Safeguarding Neuronal Integrity: Unveiling Possible Role of NFκB in the Neuroprotective Efficacy of Andrographolide Contrary to Aluminium Chloride-induced Neurotoxicity and Associated Spatial Memory Impairments in Rats.

OBJECTIVE: The current study was structured to evaluate the neuroprotective properties of andrographolide in the context of aluminum chloride (AlCl3)-induced neurotoxicity, along with its concurrent impact on spatial memory impairment in Wistar rats. The present investigation elucidated the biochemical and neurobehavioral outcomes of andrographolide treatment in rats, emphasizing the areas of the brain associated with memory, i.e., the cortex and the hippocampus. MATERIALS AND METHODS: Prolonged dosing of AlCl3 (7 mg/kg) intraperitoneally for 10 days exhibited a substantial enhancement in the values of oxidative stress markers associated with a reduction in the concentrations of antioxidant enzymes within the brain. The selection of andrographolide doses (1, 2, and 3 mg/kg) was grounded in precedent safety and toxicity investigations, with subsequent oral administration. The evaluation of behavioral parameters, specifically spatial memory, was conducted through the utilization of the Radial Eight Arm Maze (RAM) test. On the concluding day of the experiment, the assessment encompassed biochemical parameter analysis and histological scrutiny of the brain tissue. RESULTS: The oral dosing of andrographolide at 1, 2, and 3 mg/kg, in conjunction with AlCl3, effectively mitigated the behavioral deficits induced by aluminum exposure. Notably, a significant suppression of NFκB was uncovered in the rats treated with andrographolide. Furthermore, histopathological examinations of the cortex and hippocampus of rat brains provided corroborative evidence, demonstrating that andrographolide substantially alleviated the toxic impact of AlCl3, thereby maintaining the typical histoarchitectural arrangement of these regions. CONCLUSION: These findings collectively suggest that andrographolide holds the potential to counteract memory impairment instigated by aluminum toxicity, accomplished through the modulation of NFκB activity and the amelioration of the adverse consequences of AlCl3 exposure.

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.

Synthesis, Molecular Docking, Molecular Dynamic Simulation Studies, and Antitubercular Activity Evaluation of Substituted Benzimidazole Derivatives.

Tuberculosis, also known as TB, is a widespread bacterial infection that remains a significant global health issue. This study focuses on conducting a thorough investigation into the synthesis, evaluation of anti-Tb activity, molecular docking, and molecular dynamic simulation of substituted benzimidazole derivatives. A series of twelve substituted benzimidazole derivatives (1-12) were successfully synthesized, employing a scaffold consisting of electron-withdrawing and electron-donating groups. The newly synthesized compounds were defined by their FTIR, 1H NMR, and mass spectra. The microplate Alamar blue assay (MABA) was used to evaluate the antimycobacterial activity of the synthesized compound against Mycobacterium tuberculosis (Mtb). Compounds 7 (MIC = 0.8 g/mL) and 8 (MIC = 0.8 g/mL) demonstrated exceptional potential to inhibit M. tuberculosis compared to the standard drug (isoniazid). In addition, the synthesized compounds were docked with the Mtb KasA protein (PDB ID: 6P9K), and the results of molecular docking and molecular dynamic simulation confirmed the experimental results, as compounds 7 and 8 exhibited the highest binding energy of -7.36 and -7.17 kcal/mol, respectively. The simulation results such as the RMSD value, RMSF value, radius of gyration, and hydrogen bond analysis illustrated the optimum potential of compounds 7 and 8 to inhibit the M. tuberculosis strain. Hydrogen bond analysis suggested that compound 7 has greater stability and affinity towards the KasA protein compared to compound 8. Moreover, both compounds (7 and 8) were safe for acute inhalation and cutaneous sensitization. These two compounds have the potential to be potent M. tuberculosis inhibitors.

Evaluation of Utility of Invasive Electroencephalography for Definitive Surgery in Patients with Drug-Resistant Epilepsy: A Systematic Review and Meta-Analysis.

