A novel C-4-modified isotetrone acts as a potent bio-enhancer to augment the activities of anti-tuberculosis drugs against Mycobacterium tuberculosis.

Mycobacterium tuberculosis is a deadly pathogen that claims millions of lives every year. Current research focuses on finding new anti-tuberculosis drugs that are safe and effective, with lesser side effects and toxicity. One important approach is to identify bio-enhancers that can improve the effectiveness of anti-tuberculosis drugs, resulting in reduced doses and shortened treatment times. The present study investigates the use of C-4 modified isotetrones as bio-enhancers. A series of studies suggest an isotetrone, labeled as C11, inhibits growth, improves MIC, MBC and enhances the killing of M. tuberculosis H37Rv strain when used in combination with the first line and injectable anti-TB drugs in a dose-dependent manner. The combination of C11 and rifampicin also reduces the generation of spontaneous mutants against rifampicin and reaches a mutation prevention concentration (MPC) with moderate rifampicin concentrations. The identified compounds are effective against the MDR strain of M. tuberculosis and non-cytotoxic in HepG2 cells. We find that C11 induces the generation of reactive oxygen species (ROS) inside macrophages and within bacteria, resulting in better efficacy.

Effect of simethicone on the bactericidal efficacy of a high-level disinfectant.

Introduction. Simethicone is an over-the-counter product that is frequently used by clinicians during endoscopic procedures to reduce foaming and improve visualization. Published studies have found simethicone residue on endoscopes after cleaning and disinfecting the devices as per the manufacturer's instructions. Some literature suggests that simethicone residue may reduce disinfection efficacy and increase the risk of patient infections.Gap Statement. However, there appears to be a lack of direct evidence in the literature to either disprove this or correlate simethicone presence with an increased microbial risk.Aim: Research was conducted to evaluate the in vitro impact of simethicone on disinfection efficacy.Methodology. Bacteria were grown in a microtitre plate assay in the presence of a range of simethicone concentrations and then treated with a disinfectant. Bacterial growth was assessed by spotting each microtitre well onto an agar plate.Results. The results demonstrated that, under the conditions tested, simethicone did not reduce the efficacy of Cidex ortho-phthalaldehyde disinfectant, which demonstrated at least a 6-log unit reduction in bacterial viability. Additional experiments showed that direct exposure to 66 mg ml-1 of simethicone reduced bacterial viability.Conclusion. These results indicate that simethicone may not reduce the bactericidal efficacy of disinfectant during reprocessing, under certain conditions.

Food Retention at Endoscopy Among Adults Using Glucagon-Like Peptide-1 Receptor Agonists.

This cross-sectional study investigates the association between glucagon-like peptide-1 receptor agonists and food retention during esophagogastroduodenoscopy.

Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections.

We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n = 15). All patients received remdesivir and some also received nirmatrelvir-ritonavir (n = 3) or therapeutic monoclonal antibodies (n = 4). Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient sequentially treated with nirmatrelvir-ritonavir and remdesivir. In vitro characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo.

Reducing pain using vibrating device during local anesthesia among Indian pediatric dental patients.

The administration of local anesthesia constitutes one of the most anxiety-inducing and painful stimuli in pediatric dentistry. Therefore, it is of interest to evaluate the effectiveness of vibrating device in comparison to the conventional method for mitigating discomfort while administration of local anesthesia. A total of 30 children aged between 6 and 10 years, requiring local anesthesia for routine dental treatment, were allocated into two groups: a control group and an experimental group, with 15 children in each cohort. In the experimental group, a vibrating device was concurrently placed over the cheek during the administration of the local anesthesia. Pain and discomfort were assessed using both the Wong-Baker FACES Pain Rating Scale (WBFPRS) and the FLACC (Face, Legs, Activity, Cry, CONSOL ability) scale. It was observed that use of the vibrating device was found to be effective in reducing pain and discomfort during the administration of intraoral local anesthesia.

Breathomics: may it become an affordable, new tool for early diagnosis of non-small-cell lung cancer? An exploratory study on a cohort of 60 patients.

