Comparison of prevalence of depression among medical, dental, and engineering students in Patna using Beck's Depression Inventory II: A cross-sectional study.

BACKGROUND: Depression, a multi-dimensional disorder adversely affects the interpersonal, social and occupational spheres of students' life. It is the 11th leading cause of global disease burden. AIMS AND OBJECTIVES: To assess the prevalence of depressive symptoms among various professional course students including medical, dental, and engineering students in Patna, Bihar. MATERIALS AND METHODS: The present investigation was a questionnaire-based cross-sectional descriptive study. A total of 3,100 students attending government and private medical, dental, and engineering colleges in Patna were approached during the course of this study. Students were briefed about the study and questionnaire. BDI-II (Beck's Depression Inventory-II) was administered to the students and they were instructed to fill it. Beck's scores were recorded and a descriptive analysis performed. RESULTS: 2798 students out of 3,100 responded positively to the survey by completely filling out the form. The overall response rate was 90.25%. The overall prevalence of depressive symptoms was found to be 47.78%. Of the three streams, students belonging to the engineering stream (40.28%) showed a maximum prevalence of depressive symptoms followed by dental (38.50%) and medical students (34.74%). CONCLUSION: Our study showed an alarming prevalence of depression among professional course seeking students. This multi-dimensional disorder continues to affect student's performance and professionalism, thus, extending its negative impact to the community at large. This may carry out later in their lives, thus leaving a long-term negative impact. Considering the high rate of depressive symptoms, establishing a unit or facility to identify or diagnose it at an early stage and providing psychological support to students is recommended.

Probing the opportunities for designing anthelmintic leads by sub-structural topology-based QSAR modelling.

A quantitative structure-activity (QSAR) model has been developed for enriched tubulin inhibitors, which were retrieved from sequence similarity searches and applicability domain analysis. Using partial least square (PLS) method and leave-one-out (LOO) validation approach, the model was generated with the correlation statistics of [Formula: see text] and [Formula: see text] of 0.68 and 0.69, respectively. The present study indicates that topological descriptors, viz. BIC, CH_3_C, IC, JX and Kappa_2 correlate well with biological activity. ADME and toxicity (or ADME/T) assessment showed that out of 260 molecules, 255 molecules successfully passed the ADME/T assessment test, wherein the drug-likeness attributes were exhibited. These results showed that topological indices and the colchicine binding domain directly influence the aetiology of helminthic infections. Further, we anticipate that our model can be applied for guiding and designing potential anthelmintic inhibitors.

Multi-Pharmacophore Modeling of Caspase-3 Inhibitors using Crystal, Dock and Flexible Conformation Schemes.

