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Arunima Goswami, Tirthankar Koley, Madhan Vishal Rajan, Pathak Madhuri, Neelam Upadhyay, Uddipan Das, Manoj Kumar, Abdul Samath Ethayathulla, Gururao Hariprasad Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 110029, IndiaCorrespondence: Gururao Hariprasad, Tel +91-11-26594240, Fax +91-11-26588663, Email dr.hariprasadg@gmail.comPurpose: Leishmaniasis, Chagas disease, and sleeping sickness are caused by protozoa Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei, respectively. Platelet activating factor acetyl hydrolase (PAF-AH) is an inflammatory protein implicated in pathogenesis of these three infections, thereby making them attractive drug targets.Methods: PAF-AH sequences were retrieved from UniProt and aligned using Clustal Omega. Homologous models of parasitic proteins were built based on crystal structure of human PAF-AH and validated using PROCHECK server. Volumes of substrate-binding channel were calculated using the ProteinsPlus program. High throughput virtual screening using Glide program in Schrodinger was done with ZINC drug library against parasitic PAF-AH enzymes. Complexes with best hits were energy-minimized and subjected to 100 ns molecular dynamic simulation and analyzed.Results: PAF-AH enzyme sequences from protozoa Leishmania donovani, Trypanosoma cruzi, Trypanosoma brucei, and human have a minimum of 34% sequence similarity with each other. Corresponding structures show a globular conformation consisting of twisted β-pleated sheets, flanked by α-helices on either side. Catalytic triad of serine-histidine-aspartate is conserved. Substrate-binding channel residues are conserved to an extent, with a lower channel volume in human as compared to target enzymes. Drug screening resulted in identification of three molecules that had better affinities than the substrate to the target enzymes. These molecules fulfill Lipinski’s rules for drug likeness and also bind with less affinity to the human counterpart, thereby establishing a high selective index.Conclusion: Structures of PAF-AH from protozoan parasites and humans belong to the same family of enzymes and have a similar three-dimensional fold. However, they show subtle variations in residue composition, secondary structure composition, substrate-binding channel volume, and conformational stability. These differences result in certain specific molecules being potent inhibitors of the target enzymes while simultaneously having weaker binding to human homologue.Keywords: platelet activating factor acetyl hydrolase, protozoa, drug target, potent inhibitor, leishmaniasis, Leishmania donovani, Chagas disease, Trypanosoma cruzi, sleeping sickness, Trypanosoma brucei, drug efficacy

Gupta AK, Pokhriyal R, Das U, et al. Neuropsychiatr Dis Treat. 2019;15:2073–2085. The authors wish to advise of typographical errors in Figures 1 and 2 and Table 3, the correct unit of apolipoprotein E concentration is μg/ml, and not pg/ml. Page 2077, Figure 1A, y axis, the text “CSF apolipoprotein E (pg/ml)” should read “CSF apolipoprotein E (μg/ml)”. Page 2077, Figure 2, x axis, the text “CSF apolipoprotein E (pg/ml)” should read “CSF apolipoprotein E (µg/ml)”. Page 2079, Table 3, Cut-off values to differentiate neurological controls from the disease column, Apolipoprotein E and Apolipoprotein E or α-synuclein rows, the text “>3.4 pg (Parkinson’s disease)” should read “>3.4 µg (Parkinson’s disease)” and “ The authors apologize for these errors and any inconvenience. Read the original article

