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1.  Prevalence of Mupirocin Resistant Staphylococcus aureus Isolates Among Patients Admitted to a Tertiary Care Hospital 
Background:
For the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections and decolonization of MRSA carriers, the use of mupirocin a topical antibiotic is increasing day by day.
Aim:
The present study was carried out to determine the prevalence rate of high-level and low-level mupirocin resistant MRSA isolates among patients admitted to a tertiary care hospital.
Materials and Methods:
This is a prospective study carried out on MRSA isolated from the various clinical specimens from outpatient and inpatient departments during period of one year. A total of 82 MRSA isolates were recovered from 6468 different clinical specimens. Mupirocin resistant MRSA was detected by two different methods: Epsilometer test (E-test) and agar dilution method. D-shaped zone test (D-zone test) was also performed for determination of inducible clindamycin resistance in MRSA isolates.
Results:
Out of 82 non-duplicate MRSA isolates mupirocin resistance were found in 15 (18.3%) isolates by both E-test and agar dilution method. Of these 15 mupirocin resistant, 8 (53.3%) isolates were high-level resistant (MuH) and 7 (46.7%) isolates were low-level resistant (MuL). Four isolates were D-zone test positive showing simultaneous inducible clindamycin resistance among mupirocin resistant MRSA isolates.
Conclusion:
Higher prevalence of both high-level and low-level of mupirocin resistant MRSA was observed in patient from the population. It is advisable to perform routine test to detect MRSA colonization among health care workers and nasal decolonization to prevent spread of MRSA infections among hospitalized patients.
doi:10.4103/1947-2714.139293
PMCID: PMC4158649  PMID: 25210674
High-level; MRSA; MuH; MuL; Mupirocin resistance; Low-level
2.  Double tooth in mandibular incisor region: a case report 
BMJ Case Reports  2013;2013:bcr2012008647.
Double tooth is a term used to describe connate tooth and includes both dental fusion and gemination. Fusion refers to the union of two tooth germs resulting in a single large tooth. Owing to its irregular morphology, this anomaly can cause unpleasant aesthetic appearance. The diagnosis is based on the clinical findings and radiographic examination. We hereby discuss a case of fusion in a 30-year-old woman.
doi:10.1136/bcr-2013-008647
PMCID: PMC3604312  PMID: 23429027
3.  Nanoemulsions in Translational Research—Opportunities and Challenges in Targeted Cancer Therapy 
AAPS PharmSciTech  2014;15(3):694-708.
Nanoemulsion dosage form serves as a vehicle for the delivery of active pharmaceutical ingredients and has attracted great attention in drug delivery and pharmacotherapy. In particular, nanoemulsions act as an excellent vehicle for poorly aqueous soluble drugs, which are otherwise difficult to formulate in conventional dosage forms. Nanoemulsions are submicron emulsions composed of generally regarded as safe grade excipients. Particle size at the nanoscale and larger surface area lead to some very interesting physical properties that can be exploited to overcome anatomical and physiological barriers associated in drug delivery to the complex diseases such as cancer. Along these lines, nanoemulsions have been engineered with specific attributes such as size, surface charge, prolonged blood circulation, target specific binding ability, and imaging capability. These attributes can be tuned to assist in delivering drug/imaging agents to the specific site of interest, based on active and passive targeting mechanisms. This review focuses on the current state of nanoemulsions in the translational research and its role in targeted cancer therapy. In addition, the production, physico-chemical characterization, and regulatory aspects of nanoemulsion are addressed.
doi:10.1208/s12249-014-0088-9
PMCID: PMC4037485  PMID: 24510526
cancer; homogenization; microenvironment; microfluidization; nanoemulsion; size distribution; targeted delivery
4.  A Novel Use of Gentamicin in the ROS-Mediated Sensitization of NCI-H460 Lung Cancer Cells to Various Anticancer Agents 
ACS chemical biology  2013;8(12):10.1021/cb4007024.