AIM AND OBJECTIVE: Numerous caspase-3 drug discovery projects were found to have relied on single receptor as the template to recognize most promising small molecule candidates using docking approach. Alternatively, some researchers were contingent upon ligand-based alignment to build up an empirical relationship between ligand functional groups and caspase-3 inhibitory activity quantitatively. To connect both caspase-3 receptor details and its inhibitors chemical functionalities, this study was undertaken to develop receptor- and ligand-pharmacophore models based on different conformational schemes. MATERIAL AND METHODS: A multi-pharmacophore modeling strategy is carried out based on three conformational schemes of pharmacophore hypothesis generation to screen caspase-3 inhibitors from database. The schemes include (i) flexible (conformations unrestricted or flexible during pharmacophore mapping), (ii) dock (conformations obtained using FlexX docking method) and (iii) crystal (extracted from multiple caspase-3-ligand complexes from PDB repository) conformations of query ligands. The pharmacophore models developed using these conformational schemes were then used to identify probable caspase-3 inhibitors from ZINC database. RESULTS: We noticed better sensitivity with good specificity measures returned by candidate pharmacophore hypotheses across each conformation type and recognized crucial pharmacophore features that enable caspase-3 binding. Pharmacophore modeling based on flexible conformational scheme indicated that the crystal structure 3KJF (AAAADH) is the best receptor structure to perform receptor-based pharmacophore screening of caspase-3 inhibitors. When multiple crystal structures were included, the hypothesis (HAAA) is more generalized. Superimposition of multiple co-crystal ligands from various caspase-3 PDB entries in crystallographic binding mode revealed similar hypothesis (HAAA). Further, FlexX-guided dock conformations of validation dataset showed that the crystal structure 1RE1 is the best-suited for dock-based pharmacophore models. Database screening using these pharmacophore hypotheses identified N'-[6-(benzimidazol-1-yl)-5-nitro-pyrimidin-4-yl]-4 methylbenzenesulfonohydrazide and 2-nitro-N'-[5-nitro-6-[N'-(p-tolylsulfonyl)hydrazino]pyrimidin-4- yl]benzohydrazide as the probable caspase-3 inhibitors. CONCLUSION: N'-[6-(benzimidazol-1-yl)-5-nitro-pyrimidin-4-yl]-4 methylbenzenesulfonohydrazide and 2-nitro-N'-[5-nitro-6-[N'-(p-tolylsulfonyl)hydrazino]pyrimidin-4-yl]benzohydrazide may be tested for caspase-3 inhibition. We believe that potential caspase-3 inhibitors can be recognized efficiently by adapting multi-pharmacophore models in database screening.

Exploration of Mycobacterium tuberculosis structural proteome: An in-silico approach.

Pharmacophore approaches are of central contour in drug discovery. However, the dependence of ligand-based pharmacophore model on appropriate training set molecules and typical use of apo-protein or single protein-ligand complex for the construction of structure-based pharmacophore models might skip some vital information. Therefore, multiple-complex based approach was employed for the construction of pharmacophore models of the Mycobacterium structural proteome. Moreover, the strategy of clustering of common pharmacophore hypotheses was made to gain an insight about the pharmacophore-similarity across the protein classes and share of features among the inhibitors. Rationale behind the present work was to present the scenario of virtual screening and guiding principle for designing efficient inhibitor by taking into account the available pharmacophoric space.

Probiotics: A New Era of Biotherapy.

Probiotics or health-beneficial bacteria have only recently been introduced in dentistry after years of successful use in mainly gastrointestinal disorders. The concept of bacteriotherapy was first introduced in the beginning of 20th century. They are administered in different quantities that allow for colon colonization. These products help in stimulating health promoting flora and also suppressing the pathologic colonization and disease spread. The use of probiotic plays an important aspect in dentistry too, ever since the oral infections occupied the prime spot among the other infections affecting the humans. Probiotics strengthen the immune system to combat allergies, stress, exposure to toxic substances, and other diseases. This review is an attempt to discuss briefly the role of probiotics in oral health.

Exploration of interaction zones of ß-tubulin colchicine binding domain of helminths and binding mechanism of anthelmintics.

Numerous studies postulated the possible modes of anthelmintic activity by targeting alternate or extended regions of colchicine binding domain of helminth ß-tubulin. We present three interaction zones (zones vide -1 to -3) in the colchicine binding domain of Haemonchus contortus (a helminth) ß-tubulin homology model and developed zone-wise structure-based pharmacophore models coupled with molecular docking technique to unveil the binding hypotheses. The resulted ten structure-based hypotheses were then refined to essential three point pharmacophore features that captured recurring and crucial non-covalent receptor contacts and proposed three characteristics necessary for optimal zone-2 binding: a conserved pair of H bond acceptor (HBA to form H bond with Asn226 residue) and an aliphatic moiety of molecule separated by 3.75±0.44Å. Further, an aliphatic or a heterocyclic group distant (11.75±1.14Å) to the conserved aliphatic site formed the third feature component in the zone-2 specific anthelmintic pharmacophore model. Alternatively, an additional HBA can be substituted as a third component to establish H bonding with Asn204. We discern that selective zone-2 anthelmintics can be designed effectively by closely adapting the pharmacophore feature patterns and its geometrical constraints.