Ashish Kumar Gupta,1 Ruchika Pokhriyal,1 Uddipan Das,1 Mohd Imran Khan,1 Domada Ratna Kumar,1 Rishab Gupta,2 Rakesh Kumar Chadda,2 Rashmi Ramachandran,3 Vinay Goyal,4 Manjari Tripathi,4 Gururao Hariprasad11Department of Biophysics; 2Department of Psychiatry; 3Department of Anaesthesia; 4Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, IndiaBackground and objective: Dopamine plays an important role in the disease pathology of Parkinson’s disease and schizophrenia. These two neuropsychiatric disorders represent disease end points of the dopaminergic spectrum where Parkinson’s disease represents dopamine deficit and schizophrenia represents dopamine hyperactivity in the mid-brain. Therefore, current treatment strategies aim to restore normal dopamine levels. However, during treatment patients develop adverse effects due to overshooting of physiological levels of dopamine leading to psychosis in Parkinson’s disease, and extrapyramidal symptoms in schizophrenia. Absence of any laboratory tests hampers modulation of pharmacotherapy. Apolipoprotein E and α-synuclein have an important role in the neuropathology of these two diseases. The objective of this study was to evaluate cerebrospinal fluid (CSF) concentrations of apolipoprotein E and α-synuclein in patients with these two diseases so that they may serve as biomarkers to monitor therapy in Parkinson’s disease and schizophrenia.Methods: Drug-naïve Parkinson’s disease patients and Parkinson’s disease patients treated with dopaminergic therapy, neurological controls, schizophrenic patients treated with antidopaminergic therapy, and drug-naïve schizophrenic patients were recruited for the study and CSF was collected. Enzyme-linked immunosorbent assays were carried out to estimate the concentrations of apolipoprotein E and α-synuclein. Pathway analysis was done to establish a possible role of these two proteins in various pathways in these two dopamine dictated diseases.Results: Apolipoprotein E and α-synuclein CSF concentrations have an inverse correlation along the entire dopaminergic clinical spectrum. Pathway analysis convincingly establishes a plausible hypothesis for their co-regulation in the pathogenesis of Parkinson’s disease and schizophrenia. Each protein by itself or as a combination has encouraging sensitivity and specificity values of more than 55%.Conclusion: The dynamic variation of these two proteins along the spectrum is ideal for them to be pursued as pharmacotherapeutic biomarkers in CSF to monitor pharmacological efficacy in Parkinson’s disease and schizophrenia.Keywords: cerebrospinal fluid, Parkinson’s disease, schizophrenia, dopamine, apolipoprotein E, α-synuclein, biomarkers, treatment monitoring

Masoomeh Poorghorban,1 Umashankar Das,2 Osama Alaidi,1 Jackson M Chitanda,2 Deborah Michel,1 Jonathan Dimmock,1 Ronald Verrall,3 Pawel Grochulski,1,4 Ildiko Badea1 1Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, 2Department of Chemical and Biological Engineering, 3Department of Chemistry, University of Saskatchewan, Saskatoon, SK, Canada; 4Canadian Light Source, Saskatoon, SK, Canada Background: Curcumin analogs, including the novel compound NC 2067, are potent cytotoxic agents that suffer from poor solubility, and hence, low bioavailability. Cyclodextrin-based carriers can be used to encapsulate such agents. In order to understand the interaction between the two molecules, the physicochemical properties of the host–guest complexes of NC 2067 with β-cyclodextrin (CD) or β-cyclodextrin–gemini surfactant (CDgemini surfactant) were investigated for the first time. Moreover, possible supramolecular structures were examined in order to aid the development of new drug delivery systems. Furthermore, the in vitro anticancer activity of the complex of NC 2067 with CDgemini surfactant nanoparticles was demonstrated in the A375 melanoma cell line.Methods: Physicochemical properties of the complexes formed of NC 2067 with CD or CDgemini surfactant were investigated by synchrotron-based powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. Synchrotron-based small- and wide-angle X-ray scattering and size measurements were employed to assess the supramolecular morphology of the complex formed by NC 2067 with CDgemini surfactant. Lastly, the in vitro cell toxicity of the formulations toward A375 melanoma cells at various drug-to-carrier mole ratios were measured by cell viability assay.Results: Physical mixtures of NC 2067 and CD or CDgemini surfactant showed characteristics of the individual components, whereas the complex of NC 2067 and CD or CDgemini surfactant presented new structural features, supporting the formation of the host–guest complexes. Complexes of NC 2067 with CDgemini surfactants formed nanoparticles having sizes of 100–200 nm. NC 2067 retained its anticancer activity in the complex with CDgemini surfactant for different drug-to-carrier mole ratios, with an IC50 (half-maximal inhibitory concentration) value comparable to that for NC 2067 without the carrier.Conclusion: The formation of host–guest complexes of NC 2067 with CD or CDgemini surfactant has been confirmed and hence the CDgemini surfactant shows good potential to be used as a delivery system for anticancer agents. Keywords: inclusion complex, supramolecular arrangement, small-angle X-ray scattering, powder X-ray diffraction, cytotoxic activity

The aim of the present study was to evaluate cephalometrically the treatment effects of preorthodontic trainer on dentoskeletal components in individuals showing class II division I malocclusion. This study comprised of 50 class II div. I patients (20 test patients and 30 controls) in the age group of 8-12 years. The test group was treated with a preorthodontic trainer for a period of 15 months. Standardized lateral cephalograms of both groups were taken before and after the treatment period. The cephalograms were then evaluated to determine the skeletal and dental changes in the course of treatment and then compared with the normative growth data to eliminate the possible growth effects. The readings were tabulated and subjected to statistical analysis. The results of the study after excluding the changes due to growth showed reduction in ANB and OP-SN values, indicating a significant reduction in the skeletal class II relationship. An upward cant of the occlusal plane in the treatment group was noted, probably due to the forward rotation of mandible. A significant increase in the vertical dimensions of the face in general and the mandible in particular was observed with the use of preorthodontic trainer. A significant reduction in the overjet and an increase in the inclination of mandibular incisor (L1-NB deg) were noted in the treatment group when compared with control group. It can be concluded that class II corrections can be achieved with the preorthodontic trainer appliance, which appears to have mostly dentoalveolar effects with smaller but significant skeletal effects.