When noninvasive tests are unable to define the epileptogenic zone in patients, intracranial electroencephalography (iEEG) is a method of localizing the epileptogenic zone. Compared with noninvasive evaluations, it offers more precise information about patterns of epileptiform activity, which results in useful diagnostic information that supports surgical decision-making. The primary aim of the present study was to assess the utility of iEEG for definitive surgery for patients with drug-resistant epilepsy. Online databases such as PubMed, Medline, Embase, Scopus, Cochrane Library, Web of Science, and IEEE Xplore were searched for MeSH terms and free-text keywords. The ROBINS I (risk of bias in non-randomized studies - of interventions) critical appraisal tool was used for quality assessment. The prevalence from different studies was pooled together using the inverse variance heterogeneity method. Egger's regression analysis and funnel plot were used to evaluate publication bias. The systematic review included 18 studies, and the meta-analysis included 10 studies to estimate the prevalence of seizure freedom (Engel class I) in patients undergoing surgery after iEEG. A total of 526 patients were included in the meta-analysis. The follow-up period ranged from 1 to 10 years. The overall pooled estimate of the prevalence of seizure freedom (Engel class I) for patients undergoing surgery after iEEG was 53% (95% confidence interval, 44%-62%). The results additionally demonstrated that 12 studies had a moderate risk of bias and 6 had a low risk. Future studies are crucial to enhance our understanding of iEEG to guide patient choices and unravel their implications.

Role of Phytoactive-based Nanoformulation for the Treatment of Arthritis.

Joints and arthritic conditions are among the most dangerous illnesses that humans have ever encountered and it is even more worrying that there is no recognized treatment for arthritis. The researchers looked for safer alternatives, such as herbal medicines, because the traditional treatments used to treat severe joint inflammatory issues have several negative side effects. A ligand-coated nanomedicine can bind to receptors that are overexpressed by cells in chronically inflammatory tissues, increasing its efficacy and reducing its systemic side effects. This is because the pathophysiology of rheumatoid arthritis suggests that macrophages and overexpressed molecules exist within inflamed tissues, which increases permeability and allows nanomedicines to accumulate in inflamed tissue and cause retention phenomena. The anti-arthritic properties of a variety of plants, their components, extracts, and phyto-isolates have been studied to date. These plant compounds can pose stability and delivery problems, which restricts their efficacy as a treatment for inflammatory diseases. The multifunctional and adaptable features of different nanoparticles can help herbal remedies based on nanotechnology get beyond the delivery constraints of different natural ingredients. The application of nanoformulations in tissue engineering is an additional strategy for delivering drugs directly to bone and cartilage in RA patients. The medication is more therapeutically effective due to nanoformulation's improved synovium and cartilage absorption, accumulation, and penetration at inflammatory joints. Herbal medications with a nanotechnology foundation exhibit superior pharmacokinetic and drug delivery qualities, aid in better oral absorption, regulate drug release, boost in vivo retention capacity, target delivery, and have synergistic effects. This review provides an update on the use of herbal medicines based on nanotechnology, which show promise in treating arthritis and other ailments.

Manual Instruments as an Alternative to Drilling for Bony Exposure in Skull Base Surgery: Concept and Technique.

Background Drilling in neurosurgery is an integral part of surgical exposure, especially in skull base approaches and craniovertebral junction (CVJ) surgeries. Most of such drillings are done in close proximity to the neurovascular structures in skull base surgeries and cervical-medullary junction or facet/pedicle in CVJ surgeries. Reluctance to drilling among young neurosurgeons is due to less hands-on experience during training and also, in the early part of the career, due to fear of injury to neurovascular structures. Methods Five commonest bone removals for skull base region and CVJ surgeries that can be safely done using manual instruments were identified based on experiences of senior authors. The authors highlight key technical nuances to widen surgical corridors using manual instruments safely for skull base surgical approaches. Results Basic neuroanatomical concepts and basic physics help in using manual instruments safely for bone removals in various skull base surgical approaches. Conclusions Manual instruments may be used for bone removals in selected skull base surgical approaches, which help young neurosurgeons to perform these surgeries in limited-resource settings.

Comparative Analysis of Hemispherotomy in Adults versus Children- A Prospective Observational Series.

