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.

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.

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.

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.

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.

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.

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.

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.

Evaluating the performance of electrocoagulation system in the removal of polystyrene microplastics from water.

Emerging pollutants, particularly microplastics, present a significant threat to both the environment and human health. Traditional treatment methods lack targeted strategies for their removal. This study thoroughly investigated the efficacy of electrocoagulation as a method for efficiently extracting microplastics from water. Various critical operational parameters, including electrode combinations, pH levels, electrolyte concentrations, electrode geometries, configurations, current intensities, and reaction times, were systematically examined. The study systematically examined the impact of different combinations of aluminium (Al) and stainless steel (SS) electrodes, including Al-Al, SS-SS, Al-SS, and SS-Al. Among these combinations, it was found that the Al-Al pairing exhibited outstanding efficiency in microplastic removal, while simultaneously minimizing energy consumption. Initial pH emerged as a critical parameter, with a neutral pH of 7 demonstrating the highest removal efficiency. In the pursuit of optimizing parameters like electrolyte concentrations, electrode geometry, and configuration, it's noteworthy that consistently achieving removal efficiencies exceeding 90% has been a significant achievement. However, to ascertain economic efficiency, additional factors such as energy consumption, electrode usage, and post-treatment conductivity must be taken into account. To tackle the complexity posed by various parameters and criteria, using multi-criteria decision-making tools like TOPSIS is essential, as it has a track record of effectiveness in practical applications. The electrolyte concentration of 0.5 g L-1 is identified as optimal by TOPSIS analysis Additionally, the TOPSIS highlighted the superiority of cylindrical hollow wire mesh electrodes and established the monopolar parallel configuration as the most effective electrode connection method. The investigation carefully evaluated the effect of reaction time, determining that a 50-min window provides optimal microplastic removal efficiency. This refined system exhibited remarkable proficiency in eliminating microplastics of varying size ranges (0-75 µm, 75-150 µm, and 150-300 µm), achieving removal efficiencies of 90.67%, 93.6%, and 94.6%, respectively, at input concentration of 0.2 g L-1. The present study offers a comprehensive framework for optimizing electrocoagulation parameters, presenting a practical and highly effective strategy to address the critical issue of microplastic contamination in aquatic environments.

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.

Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures.

Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.

Predictive Model Evaluating Risk of Hemorrhage in Intracranial Aneurysms: Analysis from Prospectively Collected HEAT Trial Database.

OBJECTIVE: We analyzed the data of patients enrolled in the Hydrogel Endovascular Aneurysm Treatment (HEAT) trial to develop and validate a model to predict the risk of aneurysmal hemorrhage. METHODS: Analysis included data from 600 patients enrolled for the HEAT trial and included single saccular aneurysms of 3-14 mm size. Baseline characteristics were compared between patients with ruptured and unruptured aneurysms. Regression analysis was performed in the training set to identify significant risk factors and was validated in the validation dataset. The complete dataset was used to formulate a scoring model in which positive and negative predictors were assigned 1 and -1 points, respectively. RESULTS: Data from 593 patients were analyzed in which 169 (28.5%) patients had ruptured aneurysms. The training (n = 297) and validation dataset (n = 296) had a comparable proportion of ruptured aneurysms (29.3% and 27.7%). Dome-to-neck ratio >2.5 (odds ratio [OR] 3.66), irregular shape (OR 3.79), daughter sac (OR 5.89), and anterior and posterior communicating artery locations (OR 3.32 and 3.56, respectively) had a higher rupture rate. Use of aspirin was associated with lower risk of hemorrhage (OR 0.16). The area under the curve from the receiver operating curve analysis was 0.88, 0.87, and 0.87 in the training, validation, and combined data set, respectively. The scoring model created a score of -1 to 2, yielding an of aneurysmal hemorrhage probability from 1.5% (score -1) to 70% (score 2). CONCLUSIONS: This prospective study identifies dome-to-neck ratio >2.5, irregular shape, presence of daughter sac, absence of aspirin use, and aneurysm location at anterior communicating and posterior communicating artery as factors associated with increased risk of hemorrhagic presentation in small- to medium-sized intracranial aneurysms. Our model provides an estimate of rupture risk based on the presence or absence of these factors.

