Comparison of Optic Nerve Sheath Diameter (ONSD) Measurements Obtained from USG Before and After Placement of Ventriculoperitoneal Shunt in Obstructive Hydrocephalus as a Surrogate Marker for Adequacy of Shunt Function: A Prospective Observational Study.

Introduction Optic nerve sheath diameter (ONSD) measured using ultrasonography has been widely used as a surrogate marker of elevated intracranial pressure. However, literature is sparse on the correlation between ONSD and ventriculoperitoneal (VP) shunt function, especially in adults with hydrocephalus. Our study was designed to assess the correlation between ONSD measured using ultrasonography before and 12 hours after VP shunt placement and the success of VP shunt placement assessed using computed tomography (CT) of the brain. Materials and Methods Fifty-one patients between 16 and 60 years of age, with obstructive hydrocephalus scheduled for VP shunt surgery were included in this prospective, observational study. ONSD measurements were obtained from both eyes prior to induction of anesthesia, immediately after the surgery, and at 6, 12, and 24 hours after the surgery. An average of three readings was obtained from each eye. Cerebrospinal fluid (CSF) opening pressure was noted after entry into the lateral ventricle. Noncontrast CT (NCCT) brain was obtained 12 hours after the surgery and was interpreted by the same neurosurgeon for signs of successful VP shunt placement. Results There was a significant reduction in ONSD in the postoperative period compared to ONSD measured preoperatively. The average ONSD (mean ± standard deviation) measured prior to induction of anesthesia, immediately after the surgery, and at 6, 12, and 24 hours after the surgery was 5.71 ± 0.95, 5.20 ± 0.84, 5.06 ± 0.79, 4.90 ± 0.79, and 4.76 ± 0.75 mm, respectively. The mean CSF opening pressure was 19.6 ± 6.9 mm Hg. Postoperative NCCT brain revealed misplacement of the shunt tip in only one patient. Conclusion ONSD measured using ultrasonography may be used as a reliable indicator of VP shunt function in adults with obstructive hydrocephalus.

Comparison of the efficacy of 0.9% normal saline with balanced crystalloid (Plasmalyte) in maintaining the metabolic profile in head injury patients undergoing evacuation of acute subdural haematoma - A randomised controlled trial.

Background and Aims: The choice of intravenous fluids is important in patients with traumatic brain injury (TBI), where large volumes may be required for resuscitation. Our study aimed to compare 0.9% normal saline (NS) with balanced crystalloid (Plasmalyte) in TBI patients in terms of metabolic and coagulation profile, brain relaxation score (BRS) and renal functions using serum urea, creatinine and urinary tissue inhibitor of metalloproteinases-2* insulin-like growth factor binding protein-7, [TIMP-2]*[IGFBP7], value to assess the risk of acute kidney injury. Methods: This randomised controlled trial on 90 TBI patients undergoing emergency craniotomy and subdural haematoma evacuation was conducted in a tertiary care institute. The patients were randomised to receive either NS (Group NS) or Plasmalyte (Group P) as the intraoperative maintenance fluid. The primary outcome measures included the potential of hydrogen (pH), base excess (BE) and chloride values from an arterial blood gas. The secondary outcomes were the coagulation profile, BRS and urinary [TIMP-2]*[IGFBP7]. The two groups' metabolic profile differences were analysed using two-way repeated analysis of variance. BRS was analysed using the Mann-Whitney U test. A P value < 0.05 was considered to be statistically significant. Results: The pH and chloride values were significantly higher, and the BE values were significantly lower in Group P compared to Group NS (P < 0.001). Brain relaxation and coagulation profiles were comparable between the two groups. Serum creatinine (P = 0.002) and urinary [TIMP-2]*[IGFBP7] (P = 0.042) were significantly higher in the NS group. Conclusion: Plasmalyte maintains a more favourable metabolic profile than NS in TBI patients without affecting brain relaxation adversely.

Impact of HMGB1 on cancer development and therapeutic insights focused on CNS malignancy.

