Validation and Estimation of Obesity-Induced Intervertebral Disc Degeneration through Subject-Specific Finite Element Modelling of Functional Spinal Units.

(1) Background: Intervertebral disc degeneration has been linked to obesity; its potential mechanical effects on the intervertebral disc remain unknown. This study aimed to develop and validate a patient-specific model of L3-L4 vertebrae and then use the model to estimate the impact of increasing body weight on disc degeneration. (2) Methods: A three-dimensional model of the functional spinal unit of L3-L4 vertebrae and its components were developed and validated. Validation was achieved by comparing the range of motions (RoM) and intradiscal pressures with the previous literature. Subsequently, the validated model was loaded according to the body mass index and estimated stress, deformation, and RoM to assess disc degeneration. (3) Results: During validation, L3-L4 RoM and intradiscal pressures: flexion 5.17° and 1.04 MPa, extension 1.54° and 0.22 MPa, lateral bending 3.36° and 0.54 MPa, axial rotation 1.14° and 0.52 MPa, respectively. When investigating the impact of weight on disc degeneration, escalating from normal weight to obesity reveals an increased RoM, by 3.44% during flexion, 22.7% during extension, 29.71% during lateral bending, and 33.2% during axial rotation, respectively. Also, stress and disc deformation elevated with increasing weight across all RoM. (4) Conclusions: The predicted mechanical responses of the developed model closely matched the validation dataset. The validated model predicts disc degeneration under increased weight and could lay the foundation for future recommendations aimed at identifying predictors of lower back pain due to disc degeneration.

Biotransformation of maize bran-derived ferulic acid to vanillin using an adapted strain of Amycolatopsis sp. ATCC 39116.

Maize bran, an agro-processing waste residue, is a good source of ferulic acid that can be further valorized for vanillin production. However, extraction of ferulic acid from natural sources has been challenging due to low concentrations and intensive extraction procedures. In the present work, ferulic acid streams (purities ranging from 5% to 75%) extracted from maize bran using thermochemical methods were evaluated for biotransformation to vanillin, employing Amycolatopsis sp. as a whole-cell biocatalyst. Initial adaptation studies were critical in improving ferulic acid assimilation and its conversion to vanillin by 65% and 56%, respectively by the fourth adaptation cycle. The effect of cell's physiological states and vanillic acid supplementation on vanillin production was studied using standard ferulic acid as a substrate in an effort to achieve further improvement in vanillin yield. In the presence of vanillic acid, 18 h cultured cells using 2 g/L of standard and isolated ferulic acid produced vanillin concentrations of up to 0.71 and 0.48 g/L, respectively. Furthermore, intermediates involved in the ferulic acid catabolic pathway and their interrelations were studied using GC-MS analysis. Results indicated that two different routes were involved in the catabolism of standard ferulic acid, and similar metabolic routes were observed for an isolated ferulic acid stream. These findings effectively evaluated isolated ferulic acid for sustainable vanillin production while reducing agro-industrial waste pollution.

Nanogold-coated stent facilitated non-invasive photothermal ablation of stent thrombosis and restoration of blood flow.

In-stent restenosis (ISR) and stent thrombosis (ST) are the most serious complications of coronary angioplasty and stenting. Although the evolution of drug-eluting stents (DES) has significantly restricted the incidence of ISR, they are associated with an enhanced risk of ST. In the present study, we explore the photothermal ablation of a thrombus using a nano-enhanced thermogenic stent (NETS) as a modality for revascularization following ST. The photothermal activity of NETS, fabricated by coating bare metal stents with gold nanorods generating a thin plasmonic film of gold, was found to be effective in rarefying clots formed within the stent lumen in various in vitro assays including those under conditions mimicking blood flow. NETS implanted in the rat common carotid artery generated heat following exposure to a NIR-laser that led to effective restoration of blood flow within the occluded vessel in a model of ferric chloride-induced thrombosis. Our results present a proof-of-concept for a novel photothermal ablation approach by employing coated stents in the non-invasive management of ST.

Nattokinase Encapsulated Nanomedicine for Targeted Thrombolysis: Development, Improved in Vivo Thrombolytic Effects, and Ultrasound/Photoacoustic Imaging.

