell line showed to be sensitive to CPD100 and the two formulations displayed a higher hypoxic: air cytotoxicity ratio compared to the pro-drug. CPD100 elimination from the circulation after injection in mouse was characterized by a very short circulation time (~0.44h), lower area under the curve (AUC) (33μgh/mL) and high clearance (916mL/h/kg) and lower volume of distribution (17.4mL/kg).Total drug elimination from the circulation after the administration of liposomal formulation was characterized by prolonged circulation time (5.5h) along with increase in the AUC (56μgh/mL) for CPD100 Li and (9.5h) with AUC (170μgh/mL) for CPD100PEGLi. This was observed along with increase in volume of distribution and decrease in clearance for the liposomes. The systemic exposure of the free drug was much lower than that achieved with the liposomes. When evaluated for the efficacy in A549 xenograft model in mice, both the liposomes demonstrated excellent tumor suppression and reduction for 3months. The blood chemistry panel and the comprehensive blood analysis showed no increase or decrease in the markers and blood count. In summary, the pharmacokinetic analysis along with the efficacy data emphasis on how the delivery vehicle modifies and enhances the accumulation of the drug and at the same time the increased systemic exposure is not related to toxicity.

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Perlecan and vascular endothelial growth factor-encoding DNA-loaded chitosan scaffolds promote angiogenesis and wound healing

Publication date: 28 March 2017
Source:Journal of Controlled Release, Volume 250
Author(s): Megan S. Lord, April L. Ellis, Brooke L. Farrugia, John M. Whitelock, Hernan Grenett, Chuanyu Li, Robert L. O'Grady, Arthur A. DeCarlo
The repair of dermal wounds, particularly in the diabetic population, poses a significant healthcare burden. The impaired wound healing of diabetic wounds is attributed to low levels of endogenous growth factors, including vascular endothelial growth factor (VEGF), that normally stimulate multiple phases of wound healing. In this study, chitosan scaffolds were prepared via freeze drying and loaded with plasmid DNA encoding perlecan domain I and VEGF189 and analyzed in vivo for their ability to promote dermal wound healing. The plasmid DNA encoding perlecan domain I and VEGF189 loaded scaffolds promoted dermal wound healing in normal and diabetic rats. This treatment resulted in an increase in the number of blood vessels and sub-epithelial connective tissue matrix components within the wound beds compared to wounds treated with chitosan scaffolds containing control DNA or wounded controls. These results suggest that chitosan scaffolds containing plasmid DNA encoding VEGF189 and perlecan domain I have the potential to induce angiogenesis and wound healing.

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Graphical Abstracts Contents Listing

Publication date: 28 March 2017
Source:Journal of Controlled Release, Volume 250





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The Host Microbiome Regulates and Maintains Human Health: A Primer and Perspective for Non-Microbiologists

Humans consider themselves discrete autonomous organisms, but recent research is rapidly strengthening the appreciation that associated microorganisms make essential contributions to human health and well being. Each person is inhabited and also surrounded by his/her own signature microbial cloud. A low diversity of microorganisms is associated with a plethora of diseases, including allergy, diabetes, obesity, arthritis, inflammatory bowel diseases, and even neuropsychiatric disorders. Thus, an interaction of microorganisms with the host immune system is required for a healthy body. Exposure to microorganisms from the moment we are born and appropriate microbiome assembly during childhood are essential for establishing an active immune system necessary to prevent disease later in life. Exposure to microorganisms educates the immune system, induces adaptive immunity, and initiates memory B and T cells that are essential to combat various pathogens. The correct microbial-based education of immune cells may be critical in preventing the development of autoimmune diseases and cancer. This review provides a broad overview of the importance of the host microbiome and accumulating knowledge of how it regulates and maintains a healthy human system. Cancer Res; 1–30. ©2017 AACR.

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Traditional Arabic & Islamic medicine: validation and empirical assessment of a conceptual model in Qatar

Evidence indicates traditional medicine is no longer only used for the healthcare of the poor, its prevalence is also increasing in countries where allopathic medicine is predominant in the healthcare system. ...

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Association between trial registration and positive study findings: cross sectional study (Epidemiological Study of Randomized Trials—ESORT)

Objective To assess whether randomised controlled trials (RCTs) that were registered were less likely to report positive study findings compared with RCTs that were not registered and whether the...
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The growing problem of co-treatment with opioids and benzodiazepines

Since 1999, the US has witnessed a fourfold increase in deaths from overdose involving prescription opioids,1 a fact widely known by US residents. That benzodiazepines are present in over 30% of...
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Complete Elucidation of the Late Steps of Bafilomycin Biosynthesis in Streptomyces lohii [Metabolism]

Bafilomycins are an important subgroup of polyketides with diverse biological activities and possible applications as specific inhibitors of vacuolar H+-ATPase. However, the general toxicity and structural complexity of bafilomycins present formidable challenges to drug design via chemical modification, prompting interests in improving bafilomycin activities via biosynthetic approaches. Two bafilomycin biosynthetic gene clusters have been identified, but their post- polyketide synthase (PKS) tailoring steps for structural diversification and bioactivity improvement remain largely unknown. In this study, the post-PKS tailoring pathway from bafilomycin A1 (1)→C1 (2)→B1 (3) in the marine microorganism Streptomyces lohii was elucidated for the first time by in vivo gene inactivation and in vitro biochemical characterization. We found that fumarate is firstly adenylated by a novel fumarate adenylyltransferase Orf3. Then, the fumaryl transferase Orf2 is responsible for transferring the fumarate moiety from fumaryl-AMP to the 21-hydroxyl group of 1 to generate 2. Lastly, the ATP-dependent amide synthetase BafY catalyzes the condensation of 2 and 2-amino-3-hydroxycyclopent-2-enone (C5N) produced by the 5-aminolevulinic acid (5-ALA) synthase BafZ and the acyl CoA ligase BafX, giving rise to the final product 3. The elucidation of fumarate incorporation mechanism represents the first paradigm for biosynthesis of natural products containing the fumarate moiety. Moreover, the bafilomycin post-PKS tailoring pathway features an interesting crosstalk between primary and secondary metabolisms for natural product biosynthesis. Taken together, this work provides significant insights into bafilomycin biosynthesis to inform future pharmacological development of these compounds.

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Crystal Structure of the Human Alkaline Sphingomyelinase Provides Insights into Substrate Recognition [Lipids]

Absorption of dietary sphingomyelin (SM) requires its initial degradation into ceramide, a process catalyzed by the intestinal enzyme alkaline sphingomyelinase (alk-SMase, NPP7, ENPP7). Alk-SMase belongs to the nucleotide pyrophosphatase / phosphodiesterase family, the members of which hydrolyze nucleoside phosphates, phospholipids and other related molecules. NPP7 is the only paralog that can cleave SM, and its activity requires the presence of bile salts, a class of physiological anionic detergents. To elucidate the mechanism of substrate recognition, we determined the crystal structure of human alk-SMase in complex with phosphocholine, a reaction product. Although the overall fold and catalytic center is conserved relative to other NPPs, alk-SMase recognizes the choline moiety of its substrates via an NPP7-specific aromatic box composed of tyrosine residues. Mutational analysis and enzymatic activity assays identified features on the surface of the protein - a cationic patch and a unique hydrophobic loop - that are essential for accessing SM in bile salt micelles. These results shed new light on substrate specificity determinants within the NPP enzyme family.

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Defining the Crucial Domain and Amino Acid Residues in Bacterial Lon Protease for DNA Binding and Processing of DNA-interacting Substrates [Microbiology]

Lon protease has previously been shown to interact with DNA but the role of this interaction for Lon proteolytic activity has not been characterized. In this study, we used truncated Escherichia coli Lon constructs, bioinformatics analysis and site directed mutagenesis to identify Lon domains and residues crucial for Lon binding with DNA and effects on Lon proteolytic activity. We found that deletion of Lons ATPase domain abrogated interactions with DNA. Substitution of positively charged amino acids in this domain in full length Lon with residues conferring a net negative charge disrupted binding of Lon to DNA. These changes also affected the degradation of nucleic acid binding protein substrates of Lon, intracellular localization of Lon, and cell morphology. In vivo tests revealed that Lon DNA interactions are essential for Lon activity in cell division control. In summary, we demonstrate that the ability of Lon to bind DNA is determined by its ATPase domain, that this binding is required for processing protein substrates in nucleoprotein complexes, and that Lon may help regulate DNA replication in response to growth conditions.

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Calcium and Magnesium Ions Modulate the Oligomeric State and Function of Mitochondrial 2-Cys Peroxiredoxins in Leishmania Parasites [Enzymology]

Leishmania parasites have evolved a number of strategies to cope with the harsh environmental changes during mammalian infection. One of these mechanisms involves the functional gain that allowed mitochondrial 2-Cys peroxiredoxins to act as molecular chaperones when forming decamers. This function was demonstrated to be critical for the parasite infectivity in mammals and its activation was considered to be controlled exclusively by the enzyme redox state under physiological conditions. Herein, we revealed that magnesium and calcium ions play a major role in modulating the ability of these enzymes to act as molecular chaperones, surpassing the redox effect. These ions are directly involved in the mitochondrial metabolism and now also integrate a novel mechanism to stabilize the decameric form of 2-Cys peroxiredoxins in Leishmania mitochondrion. Moreover, we demonstrated that a constitutively dimeric Prx1m mutant impairs Leishmania's survival under heat stress, supporting the central role of chaperone function of Prx1m for Leishmania parasites during the transition from insect to mammalian hosts.

