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author:("vivek, S.")
1.  Integrative Analysis of T cell Motility from Multi-channel Microscopy Data using TIAM 
Integrative analytical approaches are needed to study and understand T cell motility as it is a highly coordinated and complex process. Several computational algorithms and tools are available to track motile cells in time-lapse microscopy images. In contrast, there has only been limited effort towards the development of tools that take advantage of multi-channel microscopy data and facilitate integrative analysis of cell-motility. We have implemented algorithms for detecting, tracking, and analyzing cell motility from multi-channel time-lapse microscopy data. We have integrated these into a MATLAB-based toolset we call TIAM (Tool for Integrative Analysis of Motility). The cells are detected by a hybrid approach involving edge detection and Hough transforms from transmitted light images. Cells are tracked using a modified nearest-neighbor association followed by an optimization routine to join shorter segments. Cell positions are used to perform local segmentation for extracting features from transmitted light, reflection and fluorescence channels and associating them with cells and cell-tracks to facilitate integrative analysis. We found that TIAM accurately captures the motility behavior of T cells and performed better than DYNAMIK, Icy, Imaris, and Volocity in detecting and tracking motile T cells. Extraction of cell-associated features from reflection and fluorescence channels was also accurate with less than 10% median error in measurements. Finally, we obtained novel insights into T cell motility that were critically dependent on the unique capabilities of TIAM. We found that 1) the CD45RO subset of human CD8 T cells moved faster and exhibited an increased propensity to attach to the substratum during CCL21-driven chemokinesis when compared to the CD45RA subset; and 2) attachment area and arrest coefficient during antigen-induced motility of the CD45A subset is correlated with surface density of integrin LFA1 at the contact.
doi:10.1016/j.jim.2014.11.004
PMCID: PMC4323926  PMID: 25445324
T cell motility; tracking; integrative analysis; multi-channel microscopy
2.  AI-04MECHANISMS OF GLIOMA FORMATION: PERIVASCULAR GLIOMA INVASION IS A VEGF-INDEPENDENT MECHANISM OF TUMOR VASCULARIZATION 
Neuro-Oncology  2014;16(Suppl 5):v1-v2.
Malignant glioma cells associate with various microanatomical brain structures such as blood vessels, white matter tracts, and brain parenchyma as they spread throughout the brain. However, how these distinct brain tumor invasion patterns coordinate tumor growth and influence clinical outcomes remains unknown. We have investigated how perivascular growth affects glioma growth patterning and response to anti-angiogenic therapy within the highly vascularized brain. We show that orthotopically implanted rodent and human malignant glioma cells, as well as de-novo generated endogenous mouse brain tumors, biopsies of primary human glioblastoma, and peripheral cancer metastasis to the human brain each use brain perivascular space as a means for tissue invasion. Perivascularly invading brain tumors become vascularized by normal brain microvessels as individual gliomas cells use perivascular space as a conduit for tumor invasion. We generated an agent-based computational model, which recapitulated biologically observed perivascular glioma growth without the need for neoangiogenesis. This in-silico result prompted us to test whether neoangiogenesis is indeed required for tumor progression in perivascularly invading glioma by treating tumor-bearing animals with angiogenesis inhibitors bevacizumab and DC101. These inhibitors induced the expected vessel-normalization, yet failed to reduce tumor growth or improve survival of mice implanted orthotopically with gliomas from mouse or human origin, or mice subjected to sleeping-beauty generated endogenous gliomas; in all models tested anti-angiogenics exacerbated brain tumor invasion. Our results provide compelling experimental evidence for the recently described failure of clinically used anti-angiogenics to extend the survival of human glioma patients. Given that anti-angiogenics may be beneficial in some patients suffering from certain genetically identifiable glioma subtypes, whether there are mouse or human glioma cells whose growth in-vitro can be reduced by anti-angiogenic approaches remains to be determined.
doi:10.1093/neuonc/nou238.4
PMCID: PMC4217870
3.  IB-01GLIOMA-DERIVED GALECTIN-1 IS A POTENT SUPPRESSOR OF NK IMMUNOSURVEILLANCE 
Neuro-Oncology  2014;16(Suppl 5):v107.
