Oxymatrine impedes the progression of endotoxin-induced glaucoma via redox system modulations.

This study aimed to provide irrefutable evidence of the preventive effects of oxymatine (OMT) on a model of endotoxin induced glaucoma in Wistar rats which can be attributed to its anti-inflammatory, antioxidant, and TNF-α antagonistic properties. To assess the impact of OMT on uveitic glaucoma, the normal group received 100 µL distilled water topically for 15 days, while the glaucoma control group was induced with uveitic glaucoma by applying 10 µL of 10 µg/mL lipopolysaccharide (LPS) topically for 3 consecutive days. The treatment groups were then given OMT solution at a volume of 50 µL with varying doses of 0.25%, 0.5%, and 1% once a day via topical administration for 15 days. In addition, as a standard, the animals were also given 100 µL of 1% dorzolamide topically for 15 days. All ophthalmic dosing was carried out by pulling the lower eye-lid of the experimental animals and administration of the respective solutions. The study uses cutting-edge real-time imaging of the retinal vasculature in anesthetized animals, postsacrifice lenticular picturization and biochemical evidence to support the changes in the retinal layers. LPS induced animals demonstrated increased IOP, disrupted antioxidant systems, massive lipid damage, enhanced TNF-α activity and changes in intracellular ATPase and ionic activities. The damaged retinal vasculature and lenticular opacification further supported the biochemical evidence. However, using OMT at a 1% dosage effectively enhanced the antioxidant levels, regulated intracellular ion concentration and ATPases, decreased TNF-α activity, and counteracted mechanobiological changes in the visual front and retina. Moreover, OMT can successfully normalize intraocular pressure, making it a highly beneficial treatment option for glaucoma.

Paternal Alcohol Consumption and Childhood Malnutrition: A Community-based Participatory Case-control Study among Adivasis in Rural South India.

BACKGROUND: Childhood malnutrition in India remains among the highest in the world. Adult alcohol consumption and severe malnutrition have increased among indigenous people in South India. However, the association between them is poorly understood. OBJECTIVES: We aimed to evaluate this association, which could help design better intervention strategies. METHODS: This case-control observational study was conducted in the Nilgiri district in South India. Cases included children aged 1-5 years with moderate malnutrition. Controls were defined as children in the same age group with normal weight-for-age. A questionnaire was used to collect data on demographics, socioeconomic status (SES), and parental education. The WHO Alcohol Use Disorders Identification Test (AUDIT) questionnaire was used to estimate parental alcohol use. Health-care workers collected data from within the community. RESULTS: The baseline demographics of the children in the control (n = 250) and case groups (n = 177) were similar. Paternal age and AUDIT scores were not different in the two groups. SES was lower in the malnourished group, while maternal education among cases was significantly lower. Maternal and paternal education were associated with childhood malnutrition (odds ratio [OR]: 0.728 [95% confidence interval (CI): 0.583-0.903] and OR: 0.753 [95% CI: 0.589-0.957], respectively). After adjustment for covariates, paternal alcohol use was associated with a higher risk of malnutrition (OR: 1.56 [95% CI: 1.00-2.47]), which SES partly mediated. CONCLUSION: Paternal alcohol consumption is associated with childhood malnutrition, partially mediated by lower SES. Furthermore, lower SES appeared to be strongly associated with paternal alcohol consumption.

Comparative studies on the antioxidant, anticancer and anti-inflammatory activities of green tea, orthodox black tea and CTC black tea.

