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1.
Neurology ; 103(1): e209501, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38870452

ABSTRACT

BACKGROUND AND OBJECTIVES: Generalized convulsive seizures (GCSs) are the main risk factor of sudden unexpected death in epilepsy (SUDEP), which is likely due to peri-ictal cardiorespiratory dysfunction. The incidence of GCS-induced cardiac arrhythmias, their relationship to seizure severity markers, and their role in SUDEP physiopathology are unknown. The aim of this study was to analyze the incidence of seizure-induced cardiac arrhythmias, their association with electroclinical features and seizure severity biomarkers, as well as their specific occurrences in SUDEP cases. METHODS: This is an observational, prospective, multicenter study of patients with epilepsy aged 18 years and older with recorded GCS during inpatient video-EEG monitoring for epilepsy evaluation. Exclusion criteria were status epilepticus and an obscured video recording. We analyzed semiologic and cardiorespiratory features through video-EEG (VEEG), electrocardiogram, thoracoabdominal bands, and pulse oximetry. We investigated the presence of bradycardia, asystole, supraventricular tachyarrhythmias (SVTs), premature atrial beats, premature ventricular beats, nonsustained ventricular tachycardia (NSVT), atrial fibrillation (Afib), ventricular fibrillation (VF), atrioventricular block (AVB), exaggerated sinus arrhythmia (ESA), and exaggerated sinus arrhythmia with bradycardia (ESAWB). A board-certified cardiac electrophysiologist diagnosed and classified the arrhythmia types. Bradycardia, asystole, SVT, NSVT, Afib, VF, AVB, and ESAWB were classified as arrhythmias of interest because these were of SUDEP pathophysiology value. The main outcome was the occurrence of seizure-induced arrhythmias of interest during inpatient VEEG monitoring. Moreover, yearly follow-up was conducted to identify SUDEP cases. Binary logistic generalized estimating equations were used to determine clinical-demographic and peri-ictal variables that were predictive of the presence of seizure-induced arrhythmias of interest. The z-score test for 2 population proportions was used to test whether the proportion of seizures and patients with postconvulsive ESAWB or bradycardia differed between SUDEP cases and survivors. RESULTS: This study includes data from 249 patients (mean age 37.2 ± 23.5 years, 55% female) who had 455 seizures. The most common arrhythmia was ESA, with an incidence of 137 of 382 seizures (35.9%) (106/224 patients [47.3%]). There were 50 of 352 seizure-induced arrhythmias of interest (14.2%) in 41 of 204 patients (20.1%). ESAWB was the commonest in 22 of 394 seizures (5.6%) (18/225 patients [8%]), followed by SVT in 18 of 397 seizures (4.5%) (17/228 patients [7.5%]). During follow-up (48.36 ± 31.34 months), 8 SUDEPs occurred. Seizure-induced bradycardia (3.8% vs 12.5%, z = -16.66, p < 0.01) and ESAWB (6.6% vs 25%; z = -3.03, p < 0.01) were over-represented in patients who later died of SUDEP. There was no association between arrhythmias of interest and seizure severity biomarkers (p > 0.05). DISCUSSION: Markers of seizure severity are not related to seizure-induced arrhythmias of interest, suggesting that other factors such as occult cardiac abnormalities may be relevant for their occurrence. Seizure-induced ESAWB and bradycardia were more frequent in SUDEP cases, although this observation was based on a very limited number of SUDEP patients. Further case-control studies are needed to evaluate the yield of arrhythmias of interest along with respiratory changes as potential SUDEP biomarkers.


Subject(s)
Arrhythmias, Cardiac , Electroencephalography , Humans , Female , Male , Adult , Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/diagnosis , Incidence , Middle Aged , Prospective Studies , Sudden Unexpected Death in Epilepsy/epidemiology , Seizures/epidemiology , Seizures/physiopathology , Epilepsy, Generalized/epidemiology , Epilepsy, Generalized/physiopathology , Aged , Young Adult , Electrocardiography , Adolescent
2.
Ther Drug Monit ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38723160