Sterilization is the best method to counter the threats of microorganisms. The purpose of sterilization in the field of health care is to prevent the spread of infectious diseases. In dentistry, it primarily relates to processing reusable instruments to prevent cross-infection. The aim of this study was to investigate the efficacy of 4 methods of sterilizing endodontic instruments: Autoclaving, carbon dioxide laser sterilization, chemical sterilization (with glutaraldehyde) and glass-bead sterilization. The endodontic file was sterilized by 4 different methods after contaminating it with bacillus stearothermophillus and then checked for sterility by incubating after putting it in test tubes containing thioglycollate medium. The study showed that the files sterilized by autoclave and lasers were completely sterile. Those sterilized by glass bead were 90% sterile and those with glutaraldehyde were 80% sterile. The study concluded that autoclave or laser could be used as a method of sterilization in clinical practice and in advanced clinics; laser can be used also as a chair side method of sterilization.

In Pediatric Dentistry, the use of pit and fissure sealant is one of the essential forms of prevention. Pit and fissure caries may be substantially decreased by obliteration of these developmental defects in occlusal, buccal and lingual surfaces with resin based dental sealants. Visible light-curing units, or LCUs, are an integral part of modern adhesive dentistry" They are used to cure resin based composite restoration materials, resin modified glass-ionomer and pit and fissure sealants, as well as to bond orthodontic teeth. Most recently, the argon laser has been approved for initiating the setting reaction with visible light cured-resins. Argon curing of resin materials has been show to enhance the physical properties and degree of polymerization of the resin, while reducing the polymerization time by 75 percent. The study is undertaken considering the inadequate research reports of regarding the comparison of curing ability using argon laser. LEDs and visible light as well as the resistant towards caries activity of the preventive fluoride releasing pit and fissure sealant cured by above mentioned curing units.

Background: Temporomandibular joint (TMJ) ankylosis or hypomobility involves fusion of the mandibular condyle to the base of the skull. It is a major clinical problem that affects many patients suffering from facial trauma, infection, or systemic disease. The treatment of TMJ ankylosis poses a significant challenge because of technical difficulties and a high incidence of recurrence. Case Report: This report describes a case of a 4-year-old boy with inability to open mouth, diagnosed with unilateral right bony TMJ ankylosis. The surgical approach consisted of gap arthroplasty followed by vigorous physiotherapy. Conclusion: A detailed history, clinical and functional examination, radiographic examination facilitating correct diagnosis followed by immediate surgical intervention, and physiotherapy can help us to restore physical, psychological, and emotional health of the child patient.

Objectives: The objective of this study was to evaluate tooth brushing management and ability of children in relation to age and gender. Materials and Methods: The study population consisted of 45 children, who attended Department of Pedodontics and Preventive Dentistry at V.S Dental College and Hospital Bangalore. Children were divided into three groups according to age: Group I: 3-5 years, Group II: 6-8 years, and Group III: 9-11 years. Each child selected his/her favorite toothbrush and brushed his/her teeth under supervision of one instructor. The grip type during tooth brushing was recorded on a videotape and duration of tooth brushing also was noted. The data were analyzed in relation to the age and gender using the chi-square test. ANOVA was used to find if there is any significant difference between the mean brushing times in the different groups. Results: The results of statistical analysis showed that in all cases P> 0.05 for grip preferences and P < 0.001 between age groups 3-5 years and 9-11 years with respect to the mean brushing time. Conclusion: The required manual dexterity for tooth brushing was present in younger age groups.

Alterations in the functions of the facial muscle can establish changes in facial skeleton and in the development of occlusion. The effect of mouth breathing on the facial morphology is probably greatest during the growth period. Removal of nasal obstruction, adenoids, and tonsils have not given beneficial results in the reversion of the habit unless intercepted with various muscle exercises. Hence, this study was conducted to ultrasonographically evaluate the effectiveness of circumoral muscle exercises in the developing dentofacial morphology in adenotonsillectomized children.