Nattokinase (NK), a potent thrombolytic enzyme that dissolves blood clots, is highly used in the treatment of cardiovascular disorders. However, its effective delivery remains demanding because of stability and bioavailability problems owing to its high molecular weight and proteineous nature. In this research, we have developed novel NK-loaded nontargeted liposomes (NK-LS) and targeted liposomes (RGD-NK-LS and AM-NK-LS) by the reverse phase evaporation method. The physiochemical characterizations (particle size, polydispersity index, zeta potential, and morphology) were performed by a Zetasizer, SEM, TEM, and AFM. The Bradford assay and XPS analysis confirmed the successful surface conjugation of the targeting ligands. Platelet interaction studies by CLSM, photon imager optima, and flow cytometry showed significantly higher (P < 0.05) platelet binding affinity of targeted liposomes. In vitro evaluations were performed using human blood and a fibrinolysis study by CLSM imaging demonstrating the potent antithrombotic efficacy of AM-NK-LS. Furthermore, bleeding and clotting time studies revealed that the targeted liposomes were free from any bleeding complications. Moreover, the in vivo FeCl3 model on Sprague-Dawley (SD) rats using a Doppler flow meter and ultrasound/photoacoustic imaging indicated the increased % thrombolysis and potent affinity of targeted liposomes toward the thrombus site. Additionally, in vitro hemocompatibility and histopathology studies demonstrated the safety and biocompatibility of the nanoformulations.

The heparin-binding hemagglutinin protein of Mycobacterium tuberculosis is a nucleoid-associated protein.

Nucleoid-associated proteins (NAPs) regulate multiple cellular processes such as gene expression, virulence, and dormancy throughout bacterial species. NAPs help in the survival and adaptation of Mycobacterium tuberculosis (Mtb) within the host. Fourteen NAPs have been identified in Escherichia coli; however, only seven NAPs are documented in Mtb. Given its complex lifestyle, it is reasonable to assume that Mtb would encode for more NAPs. Using bioinformatics tools and biochemical experiments, we have identified the heparin-binding hemagglutinin (HbhA) protein of Mtb as a novel sequence-independent DNA-binding protein which has previously been characterized as an adhesion molecule required for extrapulmonary dissemination. Deleting the carboxy-terminal domain of HbhA resulted in a complete loss of its DNA-binding activity. Atomic force microscopy showed HbhA-mediated architectural modulations in the DNA, which may play a regulatory role in transcription and genome organization. Our results showed that HbhA colocalizes with the nucleoid region of Mtb. Transcriptomics analyses of a hbhA KO strain revealed that it regulates the expression of ∼36% of total and ∼29% of essential genes. Deletion of hbhA resulted in the upregulation of ∼73% of all differentially expressed genes, belonging to multiple pathways suggesting it to be a global repressor. The results show that HbhA is a nonessential NAP regulating gene expression globally and acting as a plausible transcriptional repressor.

De novo sequencing, assembly, and characterization of Asparagus racemosus transcriptome and analysis of expression profile of genes involved in the flavonoid biosynthesis pathway.

Asparagus racemosus is known for its diverse content of secondary metabolites, i.e., saponins, alkaloids, and a wide range of flavonoids. Flavonoids, including phenols and polyphenols, have a significant role in plant physiology and are synthesized in several tissues. Despite the diverse role of flavonoids, genetic information is limited for flavonoid biosynthesis pathways in A. racemosus. The current study explores full-scale functional genomics information of A. racemosus by de novo transcriptome sequencing using Illumina paired-end sequencing technology to elucidate the genes involved in flavonoid biosynthesis pathways. The de novo assembly of high-quality paired-end reads resulted in ∼2.3 million high-quality reads with a pooled transcript of 45,647 comprising ∼76 Mb transcriptome with a mean length (bp) of 1,674 and N50 of 1,868bp. Furthermore, the coding sequence (CDS) prediction analysis from 45,647 pooled transcripts resulted in 45,444 CDS with a total length and mean length of 76,398,686 and 1,674, respectively. The Gene Ontology (GO) analysis resulted in a high number of CDSs assigned to 25,342 GO terms, which grouped the predicted CDS into three main domains, i.e., Biological Process (19,550), Molecular Function (19,873), and Cellular Component (14,577). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database was used to categorize 6,353 CDS into 25 distinct biological pathway categories, in which the majority of mapped CDS were shown to be related to translation (645), followed by signal transduction (532), carbohydrate metabolism (524), folding, sorting, and degradation (522). Among these, only ∼64 and 14 CDSs were found to be involved in the phenylpropanoid and flavonoid biosynthesis pathways, respectively. Quantitative Real-time PCR was used to check the expression profile of fourteen potential flavonoid biosynthesis pathway genes. The qRT-PCR analysis result matches the transcriptome sequence data validating the Illumina sequence results. Moreover, a large number of genes associated with the flavonoids biosynthesis pathway were found to be upregulated under the induction of methyl jasmonate. The present-day study on transcriptome sequence data of A. racemosus can be utilized for characterizing genes involved in flavonoid biosynthesis pathways and for functional genomics analysis in A. racemosus using the reverse genetics approach (CRISPR/Cas9 technology).