OBJECTIVES: Analysis of breath, specifically the patterns of volatile organic compounds (VOCs), has shown the potential to distinguish between patients with lung cancer (LC) and healthy individuals (HC). However, the current technology relies on complex, expensive and low throughput analytical platforms, which provide an offline response, making it unsuitable for mass screening. A new portable device has been developed to enable fast and on-site LC diagnosis, and its reliability is being tested. METHODS: Breath samples were collected from patients with histologically proven non-small-cell lung cancer (NSCLC) and healthy controls using Tedlar bags and a Nafion filter attached to a one-way mouthpiece. These samples were then analysed using an automated micro portable gas chromatography device that was developed in-house. The device consisted of a thermal desorption tube, thermal injector, separation column, photoionization detector, as well as other accessories such as pumps, valves and a helium cartridge. The resulting chromatograms were analysed using both chemometrics and machine learning techniques. RESULTS: Thirty NSCLC patients and 30 HC entered the study. After a training set (20 NSCLC and 20 HC) and a testing set (10 NSCLC and 10 HC), an overall specificity of 83.3%, a sensitivity of 86.7% and an accuracy of 85.0% to identify NSCLC patients were found based on 3 VOCs. CONCLUSIONS: These results are a significant step towards creating a low-cost, user-friendly and accessible tool for rapid on-site LC screening. CLINICAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT06034730.

Evaluating Methods for the Prediction of Cell Type-Specific Enhancers in the Mammalian Cortex.

Identifying cell type-specific enhancers in the brain is critical to building genetic tools for investigating the mammalian brain. Computational methods for functional enhancer prediction have been proposed and validated in the fruit fly and not yet the mammalian brain. We organized the 'Brain Initiative Cell Census Network (BICCN) Challenge: Predicting Functional Cell Type-Specific Enhancers from Cross-Species Multi-Omics' to assess machine learning and feature-based methods designed to nominate enhancer DNA sequences to target cell types in the mouse cortex. Methods were evaluated based on in vivo validation data from hundreds of cortical cell type-specific enhancers that were previously packaged into individual AAV vectors and retro-orbitally injected into mice. We find that open chromatin was a key predictor of functional enhancers, and sequence models improved prediction of non-functional enhancers that can be deprioritized as opposed to pursued for in vivo testing. Sequence models also identified cell type-specific transcription factor codes that can guide designs of in silico enhancers. This community challenge establishes a benchmark for enhancer prioritization algorithms and reveals computational approaches and molecular information that are crucial for the identification of functional enhancers for mammalian cortical cell types. The results of this challenge bring us closer to understanding the complex gene regulatory landscape of the mammalian brain and help us design more efficient genetic tools and potential gene therapies for human neurological diseases.

Long-term Outcomes of Traditional Braces versus Invisalign in Orthodontic Treatment.

Objective: This research targets to compare the longstanding outcomes of traditional braces versus Invisalign in orthodontic treatment, focusing on dental alignment, occlusal stability, patient satisfaction, and treatment duration. Methods: A retrospective cohort research with 200 subjects was piloted. One hundred subjects received traditional braces, while the other 100 received Invisalign. Dental models, cephalometric radiographs, and intraoral photographs were obtained at baseline, post-treatment, and at 1, 2, and 5 years follow-up. Patient satisfaction surveys were administered at each follow-up visit. Results: Both traditional braces and Invisalign effectively improved dental alignment and occlusal stability over the 5-year follow-up period. Patient satisfaction scores were consistently higher in the Invisalign group compared to the traditional braces group. However, there were no significant differences in treatment duration between the two groups. Conclusion: Invisalign may offer comparable or superior longstanding outcomes compared to traditional braces in orthodontic treatment, with higher patient satisfaction levels. These findings support the use of Invisalign as a viable alternative to traditional braces, particularly for subjects seeking esthetic and convenient orthodontic solutions.

Pain Perception During Local Anesthesia Administration in Pediatric Dental Patients and The Impact of Pre-Cooling The Injection Site: An in-vivo Study.