Natural killer (NK) cells safeguard against early tumor formation by destroying transformed target cells in a process referred to as NK immunosurveillance. However, the mechanisms used by malignant brain tumors to subvert this innate immune function remain unclear. We show that shRNA-mediated knockdown of the β-galactoside-binding lectin, galectin-1 (gal-1), in malignant glioma cells leads to the failure to form lethal intracranial tumors in RAG1-/- mice, a mouse strain devoid of adaptive immunity. However, gal-1 deficient glioma growth is fully restored on implantation into the brain of severely immunocompromised NOD-scid IL2Rg null mice, which lack both adaptive and innate immune function, thus implicating the innate immune response in the early rejection of gal-1 deficient glioma. Immunodepletion of NK cells in RAG1-/- or C57BL/6J mice using anti-asialo GM1 or anti-NK1.1 antibodies permit the growth of large gal-1 deficient gliomas. Antigen-specific IFN-γ ELISpot assays using splenocytes from immunocompetent C57BL/6J mice indicate that gal-1 deficient glioma is cleared prior to the onset of an adaptive anti-tumor immune response. Flow cytometric analysis of brain tumor-infiltrating immune cells reveal that gal-1 deficient gliomas contain significantly more granzyme B+ NK cells compared to gal-1 expressing gliomas. In-vitro experiments further show that gal-1 deficient glioma cells are over three times more sensitive to NK-mediated tumor lysis. We conclude that glioma-derived gal-1 is a powerful inhibitor of NK-mediated cytotoxicity in-vivo, and predict that its suppression will be of therapeutic value in the treatment of human malignant brain tumors by dramatically heightening anti-tumor NK immunosurveillance.
doi:10.1093/neuonc/nou257.1
PMCID: PMC4218214
4.  Yersinia pestis and Yersinia pseudotuberculosis infection: a regulatory RNA perspective 
Yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, Y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species. Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors. Here the burgeoning field of small non-coding regulatory RNAs in Yersinia pathogenesis is reviewed from the viewpoint of adaptive colonization, virulence and divergent evolution of these pathogens.
doi:10.3389/fmicb.2015.00956
PMCID: PMC4585118  PMID: 26441890
post-transcriptional regulation; RNA-binding proteins; sRNAs; riboswitch; Hfq
5.  Natural Killer Cells Eradicate Galectin-1 Deficient Glioma in the Absence of Adaptive Immunity 
Cancer research  2014;74(18):5079-5090.
Natural killer (NK) cells safeguard against early tumor formation by destroying transformed target cells in a process referred to as NK immune surveillance. However, the immune escape mechanisms used by malignant brain tumors to subvert this innate type of immune surveillance remain unclear. Here we show that malignant glioma cells suppress NK immune surveillance by overexpressing the β-galactoside-binding lectin galectin-1. Conversely, galectin-1 deficient glioma cells could be eradicated by host NK cells prior to the initiation of an anti-tumor T-cell response. In vitro experiments demonstrated that galectin-1 deficient GL26-Cit glioma cells are ~3-fold more sensitive to NK-mediated tumor lysis that galectin-1 expressing cells. Our findings suggest that galectin-1 suppression in human glioma could improve patient survival by restoring NK immune surveillance that can eradicate glioma cells.
doi:10.1158/0008-5472.CAN-14-1203
PMCID: PMC4184887  PMID: 25038230
galectin-1 (gal-1); natural killer (NK) cells; gal-1 deficient glioma
6.  A LysR-Type Transcriptional Regulator, RovM, Senses Nutritional Cues Suggesting that It Is Involved in Metabolic Adaptation of Yersinia pestis to the Flea Gut 
PLoS ONE  2015;10(9):e0137508.