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Cockayne Syndrome B Protein Regulates Recruitment of the Elongin A Ubiquitin Ligase to Sites of DNA Damage [DNA and Chromosomes]

Elongin A performs dual functions as the transcriptionally active subunit of RNA polymerase II (Pol II) elongation factor Elongin and as the substrate recognition subunit of a Cullin-RING E3 ubiquitin ligase that ubiquitylates Pol II in response to DNA damage. Assembly of the Elongin A ubiquitin ligase and its recruitment to sites of DNA damage is a tightly regulated process induced by DNA damaging agents and α-amanitin, a drug that induces Pol II stalling. In this report, we demonstrate (i) that Elongin A and the ubiquitin ligase subunit CUL5 associate in cells with the Cockayne syndrome B (CSB) protein and (ii) that this interaction is also induced by DNA damage agents and α-amanitin. In addition, we present evidence that the CSB protein promotes stable recruitment of the Elongin A ubiquitin ligase to sites of DNA damage. Our findings are consistent with the model that the Elongin A ubiquitin ligase and the CSB protein function together in a common pathway in response to Pol II stalling and DNA damage.

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Rnf11 sequestration of Smurf2 on membranes antagonizes Smad7 down-regulation of TGF{beta} signaling [Cell Biology]

The activity of the E3 ligase, Smurf2, is antagonized by an intra-molecular, auto-inhibitory interaction between its C2 and Hect domains. Relief of Smurf2 auto-inhibition is induced by TGFβ and is mediated by the inhibitory SMAD, Smad7. In a proteomic screen for endo-membrane interactants of the RING-domain E3 ligase, Rnf11, we identified Smurf2, among a cohort of Hect E3 ligases previously implicated in TGFβ signaling. Reconstitution of the Smurf2/Rnf11 complex in vitro unexpectedly revealed robust Smurf2 E3 ligase activity, with biochemical properties previously restricted to the Smurf2/Smad7 complex. Using in vitro binding assays, we find that Rnf11 can directly compete with Smad7 for Smurf2 and that binding is mutually exclusive and dependent on a proline-rich domain. Moreover, we found that co-expression of Rnf11 and Smurf2 dramatically reduced Smurf2 ubiquitylation in the cell. This effect is strictly dependent on complex formation and sorting determinants that regulate the association of Rnf11 with membranes. Rnf11 is over-expressed in certain tumors, and, importantly, we find that depletion of this protein down-regulated gene expression of several TGFβ-responsive genes, dampened cell proliferation, and dramatically reduced cell migration in response to TGFβ. Our data suggest for the first time that choice of binding partners for Smurf2 can sustain or repress TGFβ signaling and Rnf11 may promote TGFβ-induced cell migration.

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Allelopathic Activity of Extracts from Different Brazilian Peanut (Arachis hypogaea L.) Cultivars on Lettuce (Lactuca sativa) and Weed Plants

Peanut (Arachis hypogaea L.) is the fourth most consumed oleaginous plant in the world, producing seeds with high contents of lipids, proteins, vitamins, and carbohydrates. Biological activities of different extracts of this species have already been evaluated by many researchers, including antioxidant, antitumoral, and antibacterial. In this work, the allelopathic activity of extracts from different Brazilian peanut cultivars against lettuce (Lactuca sativa) and two weed plants (Commelina benghalensis and Ipomoea nil) was studied. Aerial parts, roots, seeds, and seed coats were used for the preparation of crude extracts. Seed extract partitioning was performed with n-hexane, dichloromethane, ethyl acetate, n-butanol, and aqueous residue. Germination and growth of hypocotyls and rootlets were evaluated after one and five days of incubation with plant extracts, respectively. Crude seed extract and its dichloromethanic partition displayed highest allelopathic activity. These results contribute for the study of new potential natural herbicides.

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Implementation and Optimization of GPU-Based Static State Security Analysis in Power Systems

Static state security analysis (SSSA) is one of the most important computations to check whether a power system is in normal and secure operating state. It is a challenge to satisfy real-time requirements with CPU-based concurrent methods due to the intensive computations. A sensitivity analysis-based method with Graphics processing unit (GPU) is proposed for power systems, which can reduce calculation time by 40% compared to the execution on a 4-core CPU. The proposed method involves load flow analysis and sensitivity analysis. In load flow analysis, a multifrontal method for sparse LU factorization is explored on GPU through dynamic frontal task scheduling between CPU and GPU. The varying matrix operations during sensitivity analysis on GPU are highly optimized in this study. The results of performance evaluations show that the proposed GPU-based SSSA with optimized matrix operations can achieve a significant reduction in computation time.

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Male Partners Involvement in Prevention of Mother-to-Child Transmission of HIV Services in Southern Central Ethiopia: In Case of Lemo District, Hadiya Zone

Male partners’ involvement is a vital issue to prevent human immunodeficiency virus (HIV) transmission from mother to child; because it is much expectable that women were more vulnerable and high risk group of population portion. Therefore, to save lives of mothers and their newborn from acquiring HIV, male partners should do their maximum endeavor regardless of any determinant factors as our results revealed its status in our study context and elsewhere at past time too.

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Detecting Difference between Process Models Based on the Refined Process Structure Tree

The development of mobile workflow management systems (mWfMS) leads to large number of business process models. In the meantime, the location restriction embedded in mWfMS may result in different process models for a single business process. In order to help users quickly locate the difference and rebuild the process model, detecting the difference between different process models is needed. Existing detection methods either provide a dissimilarity value to represent the difference or use predefined difference template to generate the result, which cannot reflect the entire composition of the difference. Hence, in this paper, we present a new approach to solve this problem. Firstly, we parse the process models to their corresponding refined process structure trees (PSTs), that is, decomposing a process model into a hierarchy of subprocess models. Then we design a method to convert the PST to its corresponding task based process structure tree (TPST). As a consequence, the problem of detecting difference between two process models is transformed to detect difference between their corresponding TPSTs. Finally, we obtain the difference between two TPSTs based on the divide and conquer strategy, where the difference is described by an edit script and we make the cost of the edit script close to minimum. The extensive experimental evaluation shows that our method can meet the real requirements in terms of precision and efficiency.

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Computer Simulation of Three Particles Sedimentation in a Narrow Channel

The settling of three particles in a narrow channel is simulated via the lattice Boltzmann direct-forcing/fictitious domain (LB-DF/FD) method for the Reynolds number ranging from 5 to 200. The effects of the wall and the Reynolds number are studied. It is interesting to find that at certain Reynolds numbers the left (right) particle is settling at 0.175 (0.825) of the channel width irrespective of its initial position or the channel width. Moreover, numerical results have shown that the lateral particles lead at small Reynolds numbers, while the central particle leads at large Reynolds numbers due to the combined effects of particle-particle and particle-wall interactions. The central particle will leave the lateral ones behind when the Reynolds number is large enough. Finally the effect of the Reynolds number on the trajectory of the lateral particles is presented.

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Recent Advances in Biofilmology and Antibiofilm Measures



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Expression of Somatostatin Receptor 2 in Somatotropinoma Correlated with the Short-Term Efficacy of Somatostatin Analogues

The expression of somatostatin receptor subtypes (SSTRs) in pituitary growth hormone- (GH-) secreting adenomas may predict the response to somatostatin analogues (SSA). Our aim was to evaluate the value of the immunohistochemical (IHC) scores of 2 subtypes, SSTR2 and SSTR5, in predicting the short-term efficacy of SSA therapy in patients with active acromegaly. Ninety-three newly diagnosed acromegalic patients were included in our study. These patients were categorized into either a SSA-pretreated group (SA, ) or a direct-surgery group (DS, ), depending on whether or not presurgical SSA treatment was received. IHC analysis, using a 12-grade scoring system, with rabbit monoclonal antibodies against SSTR2 and SSTR5, was performed on all adenoma tissues. The reduction of GH, IGF-1, and tumor size after treatment with SSA for 3 months was measured. Compared with that in the DS group, SSTR2 expression was lower in the SA group. Additionally, in the SA group, SSTR2 expression was positively correlated with the reduction of IGF-1 and tumor volume. However, there was no correlation between the SSTR5 score and the efficacy of SSA. In conclusion, the protein expression of SSTR2, but not of SSTR5, is a valuable indicator in predicting biochemical and tumor size response to short-term SSA treatment in acromegalic patients.

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A Novel Text Clustering Approach Using Deep-Learning Vocabulary Network

Text clustering is an effective approach to collect and organize text documents into meaningful groups for mining valuable information on the Internet. However, there exist some issues to tackle such as feature extraction and data dimension reduction. To overcome these problems, we present a novel approach named deep-learning vocabulary network. The vocabulary network is constructed based on related-word set, which contains the “cooccurrence” relations of words or terms. We replace term frequency in feature vectors with the “importance” of words in terms of vocabulary network and PageRank, which can generate more precise feature vectors to represent the meaning of text clustering. Furthermore, sparse-group deep belief network is proposed to reduce the dimensionality of feature vectors, and we introduce coverage rate for similarity measure in Single-Pass clustering. To verify the effectiveness of our work, we compare the approach to the representative algorithms, and experimental results show that feature vectors in terms of deep-learning vocabulary network have better clustering performance.