ABSTRACT

BACKGROUND: The applicability of currently available tacrolimus population pharmacokinetic models in guiding dosing for lung transplant recipients is unclear. In this study, the predictive performance of relevant tacrolimus population pharmacokinetic models was evaluated for adult lung transplant recipients. METHODS: Data from 43 lung transplant recipients (1021 tacrolimus concentrations) administered an immediate-release oral formulation of tacrolimus were used to evaluate the predictive performance of 17 published population pharmacokinetic models for tacrolimus. Data were collected from immediately after transplantation up to 90 days after transplantation. Model performance was evaluated using (1) prediction-based assessments (bias and imprecision) of individual predicted tacrolimus concentrations at the fourth dosing based on 1 to 3 previous dosings and (2) simulation-based assessment (prediction-corrected visual predictive check; pcVPC). Both assessments were stratified based on concomitant azole antifungal use. Model performance was clinically acceptable if the bias was within ±20%, imprecision was ≤20%, and the 95% confidence interval of bias crossed zero. RESULTS: In the presence of concomitant antifungal therapy, no model showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33), and pcVPC plots displayed poor model fit to the data set. However, this fit slightly improved in the absence of azole antifungal use, where 4 models showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33). CONCLUSIONS: Although none of the evaluated models were appropriate in guiding tacrolimus dosing in lung transplant recipients receiving concomitant azole antifungal therapy, 4 of these models displayed potential applicability in guiding dosing in recipients not receiving concomitant azole antifungal therapy. However, further model refinement is required before the widespread implementation of such models in clinical practice.

3.
Food Chem ; 446: 138870, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38430771

ABSTRACT

Mustard (Brassica spp.) is one of the world's oldest condiments in the food basket, which holds a significant place in the global culinary landscape due to historical prominence and perceived health benefits. This study explores the extraction of oils from Mustard seeds by employing traditional 'Kolhu' method, modern supercritical fluid, and solvent extraction techniques. This study, for the first-time, identified Aurantiamide acetate, a potent anti-cancer dipeptide in Mustard seeds using ultra-performance liquid chromatography-mass spectrometry coupled with quadrupole time-of-flight (UPLC/MS-QToF) analytical platform. The analytical methodology was meticulously validated encompassing optimal parameters such as limit of detection, limit of quantification, precision, accuracy, linearity and robustness, within the range. Interestingly, 'Kolhu' method of oil extraction exhibited better yield of Aurantiamide acetate, suggesting superior efficiency of traditional methods. This study accentuates the importance of classical extraction methods, used traditionally, and emphasizes that naturally occurring substances indeed could be harnessed for better health.


Subject(s)
Mustard Plant , Tandem Mass Spectrometry , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Liquid Chromatography-Mass Spectrometry , Dipeptides , Seeds
4.
J Neurosci ; 44(11)2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38326036

ABSTRACT

Intercellular adhesion molecule-1 (ICAM-1) is identified as an initiator of neuroinflammatory responses that lead to neurodegeneration and cognitive and sensory-motor deficits in several pathophysiological conditions including traumatic brain injury (TBI). However, the underlying mechanisms of ICAM-1-mediated leukocyte adhesion and transmigration and its link with neuroinflammation and functional deficits following TBI remain elusive. Here, we hypothesize that blocking of ICAM-1 attenuates the transmigration of leukocytes to the brain and promotes functional recovery after TBI. The experimental TBI was induced in vivo by fluid percussion injury (25 psi) in male and female wild-type and ICAM-1-/- mice and in vitro by stretch injury (3 psi) in human brain microvascular endothelial cells (hBMVECs). We treated hBMVECs and animals with ICAM-1 CRISPR/Cas9 and conducted several biochemical analyses and demonstrated that CRISPR/Cas9-mediated ICAM-1 deletion mitigates blood-brain barrier (BBB) damage and leukocyte transmigration to the brain by attenuating the paxillin/focal adhesion kinase (FAK)-dependent Rho GTPase pathway. For analyzing functional outcomes, we used a cohort of behavioral tests that included sensorimotor functions, psychological stress analyses, and spatial memory and learning following TBI. In conclusion, this study could establish the significance of deletion or blocking of ICAM-1 in transforming into a novel preventive approach against the pathophysiology of TBI.