BACKGROUND: Hemispherotomy (HS) is an effective treatment for unilateral hemispheric onset epilepsy. There are few publications for HS in adults, and there is no series comparing adults and pediatric patients of HS. OBJECTIVE: To compare the hemispherotomies done in adult patients with pediatric ones in terms of efficacy and safety. METHODS: Data was prospectively collected for HS patients (up to 18 years and more) from Aug 2014 to Aug 2018. Comparison between the groups was made for seizure onset, duration of epilepsy, frequency of seizures, number of drugs, intraoperative blood loss, postoperative seizure control, postoperative stay, postoperative motor functions, and preoperative and postoperative intelligence quotient. Follow-up was one year. RESULTS: A total of 61 pediatric and 11 adults underwent HS. The seizure onset was earlier in children, and the duration of epilepsy was longer in adults. The frequency of seizures per day was more in children being 14.62 ± 26.34 in children, and 7.71 ± 5.21 per day in adults (P - 0.49). The mean number of drugs was similar in the preoperative and postoperative periods in both. Class I seizure outcome was similar in both the groups being 85.24% in children and 90.9% in adults (P - 0.56). Blood loss, postoperative stay, was similar in both the groups. No patient had a new permanent motor deficit. Power worsened transiently in 1 pediatric patient and in 4 adult patients. The visual word reading and object naming improved in both the groups (no intergroup difference), and IQ remained the same in both groups. One adult patient had meningitis, and another had hydrocephalus requiring shunt placement. CONCLUSION: Hemispherotomy is a safe and effective procedure in adults as in children in appropriately selected patients.

Computational exploration of FOXM1 inhibitors for glioblastoma: an integrated virtual screening and molecular dynamics simulation study.

In this study, a comprehensive investigation of a set of phytochemicals to identify potential inhibitors for the Forkhead box protein M1 (FOXM1) was conducted. FOXM1 is overexpressed in glioblastoma (GBM) cells and plays a crucial role in cell cycle progression, proliferation, and invasion. FOXM1 inhibitors have shown promising results in preclinical studies, and ongoing clinical trials are assessing their efficacy in GBM patients. However, there are limited studies on the identification of novel compounds against this attractive therapeutic target. To address this, the NPACT database containing 1,574 phytochemicals was used, employing a hierarchical multistep docking approach, followed by an estimation of relative binding free energy. By fixing user-defined XP-dock and MM-GBSA cut-off scores of -6.096 and -37.881 kcal/mol, the chemical space was further narrowed. Through exhaustive analysis of molecular binding interactions and various pharmacokinetics profiles, we identified four compounds, namely NPACT00002, NPACT01454, NPACT00856, and NPACT01417, as potential FOXM1 inhibitors. To assess the stability of protein-ligand binding in dynamic conditions, 100 ns Molecular dynamics (MD) simulations studies were performed. Furthermore, Molecular mechanics with generalized Born and surface area solvation (MM-GBSA) based binding free energy estimations of the entire simulation trajectories revealed a strong binding affinity of all identified compounds towards FOXM1, surpassing that of the control drug Troglitazone. Based on extensively studied multistep docking approaches, we propose that these molecules hold promise as FOXM1 inhibitors for potential therapeutic applications in GBM. However, experimental validation will be necessary to confirm their efficacy as targeted therapies.Communicated by Ramaswamy H. Sarma.

Osteomyelitis and non-coding RNAS: A new dimension in disease understanding.

Osteomyelitis, a debilitating bone infection, presents considerable clinical challenges due to its intricate etiology and limited treatment options. Despite strides in surgical and chemotherapeutic interventions, the treatment landscape for osteomyelitis remains unsatisfactory. Recent attention has focused on the role of non-coding RNAs (ncRNAs) in the pathogenesis and progression of osteomyelitis. This review consolidates current knowledge on the involvement of distinct classes of ncRNAs, including microRNAs, long ncRNAs, and circular RNAs, in the context of osteomyelitis. Emerging evidence from various studies underscores the potential of ncRNAs in orchestrating gene expression and influencing the differentiation of osteoblasts and osteoclasts, pivotal processes in bone formation. The review initiates by elucidating the regulatory functions of ncRNAs in fundamental cellular processes such as inflammation, immune response, and bone remodeling, pivotal in osteomyelitis pathology. It delves into the intricate network of interactions between ncRNAs and their target genes, illuminating how dysregulation contributes to the establishment and persistence of osteomyelitic infections. Understanding their regulatory roles may pave the way for targeted diagnostic tools and innovative therapeutic interventions, promising a paradigm shift in the clinical approach to this challenging condition. Additionally, we delve into the promising therapeutic applications of these molecules, envisioning novel diagnostic and treatment approaches to enhance the management of this challenging bone infection.