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Strength Assessment of Broken Rock Postgrouting Reinforcement Based on Initial Broken Rock Quality and Grouting Quality

To estimate postgrouting rock mass strength growth is important for engineering design. In this paper, using self-developed indoor pressure-grouting devices, 19 groups of test cubic blocks were made of the different water cement ratio grouting into the broken rock of three kinds of particle sizes. The shear strength parameters of each group under different conditions were tested. Then this paper presents a quantitative calculation method for predicting the strength growth of grouted broken rock. Relational equations were developed to investigate the relationship between the growth rates of uniaxial compressive strength (UCS), absolute value of uniaxial tensile strength (AUTS), internal friction angle, and cohesion for post- to pregrouting broken rock based on Mohr-Coulomb strength criterion. From previous test data, the empirical equation between the growth rate of UCS and the ratio of the initial rock mass UCS to the grout concretion UCS has been determined. The equations of the growth rates of the internal friction coefficient and UCS for grouting broken rock with rock mass rating (RMR) and its increment have been established. The calculated results are consistent with the experimental results. These observations are important for engineered design of grouting reinforcement for broken rock mass.

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Geraghty Type Generalized -Contractions and Related Applications in Partial -Metric Spaces

The purpose of this paper is to introduce new concepts of -admissible Geraghty type generalized -contraction and to prove that some fixed point results for such mappings are in the perspective of partial -metric space. As an application, we inaugurate new fixed point results for Geraghty type generalized graphic -contraction defined on partial metric space endowed with a directed graph. On the other hand, one more application to the existence and uniqueness of a solution for the first-order periodic boundary value problem is also provided. Our findings encompass various generalizations of the Banach contraction principle on metric space, partial metric space, and partial -metric space. Moreover, some examples are presented to illustrate the usability of the new theory.

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Comparative Analysis of Optical Signals Emitted by Corona on a Laboratory Model of Transmission Lines Made of Various Materials

The paper presents results of comparative analyses of optical signals generated by corona discharges occurring in the vicinity and on the surface of power transmission lines made of five different materials under laboratory conditions. Three aluminium-based materials were chosen: pure aluminium, aluminium with added magnesium, and aluminium with added silicon, and for comparison purposes also, steel-based lines were considered: copper-coated steel and steel with added chromium and nickel. A three-phase triangular arrangement system operating under maximal voltage equal to 110 kV was applied for experimental tests. The optical radiation was registered using a spectrophotometer. During research works, also the influence of corona generation voltage and distance between power lines was investigated. Based on the achieved results, it was stated that the highest corona intensity was found for aluminium-based lines, for both pure aluminium and aluminium with added magnesium and silicon. The lowest corona intensity was observed for chromium- and nickel-alloyed (stainless) steel.

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Incidental Paratracheal Air Cysts on Thoracic CT and Their Association with Chronic Inflammatory Lung Disease

Purpose. To determine the association between the progression of upper lung fibrosis and paratracheal air cysts (PACs) size. Materials and Methods. The thoracic CT images of 4573 patients were reviewed for the prevalence, size, and location of PACs and their communication with trachea. In addition, the presence of upper lung fibrosis, emphysema, and bronchiectasis was evaluated in patients with PACs and compared with a control group without PACs. Upper lung fibrosis was analyzed using a fibrosis score system. Results. The prevalence of PACs was 6.8%. Communication with tracheal lumen was demonstrated by 31.5% of patients with PACs. The prevalence of fibrosis, emphysema, and bronchiectasis in patients with PACs were 67.5%, 21.9%, and 28.3%, respectively. The prevalence of fibrosis was significantly different in the two groups by univariable and multivariable analysis (odds ratio = 2.077, ). 140 patients with fibrosis among PAC group underwent a previous or follow-up CT; the prevalence with increase in PAC sizes was higher in patients with increase in fibrosis score than those without it (66.2% versus 17.3%, ). Conclusions. PACs appear to be highly related to upper lung fibrosis and moderately related to bronchiectasis. In patients with fibrosis, PAC sizes tended to increase with the progression of upper lung fibrosis.

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Synthesis, Characterization, and Evaluation of Antimicrobial Activities of Chitosan and Carboxymethyl Chitosan Schiff-Base/Silver Nanoparticles

Schiff-bases of chitosan (CS) and carboxymethyl chitosan (CMCS)/silver nanoparticles (AgNPs) have been synthesized, characterized, and evaluated as antimicrobial agents against two Gram +ve bacteria (Bacillus cereus and Staphylococcus aureus) and two Gram −ve bacteria (Escherichia coli and Pseudomonas aeruginosa) in addition to Candida albicans as a fungus. The in situ reactions of CS and/or CMCS with some pyrazole aldehyde derivatives in acidic media containing silver nitrate to yield silver nanoparticles loaded onto CS and CMCS/Schiff-bases were carried out. Characterizations of the prepared compounds via FTIR spectroscopy, SEM, TEM, and TGA were carried out. Schiff-bases/silver nanoparticles of CS and CMCS showed higher antimicrobial activity than the blank CS and CMCS. The presence of AgNO3 (3% wt%) displayed high antibacterial efficiencies with inhibition zones in the extent of 19–39 mm. TEM analysis showed that the size of the silver nanoparticles is in the range of 4–28 nm for the prepared nanocomposites.

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Cinnamon Polyphenol Extract Inhibits Hyperlipidemia and Inflammation by Modulation of Transcription Factors in High-Fat Diet-Fed Rats

We evaluated the effects of cinnamon polyphenol extract on hepatic transcription factors expressions including SREBP-1c and LXR-α in rats fed high fat diet (HFD). Twenty-eight Wistar rats were allocated into four groups: (i) normal control: animals fed with normal chow; (ii) cinnamon: animals supplemented with cinnamon polyphenol; (iii) HFD: animals fed a high-fat diet; and (iv) HFD + cinnamon: animals fed a high-fat diet and treated with cinnamon polyphenol. Obesity was linked to hyperglycemia, hyperlipidemia, and oxidative stress as imitated by elevated serum glucose, lipid profile, and serum and liver malondialdehyde (MDA) concentrations. Cinnamon polyphenol decreased body weight, visceral fat, liver weight and serum glucose and insulin concentrations, liver antioxidant enzymes, and lipid profile () and reduced serum and liver MDA concentration compared to HFD rats (). Cinnamon polyphenol also suppressed the hepatic SREBP-1c, LXR-α, ACLY, FAS, and NF-κB p65 expressions and enhanced the PPAR-α, IRS-1, Nrf2, and HO-1 expressions in the HFD rat livers (). In conclusion, cinnamon polyphenol reduces the hyperlipidemia, inflammation, and oxidative stress through activating transcription factors and antioxidative defense signaling pathway in HFD rat liver.

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Modeling month-season of birth as a risk factor in mouse models of chronic disease: from multiple sclerosis to autoimmune encephalomyelitis [Research]

Month-season of birth (M-SOB) is a risk factor in multiple chronic diseases, including multiple sclerosis (MS), where the lowest and greatest risk of developing MS coincide with the lowest and highest birth rates, respectively. To determine whether M-SOB effects in such chronic diseases as MS can be experimentally modeled, we examined the effect of M-SOB on susceptibility of C57BL/6J mice to experimental autoimmune encephalomyelitis (EAE). As in MS, mice that were born during the M-SOB with the lowest birth rate were less susceptible to EAE than mice born during the M-SOB with the highest birth rate. We also show that the M-SOB effect on EAE susceptibility is associated with differential production of multiple cytokines/chemokines by neuroantigen-specific T cells that are known to play a role in EAE pathogenesis. Taken together, these results support the existence of an M-SOB effect that may reflect seasonally dependent developmental differences in adaptive immune responses to self-antigens independent of external stimuli, including exposure to sunlight and vitamin D. Moreover, our documentation of an M-SOB effect on EAE susceptibility in mice allows for modeling and detailed analysis of mechanisms that underlie the M-SOB effect in not only MS but in numerous other diseases in which M-SOB impacts susceptibility.—Reynolds, J. D., Case, L. K., Krementsov, D. N., Raza, A., Bartiss, R., Teuscher, C. Modeling month-season of birth as a risk factor in mouse models of chronic disease: from multiple sclerosis to autoimmune encephalomyelitis.



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A multi-center phase II study and biomarker analysis of combined cetuximab and modified FOLFIRI as second-line treatment in patients with metastatic gastric cancer

To evaluate the efficacy of cetuximab combined with modified FOLFIRI (mFOLFIRI) as a second-line treatment in metastatic gastric cancer patients and to identify potential biomarkers of clinical outcomes.

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Endothelial Dll4 overexpression reduces vascular response and inhibits tumor growth and metastasization in vivo

The inhibition of Delta-like 4 (Dll4)/Notch signaling has been shown to result in excessive, nonfunctional vessel proliferation and significant tumor growth suppression. However, safety concerns emerged with t...

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Functional analysis of fatty acid binding protein 7 and its effect on fatty acid of renal cell carcinoma cell lines

Renal cell carcinomas (RCCs) overexpress fatty acid binding protein 7 (FABP7). We chose to study the TUHR14TKB cell line, because it expresses higher levels of FABP7 than other cell lines derived from renal ca...

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Establishment of patient-derived gastric cancer xenografts: a useful tool for preclinical evaluation of targeted therapies involving alterations in HER-2, MET and FGFR2 signaling pathways

Targeted therapies are emerging treatment options for gastric cancer (GC). Patient-derived tumor xenograft(PDX) models of GC closely retain the features of the original clinical cancer, offering a powerful too...

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Adipose tissue fibrosis in human cancer cachexia: the role of TGFβ pathway

Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectu...

