Use of cost-effective software for lesion localization in brain surgery: Technical note.

Lesion localization has been an important aspect of neurosurgery and has advanced significantly with technological evolution. The journey started from the localization of lesion based on clinical findings to the current era where neuronavigation and virtual reality are being used for the purpose. However, the financial implications of these advanced equipments have made them inaccessible for patients in the majority of low- and middle-income countries. The authors describe techniques to use software, which are cost effective and can be used effectively for the localization of a lesion of the brain.

"Genome-wide identification of bZIP gene family in Pearl millet and transcriptional profiling under abiotic stress, phytohormonal treatments; and functional characterization of PgbZIP9".

Abiotic stresses are major constraints in crop production, and are accountable for more than half of the total crop loss. Plants overcome these environmental stresses using coordinated activities of transcription factors and phytohormones. Pearl millet an important C4 cereal plant having high nutritional value and climate resilient features is grown in marginal lands of Africa and South-East Asia including India. Among several transcription factors, the basic leucine zipper (bZIP) is an important TF family associated with diverse biological functions in plants. In this study, we have identified 98 bZIP family members (PgbZIP) in pearl millet. Phylogenetic analysis divided these PgbZIP genes into twelve groups (A-I, S, U and X). Motif analysis has shown that all the PgbZIP proteins possess conserved bZIP domains and the exon-intron organization revealed conserved structural features among the identified genes. Cis-element analysis, RNA-seq data analysis, and real-time expression analysis of PgbZIP genes suggested the potential role of selected PgbZIP genes in growth/development and abiotic stress responses in pearl millet. Expression profiling of selected PgbZIPs under various phytohormones (ABA, SA and MeJA) treatment showed differential expression patterns of PgbZIP genes. Further, PgbZIP9, a homolog of AtABI5 was found to localize in the nucleus and modulate gene expression in pearl millet under stresses. Our present findings provide a better understanding of bZIP genes in pearl millet and lay a good foundation for the further functional characterization of multi-stress tolerant PgbZIP genes, which could become efficient tools for crop improvement.

Optochiasmatic Cavernomas: Updated systematic review and proposal of a novel classification with surgical approaches.

Cavernomas are histologically benign vascular malformations found at different sites in the brain. A rare site for such cavernomas, however, is the anterior optic pathway, comprising the optic nerve, chiasma, and optic tract-called optochiasmatic cavernomas (OCC). These lesions usually present with sudden onset or progressive vision loss, headache, and features mimicking pituitary apoplexy. In this paper, we describe a case of OCC operated at our center. We carry out an updated review of literature depicting cases of OCC, their clinical presentation, management, and postoperative complications. We also propose a novel classification system based on lesion location and further analyze these cavernoma types with respect to the surgical approach used and visual outcome. A 30-year-old lady had presented with a 3-week history of progressive bilateral vision loss and headache. Based on imaging, she was suspected to have a cavernous angioma of the chiasma and left optic tract. Due to progressive vision deterioration, the lesion was surgically excised using pterional craniotomy. Postoperatively, her visual symptoms improved, but she developed diabetes insipidus. Clinical and radiological follow-up has been done for 18 months after surgery. A total of 81 cases have been described in the literature, including the present case. Chiasmal apoplexy is the most common presentation. Surgical excision is the standard of care. Our analysis based on lesion location shows the most appropriate surgical approach to be used for each cavernoma type. Visual outcome correlates with the preoperative visual status. Visual outcome is good in patients presenting with acute chiasmal apoplexy, and when complete surgical excision is performed. The endonasal endoscopic approach was found to provide the best visual outcome. In addition to preoperative visual status, complete surgical excision predicts favorable visual outcomes in OCC. Our proposed classification system guides the appropriate surgical approach required for a particular location of the cavernoma.

A Prospective Comparative Study between 99mTc MIBI Myocardial Perfusion Single-Photon Emission Computed Tomography and Dobutamine Stress Echocardiography to Detect Viable Myocardium in Patients with Coronary Artery Disease.

