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1.  Apoptosis Induction of Centella Asiatica on Human Breast Cancer Cells 
The present study evaluated the ability of methanolic extract of Centella asiatica (Linn) Urban (Umbelliferae) to induce apoptosis in different cancer cell lines. MCF-7 cells emerged as the most sensitive cell line for in vitro growth inhibitory activity. C. asiatica extract induced apoptosis in MCF-7 cells as indicated by nuclear condensation, increased annexin staining, loss of mitochondrial membrane potential and induction of DNA breaks identified by TUNEL reactivity. It is possible that the use of C. asiatica extract as a component in herbal medicines could be justifiable.
PMCID: PMC2816528  PMID: 20162036
Apoptosis; Cancer; Centella asiatica
2.  Shedding Light on Protein Folding Landscapes by Single-molecule Fluorescence 
Chemical Society reviews  2014;43(4):1172-1188.
Single-molecule (SM) fluorescence methods have been increasingly instrumental in our current understanding of a number of key aspects of protein folding and aggregation landscapes over the past decade. With the advantage of a model free approach and the power of probing multiple subpopulations and stochastic dynamics directly in a heterogeneous structural ensemble, SM methods have emerged as a principle technique for studying complex systems such as intrinsically disordered proteins (IDPs), globular proteins in the unfolded basin and during folding, and early steps of protein aggregation in amyloidogenesis. This review highlights the application of these methods in investigating the free energy landscapes, folding properties and dynamics of individual protein molecules and their complexes, with an emphasis on inherently flexible systems such as IDPs.
doi:10.1039/c3cs60311c
PMCID: PMC3958939  PMID: 24336839
3.  A rare case of small bowel obstruction secondary to ovarian torsion in an IVF pregnancy 
BMJ Case Reports  2013;2013:bcr2013008551.
A 39- year-old woman, who conceived following in vitro fertilisation (IVF) treatment, presented at 12 weeks gestation with symptoms of ovarian hyperstimulation syndrome (OHSS), abdominal pain, vomiting and diarrhoea. Subsequent investigations found small bowel obstruction  secondary to ovarian torsion. Surgical management to remove a necrotic ovary and fallopian tube led to a good recovery from the acute illness. A postoperative ultrasound scan confirmed a viable pregnancy and the patient was discharged. Her case demonstrates a rare complication of OHSS and ovarian torsion leading to small bowel obstruction.
doi:10.1136/bcr-2013-008551
PMCID: PMC3603835  PMID: 23417952
4.  Amino Acid Profile in Oral Submucous Fibrosis: A High Performance Liquid Chromatography (HPLC) Study 
Background: Collagen is a significant structural protein, the integrity of which is essential to be maintained for proper homeostasis. Oral submucous fibrosis (OSMF), being a collagen metabolic disorder, may be subject to changes in amino acid profiling.
Aim: The present study was attempted to evaluate the amino acid profile to assess its feasibility as a biological marker in OSMF.
Materials and Methods: The study group comprised of 13 patents with OSMF and the normal group comprised of 13 normal patients without associated habits or systemic disorders. Venous blood was collected from the antecubital vein, plasma was separated and the plasma was then subjected to high profile liquid chromatographic analysis.
Results: The assay levels of threonine, alanine and tyrosine did not yield any significant results. The decreased assay levels of valine, Isoleucine and the increased assay level of methionine and glycine observed in group II yielded significant results in correlation with the control group. The decreased assay level seen in phenylalanine in group II and III in correlation with group IV is statistically significant.
Conclusion: A few amino acids have been identified which can be used as biological markers for the severity of the disease such as valine, methionine and phenyl alanine. Large scale studies are required to elucidate the potential of these biological markers.
doi:10.7860/JCDR/2014/10201.5290
PMCID: PMC4316336  PMID: 25654030
Amino acids; Collagen; OSMF; Plasma
5.  “Dentinal Microcracks After Root Canal Preparation” A Comparative Evaluation with Hand, Rotary and Reciprocating Instrumentation 
Introduction: The purpose of this study was to compare the incidence of dentinal micro cracks after instrumentation with various types of NiTi files in rotary and reciprocating motion.