Aminoglycosides are broad-spectrum antibiotics that are used for the treatment of severe Gram-negative and Gram-positive bacterial infections. While bactericidal effects of aminoglycosides are due to binding to the 30S subunit of the bacterial ribosome, aminoglycosides can affect protein synthesis, intracellular calcium levels and levels of reactive oxygen species (ROS) in eukaryotic cells. While aminoglycosides can be cytotoxic at high concentrations, our results show that at much lower doses, gentamicin can be implemented as a sensitizing agent for the NSCLC cell line NCI-H460, increasing the efficacy of camptothecin, digitoxin and vinblastine in vitro. We have also established that this sensitization is reliant on the ROS response generated by gentamicin.
doi:10.1021/cb4007024
PMCID: PMC3871214  PMID: 24093441
Aminoglycosides; Sensitization; Reactive Oxygen Species; NSCLC
5.  Comparison of Xpert MTB/RIF with Line Probe Assay for Detection of Rifampin-Monoresistant Mycobacterium tuberculosis 
Journal of Clinical Microbiology  2014;52(6):1846-1852.
The MTBDRplus line probe assay (LPA) and Xpert MTB/RIF have been endorsed by the World Health Organization for the rapid diagnosis of drug-resistant tuberculosis. However, there is no clarity regarding the superiority of one over the other. In a double-blinded prospective study, we evaluated the efficacy of the Xpert MTB/RIF on samples that were first tested by LPA under the revised national tuberculosis control program of India. A total of 405 sputum samples from suspected drug-resistant tuberculosis patients were included. Of these, 285 smear-positive samples were subjected to LPA. Seventy-two (25.8%) samples showed multidrug resistance, 62 (22.2%) showed rifampin monoresistance, 29 (10.3%) showed isoniazid monoresistance, and 116 (41.5%) were pan-susceptible. Six (2.1%) of the samples gave invalid results. Of the 62 rifampin-monoresistant samples by LPA, 38 (61.4%) showed rifampin resistance, while 21 (33.8%) were found susceptible to rifampin by Xpert MTB/RIF using cartridge version G4. Three (4.8%) samples gave an error. Of the 116 pan-susceptible samples, only 83 were available for Xpert MTB/RIF testing; 4 (5.1%) were rifampin resistant, 74 (94.8%) were susceptible, and 5 (6.0%) showed an error. The 25 discrepant samples were further subjected to MGIT960 drug susceptibility testing. The MGIT960 results showed 100% agreement with LPA results but only 64.4% agreement with Xpert MTB/RIF results. Sequencing analysis of discrepant samples showed 91.3% concordance with LPA but only 8.7% concordance with the Xpert MTB/RIF assay. These findings indicate that by using Xpert MTB/RIF testing we might be underestimating the burden of drug-resistant tuberculosis and indicate that country-specific probes need to be designed to increase the sensitivity of the Xpert MTB/RIF.
doi:10.1128/JCM.03005-13
PMCID: PMC4042801  PMID: 24648554
6.  Analysis of Genetic Diversity and Population Structure of Rice Germplasm from North-Eastern Region of India and Development of a Core Germplasm Set 
PLoS ONE  2014;9(11):e113094.
The North-Eastern region (NER) of India, comprising of Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland and Tripura, is a hot spot for genetic diversity and the most probable origin of rice. North-east rice collections are known to possess various agronomically important traits like biotic and abiotic stress tolerance, unique grain and cooking quality. The genetic diversity and associated population structure of 6,984 rice accessions, originating from NER, were assessed using 36 genome wide unlinked single nucleotide polymorphism (SNP) markers distributed across the 12 rice chromosomes. All of the 36 SNP loci were polymorphic and bi-allelic, contained five types of base substitutions and together produced nine types of alleles. The polymorphic information content (PIC) ranged from 0.004 for Tripura to 0.375 for Manipur and major allele frequency ranged from 0.50 for Assam to 0.99 for Tripura. Heterozygosity ranged from 0.002 in Nagaland to 0.42 in Mizoram and gene diversity ranged from 0.006 in Arunachal Pradesh to 0.50 in Manipur. The genetic relatedness among the rice accessions was evaluated using an unrooted phylogenetic tree analysis, which grouped all accessions into three major clusters. For determining population structure, populations K = 1 to K = 20 were tested and population K = 3 was present in all the states, with the exception of Meghalaya and Manipur where, K = 5 and K = 4 populations were present, respectively. Principal Coordinate Analysis (PCoA) showed that accessions were distributed according to their population structure. AMOVA analysis showed that, maximum diversity was partitioned at the individual accession level (73% for Nagaland, 58% for Arunachal Pradesh and 57% for Tripura). Using POWERCORE software, a core set of 701 accessions was obtained, which accounted for approximately 10% of the total NE India collections, representing 99.9% of the allelic diversity. The rice core set developed will be a valuable resource for future genomic studies and crop improvement strategies.
