Three-dimensional electroanatomical mapping guided right bundle branch pacing in congenitally corrected transposition of great arteries.

AIMS: The ideal pacing strategy has been the Achilles' heel for patients with congenitally corrected transposition of great arteries (ccTGA) with bradycardia. Various pacing modalities were documented in the literature. This article describes a novel pacing strategy and its feasibility in ccTGA with an intact ventricular septum. METHODS AND RESULTS: We prospectively recruited three patients with ccTGA who presented with symptomatic complete heart block to our institute and were evaluated. All patients were planned for conduction system pacing. Those who had more than moderate or severe systemic atrioventricular regurgitation and systemic ventricular dysfunction were planned for conduction system pacing with an additional lead in the coronary sinus (CS) tributary, i.e. bundle branch pacing optimized cardiac resynchronization therapy with the intention to achieve incremental benefit. Since right bundle pacing is not described previously and in view of anatomical complexity in location, three-dimensional (3D) anatomical mapping was done with the EnSite system and later right bundle capture is identified conventionally as that of a left bundle in a normal heart. All three patients have stable lead positions and adequate thresholds at short-term follow-up. CONCLUSION: In this report, we demonstrated the feasibility of permanent physiological pacing of the systemic ventricle by capturing the right bundle with 3D anatomical mapping guidance, which results in physiological activation of the systemic ventricle.

Passive trapping of rigid rods due to conformation-dependent electrophoretic mobility.

We present computer simulations of a rigid rod in a combination of an extensional fluid flow and extensional electric field. The electrophoretic mobility of the rod is different parallel or perpendicular to the rod. The dependence of the mobility on the conformation (orientation) leads to a new phenomenon where the rods can be passively trapped in all directions at the stagnation point. This contrasts with the behavior in either fluid flow or electric field alone, in which an object can be pushed towards the stagnation point along some directions but is pushed away in others. We have determined the state space where trapping occurs and have developed a model that describes the strength of trapping when it does occur. This new phenomenon could be used in the future to separate objects based on a coupling between their mobility and ability to be oriented.

Antibacterial and antibiofilm efficacy of green synthesized ZnO nanoparticles using Saraca asoca leaves.

Biofilms are made up of bacterial colonies and their extracellular polymeric substances (EPS) matrix, which protects the bacteria from adverse environmental conditions. The increasing drug resistivity of pathogenic bacteria is becoming an emergency for developing new antibacterial agents. In this study, we have synthesized the zinc oxide nanoparticles (ZnO NPs) using the leaf extract of Saraca asoca plant, and the antibacterial and antibiofilm activity of green synthesized ZnO NPs was measured against the biofilm-producing bacteria Bacillus subtilis. The disk diffusion data reveals that the zone of inhibition (ZOI) starts at a concentration of 0.5 mg/mL and minimum inhibition concentration (100 µg/mL) and minimum bactericidal concentration (150 µg/mL) values were also evaluated for green synthesized ZnO nanomaterials. Crystal violet test and microscopic examination were used to assess the impact of produced nanoparticles on biofilm development. The findings indicated a nearly 45%, 64%, and 83% suppression of biofilm development at 0.5 × MIC, 0.75 × MIC, and 1 × MIC value, respectively. The biofilm biomass of the preformed or matured biofilms by the ZnO NPs was evaluated to be 68%, 50%, and 33% at concentrations of 0.5 × MIC, 0.75 × MIC, and 1 × MIC which was concentration-dependent. Moreover, flow cytometry results suggest damage to the bacterial cell membrane. The data indicated that the proportion of dead cells increased with NP concentration in comparison to the control. Therefore, it can be concluded that the green synthetic ZnO nanoparticles showed excellent antibacterial and antibiofilm activity against the Bacillus subtilis bacteria that produce biofilms and that they could be a promising substitute agent for the treatment of biofilms and drug-resistant bacteria.

In silico screening of Pueraria tuberosa (PTY-2) for targeting COVID-19 by countering dual targets Mpro and TMPRSS2.