Subject(s)
Brain Injuries, Traumatic , Intercellular Adhesion Molecule-1 , Animals , Female , Humans , Male , Mice , Brain/metabolism , Brain Injuries, Traumatic/metabolism , CRISPR-Cas Systems , Endothelial Cells/metabolism , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Leukocytes , Paxillin , rho GTP-Binding Proteins/metabolism
5.
Ann Neurol ; 95(5): 998-1008, 2024 May.
Article in English | MEDLINE | ID: mdl-38400804

ABSTRACT

OBJECTIVE: Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy. METHODS: We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact-free respiratory signal were analyzed. RESULTS: ICA was seen in 55 of 179 (30.7%) seizures. Presence of ICA predicted a mesial temporal seizure onset compared to those without ICA (odds ratio = 3.8, 95% confidence interval = 1.3-11.6, p = 0.01). ICA specificity was 0.82. ICA onset was correlated with increased high-frequency broadband gamma (60-150Hz) activity in specific mesial or basal temporal regions, including amygdala, hippocampus, and fusiform and lingual gyri. Based on our results, ICA has an almost 4-fold greater association with mesial temporal seizure onset zones compared to those without ICA and is highly specific for mesial temporal seizure onset zones. As evidence of symptomatogenic areas, onset-synchronous increase in high gamma activity in mesial or basal temporal structures was seen in early onset ICA, likely representing anatomical substrates for ICA generation. INTERPRETATION: ICA recognition may help anatomoelectroclinical localization of clinical seizure onset to specific mesial and basal temporal brain regions, and the inclusion of these regions in SEEG evaluations may help accurately pinpoint seizure onset zones for resection. ANN NEUROL 2024;95:998-1008.


Subject(s)
Epilepsy, Temporal Lobe , Humans , Male , Female , Adult , Middle Aged , Epilepsy, Temporal Lobe/physiopathology , Epilepsy, Temporal Lobe/diagnosis , Sleep Apnea, Central/physiopathology , Sleep Apnea, Central/diagnosis , Drug Resistant Epilepsy/physiopathology , Drug Resistant Epilepsy/diagnostic imaging , Drug Resistant Epilepsy/diagnosis , Seizures/physiopathology , Seizures/diagnosis , Young Adult , Electrocorticography/methods , Electroencephalography/methods , Adolescent , Epilepsies, Partial/physiopathology , Epilepsies, Partial/diagnosis
6.
Sci Rep ; 14(1): 2127, 2024 01 25.
Article in English | MEDLINE | ID: mdl-38267471

ABSTRACT

Cashew is cultivated in varied agro-ecological regions of India and yield levels vary with regions. Therefore, to identify stable genotype for yield, 18 genotypes were tested in four environments for nut yield and ancillary traits during 2008 to 2018 in randomized block design with two replications. The data of 6th annual harvest and cumulative nut yield of six years was analyzed employing additive main effect and multiplicative interaction (AMMI) and genotype and genotype by environment (GGE) methods. Analysis of variance for 6th annual harvest indicated significant differences (p < 0.01) for eight traits. Environments varied significantly (p < 0.01) for seven traits. Genotype by environment (G × E) interactions were significant (p < 0.01) for all traits. Analysis of variance for cumulative yield revealed significant variations between genotypes, environments, G x E interactions. Interaction principal component analysis (IPCA) 1 (84.39%) and IPCA 2 (10.27%) together captured 95% of variability. Genotypes, environments and G × E interaction were accounted for 16.18%, 4.50% and 77.22% respectively of total variation. The environment Pilicode discriminated better while Vridhachalam was representative. BPP-8 and Vengulra-7 were the winning genotypes in Bhubaneswar while Kanaka and Priyanka in Pilicode, Vengurla-4 in Jhargram and UN-50 in Vridhachalam. Therefore, promoting cultivation of these winning genotypes in the corresponding environments is highly recommended to enhance cashew nut production. As per ASV (AMMI stability value,) K-22-1 was stable genotype followed by Bhubaneswar-1. As per YSI (yield stability index), Bhubaneswar-1 was stable and high yielding followed by K-22-1 and BPP-8. Thus stable genotypes identified in this study viz., K-22-1 and Bhuvaneswar-1 are recommended for cultivation in west and east regions of India which have most cashew growing areas for increasing the cashew nut production.