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Neuroretinitis with vitiligo: A rare case report

Anubhav Chauhan, Lalit Gupta

CHRISMED Journal of Health and Research 2017 4(2):147-149

Optic neuritis (ON) is an acute inflammatory disorder of the optic nerve and is characterized by a unilateral sudden visual loss in the affected eye, often accompanied by periocular pain. We report a classical case of neuroretinitis (a subtype of ON) with vitiligo in a 52-year-old female. Vitiligo is associated with a few ocular disorders, and neuroretinitis is not one of them. Autoimmune etiologies are associated with both the diseases. To the best of our knowledge and after extensive literature search, this is probably the first reported case of neuroretinitis with vitiligo.

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A descriptive analysis of psychological traits among the health-care providers

Farah Ahmed, Tahseer Khan, Wajiha Rashid, Soubia Akhtar, Zaeem Ur Rehman Khan, Bilal Ahmed

CHRISMED Journal of Health and Research 2017 4(2):76-80

Objective: The objective of this study is to access various personality traits of doctors of hospital subspecialties. Introduction: One of the most common perceptions in our society is that of medicine being a very stressful profession. The demands of practicing medicine can have significant effects on general health, work satisfaction, professional, and nonprofessional life. To increase the profitability, organizations curtail the staff to reduce the costs. Hence, it can be argued that doctors are subjected to extreme amounts psychiatric duress. Methodology: A descriptive study was conducted in a tertiary care hospital. In which one hundred and twenty-one doctors were approached randomly varying from different specialties. The short form of the psychopathic personality inventory (PPI-SF) was used as a questionnaire. Results: One hundred and one (81 females and 20 males) doctors from various specialties responded and completed the PPI-SF questionnaire. The subspecialty analysis of the doctors' responses was subdivided into pediatrics, gynecology, medical specialties, surgery, anesthetics, and radiology. Surgeons and GyneObs were the highest scorers on the PPI-SF, with scores of 138 and 149, respectively. Conclusion: This study showed that doctors score higher on a scale of psychopathic personality than the general population. This study also showed that stress immunity is the overriding personality trait in doctors which may, in turn, facilitate better overall patient care. Stress immunity may better facilitate empathy in certain acute situations, which plays a vital role in being a proficient doctor and providing satisfactory patient care and counseling.

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Implant-supported rehabilitation of unicystic ameloblastoma: A 2 years follow-upclinical report

Nitasha Gandhi, Sumir Gandhi, Nirmal Kurian

CHRISMED Journal of Health and Research 2017 4(2):132-135

Ameloblastoma is a rare, benign, epithelial odontogenic tumor that tends to grow slowly in the mandible or maxilla but is locally invasive and can be highly destructive of the surrounding dental anatomy. Osseous resection with clear margins is the recommended treatment modality taking into consideration of 50% rate of recurrence within 5 postoperative years. Loss of the continuity of the mandible destroys the balance and the symmetry of mandibular function, leading to altered mandibular movements and deviation of the residual fragment toward the surgical side. The use of osseointegrated dental implants for rehabilitation is advisable, as it allows the recovery of the masticatory function. This clinical report reveals 2 years follow-up of rehabilitation of a 19-year-old patient who underwent surgical enucleation for the treatment of unicystic ameloblastoma followed by dental implant placement.

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Serum lipids in chronic viral hepatitis B patients in Makurdi, Nigeria

Ayu Agbecha, Chinyere Adanna Usoro, Maisie Henrietta Etukudo

CHRISMED Journal of Health and Research 2017 4(2):81-86

Background: One of the major causes of liver disease in the world is hepatitis B virus (HBV) infection. The liver as a homeostatic organ plays a pivotal role in maintaining the relative balance of lipid and lipoprotein metabolism in the body. Aim: The study aimed at determining the impact of chronic hepatitis B (CHB) disease on serum lipids and the effect of the stages of this disease on lipid pattern in infected patients. Methodology: The study involved the selection of 70 CHB patients attending clinic at a Tertiary Hospital in Makurdi, Nigeria. After fulfilling the inclusion criteria, 65 anthropometrically matched apparently healthy individuals were selected as control to the CHB group. CHB is defined in the study as persistent infection evidenced by seropositivity for hepatitis B surface antigen without remission for up to 1-year. Results: There was a significantly reduced (P = 0.001) high-density lipoprotein cholesterol (HDL-C) and raised (P = 0.044) low-density lipoprotein cholesterol (LDL-C) in chronic HBV compared to seronegative controls. There was a significantly lowered HDL-C (P = 0.017), very LDL-C (P = 0.005), and triglyceride (P = 0.034) in asymptomatic CHB compared to the matched controls. There was a significantly lowered total cholesterol (P = 0.019) and HDL-C (P = 0.017) in symptomatic CHB compared to the matched controls. Conclusion: Lowered serum lipids are associated with CHB disease and likely to be mediated altered liver metabolism. However, reasons for the low levels of lipids in this viral disease still remains unclear.

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Insight into nicotine addiction

Sahil Handa, Haneet Kour, Charu Khurana

CHRISMED Journal of Health and Research 2017 4(2):69-75

The emergence of the epidemic of nicotine addiction in India and other nations is a global public health tragedy of untoward proportions. Smoking or chewing tobacco can seriously affect general, as well as oral health. Smoking-caused disease is a consequence of exposure to toxins in tobacco smoke and addiction to nicotine is the proximate cause of these diseases. This article focuses on nicotine as a determinant of addiction to tobacco and the pharmacologic effects of nicotine that sustain cigarette smoking. The pharmacologic reasons for nicotine use are an enhancement of mood, either directly or through relief of withdrawal symptoms and augmentation of mental or physical functions. Tobacco cessation is necessary to reduce morbidity and mortality related to tobacco use. Strategies for tobacco cessation involves 5A's and 5R's approach and pharmacotherapy. Dental professionals play an important role in helping patients to quit tobacco at the community and national levels, to promote tobacco prevention and control nicotine addiction. Dentists are in a unique position to educate and motivate patients concerning the hazards of tobacco to their oral and systemic health, and to provide intervention programs as a part of routine patient care.

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Compliance and patterns of iron-folic acid intake among adolescent girls and antenatal women in rural Tamil Nadu

Kalaiselvi Selvaraj, P Arumugasamy, Sonali Sarkar

CHRISMED Journal of Health and Research 2017 4(2):87-93

Background: Anemia continues to be a major public health problem in India despite its long-recognized negative impact on health, especially of women. In a scenario where there is little increase in Hb levels even with implementation of various iron supplementation program apart from compliance, their dietary pattern also may play a role. Moreover, majority of the current literature assessed compliance to Iron Folic Acid (IFA) supplements in facility based settings. Objectives: This study aims to identify the compliance to Iron Folic Acid intake and dietary pattern which could influence the absorption of iron among anaemic pregnant women and adolescent girls in a rural area of Tamil Nadu. Methods: This community based cross sectional study was carried out in one of the primary health centres (PHC) in Tamil Nadu during the period of Feb-Mar 2013 among pregnant women and adolescent girls. From the eligible pregnant women and adolescent girls, information regarding socio economic characteristics, practices related to personal hygiene, dietary patterns, consumption of Iron Folic Acid tablets, and reason for non compliance were collected using structured questionnaires during house-to-house visit. Following this, Haemoglobin was estimated among all study participants. Results: Totally 147 (99.3%), 99 (56.6%) pregnant women, adolescent girls were found to be anemic respectively. Out of these, Iron folic acid tablets were consumed by 136 (91.9%), 60 (60.6%) of pregnant women and adolescent girls respectively. Around 90% of the anemic participants consumed IFA tablets during the night time, immediately after food in rice based diet. Pregnant women who were in their third trimester (OR 0.27, 95% CI: 0.10 to 0.69) and high socio economic status (OR 0.10, 95% CI: 0.02 to 0.55) had significant poor compliance compared to women in second trimester and low socio economic status respectively. Among the adolescent girls, increasing age and current school going status had facilitated the consumption of more number of IFA tablets. Conclusion: In this backward district, prevalence of anemia among pregnant women and adolescent girls were extremely high. Compliance to IFA tablets among pregnant women is favourable whereas among adolescent girls is extremely poor. Some of the dietary practices followed in this region could impair the iron absorption level and treatment effect.

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Siblings with pierre robin sequence

Medhini Madi, Subhas G Babu, Sonika Achalli, Supriya Bhat, Kumuda Rao, Ananya Madiyal

CHRISMED Journal of Health and Research 2017 4(2):139-143

Pierre Robin anomalad is a syndrome characterized by cleft of the palate, micrognathia of the mandible, and glossoptosis. This syndrome can occur as an individual presentation, or it may be associated with a wide variety of syndromes and anomalies. Such patients are burdened with several problems, some obvious and some less so. The most obvious problems such as the psychological difficulties the patients will have to face due to the appearance and associated problems such as feeding and speech difficulties and serious consequences such as airway obstruction. Here, we report two cases of Pierre Robin sequence seen in the same family in two children of the same parents.

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Prescribing pattern and cost analysis of antihypertensives in India

Hemalatha Vummareddy, Mohanraj Rathinavelu Mudhaliar, Shaik Mohammad Ghouse Ishrar, Balaiah Sandyapakula, Lokesh Vobbineni, Bijoy Thomas

CHRISMED Journal of Health and Research 2017 4(2):94-98

Background: Hypertension has been reported to be the strongest modifiable global risk factor for cardiovascular morbidity, mortality as well as health burdens. Antihypertensive pharmacotherapy effectively reduces hypertension-related morbidity and mortality. Prescribing pattern surveys are one of the drug use evaluation techniques providing an unbiased picture and identification of suboptimal prescribing patterns. Objective: The 6-month cross-sectional study was designed to assess the prescription pattern and cost of antihypertensives therapy in a health-care resource-limited setting of India. Materials and Methods: The hypertensive patients were divided into two groups according to risk assessment using the World Health Organization and International Society of Hypertension guidelines for the management of hypertension. The average drug acquisition and the percentage expenditure costs were calculated for each drug class on a daily and annual basis, and InStat GraphPad Prism was the statistical tool used. Results: In our study of 100 patients, the most commonly prescribed antihypertensives were calcium channel blockers in 49.81% and beta-blockers in 12.73% patients, respectively. The cost analysis on antihypertensive medications utilized showed a total expenditure of Rs. 3823.58 invested in 1 year. Conclusion: The drug use pattern of antihypertensives was evidenced based but imposed economic burden in patients. Hence, rational use of generic medications was recommended.