Materials and Methods: One hundred human extracted mandibular central incisors were taken and divided into 10 groups (n=10 teeth per group). Group 1- No preparation, Group 2 – Hand instrumentation, Groups 3,4 - ProTaper files in rotary and reciprocating motion, Groups 5,6 - ProTaper Next files in rotary and reciprocating motion, Groups 7,8 – Oneshape files in rotary and reciprocating motion, Groups 9,10 – Reciproc files in rotary and reciprocating motion. Specimens were sectioned horizontally at 3,6 and 9 mm from the apex and dentinal micro cracks were observed under a stereomicroscope.
Results: There was a statistically significant difference between the groups (p<0.05). There were no significant differences in crack formation between the groups (Protaper Next - Rot, Protaper Next - Rec, Reciproc – Rec); (ProTaper - Rot, ProTaper - Rec, Oneshape – Rot), (Oneshape – Rot, Reciproc – Rot), (One shape Reciproc, Reciproc – Rec); (p >.05).
Conclusion: Least cracks were seen in canals instrumented with Pro Taper Next files both in rotary and reciprocating motion. Full sequence rotary systems showed less cracks than single file systems and full sequence rotary systems showed less cracks in reciprocating motion than in rotary motion.
doi:10.7860/JCDR/2014/11437.5349
PMCID: PMC4316342  PMID: 25654036
Dentinal defects; Full sequence rotary systems; Nickel titanium; Reciprocating; Single file systems
6.  Auxiliary proteins promote modal gating of AMPA- and kainate-type glutamate receptors 
The European journal of neuroscience  2014;39(7):1138-1147.
The gating behavior of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors is modulated by association with the auxiliary proteins: transmembrane AMPA receptor regulatory proteins (TARPs) and neuropilin tolloid-like (Netos), respectively. Although the mechanisms underlying receptor modulation differ for both AMPA and kainate receptors, association with these auxiliary subunits results in the appearance of a slow component in the decay of ensemble responses to rapid applications of saturating concentrations of glutamate. We show here that these components arise from distinct gating behaviors, characterized by substantially higher open probability (Popen), which we only observe when core subunits are associated with their respective auxiliary partners. We refer to these behaviors as gating modes, because individual receptors switch between the low- and high-Popen gating on a time-scale of seconds. At any given time, association of AMPA and kainate receptors with their auxiliary subunits results in a heterogeneous receptor population, some of which are in the high-Popen mode and others that display gating behavior similar to that seen for receptors formed from core subunits alone. While the switching between modes is infre quent, the presence of receptors displaying both types of gating has a large impact on both the kinetics and amplitude of ensem ble currents similar to those seen at synapses.
doi:10.1111/ejn.12519
PMCID: PMC4311398  PMID: 24712993
glutamate; kinetics; modulation; Neto2; TARPs
7.  Depression is not associated with diabetes control in minority elderly 
Aims
We investigated the longitudinal association of depression, with and without cognitive dysfunction, with hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and low-density lipoprotein (LDL) in a predominantly minority cohort.
Methods
There were 613 participants. Presence of depression was defined by a score ≥ 7 on the Short-CARE depression scale. We tested participants for executive dysfunction using the Color Trails Test (CTT), part 2, and for memory dysfunction using the total recall task of the Selective Reminding Test (TR-SRT). We classified performance in these tests as abnormal based on standardized score cutoffs (<16th percentile and one standard deviation below the sample mean). Random effects models were used to compare repeated measures of the diabetes control measures between those with depression versus those without depression and ever versus never cognitively impaired.
Results
Baseline depression was present in 36% of participants. Over a median follow-up of 2 years, depression was not related to worse HbA1c, SBP, or LDL. The presence of (1) abnormal performance on a test of executive function and depression (n = 57) or (2) abnormal performance on a test of verbal recall and depression (n = 43) was also not associated with clinically significant worse change in diabetes control.
Conclusions
Depression, with or without low performance in tests of executive function and memory, may not affect clinically significant measures of diabetes control in the elderly.
doi:10.1016/j.jdiacomp.2014.06.014
PMCID: PMC4310458  PMID: 25156987
Diabetes; Depression; Diabetes control; Cognitive dysfunction; Older adults
8.  Admixture Analysis of Spontaneous Hepatitis C Virus Clearance in Individuals of African-Descent 
Genes and immunity  2014;15(4):241-246.