Introduction: The objective of this study was to compare 99mTc MIBI myocardial perfusion SPECT and Dobutamine Stress Echocardiography (DSE) in detecting viable myocardium in patients with Coronary Artery Disease. Materials and Methods: Total of 50 patients who with CAD and poor LV function were idenitifed on 2D Echo using 16 segment cardiac model. These patients underwent 99mTc MIBI myocardial perfusion SPECT and Dobutamine Stress Echocardiography and the results were compared with the gold standard 18F-FDG PET-CT findings. Results: A Total of 550 dysfunctional segments were identified in datasets of 50 patients on 2D echo. No significant difference was noted between the pairwise positive outcome of viable segment between MIBI SPECT and DSE (p=0.875). MIBI SPECT showed a sensitivity of 86.5% and specificity of 90.0% when compared with 18F-FDG PET-CT which was comparable with DSE having a sensitivity of 87.6% and specificity of 90.7%. Conclusion: 99mTc MIBI SPECT is an effective good alternative for evaluation of viable myocardial segments in patients with dysfunctional myocardium and can be considered especially in elderly or obese patients and patients with lung disease having poor echocardiographic imaging window due to lack of an optimal acoustic window.

Use of Multimodality Intraoperative Neuromonitoring in Tethered Cord Syndrome - Experience from a Tertiary Care Center.

Detethering of the spinal cord is done in nearly all cases of tethered cord syndrome (TCS), which can damage nerve roots, and hence, there is a need to identify filum terminale during surgery. Multimodality intraoperative neuromonitoring (IONM) may be useful in this regard to prevent postoperative morbidity. Twenty-six patients (13 males and 13 females, age range: one year to 56 years) with TCS were recruited for the study. Triggered electromyography (t-EMG), transcranial motor evoked potential (TcMEP) and free-running electromyography (f-EMG) were used in the study on a case-to-case basis. Warning criteria were followed according to the standard guidelines. Nerve roots and filum terminale were successfully identified and detethered in all cases. There was no new postoperative deficit seen. Transcranial motor evoked potentials did not change during surgery and no new limb weakness was seen in any of the investigated cases. Triggered EMG successfully helps in identifying nerve roots and filum terminale, while TcMEP is a good prognostic indicator of motor viability. Multimodality IONM use during tethered cord surgery should be encouraged to prevent postoperative deficits.

The status of COVID-19 vaccines in India: A review.

The outbreak of SARS-CoV-2, an etiologic agent of the COVID-19 pandemic disease in late December 2019 has left the whole world aghast with huge health and economic losses. Due to a lack of specific knowledge and understanding at the initial stages, an unprecedented rise in COVID-19 cases has been recorded globally. Various preventive measures and strategies were implemented, however, for the radical control of SARS-CoV-2 infections; it seems that the only effective way to control the ongoing infections is large-scale vaccination. So far, WHO has approved 11 vaccines for emergency use namely Pfizer/BioNTech, Oxford/Astra Zeneca, Johnson and Johnson, Moderna, Covilo, Novavax, Covovax, Spikevax, Can Sino, Comirnaty, and Coronavac while five other needs approval. The worldwide vaccination dataset reveals that 65.7% of the world population has received their first dose of the COVID-19 vaccine. As a consequence of the proactive implementation of India's vaccination program, a historical milestone of administering over 1.9 billion doses of COVID-19 vaccines have been achieved on 19th May 2022. This review summarizes the different types of traditional and modern vaccine designing strategies with an emphasis on COVID-19. Moreover, the review highlights the status of vaccines for COVID-19 approved in India which includes both indigenous and non-indigenous vaccines. The present article also encompasses vaccine designing and developmental strategies, efficacy, safety profile and usage among the population, and the efficacy of modern vaccines over traditional ones.

El brote de SARS-CoV-2, un agente etiológico de la enfermedad pandémica COVID-19, a fines de diciembre de 2019, ha dejado al mundo entero horrorizado con enormes pérdidas económicas y de salud. Debido a la falta de conocimiento y comprensión específicos en las etapas iniciales, se ha registrado un aumento sin precedentes en los casos de COVID-19 a nivel mundial. Sin embargo, se implementaron diversas medidas y estrategias preventivas para el control radical de las infecciones por SARS-CoV-2; parece que la única forma eficaz de controlar las infecciones en curso es la vacunación a gran escala. Hasta el momento, la OMS ha aprobado 11 vacunas para uso de urgencia Pfizer/BioNTech, Oxford/Astra Zeneca, Johnson and Johnson, Moderna, Covilo, Novavax, Covovax, Spikevax, Can Sino, Comirnaty y Coronavac, mientras que otras cinco necesitan aprobación. El conjunto de datos de vacunación mundial revela que el 65,7% de la población mundial ha recibido su primera dosis de la vacuna COVID-19. Como consecuencia de la implementación proactiva del programa de vacunación de la India, el 19 de mayo de 2022 se logró un hito histórico de administrar más de 1900 millones de dosis de vacunas contra el COVID-19. Esta revisión resume los diferentes tipos de estrategias de diseño de vacunas tradicionales y modernas con énfasis sobre COVID-19. Además, la revisión destaca el estado de las vacunas para COVID-19 aprobadas en India, que incluye vacunas tanto indígenas como no indígenas. El presente artículo también abarca estrategias de diseño y desarrollo de vacunas, eficacia, perfil de seguridad y uso entre la población, y la eficacia de las vacunas modernas sobre las tradicionales.