The present study explores the complex roles of High Mobility Group Box 1 (HMGB1) in the context of cancer development, emphasizing glioblastoma (GBM) and other central nervous system (CNS) cancers. HMGB1, primarily known for its involvement in inflammation and angiogenesis, emerges as a multifaceted player in the tumorigenesis of GBM. The overexpression of HMGB1 correlates with glioma malignancy, influencing key pathways like RAGE/MEK/ERK and RAGE/Rac1. Additionally, HMGB1 secretion is linked to the maintenance of glioma stem cells (GSCs) and contributes to the tumor microenvironment's (TME) vascular leakiness. Henceforth, our review discusses the bidirectional impact of HMGB1, acting as both a promoter of tumor progression and a mediator of anti-tumor immune responses. Notably, HMGB1 exhibits tumor-suppressive roles by inducing apoptosis, limiting cellular proliferation, and enhancing the sensitivity of GBM to therapeutic interventions. This dualistic nature of HMGB1 calls for a nuanced understanding of its implications in GBM pathogenesis, offering potential avenues for more effective and personalized treatment strategies. The findings underscore the need to explore HMGB1 as a prognostic marker, therapeutic target, and a promising tool for stimulating anti-tumor immunity in GBM.

A critical review on therapeutic approaches of CRISPR-Cas9 in diabetes mellitus.

Diabetes mellitus (D.M.) is a common metabolic disorder caused mainly by combining two primary factors, which are (1) defects in insulin production by the pancreatic ß-cells and (2) responsiveness of insulin-sensitive tissues towards insulin. Despite the rapid advancement in medicine to suppress elevated blood glucose levels (hyperglycemia) and insulin resistance associated with this hazard, a demand has undoubtedly emerged to find more effective and curative dimensions in therapeutic approaches against D.M. The administration of diabetes treatment that emphasizes insulin production and sensitivity may result in unfavorable side effects, reduced adherence, and potential treatment ineffectiveness. Recent progressions in genome editing technologies, for instance, in zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR-Cas)-associated nucleases, have greatly influenced the gene editing technology from concepts to clinical practices. Improvements in genome editing technologies have also opened up the possibility to target and modify specific genome sequences in a cell directly. CRISPR/Cas9 has proven effective in utilizing ex vivo gene editing in embryonic stem cells and stem cells derived from patients. This application has facilitated the exploration of pancreatic beta-cell development and function. Furthermore, CRISPR/Cas9 enables the creation of innovative animal models for diabetes and assesses the effectiveness of different therapeutic strategies in treating the condition. We, therefore, present a critical review of the therapeutic approaches of the genome editing tool CRISPR-Cas9 in treating D.M., discussing the challenges and limitations of implementing this technology.

Comparison of Dexmedetomidine Versus Fentanyl-Based Anesthetic Protocols Under Patient State Index Guidance in Patients Undergoing Elective Neurosurgical Procedures with Intraoperative Neurophysiological Monitoring.

Objectives The study was designed to elucidate the effects of dexmedetomidine as an anesthetic adjunct to propofol in total intravenous anesthesia (TIVA) on anesthetic dose reduction, the quality of intraoperative neurophysiological monitoring (IONM) recordings, analgesic requirements, and recovery parameters in patients undergoing neurosurgical procedures with neurophysiological monitoring. Methods A total of 54 patients for elective neurosurgical procedures with IONM were randomized to group D (dexmedetomidine) and group F (fentanyl). A loading dose of the study drug of 1µg/kg followed by 0.5 µg/kg/h infusion was used in two groups. Propofol-based TIVA with a Schneider target-controlled infusion model was used for induction and maintenance with effect site concentration of 4-5 and 2.5-4 µg/mL, respectively, titrated to a Patient State Index (PSI) of 25-40. Baseline IONM recordings were obtained after induction. The mean propofol consumption, number of patient movements, quality of IONM recordings, number of fentanyl boluses, hemodynamic characteristics, and recovery parameters were recorded. Results The mean propofol consumption was significantly lower in group D when compared to group F (101.4 ± 13.5 µg/kg/min vs 148.0 ± 29.8 µg/kg/min). Baseline IONM recordings were acquired in all patients without any difficulty. The two groups were comparable with respect to the number of additional boluses of fentanyl, patient movements, and recovery characteristics. Conclusion Dexmedetomidine as an adjuvant to propofol in TIVA reduces the requirement of the latter, without affecting the IONM recordings. The addition of dexmedetomidine also ensures stable hemodynamics and decreases the requirement of opioids with similar recovery characteristics.

Comparison of two techniques of goal directed fluid therapy in elective neurosurgical patients - a randomized controlled study.