Hepatitis C virus (HCV) infects an estimated 3% of the global population with the majority of individuals (75–85%) failing to clear the virus without treatment, leading to chronic liver disease. Individuals of African-descent have lower rates of clearance compared to individuals of European-descent and this is not fully explained by social and environmental factors. This suggests that differences in genetic background may contribute to this difference in clinical outcome following HCV infection. Using 473 individuals and 792,721 SNPs from a genome-wide association study (GWAS), we estimated local African ancestry across the genome. Using admixture mapping and logistic regression we identified two regions of interest associated with spontaneous clearance of HCV (15q24, 20p12). A genome-wide significant variant was identified on chromosome 15 at the imputed SNP, rs55817928 (P=6.18×10−8) between the genes SCAPER and RCN. Each additional copy of the African ancestral C allele is associated with 2.4 times the odds of spontaneous clearance. Conditional analysis using this SNP in the logistic regression model explained one-third of the local ancestry association. Additionally, signals of selection in this area suggest positive selection due to some ancestral pathogen or environmental pressure in African, but not in European populations.
doi:10.1038/gene.2014.11
PMCID: PMC4308959  PMID: 24622687
Hepatitis C; Chronic Infection; Admixture; African Ancestry
9.  Hippocampal structure and human cognition: key role of spatial processing and evidence supporting the efficiency hypothesis in females 
Intelligence  2013;41(2):129-140.
Here we apply a method for automated segmentation of the hippocampus in 3D high-resolution structural brain MRI scans. One hundred and four healthy young adults completed twenty one tasks measuring abstract, verbal, and spatial intelligence, along with working memory, executive control, attention, and processing speed. After permutation tests corrected for multiple comparisons across vertices (p < .05) significant relationships were found for spatial intelligence, spatial working memory, and spatial executive control. Interactions with sex revealed significant relationships with the general factor of intelligence (g), along with abstract and spatial intelligence. These correlations were mainly positive for males but negative for females, which might support the efficiency hypothesis in women. Verbal intelligence, attention, and processing speed were not related to hippocampal structural differences.
doi:10.1016/j.intell.2013.01.002
PMCID: PMC4306583  PMID: 25632167
Hippocampus; Intelligence; Working memory; Executive control; Attention; Processing speed; Sex differences
10.  High-resolution genetic mapping of allelic variants associated with cell wall chemistry in Populus 
BMC Genomics  2015;16(1):24.
Background
QTL cloning for the discovery of genes underlying polygenic traits has historically been cumbersome in long-lived perennial plants like Populus. Linkage disequilibrium-based association mapping has been proposed as a cloning tool, and recent advances in high-throughput genotyping and whole-genome resequencing enable marker saturation to levels sufficient for association mapping with no a priori candidate gene selection. Here, multiyear and multienvironment evaluation of cell wall phenotypes was conducted in an interspecific P. trichocarpa x P. deltoides pseudo-backcross mapping pedigree and two partially overlapping populations of unrelated P. trichocarpa genotypes using pyrolysis molecular beam mass spectrometry, saccharification, and/ or traditional wet chemistry. QTL mapping was conducted using a high-density genetic map with 3,568 SNP markers. As a fine-mapping approach, chromosome-wide association mapping targeting a QTL hot-spot on linkage group XIV was performed in the two P. trichocarpa populations. Both populations were genotyped using the 34 K Populus Infinium SNP array and whole-genome resequencing of one of the populations facilitated marker-saturation of candidate intervals for gene identification.
Results
Five QTLs ranging in size from 0.6 to 1.8 Mb were mapped on linkage group XIV for lignin content, syringyl to guaiacyl (S/G) ratio, 5- and 6-carbon sugars using the mapping pedigree. Six candidate loci exhibiting significant associations with phenotypes were identified within QTL intervals. These associations were reproducible across multiple environments, two independent genotyping platforms, and different plant growth stages. cDNA sequencing for allelic variants of three of the six loci identified polymorphisms leading to variable length poly glutamine (PolyQ) stretch in a transcription factor annotated as an ANGUSTIFOLIA C-terminus Binding Protein (CtBP) and premature stop codons in a KANADI transcription factor as well as a protein kinase. Results from protoplast transient expression assays suggested that each of the polymorphisms conferred allelic differences in the activation of cellulose, hemicelluloses, and lignin pathway marker genes.