Yersinia pestis has evolved as a clonal variant of Yersinia pseudotuberculosis to cause flea-borne biofilm–mediated transmission of the bubonic plague. The LysR-type transcriptional regulator, RovM, is highly induced only during Y. pestis infection of the flea host. RovM homologs in other pathogens regulate biofilm formation, nutrient sensing, and virulence; including in Y. pseudotuberculosis, where RovM represses the major virulence factor, RovA. Here the role that RovM plays during flea infection was investigated using a Y. pestis KIM6+ strain deleted of rovM, ΔrovM. The ΔrovM mutant strain was not affected in characteristic biofilm gut blockage, growth, or survival during single infection of fleas. Nonetheless, during a co-infection of fleas, the ΔrovM mutant exhibited a significant competitive fitness defect relative to the wild type strain. This competitive fitness defect was restored as a fitness advantage relative to the wild type in a ΔrovM mutant complemented in trans to over-express rovM. Consistent with this, Y. pestis strains, producing elevated transcriptional levels of rovM, displayed higher growth rates, and differential ability to form biofilm in response to specific nutrients in comparison to the wild type. In addition, we demonstrated that rovA was not repressed by RovM in fleas, but that elevated transcriptional levels of rovM in vitro correlated with repression of rovA under specific nutritional conditions. Collectively, these findings suggest that RovM likely senses specific nutrient cues in the flea gut environment, and accordingly directs metabolic adaptation to enhance flea gut colonization by Y. pestis.
doi:10.1371/journal.pone.0137508
PMCID: PMC4562620  PMID: 26348850
7.  Novel MEN 1 gene findings in rare sporadic insulinoma—a case control study 
Background
Insulinomas, which are rare tumors causing hyperinsulinemic hypoglycemia are usually sporadic but may also occur in association with multiple endocrine neoplasia type 1 (MEN-1) syndrome an autosomal dominant disorder caused by MEN1 gene mutations. MEN1 encodes a nuclear protein Menin, a tumor suppressor which acts as an adapter and interacts with partner proteins involved in crucial activities like transcriptional regulation, cell division, proliferation and genome stability.
This study reports on clinical findings and mutation screening in sporadic insulinoma patients.
Methods
Seventeen patients diagnosed with insulinoma were recruited along with 30 healthy volunteers who acted as controls for the present study. The patients presented with symptoms of sweating, tremors, drowsiness, palpitations, loss of consciousness, abnormal behavior, seizures and weight gain. Detailed clinical and family history was collected from all the participants along with 5 ml of blood sample after taking informed consent.
Genomic DNA isolated from blood was subjected to MEN1 gene amplification followed by direct sequencing. Nucleotide sequences obtained were compared with published MEN1 cDNA sequences. Prediction of functional effects of novel changes was done using various bioinformatics algorithms.
Results
Molecular analysis revealed presence of three novel exonic mutations (M561K, Q192K and Q261Q), two novel intronic variations c.445-44G → A and c.913-42G → C in introns two and six respectively and three reported exon SNPs; H433H (rs540012), D418D (rs2071313), A541T (rs2959656) and one intronic SNP (rs669976).
Conclusions
The study identified presence of novel pathogenic MEN1 mutations in sporadic cases of insulinoma. The new mutations identified were in regions involved in defective binding of menin to proteins implicated in genetic and epigenetic mechanisms. The outcome of the study extends the growing list of MEN1 pathogenic mutations even in sporadic cases providing consequential insight into phenotypic heterogeneity and in the expression of individual mutations.