Aim: Examining how pre-cooling affects children's experience of pain during local anesthetic administration is the primary goal of this study. Material and Methods: This study was conducted in vivo and involved 60 child patients who required local anesthetic in order to undergo dental procedures. Patients were divided into two groups based on a random chance: Group I was the control group, which did not receive any pre-cooling. Group II was the pre-cooling group, which allowed the injection site to be chilled with an ice pack for one minute prior to the administration of anesthesia. The Wong-Baker FACES Pain Rating Scale was used to evaluate the participants' level of pain perception immediately following the administration of the anesthetic injection. Results: The group that received pre-cooling showed a reduction in pain levels that was statistically significant when compared to the group that received control (P < 0.05). Conclusion: Pediatric dental patients may decrease local anesthesia pain by pre-cooling the injection site. This technique can be simply used in dental practices to improve patient experience, especially for children with dental anxiety or needle phobia.

The neuroprotective effect of short-chain fatty acids against hypoxia-reperfusion injury.

Gut microbe-derived short-chain fatty acids (SCFAs) are known to have a profound impact on various brain functions, including cognition, mood, and overall neurological health. However, their role, if any, in protecting against hypoxic injury and ischemic stroke has not been extensively studied. In this study, we investigated the effects of two major SCFAs abundant in the gut, propionate (P) and butyrate (B), on hypoxia-reperfusion injury using a neuronal cell line and a zebrafish model. Neuro 2a (N2a) cells treated with P and B exhibited reduced levels of mitochondrial and cytosolic reactive oxygen species (ROS), diminished loss of mitochondrial membrane potential, suppressed caspase activation, and lower rates of cell death when exposed to CoCl2, a chemical commonly used to simulate hypoxia. Furthermore, adult zebrafish fed SCFA-supplemented feeds showed less susceptibility to hypoxic conditions compared to the control group, as indicated by multiple behavioral measures. Histological analysis of 2,3,5-Triphenyltetrazolium chloride (TTC) stained brain sections revealed less damage in the SCFA-fed group. We also found that Fatty Acid Binding Protein 7 (FABP7), also known as Brain Lipid Binding Protein (BLBP), a neuroprotective fatty acid binding protein, was upregulated in the brains of the SCFA-fed group. Additionally, when FABP7 was overexpressed in N2a cells, it protected the cells from injury caused by CoCl2 treatment. Overall, our data clearly demonstrate a neuroprotective role of P and B against hypoxic brain injury and suggest the potential of dietary supplementation with SCFAs to mitigate stroke-induced brain damage.

Epigallocatechin-3-gallate Synergistically Inhibits the Proliferation of Lung Cancer Cells with Gemcitabine by Induction of Apoptosis Mediated by ROS Generation.

The present study focused on the formulation, characterization, and evaluation of solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) for lung cancer treatment. A 2-level, 3-factor factorial design was used to optimize various process parameters in the preparation of SLNs. The average particle size and polydispersity index (PDI) of GEM-EGCG SLNs were found to be 122.8 ± 8.02 and 0.1738 ± 0.02, respectively. Drug loading and release studies indicated a sustained release behavior for GEM-EGCG SLNs, with release kinetics confirmed by the Higuchi model. Cell viability and anticancer activities were assessed using the MTT assay, which determined an IC50 value of 12.5 µg/mL for GEM-EGCG SLNs against A549 cell lines (lung carcinoma epithelial cells). The SLNs were able to internalize into the nuclei of cells, likely due to their small particle size, and were effective in killing cancer cells. Additionally, a study of ROS production-mediated apoptosis of A549 cells was performed through FACS. GEM-EGCG SLNs were found to be stable for 3 months. In vivo studies revealed better drug distribution in the lungs and improved pharmacokinetic profile compared with pure drugs. Overall, the results suggest that combining GEM and EGCG in biocompatible SLNs has resulted in synergistic antitumor potential and improved bioavailability for both drugs, making it a promising anticancer therapeutic regimen against lung cancer.

Isothermal recombinase polymerase amplification and silver nanoparticle assay: a sustainable approach for ultrasensitive detection of Klebsiella pneumoniae.