Conclusion
This study illustrates the utility of complementary QTL and association mapping as tools for gene discovery with no a priori candidate gene selection. This proof of concept in a perennial organism opens up opportunities for discovery of novel genetic determinants of economically important but complex traits in plants.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1215-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s12864-015-1215-z
PMCID: PMC4307895  PMID: 25613058
QTL cloning; Association genetics; Cell wall recalcitrance; Lignin; Cellulose; Hemicellulose
11.  Respiratory Syncytial Virus Increases the Virulence of Streptococcus pneumoniae by Binding to Penicillin Binding Protein 1a. A New Paradigm in Respiratory Infection 
Rationale: Respiratory syncytial virus (RSV) and Streptococcus pneumoniae are major respiratory pathogens. Coinfection with RSV and S. pneumoniae is associated with severe and often fatal pneumonia but the molecular basis for this remains unclear.
Objectives: To determine if interaction between RSV and pneumococci enhances pneumococcal virulence.
Methods: We used confocal microscopy and Western blot to identify the receptors involved in direct binding of RSV and pneumococci, the effects of which were studied in both in vivo and in vitro models of infection. Human ciliated respiratory epithelial cell cultures were infected with RSV for 72 hours and then challenged with pneumococci. Pneumococci were collected after 2 hours exposure and changes in gene expression determined using quantitative real-time polymerase chain reaction.
Measurements and Main Results: Following incubation with RSV or purified G protein, pneumococci demonstrated a significant increase in the inflammatory response and bacterial adherence to human ciliated epithelial cultures and markedly increased virulence in a pneumonia model in mice. This was associated with extensive changes in the pneumococcal transcriptome and significant up-regulation in the expression of key pneumococcal virulence genes, including the gene for the pneumococcal toxin, pneumolysin. We show that mechanistically this is caused by RSV G glycoprotein binding penicillin binding protein 1a.
Conclusions: The direct interaction between a respiratory virus protein and the pneumococcus resulting in increased bacterial virulence and worsening disease outcome is a new paradigm in respiratory infection.
doi:10.1164/rccm.201311-2110OC
PMCID: PMC4226051  PMID: 24941423
respiratory syncytial virus; pneumococcus; cilia; virulence; G protein
12.  Mild Cognitive Dysfunction Does Not Affect Diabetes Mellitus Control in Minority Elderly Adults 
OBJECTIVES
To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction.
DESIGN
Prospective cohort study.
SETTING
A minority cohort in New York City previously recruited for a trial of telemedicine.
PARTICIPANTS
Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black).
MEASUREMENTS
Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction.
RESULTS
Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction.
CONCLUSION
Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control.
doi:10.1111/jgs.13129
PMCID: PMC4288580  PMID: 25439094
cognition; diabetes mellitus; control; elderly
13.  Shape analysis of the corpus callosum in Alzheimer’s disease and frontotemporal lobar degeneration subtypes 
Morphology of the corpus callosum is a useful biomarker of neuronal loss, as different patterns of cortical atrophy help to distinguish between dementias such as Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD).
We used a sophisticated morphometric analysis of the corpus callosum in FTLD subtypes including frontotemporal dementia (FTD) semantic dementia (SD), and progressive non-fluent aphasia (PNFA), and compared them to AD patients and 27 matched controls.
FTLD patient subgroups diverged in their callosal morphology profiles, with: FTD patients showing marked widespread differences, PNFA patients with differences largely in the anterior half of the callosum, and SD patients differences in a small segment of the genu. AD patients showed differences in predominantly posterior callosal regions.
This study is consistent with our previous findings showing significant cortical and subcortical regional atrophy across FTLD subtypes, and suggests that callosal atrophy patterns differentiate AD from FTLD, and FTLD subtypes.
doi:10.3233/JAD-131853
PMCID: PMC4288754  PMID: 24531157
Frontotemporal dementia; Alzheimer’s disease; neuroimaging; morphometry; corpus callosum; white matter; atrophy; magnetic resonance imaging
14.  In vivo thermal ablation monitoring using ultrasound echo decorrelation imaging 
Ultrasound in medicine & biology  2013;40(1):10.1016/j.ultrasmedbio.2013.09.007.