Multi-level structure-based pharmacophore modelling of caspase-3-non-peptide complexes: Extracting essential pharmacophore features and its application to virtual screening.

Enormous caspase-3-non-peptide crystal structures have been developed to study the structural basis of caspase-3 enzyme inhibition using active site directed small molecular design. These complexes have not been explored thoroughly to decipher the essential non-covalent interactions made by crystal ligands. We present here a multi-level analysis of these caspase-3 complexes using structure-based pharmacophore approach wherein numerous candidate pharmacophore hypotheses were assessed for its ability to cover available caspase-3 small molecular inhibitor dataset. The reliability of the resultant pharmacophores was evaluated using three different validation sets comprising focussed caspase-3 inhibitors, focussed + random decoys, and focussed + structurally similar random decoys and its performance was measured by the Güner-Henry (GH) scoring and enrichment statistics. Furthermore, the effect on excluded volumes toward caspase-3 inhibitors mapping was investigated by an iterative deletion in the structure-based models and created optimal structure-based pharmacophore models to enable effective design of caspase-3 small molecular inhibitor design.

Pharmacophore model prediction, 3D-QSAR and molecular docking studies on vinyl sulfones targeting Nrf2-mediated gene transcription intended for anti-Parkinson drug design.

Despite intense research efforts towards clinical and molecular causes of Parkinson disease (PD), the etiology of disease still remains unclear. However, recent studies have provided ample evidences that the oxidative stress is the key player that contributes a lot to dopaminergic (DAergic) neurodegeneration in brain. It is due to the discrepancy of antioxidant defence system of which nuclear factor erythroid 2-related factor 2 (Nrf2) signalling is of central contour. In the current study, potent heme oxygenase-1 agonists (Nrf2 signalling regulator), vinyl sulfones, were selected and an optimal pharmacophore model was brought forth which was examined using a decoy set by atom-based 3D-QSAR. The best four-feature model consists of two hydrogen bond acceptors and two aromatic rings, which has the highest correlation coefficient, R(2) = .71 and [Formula: see text] = .73 in QSAR. These ligands were further studied for molecular docking with Nrf2-keap protein to gain insight into the major binding motifs followed by analysing pharmacokinetic properties to evaluate their bioavailability dominance. From this study, it is concluded that vinyl sulfones could be ideal compounds for targeting Nrf2 pathway which in turn halt the PD progression. Hence, these can be considered as potential leads for drug development against the same.

Curcumin - Pharmacological Actions And its Role in Oral Submucous Fibrosis: A Review.

Turmeric has been in use for thousands of years as a dye, flavouring and a medicinal herb. Ancient Indian medicine has touted turmeric as an herb with the ability to provide glow and lustre to the skin as well as vigour and vitality to the entire body. Since curcumin has antimicrobial, antioxidant, astringents and other useful properties, it is quite useful in dentistry also. Curcumin, the most active polyphenolic constituent, is the active ingredient in the traditional herbal remedy and dietary spice turmeric. In gel form it is a component in local drugs delivery system. The objective of this article is to review the pharmacological action of turmeric and its use in treating oral submucous fibrosis.

Evaluation of masseter muscle hypertrophy in oral submucous fibrosis patients -an ultrasonographic study.

BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic insidious disease of the oral mucosa, commonly seen in South East Asia. It occurs mainly due to the habit of quid or gutkha chewing. There is a clear dose dependent relationship between gutkha chewing and development of OSMF, also due to continuous chewing for larger intervals of time unnecessary forces are exerted on the muscles mainly the masseter muscle. So, the present study was done to evaluate the thickness of masseter muscle in OSMF patients and to compare it with normal patients. MATERIALS AND METHODS: The present study involved 50 subjects, 25 OSMF patients and 25 normal individuals. The thickness of masseter muscle was evaluated by ultrasonography (5-11mHz). RESULTS: There is a positive association between masseter muscle hypertrophy and OSMF (p-value 0.001). Thickness of masseter muscle was found to be more in OSMF patients as compared to control group and also thickness is more during contraction as compared to relaxation in both OSMF patients and normal individuals.