doi:10.1371/journal.pone.0113094
PMCID: PMC4239046  PMID: 25412256
7.  Plasma rennin activity: Early indicator of renal injury in bilateral pelviureteric junction obstruction in children 
Urology Annals  2014;6(4):295-297.
Objective:
The objective of the present study is to analyze the early indicators of renal injury in children with bilateral pelviuretric junction obstruction.
Materials and Methods:
We investigated 23 children, 46 kidney units who were diagnosed with bilateral pelvi-ureteric junction obstruction (PUJO) and underwent unilateral or bilateral pyeloplasty between January 2001 and December 2011. Ipsilateral kidney biopsy was performed during pyeloplasty. Kidney biopsy results were divided into three categories. Pre-operative investigation included ultrasonography with the Society of Fetal Urology (SFU) grading, plasma rennin activity (PRA) and differential renal function (DRF).
Results:
Out of 23 children there were 17 (73.9%) boys while 6 (26.1%) girls. Median age at operation was 35.4 months (range: 9-60 months). Unilateral pyeloplasty was performed in 14 (60.8%), simultaneous bilateral pyeloplasty in 2 (8.6%) and sequential bilateral pyeloplasty in 7 (30.4%).
Conclusion:
In bilateral PUJO where DRF and SFU grading of hydronephrosis did not correctly reflect renal injury, PRA showed a significant relationship with renal histopathologic grade and could be an early indicator of renal injury in bilateral PUJO.
doi:10.4103/0974-7796.140981
PMCID: PMC4216533  PMID: 25371604
Bilateral pelvi-ureteric junction obstruction; lumbotomy; plasma renin; pyeloplasty; renal histology
8.  Intra-oral Plastic Pressure Dressing: A Technical Note 
Post-operative swelling in the maxillofacial region is a common finding, especially in the cheek region. There is abundance of soft tissue and lack of any anatomical barrier to inhibit the swelling in the cheek region. External pressure dressing is the most commonly followed norm along with steroids. This protocol usually is insufficient to counter the swelling. In our Technical note we are describing a technique of use of intra-oral plastic sheet pressure dressing along with the conventional treatment protocol. The use of intra-oral plastic sheet is a cheap, safe, readily available in the OR and effective method of compression dressing.
doi:10.1007/s12663-012-0372-8
PMCID: PMC3777033  PMID: 24431868
Pressure dressing; Buccal swelling; Post-operative swelling
9.  Recent Advances in Polyamine Metabolism and Abiotic Stress Tolerance 
BioMed Research International  2014;2014:239621.
Global warming is an alarming problem in agriculture and its effect on yield loss has been estimated to be five per cent for every degree centigrade rise in temperature. Plants exhibit multiple mechanisms like optimizing signaling pathway, involvement of secondary messengers, production of biomolecules specifically in response to stress, modulation of various metabolic networks in accordance with stress, and so forth, in order to overcome abiotic stress factors. Many structural genes and networks of pathway were identified and reported in plant systems for abiotic stress tolerance. One such crucial metabolic pathway that is involved in normal physiological function and also gets modulated during stress to impart tolerance is polyamine metabolic pathway. Besides the role of structural genes, it is also important to know the mechanism by which these structural genes are regulated during stress. Present review highlights polyamine biosynthesis, catabolism, and its role in abiotic stress tolerance with special reference to plant systems. Additionally, a system based approach is discussed as a potential strategy to dissect the existing variation in crop species in unraveling the interacting regulatory components/genetic determinants related to PAs mediated abiotic stress tolerance.
doi:10.1155/2014/239621
PMCID: PMC4124767  PMID: 25136565
10.  MALT Lymphoma of Caecum Presenting as Acute Intestinal Obstruction: A Case Report 
The Indian Journal of Surgery  2012;75(Suppl 1):286-289.