Our study addresses the urgent need for effective detection of Klebsiella pneumoniae, a recognized threat by the World Health Organization (WHO). Current challenges in managing K. pneumoniae infections include the lack of rapid and affordable detection tools, particularly in resource-limited point-of-care (POC) settings. To tackle this, we developed an innovative molecular detection pipeline combining three POC-compatible methods. Firstly, we employed Insta DNA™ card-based sample collection and DNA extraction for simplicity and ease of use. Next, we utilized recombinase polymerase amplification (RPA) targeting the Klebsiella hemolysin gene, khe, specific to the K. pneumoniae species complex (KpSC). Finally, we integrated a silver nanoparticle (AgNP) aggregation assay for visual detection, offering a rapid, sensitive, and specific method capable of detecting as few as ∼3 bacteria of K. pneumoniae within ∼45 minutes. This approach eliminates the need for complex equipment, making it highly suitable for field and resource-limited POC applications. Moreover, our method introduces an environmentally significant detection strategy. The method developed minimizes chemical reagent usage and reduces the carbon footprint associated with sample transportation. Furthermore, our method reduces waste compared to the traditional detection techniques, offering a safer alternative to ethidium bromide or other DNA dyes which are often genotoxic and mutagenic in nature. Silver nanoparticles, being environmentally safer, can also be recycled from the waste, contributing to sustainability in nanoparticle production and disposal. Overall, our technique presents a promising solution for detecting K. pneumoniae in various settings, including environmental, water, and food samples, as well as industrial or hospital effluents. By aligning with global efforts to improve public health and environmental sustainability, our approach holds significant potential for enhancing disease management and reducing environmental impact.

A Longitudinal Evaluation of the Effects of Moderate Physical Activity on Health, Metabolic, and Physiological Parameters in Individuals With Type 2 Diabetes Mellitus: A Comprehensive Study.

Background Diabetes mellitus (DM), especially type 2 diabetes mellitus (T2DM), is a serious worldwide health concern that is becoming more common and often develops at a young age, particularly in developing countries. Given the increasing incidence of diabetes in India, efficient management techniques are advantageous. The aim of this study is to evaluate the impact of physical activity on body measurements, biochemical markers, and clinical outcomes in Indian individuals with T2DM. Methodology Utilizing a universal sampling approach, a longitudinal interventional study was performed with T2DM patients at a metropolitan health and training facility over an eight-month duration. Over the course of six months, they were told to walk briskly for 2.5 hours each week. Initial and follow-up evaluations included monitoring arterial pressure, body mass, abdominal circumference, and glucose concentrations. During monthly follow-ups, participants self-reported their compliance. Results The study of 210 participants shows a diverse age distribution with the majority in the 35-54 years range and a higher number of females (56.19%) compared to males (43.81%). Most were Hindu (77.6%), with varying education levels and a predominance of unemployment (69.5%) and marital status (91.0% married). Post-exercise, significant improvements were observed in fasting blood glucose (160.45 to 140.20 mg/dL; p = 0.004), postprandial blood glucose (270.35 to 240.55 mg/dL; p = 0.002), body weight (70.00 to 66.50 kg; p = 0.03), and waist circumference (95.00 to 90.50 cm; p = 0.01). Conclusion The outcomes of this prolonged study reveal that along with promoting weight reduction in T2DM patients, regular engagement in moderate exercise can substantially improve both fasting and post-meal blood glucose levels.

A Systematic Review of Recent Studies on Hospital Readmissions of Patients With Diabetes.

Hospital readmissions are a major area of concern across the healthcare ecosystem. Diabetes mellitus (DM) and associated complications significantly contributed to hospital readmissions in 2018, placing it among the leading causes alongside septicemia and heart failure. Diabetes is an urgent public health concern that has reached epidemic proportions globally. Compared to the early 2000s, the prevalence of diabetes among individuals aged 20-79 years in the US has significantly increased. This research provides an in-depth examination of diabetes-related hospital readmissions and reviews recent studies (2015-2023) to understand the characteristics, risk factors, and potential outcomes for re-admitted diabetes patients. The study identified 21 articles that met the inclusion criteria to provide valuable insights and analyze risk factors associated with these readmissions. The findings indicated that risk factors such as age, demographics, income, insurance type, severity of illness, and comorbidities among diabetic patients were critical and warranted further investigation. Diabetes awareness, quality of hospital care, involvement of healthcare providers, timely screening, and lifestyle changes were noted as important factors to improve the effectiveness of healthcare delivery, reduce diabetes-related complications, and eventually lower preventable hospital readmissions.