Tea is a natural dietary supplement rich in polyphenols and based on the manufacturing process, their polyphenol content also varies. In the present study, we have compared the in vitro antioxidant, anticancer and anti-inflammatory activities of green tea (GT), orthodox black tea (oBT) and CTC black tea (cBT). The analysis was carried out in 50:50 ethanol:water extracts. The total antioxidant capacity, total polyphenol content and free radical scavenging activity were found to be high in GT samples. HPLC profiling indicated a higher percentage of polyphenols like catechin, epicatechin, epigallocatechin and epigallocatechin-gallate in GT when compared to other samples. The comparison of the anticancer potential was done in breast cancer MDA MB-231 cells and it was found that GT has a higher percentage of cell growth inhibition than oBT and cBT. Anti-inflammatory effects were done in LPS stimulated RAW264.7 macrophage cells and here also GT showed maximum effects. This was confirmed by the lower production of iNOS, reduced level of ROS generation and proinflammatory cytokines such as MCP-1, IL-1ɑ, and IL-6 by GT. To conclude, the order for the biological effectiveness of different teas tested is in the order GT > oBT > cBT.

Chitosan-encapsulated microbial biofertilizer: A breakthrough for enhanced tomato crop productivity.

Encapsulation technology protects the beneficial microorganisms, which are the sources of Nitrogen (N), Phosphorus (P), and Potassium (K), with a carrier material and improves the nutrient uptake from the soil. Pseudomonas fluorescens, gram-negative bacteria, was selected as the microorganism for encapsulation. A chitosan carrier (3 %), a polysaccharide, was chosen for the encapsulation of the bacterial strain to use as biofertilizers by standardization with two carriers, sodium alginate and chitosan. P. fluorescens encapsulated with chitosan showed a higher shelf life than sodium alginate. The shelf life of the encapsulated culture (7 × 1010 CFU/mL) was maintained for ten months. Studies were performed with the encapsulated P. fluorescens to analyze its nature and characteristics. The pot and field studies were conducted with the encapsulated P. fluorescens for the tomato crop. The difference between the treated and control plants was observed based on biometric parameters like shoot length and root length, fruit weight, and number of branches and fruits per plant. This study reveals that encapsulated P. fluorescens improved the yield of the crops. In addition, soil health and fertility were also enhanced. Thus, encapsulated P. fluorescens could be a superior solution for promoting soil health and crop productivity for sustainable agriculture.

Metformin-Induced Nightmares: An Uncommon Event.

Metformin is well-known in the treatment of type 2 diabetes mellitus (DM). Metformin has become a drug of choice due to its affordability, cost-effectiveness, and established safety record. It primarily works by inhibiting hepatic gluconeogenesis. Common side effects include gastrointestinal issues, with rare complications, such as lactic acidosis and vitamin B12 malabsorption. This study discussed a 72-year-old male with type 2 DM who experienced recurrent nightmares upon initiating metformin, which ceased after discontinuation. The mechanism of metformin-associated nightmares remains poorly understood. Despite metformin's benefits, this case highlights the importance of recognizing rare adverse effects like nightmares, which can significantly impact patients' quality of life.

Bark extract of Chaetocarpus castanocarpus (Roxb.) exhibits potent sedative, anxiolytic, and antidepressant effects through an in vivo approach in Swiss albino mice.

OBJECTIVE: Standard phytochemical investigations were performed to identify the secondary metabolites in the methanol extract of Chaetocarpus castanocarpus bark (MECC) and investigate the neuropharmacological potential of MECC in Swiss albino mice. MATERIALS AND METHODS: Swiss albino mice were used in the forced swimming test (FST) and tail suspension test (TST) to evaluate the antidepressant effect of MECC. Also, the hole board test (HBT) and elevated plus maze (EPM) were conducted to examine anxiolytic activities. In contrast, the open field test (OFT) and hole cross test (HCT) were employed to evaluate sleeping disorders. RESULTS: Alkaloids, glycosides, flavonoids, terpenoids, coumarins, and tannins are only a few secondary metabolites identified in MECC by qualitative and quantitative phytochemical investigations. The oral administration of MECC considerably shortened the immobility duration during FST and TST. Encouraging dose-dependent anxiolytic effects were also observed in all relevant experiments compared to the control. Additionally, during the OFT and HCT assessment, a noteworthy decline in the locomotor activities of the experimental animals was observed. CONCLUSIONS: The results of this investigation suggest that the Chaetocarpus castanocarpus bark is a possible source of therapeutic candidates for treating neurological disorders.