Mucous Extractor for Tumor Tissue Sampling in Neurosurgery.

Objective Collection of sample for histopathological analysis is highly important during any surgical procedure. The histopathology report helps determine the diagnosis, prognosis further management, and follow-up plan. The use of a reliable sample collection technique is doubly important in neurosurgical procedures because lesions are often deep-seated and difficult to access. Materials and Methods Conventional techniques of sample collection, such as use of tumor-grasping forceps and collection of material from the ultrasonic aspirator device suffer from limitations of access and unreliability. We propose a novel technique of sample collection using readily available mucous aspirator device. Results This device is economical, sterile, and disposable. It can be used even in low-resource settings because it is easily available. It can also be connected to suction cannula and the negative pressure settings can be adjusted as required. Conclusion The use of this device for neurosurgical procedures has been tried in the transcranial and transnasal neurosurgical procedures and found to be effective. The sample collected in the canister of the mucous aspirator can be directly sent to the laboratory for histopathological analysis.

MYB Transcription Factor Family in Pearl Millet: Genome-Wide Identification, Evolutionary Progression and Expression Analysis under Abiotic Stress and Phytohormone Treatments.

Transcription factors (TFs) are the regulatory proteins that act as molecular switches in controlling stress-responsive gene expression. Among them, the MYB transcription factor family is one of the largest TF family in plants, playing a significant role in plant growth, development, phytohormone signaling and stress-responsive processes. Pearl millet (Pennisetum glaucum L.) is one of the most important C4 crop plants of the arid and semi-arid regions of Africa and Southeast Asia for sustaining food and fodder production. To explore the evolutionary mechanism and functional diversity of the MYB family in pearl millet, we conducted a comprehensive genome-wide survey and identified 279 MYB TFs (PgMYB) in pearl millet, distributed unevenly across seven chromosomes of pearl millet. A phylogenetic analysis of the identified PgMYBs classified them into 18 subgroups, and members of the same group showed a similar gene structure and conserved motif/s pattern. Further, duplication events were identified in pearl millet that indicated towards evolutionary progression and expansion of the MYB family. Transcriptome data and relative expression analysis by qRT-PCR identified differentially expressed candidate PgMYBs (PgMYB2, PgMYB9, PgMYB88 and PgMYB151) under dehydration, salinity, heat stress and phytohormone (ABA, SA and MeJA) treatment. Taken together, this study provides valuable information for a prospective functional characterization of the MYB family members of pearl millet and their application in the genetic improvement of crop plants.

Synthetic sub-genomic transcript promoter from Horseradish Latent Virus (HRLV).

MAIN CONCLUSION: We characterized an efficient chimeric sub-genomic transcript promoter from Horseradish Latent Virus, FHS4, active in both dicot and monocot plants, and it could be a potential tool for plant biotechnology. Plant pararetroviruses are a rich source of novel plant promoters widely used for biotechnological applications. Here, we comprehensively characterized a unique sub-genomic transcript (Sgt) promoter of Horseradish Latent Virus (HRLV) and identified a fragment (HS4; - 340 to + 10; 351 bp) that showed the highest expression of reporter genes in both transient and transgenic assays as evidenced by biochemical, histochemical GUS reporter assay and transcript analysis of uidA gene by qRT-PCR. Phylogenetic analysis showed that the HSgt promoter was closely related to the sub-genomic promoter of the Cauliflower Mosaic Virus (CaMV19S). We found that the as-1 element and W-box played an important role in the transcriptional activity of the HS4 promoter. Furthermore, the HS4 promoter was also induced by salicylic acid. Alongside, we enhanced the activity of the HS4 promoter by coupling the enhancer region from Figwort Mosaic Virus (FMV) promoter to the upstream region of it. This hybrid promoter FHS4 was around 1.1 times stronger than the most commonly used promoter, 35S (Cauliflower Mosaic Virus full-length transcript promoter), and was efficient in driving reporter genes in both dicot and monocot plants. Subsequently, transgenic tobacco plants expressing an anti-microbial peptide BrLTP2.1 (Brassica rapa lipid transport protein 2.1), under the control of the FHS4 promoter, were developed. The in vitro anti-fungal assay revealed that the plant-derived BrLTP2.1 protein driven by an FHS4 promoter manifested increased resistance against an important plant fungal pathogen, Alternaria alternata. Finally, we concluded that the FHS4 promoter can be used as an alternative to the 35S promoter and has a high potential to become an efficient tool in plant biotechnology.