Cancer-Associated Fibroblast Proteins as Potential Targets against Colorectal Cancers.

In colorectal cancer (CRC), attempts to identify cancer cell-specific markers to guide antibody-mediated therapeutics have failed to uncover markers that are both exclusive to cancer tissues and abundant across CRCs. Alternatively, cancer-associated fibroblasts (CAFs), which are abundant in the tumor microenvironment and upregulate unique surface markers, are not found in healthy tissues. Here, we evaluated the expression patterns of CAF-associated proteins α-smooth muscle actin (αSMA), fibroblast activation protein (FAP), podoplanin (PDPN), matrix metalloproteinase-2 (MMP2), transgelin (TAGLN), and THY1. While αSMA and THY1 were abundant in cancer tissues, high abundance in normal tissues limited their targeting potential. FAP was present in 94.5% of primary and metastatic CRC tissues and absent in 93.7% of adjacent normal colon and liver tissues assessed. These results indicate that FAP is a promising target for antibody conjugates with potential for broad application in CRC. Co-expression analyses showed that CRCs simultaneously expressing high levels of PDPN, MMP2, and THY1 were enriched for immune-related signatures, indicating potential for antibody-mediated immune engagers. Overall, this work highlights the potential of CAF proteins to act as therapeutic targets for novel anticancer agents and become important therapeutic biomarkers.

Insights to the emerging potential of glucokinase activators as antidiabetic agent.

The glucokinase enzyme (belongs to the hexokinase family) is present in liver cells and ß-cells of the pancreas. Glucokinase acts as a catalyst in the conversion of glucose-6-phosphate from glucose which is rate-limiting step in glucose metabolism. Glucokinase becomes malfunctional or remains inactivated in diabetes. Glucokinase activators are compounds that bind at the allosteric site of the glucokinase enzyme and activate it. This article highlights the patent and recent research papers history with possible SAR from year 2014-2023. The data comprises the discussion of novel chemotypes (GKAs) that are being targeted for drug development and entered into clinical trials. GK activators have attracted massive interest since successful results have been reported from clinical trials data.

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Pre-pregnancy substance use and first trimester cardiovascular health among nulliparous pregnant people: The nuMoM2b Study.

BACKGROUND: Suboptimal pre-pregnancy health, including substance use and cardiovascular risk factors, is associated with higher risks of maternal-foetal morbidity and mortality. OBJECTIVE: To determine if pre-pregnancy substance use is associated with early pregnancy cardiovascular health (CVH). It is hypothesised that pre-pregnancy use of substances is associated with worse CVH in the first trimester of pregnancy. METHODS: This is a secondary analysis from the 2010-2015 United States nuMoM2b cohort (n = 9895). Pre-pregnancy alcohol, tobacco, marijuana, and illicit substance use were assessed through questionnaires. Latent class analysis categorised participants based on their 3-month pre-pregnancy or ever(*) substance use: (1) Illicit substances*, marijuana*, and alcohol use (n = 1234); (2) marijuana* and alcohol use (n = 2066); (3) tobacco and alcohol use (n = 636); and (4) alcohol only use (n = 3194). The referent group reported no pre-pregnancy substance use (n = 2765). First trimester CVH score from 0 (least healthy) to 100 (most healthy) was calculated using a modified American Heart Association Life's Essential 8 framework and included body mass index (BMI), blood pressure, blood glucose, non-HDL cholesterol, diet, sleep, and physical activity. Multiple linear regression evaluated the relationship between pre-pregnancy substance use classes and CVH scores. RESULTS: CVH score varied by class: No substance use (mean: 65, SD: ±1.3), illicit substances*, marijuana*, and alcohol use (68 ± 1.3), marijuana* and alcohol use (67 ± 1.3), tobacco and alcohol use (62 ± 1.4), and alcohol only use (67 ± 1.3). In adjusted models, those who used tobacco and alcohol compared to the no substance use class had a lower CVH score (-2.82); other classes had scores ranging from 1.81 to 2.44 points higher than the no substance use class. Individual CVH component scores followed similar patterns. CONCLUSIONS: All groups, but most markedly those who used tobacco and alcohol prior to pregnancy, began pregnancy with only moderate CVH and may benefit from CVH promotion efforts along with substance use treatment.