Setting Up a Department of Neurosurgery in a Government Hospital in an LMIC: Jodhpur, India.

BACKGROUND: The number of government institutes offering affordable super specialty and tertiary healthcare in India has traditionally not been able to keep pace with the growth in population, most of whom are too poor to be able to afford private healthcare services. To meet this mandate, 6 new institutes built on the template of the premier institute of the country-the All India Institute of Medical Sciences, New Delhi-were founded and began operations in 2012. Using the progress of our department as an example, the aim of this report is to outline the principles that were followed to set up the department of neurosurgery. METHODS: The Department of Neurosurgery at All India Institute of Medical Sciences, Jodhpur, began providing services in August 2017. Data related to the inception and development of the department were collected. RESULTS: The department has grown during the past 5 years from 400 outpatients and 79 inpatients in 2017 to 11,144 outpatients and 1624 inpatients in 2022. Only 59 surgeries were performed in 2017 compared with 597 routine and 311 emergency procedures performed in 2022. Currently, the department has 7 faculty members performing all forms of complex skull base, craniovertebral junction, vascular, endovascular, epilepsy, and functional surgeries. A total of 134 studies have been reported in national and international journals, and 8 patents have been granted. CONCLUSIONS: We report the unique experiences of one department that could be useful as a template and as guidelines for the establishment process of a new department.

Trends in Stereotactic Radiosurgery for Intracranial and Spinal Pathologies: Analysis of the Top 100 Most Cited Articles.

There is a plethora of papers on the role of stereotactic radiosurgery (SRS) in various benign and malignant intracranial tumors, and it is possible to overlook the most important and landmark studies. Thus, the necessity of citation analysis arises, which reviews the most cited articles and recognizes the impact made by these articles. Utilizing the 100 most cited articles describing the use of SRS for intracranial and spinal pathologies, this article aims to provide meaningful information regarding the historical trends and recent directions in which this field is headed. We performed a search of the Web of Science database using the keywords "stereotactic radiosurgery," "gamma knife," "GKRS," "gamma knife radiosurgery," "LINAC," and "Cyberknife" on May 14, 2022. Our search retrieved a total of 30,652 articles published between the years 1968 and 2017. The top 100 cited articles were arranged in descending order based on citation count (CC) and citation per year (CY). The journal with the largest number of publications as well as citation count was the International Journal of Radiation Oncology Biology Physics (n = 33), followed by Journal of Neurosurgery (n = 25). The most cited article was authored by Andrews, which was published in 2004 in The Lancet (1699 CC, 89.42 CY). Flickinger, with 25 papers and 7635 total citations, was the author with the highest impact. Lunsford, with 25 publications and total citations of 7615, was a close second. The USA was the leading country with the maximum number of total citations (n = 23,054). Ninety-two articles described the use of SRS for intracranial pathologies (metastases, n = 38; AVM, n = 16; vestibular schwannoma, n = 9; meningioma, n = 8; trigeminal neuralgia, n = 6; sellar lesion, n = 2; glioma, n = 2; functional, n = 1; and procedure related, n = 10). Eight studies describing spinal radiosurgery were included, out of which four were on spinal metastases. Citation analyses of the top 100 articles revealed that the focus of research in the field of SRS started with functional neurosurgery and progressed to benign intracranial tumors and AVMs. More recently, central nervous system (CNS) metastases have received the maximum attention with 38 articles, including 14 randomized controlled trials finding a place in the top 100 cited articles. Presently, the use of SRS is concentrated in developed countries. Efforts need to be made for more widespread use in developing nations to bring the maximum possible benefits of this focused noninvasive treatment to a wider population.