New Late Cretaceous titanosaur sauropod dinosaur egg clutches from lower Narmada valley, India: Palaeobiology and taphonomy.

The Upper Cretaceous (Maastrichtian) Lameta Formation is well-known for its osteological and oological remains of sauropods from the eastern and western parts of the Narmada Valley, central India. The newly documented ninety-two titanosaur clutches from Dhar District (Madhya Pradesh State, central India) add further to this extensive data. Previously parataxonomy of these titanosaur clutches was carried out with a few brief reports on palaeobiological and taphonomic aspects. The quantitative data collected from the new clutches (this study) opens avenues to additionally understand more about titanosaur palaeobiology and to qualitatively understand preservation and taphonomical aspects of their egg clutches. Herein, we document 256 eggs and three clutch patterns (viz. circular, combination, linear) that are assignable to six oospecies. The high oospecies diversity points to a possible high diversity in titanosaur taxa in the Indian sub-continent though it is not reflected in titanosaurid body fossils. All the macro- and micro-structures helped in understanding egg deformation and preservation from a taphonomic point of view. Additionally, a pathologic egg documented from the study area helped in understanding the reproductive biology of titanosaurs, such as the possibility of segmented oviduct and sequential laying of eggs by titanosaurs. In addition, we made an attempt to infer aspects such as egg burial, absence of parental care, colonial nesting behavior. All the egg clutches were observed within sandy limestone and calcareous sandstone lithologies that occur in scattered outcrops with rocks showing floating siliciclastic grains in a micritic groundmass. Further, the presence of ferruginous sandstone in the Jamniapura and Padlya regions (Dhar District, central India) is indicative of a possible alluvial/fluvial setting. The presence of grainy intraclastic fabric, alveolar-septal fabrics, brecciation and shrinkage cracks observed in the clutch-bearing rocks are indicative of a low energy-low gradient palustrine depositional condition in a fluvial/alluvial setting. Finally, we envisage that a few egg clutches of this area were laid close to lake/pond margins while most were laid away from the lake/pond margins, and thus, were hatched.

Delayed post-operative aggravation of sleep related disturbances in patients of basilar invagination with Chiari malformation: case report and review of the literature.

Sleep apnoea is common in patients with Basilar Invagination with Arnorld Chiari Malformation (ACM). Various studies have shown its incidence in the range of 60-70% among such patients. Most of the studies have shown improvement in sleep disturbances after decompressive surgeries for Chiari Malformations. There is no report of postoperative deterioration due to sleep apnoea in these patients. Authors report two cases of basilar invagination associated with ACM and Platybasia, who deteriorated probably due to worsening of pre-existing sleep disorders on 3rd and 7th postoperative days after their surgeries, despite clinico-radiological improvements during their early post-operative courses. Authors discuss literature related to sleep apnoea in basilar invagination associated with Chiari Malformations and share precautions, which are relevant and should be undertaken in such patients especially during early post-operative periods to avoid alarming complication which may occur even in experienced hands.

Inguinal Lymphadenopathy: A Rare Initial Site of Metastatic Lung Carcinoma.

Solid-organ tumors involving inguinal lymph nodes commonly originate from genitourinary tract, skin, ano-rectum, or the urinary bladder. Thus, solitary metastatic involvement of inguinal lymph nodes from extra-abdominal primary malignancies is extremely rare. However, involvement of nonregional lymph nodes upstages the disease to M1b with poor prognosis. Identification of the site of metastases is extremely crucial for deciding the management of patients. This is the first ever case reported of de-novo or synchronous oligometastatic disease of carcinoma lung with inguinal lymph node involvement. In addition, it highlights the importance of 18 FDG PET-CT to diagnose the involvement of inguinal lymph node that was further proved on fine needle aspiration cytology. Only two such cases of lung cancer have been reported, but both of them had inguinal lymph node during the follow-up and none was present at initial presentation.

