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1.  The effect of ferrule presence and type of dowel on fracture resistance of endodontically treated teeth restored with metal-ceramic crowns 
The purpose of the present study was to comparatively evaluate the effect of presence of a 2 mm ferrule and different type of dowels on fracture resistance of mandibular premolars.
Materials and Methods:
Fifty uniradicular mandibular premolars were divided into five groups (n = 10). Ten teeth received no treatment (group I). Samples in group II & III were decoronated 2 mm above cemento-enamel junction and received custom cast dowel-core and fiber dowel-composite core respectively, with 2 mm ferrule. Samples in group IV & V were decoronated at CEJ and were restored using cast dowels and fiber dowel-composite cores, without any ferrule. The restored teeth received metal ceramic crowns and were mechanically loaded. The specimens were subjected to a static load, until fracture, to determine the fracture resistance and fracture mode.
The samples with 2 mm ferrule had a higher fracture resistance than non ferrule groups. Within non ferrule groups, there were no significant differences in the fracture resistance. Specimen restored with cast dowel had more incidence of non-repairable fracture.
Presence of ferrule increased the fracture resistance of endodontically treated teeth. In case of absence of ferrule, fiber dowels had similar fracture resistance as that of cast dowels and showed increased incidence of repairable fracture.
PMCID: PMC4001279  PMID: 24778519
Cast dowel; Fiber dowels; Fracture resistance; Fracture mode
2.  A Study on the Prevalence of Alcohol Consumption, Tobacco Use and Sexual Behaviour among Adolescents in Urban Areas of the Udupi District, Karnataka, India 
The aim of this study was to assess the prevalence of alcohol consumption, tobacco use and risky sexual behaviour among adolescents, and to evaluate the socioeconomic factors potentially influencing these behaviours.
This cross-sectional study was conducted from January to April 2011 among 376 adolescents (15–19 years old) studying in different schools and colleges in Udupi, India. The Youth Risk Behavior Survey questionnaire and guidelines were followed for data collection. Participants’ alcohol consumption, smoking habits and sexual behaviour patterns were explored. Univariate analysis followed by multivariate logistic regression was done.
The prevalence of alcohol consumption, tobacco use and sexual activity was found to occur in 5.7%, 7.2% and 5.5% of participants, respectively. The mean age of the participants’ first sexual activity, consumption of alcohol and tobacco use was reported to be approximately 16.8 years. Multivariate analysis showed that males were more likely to have used alcohol and tobacco. Other factors, such as religion and tobacco use among family members, were found to be influential.
The potential coexistence of multiple risk behaviours in a student demands an integrated approach. Emphasis should be placed on health education in schools and an increased awareness among parents in order to prevent adolescents’ behaviours from becoming a risk to their health.
PMCID: PMC3916261  PMID: 24516739
Adolescents; Risk Behaviors; Tobacco; Alcoholic Beverages; Sexual Behavior; India
3.  HIV-TB coinfection: Clinico-epidemiological determinants at an antiretroviral therapy center in Southern India 
HIV–TB (tuberculosis) coinfection has emerged as a major public health threat. Given the multifactorial enabling environment in a resource-constrained setting like India, the consequences are of epidemic proportions.
This study was aimed at identifying the clinical and epidemiological determinants underlying HIV–TB coinfection.
Settings and Design:
A retrospective review of patient records was done from the antiretroviral therapy center (ART) center at a district hospital in southern India between May and August 2012.
Materials and Methods:
Secondary data of 684 patients on ART as well as pre-ART were collected between July 2008 and June 2012 and were analyzed.
Statistical Analysis:
Descriptive analysis, χ2, and Wilcoxon signed rank tests were used with SPSS version 15.0 to draw significant statistical inferences.
HIV–TB coinfection was diagnosed in 18.9% with higher prevalence among males (75.3%), in the sexually active age group 31-45 years (61.3%), with less than primary education (44.15%), who were married (56.1%), laborers (42.4%), from rural backgrounds (88.2%), and having low income-earning capacity (94.4%). Transmission was predominantly through the heterosexual route. The key entry point was the integrated counseling and testing center (ICTC) (47.4%). Pulmonary tuberculosis (58.8%) was predominantly found followed by extrapulmonary tuberculosis (38.2%) and both in 3.1%. A favorable outcome was observed in 69.3% of coinfected patients with 89.2% on ART and 97.2% currently on DOTS therapy. The Wilcoxon signed-rank test found significant association between rises in CD4 counts after the 6th-month follow up (P < 0.05). Coinfected patients had a case fatality rate of 25%.