doi:10.1186/s12902-015-0041-2
PMCID: PMC4549893  PMID: 26307114
8.  On the interaction of speakers’ voice quality, ambient noise and task complexity with children’s listening comprehension and cognition 
Suboptimal listening conditions interfere with listeners’ on-line comprehension. A degraded source signal, noise that interferes with sound transmission, and/or listeners’ cognitive or linguistic limitations are examples of adverse listening conditions. Few studies have explored the interaction of these factors in pediatric populations. Yet, they represent an increasing challenge in educational settings. We will in the following report on our research and address the effect of adverse listening conditions pertaining to speakers’ voices, background noise, and children’s cognitive capacity on listening comprehension. Results from our studies clearly indicate that children risk underachieving both in formal assessments and in noisy class-rooms when an examiner or teacher speaks with a hoarse (dysphonic) voice. This seems particularly true when task complexity is low or when a child is approaching her/his limits of mastering a comprehension task.
doi:10.3389/fpsyg.2015.00871
PMCID: PMC4478373  PMID: 26157416
comprehension; voice; noise; cognition; children
9.  Role of the PhoP–PhoQ gene regulatory system in adaptation of Yersinia pestis to environmental stress in the flea digestive tract 
Microbiology  2015;161(Pt 6):1198-1210.
The Yersinia pestis PhoPQ gene regulatory system is induced during infection of the flea digestive tract and is required to produce adherent biofilm in the foregut, which greatly enhances bacterial transmission during a flea bite. To understand the in vivo context of PhoPQ induction and to determine PhoP-regulated targets in the flea, we undertook whole-genome comparative transcriptional profiling of Y. pestis WT and ΔphoP strains isolated from infected fleas and from temperature-matched in vitro planktonic and flow-cell biofilm cultures. In the absence of PhoP regulation, the gene expression program indicated that the bacteria experienced diverse physiological stresses and were in a metabolically less active state. Multiple stress response genes, including several toxin–antitoxin loci and YhcN family genes responsible for increased acid tolerance, were upregulated in the phoP mutant during flea infection. The data implied that PhoPQ was induced by low pH in the flea gut, and that PhoP modulated physiological adaptation to acid and other stresses encountered during infection of the flea. This adaptive response, together with PhoP-dependent modification of the bacterial outer surface that includes repression of pH 6 antigen fimbriae, supports stable biofilm development in the flea foregut.
doi:10.1099/mic.0.000082
PMCID: PMC4635514  PMID: 25804213
10.  Categories of foot at risk in patients of diabetes at a tertiary care center: Insights into need for foot care 
Objective:
Diabetic foot ulcers and amputations are preventable. Aim of this study was to determine the distribution of categories of foot at risk in patients with diabetes, attending a tertiary care hospital and factors that affect it.
Materials and Methods:
Detail history and examination including neurological and vascular assessment were performed in 100 patients with diabetes attending a Tertiary Care Hospital. Foot at risk was classified according to the task force of foot care interest Group of American Diabetes Association. Category of foot at risk was correlated with demographic and clinical features.
Results:
Fifty-two percent patients had foot at risk-category 1 and 2. Loss of protective sensation (LOPS) was present in 33% (category 1). Peripheral arterial disease (PAD) was present in 19% (category 2). Both LOPS and PAD were present in 10% patients. 95% had never received foot care advice by health professionals, let alone prescriptive footwear or vascular consultation.
Conclusions:
This study brings forth that foot at risk of ulcer is rampant in patients with diabetes. There are lacunae in diabetic foot care at all levels of care. With the increase in diabetes, cost effective steps are required to improve foot care among diabetes in India. Considering the demographic profile of patients in our study, growing number of patients with diabetes, lack of time and staff allocated for foot care in our setup, audiovisual aids seems a good option to spread foot care awareness among diabetes.