Mucosa-associated lymphoid tissue lymphomas (MALT lymphoma) are well known, but colonic MALT lymphomas are extremely rare. We report the first case of mucosa-associated lymphoid tissue (MALT) lymphoma in the cecum from India presenting as acute intestinal obstruction with mass in right iliac fossa showing diffuse thickening of ascending colon and caecum with obliterated lumen along with nodular mass on CECT scan of abdomen. On video colonoscopy, circumferential ulcerated growth was seen at cecum, and the rest of the colon was normal. Multiple biopsies from growth suggested malignancy. Right hemicolectomy was performed. The histopathology of resected specimen demonstrated low-grade B-cell MALT lymphoma of the cecum, and the depth of invasion was up to the muscular layer. This was confirmed by immunohistochemistry.
doi:10.1007/s12262-012-0672-8
PMCID: PMC3693229  PMID: 24426593
GI tract; Cecum; MALT lymphoma; Immunohistochemistry; Intestinal obstruction; B-cell lymphoma; H. pylori
11.  A Toolbox for Tuberculosis (TB) Diagnosis: An Indian Multi-Centric Study (2006-2008); Evaluation of Serological Assays Based on PGL-Tb1 and ESAT-6/CFP10 Antigens for TB Diagnosis 
PLoS ONE  2014;9(5):e96367.
Background
The aim of this multi-centric prospective study in India was to assess the accuracy of a serological test as an additional tool for diagnosing active tuberculosis (ATB). In particular, an assay based on ELISA using a phenolic glycolipid (PGL-Tb1) or a fusion protein (ESAT-6/CFP10) was compared to the tuberculin skin test (TST) and the microbiological results according to HIV status.
Methods
Individuals with and without ATB and HIV infection were enrolled. Serology and TST results were analyzed per se and in combination with the microbiological data.
Results
Among the 778 ATB patients, 102 were HIV-infected, 316 HIV-uninfected and 360 had an HIV-unknown status. Of the 945 non-ATB subjects, 559 were at low risk (community adults) and 386 at high risk of M. tuberculosis exposure. Among those with ATB, the sensitivity of ELISA-PGL-Tb1 for ATB was higher than that of ELISA-ESAT-6/CFP10, both in HIV-infected (72.3% versus 63.7%, p = 0.29) and HIV-uninfected/HIV-unknown groups (40.5% versus 28.6%; p<0.0001), whereas the specificity was around 91% for both tests. Sensitivity for ATB increased when the results of the two ELISA were combined, reaching 75.5% in the HIV-infected and 50.9% in the group of HIV-uninfected/HIV-unknown ATB, with a significant decrease of the global specificity (83.9%). Analyzing the ELISA results with the microbiological results, we observed that the sensitivity of both serology tests was independent of the ATB patients' smear microscopy (SM) status and grade. Combining the results of SM with both ELISA, the detection of ATB patients significantly increased (p<0.0001), particularly in those with extrapulmonary TB (up to 45.1%) or HIV infection (up to 83.3%). No significant association was observed between TST and serology results.
Conclusions
In this prospective multi-centric study, the combination of two rapid tests, such as SM and serology, might be useful in detecting ATB, especially in HIV-infected patients.
doi:10.1371/journal.pone.0096367
PMCID: PMC4010510  PMID: 24797271
12.  Spontaneous Cholecystocolic Fistula: Case Report 
Cholecystocolic fistula is a rare billiary-enteric fistula with variable clinical presentation. Despite modern diagnostic tool a high degree of suspicion is required to diagnose it preoperatively. These fistulae are treated by open as well as laparoscopic surgery, with no difference in intraoperative and postoperative complications. We are describing a 50-year-old female patient with the diagnosis of chronic cholecystitis with cholelithiasis, which was investigated with routine lab investigations, and abdominal ultrasonography but none of these gave us any clue to the presence of fistula, were discovered incidentally during an open surgery and were appropriately treated.