Subject(s)
Anacardium , Cyanoacrylates , Nuts/genetics , Phenotype , Genotype
7.
Polymers (Basel) ; 15(19)2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37836081

ABSTRACT

The ever-increasing global population necessitates a secure and ample energy supply, the majority of which is derived from fossil fuels. However, due to the immense energy demand, the exponential depletion of these non-renewable energy sources is both unavoidable and inevitable in the approaching century. Therefore, exploring the use of polymer electrolytes as alternatives in proton-conducting batteries opens an intriguing research field, as demonstrated by the growing number of publications on the subject. Significant progress has been made in the production of new and more complex polymer-electrolyte materials. Specific characterizations are necessary to optimize these novel materials. This paper provides a detailed overview of these characterizations, as well as recent advancements in characterization methods for proton-conducting polymer electrolytes in solid-state batteries. Each characterization is evaluated based on its objectives, experimental design, a summary of significant results, and a few noteworthy case studies. Finally, we discuss future characterizations and advances.

8.
Exp Brain Res ; 241(8): 2107-2123, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37466694

ABSTRACT

MicroRNAs (miRNAs) are non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. They are profound mediators of molecular and cellular changes in several pathophysiological conditions. Since miRNAs play major roles in regulating gene expression after traumatic brain injury (TBI), their possible role in diagnosis, prognosis, and therapy is not much explored. In this study, we aimed to identify specific miRNAs that are involved in the pathophysiological conditions in the first 24 h after mild TBI (mTBI). The genome-wide expression of miRNAs was evaluated by applying RNA sequence in the injury area of the cerebral cortex 24 after inflicting the injury using a mouse model of mild fluid percussion injury (FPI; 10 psi). Here, we identified different annotated, conserved, and novel miRNAs. A total of 978 miRNAs after 24 h of TBI were identified, and among these, 906 miRNAs were differentially expressed between control and mTBI groups. In this study, 146 miRNAs were identified as novel to mTBI and among them, 21 miRNAs were significant (p < 0.05). Using q-RT-PCR, we validated 10 differentially and significantly expressed novel miRNAs. Further, we filtered the differentially expressed miRNAs that were linked with proinflammatory cytokines, apoptosis, matrix metalloproteinases (MMPs), and tight junction and junctional adhesion molecule genes. Overall, this work shows that mTBI induces widespread changes in the expression of miRNAs that may underlie the progression of the TBI pathophysiology. The detection of several novel TBI-responsive miRNAs and their solid link with pathophysiological genes may help in identifying novel therapeutic targets.


Subject(s)
Brain Concussion , Brain Injuries, Traumatic , MicroRNAs , Humans , Brain Concussion/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Brain Injuries, Traumatic/genetics , Brain Injuries, Traumatic/metabolism , Gene Expression Regulation , Cerebral Cortex/pathology
9.
Polymers (Basel) ; 15(14)2023 Jul 21.
Article in English | MEDLINE | ID: mdl-37514503

ABSTRACT

Over the past three decades, chemical and biological water contamination has become a major concern, particularly in the industrialized world. Heavy metals, aromatic compounds, and dyes are among the harmful substances that contribute to water pollution, which jeopardies the human health. For this reason, it is of the utmost importance to locate methods for the cleanup of wastewater that are not genuinely effective. Owing to its non-toxicity, biodegradability, and biocompatibility, starch is a naturally occurring polysaccharide that scientists are looking into as a possible environmentally friendly material for sustainable water remediation. Starch could exhibit significant adsorption capabilities towards pollutants with the substitution of amide, amino, carboxyl, and other functional groups for hydroxyl groups. Starch derivatives may effectively remove contaminants such as oil, organic solvents, pesticides, heavy metals, dyes, and pharmaceutical pollutants by employing adsorption techniques at a rate greater than 90%. The maximal adsorption capacities of starch-based adsorbents for oil and organic solvents, pesticides, heavy metal ions, dyes, and pharmaceuticals are 13,000, 66, 2000, 25,000, and 782 mg/g, respectively. Although starch-based adsorbents have demonstrated a promising future for environmental wastewater treatment, additional research is required to optimize the technique before the starch-based adsorbent can be used in large-scale in situ wastewater treatment.