Kocher debre semelaigne syndrome: a rare case report with orofacial manifestations.

Kocher Debre Semelaigne Syndrome is a rare syndrome with clinical manifestation of hypothyroidism associated with pseudomuscular hypertrophy. Very few cases have been reported on kocher-debre semelaigne syndrome in the literature with the incidence reported to be less than 10%. As per our knowledge; until now, only one case of oro-facial manifestations has been reported. Here we report one such case of Kocher debre semelaigne syndrome in an 11 year old boy, showing features of macroglossia, multiple impacted teeth, puffed lips and anterior open bite.

Hemifacial Hyperplasia: A Case Report.

Hemifacial hyperplasia is a rare developmental anomaly exhibiting asymmetric growth of one or more body parts. It is characterized by hyperplasia of tissues rather than a hypertrophy, so it is better to call it hyperplasia rather than hypertrophy. Hemifacial hyperplasia may be associated with deformities of the skeletal system, including macrodactyly, polydactyly, syndactyly, scoliosis, tilting of the pelvis, and clubfoot. Though the etiology is unknown, various factors have been described. To date, very few cases have been reported thus far, according to the data we have collected. Through literature search, hemifacial hyperplasia was often implicated on the right side compared to the left. In contrast, we describe a case of hemifacial hyperplasia on the left side of the face in this report. This is a rare presentation for the condition which is detailed in this case report of hemifacial hyperplasia in a 50-year-old female who presented with unilateral facial enlargement since birth.

Solvatochromic shift of phenol blue in water from a combined Car-Parrinello molecular dynamics hybrid quantum mechanics-molecular mechanics and ZINDO approach.

The present work addresses the solvatochromic shift of phenol blue (PB) dye. For this purpose the results of Car-Parrinello molecular dynamics (CPMD) simulations for PB in gas phase are compared with results obtained for PB in water from CPMD hybrid quantum mechanics-molecular mechanics (CPMD-QM/MM) calculations. The absorption spectra were obtained using the intermediate neglect of differential overlap/spectroscopic-configuration interaction (INDO/CIS) method and were calculated for a multitude of configurations of the trajectory. The calculated lambda(max) for PB in gas phase was found to be about 535 nm, which is considerably lower than the lambda(max) reported for PB in nonpolar solvents. Different solvation shells for PB in water have been defined based on the solute-all-atoms and solvent center of mass radial distribution function (g(r(X-O))). The electronic excitation energies for PB computed in the presence of solvent molecules in an increasing number of solvation shells were calculated in a systematic way to evaluate their contributions to the solvatochrmic shift. The inclusion of solvent molecules in the hydration shell yields a lambda(max) of 640 nm, which contributes to almost 78% of the solvatochromic shift. The inclusion of solvent molecules up to 10 A in the g(r(X-O)) rdf yields a lambda(max) of 670 nm which is in good agreement with the experimentally reported value of 654-684 nm. Overall, the present study suggests that the combined CPMD-QM/MM and INDO-CIS approach can be used successfully to model solvatochromic shifts of organic dye molecules.

Two- and three-photon absorption of organic ionic pyrylium based materials.

Pyrylium dyes having the same basic chemical structure, differing only to a specific substituent, have been used as novel materials for multiphoton three-dimensional data storage. Electronic absorption spectra, two-photon and three-photon absorption properties of this class of pyrylium dyes, have been studied theoretically and compared to experimental results. The effects of the counteranion, the surrounding solvent, and electron releasing and electron withdrawing groups in specific positions of the basic structure have been explored in detail. It is argued that on grounds of the quality of experimental spectroscopic agreement, the computed two- and three-photon data may be used in pulse propagation simulations of three-dimensional recording in optical memories.

Spin multiplicity dependence of nonlinear optical properties.

