Characteristics Associated with Substance Use and Non-use Among Street Children in Delhi, India: A Community-based Cross-sectional Epidemiological Study.

Background: Street children are vulnerable to adverse health and risk behaviors and drug use. Substance use among street children has been well documented in several countries. This study reports sociodemographic and peer, family, and stress-related factors associated with substance use and non-use in a representative sample of street children of Delhi. Methods: This cross-sectional survey was conducted through six NGOs working with street children, using Respondent Driven Sampling, in nine districts of Delhi (n = 766, 7-18 years). The multivariable model was developed by applying binary logistic regression analysis. Results: The rate of substance use was 49%. Significant association was found between substance use in the past year and increasing age [Odds Ratio: OR (95% Confidence Interval)] [1.22(1.12,1.33)], male sex [4.34 (2.28,8.26)], lacking psychosocial support from family/relatives [3.27(1.84,5.80)], being engaged in earning from illegal sources, [3.04(1.75,5.29)], family use of substance [2.59(1.38,4.89)], presence of substance-using peers [29.86(14.38,62.01)], lack of non-drug-using peers [2.35(1.46,3.79)], and not possessing basic amenities [2.26(1.31,3.93)]. Conclusion: Multiple modifiable factors exist within the family and peer group, including risk and protective factors or a consequence of substance use. Some challenges in the form of difficulty in reaching out to them and poor treatment seeking by those using substances warrant intensification in both primary and secondary prevention initiatives.

Repurposing of potential antiviral drugs against RNA-dependent RNA polymerase of SARS-CoV-2 by computational approach.

The high incidences of COVID-19 cases are believed to be associated with high transmissibility rates, which emphasizes the need for the discovery of evidence-based antiviral therapies for curing the disease. The rationale of repurposing existing classes of antiviral small molecule therapeutics against SARS-CoV-2 infection has been expected to accelerate the tedious and expensive drug development process. While Remdesivir has been recently approved to be the first treatment option for specific groups of COVID-19 patients, combinatory therapy with potential antiviral drugs may be necessary to enhance the efficacy in different populations. Hence, a comprehensive list of investigational antimicrobial drug compounds such as Favipiravir, Fidaxomicin, Galidesivir, GC376, Ribavirin, Rifabutin, and Umifenovir were computationally evaluated in this study. We performed in silico docking and molecular dynamics simulation on the selected small molecules against RNA-dependent RNA polymerase, which is one of the key target proteins of SARS-CoV-2, using AutoDock and GROMACS. Interestingly, our results revealed that the macrocyclic antibiotic, Fidaxomicin, possesses the highest binding affinity with the lowest energy value of -8.97 kcal/mol binding to the same active sites of RdRp. GC376, Rifabutin, Umifenovir and Remdesivir were identified as the next best compounds. Therefore, the above-mentioned compounds could be considered good leads for further preclinical and clinical experimentations as potentially efficient antiviral inhibitors for combination therapies against SARS-CoV-2.

Ellagic Acid as a Potential Inhibitor against the Nonstructural Protein NS3 Helicase of Zika Virus: A Molecular Modelling Study.

Zika virus is a member of the Flaviviridae family and genus Flavivirus, which has a phylogenetic relationship with spondweni virus. It spreads to humans through a mosquito bite. To identify potential inhibitors for the Zika virus with biosafety, we selected natural antiviral compounds isolated from plant sources and screened against NS3 helicase of the Zika virus. The enzymatic activity of the NS3 helicase is associated with the C-terminal region and is concerned with RNA synthesis and genome replication. It serves as a crucial target for the Zika virus. We carried out molecular docking for the target NS3 helicase against the selected 25 phytochemicals using AutoDock Vina software. Among the 25 plant compounds, we identified NS3 helicase-ellagic acid (-9.9 kcal/mol), NS3 helicase-hypericin (-9.8 kcal/mol), and NS3 helicase-pentagalloylglucose (-9.5 kcal/mol) as the best binding affinity compounds based on their binding energies. To understand the stability of these complexes, molecular dynamic simulations were executed and the trajectory analysis exposed that the NS3 helicase-ellagic acid complex possesses greater stability than the other two complexes such as NS3 helicase-hypericin and NS3 helicase-pentagalloylglucose. The ADMET property prediction of these compounds resulted in nontoxicity and noncarcinogenicity.

Plant-Derived Antiviral Compounds as Potential Entry Inhibitors against Spike Protein of SARS-CoV-2 Wild-Type and Delta Variant: An Integrative in SilicoApproach.