BACKGROUND: Goal directed fluid therapy (GDFT) may be a rational approach to adopt in neurosurgical patients, in whom intravascular volume optimization is of utmost importance. Most of the parameters used to guide GDFT are derived invasively. We postulated that the total volume of intraoperative intravenous fluid administered during elective craniotomy for supratentorial brain tumours would be comparable between two groups receiving GDFT guided either by the non-invasively derived plethysmography variability index (PVI) or by stroke volume variation (SVV). METHODS: 60 ASA category 1, 2 and 3 patients between 18 and 70 years of age were randomized to receive intraoperative fluid guided either by SVV (SVV group; n = 31) or PVI (PVI group; n = 29). The total volume of fluid administered intraoperatively was recorded. Serum creatinine was measured before the surgery, at the end of the surgery, 24 h after surgery and on the fifth post-operative day. Arterial cannulation was performed before induction in all patients. Serum lactate was measured before induction, once in 2 h intraoperatively, at the end of the surgery and 24 h after the surgery. Brain relaxation score was assessed by the surgeon during dural opening and dural closure. Patients were followed up till discharge or death. The duration of mechanical ventilation and the duration of hospital stay was noted for all patients. RESULTS: The volume of fluid given intraoperatively was significantly higher in the SVV group (p = 0.005). The two groups were comparable with respect to serum lactate and serum creatinine measured at pre-determined time intervals. Brain relaxation score was also comparable between the groups. SVV and PVI displayed moderate to strong correlation intraoperatively. The duration of mechanical ventilation and the length of the hospital stay were comparable between the two groups. CONCLUSIONS: PVI and SVV are equally effective in guiding GDFT in adults undergoing elective craniotomy for supratentorial brain tumours.

Marine bioactive compounds as antibiofilm agent: a metabolomic approach.

The ocean is a treasure trove of both living and nonliving creatures, harboring incredibly diverse group of organisms. A plethora of marine sourced bioactive compounds are discovered over the past few decades, many of which are found to show antibiofilm activity. These are of immense clinical significance since the formation of microbial biofilm is associated with the development of high antibiotic resistance. Biofilms are also responsible to bring about problems associated with industries. In fact, the toilets and wash-basins also show degradation due to development of biofilm on their surfaces. Antimicrobial resistance exhibited by the biofilm can be a potent threat not only for the health care unit along with industries and daily utilities. Various recent studies have shown that the marine members of various kingdom are capable of producing antibiofilm compounds. Many such compounds are with unique structural features and metabolomics approaches are essential to study such large sets of metabolites. Associating holobiome metabolomics with analysis of their chemical attribute may bring new insights on their antibiofilm effect and their applicability as a substitute for conventional antibiotics. The application of computer-aided drug design/discovery (CADD) techniques including neural network approaches and structured-based virtual screening, ligand-based virtual screening in combination with experimental validation techniques may help in the identification of these molecules and evaluation of their drug like properties.

Analysis of Antibiofilm Activities of Bioactive Compounds from Honeyweed (Leonurus sibiricus) Against P. aeruginosa: an In Vitro and In Silico Approach.

Leonurus sibiricus (Red verticilla, honeyweed) is a type of herbaceous plant predominantly found in Asian subcontinents as weed in crop fields and is widely used for treating diabetes, bronchitis, and menstrual irregularities. However, there is a dearth of study in the application of the plant phytocompounds for treating biofilm-associated chronic infections. The bioactive compounds mainly comprise of tri-terpenes, di-terpenes, phenolic acid, and flavonoids which may have potential role as antimicrobial and antibiofilm agents. Acute and chronic infection causing microbes usually form biofilm and develop virulence factors and antibiotic resistance through quorum sensing (QS). In this study, the bioactive compounds leosibirin, sibiricinone A, leosibirone A, leonotin, quercetin, lavandulifolioside, and myricetin were identified using GC-MS analysis. These were used for analyzing the antibiofilm and anti-quorum sensing activities (rhamnolipid, AHL assay, swarming motility assay) against the biofilm formed by Pseudomonas aeruginosa, the most significant nosocomial disease-causing bacteria. The compounds were able to bring about maximum inhibition in biofilm formation and QS. Although the antibiofilm activity of the phytoextract was found to be higher than that of individual phytocompounds at a concentration of 250 µg/mL, quercetin and myricetin showed highest antibiofilm activity against Pseudomonas aeruginosa, respectively, at MIC values of 135 µg/mL and 150 µg/mL against P aeruginosa. FT-IR study also revealed that the active ingredients were able to bring about the destruction of exopolysaccharides (EPS). These observations were further validated by molecular docking interactions that showed the active ingredients inhibit the functioning of QS sensing proteins by binding with them. It was observed that myricetin showed better interactions with the QS proteins of P. aeruginosa. Myricetin and quercetin show considerable inhibition of biofilm in comparison to the phytocompounds. Thus, the present study suggests that the active compounds from L. sibiricus can be used as an alternate strategy in inhibiting the biofilm formed by pathogenic organisms.