Previous work has shown ultrasound echo decorrelation imaging can track and quantify changes in echo signals to predict thermal damage during in vitro radiofrequency ablation (RFA). In the in vivo studies reported here, the feasibility of using echo decorrelation imaging as a treatment monitoring tool is assessed. RFA was performed on a normal swine liver (N = 5) and ultrasound ablation using image-ablate arrays was performed on a rabbit liver implanted with VX2 tumors (N = 2). Echo decorrelation and integrated backscatter were computed from Hilbert transformed pulse-echo data acquired during RFA and ultrasound ablation treatments. Receiver operating characteristic (ROC) curves were employed to assess the ability of echo decorrelation imaging and integrated backscatter to predict ablation. Area under the ROC curves (AUROC) was determined for RFA and ultrasound ablation using echo decorrelation imaging. Ablation was predicted more accurately using echo decorrelation imaging (AUROC 0.832 and 0.776 for RFA and ultrasound ablation respectively) than using integrated backscatter (AUROC 0.734 and 0.494).
doi:10.1016/j.ultrasmedbio.2013.09.007
PMCID: PMC3849110  PMID: 24239361
Echo decorrelation imaging; therapy monitoring; bulk ultrasound ablation; radiofrequency ablation
15.  Noninvasive assessment of alveolar microvascular recruitment in conscious nonsedated rats 
Respiratory physiology & neurobiology  2013;190:10.1016/j.resp.2013.09.010.
Recruitment of alveolar microvascular reserves, assessed from the relationship between pulmonary diffusing capacity (DLCO) and perfusion (Q̇c), is critical to maintenance of arterial blood oxygenation. Leptin-resistant ZDF fatty diabetic (fa/fa) rats exhibit restricted cardiopulmonary physiology under anesthesia. To assess alveolar microvascular function in conscious, non-sedated, non-instrumented, and minimally restrained animals, we adapted a rebreathing technique to fa/fa and control non-diabetic (+/+) rats (4-5 and 7-11 mo old) at rest and mild spontaneous activity. Measurements included O2 uptake, lung volume, Q̇c, DLCO, membrane diffusing capacity (DMCO), capillary blood volume (Vc) and septal tissue-blood volume. In older fa/fa than +/+ animals, DLCO and DMCO at a given Q̇c were lower; Vc was reduced in proportion to Q̇c. Results demonstrate the consequences of alveolar microangiopathy in metabolic syndrome: lung volume restriction, reduced Q̇c, and elevated membrane resistance to diffusion. At a given Q̇c, DLCO is lower in rats and guinea pigs than dogs or humans, consistent with limited alveolar microvascular reserves in small animals.
doi:10.1016/j.resp.2013.09.010
PMCID: PMC3864700  PMID: 24100202
Lung diffusing capacity; pulmonary blood flow; obesity; type-2 diabetes mellitus; metabolic syndrome; alveolar microangiopathy
16.  Calcineurin inhibitors in HLA-identical living related donor kidney transplantation 
Background
Given the nephrotoxicity of calcineurin inhibitors (CNIs), we asked whether their addition improved living related donor (LRD) human leukocyte antigen (HLA) identical kidney transplant recipient outcomes.
Methods
We performed a comprehensive literature review and a single-center study comparing patient survival (PS) and graft survival (GS) of LRD HLA-identical kidney transplants for three different immunosuppression eras: Era 1 (up to 1984): anti-lymphocyte globulin (ALG) induction and maintenance immunosuppression with prednisone and azathioprine (AZA) (n = 114); Era 2a (1984–99): CNI added; evolution from ALG to thymoglobulin; AZA to mycophenolate (n = 262). Era 2b (1999–2011): rapid discontinuation of prednisone (thymoglobulin induction, CNI and mycophenolate) in recipients having first or second transplant and not previously on prednisone (n = 77).
Results
Demographics differed by era: recipient (P < 0.0001) and donor age (P < 0.0001) increased and the proportion of Caucasian donors (P = 0.02) and recipients (P = 0.003) decreased with each advancing era. There was no significant difference in PS (P = 0.6); cause of death (P = 0.5); death-censored GS (P = 0.8) or graft loss from acute rejection by era. Graft loss from chronic allograft nephropathy (P = 0.02) and hypertension (P = 0.005) were greater in the CNI eras. There were no significant differences in the 1/creatinine slopes between eras for the first (P = 0.6), second (P = 0.9) or >2 years post-transplant (P = 0.4). Literature review revealed no clear benefits for CNI in these human leukocyte antigen (HLA) identical LRD graft recipients.