doi:10.4103/2230-8210.152789
PMCID: PMC4366782  PMID: 25932399
Diabetic foot; foot at risk; loss of protective sensation
11.  Impact of a novel 14 bp MEN1 deletion in a patient with hyperparathyroidism and gastrinoma 
Summary
Multiple endocrine neoplasia type 1 (MEN-1) is a rare autosomal-dominant disease characterized by tumors in endocrine and/or non endocrine organs due to mutations in MEN1 encoding a nuclear scaffold protein‘menin’ involved in regulation of different cellular activities. We report a novel 14 bp MEN1 deletion mutation in a 35-year-old female with history of recurrent epigastric pain, vomiting, loose stools and weight loss. On evaluation she was diagnosed to have multifocal gastro-duodenal gastrinoma with paraduodenal lymph nodes and solitary liver metastasis. She was also found to have primary hyperparathyroidism with bilateral inferior parathyroid adenoma. Pancreatico-duodenectomy with truncalvagotomy was performed. Four months later, radiofrequency ablation (RFA) of segment 4 of the liver was done followed by three and a half parathyroidectomy. MEN1 screening was carried out for the patient and her family members. MEN-1 sequencing in the patient revealed a heterozygous 14 bp exon 8 deletion. Evaluation for pathogenicity and protein structure prediction showed that the mutation led to a frameshift thereby causing premature termination resulting in a truncated protein. To conclude, a novel pathogenic MEN1 deletion mutation affecting its function was identified in a patient with hyperparathyroidism and gastrinoma. The report highlights the clinical consequences of the novel mutation and its impact on the structure and function of the protein. It also provides evidence for co-existence of pancreatic and duodenal gastrinomas in MEN1 syndrome. MEN1 testing provides important clues regarding etiology and therefore should be essentially undertaken in asymptomatic first degree relatives who could be potential carriers of the disease.
Learning points
Identification of a novel pathogenic MEN1 deletion mutation. MEN1 mutation screening in patients with pituitary, parathyroid and pancreatic tumors, and their first degree relatives gives important clues about the etiology.Pancreatic and duodenal gastrinomas may co-exist simultaneously in MEN1 syndrome.
doi:10.1530/EDM-15-0011
PMCID: PMC4482156  PMID: 26191410
12.  Psychotropic drug use in adolescents born with an orofacial cleft: a population-based study 
BMJ Open  2015;5(4):e005306.
Objectives
Being born with an orofacial cleft (OFC) can, due to an incomplete closure of the lip and/or palate, convey a deviant speech and/or deviant facial aesthetics, which may in turn increase the risk for poor psychological health later in life. Previous investigations have been based on small samples and self-reports, not distinguishing between the three different types of OFC: cleft lip (CL), CL and palate (CLP) and cleft palate only (CPO). We present a large population-based study, considering psychotropic drug use as a proxy for poor psychological health and distinguishing between three different types of OFC.
Design and methods
Using the Swedish Medical Birth Register, and linking to it the Swedish Prescribed Drug Register, the National Mortality Register, the Emigration Register and the National Inpatient Register, we identified all singletons born to native mothers in Sweden between 1987 and 1993, alive and residing in Sweden at the end of an 18-year follow-up period (N=626 109). We compared psychotropic drug use among individuals with and without OFC during the individuals’ adolescence (2005–2008) by multiple logistic regressions, using ORs with 95% CIs.
Results
When adjusted for potential confounders, having a CL (OR=1.63, 95% CI 1.08 to 2.46) or a CPO (OR=1.54, 95% CI 1.18 to 2.01) increased the risk of psychotropic drug use. Results were not significant regarding adolescents who had a CLP (OR=1.21, 95% CI 0.81 to 1.80).
Conclusions
Being born with a CL or a CPO increases the risk for psychotropic drug use in adolescence, but not for adolescents born with a CLP. Our findings suggest that, since the three OFC types are associated with different long-term risks of poor psychological health, the three groups should be studied separately concerning long-term psychosocial consequences.
doi:10.1136/bmjopen-2014-005306
PMCID: PMC4390737  PMID: 25838502
EPIDEMIOLOGY; MENTAL HEALTH; PAEDIATRICS; ORAL & MAXILLOFACIAL SURGERY
14.  Multiple Synchronous Verrucous Carcinomas of the Scalp in the Background of Generalized Verruca Vulgaris 
Indian Journal of Dermatology  2015;60(2):182-184.