10.
PLoS One ; 18(6): e0287576, 2023.
Article in English | MEDLINE | ID: mdl-37384714

ABSTRACT

OBJECTIVE: Validate the performance characteristics of two analyte specific, laboratory developed tests (LDTs) for the quantification of SARS-CoV-2 subgenomic RNA (sgRNA) and viral load on the Hologic Panther Fusion® using the Open Access functionality. METHODS: Custom-designed primers/probe sets targeting the SARS-CoV-2 Envelope gene (E) and subgenomic E were optimized. A 20-day performance validation following laboratory developed test requirements was conducted to assess assay precision, accuracy, analytical sensitivity/specificity, lower limit of detection and reportable range. RESULTS: Quantitative SARS-CoV-2 sgRNA (LDT-Quant sgRNA) assay, which measures intermediates of replication, and viral load (LDT-Quant VLCoV) assay demonstrated acceptable performance. Both assays were linear with an R2 and slope equal to 0.99 and 1.00, respectively. Assay precision was evaluated between 4-6 Log10 with a maximum CV of 2.6% and 2.5% for LDT-Quant sgRNA and LDT-Quant VLCoV respectively. Using negative or positive SARS-CoV-2 human nasopharyngeal swab samples, both assays were accurate (kappa coefficient of 1.00 and 0.92). Common respiratory flora and other viral pathogens were not detected and did not interfere with the detection or quantification by either assay. Based on 95% detection, the assay LLODs were 729 and 1206 Copies/mL for the sgRNA and VL load LDTs, respectively. CONCLUSION: The LDT-Quant sgRNA and LDT-Quant VLCoV demonstrated good analytical performance. These assays could be further investigated as alternative monitoring assays for viral replication; and thus, medical management in clinical settings which could inform isolation/quarantine requirements.


Subject(s)
COVID-19 , Humans , COVID-19/diagnosis , SARS-CoV-2/genetics , Subgenomic RNA , Viral Load , Biological Assay , RNA
11.
Epilepsia ; 64(7): 1925-1938, 2023 07.
Article in English | MEDLINE | ID: mdl-37119434

ABSTRACT

OBJECTIVE: We aimed to identify corticothalamic areas and electrical stimulation paradigms that optimally enhance breathing. METHODS: Twenty-nine patients with medically intractable epilepsy were prospectively recruited in an epilepsy monitoring unit while undergoing stereoelectroencephalographic evaluation. Direct electrical stimulation in cortical and thalamic regions was carried out using low (<1 Hz) and high (≥10 Hz) frequencies, and low (<5 mA) and high (≥5 mA) current intensities, with pulse width of .1 ms. Electrocardiography, arterial oxygen saturation (SpO2 ), end-tidal carbon dioxide (ETCO2 ), oronasal airflow, and abdominal and thoracic plethysmography were monitored continuously during stimulations. Airflow signal was used to estimate breathing rate, tidal volume, and minute ventilation (MV) changes during stimulation, compared to baseline. RESULTS: Electrical stimulation increased MV in the amygdala, anterior cingulate, anterior insula, temporal pole, and thalamus, with an average increase in MV of 20.8% ± 28.9% (range = 0.2%-165.6%) in 19 patients. MV changes were associated with SpO2 and ETCO2 changes (p < .001). Effects on respiration were parameter and site dependent. Within amygdala, low-frequency stimulation of the medial region produced 78.49% greater MV change (p < .001) compared to high-frequency stimulation. Longer stimulation produced greater MV changes (an increase of 4.47% in MV for every additional 10 s, p = .04). SIGNIFICANCE: Stimulation of amygdala, anterior cingulate gyrus, anterior insula, temporal pole, and thalamus, using certain stimulation paradigms, enhances respiration. Among tested paradigms, low-frequency, low-intensity, long-duration stimulation of the medial amygdala is the most effective breathing enhancement stimulation strategy. Such approaches may pave the way for the future development of neuromodulatory techniques that aid rescue from seizure-related apnea, potentially as a targeted sudden unexpected death in epilepsy prevention method.


Subject(s)
Electrocorticography , Epilepsy , Respiratory Rate , Respiration , Respiratory Rate/physiology , Amygdala , Temporal Lobe , Thalamus , Prospective Studies
12.
Asian J Psychiatr ; 82: 103461, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36682156

ABSTRACT

Mothers with severe mental illness in the postpartum may have problems in bonding with their infants and there is a need to develop effective and acceptable interventions. Yoga has been shown to improve social cognition as well as increase oxytocin levels and maybe of value. This paper describes the feasibility and acceptability of a mother-infant yoga intervention in 14 mothers with severe mental illness admitted to a Mother Baby Unit in India. Mothers found the module acceptable and completion rates for mother-infant dyads were adequate.