Analysis of SARS-CoV-2 mutations in the main viral protease (NSP5) and its implications on the vaccine designing strategies.

SARS-CoV-2 (Severe Acute Respiratory Syndrome), an etiolating agent of novel COVID-19 (coronavirus 2019) pandemic, rapidly spread worldwide, creating an unprecedented public health crisis globally. NSP5, the main viral protease, is a highly conserved protein, encoded by the genome of SARS-CoV-2 and plays an important role in the viral replication cycle. In the present study, we detected a total of 33 mutations from 675 sequences submitted from India in the month of March 2020 to April 2021. Out of 33 mutations, we selected 8 frequent mutations (K236R, N142L, K90R, A7V, L75F, C22N, H246Y and I43V) for further analysis. Subsequently, protein models were constructed, revealing significant alterations in the 3-D structure of NSP5 protein when compared to the wild type protein sequence which also altered the secondary structure of NSP5 protein. Further, we identified 9 B-cell, 10 T-cell and 6 MHC-I promising epitopes using predictive tools of immunoinformatics, out of these epitopes some were non-allergenic as well as highly immunogenic. Results of our study, however, revealed that 10 B-cell epitopes reside in the mutated region of NSP5. Additionally, hydrophobicity, physiochemical properties, toxicity and stability of NSP5 protein were estimated to demonstrate the specificity of the multiepitope candidates. Taken together, variations arising as a consequence of multiple mutations may cause alterations in the structure and function of NSP5 which generate crucial insights to better understand structural aspects of SARS-CoV-2. Our study also revealed, NSP5, a main protease, can be a potentially good target for the design and development of vaccine candidate against SARS-CoV-2.

El SARS-CoV-2 (Síndrome Respiratorio Agudo Severo), un agente etiológico de la nueva pandemia de COVID-19 (coronavirus 2019), se propagó rápidamente por todo el mundo y creó una crisis de salud pública sin precedentes a nivel mundial. El NSP5, la proteasa viral principal, es una proteína altamente conservada, codificada por el genoma del SARS-CoV-2 y juega un papel importante en el ciclo de replicación viral. En el presente estudio se detectaron un total de 33 mutaciones de 675 secuencias presentadas desde la India en el mes de marzo de 2020 a abril de 2021. De 33 mutaciones, se seleccionaron 8 mutaciones frecuentes (K236R, N142L, K90R, A7V, L75F, C22N, H246Y e I43V) para su posterior análisis. Posteriormente, se construyeron modelos proteicos que revelaron alteraciones significativas en la estructura 3D de las proteínas NSP5 en comparación con la secuencia de proteínas de tipo silvestre que también alteraron la estructura secundaria de la proteína NSP5. Además, se identificaron 9 epítopos prometedores de células B, 10 de células T y 6 de MHC-I, utilizando herramientas predictivas de inmunoinformática, algunos no alergénicos y altamente inmunogénicos. Los resultados de nuestro estudio, sin embargo, revelaron que 10 epítopos de células B residen en la región mutada de NSP5. Adicionalmente, se estimó la hidrofobicidad, propiedades fisicoquímicas, toxicidad y estabilidad de la proteína NSP5 para demostrar la especificidad de los candidatos multiepítopos. En conjunto, las variaciones que surgen como consecuencia de múltiples mutaciones pueden causar alteraciones en la estructura y función del NSP5 que generan conocimientos cruciales para entender mejor los aspectos estructurales del SARS-CoV-2. Nuestro estudio también reveló que el NSP5, una proteasa principal, puede ser un blanco potencialmente bueno para el diseño y desarrollo de la vacuna candidata contra el SARS-CoV-2.

Handmade models for aneurysm surgery: A useful tool for training.