doi:10.7860/JCDR/2014/7298.4149
PMCID: PMC4003626  PMID: 24783121
Biliary-enteric fistula; Cholecystectomy; Cholelithiasis
13.  Metastatic Primary Signet Ring Cell Carcinoma of Rectum: A Case Report of 10-Year-old Male Child 
Signet ring cell carcinomas of the colon and rectum are well documented in the adult population, but the incidence is very low in the paediatric population. Signet ring cell carcinoma has more malignant potential, mostly present as advanced stage and carries very poor prognosis. We are describing a 10-year-old male patient who presented with acute intestinal obstruction; radiology revealed large bowel obstruction and was diagnosed metastatic primary signet ring cell carcinoma of rectum on biopsy. We have discussed the diagnostic work-up and the management of this rare entity. Due to the high mortality that can be caused by a delay in making the correct diagnosis, signet ring cell carcinoma of colorectum represents a special diagnostic and surgical challenge.
doi:10.7860/JCDR/2014/6988.4051
PMCID: PMC3972554  PMID: 24701526
Mucinous Tumor; Colorectal Neoplasm; Intestinal obstruction
16.  Methylenetetrahydrofolate reductase C677T variant in Indian children with craniosynostosis: Its role in the pathogenesis, risk of craniosynostosis 
Indian Journal of Human Genetics  2014;20(2):155-159.
BACKGROUND:
677C to T allele in the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene has been implicated in the etiology of various syndromes and nonsyndromic diseases but till date no direct studies have been reported with craniosynostosis.
OBJECTIVES:
The aim was to study the family-based association of MTHFR polymorphism in different categories of craniosynostosis patients.
MATERIALS AND METHODS:
This was a cross-sectional study in which 30 patients classified as Apert syndrome, Pfeiffr syndrome and nonsyndromic craniosynostosis patients with their family were recruited. A sample of 3 ml intravenous blood was taken from patients and from their family members (father and mother) in ethylenediaminetetraacetic acid-anticoagulated vacutainer for the purpose of the study. Genomic DNA was extracted from peripheral blood lymphocytes by phenol chloroform extraction method. Primers for MTHFR gene were designed. The polymerase chain reaction was carried out. After successful amplification, a small aliquot (5 μl) of the MTHFR reaction mixture was treated with 1 units of Hinf I restriction enzyme (NEB). Results were obtained and compiled.
RESULTS:
A total of 30 patients/participants with craniosynostosis of Indian descent and their parents formed the study group. The genotyping did not confirm an association between the MTHFR 677C to T polymorphism and between different categories of craniosynostosis. When comparing the offspring of mothers statistically significant differences were found.
CONCLUSION:
C667T polymorphism of the MTHFR gene is unlikely to play a role in the pathogenesis of craniosynostosis though maternal MTHFR C677T polymorphism may be a genetic risk factor.
doi:10.4103/0971-6866.142882
PMCID: PMC4228567  PMID: 25400344
Craniosynostosis; gene; methylenetetrahydrofolate reductase polymorphism
17.  Antimicrobial Susceptibility Profile of Extended Spectrum β-Lactamase (ESBL) Producing Escherichia coli from Various Clinical Samples 
Infectious Diseases  2014;7:1-8.
BACKGROUND
Extended spectrum β-lactamase (ESBL) producing Escherichia coli has tremendously increased worldwide and it is one of the most common causes of morbidity and mortality associated with hospital-acquired infections. This could be attributed to association of multi drug resistance in ESBL producing isolates. The present study was aimed to determine the antimicrobial sensitivity profile of ESBL producing E. coli isolates from various clinical samples.
MATERIALS AND METHODS
Clinical samples, which consist of pus, urine, blood, cerebrospinal fluid (CSF), stool, sputum, swabs, and different body fluids, are included in the study. Samples were processed and identified as per routine laboratory protocol. ESBL screening and confirmation along with antimicrobial susceptibility test was done according to the Clinical Laboratory Standards Institute (CLSI) guidelines.