Verrucous carcinoma (VC) is a clinicopathologic entity which is defined as a locally aggressive, clinically exophytic, slow-growing, well-differentiated, squamous cell carcinoma with negligible metastatic potential. The cutaneous form of VC is typically known to arise from the palmoplantar and the genitocrural areas. Involvement of the scalp is extremely rare. Multiple synchronous involvement of the scalp by VC along with associated generalized verruca vulgaris has possibly never been reported before. We present this unique report of VC in a 38-year-old male patient with emphasis on its atypical clinical presentation and the resultant challenges in management. Interestingly, the tumor cells of our patient were confirmed to be positive for human papillomavirus infection by polymerase chain reaction and by p16 immunohistochemistry.
doi:10.4103/0019-5154.152524
PMCID: PMC4372913  PMID: 25814709
Human papillomavirus; scalp tumors; verrucous carcinoma
15.  Histomorphometric effects of gemcitabine on Swiss albino mice spermatogenesis 
Background:
Spermatogenesis is a highly conserved and regulated process and it is sensitive to fluctuations in the physical and chemical environment. Gemcitabine is a novel antimetabolic anticancer drug used frequently in the treatment of many cancers. This study aimed to investigate the histomorphometric effects of gemcitabine on spermatogenesis in Swiss albino mice.
Materials and Methods:
Gemcitabine in high and low doses (80 and 40 mg/kg) injected intraperitoneally to inbred Swiss albino mice. Gross testicular features and seminiferous tubular histomorphometry was studies at the end of 7th, 14th day and at 2 months sperm shape abnormalities were studied.
Results:
Seminiferous tubular morphology was altered significantly, showing a reduction in height, perimeter and area in a dose dependent manner. Sertoli cell number decreased. Basement membrane thickness was reduced and it appeared to be permanent, with statistically insignificant changes even after 2 months. There was a reduction of intertubular spaces. Sperms have shown banana heading, decapitation and loss of normal hook of head. The effects were partially reversible at the end of 2 months.
Conclusion:
It was concluded that gemcitabine affects the process of spermatogenesis adversely in a dose and time dependent manner and the effects are partially reversible.
doi:10.4103/2277-9175.150423
PMCID: PMC4333483  PMID: 25709994
Gemcitabine; seminiferous tubules; Sertoli cells; spermatogenesis; Swiss albino mice
16.  Integrative analysis of T cell motility from multi-channel microscopy data using TIAM 
Integrative analytical approaches are needed to study and understand T cell motility as it is a highly coordinated and complex process. Several computational algorithms and tools are available to track motile cells in time-lapse microscopy images. In contrast, there has only been limited effort towards the development of tools that take advantage of multi-channel microscopy data and facilitate integrative analysis of cell-motility. We have implemented algorithms for detecting, tracking, and analyzing cell motility from multi-channel time-lapse microscopy data. We have integrated these into a MATLAB-based toolset we call TIAM (Tool for Integrative Analysis of Motility). The cells are detected by a hybrid approach involving edge detection and Hough transforms from transmitted light images. Cells are tracked using a modified nearest-neighbor association followed by an optimization routine to join shorter segments. Cell positions are used to perform local segmentation for extracting features from transmitted light, reflection and fluorescence channels and associating them with cells and cell-tracks to facilitate integrative analysis. We found that TIAM accurately captures the motility behavior of T cells and performed better than DYNAMIK, Icy, Imaris, and Volocity in detecting and tracking motile T cells. Extraction of cell-associated features from reflection and fluorescence channels was also accurate with less than 10% median error in measurements. Finally, we obtained novel insights into T cell motility that were critically dependent on the unique capabilities of TIAM. We found that 1) the CD45RO subset of human CD8 T cells moved faster and exhibited an increased propensity to attach to the substratum during CCL21-driven chemokinesis when compared to the CD45RA subset; and 2) attachment area and arrest coefficient during antigen-induced motility of the CD45A subset is correlated with surface density of integrin LFA1 at the contact.