A Very Bad Hair Day: Minoxidil Ingestion Causing Shock and Heart Failure.

Minoxidil is a potent directly acting vasodilator previously used in treatment-resistant hypertension. It possesses several serious side effects including fluid retention, worsening of heart failure, reflex tachycardia, angina, myocardial infarction, pericardial effusion, and hypotension. It is currently reserved for treating alopecia and readily available over the counter as a topical formulation. Intentional/accidental ingestion of topical minoxidil can cause refractory circulatory shock requiring aggressive hydration and vasopressor support. We present a case of a young female with unintentional ingestion of minoxidil leading to severe circulatory shock and acute pulmonary edema. Minoxidil, a common hair loss treatment, is highly dangerous if ingested. Immediate identification and treatment are crucial, involving fluid resuscitation and vasopressors for severe circulatory shock. Midodrine, an alpha-adrenergic agonist, can reduce ICU stay by shortening IV vasopressor usage.

Mitochondrial dsRNA from B-ALL cells stimulates mesenchymal stromal cells to become cancer associated fibroblasts.

Cancer associated fibroblasts (CAF) arising from bone marrow-derived mesenchymal stromal cells (MSC) are prominent in B-precursor acute lymphoblastic leukaemia (B-ALL). We have previously shown that CAF formation is triggered by exposure to reactive oxygen species-inducing chemotherapy and that CAF support chemoresistance by donating mitochondria to the cancer cells, through tunnelling nanotubes. In the present study, we show that exposure of MSC to ALL cell lines, patient-derived xenografts and primary cells or their conditioned media can also trigger CAF formation. Using bulk RNA sequencing in cell lines, we show that the MSC to CAF transition is accompanied by a robust interferon pathway response and we have validated this finding in primary cells. Using confocal microscopy and flow cytometry, we identify the take-up of leukaemia cell-derived mitochondrial dsRNA by MSC as a proximate trigger for the MSC to CAF transition. We show that inhibition of dsRNA formation in ALL cells by treatment with low-dose ethidium or the mitochondrial transcription inhibitor IMT1 or degradation of dsRNA in conditioned media by 100°C exposure ablates the ability of the ALL conditioned media to stimulate MSC to CAF transition. Our data reveal a novel and previously undescribed mechanism by which cancer cells induce a CAF phenotype in stromal cells, showing how B-ALL cells can directly induce the previously described niche-mediated protection within the bone marrow.

Mild Blast Exposure Dysregulates Metabolic Pathways and Correlation Networking as Evident from LC-MS-Based Plasma Profiling.

Blast-induced trauma is emerging as a serious threat due to its wide pathophysiology where not only the brain but also a spectrum of organs is being affected. In the present study, we aim to identify the plasma-based metabolic dysregulations along with the associated temporal changes at 5-6 h, day 1 and day 7 post-injury in a preclinical animal model for blast exposure, through liquid chromatography-mass spectrometry (LC-MS). Using significantly advanced metabolomic and statistical bioinformatic platforms, we were able to elucidate better and unravel the complex networks of blast-induced neurotrauma (BINT) and its interlinked systemic effects. Significant changes were evident at 5-6 h with maximal changes at day 1. Temporal analysis also depicted progressive changes which continued till day 7. Significant associations of metabolic markers belonging to the class of amino acids, energy-related molecules, lipids, vitamin, hormone, phenolic acid, keto and histidine derivatives, nucleic acid molecules, uremic toxins, and uronic acids were observed. Also, the present study is the first of its kind where comprehensive, detailed pathway dysregulations of amino acid metabolism and biosynthesis, perturbed nucleotides, lipid peroxidation, and nucleic acid damage followed by correlation networking and multiomics networking were explored on preclinical animal models exposed to mild blast trauma. In addition, markers for systemic changes (renal dysfunction) were also observed. Global pathway predictions of unannotated peaks also presented important insights into BINT pathophysiology. Conclusively, the present study depicts important findings that might help underpin the biological mechanisms of blast-induced brain or systemic trauma.