The prevalence of HIV–TB coinfection recorded in this sample was 18.86%. ICTC implemented by NACO emerged as an effective entry point, while Revised National Tuberculosis Control Program referred 1.6% (n = 11) of the patients to the ART center. Coinfection is associated with lower CD4 counts than those with HIV alone, which could translate into increased morbidity and progression of HIV to AIDS.
PMCID: PMC3841686  PMID: 24339487
ART; CD4; DOTS; HIV–TB coinfection; ICTC
4.  Mutations of TCF12, encoding a basic-helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis 
Nature genetics  2013;45(3):304-307.
Craniosynostosis, the premature fusion of the cranial sutures, is a heterogeneous disorder with a prevalence of ~1 in 2,200 (refs. 1,2). A specific genetic etiology can be identified in ~21% of cases3, including mutations of TWIST1, which encodes a class II basic helix-loop-helix (bHLH) transcription factor, and causes Saethre-Chotzen syndrome, typically associated with coronal synostosis4-6. Starting with an exome sequencing screen, we identified 38 heterozygous TCF12 mutations in 347 samples from unrelated individuals with craniosynostosis. The mutations predominantly occurred in patients with coronal synostosis and accounted for 32% and 10% of subjects with bilateral and unilateral pathology, respectively. TCF12 encodes one of three class I E-proteins that heterodimerize with class II bHLH proteins such as TWIST1. We show that TCF12 and TWIST1 act synergistically in a transactivation assay, and that mice doubly heterozygous for loss-of-function mutations in Tcf12 and Twist1 exhibit severe coronal synostosis. Hence, the dosage of TCF12/TWIST1 heterodimers is critical for coronal suture development.
PMCID: PMC3647333  PMID: 23354436
5.  Reduced dosage of ERF causes complex craniosynostosis in humans and mice, and links ERK1/2 signaling to regulation of osteogenesis 
Nature genetics  2013;45(3):308-313.
The extracellular signal-related kinases (ERK1/2) are key proteins mediating mitogen-activated protein kinase signaling downstream of RAS: phosphorylation of ERK1/2 leads to nuclear uptake and modulation of multiple targets1. Here we show that reduced dosage of ERF, which encodes an inhibitory ETS transcription factor directly bound by ERK1/2 (refs 2-7), causes complex craniosynostosis (premature fusion of the cranial sutures) in humans and mice. Features of this newly recognized clinical disorder include multiple suture synostosis, craniofacial dysmorphism, Chiari malformation and language delay. Mice with functional Erf reduced to ~30% of normal exhibit postnatal multisuture synostosis; by contrast, embryonic calvarial development appears mildly delayed. Using chromatin immunoprecipitation in mouse embryonic fibroblasts and high-throughput sequencing, we find that ERF binds preferentially to distal regulatory elements containing RUNX or AP1 motifs. This work identifies ERF as a novel regulator of osteogenic stimulation by RAS-ERK signaling, potentially by competing with activating ETS factors in multifactor transcriptional complexes.
PMCID: PMC3683605  PMID: 23354439
6.  Efficacy and tolerability of fixed dose combination of metoprolol and amlodipine in Indian patients with essential hypertension 
Journal of Mid-Life Health  2013;4(3):160-166.
This open-labeled, post-marketing study was conducted to assess the efficacy and tolerability of fixed dose combination of amlodipine and metoprolol extended release capsules in mild to moderate hypertension in adult Indian patients.
Materials and Methods:
Of 101 enrolled patients, 64 drug naïve patients were treated with regimen A (amlodipine 5 mg + metoprolol 25 mg) and those with prior history of hypertension (n = 37) were treated with regimen B (amlodipine 5 mg + metoprolol 50 mg) for 8 weeks. Treatment response was assessed at week 4 and 8. Dose up titration to regimen B was carried out for those who failed to achieve the target blood pressure (BP) at week 4 in regimen A and additional antihypertensives were added to those in regimen B. Safety laboratory tests were performed at baseline and end of study.