COVID-19 pandemic was started in Wuhan city of China in December 2019; immensely affected global population. Herein, an effort was made to identify potential inhibitors from active phytochemicals of Pueraria tuberosa (PTY-2) via molecular docking study. Our study showed five potential inhibitors (Robinin, Genistin, Daidzin, Hydroxytuberosone, Tuberostan) against Mpro and five inhibitors (Robinin, Anhydrotuberosin, Daidzin, Hydroxytuberosone, Stigmasterol) against TMPRSS2. Out of these, Robinin, Daidzin and Hydroxytuberosone were common inhibitors for Mpro and TMPRSS2. Among these, Robinin showed the highest binding affinity, therefore, tested for MD simulation runs and found stable. ADMET analysis revealed the best-docked compounds are safe and follow the Lipinski Rule of Five. Thus, it could be suggested that phytochemicals of PTY-2 could serve as potential inhibitors for COVID-19 targets.Communicated by Ramaswamy H. Sarma.

Toxicity profile of honey and ghee, when taken together in equal ratio.

Honey and ghee are an essential component of our diet. They play an important role like anti-inflammatory, antioxidative, antimicrobial, etc. It is written in Charak Samhita that an equal mixture of honey and ghee turn into a harmful component for health. This study was designed to explore the mechanism of toxicity through the biochemical and histological parameters in Charles foster rats (24 rats were used). We have divided these rats into four groups (n = 6) - normal, honey (0.7 ml/100 g bw), ghee (0.7 ml/100 g bw), and honey + ghee (1:1) (1.5 ml/100 g bw). Treatment was given orally for 60 days. All rats were sacrificed on 61 days. Biochemical parameters like liver function test, kidney function test, Oxidative stress, Glycemic, and some protein modification parameters were done in blood plasma. We found weight loss, hair loss, red patches on ear, and increased liver function test, oxidative stress, Amadori product formation, advanced glycation end-product formation, dipeptidyl protease (DPP-4) and decreased incretins (glucagon-like peptide-1(GLP-1) and gastric inhibitory polypeptide (GIP)) in honey + ghee group. H&E and immunohistochemistry results showed mild inflammation in liver tissue but no changes in the kidney, intestine and, pancreas. Thus it concluded that the increased formation of Amadori product, DPP-4 activity and low incretins (GLP-1, GIP) activity resulting high postprandial hyperglycemic response could be collectively responsible for oxidative stress-mediated toxicity of honey and ghee in the equal mixture.

GLP 1 Regulated Intestinal Cell's Insulin Expression and Selfadaptation before the Onset of Type 2 Diabetes.

Purpose: Basically insulin is known to be secreted by ß cells of the pancreas. Recently, it has also been found to be produced and expressed by intestinal epithelial cells with the help of L cells secreting glucagon like peptide 1 (GLP 1). Here, we have studied the same intestinal insulin expression property in T2D rats. Methods: Following 2 weeks of high fat diet (HFD) consumption, we have been given a single dose of streptozotocin (STZ) (35 mg/kg bw). Rats were then sacrificed after 1, 7 and 21 days. The GLP 1 analogue, liraglutide was also given to one group of diabetic rats, upto their respective durations. Intestinal cells apoptosis were checked by tunnel assay, Incretin hormones secretion and dipeptidyl peptidase 4 (DPP-IV) activity were analyzed through ELISA and immunohistochemistry was used to determine the insulin expression of intestine at different time interval during diabetes progression. Results: As compared to 1 and 21 days, we have found minor cells apoptosis in 7 days group along with high level of GLP 1 in diabetic model. Further, these effects were enhanced by liraglutide. In response to these we have found, decreased insulin expression after 21 days and with no significant effect upto 7 days in diabetic control groups. In contrast to this, GLP-1 level and insulin expression enhances prominently after 7 days of liraglutide treatment. Conclusion: These results explain the self-adapting approach of intestinal cells against diabetes onset and insulin expression enhancing property of liraglutide under stressful conditions. This study should be continued in future for the development of intestinal insulin producing drugs, to control diabetes under irreversible ß cells damage.

Anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory conditions induced by PTY-2 against STZ-induced stress in islets.