doi:10.1016/j.jim.2014.11.004
PMCID: PMC4323926  PMID: 25445324
T cell motility; Tracking; Integrative analysis; Multi-channel microscopy
17.  Prediabetes and type 2 diabetes mellitus: Evidence for effect of yoga 
doi:10.4103/2230-8210.141318
PMCID: PMC4192976  PMID: 25364666
18.  Linear nevus sebaceous syndrome 
doi:10.4103/0972-2327.144042
PMCID: PMC4251029  PMID: 25506177
19.  Analysis of Patterns and Treatment Strategies for Mandibular Condyle Fractures: Review of 175 Condyle Fractures with Review of Literature 
This study aims to evaluate incidence, patterns and epidemiology of mandibular condylar fractures (MCF) to propose a treatment strategy for managing MCF and analyze the factors which influence the outcome. One hundred and seventy-five MCF’s were evaluated over a four year period and their pattern was recorded in terms of displacement, level of fracture, age of incidence and dental occlusion. Of the 2,718 facial bone fractures, MCF incidence was the third most common at 18.39 %. Of 175 MCF 58.8 % were unilateral and 41.12 % were bilateral. 67 % of bilateral fractures and 43.8 % of unilateral fractures were associated with midline symphysis and contralateral parasymphysis fractures respectively. Most of the MCF was seen in the age group of above 16 years and 50 % of them were at subcondylar level (below the neck of the condyle). Majority of MCF sustained due to inter personal violence were undisplaced (72.7 %) and contrary to this majority of MCF sustained during road traffic accident were displaced. 62.9 % of total fractures required open reduction and rigid fixation and 37.1 % were managed with closed reduction. 80 % of MCF managed with closed reduction were in the age group of below 16 years. From this study it can be concluded that the treatment algorithm proposed for managing MCF is reliable and easy to adopt. We observed that absolute indication for open reduction of MCF is inability to achieve satisfactory occlusion by closed method and absolute contraindication for open reduction is condylar head fracture irrespective of the age of the patient.
Electronic supplementary material
The online version of this article (doi:10.1007/s12663-012-0428-9) contains supplementary material, which is available to authorized users.
doi:10.1007/s12663-012-0428-9
PMCID: PMC3777042  PMID: 24431859
Mandibular condyle fractures; Temporomandibular joint; Dental occlusion; Age distribution of fractures; Treatment algorithm
20.  Acanthosis nigricans in insulinoma 
doi:10.4103/2230-8210.139223
PMCID: PMC4171903  PMID: 25285297
21.  A Preliminary Model of Gastrointestinal Electromechanical Coupling 
Motility in much of the gastrointestinal (GI) tract is coordinated by an electrical event known as slow waves, and several GI motility disorders are associated with slow wave arrhythmias. The GI smooth muscle cells (SMC) generate contraction, but slow waves are actively regenerated by specialized pacemaker cells called the interstitial cells of Cajal (ICC), which are coupled to the SMC. This unique electrical coupling presents an added layer of complexity to GI electromechanical models, and a major current barrier to further progress is the lack of a framework for ICC-SMC-contraction coupling. In this study, an initial framework for the electromechanical coupling was developed in a 2D model. At each solution step, the slow wave propagation was solved first and the intracellular calcium concentration in the SMC model was related to an adapted tension-extension-calcium relationship to simulate active contraction. With identification of more GI-specific constitutive laws, the ICC-SMC-contraction approach will underpin future GI electromechanical models of health and disease states.
doi:10.1109/TBME.2011.2166155
PMCID: PMC4129377  PMID: 21878406
bidomain; ICC; SMC; slow waves; motility
22.  Mechanisms of Glioma Formation: Iterative Perivascular Glioma Growth and Invasion Leads to Tumor Progression, VEGF-Independent Vascularization, and Resistance to Antiangiogenic Therapy12 
Neoplasia (New York, N.Y.)  2014;16(7):543-561.