Conclusions
This study confirmed that there are no benefits of CNIs for HLA-identical LRD recipients. Moreover, we did find evidence of potential harm. Thus, monotherapy or early discontinuation of CNI should be given consideration in these patients.
doi:10.1093/ndt/gft447
PMCID: PMC3888312  PMID: 24414376
calcineurin inhibitors; cyclosporine; HLA identical; renal transplant; tacrolimus
17.  Can Apneagraphy Change Our Approach in Management of Snoring and Sleep Apnoea? 
To evaluate role of overnight domiciliary apneagraph in diagnosing severity of sleep apnoea. Prospective audit of 37 patients with Epworth sleepiness score over ten and all patients with history of sleep apnoea presenting to ENT outpatient clinic investigated with apneagraph. Data analysed initially with pulse oximetry findings alone followed by analysis with full apneagraph findings. Results: Data analysed with pulse oximetry alone showed 31 patients to be simple snorers, but on analysis with apneagraph, 11 of these were shown to be suffering from moderate and one with severe sleep apnoea. There was no correlation between Epworth sleepiness score and severity of sleep apnoea. Conclusion: Management plan can be more evidence based by using apneagraph as a mini sleep study in investigating patients with history of obstructive sleep apnoea. Apneagraph could also be used in diagnosing the level of obstruction in snorers; however, this aspect needs further studying.
doi:10.1007/s12070-011-0344-1
PMCID: PMC3918317  PMID: 24533368
Apneagraph; Obstructive sleep apnoea; Snoring; Sleep study
18.  Extremes of Age Are Associated with Indeterminate QuantiFERON-TB Gold Assay Results 
Journal of Clinical Microbiology  2014;52(7):2694-2697.
Results from 3,263 QuantiFERON-TB Gold in-tube (QFT-GIT) assays were analyzed to determine the impact of age on test performance. The proportion of indeterminate results was significantly higher in pediatric and elderly (9.1% and 7.4%, respectively) than in adult (2.6%; chi-square test, P < 0.0001) patients. A detailed analysis of indeterminate QFT-GIT assay results is presented.
doi:10.1128/JCM.00814-14
PMCID: PMC4097686  PMID: 24829238
19.  Cost-Effectiveness of MODY Genetic Testing: Translating Genomic Advances Into Practical Health Applications 
Diabetes Care  2013;37(1):202-209.
OBJECTIVE
To evaluate the cost-effectiveness of a genetic testing policy for HNF1A-, HNF4A-, and GCK-MODY in a hypothetical cohort of type 2 diabetic patients 25–40 years old with a MODY prevalence of 2%.
RESEARCH DESIGN AND METHODS
We used a simulation model of type 2 diabetes complications based on UK Prospective Diabetes Study data, modified to account for the natural history of disease by genetic subtype to compare a policy of genetic testing at diabetes diagnosis versus a policy of no testing. Under the screening policy, successful sulfonylurea treatment of HNF1A-MODY and HNF4A-MODY was modeled to produce a glycosylated hemoglobin reduction of −1.5% compared with usual care. GCK-MODY received no therapy. Main outcome measures were costs and quality-adjusted life years (QALYs) based on lifetime risk of complications and treatments, expressed as the incremental cost-effectiveness ratio (ICER) (USD/QALY).
RESULTS
The testing policy yielded an average gain of 0.012 QALYs and resulted in an ICER of 205,000 USD. Sensitivity analysis showed that if the MODY prevalence was 6%, the ICER would be ∼50,000 USD. If MODY prevalence was >30%, the testing policy was cost saving. Reducing genetic testing costs to 700 USD also resulted in an ICER of ∼50,000 USD.