Mean age (±SD) of patients was 53.36 (±11.26) years and body weight (±SD) 63.40 (10.03) kg. Ninety five patients (94.06%) were only hypertensive and 6 (5.94%) had hypertension with history of coronary artery disease; mean duration (±SD) of hypertension was 42.50 (48.07) months. At baseline, patients had a mean (±SD) systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 154.98 (±7.76) mmHg and 95.55 (±5.70) mmHg respectively. There was a statistically significant (P < 0.001) reduction of 12.16% and 14.69% in SBP, 11.49% and 14.65% in DBP at week 4 and week 8 respectively, compared to baseline. Normalization of overall BP was achieved in 49.49% and 70.71% patients at week 4 and 8, respectively. Peripheral edema was reported in 2.97% (3/101) patients.
This combination was safe, efficacious, and well-tolerated in study population.
PMCID: PMC3952407  PMID: 24672188
Amlodipine and metoprolol; essential hypertension; fixed dose combination; peripheral edema
7.  The Human EKC/KEOPS Complex Is Recruited to Cullin2 Ubiquitin Ligases by the Human Tumour Antigen PRAME 
PLoS ONE  2012;7(8):e42822.
The human tumour antigen PRAME (preferentially expressed antigen in melanoma) is frequently overexpressed during oncogenesis, and high PRAME levels are associated with poor clinical outcome in a variety of cancers. However, the molecular pathways in which PRAME is implicated are not well understood. We recently characterized PRAME as a BC-box subunit of a Cullin2-based E3 ubiquitin ligase. In this study, we mined the PRAME interactome to a deeper level and identified specific interactions with OSGEP and LAGE3, which are human orthologues of the ancient EKC/KEOPS complex. By characterizing biochemically the human EKC complex and its interactions with PRAME, we show that PRAME recruits a Cul2 ubiquitin ligase to EKC. Moreover, EKC subunits associate with PRAME target sites on chromatin. Our data reveal a novel link between the oncoprotein PRAME and the conserved EKC complex and support a role for both complexes in the same pathways.
PMCID: PMC3418287  PMID: 22912744
8.  SS18 Together with Animal-Specific Factors Defines Human BAF-Type SWI/SNF Complexes 
PLoS ONE  2012;7(3):e33834.
Nucleosome translocation along DNA is catalyzed by eukaryotic SNF2-type ATPases. One class of SNF2-ATPases is distinguished by the presence of a C-terminal bromodomain and is conserved from yeast to man and plants. This class of SNF2 enzymes forms rather large protein complexes that are collectively called SWI/SNF complexes. They are involved in transcription and DNA repair. Two broad types of SWI/SNF complexes have been reported in the literature; PBAF and BAF. These are distinguished by the inclusion or not of polybromo and several ARID subunits. Here we investigated human SS18, a protein that is conserved in plants and animals. SS18 is a putative SWI/SNF subunit which has been implicated in the etiology of synovial sarcomas by virtue of being a target for oncogenic chromosomal translocations that underlie synovial sarcomas.
Methodology/Principal Findings
We pursued a proteomic approach whereby the SS18 open reading frame was fused to a tandem affinity purification tag and expressed in amenable human cells. The fusion permitted efficient and exclusive purification of so-called BAF-type SWI/SNF complexes which bear ARID1A/BAF250a or ARID1B/BAF250b subunits. This demonstrates that SS18 is a BAF subtype-specific SWI/SNF complex subunit. The same result was obtained when using the SS18-SSX1 oncogenic translocation product. Furthermore, SS18L1, DPF1, DPF2, DPF3, BRD9, BCL7A, BCL7B and BCL7C were identified. ‘Complex walking’ showed that they all co-purify with each other, defining human BAF-type complexes. By contrast,we demonstrate that human PHF10 is part of the PBAF complex, which harbors both ARID2/BAF200 and polybromo/BAF180 subunits, but not SS18 and nor the above BAF-specific subunits.
SWI/SNF complexes are found in most eukaryotes and in the course of evolution new SWI/SNF subunits appeared. SS18 is found in plants as well as animals. Our results suggest that in both protostome and deuterostome animals, a class of BAF-type SWI/SNF complexes will be found that harbor SS18 or its paralogs, along with ARID1, DPF and BCL7 paralogs. Those BAF complexes are proteomically distinct from the eukaryote-wide PBAF-type SWI/SNF complexes. Finally, our results suggests that the human bromodomain factors BRD7 and BRD9 associate with PBAF and BAF, respectively.
PMCID: PMC3307773  PMID: 22442726
BMJ : British Medical Journal  2008;336(7634):52.
PMCID: PMC2174769

Results 1-9 (9)