Subject(s)
Mothers , Yoga , Female , Infant , Humans , Inpatients , Feasibility Studies , Mother-Child Relations , Postpartum Period
13.
Appl Biochem Biotechnol ; 195(6): 3941-3965, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35298766

ABSTRACT

The current investigation focused on the synthesis and characterization of Zn1-xHoxO (X = 0, 0.02, 0.04, 0.06, and 0.08) materials. The rare-earth Ho3+-doped ZnO materials have been prepared using a chemical precipitation process. The phase pure hexagonal structured ZnO crystal system has been observed by powder X-ray diffraction (XRD) characterization. The detailed structural analysis of prepared materials has been investigated by the Rietveld refinement method. The surface morphology and elemental composition of the prepared materials have been characterized using scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDAX). The presence of vibrational links associated with various functional groups has been displayed by FTIR spectroscopy. The energy gap of synthesized materials has been studied using UV-Vis spectroscopy. To study the luminescence activity of produced materials, photoluminescence (PL) analysis has been utilized. The light-green emission at around 507 nm has been obtained by synthesized materials under 380-nm excitation. In addition, the electron density distribution has been accomplished in synthesized materials. At 6% of Ho3+, substituted ZnO exposes the maximum covalent and ionic nature between Zn-O bond along with horizontal and vertical axis, respectively. Moreover, the antibacterial activity of synthesized materials has been done through Proteus vulgaris and Enterococcus faecalis. Following that the destruction of human red blood cells has been examined by hemolysis investigation. All experimental results suggested that the 6% of Ho3+ dopant is the optimized level of ZnO host lattice. The present work paves a promising path to get efficient material for biomedical applications.


Subject(s)
Zinc Oxide , Humans , Zinc Oxide/pharmacology , Zinc Oxide/chemistry , Electrons , Luminescence , Microscopy, Electron, Scanning , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
14.
Int J Cardiol ; 372: 101-109, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36481261

ABSTRACT

BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the severe complications of diabetes with no known biomarkers for early detection. Mitochondria-associated endoplasmic reticulum membranes (MAM) are less studied subcellular targets but an emerging area for exploration in metabolic disorders including DCM. We herein studied the role of MAMs and downstream mitochondrial functions in DCM. We also explored the efficacy of ferulic acid (FeA) against DCM via modulation of MAM and its associated signaling pathway. METHODS: The H9c2 cardiomyoblast cells were incubated with high concentration (33 mM) of d-glucose for 48 h to create a high glucose ambience in vitro. The expression of various critical proteins of MAM, mitochondrial function, oxidative phosphorylation (OxPhos) and the genesis of apoptosis were examined. The rats fed with high fat/high fructose/streptozotocin (single dose, i.p.) were used as a diabetic model and analyzed the insulin resistance and markers of cardiac hypertrophy and apoptosis. RESULTS: High glucose conditions caused the upregulation of MAM formation via PACS2, IP3R2, FUNDC1, and VDAC1 and decreased mitochondrial biogenesis, fusion and OxPhos. The upregulation of mitochondria-driven SMAC-HTRA2-ARTS-XIAP apoptosis and other cell death pathways indicate their critical roles in the genesis of DCM at the molecular level. The diabetic rats also showed cardiomyopathy with increased heart mass index, TNNI3K, troponin, etc. FeA effectively prevented the high glucose-induced MAM alterations and associated cellular anomalies both in vitro and in vivo. CONCLUSION: High glucose-induced MAM distortion and subsequent mitochondrial dysfunctions act as the stem of cardiomyopathy. MAM could be explored as a potential target to treat diabetic cardiomyopathy. Also, the FeA could be an attractive nutraceutical agent for diabetic cardiomyopathy.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Cardiomyopathies , Animals , Rats , Apoptosis , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/pharmacology , Apoptosis Regulatory Proteins/therapeutic use , Diabetes Mellitus, Experimental/metabolism , Diabetic Cardiomyopathies/drug therapy , Diabetic Cardiomyopathies/metabolism , Glucose/toxicity , Glucose/metabolism , Membrane Proteins , Mitochondrial Proteins/pharmacology , Myocytes, Cardiac/metabolism , Vesicular Transport Proteins/metabolism , Voltage-Dependent Anion Channel 1/metabolism , Voltage-Dependent Anion Channel 1/therapeutic use , Mitochondria/metabolism , Endoplasmic Reticulum/metabolism
15.
J Biochem Mol Toxicol ; 36(12): e23215, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36117386