Suction cannula design for safe microneurosurgery.

INTRODUCTION: Suction cannula (SC) is an important instrument for a neurosurgeon. Currently used suction control valves, kept in the sterile field, are controlled by the surgeon, for which he needs to leave the surgical dissection or by assistant or by operation room personnel to adjust the pressure of the equipment (suction machine or central suction), which lies in the unsterile field. Authors studied relationships of the different diameters of SC and the thumb hole (TH) of the SC and present their findings. METHODS: Seven SC with various diameters of their lumen and TH were used for the study. Suction pressures were measured with suction tip open, immersed in saline and TH open and closed. TH of 2 SC were made smaller using adhesive tape over the TH and making smaller hole over the tape and two additional measurements were taken using changed SC with modified TH. SPSS Statistics 23.0 (IBM India Pvt Ltd, Bangaluru, India) was used for statistical analysis of the pressure recordings and SC features. RESULTS: Pressure and diameter of ST or TH were related in opposite direction. As the diameter increases the pressure decreases. A strong negative association was observed between the diameter of TH and the pressure. CONCLUSION: TH diameter of SC is important to control suction pressure with any size of SC. One should use tear-drop type TH or appropriate diameter of the circular type of TH to contemplate safe microneurosurgery.

Post traumatic stress disorder following facial and dental trauma: preliminary findings from a study conducted in India.

This study was conducted to identify and study the prevalence of post traumatic stress disorder (PTSD) in patients, who had sustained traumatic facial and dental injuries along with other variables that may affect the psychological response. MATERIAL AND METHODS: 241 patients suffering from traumatic facial and dental injuries presenting to the Ahmadabad Municipal Dental College and Hospital were included in the study. 110 patients (males - 87, females - 23) suffered disfiguring injuries and/or loss of multiple front teeth (DF). 131 patients (males - 102, females - 29) suffered no disfigurement (NDF). Assessment was carried out on day of discharge (D.O.D), 1 month, and 6 months. Impact of Event Scale (I.E.S-R) was used to assess the presence of post traumatic stress disorder in the patients. RESULTS: Patients with DF injuries had statistically significant higher mean scores than patients suffering NDF injuries. Female patients had comparatively higher scores at D.O.D, 1 month, and 6 months. Patients treated with maxillomandibular fixation and between ages 18 and 40 years also had significantly higher scores. CONCLUSION: Patients with DF facial injuries including multiple anterior teeth loss had significantly higher mean (I.E.S-R) scores for PTSD in comparison with patients with NDF facial injuries.

Delusional parasitosis: Report on response to olanzapine in a case series of 04 patients.

Delusional parasitosis (DP) is a type of delusional disorder which is characterised by single hypochondriacal delusion in which patient believes that he/she is infested with insects/worms/parasite. The authors present a case series of four cases of DP which were assessed in the outpatient department of psychiatry of a tertiary care hospital in Western Maharashtra. The patients with DP were predominantly women around 50 years of age who were treated successfully with Tab Olanzapine and psychotherapy with favourable response.

Management of Pediatric and Adolescent Traumatic Thoracolumbar Spondyloptosis.

Background: Complete subluxation of >100% of one vertebral body with respect to the adjacent vertebra is defined as spondyloptosis. It is the severest form of injury caused by high-energy trauma. Pediatric patients with a traumatic spine injury, particularly spondyloptosis are surgically demanding as reduction and achieving realignment of the spinal column requires diligent planning and execution. Objective: To enlighten readers about this rare but severest form of thoracolumbar spine injury and its management. Methods: Retrospective analysis of patients treated here with spondyloptosis between 2008 and 2016 was done. Results: Seven children, ranging from 9 to 18 years (mean years) age were included in the study. Five patients had spondyloptosis at thoracolumbar junction and one each in the lumbar and thoracic spine. All patients underwent single-stage posterior surgical reduction and fixation except one patient who refused surgery. Intraoperatively, cord transection was seen in five patients while dura was intact in one patient. The mean follow-up period was 17 months (1-36 months) during which one patient expired due to complications arising from bedsores. All patients remained American Spinal Injury Association (ASIA) A neurologically. Conclusions: Traumatic spondyloptosis is a challenging proposition to treat and the aim of surgery is to stabilize the spine. Rehabilitation remains the most crucial but the neglected part and dearth of proper rehabilitation centers inflict high mortality and morbidity in developing countries.