The wild-type SARS-CoV-2 has continuously evolved into several variants with increased transmissibility and virulence. The Delta variant which was initially identified in India created a devastating impact throughout the country during the second wave. While the efficacy of the existing vaccines against the latest SARS-CoV-2 variants remains unclear, extensive research is being carried out to develop potential antiviral drugs through approaches like in silico screening and drug-repurposing. This study aimed to conduct the docking-based virtual screening of 50 potential phytochemical compounds against a Spike glycoprotein of the wild-type and the Delta SARS-CoV-2 variant. Subsequently, molecular docking was performed for the five best compounds, such as Lupeol, Betulin, Hypericin, Corilagin, and Geraniin, along with synthetic controls. From the results obtained, it was evident that Lupeol exhibited a remarkable binding affinity towards the wild-type Spike protein (-8.54 kcal/mol), while Betulin showed significant binding interactions with the mutated Spike protein (-8.83 kcal/mol), respectively. The binding energy values of the selected plant compounds were slightly higher than that of the controls. Key hydrogen bonding and hydrophobic interactions of the resulting complexes were visualized, which explained their greater binding affinity against the target proteins-the Delta S protein of SARS-CoV-2, in particular. The lower RMSD, the RMSF values of the complexes and the ligands, Rg, H-bonds, and the binding free energies of the complexes together revealed the stability of the complexes and significant binding affinities of the ligands towards the target proteins. Our study suggests that Lupeol and Betulin could be considered as potential ligands for SARS-CoV-2 spike antagonists. Further experimental validations might provide new insights for the possible antiviral therapeutic interventions of the identified lead compounds and their analogs against COVID-19 infection.

Rare Mixed Thyroid Carcinomas: A Report of Two Cases.

INTRODUCTION: Thyroid cancers constitute 0.5%- 1% of all cancers of which differentiated cancers are most common. Mixed thyroid carcinomas are rare entities comprising only 0.5% of thyroid cancers. These tumours pose challenges in diagnosis by fine needle aspiration cytology. CASE REPORT: Here, we present two rare cases of these mixed thyroid carcinomas. The first is that of a 21 year old female diagnosed with medullary thyroid carcinoma by the method of fine needle aspiration cytology (FNAC). She underwent definitive surgical treatment. Final histopathology revealed diagnosis of a nodular tumour with mixed features predominantly medullary carcinoma with areas of follicular carcinoma, confirmed on immunohistochemistry. Second report is that of a 45-year- old female diagnosed as medullary thyroid carcinoma on fine needle aspiration cytology (FNAC). Definitive surgical treatment was performed. Histopathology showed a mixed tumour with medullary and papillary components as confirmed through the process of immunohistochemistry. CONCLUSIONS: The knowledge of these rare carcinomas is important in avoiding a dilemma in management of this condition. Detection of these mixed tumours is difficult by FNAC. The definitive treatment essentially requires recognition of medullary component. We re-emphasize the importance of immune-histochemistry in arriving at an accurate diagnosis.

Fracture-dislocation of the thoracolumbar spine without neurological deficit: a report of two cases and literature review.

INTRODUCTION: We report two cases of fracture-dislocation of the thoracolumbar spine without neurological deficit and outline the putative mechanisms responsible for the escape of neural tissues from injurious forces and the surgical management strategies for this type of injury. We also review similar cases described in the literature. CASE REPORTS: A 24-year-old female with post-traumatic fracture dislocation at the T10-T11 level without neurological deficit, along with a right femoral shaft fracture, was managed with laminectomy of T10-T11 levels with bilateral facetectomy and transpedicular screws and with an intramedullary interlocking nail for the femur fracture. Another 26-year-old female (post-traumatic fracture dislocation at the T12 - L1 level treated by open reduction and pedicle screw instrumentation elsewhere) presented with implant failure and re-dislocation which was managed with laminectomy of T12- L1 levels, facetectomy and discectomy, and deformity correction, followed by 9 mm × 25 mm bullet cage insertion and fixation using transpedicular screws. Neurological function was preserved postoperatively. Both individuals returned to household activity 6 months postoperatively. DISCUSSION: Fracture-dislocations of the thoracolumbar spine without neurological deficit have been infrequently reported. The mechanism responsible for the preservation of normal neurological function; is either posterior element fractures leading to free-floating laminae or a fracture-separation of the vertebral arch, in which pedicle fractures allow the posterior elements to remain nearly aligned, with preservation of the spinal canal integrity and maintenance of normal spinal cord function. These fracture-dislocations need to be managed carefully to achieve a good outcome.

Assessment of voice related quality of life and its correlation with socioeconomic status after total laryngectomy.