Virtual Planning and Augmented Reality-Guided Microsurgical Resection of a Frontal Arteriovenous Malformation.

Arteriovenous malformations (AVMs) are complex vascular lesions that can pose significant risk for spontaneous hemorrhage, seizures, and symptoms related to ischemia and venous hypertension.1 Microsurgical management of AVMs requires a deep understanding of the surrounding anatomy and precise identification of the lesion characteristics. We demonstrate the use of augmented reality in the localization of arterial feeders and draining veins in relation to bordering normal structures (Video 1). A 66-year-old man presented with several episodes of severe right frontal headaches. Magnetic resonance imaging revealed an AVM along the right frontal pole. Subsequent computed tomography angiography demonstrated arterial supply from the right anterior cerebral artery with venous drainage to the superior sagittal sinus. Due to the size, noneloquent location, and superficial pattern of venous drainage, the patient elected to proceed with microsurgery. A virtual planning platform was used in preparation for surgery. Augmented reality integrated with neuronavigation was used during microsurgical resection. Postoperative angiography showed complete resection of the AVM. The patient was discharged home on postoperative day 3 with no complications. He remains neurologically well at 4 months of follow-up.

Microsurgical Treatment of Pineal Tumors: Anatomy and Techniques.

Pineal region tumors are challenging lesions in terms of surgical accessibility and removal.1 The complexity is compounded by the infrequency and heterogeneity of pineal neoplasms.2,3 In Video 1, we present the case of a 39-year-old woman who presented with progressive headaches and vision impairment. She underwent microsurgical resection for a pineal parenchymal tumor of intermediate differentiation. We discuss the rationale, risks, and benefits of treatment for this patient, as well as provide a detailed overview of the alternative approaches that may be considered. Additionally, we discuss the unique anatomic considerations for each approach and include a virtual reality-compatible 3-dimensional fly-through to highlight the relationship between the tumor and relevant venous anatomy. The patient tolerated the procedure well with excellent neurologic outcome, and her follow-up imaging showed no evidence of tumor recurrence.

The use of Microsurgical Exploration of the External Carotid Artery for Removal of a Retained Microcatheter After Middle Meningeal Artery Embolization Using Live Fluoroscopy: A Technical Note.

BACKGROUND: Fragmentation, disconnection, or entrapment of an in-use microcatheter during neuro-endovascular procedures is a known risk. Often a benign entity, retained catheters are not infrequently observed, but severe complications including thrombus, thromboembolic events, pseudoaneurysm, and limb ischemia have been described, necessitating retrieval. This technical case report demonstrates the safe use of an external carotid artery (ECA) approach for ligation and removal of a retained microcatheter after middle meningeal artery (MMA) embolization. This article also demonstrates the use of live intraoperative fluoroscopy as a surgical adjunct to ensure that the catheter is fully removed without any injury, shearing, or breakage during removal. METHODS: A 66-year-old male patient presented with bilateral subdural hematomas to an outside hospital. He subsequently underwent evacuation of the hematomas followed by a right-sided MMA embolization, complicated by Onyx (Medtronic, Minneapolis, MN) entrapment of the microcatheter in the MMA. The patient was asymptomatic, but there was significant concern about continuing antiplatelet/anticoagulation therapy in the presence of the subdural hematoma. We proceeded with an open surgical approach for catheter retrieval. As the catheter was withdrawn, intraoperative fluoroscopy demonstrated complete removal without any retained fragments. RESULTS: The patient recovered without event and was discharged on postoperative day 1. On follow-up the patient continued to do well without any complications from the fragment that remained in the external carotid circulation. CONCLUSIONS: This case and accompanying video demonstrates the effective use of open ECA surgical approach to retrieve the retained microcatheter after an MMA embolization. This approach allowed for safe and effective removal of the microcatheter while significantly reducing complication risks.

Quantifying intra-tumoral genetic heterogeneity of glioblastoma toward precision medicine using MRI and a data-inclusive machine learning algorithm.