Clinical utility of ultrasonography, pulse oximetry and arterial line derived hemodynamic parameters for predicting post-induction hypotension in patients undergoing elective craniotomy for excision of brain tumors - A prospective observational study.

Background: Hypotension, which is a common adverse effect of induction of anesthesia, may be especially detrimental in neurosurgical patients. Hence, it is important to investigate hemodynamic parameters which may be useful in identifying patients at risk of hypotension, following induction. Our study was designed to assess the utility of parameters derived from ultrasonography, pulse oximeter and arterial line for predicting post-induction hypotension. Methods: The study was designed as a prospective, observational trial. Written informed consent was obtained from 100 American Society of Anesthesiologists (ASA) 1 and 2 patients, between 18-60 years of age, scheduled for elective craniotomy for brain tumors. Arterial cannula was inserted before induction of anesthesia and connected to Vigileo cardiac output monitor. Baseline stroke volume variation (SVV), stroke volume (SV), cardiac index (Ci), cardiac output (CO) and pulse pressure variation (PPV) were recorded. Plethysmography variability index (PVI) and perfusion index (PI) were obtained from the Masimo rainbow SET® Radical-7® pulse oximeter. Ultrasonographic assessment of the inferior vena cava (IVC) was performed before induction of anesthesia and again within 15 min after induction. Maximum and minimum IVC diameters (dIVCmax and dIVCmin) and collapsibility index (CI) were measured. All the other aforementioned parameters were recorded every minute starting at induction, until the 15th minute following induction. Results: PI, CI and dIVCmax were found to have the largest AUCROC for the prediction of post-induction hypotension (AUCROC 0.852, 0.823 and 0.781 respectively). Multiple logistic regression analysis revealed CI to be the most significant independent factor for the prediction of post-induction hypotension. Conclusion: Non-invasively derived hemodynamic parameters like dIVCmax, CI and PI were more accurate for the prediction of post-induction hypotension, compared to invasively derived parameters.

Citrus Essential Oils: a Treasure Trove of Antibiofilm Agent.

Biofilms are groups of adherent cell communities that cohere to the biotic and abiotic surfaces with the help of extracellular polymeric substances (EPS). EPS allow bacteria to form a biofilm that facilitates their binding to biotic and abiotic surfaces and provides resistance to the host immune responses and to antibiotics. There are efforts that have led to the development of natural compounds that can overcome this biofilm-mediated resistance. Essential oils (EOs) are a unique mixture of compounds that plays a key role in preventing the development of biofilm. The present overview focusses on the role of various types of citrus essential oils in acting against the biofilm, and the antibiofilm properties of natural compounds that may show an avenue to treat the multidrug-resistant bacteria.

Immobilized enzymes as potent antibiofilm agent.

Biofilm has been a point of concern in hospitals and various industries. They not only cause various chronic infections but are also responsible for the degradation of various medical appliances. Since the last decade, various alternate strategies are being adopted to combat the biofilm formed on various biotic and abiotic surfaces. The use of enzymes as a potent anti-fouling agent is proved to be of utmost importance as the enzymes can inhibit biofilm formation in an eco-friendly and cost-effective way. The physical and chemical immobilization of the enzyme not only leads to the improvement of thermostability and reusability of the enzyme, but also gains better efficiency of biofilm removal. Immobilization of amylase, cellobiohydrolase, pectinase, subtilisin A and ß-N-acetyl-glucosaminidase (DspB) are proved to be most effective in inhibition of biofilm formation and removal of matured biofilm than their free forms. Hence, these immobilized enzymes provide greater eradication of biofilm formed on various surfaces and are coming up to be the potent antibiofilm agent.

Seafood Discards: A Potent Source of Enzymes and Biomacromolecules With Nutritional and Nutraceutical Significance.