ABSTRACT

Diabetes-related health issues are increasing day by day in public, and diabetic cardiomyopathy (DCM) is one serious issue among them. There is a lack of proper strategy to control and manage DCM. Here we are attempting a nutraceutical-based approach to protect the heart from DCM. The beneficial effect of cinnamic acid (CiA), was evaluated in an experimental model of diabetes. For this, diabetic model was created by feeding male Wistar rats with a high fat, high fructose diet for 6 months and a single dose of streptozotocin (25 mg/kg bwt). Metformin was used as the positive control. The diabetic rats showed insulin resistance, myocardial injury, and a significant increase of total cholesterol, triglycerides, and LDL. Development of DCM was evident from the increased cardiac mass index, LDH, CKMB, ANP, and CRP levels in the diabetic group. There was a significant increase in the levels of cardiac hypertrophy markers like TGF-ß and ß-MHC in the hearts of diabetic rats revealing DCM. Pro-inflammatory cytokines (TNF-α, IL-6) and lipid peroxides were significantly elevated in the serum of diabetic rats. Histopathology revealed inflammation and necrosis in the heart of diabetic rats confirming DCM. Oral administration of CiA (5 and 10 mg/kg bwt) prevented the development of DCM via its cardioprotective, anti-inflammatory, anti-dyslipidemia potential, and antidiabetic properties. Similarly, metformin (50 mg/kg bwt) has also shown protection against DCM. We conclude from this study that CiA is found to be beneficial against DCM and recommend more detailed preclinical and clinical studies to develop CiA-based nutraceutical against DCM.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Cardiomyopathies , Metformin , Male , Rats , Animals , Diabetic Cardiomyopathies/drug therapy , Diabetic Cardiomyopathies/prevention & control , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Rats, Wistar , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Metformin/pharmacology , Metformin/therapeutic use
16.
Cureus ; 14(7): e26536, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35936175

ABSTRACT

INTRODUCTION: School children are a means to reach and sensitize the community on the prevention of seasonal diseases such as malaria and dengue. The current study aims to determine the impact of school-based educational interventions on the knowledge of students toward the prevention and control of malaria and dengue in higher secondary schools. METHODS: This pre- and post-intervention study was conducted in three higher secondary schools in Zone IV, North Chennai, from September to December 2021. A total of 284 students in the age group of 13-17 years participated in the study. School-based educational interventions were delivered through PowerPoint-assisted lectures, participatory group activities, and demonstration of mosquito larvae and their control. The impact of the interventions as the change in knowledge level was analyzed using McNemar's test, with a p-value of <0.05. RESULTS:  Educational interventions led to the improvement in knowledge about malaria symptoms, such as fever (43.7% to 76.1%; p<0.001), chills (45.1% to 82.4%; p<0.001), and headache (46.1% to 86.6%; p<0.001), and the knowledge of Aedes mosquito bites as the cause of dengue transmission enhanced (41.9% to 92.2%; p<0.001). Similarly, there was an increase in knowledge on the identification of vector mosquito breeding sites inside the house (11.9% to 67.9%; p<0.001) and outside the house (10.9% to 69.7%; p<0.001) and mosquito net usage (21.5% to 76.1%; p<0.001) after the interventions. CONCLUSION: School-based educational interventions had a significant impact on enhancing the knowledge on the prevention and control of malaria and dengue among school children. Involving school children can strengthen existing malaria and dengue prevention and control strategies in endemic areas.

17.
Comput Intell Neurosci ; 2022: 8419308, 2022.
Article in English | MEDLINE | ID: mdl-35990128

ABSTRACT

This work is implemented for the management of patients with epilepsy, and methods based on electroencephalography (EEG) analysis have been proposed for the timely prediction of its occurrence. The proposed system is used for crisis detection and prediction system; it is useful for both patients and medical staff to know their status easily and more accurately. In the treatment of Parkinson's disease, the affected patients with Parkinson's disease can assess the prognostic risk factors, and the symptoms are evaluated to predict rapid progression in the early stages after diagnosis. The presented seizure prediction system introduces deep learning algorithms into EEG score analysis. This proposed work long short-term memory (LSTM) network model is mainly implemented for the identification and classification of qualitative patterns in the EEG of patients. While compared with other techniques like deep learning models such as convolutional neural networks (CNNs) and traditional machine learning algorithms, the proposed LSTM model plays a significant role in predicting impending crises over 4 different qualifying intervals from 10 minutes to 1.5 hours with very few wrong predictions.