BACKGROUND AND OBJECTIVE: Glioblastoma (GBM) is one of the most aggressive and lethal human cancers. Intra-tumoral genetic heterogeneity poses a significant challenge for treatment. Biopsy is invasive, which motivates the development of non-invasive, MRI-based machine learning (ML) models to quantify intra-tumoral genetic heterogeneity for each patient. This capability holds great promise for enabling better therapeutic selection to improve patient outcome. METHODS: We proposed a novel Weakly Supervised Ordinal Support Vector Machine (WSO-SVM) to predict regional genetic alteration status within each GBM tumor using MRI. WSO-SVM was applied to a unique dataset of 318 image-localized biopsies with spatially matched multiparametric MRI from 74 GBM patients. The model was trained to predict the regional genetic alteration of three GBM driver genes (EGFR, PDGFRA and PTEN) based on features extracted from the corresponding region of five MRI contrast images. For comparison, a variety of existing ML algorithms were also applied. Classification accuracy of each gene were compared between the different algorithms. The SHapley Additive exPlanations (SHAP) method was further applied to compute contribution scores of different contrast images. Finally, the trained WSO-SVM was used to generate prediction maps within the tumoral area of each patient to help visualize the intra-tumoral genetic heterogeneity. RESULTS: WSO-SVM achieved 0.80 accuracy, 0.79 sensitivity, and 0.81 specificity for classifying EGFR; 0.71 accuracy, 0.70 sensitivity, and 0.72 specificity for classifying PDGFRA; 0.80 accuracy, 0.78 sensitivity, and 0.83 specificity for classifying PTEN; these results significantly outperformed the existing ML algorithms. Using SHAP, we found that the relative contributions of the five contrast images differ between genes, which are consistent with findings in the literature. The prediction maps revealed extensive intra-tumoral region-to-region heterogeneity within each individual tumor in terms of the alteration status of the three genes. CONCLUSIONS: This study demonstrated the feasibility of using MRI and WSO-SVM to enable non-invasive prediction of intra-tumoral regional genetic alteration for each GBM patient, which can inform future adaptive therapies for individualized oncology.

Image-localized biopsy mapping of brain tumor heterogeneity: A single-center study protocol.

Brain cancers pose a novel set of difficulties due to the limited accessibility of human brain tumor tissue. For this reason, clinical decision-making relies heavily on MR imaging interpretation, yet the mapping between MRI features and underlying biology remains ambiguous. Standard (clinical) tissue sampling fails to capture the full heterogeneity of the disease. Biopsies are required to obtain a pathological diagnosis and are predominantly taken from the tumor core, which often has different traits to the surrounding invasive tumor that typically leads to recurrent disease. One approach to solving this issue is to characterize the spatial heterogeneity of molecular, genetic, and cellular features of glioma through the intraoperative collection of multiple image-localized biopsy samples paired with multi-parametric MRIs. We have adopted this approach and are currently actively enrolling patients for our 'Image-Based Mapping of Brain Tumors' study. Patients are eligible for this research study (IRB #16-002424) if they are 18 years or older and undergoing surgical intervention for a brain lesion. Once identified, candidate patients receive dynamic susceptibility contrast (DSC) perfusion MRI and diffusion tensor imaging (DTI), in addition to standard sequences (T1, T1Gd, T2, T2-FLAIR) at their presurgical scan. During surgery, sample anatomical locations are tracked using neuronavigation. The collected specimens from this research study are used to capture the intra-tumoral heterogeneity across brain tumors including quantification of genetic aberrations through whole-exome and RNA sequencing as well as other tissue analysis techniques. To date, these data (made available through a public portal) have been used to generate, test, and validate predictive regional maps of the spatial distribution of tumor cell density and/or treatment-related key genetic marker status to identify biopsy and/or treatment targets based on insight from the entire tumor makeup. This type of methodology, when delivered within clinically feasible time frames, has the potential to further inform medical decision-making by improving surgical intervention, radiation, and targeted drug therapy for patients with glioma.