As glioma cells infiltrate the brain they become associated with various microanatomic brain structures such as blood vessels, white matter tracts, and brain parenchyma. How these distinct invasion patterns coordinate tumor growth and influence clinical outcomes remain poorly understood. We have investigated how perivascular growth affects glioma growth patterning and response to antiangiogenic therapy within the highly vascularized brain. Orthotopically implanted rodent and human glioma cells are shown to commonly invade and proliferate within brain perivascular space. This form of brain tumor growth and invasion is also shown to characterize de novo generated endogenous mouse brain tumors, biopsies of primary human glioblastoma (GBM), and peripheral cancer metastasis to the human brain. Perivascularly invading brain tumors become vascularized by normal brain microvessels as individual glioma cells use perivascular space as a conduit for tumor invasion. Agent-based computational modeling recapitulated biological perivascular glioma growth without the need for neoangiogenesis. We tested the requirement for neoangiogenesis in perivascular glioma by treating animals with angiogenesis inhibitors bevacizumab and DC101. These inhibitors induced the expected vessel normalization, yet failed to reduce tumor growth or improve survival of mice bearing orthotopic or endogenous gliomas while exacerbating brain tumor invasion. Our results provide compelling experimental evidence in support of the recently described failure of clinically used antiangiogenics to extend the overall survival of human GBM patients.
doi:10.1016/j.neo.2014.06.003
PMCID: PMC4198934  PMID: 25117977
23.  Prevalence of ancylostomiasis in people living in slum area, Philhousepet of Eluru, West Godavari District (Andhra Pradesh) 
Hookworm infection was found in the slum area of Eluru, West Godavari District, A.P. which has scheduled caste population. Infection is related to different climatic conditions and socio-economic status of the population. The inhabitants are coolies in agricultural fields and household workers with a poor level of hygiene and sanitation. All the infected positive cases showed Ancylostoma duodenale infection. The prevalence of hookworm infection was 15.6, 17.9 and 14 % in children, 23.5, 27.9 and 20.5 % in adults during summer, rainy and winter seasons respectively. Single species infection was studied in three periods. Out of 264 faecal samples, 128 children (40 males, 32.5 %) and 136 adults (64 men, 25 % and 72 women, 30.5 %) showed helminthic infection in rainy season. Much variation is seen in the prevalence of disease in rainy and winter seasons in all the age groups. The infected individuals were treated with albendazole just after rainy season. Three weeks after antihelminthic treatment, the infection rate among them was lowered; health education also plays a role in reducing the % of infection.
doi:10.1007/s12639-012-0125-0
PMCID: PMC3590392  PMID: 24431537
Hookworm infection; Philhousepet; Eluru
24.  Transcriptional insights into the CD8+ T cell response to infection and memory T cell formation 
Nature immunology  2013;14(4):404-412.
After infection, many factors coordinate the population expansion and differentiation of CD8+ effector and memory T cells. Using data of unparalleled breadth from the Immunological Genome Project, we analyzed the CD8+ T cell transcriptome throughout infection to establish gene-expression signatures and identify putative transcriptional regulators. Notably, we found that the expression of key gene signatures can be used to predict the memory-precursor potential of CD8+ effector cells. Long-lived memory CD8+ cells ultimately expressed a small subset of genes shared by natural killer T and γδ T cells. Although distinct inflammatory milieu and T cell precursor frequencies influenced the differentiation of CD8+ effector and memory populations, core transcriptional signatures were regulated similarly, whether polyclonal or transgenic, and whether responding to bacterial or viral model pathogens. Our results provide insights into the transcriptional regulation that influence memory formation and CD8+ T cell immunity.
doi:10.1038/ni.2536
PMCID: PMC3689652  PMID: 23396170

Results 1-25 (71)