The earlier assessment of Pueraria tuberosa (PT) has shown anti-diabetic effects through enhancing incretin action and DPP-IV (Dipeptidyl peptidase-IV) inhibition. The aim of this work was to further explore the protective role of aqueous extract of Pueraria tuberosa tuber (PTY-2) against streptozotocin (STZ) induced islet stress in rats. Diabetes was induced by STZ (65 mg/kg body weight) in charles foster male rats. After 60 days of STZ administration, animals with blood glucose levels > 200 g/dL were considered as diabetic. All the rats were later divided into three groups: Group-1 (STZ untreated normal rats), Group-2 (Diabetic control), and Group-3 (PTY-2 [50 mg/100 g bw treatment for next 10 days to diabetic rats). The rats were then sacrificed after the 10th day of treatment accordingly. STZ treatment led to an increase in expression of Matrix metalloproteinases-9 (MMP-9), Tumour necrosis factor-α (Tnf-α), Hypoxia inducible factor-α (HIF-1α), Vascular endothelial growth factor (VEGF), Interleukin-6 (IL-6), Protein kinase C-ε (PKC-ε), Nuclear factor kappa-light-chain-enhancer of activated B-cells (NFkB), and Caspase-3. Reverse Transcriptase-PCR (RT-PCR), Immunohistochemistry and Western-Blot analysis showed an increase in the expressions of Superoxide Dismutase (SOD) and Nephrin, and a decrease in the expressions of NFkB, PKC-ε, TNF-α, MMP-9, HIF-1α, VEGF, Caspase-3 and IL-6 after 10 days of PTY-2 treatment. The results showed that PTY-2 favorably changed all the expressions via anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory pathways, making itself as a protective agent against STZ induced islet stress. Further evaluation of PTY-2 might be helpful in establishing its role in the management of diabetes mellitus.

Expression kinetics reveal the self-adaptive role of ß cells during the progression of diabetes.

OBJECTIVE: To determine the histopathological and molecular changes in ß-cells at different time intervals following streptozotocin (STZ)-induced diabetes. METHODS: STZ (65 mg/kg body weight) was given to overnight fasted rats that were sacrificed after 1, 3, and 10 days of injection. Changes in islet morphology and in the expression of various factors involved in ß-cell proliferation, inflammation and apoptosis were analyzed. RESULTS: Superoxide dismutase (Sod) expression was completely reduced and that of NF-kB and iNOS were significantly increased, along with lymphocytic infiltration in the islets within 24 h of STZ injection. In addition, the ß-cell protective markers Bcl-2, IL-6, Ki67, Hif-1α, VEGF and insulin were also enhanced, indicating a compensatory response of the ß-cells to the initial damaging effects. Lymphocytic infiltration decreased after 3 days of injection, accompanied by enhanced expression of both GLP-1R and GIP R. The unresponsiveness of the incretin ligands after STZ administration further suggested a compensatory approach by the incretin receptors independent of glucose regulation. After 10 days, lymphocytic infiltration and inflammatory markers again increased, along with a concomitant reduction in the expression of incretin receptors, and upregulation of the protective markers. Furthermore, the saturation peak of blood glucose indicated progressive diabetes. CONCLUSIONS: The ß-cells follow a biphasic pattern of expression of certain factors in order to achieve a balance between apoptosis, autophagy, neo-genesis, hypoxia and proliferation, and achieve homeostatic protection before the onset of diabetes. The drug interventions at an early stage, which are specific to these pathways, could be beneficial in preventing the progression of diabetes pathogenesis.

Incretin hormones receptor signaling plays the key role in antidiabetic potential of PTY-2 against STZ-induced pancreatitis.

AIMS: Incretin therapy is one of the most potential approaches in the treatment of diabetes. In contrast to markedly available drugs, the herbal incretin modulators have lesser side effects with low economic cost. The main aim of this work was to analyze the potential of previously reported DPPIV inhibitor, aqueous extract of Pueraria tuberosa tubers (PTY-2) as incretin hormones receptor agonist against streptozotocin (STZ)-induced diabetes. METHODS: Chronic diabetes was induced with STZ (65mg/kg bw) in rats for 60days and grouped into diabetic control and PTY-2. Expression of genes was assessed by PCR, IHC, and ELISA. Morphological analysis of tissue was observed using H & E stain. In silico molecular docking approach has been used to see the interaction of active phytochemicals of PTY-2 on the basis of their binding energy [kcal/mol] and dissociation constant [pM] using YASARA software. Interactive visualization was done using Discovery studio 3.0. RESULTS: In comparison to diabetic control, the size and number of islet cells along with the plasma level of GLP-1, GIP, and pancreatic expressions of GLP-1R, GIP-R, Bcl2, and insulin were enhanced significantly after PTY-2 treatment. Through in silico molecular docking, tuberostan showed the best interaction for GLP-1R with binding energy at 8.15kcal/mol and dissociation constant at 1061624.125 pM. Puererone showed the best interaction for GIP-R with binding energy at 8.31kcal/mol and dissociation constant at 810381 pM. CONCLUSIONS: In addition to previously studied DPPIV inhibitor, PTY-2 also acts as incretin receptors agonist and protects against STZ-induced diabetes by down regulating ß cells apoptosis.