Silver-catalyzed synthesis of nitrogen heterocycles: recent advancements.

Heterocyclic chemistry is an ever-expanding field without boundaries. Heterocycles play a significant role in medicinal and pharmaceutical chemistry, the agricultural industry and materials science. Among heterocycles, N-heterocycles constitute a large family. Their ubiquity in living and non-living systems makes them an endless topic for research. Being a part of the research community, we need to balance environmental concerns with scientific and economic development. So, research that is coherent with nature is a trending domain at all times. Silver catalysis possesses a greener face in organic synthesis. The simple, rich and extensive chemistry shown by silver makes it an attractive choice for catalysis. Inspired by its versatility and uniqueness we have compiled here recent developments in the silver-catalyzed synthesis of nitrogen-containing heterocycles since 2019. The high efficiency, regioselectivity, chemoselectivity, recyclability of the catalytic system, greater atom economy and simple reaction setup are the major highlights of this protocol. It is a hot research topic which is evident from the large number of works carried out for the fabrication of a range of N-heterocycles with varying complexities.

A CD36 transmembrane domain peptide interrupts CD36 interactions with membrane partners on macrophages and inhibits atherogenic functions.

CD36 is a transmembrane glycoprotein receptor for oxidized low density lipoprotein (LDL) and other endogenous danger signals and promotes athero-thrombotic processes. CD36 has been shown to associate physically with other transmembrane proteins, including integrins, tetraspanins, and toll-like receptors, which modulate CD36-mediated cell signaling. The CD36 N-terminal transmembrane domain (nTMD) contains a GXXXG sequence motif that mediates protein-protein interactions in many membrane proteins. We thus hypothesized that the nTMD is involved in CD36 interactions with other membrane proteins. CD36 interactions with partner cell surface proteins on murine peritoneal macrophages were detected with an immunofluorescence-based proximity ligation cross linking assay (PLA) and confirmed by immunoprecipitation/immunoblot. Prior to performing these assays, cells were incubated with a synthetic 29 amino acid peptide containing the 22 amino acid of CD36 nTMD or a control peptide in which the glycine residues in GXXXG motif were replaced by valines. In functional experiments, macrophages were preincubated with peptides and then treated with oxLDL to assess LDL uptake, foam cell formation, ROS formation and cell migration. CD36 nTMD peptide treated cells compared to untreated or control peptide treated cells showed decreased CD36 surface associations with tetraspanin CD9 and ameliorated pathologically important CD36 mediated responses to oxLDL, including uptake of DiI-labeled oxLDL, foam cell formation, ROS generation, and inhibition of migration.

Molecular docking and dynamic simulation studies of α4ß2 and α7 nicotinic acetylcholine receptors with tobacco smoke constituents nicotine, NNK and NNN.

Smoking constitutes a major global health problem. As it triggers various health hazards including cancers, cardiac and pulmonary illness, it is imperative to understand the mechanism of action of various smoke constituents on our cellular processes. Various in vitro studies have compiled the affinity of cigarette smoke constituents on various nicotinic acetylcholine receptors (nAChRs). But the nature of the intermolecular interactions contributing to this affinity and the key amino acids in the receptor active sites involved in this are not investigated so far. Here, we are examining the interaction of α7nAChR and α4ß2nAChR on nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N-nitrosornicotine (NNN), the physiologically significant constituents in smoke, through molecular docking and dynamics simulations study. The docking of α4ß2nAChR structure with the ligands nicotine, NNK and NNN yielded docking scores of -41.45 kcal/mol, -59.28 kcal/mol and -54.60 kcal/mol, respectively, and that of α7nAChR receptor molecule with the ligands yielded docking scores of -59.54 kcal/mol, -71.06 kcal/mol and -70.86 kcal/mol, respectively. The study showed that NNK exhibited the highest affinity with the ligands which was confirmed by dynamics simulation. But higher stability of interactions as surmised from Molecular dynamics simulations was found for nicotine with α4ß2nAChR and NNN with α7nAChR. The findings validate the in vitro studies comparing the affinities of these compounds. The study will be useful in formulating effective nAChR agonists to treat neurological disorders and antagonists for smoke deaddiction and improve health standards.Communicated by Ramaswamy H. Sarma.