Use of Assessment Tools in Cervical Spondylotic Myelopathy-Results of An Anonymized Survey Among Indian Spine Surgeons.

Background: Cervical spondylotic myelopathy (CSM) is the commonest cause of cervical myelopathy. It contributes to high morbidity and consequent economic burden for society. Many measurement tools have been devised to quantify the disease severity, assist in decision-making, and to evaluate the outcome of surgical intervention. Objective: Most of the assessment scales are used for research purposes only and rarely in clinical practice. The purpose of this survey was to check the awareness of spine surgeons about these assessment scales and their role in the management of patients with CSM. Methods: An online questionnaire using the application "Google Forms" made consisting of 10 questions regarding the experience of treating the CSM patients and their preference for various parameters in assessing these patients. Statistical analysis was done using the statistical programming language R. Results: One-hundred and sixty-three responses were analyzed. About 90% of the respondents were aware of the assessment tools and only 57% of them used any in management. Nurick's grade was the most well known among all groups. The commonest reason for surgeons not using any of these assessment scales despite being aware of these scales was their perception that it is very time-consuming to complete these assessment scales. Conclusion: Assessment scales have a role in the management and follow-up of CSM patients. While awareness regarding these tools is well spread, time constraint plays a major role in limiting its usage.

Extranodal natural-killer/T-cell lymphoma, nasal type: An immunomorphological study from a regional cancer institute in India.

Introduction: Extranodal natural-killer/T-cell lymphoma, nasal type (ENKTL), is a rare, aggressive, predominantly extranodal non-Hodgkin lymphoma (NHL) of putative natural-killer (NK) cell and rarely T-cell origin, always associated with Epstein-Barr virus (EBV) infection and characterized by highly distinctive histopathological features with predilection for the upper aerodigestive tract. While the nasal cavity is the prototypical site, less frequently extranasal ENKTL can also occur. The objective of this case series is to study the immunomorphological features of ENKTL from a tertiary cancer centre as the data are sparse from India despite it being a distinct entity with characteristic clinicopathological features. Methods: We identified 11 cases of ENKTL from the departmental archives between January 2015 and June 2018. The clinicopathological and immunohistochemistry (IHC) findings of these tumors were analyzed. EBV encoded RNA (EBER) in situ hybridization (EBER-ISH) for EBV was done in eight cases. Results: The disease was more common in males (male: female ratio 1.8:1) with the mean age of 45 years (range 31-65 years). Sinonasal region was the most common site with 9 cases and skin and penis were involved in one case each. The patient with penile involvement on further investigations was found to have occult nasal involvement, Histomorphological features such as angiocentricity/angioinvasion was seen in seven cases (63.6%) and significant necrosis was present in all 11 cases (100%). All cases were uniformly positive for cytoplasmic CD3 and CD56 with high Ki67 proliferating index and EBER-ISH test for EBV was positive in all the eight cases. Conclusion: ENKTL is an aggressive NHL and should be differentiated from other T- and B-cell lymphomas as the prognosis and therapy differ. Nasal biopsies showing predominant necrosis and atypical lymphoid cells with angiocentricity must raise the suspicion of ENKTL and should be confirmed by immunomorphological and molecular studies.

Aberrant Vessel with Potential Catastrophic Vascular Complications in a Patient with Chiari Malformation.

Craniovertebral junction anomalies are known to be associated with many bony, soft tissue, and vascular anomalies. We encountered a case of Chiari malformation type 1 with C2-D2 syrinx, in which computed tomography angiography showed an aberrant vessel (probably vein) coursing through the soft tissue along the posterior aspect of C1-C7 vertebral bodies along the right-sided joints, superiorly coursing posterior to C1-C2 joint and curving anteriorly over C1 to enter into the foramen magnum. Had this abnormality not been detected, catastrophic vascular consequences could have occurred.