CONCLUSIONS
Our simulated model suggests that a policy of testing for MODY in selected populations is cost-effective for the U.S. based on contemporary ICER thresholds. Higher prevalence of MODY in the tested population or decreased testing costs would enhance cost-effectiveness. Our results make a compelling argument for routine coverage of genetic testing in patients with high clinical suspicion of MODY.
doi:10.2337/dc13-0410
PMCID: PMC3867988  PMID: 24026547
20.  Odontogenic Keratocyst: A Case Series of five Patients 
During the time period of August 2009 to August 2010, five cases of odontogenic keratocyst were admitted and treated under the care of Department of Otorhinolaryngology, MGMC and RI, Puducherry. Patients came to the ENT OPD with history of swelling in the cheek region, nasal obstruction, numbness in the upper alveolar region. On examination diffuse swelling of size 7 × 3 cm in one patient and size of 5 × 3 cm in two patients, and other two patients size of 6 × 3 cm present in the maxillary region with ill defined borders, the swelling was firm in consistency, no warmth, non tender. Anterior rhinoscopy reveals mass pushing the lateral wall medially, septum pushed to opposite side, mucopus present in nasal cavity, airway reduced on the side of swelling. On examination of oral cavity, a small granulation of size 1.0 × 0.5 cm present in two patient and swelling of size 1.5 × 1.0 cm seen in two patients in vestibule, no swelling in one patient and swelling of size 3 × 2 cm seen in hard palate of two patients and no swelling in three patients, no loosening of tooth seen in all patients. X-ray PNS reveals maxillary hazziness, diagnostic nasal endoscopy reveals lateral wall of nose pushed medially and septum pushed to opposite side. FNAC reveals resolving inflammatory aspirate in one patient, few macrophages seen in two of patients, few keratinocytes seen in two of the patients. CT nose and PNS revealed a large cystic lesion with erosion of anterior and medial wall and floor of maxilla in relation to the root of the last molar tooth in two patients and there is erosion of anterior and medial wall in other three patients. A combined endonasal and external sublabial (Caldwell-luc) approach was performed in four patients and the cystic lesion was removed and in other one patient only endonasal approach was done and cystic lesion was removed and sent for biopsy. Biopsy sent for HPE revealed odontogenic keratocyst.
doi:10.1007/s12070-012-0544-3
PMCID: PMC3938692  PMID: 24605295
Odontogenic cysts; Keratocyst; Tumours of mandible and maxilla
21.  MicroRNAs (miRNAs) as Biomarker(s) for Prognosis and Diagnosis of Gastrointestinal (GI) Cancers 
Current pharmaceutical design  2014;20(33):5287-5297.
Gastrointestinal (GI) cancers remain one of the most common malignancies and are the second common cause of cancer deaths worldwide. The limited effectiveness of therapy for patients with advanced stage and recurrent disease is a reflection of an incomplete understanding of the molecular basis of GI carcinogenesis. Major advancements have improved our understanding of pathology and pathogenesis of GI cancers, but high mortality rates, unfavorable prognosis and lack of clinical predictive biomarkers provide an impetus to investigate new sensitive and specific diagnostic and prognostic markers for GI cancers. MicroRNAs (miRNAs) are short (19–24 nucleotides) noncoding RNA molecules that regulate gene expression at the posttranscriptional level thus playing an important role in modulating various biological processes including, but not limited, to developmental processes, proliferation, apoptosis, metabolism, differentiation, epithelial-mechenchymal transition and are involved in the initiation and progression of various human cancers. Unique miRNA expression profiles have been observed in various cancer types at different stages, suggesting their potential as diagnostic and prognostic biomarkers. Due to their tumor-specific and tissue-specific expression profiles, stability, robust clinical assays for detection in serum as well as in formalin-fixed tissue samples, miRNAs have emerged as attractive candidates for diagnostic and prognostic applications. This review summarizes recent research supporting the utility of miRNAs as novel diagnostic and prognostic tools for GI cancers.
PMCID: PMC4113605  PMID: 24479799
Gastrointestinal cancers; Diagnosis; Prognosis; miRNAs
22.  Formulation and evaluation of clindamycin HCL in situ gel for vaginal application 
Objective:
The vagina has been studied as a favorable site for the local and systemic delivery of drugs, for female associated conditions. Vaginal preparations, although generally perceived as safer most still associated with number of problems including multiple days of dosing, dripping, leakage and messiness, causing discomfort to users and expulsion due to the self-cleansing action of the vaginal tract. These limitations lead to poor patient compliance and failure of the desired therapeutic effects. For efficient vaginal delivery of drugs, the delivery system should reside at the site of infection for a prolonged period of time. In situ gel formulation which combines advantages of both gels and solution so that an accurate dose can be administered with ease. These formulations remain in solution state before administration and transforms to gel after administration in to vaginal cavity.