Coarse-grained model of conformation-dependent electrophoretic mobility and its influence on DNA dynamics.

The electrophoretic mobility of molecules such as λ-DNA depends on the conformation of the molecule. It has been shown that electrohydrodynamic interactions between parts of the molecule lead to a mobility that depends on conformation and can explain some experimental observations. We have developed a new coarse-grained model that incorporates these changes of mobility into a bead-spring chain model. Brownian dynamics simulations have been performed using this model. The model reproduces the cross-stream migration that occurs in capillary electrophoresis when pressure-driven flow is applied parallel or antiparallel to the electric field. The model also reproduces the change of mobility when the molecule is stretched significantly in an extensional field. We find that the conformation-dependent mobility can lead to a new type of unraveling of the molecule in strong fields. This occurs when different parts of the molecule have different mobilities and the electric field is large.

Effect of fluoridated toothpaste on white spot lesions in postorthodontic patients.

INTRODUCTION: This article illustrates a new treatment approach and evaluates the effect of use of fluoridated toothpaste on the remineralization of white spot lesions (WSLs) diagnosed at debonding. MATERIALS AND METHODS: Thirty-one orthodontic patients (mean age: 19.6 years), with a minimum of four WSLs on the buccal surfaces of the maxillary and mandibular incisors, canines, premolars and first molars after orthodontic therapy, were enrolled in a double-blind, randomized, longitudinal trial lasting 8 weeks. The subjects were divided into two groups using fluoridated toothpaste (test group, n = 31) and nonfluoridated toothpaste (control group, n = 31). A custom-made mouth tray, covering the maxillary dentition, was used while brushing with the fluoridated toothpaste three times per day. Maxillary dentition acted as control and mandibular as the test. The WSLs were scored by using the International Caries Detection and Assessment System (ICDAS II) index, at baseline and 8 weeks after debonding. RESULTS: The ICDAS II index of the WSLs decreased in the test group in the mandibular dentition but not on the maxillary dentition during the 8-week trial (p < 0.0001). There was also a slight improvement in the control group (not significant). CONCLUSION: The frequent use of fluoridated toothpaste had a remineralizing effect on WSLs. How to cite this article: Agarwal A, Pandey H, Pandey L, Choudhary G. Effect of Fluoridated Toothpaste on White Spot Lesions in Postorthodontic Patients. Int J Clin Pediatr Dent 2013;6(2):85-88.

Changes in Cranial Base Morphology in Class I and Class II Division 1 Malocclusions.

INTRODUCTION: The cranial base plays a key role in craniofacial growth; it helps to integrate spatially and functionally different patterns of growth in various adjoining regions of the skull such as components of the brain, the nasal and oral cavity and the pharynx. The aim of this study was to evaluate the difference in cranial base flexure between skeletal and dental Class I and Class II division 1. MATERIALS & METHODS: Lateral cephalometric radiograph, of Class I and Class II with an average growth pattern were analyzed and compared. A total of 103 patients having class I (n=52) and class II (n=51) malocclusion, were taken from Department of Orthodontics, Rajasthan Dental College & Hospital, Jaipur. Cranial base angle (N-S-Ar) and ANB were measured on pre treatment lateral cephalograms. RESULTS: In this study cranial base angle did not show statistically significant difference between the two groups studied. CONCLUSION: In the assessment of orthodontic problems involving anteroposterior malrelationships of the jaws, the problem is usually the result of size, form and position of the jaw. The present study failed to find any differences in cranial base angle between sagittal malocclusions. How to cite this article: Agarwal A, Pandey H, Bajaj K, Pandey L. Changes in Cranial Base Morphology in Class I and Class II Division 1 Malocclusion. J Int Oral Health 2013; 5(1):39-42.