Background: Aneurysm surgery is considered difficult by young and trainee neurosurgeons. This is due to difficulty in understanding orientation of aneurysm complex (proximal and distal vessels, aneurysm neck, and fundus) in relation to the surrounding structures (skull, brain, vessels, and nerves) after head is rotated, extended, and fixed on the head frame. Virtual three-dimensional (3D) imaging studies and 3D-printed models help young neurosurgeons but are not accessible to most of the centers due to need for resources (human and equipment). Authors used handmade 3D models of aneurysm complex to train young neurosurgeons before and during surgery to make them understand steps to treat it. Methods: RadiAnt DICOM viewer software (2022.1.1, 64-bit, Medixant, Poznan, Poland) was used for acquiring 3D Volume Rendering Technique images to make aneurysm models preoperatively. Twisted 20 Gauze galvanized iron wires were used for making proximal and distal branches and Epoxy Putty (M-seal, Pidilite ® industries, Mumbai, India) was used to make smooth surfaces of the vessels, aneurysm necks, and fundi. Models were used in operating room (OR) before and during surgery to help surgeons and trainees get oriented to the aneurysm complexes. Results: Handmade models, oriented as per patients' head position, were useful to make surgeons and trainees to understand projection of various components of the aneurysm complex in relation to adjacent structures, especially skull base, during both preoperative planning and in OR even before completion of the dissection. Conclusion: Handmade models of aneurysms are inexpensive tool and can help trainee neurosurgeons to plan and execute surgical management of aneurysms.

Genome sequence analysis of nsp15 from SARS-CoV-2.

SARS-CoV-2 (Severe Acute Respiratory Syndrome), a causative agent of COVID-19 disease created a pandemic situation worldwide. Nsp15 is a uridine specific endoribonuclease encoded by the genome of SARS-CoV-2. It plays important role in processing viral RNA and, thus evades the host immune system. Therefore, it is of interest to identify mutants of nsp15 amongst Asian SARS-CoV-2 isolates, where a total of 1795 mutations, from 7793 sequences of Asia submitted till 31st January 2022, amongst which A231V, H234Y, K109N, K259R and S261A mutations were found frequent. Hence, we report data on the predicted secondary structure of wild type form followed by hydropathy plot, physiochemical properties, Ramachandran plot, B-cell epitopes prediction and protein modeling of wild type and mutant of nsp15 protein. Data shows that nsp15 of SARS-CoV-2 is a pontential candidate for the development of vaccine to control the infections of SARS-CoV-2.

Methylmethacrylate Inter-Facetal and Inter-Vertebral Body Spacers for Cranio-Vertebral Junction and Various Spine Surgeries: Technical Note.

STUDY DESIGN: Prospective. PURPOSE: Over past one and half decade, ready-to-use magnetic resonance imaging (MRI) compatible spinal implants have changed the clinical practice and economics of spinal surgery. These are beyond reach of majority of population of developing countries like India due to financial reasons and also availability in remote areas. There is a growing need for a MRI compatible cost-effective spinal implant of proven quality. The authors used bone cement spacers for the said purpose for various level spine surgeries. OVERVIEW OF LITERATURE: Methylmethacrylate, known as bone cement, was used extensively for spinal surgeries from craniovertebral junction to sacrum for augmentation and replacement of various spinal elements. Its biochemical and biomechanical properties were tested for safe clinical use and was a favored material for spinal surgeons. MATERIALS AND METHODS: The authors made molds for making bone cement spacers for various spine levels with the help of silicone material. RESULTS: Sixteen patients (12 males, 4 females with an average age of 31 years) of various spine level surgeries were done where bone cement spacers were used. It included patients of basilar invagination (n = 9), dorsal Pott's disease (n = 1), lumbar (n = 2), and lumbo-sacral spondylolisthesis (n = 1). Spacers could be used without any difficulties and postoperative day 1- and 3-months follow-up computed tomography scan of the patients revealed no change in the dimensions of the spacer and fusion at 3 months of operated levels. CONCLUSION: The authors feel that bone cement spacers may be an effective and low-cost alternative to the existing costly alternatives.

Identification of recurrent mutations in exonuclease (nsp14); a potential drug target in SARS-CoV-2.