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Seroprevalence of sexually transmitted diseases (herpes, Chlamydia, and syphilis) in pregnant women in Warri, Nigeria

Favour Osazuwa, Otutu-Moses Ifueko

CHRISMED Journal of Health and Research 2017 4(2):155-156



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A descriptive study to assess the knowledge and practice regarding menstrual hygiene among adolescent girls of Government School of Shimla, Himachal Pradesh

Anjali Mahajan, Kanica Kaushal

CHRISMED Journal of Health and Research 2017 4(2):99-103

Introduction: Adolescent girls belong to vital age group, not only because they are the entrant population to motherhood but also because they are threshold between childhood and motherhood. The girls should be educated about significance of menstruation and development of secondary sexual characteristics, selection of sanitary menstrual absorbent and its proper disposal. Aims and Objectives: The objectives of the present study were to assess the existing knowledge and practice regarding menstrual hygiene among adolescent girls and to determine the co-relation of knowledge and practice score among the adolescent girls. Materials and Methods: The study conducted was a descriptive cross sectional study done on 100 adolescent girls from class 9th to 12th of Govt. Girls School in Shimla, Himachal Pradesh (Convenience sampling). Prior to the commencement of the study, they were explained the purpose and nature of the study. Information on demographic variables which include age, class, type of family, education of mother, family income, age of menarche were collected from the participants. Results: The data on knowledge scores revealed that 29% had adequate knowledge about menstrual hygiene, 71% had inadequate knowledge about menstrual hygiene. The data revealed on practice scores revealed that 19%, 69%, 12% samples had poor, fair and good score of practices regarding menstrual hygiene respectively. Knowledge and practice scores of participants shows positive correlation between the two scores (*P < 0.001). Conclusion: Lack of information about menstrual hygiene can be attributed to various factors which need to be studied separately. The above findings reinforce the need to encourage safe and hygienic practices among the adolescent girls and bring them out of traditional beliefs, misconceptions and restrictions regarding menstruation. The investigators improved the general awareness about cause of menstruation and the organs involved. Use of sanitary napkins was promoted and various schemes regarding menstrual health were briefed to the students. Early awareness can prevent students from suffering from the various reproductive tract infections.

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Implant-retained overdenture as a standard treatment modality for severely resorbed mandibular ridges

Angleena Y Daniel, Supneet Singh Wadhwa, B Vinod

CHRISMED Journal of Health and Research 2017 4(2):128-131

Edentulous patients are a diverse group comprised those who are anatomically deficient, medically compromised, economically depressed, geriatric as well as the general population that, for a number of other reasons have been rendered edentulous. Satisfying a completely edentulous patient is always considered a difficult task. Various treatment options for rehabilitation of a completely edentulous patient are available: conventional complete dentures, overdentures, implant-supported overdenture, and full arch fixed implant-supported prosthesis. While the conventional denture may meet the needs of many patients, others require more retention, stability, function, and esthetics, especially in the mandible. With the continued advancements in dental implant therapy, it is becoming increasingly easier for the clinician to provide treatment solutions that can effectively meet functional, economic, and social expectations of each individual patient. This paper presents a case report of prosthetic rehabilitation of a completely edentulous patient with implant-retained overdenture.

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The effects of Moringa Oleifera on lipid profile status, heart histology, and liver histochemistry in adult Wistar rats

Adelaja Abdulazeez Akinlolu, Elizabeth Oluwafunmilayo Bayode, Kamal Olaide Ghazali, Mubarak Oloduowo Ameen

CHRISMED Journal of Health and Research 2017 4(2):104-109

Background: Moringa oleifera's leaves are globally used for nutritional and medicinal purposes. We evaluated lipid profile status, heart and liver histology, and the activities of alanine and aspartate transaminases of the liver in M. oleifera-treated adult Wistar rats. Materials and Methods: Twenty-four adult male Wistar rats were employed in the study. Rats of control Group I received physiological saline while rats of Groups II–IV received 250, 500, and 750 mg/kg bodyweight of methanolic extract of M. oleifera, respectively, for 21 days. Results: No gross morphological or behavioral anomalies were observed in rats of Groups I–IV. Histological examinations showed normal histoarchitecture of the heart in Group I and the liver of Groups I–III. Comparative histological analyses showed dose-dependent increased nucleated cells in heart tissues of rats of Groups II–IV than those of Group I. Furthermore, histological evaluations showed hypertrophy of central vein of the liver in rats of Group IV when compared to Group I. Statistical analyses showed dose-dependent nonsignificant higher mean levels (P > 0.05) of total cholesterol and triglycerides in the sera of rats of Groups II–IV compared to rats of Group I. Evaluations of levels of alanine and aspartate transaminases showed a statistically significant higher mean values (P < 0.05) in Group II, but statistically nonsignificant higher mean values (P > 0.05) in Groups III–IV compared to Group I. Conclusions: No significant adverse effects on lipid profile status, heart histology, and liver histochemistry were observed in M. oleifera-treated rats.

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Ovarian filariasis presenting as tubo-ovarian mass: Report of a rare case

Santosh Kumar Mondal, Anindya Adhikari, Rohini Nandan Chakraborty, Saikat Mandal

CHRISMED Journal of Health and Research 2017 4(2):136-138

Filariasis of ovary is rare. Exact incidence is not known. Herein, we report a case of filarial worm affecting right ovary in a 35-year-old female patient who presented with chronic pelvic pain. Ultrasonography of lower abdomen revealed a tubo-ovarian mass on the right side. Right-sided salpingo-oophorectomy was done. Grossly, ovary was slightly enlarged in size (5 cm × 2.5 cm × 2 cm). Cut surface showed several tiny cysts at the periphery. The lumen of the fallopian tube was blocked. Histopathological examination of the ovary showed lymphangiectasia with microfilaria in one of the dilated lymphatics. Few cystic follicles were also seen in the sections. Section from the tube showed features of chronic salpingitis. She was given a course of diethylcarbamazine citrate (DEC) for 3 weeks postoperatively. On follow-up, the patient was doing well without any complication.

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Assessment of quality of life in children with epilepsy in rural settings of South India: A cross sectional study

Mullazy Paramadam Srujana, Easwaran Vigneshwaran, Gandesiri Sangeeth Kumar, Kolisetty Jyoshna, Mantargi Md Jaffar Sadiq

CHRISMED Journal of Health and Research 2017 4(2):110-116

Background: Epilepsy is the most common pediatric neurological disorder which alters the conscious, behavior, motor activity, and autonomy function leads to compromised quality of life (QoL) in children. Objective: The aim is to assess the QoL, and to evaluate the influence of demographic and clinical factors on QoL in children with epilepsy. Materials and Methods: This is a cross-sectional study conducted over 1 year from October 2013 to September 2014. Baseline demographic characteristics and other details were collected from patient case data and through a semi-structured interview during their recruitment into the present investigation. The child version of TNO-AZL Children's QoL questionnaire was administered by the trained research coordinator to collect data from and about the study subjects. Statistical Analysis: ANOVA and student t-test were performed for the statistical analysis. The data analysis was performed using Graph pad instat 3.0.10.0. Results: The educational status, socioeconomic status, and maternal education were the demographic characters that significantly affected the QoL of study subjects. Type of seizures, early childhood history of seizures, duration of therapy and duration of epilepsy were the most important clinical characteristics that could significantly affect the QoL of study subjects. Conclusion: Further QoL studies and interventional programs may be conducted to improve the QoL and to individualize management in rural resident children with epilepsy.

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Thyroid hormone resistance misdiagnosed as Graves' disease

Manish Gutch, Annesh Bhattacharya, Sukriti Kumar, Syed Mohd Razi, Rao Somendra Singh, Rajendra Kumar Pahan

CHRISMED Journal of Health and Research 2017 4(2):144-146

Resistance to thyroid hormone (RTH) syndrome is a very rare disorder characterized by mutations of the thyroid hormone receptor beta and is usually inherited as an autosomal dominant trait. Patients with RTH are usually euthyroid but rarely may present with signs and symptoms consistent with hyperthyroidism. Here, we describe the case of a young girl with goiter who was previously misdiagnosed to have hyperthyroidism and was subsequently diagnosed to be suffering from RTH.