Open-shell spin-restricted time-dependent density functional theory is applied to explore the spin multiplicity dependence of linear and nonlinear optical properties. An open-shell neutral conjugated system, the C(4)H(4)N radical in the doublet X(2)A(2), quartet X(4)A(2), and sextet X(6)A(1) states, is chosen as a model system to illustrate various aspects of the theory. It is found that irrespective of the exchange-correlation functional employed, the components of the polarizability alpha(-omega,omega) and first hyperpolarizability beta(-2 omega,omega,omega) show very different dependency with respect to the multiplicity, with an increasing trend for higher spin states. This is rationalized by the decrease in conjugation and stability of the system with increasing multiplicity, and by the way the interaction between unpaired electrons and the external field is shielded by remaining electrons of the molecule. The study suggests the applicability of open-shell systems for frequency-dependent nonlinear optical properties and for the possibility of spin control for such properties.

Modeling two photon absorption cross sections of open-shell systems.

We demonstrate the prospects of computing two photon absorption cross sections of open-shell systems by applying recently developed spin-restricted time-dependent density functional response theory using the pyrrole radical as an example. The spin multiplicity effects on two photon absorption cross sections of this species are investigated for the doublet, quartet, and sextet states. It is found that irrespective of the exchange-correlation functional employed, the two photon cross sections increase with the increase in spin multiplicity. This result indicates that two photon cross sections of paramagnetic compounds can be controlled by manipulating their spin states and this opens new possibilities for design of hybrid magneto-optical materials.

Searching of potential energy curves for the benzene dimer using dispersion-corrected density functional theory.

The present work aims to establish the utility of dispersion-corrected density functional theory for potential energy curves of the benzene dimer, a problem that has received significant attention for a long time. The interaction energies of parallel-stacked, T-shaped and parallel-displaced benzene dimer configurations have been evaluated using both dispersion- and normal gradient-corrected Perdew-Burke-Ernzerhof functionals along with Dunning's augmented correlation-consistent polarized valence triple-zeta (aug-cc-pVTZ) basis functions and compared with explicit correlation methods. The potential energy curves for the parallel-stacked and parallel-displaced benzene dimers are in excellent agreement with highly accurate coupled cluster (CCSD(T)) results, while for the T-shaped benzene dimer the dispersion-corrected results show a distinct deviation, being closer in that case to the MP2 level of results. The overestimation of interaction energy in the T-shaped dimer may be attributed to the presence of a permanent dipole moment in this configuration and indicates a structural dependence of the dispersion-corrected density functional method.

Time-dependent density functional theory for nonlinear properties of open-shell systems.

This paper presents response theory based on a spin-restricted Kohn-Sham formalism for computation of time-dependent and time-independent nonlinear properties of molecules with a high spin ground state. The developed approach is capable to handle arbitrary perturbations and constitutes an efficient procedure for evaluation of electric, magnetic, and mixed properties. Apart from presenting the derivation of the proposed approach, we show results from illustrating calculations of static and dynamic hyperpolarizabilities of small Si(3n+1)H(6n+3) (n=0,1,2) clusters which mimic Si(111) surfaces with dangling bond defects. The results indicate that the first hyperpolarizability tensor components of Si(3n+1)H(6n+3) have an ordering compatible with the measurements of second harmonic generation in SiO2/Si(111) interfaces and, therefore, support the hypothesis that silicon surface defects with dangling bonds are responsible for this phenomenon. The results exhibit a strong dependence on the quality of basis set and exchange-correlation functional, showing that an appropriate set of diffuse functions is required for reliable predictions of the first hyperpolarizability of open-shell compounds.

Juvenile polyps in the small intestine presenting as jejunojejunal intussusception in a 10-year-old child: report of a case.

We report herein the case of a 10-year-old child with small bowel obstruction caused by jejunojejunal intussusception of a juvenile polyp. To the best of our knowledge, this is only the third case reported of a juvenile polyp in the small intestine and the first case to be documented in the English literature.