Children aged 6-15 years old experience more injuries to their teeth and the injuries sustained are more serious as evidenced by a higher percentage of luxations, avulsions, fractures and dislocations. The mandible is the most frequently fractured facial bone and mandibular alveolar injuries have been reported to range between 8.1-50.6%. Those with mandibular or midface fractures have a higher incidence of associated chest, extremity, abdomen and cervical spine injuries. The growing patient with facial injuries presents the clinician with a series of thought-provoking circumstances. Dentoalveolar and mandibular injuries are especially important to understand because of the potential complications related to tooth eruption, alveolar development, occlusion and facial growth. However, the principles involved in the treatment for children need to be modified by certain anatomical, physiological and psychological factors specifically related to childhood. This case report documents the trauma, management and follow-up care of an 11-year-old boy who sustained undisplaced infraorbital, nasal fractures and mandibular dentoalveolar fracture along with other associated injuries of the extremities.

The peripheral ossifying fibroma (POF) is a reac-tive gingival overgrowth occurring frequently in the anterior maxilla in teenagers and young adults. The pediatric patient with a POF has special manage-ment considerations compared to the adult, as it requires early recognition and treatment by the dentist. It requires proper treatment protocol with close postoperative follow-up. The present report describes a case of POF in a girl, which was surgically excised from the palatal mucosa in the maxillary incisor area. Some features of the differential diagnosis and therapy when it occurs are discussed.

Background: Oral health is an essential component of health throughout life. However, millions of individuals suffer from dental caries and periodontal disease, resulting in unnecessary pain, difficulty in chewing, swallowing and speaking, and increased medical costs; hence, the present study was conducted to evaluate the oral health status of school children which would help us in planning and implementing necessary preventive measures. Aims and Objectives: 1. To assess the prevalence of dental caries among school children, using the Dentition Status and Treatment Needs Index. 2. To assess the prevalence of malocclusion among the study population, using the WHO criteria. 3. To assess the prevalence of dental calculus among the study population using the criteria of Community Periodontal Index of Treatment Needs. Materials and Methods: The study was conducted at a school in Bangalore city. The study population comprised of school children of two age groups - 6 and 12 years. A total of 430 subjects of both the sexes were surveyed, out of which 229 were in 6-year age group and 201 in 12-year age group. Results: No significant difference was observed between the age groups - 6 and 12 years - with respect to the proportion of dental caries (P > 0.05). Highly significant difference was noticed between the two age groups with respect to calculus (P < 0.01) and malocclusion (P < 0.05).

Children are uniquely susceptible to cranio facial trauma because of their greater cranial mass to body ratio. Below the age of 5, the incidence of pediatric facial fractures in relation to the total is very low ranging from 0.6-1.2%. Maxillo-facial injuries may be quite dramatic causing parents to panic and the child to cry uncontrollably with blood, tooth and soft tissue debris in the mouth. The facial disfigurement caused by trauma can have a deep psychological impact on the tender minds of young children and their parents. This case report documents the trauma and follow up care of a 4-year-old patient with maxillofacial injuries.

We present the largest optical photometry compilation of gamma-ray bursts (GRBs) with redshifts (z). We include 64813 observations of 535 events (including upper limits) from 28 February 1997 to 18 August 2023. We also present a user-friendly web tool grbLC which allows users to visualize photometry, coordinates, redshift, host galaxy extinction, and spectral indices for each event in our database. Furthermore, we have added a Gamma-ray Coordinate Network (GCN) scraper that can be used to collect data by gathering magnitudes from the GCNs. The web tool also includes a package for uniformly investigating colour evolution. We compute the optical spectral indices for 138 GRBs, for which we have at least four filters at the same epoch in our sample, and craft a procedure to distinguish between GRBs with and without colour evolution. By providing a uniform format and repository for the optical catalogue, this web-based archive is the first step towards unifying several community efforts to gather the photometric information for all GRBs with known redshifts. This catalogue will enable population studies by providing light curves (LCs) with better coverage since we have gathered data from different ground-based locations. Consequently, these LCs can be used to train future LC reconstructions for an extended inference of the redshift. The data gathering also allows us to fill some of the orbital gaps from Swift in crucial points of the LCs, e.g. at the end of the plateau emission or where a jet break is identified. [ABSTRACT FROM AUTHOR]