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Knowledge, attitude, and behavioral practices pertaining to human immunodeficiency virus/acquired immune deficiency syndrome among secondary school adolescents in makurdi, Nigeria

Ayu Agbecha, James Saa-Aondo Gberindyer

CHRISMED Journal of Health and Research 2017 4(2):117-124

Background: Adolescents knowledge with their safe practices pertaining to human immunodeficiency virus (HIV) has a critical impact on the prevention of contracting and spreading HIV. Reports have shown that adolescents in the general setting engage in activities that enhance the spread of the virus. Aim: The study assessed school adolescent's HIV/acquired immune deficiency syndrome (AIDS) knowledge, with its impact on their behaviors and attitudes regarding the infection. Materials and Methods: Two hundred randomly selected adolescent students from 10 different schools in the city metropolis were involved in the cross-sectional study. Primary data were collected using a validated self-administered questionnaire on students HIV/AIDS knowledge, attitude toward people living with HIV/AIDS (PLWHA), and safe practices preventing the spread of HIV/AIDS. Results: The study observed that majority of the students had good knowledge about HIV/AIDS, had good attitude toward PLWHA, and engaged in safe practices that prevent the spread of HIV. The sources of HIV/AIDS information were hospital, school, home, electronic, and print media. The study also found that HIV/AIDS knowledge instilled good attitudes and behavioral practices in the students. Conclusion: The study shows that school sex education, as well as health promotion campaigns through media platforms, could impact positively on the knowledge, attitude, and behavioral practices of adolescents in curbing the spread of HIV/AIDS.

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Goldenhar syndrome: A case report and review

Sonika Achalli, Subhas G Babu, Murali Patla, Medhini Madi, Shishir Ram Shetty

CHRISMED Journal of Health and Research 2017 4(2):150-154

Goldenhar syndrome (GS) is also known as hemifacial microsomia or oculo-auriculo-vertebral dysplasia. This condition mainly affects the oral cavity, eyes, ear, and vertebrae. This is a rare congenital anomaly. Here, we present a case of GS with a brief review on its etiology, clinical and radiographic features, differential diagnosis, and management.

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Neuroradiological and histopathological findings of intraventricular central neurocytoma

Reddy Ravikanth

CHRISMED Journal of Health and Research 2017 4(2):125-127

Central neurocytomas are rare neuroectodermal tumors believed to arise from the subependymal matrix of the lateral ventricles. Intraventricular central neurocytoma is a benign primary central nervous system tumor of neuronal origin that is usually located within the lateral and third ventricles. Central neurocytoma should be considered in the differential diagnosis of lesions involving bilateral lateral ventricles with symmetrical growth around the center of septum pellucidum in young patients. Here, we report the radiological and histopathological findings in a rare case of intraventricular central neurocytoma.

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Swachh bharat: A long voyage from rhetoric to implementation

Rohit Sharma, PK Prajapati

CHRISMED Journal of Health and Research 2017 4(2):157-159



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Mobile health technology in the prevention and management of Type 2 diabetes

Shruti Muralidharan, Harish Ranjani, Ranjit Mohan Anjana, Steven Allender, Viswanathan Mohan

Indian Journal of Endocrinology and Metabolism 2017 21(2):334-340

Essential steps in diabetes prevention and management include translating research into the real world, improving access to health care, empowering the community, collaborative efforts involving physicians, diabetes educators, nurses, and public health scientists, and access to diabetes prevention and management efforts. Mobile phone technology has shown wide acceptance across various ages and socioeconomic groups and offers several opportunities in health care including self-management as well as prevention of Type 2 diabetes mellitus (T2DM). The future seems to lie in mobile health (mHealth) applications that can use embedded technology to showcase advanced uses of a smartphone to help with prevention and management of chronic disorders such as T2DM. This article presents a narrative review of the mHealth technologies used for the prevention and management of T2DM. Majority (48%) of the studies used short message service (SMS) technology as their intervention while some studies (29%) incorporated applications for medication reminders and insulin optimization for T2DM management. Few studies (23%) showed that, along with mHealth technology, health-care professionals' support resulted in added positive outcomes for the patients. This review highlights the fact that an mHealth intervention need not be restricted to SMS alone.

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Occurrence of diabetes mellitus in obese nondiabetic patients, with correlative analysis of visceral fat, fasting insulin, and insulin resistance: A 3-year follow-up study (mysore visceral adiposity in diabetes follow-up study)

M Premanath, H Basavanagowdappa, M Mahesh, M Suresh Babu

Indian Journal of Endocrinology and Metabolism 2017 21(2):308-315

Objective: To assess the occurrence of diabetes in obese nondiabetic patients over a 3-year follow-up period with a correlative analysis of visceral fat (VF), fasting insulin levels, (FILs) and insulin resistance (IR). Material and Methods: Thirty-seven obese and nineteen nonobese nondiabetics of our previous study, Mysore Visceral Adiposity in Diabetes were followed for the next 3 years. Their blood pressure, body mass index, waist circumference (WC), fasting blood sugar (FBS), FIL, lipid profile and subcutaneous fat (SCF), and VF measurement by US method were repeated every 6 months for the next 3 years. The findings were analyzed with appropriate statistical methods. Results: Twenty-three obese and 18 nonobese nondiabetics completed the study. There were 17 dropouts. The changes in the physical and biochemical characteristics of the two groups before and after the study were not significant. SCF had no correlation with IR whereas VF correlated with FIL and IR. There were three diabetics in the obese group and two from the control group at the end of the study. There were 12 impaired glucose tolerance (IGT) in the test group and 2 in the control group. Those who developed diabetes had higher VF, WC, FBS, FIL, and IR. Those who showed IGT also had these at higher levels compared to others. There was no change in the VF at the end of the study. Conclusions: This follow-up study on South Indians has shown that VF is a significant risk factor for the development of IR. IR can develop without any increase in the volume of the VF, is the essential finding of this study. SCF has not shown any significant relationship with IR. We recommend FBS and FIL in all the obese nondiabetics to calculate IR, which has given much insight in the development of IGT and diabetes. Large multicentric, longitudinal studies are required to establish the cause of IR.

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Transgenerational karma

Bharti Kalra, Sanjay Kalra, AG Unnikrishnan, Manash P Baruah, Deepak Khandelwal, Yashdeep Gupta

Indian Journal of Endocrinology and Metabolism 2017 21(2):265-267



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Cytochrome P450 oxidoreductase deficiency: Novel cause of ambiguity with primary amenorrhea

Kranti Shreesh Khadilkar, Varsha Jagtap, Anurag Lila, Tushar Bandgar, Nalini S Shah

Indian Journal of Endocrinology and Metabolism 2017 21(2):360-362



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Interaction, information, involvement (the 3I strategy): Rebuilding trust in the medical profession

Sanjay Kalra, AG Unnikrishnan, Manash P Baruah

Indian Journal of Endocrinology and Metabolism 2017 21(2):268-270



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Patient and health-care professional satisfaction with a new, simple, high accuracy blood glucose meter with color range indicator

Laurence B Katz, Mike Grady, Lorna Stewart, Hilary Cameron, Pamela A Anderson, Anish Desai

Indian Journal of Endocrinology and Metabolism 2017 21(2):322-328

Background: Accurate self-monitoring of blood glucose (BG) is a key component of effective self-management of glycemic control. Methods: The OneTouch Select Plus Simple™ (OTSPS) BG monitoring system (BGMS) was evaluated for accuracy in a clinical setting. Results: OTSPS was accurate over a wide glucose range and met lay user and system accuracy BG standards described in ISO 15197:2013. Patients also used OTSPS for a 1-week trial period and reported their level of satisfaction with meter features. In a separate study, health-care professionals (HCPs) in India naïve to OTSPS experienced OTSPS online using a variety of interactive demonstrations of the BGMS and answered questions about its potential utility to their patients. Summary: Patients and HCPs felt the features of OTSPS, including a color range indicator, could provide significant benefits to them and their patients.

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Perceptions about training during endocrinology residency programs in India over the years: A cross-sectional study (PEER India Study)

Deepak Khandelwal, Deep Dutta, Rajiv Singla, Vineet Surana, Sameer Aggarwal, Yashdeep Gupta, Sanjay Kalra, Rajesh Khadgawat, Nikhil Tandon

Indian Journal of Endocrinology and Metabolism 2017 21(2):271-276

Background: Residents' perception on quality of endocrinology training in India is not known. This study aimed to evaluate the perceptions about endocrinology residency programs in India among current trainees as compared to practicing endocrinologists. Methods: Trainees attending a preconference workshop at the annual conference of Endocrine Society of India (ESI) were given a questionnaire designed to evaluate their perceptions on their training. These evaluated the reasons for choosing endocrinology, their experiences during residency, and career plans. Practicing endocrinologists attending ESICON with at least 5-year experience were evaluated as controls. Results: Questionnaires from 63 endocrine trainees and 78 practicing endocrinologists were analyzed. Endocrinology is perceived to be the super-specialty with the best quality of life (QOL) but fair with regard to financial remuneration. Among current trainees, 61.89%, 31.74%, and 34.91% are satisfied with training in clinical endocrinology, laboratory endocrinology, and clinical/translational research, respectively. The corresponding figures for practicing endocrinologists are 71.78%, 25.63%, and 30.75%, respectively. Exposure to national endocrinology conferences during their endocrinology residency was adequate. However, exposure to international endocrinology conferences, research publications, project writing, and grant application are limited. Laboratory endocrinology is rated as the most neglected aspect during endocrine residency. Most of the trainees want to establish their own clinical practice in the long run. Very few trainees (17.46%) wish to join the medical education services. Conclusion: There is a good perception of QOL in endocrinology in spite of average financial remuneration. There is dissatisfaction with the quality of training in laboratory endocrinology and clinical research. Very few endocrine trainees consider academics as a long-term career option in India.