Material and Methods:
In these formulations we prepared clindamycin loaded hydroxypropyl methycellulose (0.1%) (bioadhesive) and gellan gum (ion activated gelling polymer) based in situ gel system for vaginal application. NaCl (0.9%) was added as an isotonic agent. The developed formulation was characterized for various in vitro parameters such as clarity, refractive index, pH, viscosity, drug release profile, statistical release kinetics, bioadhesive force, and microbial efficacy along with stability studies. To simulate vaginal conditions, synthetic membrane (cellophane hydrated with modified simulated vaginal fluid) was used as model membranes.
Results and Discussion:
The developed formulation was found to be nonirritant, bioadhesive with good retention properties. Formulations have satisfactory appearance, clarity and drug content in the range 98.1-101%. Refractive index of the gel is ranging from 1.335 to 1.337, proofing the transparency of gel. Furthermore, formulation displayed 33.3% cumulative drug release after 2 h. 67.4% after 6 h and 98.9% after 12 h.
Conclusion:
Developed formulation should be stable. Hence, formulation is thus a viable alternative to conventional vaginal dosage forms.
doi:10.4103/2230-973X.147233
PMCID: PMC4286835  PMID: 25599033
Clindamycin HCl; gellan gum; hydroxypropyl methycellulose; in situ gel
23.  An In Vitro Comparative Study of Shear Bond Strength of Composite Resin to Bleached Enamel using Synthetic and Herbal Antioxidants 
Background:
The bond strength to bleached enamel is reduced, if adhesive restorations are carried out immediately. So the purpose of this in vitro study was an attempt to regain the lost bond strength, for which, the comparison of shear bond strength of composite resin to bleached enamel was carried out using various antioxidants: 10% Sodium ascorbate, Rosemary extracts, Pedicularis extracts.
Materials and Methods:
Fifty human extracted single rooted teeth were collected. They were decoronated and coronal portions were embedded in self cure acrylic resin with their buccal surfaces facing upwards. The samples were randomly divided into positive, negative control groups and three experimental groups (n = 10). In positive control group, specimens were not bleached, before bonding procedure. In negative control group, bleaching was done with 10% carbamide peroxide and bonding was carried out immediately. In experimental groups, following antioxidants were used after bleaching: Group A: 10% Sodium ascorbate, Group B: Rosemary extracts, Group C: Pedicularis extracts. Then the bonding procedures were carried out in all the groups and were subjected for shear bond strength analysis.
Results:
Results clearly showed that groups A and B were effective in reversal of bond strength immediately.
Conclusion:
10% sodium ascorbate solution and rosemary extracts were effective in reversal of shear bond strength immediately after bleaching.
PMCID: PMC4295461  PMID: 25628489
Artificial saliva; 10% carbamide peroxide; shear bond strength; 10% sodium ascorbate
24.  Complete duplication of the urinary bladder: An extremely rare congenital anomaly 
Urology Annals  2015;7(1):91-93.
A case of complete bladder duplication with urethra duplication, diphallus, anorectal malformation and rightsided renal agensis with ipsilateral gonadal agenesisis was reported because of its rarity. Possible deranged embryology resulting in these anomalies has been reviewed with relevant hypothesis. The patient underwent several investigations and undergoing multistage surgical intervention.
doi:10.4103/0974-7796.148629
PMCID: PMC4310128  PMID: 25657554
ARM; bladder duplication; diphallus
25.  Common pitfalls in statistical analysis: “No evidence of effect” versus “evidence of no effect” 
This article is the first in a series exploring common pitfalls in statistical analysis in biomedical research. The power of a clinical trial is the ability to find a difference between treatments, where such a difference exists. At the end of the study, the lack of difference between treatments does not mean that the treatments can be considered equivalent. The distinction between “no evidence of effect” and “evidence of no effect” needs to be understood.
doi:10.4103/2229-3485.148821
PMCID: PMC4314850  PMID: 25657905
Biostatistics; bias; statistical

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