CONTEXT: The rapid outbreak of SARS-CoV-2 has become a significant global health concern, highlighting the dire need for antiviral therapeutic agents. RNA-dependent RNA polymerase (RdRp) of coronavirus plays crucial roles in RNA synthesis, and hence remains the druggable target for the treatment of this disease. The most potent broad-spectrum inhibitors of viral RdRp are members of nucleoside analogs (NAs). However, SARS-CoV-2 proved to be a challenging one for the novel NA drug designing strategy because coronavirus possesses an exonuclease (ExoN) domain that is capable of excising NAs, thus showing resistance to existing antiviral drugs. AIM: The objective of our study was to compare the SARS-CoV-2 exonuclease (nsp14) protein sequence of Wuhan-type virus with those of Indian SARS-Cov-2 isolates and to study the effect of multiple mutations on the secondary structure alterations of proteins. SUBJECTS AND METHODS: Multiple-sequence alignment of exonuclease amino-acid sequences followed by phylogenetic analysis and prediction of its secondary structure of the protein was performed. RESULTS: Altogether, seven mutations were detected in the nsp14 of Indian SARS-CoV-2 isolates. Subsequently, prediction of their secondary structures revealed that mutations altered the structural stability of exonuclease proteins. CONCLUSIONS: Present findings, therefore, further suggest that evolvability of SARS-CoV-2 is primarily associated with the onset of multiple novel mutations that rapidly spread at several new locations of the viral genome and also provides important insight to develop specific control strategies to fight against COVID-19 infections.

Identification and characterization of mutations in the SARS-CoV-2 RNA-dependent RNA polymerase as a promising antiviral therapeutic target.

The causative agent of COVID-19 is a novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV-2), which has emerged as a pandemic of global concern. Considering its rapid transmission, WHO has declared public health emergency on 11th March 2020 worldwide. SARS-CoV-2 is a genetically diverse positive sense RNA virus that typically exhibit high rates of mutation than DNA viruses. Higher rates of mutation bring higher genomic variability which may lead to viral evolution and enabling viruses to evade the pre-existing immunity of host and quickly acquire drug resistance properties. The objective of our study was to compare the SARS-CoV-2 RdRp sequences of Indian SARS-CoV-2 isolates with those of Wuhan type virus. A total of 384 point mutations were detected from 488 sequence of the RdRp protein of Indian SARS-CoV-2 genome, out of which seven were used for subsequent study. Furthermore, prediction of secondary structure, protein modeling and its dynamics were performed which revealed that seven mutations (R118C, T148I, Y149C, E802A, Q822H, V880I and D893Y) significantly altered the stability and flexibility of RdRp protein. Present study was therefore, undertaken to analyze the variations occurring in RdRp due to multiple mutations leading to the alterations in the structure and function of RNA-dependent RNA polymerase which is essential for the replication /transcription of this virus and hence can be utilized as a promising therapeutic target to curb SARS-CoV-2 infections.

Simulation of surgery for supratentorial gliomas in virtual reality using a 3D volume rendering technique: a poor man's neuronavigation.

OBJECTIVE: Different techniques of performing image-guided neurosurgery exist, namely, neuronavigation systems, intraoperative ultrasound, and intraoperative MRI, each with its limitations. Except for ultrasound, other methods are expensive. Three-dimensional virtual reconstruction and surgical simulation using 3D volume rendering (VR) is an economical and excellent technique for preoperative surgical planning and image-guided neurosurgery. In this article, the authors discuss several nuances of the 3D VR technique that have not yet been described. METHODS: The authors included 6 patients with supratentorial gliomas who underwent surgery between January 2019 and March 2021. Preoperative clinical data, including patient demographics, preoperative planning details (done using the VR technique), and intraoperative details, including relevant photos and videos, were collected. RadiAnt software was used for generating virtual 3D images using the VR technique on a computer running Microsoft Windows. RESULTS: The 3D VR technique assists in glioma surgery with a preoperative simulation of the skin incision and craniotomy, virtual cortical surface marking and navigation for deep-seated gliomas, preoperative visualization of morbid cortical surface and venous anatomy in surfacing gliomas, identifying the intervenous surgical corridor in both surfacing and deep-seated gliomas, and pre- and postoperative virtual 3D images highlighting the exact spatial geometric residual tumor location and extent of resection for low-grade gliomas (LGGs). CONCLUSIONS: Image-guided neurosurgery with the 3D VR technique using RadiAnt software is an economical, easy-to-learn, and user-friendly method of simulating glioma surgery, especially in resource-constrained countries where expensive neuronavigation systems are not readily available. Apart from cortical sulci/gyri anatomy, FLAIR sequences are ideal for the 3D visualization of nonenhancing diffuse LGGs using the VR technique. In addition to cortical vessels (especially veins), contrast MRI sequences are perfect for the 3D visualization of contrast-enhancing high-grade gliomas.