BACKGROUND: After total laryngectomy for laryngeal cancer, the major determinants of QOL is the patient's voice related quality of life (V-RQOL). The primary aim of this study was to assess the V-RQOL and impact of socioeconomic status over it in Indian population by using two validated scales [voice handicap index (VHI) and V-RQOL questionnaires]. METHODS: Total 104 patients underwent total laryngectomy but 71 were eligible for study. Patients filled the VHI and V-RQOL questionnaires after completion of 1 year of usage of the TEP voice. The socioeconomic status of the patients was calculated according to various domains related to their life and were divided into lower and higher status. RESULTS: A total of 76.1% patients had VHI score between 0 to 30 (minimal voice handicap), 19.7% had score between 31 to 60 (moderate voice handicap) and only 4.2% patients had VHI score more than 61 (serious voice handicap). On V-RQOL scores, 16.9% patients had score between 10 to 15 (excellent), 40.8% patients, between 16 to 20 (very good), 22.5% patients, between 21 and 25 (good voice), 15.5% patients, between 26 and 30 (fair) and only 4.2% patients scored more than 30 with poor quality of voice. Patients with lower socioeconomic group had better V-RQOL than with high socioeconomic group. CONCLUSIONS: VHI and V-RQOL scores in our series were superior to other studies due to major population with lower socioeconomic status and better social support which exists in our society.

Vallecular cyst in neonates: case series-a clinicosurgical insight.

The objective of the case series is to understand the clinical and surgical aspects of new minimally invasive technique of coblation in cases of vallecular cysts in neonates. Method of Study. Four neonates underwent surgery for vallecular cyst by using Arthrocare ENT coblator system. Results Obtained. All the four cases presented in stridor and difficult intubation was also a concern which necessitated a swift, high precision instrument with almost immediate results. Coblation excision includes direct contact with vallecular cyst, improved targeting of the cyst, and preservation of normal tissue. All the four cases had an uneventful postoperative period and smooth recovery and had an early discharge from the hospital. Conclusions. Early diagnosis and intervention hold the key for an early recovery and for minimizing nutritional disturbances secondary to poor feeding in cases of neonatal vallecular cysts.

Recurrent rhinosporidiosis: coblation assisted surgical resection-a novel approach in management.

Recurrent rhinosporidiosis is a chronic granulomatous disease with a known tendency to reoccur. Coblation EVAC 70 is a novel surgical tool which seems to provide excellent option in management of this notorious disease. We present an interesting case and the innovative approach in its management, using Coblation system. Introduction. Rhinosporidiosis seeberi causes a chronic granulomatous disease of upper airway, usually involving the nose and nasopharynx, and has a notorious tendency to reoccur. The current line of management is surgical excision of the lesion along with cauterization of the base, which does not prevent reoccurrence of the disease. Case Presentation. A 65-year-old male resident of rural India reported a history of breathing difficulty and change in voice. Patient is a Hindu priest by profession, who according to their rituals has to take bath in local pond or river. Conclusion. Rhinosporidiosis is a difficult to treat pathology due to its tendency to reoccur. Till date the management of the disease is far from satisfactory. Coblation system which has already found its roots in otorhinolaryngology can be used as a novel tool in surgical resection of recurrent rhinosporidiosis and has added advantage of low temperature dissection along with clear surgical field due to constant suctioning.

Inflammatory myofibroblastic tumor of trachea.

Inflammatory myofibroblastic tumor (IMT) is an uncommon entity usually encountered among children and involving the lungs. Involvement of trachea, however, is extremely rare with only a few published case reports. The condition may present with deceptive clinical features. We report a case of tracheal IMT in a 23-year-old female who presented with clinical symptoms mimicking asthma. On further evaluation, she was detected to have a tracheal mass that was diagnosed as IMT on histopathology and was successfully treated surgically. This case report highlights the rarity and diagnostic challenge associated with the condition.

Receptive field properties of near neighbor orientation selective neurons in the visual cortex: a modeling study.

The primary visual cortex is organized into clusters of cells having similar receptive fields (RFs). A purely feedforward model has been shown to produce realistic simple cell receptive fields. The modeled cells capture a wide range of receptive field properties of orientation selective cortical cells. We have analyzed the responses of 78 nearby cell pairs to study which RF properties are clustered. Orientation preference shows strongest clustering. Orientation tuning width (hwhh) and tuning height (spikes/sec) at the preferred orientation are not as tightly clustered. Spatial frequency is also not as tightly clustered and RF phase has the least clustering. Clustering property of orientation preference, orientation tuning height and width depend on the location of cells in the orientation map. No such location dependence is observed for spatial frequency and RF phase. Our results agree well with experimental data.

QSAR study on phenolic activity: need of positive hydrophobic term (log P) in QSAR.

The phenolic activity (log 1/C) of a large series of phenols against L1210 leukaemia cells was modelled using physicochemical parameters other than conventional electronic and steric parameters. Attempts have also been made to examine need or otherwise of the hydrophobic parameter, log P, in such studies. The results have shown that contribution of log P in modelling log 1/C is favourable.