RESULTS
Out of 180 third generation cephalosporins resistant E. coli, 100 (55.55%) isolates were ESBL producers showing a greater degree of resistance to antibiotics.
CONCLUSION
The prevalence of ESBL is increasing day by day in nearly every center of different countries and necessary steps to prevent the spread and emergence of resistance should be taken.
doi:10.4137/IDRT.S13820
PMCID: PMC4024053  PMID: 24847178
ESBL; E. coli; ESBL producing E. coli; DDS
18.  Redox-responsive targeted gelatin nanoparticles for delivery of combination wt-p53 expressing plasmid DNA and gemcitabine in the treatment of pancreatic cancer 
BMC Cancer  2014;14:75.
Background
Pancreatic adenocarcinoma is one of the most dreaded cancers with very low survival rate and poor prognosis to the existing frontline chemotherapeutic drugs. Gene therapy in combination with a cytotoxic agent could be a promising approach to circumvent the limitations of previously attempted therapeutic interventions.
Method
We have developed a redox-responsive thiolated gelatin based nanoparticle system that efficiently delivers its payload in the presence of glutathione-mediated reducing intra-cellular environment and could be successfully used for site-specific wt-p53 expressing plasmid DNA as well as gemcitabine delivery by targeting epidermal growth factor receptor (EGFR). Efficacy studies were performed in subcutaneous human adenocarcinoma bearing SCID beige mice along with molecular level p53 plasmid and apoptotic marker expression by PCR and western blot for all study groups.
Results
Efficacy studies demonstrate an improved in vivo targeting efficiency resulting in increased transfection efficiency and tumor growth suppression. In all the treatment groups, the targeted nanoparticles showed better anti-tumor activity than their non-targeted as well as non-encapsulated, naked therapeutic agent counterparts (50.1, 61.7 and 77.3% tumor regression by p53 plasmid alone, gemcitabine alone and in combination respectively). Molecular analysis revealed a higher mRNA expression of transfected p53 gene, its corresponding protein and that the tumor cell death in all treatment groups was due to the induction of apoptotic pathways.
Conclusions
Gene/drug combination treatment significantly improves the therapeutic performance of the delivery system compared to the gene or drug alone treated groups. Anti-tumor activity of the thiolated gelatin loaded wt-p53 plasmid or gemcitabine-based therapy was attributed to their ability to induce cell apoptosis, which was confirmed by a marked increase in mRNA level of proapoptotic transcription factors, as well as, protein apoptotic biomarker expression and significant decrease in the anti-apoptotic transcription factors.
doi:10.1186/1471-2407-14-75
PMCID: PMC3927583  PMID: 24507760
Thiolated gelatin; Wt-p53 expressing plasmid DNA; Gemcitabine; Pancreatic Adenocarcinoma; Apoptosis
19.  Reengineering Redox Sensitive GFP to Measure Mycothiol Redox Potential of Mycobacterium tuberculosis during Infection 
PLoS Pathogens  2014;10(1):e1003902.
Mycobacterium tuberculosis (Mtb) survives under oxidatively hostile environments encountered inside host phagocytes. To protect itself from oxidative stress, Mtb produces millimolar concentrations of mycothiol (MSH), which functions as a major cytoplasmic redox buffer. Here, we introduce a novel system for real-time imaging of mycothiol redox potential (EMSH) within Mtb cells during infection. We demonstrate that coupling of Mtb MSH-dependent oxidoreductase (mycoredoxin-1; Mrx1) to redox-sensitive GFP (roGFP2; Mrx1-roGFP2) allowed measurement of dynamic changes in intramycobacterial EMSH with unprecedented sensitivity and specificity. Using Mrx1-roGFP2, we report the first quantitative measurements of EMSH in diverse mycobacterial species, genetic mutants, and drug-resistant patient isolates. These cellular studies reveal, for the first time, that the environment inside macrophages and sub-vacuolar compartments induces heterogeneity in EMSH of the Mtb population. Further application of this new biosensor demonstrates that treatment of Mtb infected macrophage with anti-tuberculosis (TB) drugs induces oxidative shift in EMSH, suggesting that the intramacrophage milieu and antibiotics cooperatively disrupt the MSH homeostasis to exert efficient Mtb killing. Lastly, we analyze the membrane integrity of Mtb cells with varied EMSH during infection and show that subpopulation with higher EMSH are susceptible to clinically relevant antibiotics, whereas lower EMSH promotes antibiotic tolerance. Together, these data suggest the importance of MSH redox signaling in modulating mycobacterial survival following treatment with anti-TB drugs. We anticipate that Mrx1-roGFP2 will be a major contributor to our understanding of redox biology of Mtb and will lead to novel strategies to target redox metabolism for controlling Mtb persistence.