Subject(s)
Artificial Intelligence , Parkinson Disease , Electroencephalography/methods , Humans , Neural Networks, Computer , Seizures/diagnosis
18.
Comput Intell Neurosci ; 2022: 2213273, 2022.
Article in English | MEDLINE | ID: mdl-35242176

ABSTRACT

The emergence of powerful deep learning architectures has resulted in breakthrough innovations in several fields such as healthcare, precision farming, banking, education, and much more. Despite the advantages, there are limitations in deploying deep learning models in resource-constrained devices due to their huge memory size. This research work reports an innovative hybrid compression pipeline for compressing neural networks exploiting the untapped potential of z-score in weight pruning, followed by quantization using DBSCAN clustering and Huffman encoding. The proposed model has been experimented with state-of-the-art LeNet Deep Neural Network architectures using the standard MNIST and CIFAR datasets. Experimental results prove the compression performance of DeepCompNet by 26x without compromising the accuracy. The synergistic blend of the compression algorithms in the proposed model will ensure effortless deployment of neural networks leveraging DL applications in memory-constrained devices.


Subject(s)
Data Compression , Algorithms , Cluster Analysis , Data Compression/methods , Neural Networks, Computer
19.
Bull Environ Contam Toxicol ; 109(3): 502-510, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35322279

ABSTRACT

Carbonaceous species [organic carbon (OC), elemental carbon (EC), elemental matter (EM), primary organic carbon (POC), secondary organic carbon (SOC), total carbon (TC), and total carbonaceous matter (TCM)] of PM2.5 were analyzed to study the seasonal variability and long-term trend of carbonaceous aerosols (CAs) in megacity Delhi, India from January, 2012 to April, 2021. The average concentrations (± standard deviation) of PM2.5, OC, EC, TC, EM, TCM, POC and SOC were 127 ± 77, 15.7 ± 11.6, 7.4 ± 5.1, 23.1 ± 16.5, 8.2 ± 5.6, 33.3 ± 23.9, 9.3 ± 6.3 and 6.5 ± 5.3 µg m-3, respectively during the sampling period (10-year average). The average CAs accounted for 26% of PM2.5 concentration during the entire sampling period. In addition, the seasonal variations in PM2.5, OC, EC, POC, SOC, and TCM levels were recorded with maxima in post-monsoon and minima in monsoon seasons. The linear relationship of OC and EC, OC/EC and EC/TC ratios suggested that the vehicular emissions (VE), fossil fuel combustion (FFC) and biomass burning (BB) are the major sources of CAs at megacity Delhi, India.


Subject(s)
Air Pollutants , Particulate Matter , Aerosols/analysis , Air Pollutants/analysis , Carbon/analysis , China , Environmental Monitoring , India , Particle Size , Particulate Matter/analysis , Seasons
20.
Proc Biol Sci ; 289(1967): 20212669, 2022 01 26.
Article in English | MEDLINE | ID: mdl-35078364

ABSTRACT

Although life-history trade-offs are central to life-history evolution, their mechanistic basis is often unclear. Traditionally, trade-offs are understood in terms of competition for limited resources among traits within an organism, which could be mediated by signal transduction pathways at the level of cellular metabolism. Nevertheless, trade-offs are also thought to be produced as a consequence of the performance of one activity generating negative consequences for other traits, or the result of genes or pathways that simultaneously regulate two life-history traits in opposite directions (antagonistic pleiotropy), independent of resource allocation. Yet examples of genes with antagonistic effects on life-history traits are limited. This study provides direct evidence for a gene-RLS1, that is involved in increasing survival in nutrient-limiting environments at a cost to immediate reproduction in the single-celled photosynthetic alga, Chlamydomonas reinhardtii. Specifically, we show that RLS1 mutants are unable to properly suppress their reproduction in phosphate-deprived conditions. Although these mutants have an immediate reproductive advantage relative to the parental strain, their long-term survival is negatively affected. Our data suggest that RLS1 is a bona fide life-history trade-off gene that suppresses immediate reproduction and ensures survival by downregulating photosynthesis in limiting environments, as part of the general acclimation response to nutrient deprivation in photosynthetic organisms.


Subject(s)
Reproduction , Phenotype , Reproduction/physiology
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