Coal, a fossil fuel, has been one of the most prominent sources of energy throughout the globe. Alongside its many blessings of being a reliable energy source, it has some curses, including global warming and air, water pollution, and environmental impacts. Born from ancient flora, decaying through epochs past, carbon-laden, fuelling eons in a vast contrast. Anthracite, bituminous, a trove of diverse grades, a worldwide energy titan, but with environmental shades. This study explores into the intricate impacts of coal-fired power plants, navigating the intersection of energy demand, environmental responsibility, and the historical legacy of this carbon-rich resource. In doing so, it employs the "cradle-to-gate" method of life cycle assessments (LCA), a well-researched approach that scrutinizes the entire life cycle of coal-fired power generation. During all three stages, fuel extraction, fuel transportation, and plant operation, basic hotspots of pollution are identified and their adverse effects on the environment are looked into. An analysis of a 530 MW power plant in China has been considered. This report uses both CML (Centrum voor Milieukunde Leiden) 2001 (Baseline) and ReCiPe Midpoint (H) analyses to conduct a detailed comparative examination of the environmental implications of the plant's operation in addition to only the electricity generation. Climate change, freshwater aquatic ecotoxicity, acidification potential, marine aquatic ecotoxicity, etc are some of the hazards identified during the study. A better scientific approach following standard guidance and efficient management can help to mitigate the pollution caused. The article presents the results of studies of the diverse impact of coal generation on the environment and discusses the most environmentally friendly methods of using this type of fuel to generate electricity. [ABSTRACT FROM AUTHOR]

This study investigates the unsteady, magnetohydrodynamic, incompressible, Couette flow of viscoelastic fluid through equidistant upright plates in the presence of permeable media, continuous heat fluxes, heat source, and energy dissipation. The flow is restricted by the flow between two equidistant upright plates, one moving and the other at rest, and the formation of free convection due to a fixed wall at a time-dependent temperature, while heat flow is constant on the wall moving upwards in its plane. The problem is solved analytically, and the expression for velocity and temperature are derived. The effect of numerous physical parameters on the flow is discussed. The local skin friction is also represented graphically, and the Nusselt number is given in the table. [ABSTRACT FROM AUTHOR]

No experimental study has been done so far on the natural degradation of the traditional Sanchi manuscripts made from the bark of agarwood (aloeswood, i.e. Acquilaria agallocha Roxb., locally known as Sanchi tree in Assam, North East India). In this study, SEM, FTIR, XRD and stress-strain test using UTM were carried out on lignocellulosic Sanchi manuscripts to determine cellulosic variations. Reduction of crystallinity index of cellulose, decrease in tensile strength and toughness indicated the natural degradation of Sanchi manuscript. The study reveals that the Sanchi manuscripts are highly vulnerable to natural degradation, and therefore need scientific techniques and treatments to prolong lignocellulosic changes. [ABSTRACT FROM AUTHOR]

Background: Callosobruchus chinensis (Fabricius) (Coleoptera: Bruchidae) is one of the major insect pests of Phaseolus vulgaris L. grains, commonly known as rajma seeds, in Europe and Asia including India. Infestations of these insects destroy majority of legume seeds including rajma which causes a great economic loss. Hence, a proper sustainable pest management measures are necessary for storage of rajma seeds. For this, the study aims to identify and quantify the n-alkane profile from the surface waxes of rajma seeds and their role as olfactory cue in C. chinensis. Individual synthetic alkane followed by the synthetic blends mimicking rajma seed surface wax n-alkanes as olfactory cue was also evaluated. Methods: Collected rajma seeds were solvent extracted to isolate surface waxes. The extract then fractioned by thin-layer chromatography and followed by gas chromatography-mass spectrometry analyses to purify, quantify and identify n-alkanes. Result: Rajma seeds' surface waxes analysis revealed 18 n-alkanes between n-C15 and n-C33. The predominant alkanes were noctacosane and n-hexadecane. n-Octadecane was the least abundant alkane in seeds. Total alkane content was 3502.67±12.82μg from 100 g (number 200 ± 5.13) seeds. Adult female C. chinensis elicited attraction towards the surface wax alkanes at concentrations of 0.5, 1, 2, 4 and 6 seed(s) equivalent of rajma seed(s) in the Y-tube olfactometer bioassay, but the highest attraction was observed at 6 seeds equivalent. Hence, a synthetic alkane blend resembling of 6 seeds equivalent, present in seeds' surface wax alkane or a combination of nine (which elicited positive response) synthetic alkane blend resembling 6 seeds equivalent could be used as lures in developing baited trap in insect pest management programme. [ABSTRACT FROM AUTHOR]