Author Summary
Approximately 30% of the global population is infected with Mycobacterium tuberculosis (Mtb). Persistence of Mtb in host phagocytes depends on its ability to resist oxidant-mediated antibacterial responses. Mycothiol (MSH) is the main antioxidant that provides an abundant source of reducing equivalent, which protects Mtb from oxidative stress encountered during infection. The majority of research into redox signaling in Mtb has relied on chemical analysis of MSH in whole cell extract, which creates oxidation artifacts and prohibits dynamic imaging of MSH redox state during infection. We have successfully developed a novel and noninvasive tool based on genetically encoded redox sensitive fluorescent probes to perform real-time measurement of mycothiol redox potential (EMSH) in Mtb during infection. For the first time we reveal the EMSH of virulent and avirulent mycobacterial strains, including drug-resistant clinical isolates. We used this technology and came to the surprising conclusion that within a single infected macrophage there is heterogeneity in the redox signature of individual Mtb bacilli. Importantly, we show that anti-TB drugs accelerate oxidative stress in Mtb within infected macrophages and redox heterogeneity can contribute to emergence of drug tolerant population. These findings have implications for mycobacterial persistence following treatment with anti-TB drugs.
doi:10.1371/journal.ppat.1003902
PMCID: PMC3907381  PMID: 24497832
20.  Domain specific genetic mosaic system in the Drosophila eye 
SUMMARY
Genetic mosaic approach is commonly employed in the Drosophila eye by completely abolishing or misexpressing a gene within a subset of cells to unravel its role during development. Classical genetic mosaic approach involves random clone generation in all developing fields. Consequently, a large sample size needs to be screened to generate and analyze clones in specific domains of the developing eye. To address domain specific functions of genes during axial patterning, we have developed a system for generating mosaic clones by combining Gal4/UAS and FLP/FRT system which will allow generation of loss-of-function as well as gain-of-function clones on the dorsal and ventral eye margins. We used the bifid-Gal4 driver to drive expression of UAS-flippase (FLP). This reagent can have multiple applications in (i) studying spatio-temporal function of a gene during dorso-ventral axis specification in the eye, (ii) analyzing genetic epistasis of genes involved in DV patterning and (iii) conducting genome wide screens in a domain specific manner.
doi:10.1002/dvg.22355
PMCID: PMC3547150  PMID: 23109378
Drosophila eye; Dorso-ventral (DV) axis; patterning; genetic mosaic; Gal4/UAS technique; compartments
21.  Benign papillomatosis of common bile duct in children: A rare case report 
In children benign neoplasms are rare events in the extrahepatic biliary ducts and scanty literary references on the subject are available. We are reporting a rare case of a 3-year-old female child having biliary papillomatosis in lower common bile duct.
doi:10.4103/0971-9261.125966
PMCID: PMC3935301  PMID: 24604985
Extrahepatic biliary papillomatosis; lower common bile duct; polyp
23.  Role of erythrocyte sedimentation rate in ischemic stroke as an inflammatory marker of carotid atherosclerosis 
Background:
Inflammation mediates a key role in the pathogenesis of atherosclerosis which is an important cause of ischemic stroke. An elevated erythrocyte sedimentation rate (ESR) may, therefore, be a marker of the extent andor intensity of a general atherosclerotic process and thus a marker for advanced atherosclerosis heralding increased risk of arterial thrombosis leading to ischemic stroke.