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Levosulpiride and serum prolactin levels

Mohammad Shafi Kuchay, Ambrish Mithal

Indian Journal of Endocrinology and Metabolism 2017 21(2):355-358

Levosulpiride is the levorotatory enantiomer of sulpiride used in dyspeptic syndromes of various etiologies. The prokinetic effect of levosulpiride is mediated through the blockade of enteric inhibitory dopaminergic type 2 (D2) receptors. The antagonism of central D2 receptors leads to both therapeutic (e.g. antiemetic effect due to D2 receptor blockade in the chemoreceptor trigger zone) and adverse (including hyperprolactinemia) effects. Dopamine is the main endogenous inhibitor of prolactin synthesis and secretion in the anterior pituitary. Levosulpiride causes significant elevation of serum prolactin levels in significant number of patients. The resultant hyperprolactinemia often manifests as distressing menstrual abnormalities and galactorrhoea in females. A significant number of patients who use levosulpiride develop serum prolactin levels of > 200 ng/mL that goes against the classical textbook teaching where pituitary tumor is supposed to be the mostly likely cause. Careful drug history in patients presenting with high serum prolactin levels will be of great help in reaching the exact diagnosis and avoiding unnecessary brain imaging.

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Improving bethesda reporting in thyroid cytology: A team effort goes a long way and still miles to go…

Subramanian Kannan, Nalini Raju, Vikram Kekatpure, Naveen Hedne Chandrasekhar, Vijay Pillai, A Renuka Keshavamurthy, Moni Abraham Kuriakose, Pobbisetty Radhakrishnagupta Rekha, Nisheena Raghavan, Akhila Lakhsmikantha, Srinivas Ramaiah, Brijal Dave

Indian Journal of Endocrinology and Metabolism 2017 21(2):277-281

Context: Fine-needle aspiration cytology is the first step in evaluation of thyroid nodules. Although the Bethesda classification for reporting thyroid cytology has been purported that this uniformity in reporting cytology thereby facilitating clinical decision-making, there are also studies indicating that the reporting percentage and the rates of malignancy in each category vary considerably from center to center making the clinical decision more difficult. Aim and Materials and Methods: We looked at our retrospective cytology and histopathology data of thyroid nodules operated between 2012 and 2014 and then prospectively collected data during 2015–2016. In the prospective arm, for every thyroid nodule that was sampled, there was a discussion between the endocrinologist and the cytopathologist on the risk of thyroid cancer (based on the patient's history, examination findings, sonographic pattern, and the cytological appearance). Results: We noted that there was considerable improvement in reporting standards with the rates of nondiagnostic cytology dropping from 11% to 5%, an increased reporting of Bethesda Category 2 and 6 which are the definitive strata of benign and malignant nodules (38% to 41% in Category 2 and 7% to 11% in Category 6) with a high specificity (100%). There was a decline in numbers of Category 4 and 5 (13% to 9% in Category 4 and 12% to 3% in Category 5). The reporting prevalence of Category 3 increased from 19% to 27%. Conclusions: We conclude that a team approach between the clinician who performs the ultrasound and the reporting cytopathologist improves Bethesda reporting, its predictive value, and thus potentially avoiding unnecessary thyroidectomies in benign thyroid nodules and hemithyroidectomies in thyroid cancers.

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Patient-centered blood pressure: Thresholds, targets, and tools in diabetes

Sanjay Kalra, Kamal Kishor, Yashdeep Gupta

Indian Journal of Endocrinology and Metabolism 2017 21(2):261-264



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Cardiac autonomic neuropathy in patients with Type 2 diabetes mellitus at high risk for foot ulcers

Anil S Menon, Abhinav Dixit, MK Garg, R Girish

Indian Journal of Endocrinology and Metabolism 2017 21(2):282-285

Aim: To study the prevalence of cardiac autonomic neuropathy (CAN) in patients with Type 2 diabetes mellitus at high risk for foot ulcers. Materials and Methods: We screened patients attending diabetic clinic for identifying patients at high risk for foot ulcers. Those with foot risk category 1, 2 and 3 as per criteria of Foot Care Interest Group were subjected to battery of cardiovascular autonomic reflex tests. Those with one abnormal test were termed as probable CAN and those with two abnormal tests as definite CAN. Those with postural fall in blood pressure with one other abnormal test were termed to have advanced CAN. Results: A total of 74 patients were recruited in the study. The prevalence of abnormal cardiovascular autonomic reflex test was sustained hand grip 81%, E/I ratio 66.2%, 30:15 ratio 28.3% and orthostatic hypotension 13.5%. The prevalence of possible CAN was 31.0% (23/74) and definite CAN was 66.2% (49/74). Ten patients had advanced CAN. There was no observable difference in presence of probable or definite CAN in three risk category for foot ulcers. Conclusion: We found a high prevalence of CAN in subgroup of diabetic patients at increased risk for foot ulcer.

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Antiretroviral therapy-induced insulin resistance and oxidative deoxy nucleic acid damage in human immunodeficiency virus-1 patients

Vaishali Kolgiri Honnapurmath, VW Patil

Indian Journal of Endocrinology and Metabolism 2017 21(2):316-321

Background and Objectives: Insulin resistance (IR) is frequent in human immunodeficiency virus (HIV) infection and may be related to antiretroviral therapy (ART). Increased oxidative stress parameters and carbonyl protein are linked to insulin sensitivity. The present study is aimed to determine IR, its association with oxidative deoxy nucleic acid (DNA) damage in HIV-1-infected patients with different ART status. Materials and Methods: In this case–control study, a total 600 subjects were included. We used plasma levels of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG), as our biomarker of oxidative DNA damage. 8-OHdG was measured with the highly sensitive 8-OHdG check enzyme-linked immunosorbent assay kit. IR was determined using homeostasis model assessment. Results: All subjects were randomly selected and grouped as HIV-negative (control group) (n = 300), HIV-positive without ART (n = 100), HIV-positive with ART first line (n = 100), and HIV-positive with ART second line (n = 100). IR and oxidative DNA damage were significantly higher in HIV-positive patients with second-line ART and HIV-positive patients with first-line ART than ART-naive patients. In a linear regression analysis, increased IR was positively associated with the increased DNA damage (odds ratio: 3.052, 95% confidence interval: 2.595–3.509) P < 0.001. Interpretation and Conclusions: In this study, we observed that ART plays a significant role in the development of IR and oxidative DNA damage in HIV-positive patients taking ART. Awareness and knowledge of these biomarkers may prove helpful to clinicians while prescribing ART to HIV/AIDS patients. Larger studies are warranted to determine the exact role of ART in the induction of IR and DNA damage.

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Long-term efficacy and safety of empagliflozin monotherapy in drug-naïve patients with type 2 diabetes in Indian subgroup: Results from a 76-week extension trial of phase iii, double-blind, randomized study

Sunil Gupta, Shehla Shaikh, Pooja Joshi, Shraddha Bhure, Viraj Suvarna

Indian Journal of Endocrinology and Metabolism 2017 21(2):286-292

Background and Objectives: Empagliflozin, a sodium glucose cotransporter-2 inhibitor, was recently evaluated in a randomized, controlled trial (RCT) in drug-naïve Type 2 diabetes mellitus (T2DM) patients managed on diet and exercise therapy. Efficacy and safety of empagliflozin in Indian subgroup of patients from a 76-week extension study of the initial multicentric RCT are reported in this article. Materials and Methods: In this study, patients were randomized to empagliflozin 10 mg (E10, n = 24), empagliflozin 25 mg (E25, n = 29), placebo (n = 28) and sitagliptin 100 mg (S100, n = 27). Exploratory efficacy endpoints were changed from baseline to week 76 in glycosylated hemoglobin (HbA1c, %) and fasting blood glucose (mg/dL) along with body weight (kg) and blood pressure (BP) (mmHg) reduction. Safety analysis included clinically relevant adverse events (AEs). Results: In 108 randomized patients, adjusted mean reduction in HbA1c compared to placebo was significant with E10 (−0.81, 95% confidence interval (CI) −1.33, −0.28; P = 0.0029) and E25 (−1.11, 95% CI − 1.60, −0.61; P < 0.0001). HbA1c below 7% at week 76 was achieved in significantly higher number of patients with E10 (20.8%, P < 0.0001) and E25 (28.0%, P < 0.0001). There was significant reduction in adjusted mean weight as compared to placebo with E10 (−1.41, 95% CI − 2.51, −0.31; P = 0.0125) and E25 (−1.50, 95% CI − 2.54, −0.46; P = 0.0051) but nonsignificant with S100 (−0.75 95% CI − 1.86, −0.36; P = 0.1842). BP reduction was numerically higher with empagliflozin compared to placebo. AEs were similar in all treatment groups except for genital infections which were more common in E10 (20.8%) but not in E25 (3.4%) as compared to placebo (3.6%). All treatments were well tolerated with no severe AEs. Conclusion: Treatment with empagliflozin was well tolerated and resulted in sustained glycemic efficacy over long-term (76 weeks) in drug-naïve Indian T2DM patients.

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Lack of association of B-type raf kinase V600E mutation with high-risk tumor features and adverse outcome in conventional and follicular variants of papillary thyroid carcinoma

C Gopalakrishnan Nair, Misha Babu, Lalitha Biswas, Pradeep Jacob, Riju Menon, AK Revathy, Krishnanunni Nair

Indian Journal of Endocrinology and Metabolism 2017 21(2):329-333

Introduction: Somatic B-type Raf kinase (BRAF) V600E mutation in exon 15 was frequently found in high frequencies associated with papillary thyroid cancer (PTC). The phenotype of these cancers expressed aggressive clinical and pathological features. The present study aimed to assess the prevalence of BRAF V600E mutation among conventional and follicular variants of PTC and its association with aggressive tumor factors and outcome. Study Design: Patients who were operated and received further treatment for PTC during 2012 were included in the study. BRAF V600E mutation analysis was done by extracting genomic DNA from tumor tissue. Results: Of the 59 patients included in the study, 51% harbored BRAF V600E mutation, but the mutation status was not associated with aggressive tumor factors and adverse outcome. Conclusion: BRAF V600E mutation was not significant predictor of aggressive tumor behavior in conventional and follicular variants of PTC.