In recent times, the seafood industry is found to produce large volumes of waste products comprising shrimp shells, fish bones, fins, skins, intestines, and carcasses, along with the voluminous quantity of wastewater effluents. These seafood industry effluents contain large quantities of lipids, amino acids, proteins, polyunsaturated fatty acids, minerals, and carotenoids mixed with the garbage. This debris not only causes a huge wastage of various nutrients but also roots in severe environmental contamination. Hence, the problem of such seafood industry run-offs needs to be immediately managed with a commercial outlook. Microbiological treatment may lead to the valorization of seafood wastes, the trove of several useful compounds into value-added materials like enzymes, such as lipase, protease, chitinase, hyaluronidase, phosphatase, etc., and organic compounds like bioactive peptides, collagen, gelatin, chitosan, and mineral-based nutraceuticals. Such bioconversion in combination with a bio-refinery strategy possesses the potential for environment-friendly and inexpensive management of discards generated from seafood, which can sustainably maintain the production of seafood. The compounds that are being produced may act as nutritional sources or as nutraceuticals, foods with medicinal value. Determining utilization of seafood discard not only reduces the obnoxious deposition of waste but adds economy in the production of food with nutritional and medicinal importance, and, thereby meets up the long-lasting global demand of making nutrients and nutraceuticals available at a nominal cost.

Understanding the function and regulation of Sox2 for its therapeutic potential in breast cancer.

Sox family of transcriptional factors play essential functions in development and are implicated in multiple clinical disorders, including cancer. Sox2 being their most prominent member and performing a critical role in reprogramming differentiated adult cells to an embryonic phenotype is frequently upregulated in multiple cancers. High Sox2 levels are detected in breast tumor tissues and correlate with a worse prognosis. In addition, Sox2 expression is connected with resistance to conventional anticancer therapy. Together, it can be said that inhibiting Sox2 expression can reduce the malignant features associated with breast cancer, including invasion, migration, proliferation, stemness, and chemoresistance. This review highlights the critical roles played by the Sox gene family members in initiating or suppressing breast tumor development, while primarily focusing on Sox2 and its role in breast tumor initiation, maintenance, and progression, elucidates the probable mechanisms that control its activity, and puts forward potential therapeutic strategies to inhibit its expression.

Phytocompound Mediated Blockage of Quorum Sensing Cascade in ESKAPE Pathogens.

Increased resistance of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp. (ESKAPE) pathogens against various drugs has enhanced the urge for the development of alternate therapeutics. Quorum sensing (QS) is a density dependent cell-to-cell communication mechanism responsible for controlling pathogenicity with the regulation of gene expression. Thus, QS is considered a potential target for the development of newer anti-biofilm agents that do not depend on the utilization of antibiotics. Compounds with anti-QS effects are known as QS inhibitors (QSIs), and they can inhibit the QS mechanism that forms the major form in the development of bacterial pathogenesis. A diverse array of natural compounds provides a plethora of anti-QS effects. Over recent years, these natural compounds have gained importance as new strategies for combating the ESKAPE pathogens and inhibiting the genes involved in QS. Different pharmacognostical and pharmacological studies have been carried out so far for identification of novel drugs or for the discovery of their unique structures that may help in developing more effective anti-biofilm therapies. The main objective of this review is to discuss the various natural compounds, so far identified and their employed mechanisms in hindering the genes responsible for QS leading to bacterial pathogenesis.

Evaluation of algal active compounds as potent antibiofilm agent.

Biofilm is the syntrophic association of microbial colonies that remain adhered to the biotic and abiotic surfaces with the help of self-secreted polymeric substances also termed extracellular polymeric substances. Chronic pathogenicity caused by biofilm-associated pathogenic microorganisms becomes a significant threat in biomedical research. An extensive search is being made for the antibiofilm agents made from natural sources or their biogenic derivatives due to their effectivity and nontoxicity. Algae being the producer of various biogenic substances are found capable of disintegrating biofilm matrix and eradication of biofilm without exerting any deterrent effect on other biotas in the ecosystem. The current trend in phycological studies includes the exploration of antifouling efficacy among various algal groups. The extracts prepared from about 225 microalgae and cyanobacteria species are found to have antibiofilm activity. Polyunsaturated fatty acids are the most important component in the algal extract with antibacterial and antibiofilm properties. The antibiofilm activity of the sulfated polysaccharides extracted from a marine alga could be effectively used to remove dental biofilm. Algal extracts are also being used for the preparation of different biogenically synthesized nanoparticles, which are being used as potent antibiofilm agents. Genome editing of algal species by CRISPR/Cas9 may make precise modifications in the algal DNA for improving the algal strains and production of a more effective antibiofouling agent.