Materials and Methods:
ESR was calculated in ischemic stroke patients by Westergren's method along with carotid sonography using high resolution 7.5 MHz techniques to find the prevalence of increased carotid intima-media thickness (CIMT) and presence of plaque according to Mannheim Carotid Intima-Media Thickness Consensus.
Results:
Average value of ESR in all patients was 27.89 ± 9.73 mm/h. A significant association was found between ESR and markers of carotid atherosclerosis, that is, high CIMT of more than 0.8 mm (P < 0.0001) and presence of plaque (P-0.026) in univariate analysis. Also, a significant positive correlation was found between ESR and serum fibrinogen, another inflammatory marker. (r = 0.88, P < 0.0001).
Conclusion:
The extent of inflammation may reflect in part the propensity of atherosclerotic lesions to lead to clinical disease. Study shows the association of ESR with markers of atherosclerosis confirming the strength of the inflammatory response associated with carotid atherosclerosis and might conceivably carry important prognostic information regarding occurrence of such catastrophic events in future.
doi:10.4103/0976-3147.127870
PMCID: PMC3985355  PMID: 24741248
Arterial thrombosis; atherosclerosis; cerebrovascular disease; inflammation; ischemic stroke; plaque
24.  Protective effects of Aegle marmelos fruit pulp on 2,4,6-trinitrobenzene sulfonic acid-induced experimental colitis 
Pharmacognosy Magazine  2014;10(Suppl 1):S147-S152.
Background:
Aegle marmelos (AM) fruit has been advocated in indigenous system of medicine for the treatment of various gastrointestinal disorders, fever, asthma, inflammations, febrile delirium, acute bronchitis, snakebite, epilepsy, leprosy, myalgia, smallpox, leucoderma, mental illnesses, sores, swelling, thirst, thyroid disorders, tumours and upper respiratory tract infections.
Objective:
The objective of this study was to study the curative effect of 50% ethanol extract of dried fruit pulp of AM (AME) against 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis.
Materials and Methods:
AME (200 mg/kg) was administered orally, once daily for 14 days after TNBS-induced colitis. Rats were given intracolonic normal saline or TNBS alone or TNBS plus oral AME. AME was studied for its in vitro antibacterial activity against Gram-negative intestinal bacteria and on TNBS-induced changes in colonic damage, weight and adhesions (macroscopic and microscopic), diarrhea, body weight and colonic levels of free radicals (nitric oxide and lipid peroxidation), antioxidants (superoxide dismutase, catalase and reduced glutathione) and pro-inflammatory marker (myeloperoxidase [MPO]) in rats.
Results:
AME showed antibacterial activity against intestinal pathogens and decreased colonic mucosal damage and inflammation, diarrhea, colonic free radicals and MPO and enhanced body weight and colonic antioxidants level affected by TNBS. The effects of AME on the above parameters were comparable with sulfasalazine, a known colitis protective drug (100 mg/kg, oral).
Conclusion:
AME shows curative effects against TNBS-induced colitis by its antibacterial activity and promoting colonic antioxidants and reducing free radicals and MPO-induced colonic damage.
doi:10.4103/0973-1296.127366
PMCID: PMC4047580  PMID: 24914296
Aegle marmelos fruit; antioxidants; free radicals; myeloperoxidase; 2,4,6-trinitrobenzene sulfonic acid-induced colitis
25.  Hollow Mill for Extraction of Stripped Titanium Screws: An Easy, Quick, and Safe Technique 
Removal of jammed titanium screws can be difficult due to the problem of stripping of the hexagonal heads of the screws. We present a technique of extraction of stripped screws with the use of a standard 4.5 mm stainless steel hollow mill in a patient of peri-implant fracture of the radius fixed with a titanium locking plate 2 years back. The technique is quick, safe, and cost effective.
doi:10.4103/2006-8808.135135
PMCID: PMC4090986  PMID: 25013544
Hollow mill; stripped screws; titanium locked plates; titanium plates

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