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Footboards: Indigenous and novel method of screening for diabetes peripheral neuropathy – A pilot study

Akram Hussain Bijli, Altaf Rasool, Adil Hafeez Wani, Mir Yasir, Tanveer Ahmad Bhat, Bashir Ahmad Laway

Indian Journal of Endocrinology and Metabolism 2017 21(2):293-296

Background: To validate the effectiveness of indigenously designed “footboard (FB)” in early diagnosis of diabetic peripheral neuropathy (PNP) by comparing it with Semmes–Weinstein monofilament (SWM) and vibration perception (VP). Materials and Methods: Two hundred and forty-four patients with diabetes were examined for PNP using SWM and 128 Hz tuning fork. The findings were compared with indigenously designed FBs with 1, 2, and 3 mm elevations. Results: Out of 108 patients who did not have protective sensation as per SWM, only 10 (9.2%) felt 1 mm board bearings, and out of 72 patients who did not feel vibration, only 8 (11.1%) felt 1 mm board bearings. Out of 136 patients who had protective sensation, 128 (94.11%) felt 2 mm elevated board bearings, and out of 172 patients who had VP, only 152 patients (88.3%) felt 2 mm board bearings. With SWM as standard, the sensitivities and specificities, respectively, were 63% and 90% (1 mm board), and 94% and 60% (2 mm board). With VP, the sensitivities and specificities, respectively, were 59% and 90% (1 mm board), and 88% and 61% (2 mm board). Conclusions: FB, which simultaneously tests touch and pressure sensation, shows a high level of performance in detecting at-risk feet. FB may be simple, time-efficient, and inexpensive test for detection of neuropathy and needs further validation in a larger study.

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Consensus statement on dose modifications of antidiabetic agents in patients with hepatic impairment

Kalyan Kumar Gangopadhyay, Parminder Singh

Indian Journal of Endocrinology and Metabolism 2017 21(2):341-354

Liver disease is an important cause of mortality in type 2 diabetes mellitus (T2DM). It is estimated that diabetes is the most common cause of liver disease in the United States. Virtually, entire spectrum of liver disease is seen in T2DM including abnormal liver enzymes, nonalcoholic fatty liver disease, cirrhosis, hepatocellular carcinoma, and acute liver failure. The treatment of diabetes mellitus (DM) in cirrhotic patients has particular challenges as follows: (1) about half the patients have malnutrition; (2) patients already have advanced liver disease when clinical DM is diagnosed; (3) most of the oral antidiabetic agents (ADAs) are metabolized in the liver; (4) patients often have episodes of hypoglycemia. The aim of this consensus group convened during the National Insulin Summit 2015, Puducherry, was to focus on the challenges with glycemic management, with particular emphasis to safety of ADAs across stages of liver dysfunction. Published literature, product labels, and major clinical guidelines were reviewed and summarized. The drug classes included are biguanides (metformin), the second- or third-generation sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and currently available insulins. Consensus recommendations have been drafted for glycemic targets and dose modifications of all ADAs. These can aid clinicians in managing patients with diabetes and liver disease.

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Association of fat mass and obesity-associated gene variant with lifestyle factors and body fat in Indian Children

Lavanya S Parthasarthy, Nikhil Phadke, Shashi Chiplonkar, Anuradha Khadilkar, Kavita Khatod, Veena Ekbote, Surabhi Shah, Vaman Khadilkar

Indian Journal of Endocrinology and Metabolism 2017 21(2):297-301

Context: Common intronic variants of the fat mass and obesity-associated (FTO) gene have been associated with obesity-related traits in humans. Aims: (1) The aim of this study is to study the distribution of FTO gene variants across different body mass index (BMI) categories and (2) to explore the association between FTO gene variants and lifestyle factors in obese and normal weight Indian children. Subjects and Methods: Fifty-six children (26 boys, mean age 10.3 ± 2.2 years) were studied. Height, weight, and waist and hip circumference were measured. Physical activity (questionnaire) and food intake (food frequency questionnaire) were assessed. Body fat percentage (%BF) was measured by dual-energy X-ray absorptiometry. FTO allelic variants at rs9939609 site were detected by SYBR Green Amplification Refractory Mutation System real-time polymerase chain reaction using allele-specific primers. Generalized linear model was used to investigate the simultaneous influence of genetic and lifestyle factors on %BF. Results: Mean height, weight, and BMI of normal and obese children were 130.6 ± 7.1 versus 143.2 ± 15.6, 24.0 ± 5.2 versus 53.1 ± 15.8, and 13.9 ± 2.1 versus 25.3 ± 3.2, respectively. The frequency of AA allele was 57% among obese children and 35% in normal weight children. Children with the AA allele who were obese had least physical activity, whereas children with AT allele and obesity had the highest intake of calories when compared to children who had AT allele and were normal. %BF was positively associated with AA alleles and junk food intake and negatively with healthy food intake and moderate physical activity. Conclusions: Healthy lifestyle with high physical activity and diet low in calories and fat may help in modifying the risk imposed by FTO variants in children.

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Tuberculosis and diabetes mellitus, tackling dual maladies: Comment on Bangladeshi tuberculosis-diabetes mellitus guidelines

Jyothi Idiculla

Indian Journal of Endocrinology and Metabolism 2017 21(2):359-359



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The thyroid registry: Clinical and hormonal characteristics of adult indian patients with hypothyroidism

Bipin Sethi, Sumitav Barua, MS Raghavendra, Jagdish Gotur, Deepak Khandelwal, Upal Vyas

Indian Journal of Endocrinology and Metabolism 2017 21(2):302-307

Objectives: Appropriate treatment of hypothyroidism requires accurate diagnosis. This registry aimed to study the disease profile and treatment paradigm in hypothyroid patients in India. Materials and Methods: We registered 1500 newly diagnosed, treatment-naïve, adult hypothyroid males and nonpregnant females across 33 centers and collected relevant data from medical records. The first analysis report on baseline data is presented here. Results: The mean age of the study population was 41.1 ± 14.01 years with a female to male ratio of 7:3. The most frequently reported symptoms and signs were fatigue (60.17%) and weight gain with poor appetite (36.22%). Menstrual abnormalities were reported in all women (n = 730) who had not attained menopause. Grades 1 and 2 goiter (as per the WHO) were observed in 15.41% and 3.27% patients, respectively. Comorbidities were reported in 545 patients (36.36%), type 2 diabetes mellitus being the most prevalent (13.54%) followed by hypertension (11.34%). Total serum thyroxine (T4) and thyroid-stimulating hormone (TSH) levels were assessed in 291 (19.47%) patients only. In majority of patients (81%), treatment was based on serum TSH levels alone. The dose of levothyroxine ranged from 12.5 to 375 mcg. Conclusions: Guidelines suggest a diagnosis of hypothyroidism based on TSH and T4 levels. However, most of the patients as observed in this registry received treatment with levothyroxine based on TSH levels alone, thus highlighting the need for awareness and scientific education among clinicians in India. The use of standard doses (100, 75, and 25 mcg) of levothyroxine may point toward empirical management practices.

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Utility of cinacalcet in familial hypocalciuric hypercalcemia

Bipin Kumar Sethi, V Sri Nagesh, Jayant Kelwade, Harsh Parekh, Vaibhav Dukle

Indian Journal of Endocrinology and Metabolism 2017 21(2):362-363



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Trajectories of urinary incontinence in childhood and bladder and bowel symptoms in adolescence: prospective cohort study

Objectives

To identify different patterns (trajectories) of childhood urinary incontinence and examine which patterns are associated with bladder and bowel symptoms in adolescence.

Design

Prospective cohort study.

Setting

General community.

Participants

The starting sample included 8751 children (4507 men and 4244 women) with parent-reported data on frequency of bedwetting and daytime wetting for at least three of five time points (41/2, 51/2, 61/2, 71/2 and 91/2 years—hereafter referred to as 4–9 years). Study children provided data on a range of bladder and bowel symptoms at age 14 (data available for 5899 participants).

Outcome measures

Self-reported bladder and bowel symptoms at 14 years including daytime wetting, bedwetting, nocturia, urgency, frequent urination, low voided volume, voiding postponement, passing hard stools and low stool frequency.

Results

We extracted 5 trajectories of urinary incontinence from 4 to 9 years using longitudinal latent class analysis: (1) normative development of daytime and night-time bladder control (63.0% of the sample), (2) delayed attainment of bladder control (8.6%), (3) bedwetting alone (no daytime wetting) (15.6%), (4) daytime wetting alone (no bedwetting) (5.8%) and (5) persistent wetting (bedwetting with daytime wetting to age 9) (7.0%). The persistent wetting class generally showed the strongest associations with the adolescent bladder and bowel symptoms: OR for bedwetting at 14 years=23.5, 95% CI (15.1 to 36.5), daytime wetting (6.98 (4.50 to 10.8)), nocturia (2.39 (1.79 to 3.20)), urgency (2.10 (1.44 to 3.07)) and passing hard stools (2.64 (1.63 to 4.27)) (reference category=normative development). The association with adolescent bedwetting was weaker for children with bedwetting alone (3.69 (2.21 to 6.17)).

Conclusions

Trajectories of childhood urinary incontinence are differentially associated with adolescent bladder and bowel symptoms. Children exhibiting persistent bedwetting with daytime wetting had the poorest outcomes in adolescence.



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