Novel cost-effective design for bio-volatilization studies in photosynthetic microalgae exposed to arsenic with emphasis on growth and glutathione modulation.

A novel laboratory model was designed to study the arsenic (As) biotransformation potential of the microalgae Chlorella vulgaris and Nannochloropsis sp. and the cyanobacterium Anabaena doliolum. The Algae were treated under different concentrations of As(III) to check their growth, toxicity optimization, and volatilization potential. The results revealed that the alga Nannochloropsis sp. was better adopted in term of growth rate and biomass than C. vulgaris and A. doliolum. Algae grown under an As(III) environment can tolerate up to 200 µM As(III) with moderate toxicity impact. Further, the present study revealed the biotransformation capacity of the algae A. doliolum, Nannochloropsis sp., and Chlorella vulgaris. The microalga Nannochloropsis sp. volatilized a large maximum amount of As (4,393 ng), followed by C. vulgaris (4382.75 ng) and A. doliolum (2687.21 ng) after 21 days. The present study showed that As(III) stressed algae-conferred resistance and provided tolerance through high production of glutathione content and As-GSH chemistry inside cells. Thus, the biotransformation potential of algae may contribute to As reduction, biogeochemistry, and detoxification at a large scale.

Major phenolic compounds, antioxidant, antimicrobial, and cytotoxic activities of Selinum carvifolia (L.) collected from different altitudes in India.

Antibiotic resistance poses a serious threat to public health, raising the number of diseases in the community. Recent research has shown that plant-derived phenolic compounds have strong antimicrobial, antifungal, and cytotoxic properties against a variety of microorganisms and work as great antioxidants in such treatments. The goal of the current work is to evaluate the anticancerous, antibacterial, antifungal, antioxidant, and cytotoxicity activities in the extracts of the different plant parts (leaves, stems, and roots) of S. carvifolia (L.) L. This is a medicinally important plant and has been used for different kinds of diseases and ailments such as hysteria and seizures. The phenolic compounds from the different plant parts were analyzed using HPLC and the following were found to be present: chlorogenic acid, gallic acid, rutin, syringic acid, vanillic acid, cinnamic acid, caffeic acid, and protocatechuic acid. Gallic acid was found to have the highest concentration (13.93 mg/g), while chlorogenic acid (0.25 mg/g) had the lowest. The maximum TPC value, which ranged from 33.79 to 57.95 mg GAE/g dry extract weight, was found in the stem. Root extract with 9.4 mg RE/g had the greatest TFC level. In the leaf and stem extracts, the RSC ranged from 0.747 mg/mL to 0.734 mg/1 mL GE/g dry extract weight, respectively. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to measure in vitro antioxidant activity. In a concentration-dependent way, promising antioxidant activity was reported. Moreover, 3,5-dinitrosalicylic acid (DNSA) and the Folin-Ciocalteu phenol reagent technique were used to determine reducing sugar content and total phenolic content, respectively. Antibacterial activity against eight strains (MIC: 250-1,000 µg/mL) was analyzed, and the stem extract exhibited maximum activity. Antifungal activity was also assessed, and potent activity was reported especially in the extract obtained from the stem. Cytotoxicity was evaluated using an MTT assay in the A549 cell line, where different doses (0.0625, 0.125, 0.25, 0.5, and 1 mg/mL) of leaf, root, and stem extracts were used. Treatment with these extracts reduced the cell viability, indicating that S. carvifolia may possess anticancer potential, which can be of great therapeutic value.

Chitosan-g-estrone Nanoparticles of Palbociclib Vanished Hypoxic Breast Tumor after Targeted Delivery: Development and Ultrasound/Photoacoustic Imaging.

Breast cancer is the leading cause of death among women globally. Approximately 80% of all breast cancers diagnosed are overexpressed with estrogen receptors (ERs). In this study, we have developed an estrone (Egen)-grafted chitosan-based polymeric nanocarrier for the targeted delivery of palbociclib (PLB) to breast cancer. The nanoparticles (NPs) were prepared by solvent evaporation using the ionic gelation method and characterized for particle size, zeta potential, polydispersity, surface morphology, surface chemistry, drug entrapment efficiency, cytotoxicity assay, cellular uptake, and apoptosis study. The developed PLB-CS NPs and PLB-CS-g-Egen NPs had a particle size of 116.3 ± 1.53 nm and 141.6 ± 1.97 nm, respectively. The zeta potential of PLB-CS NPs and PLB-CS-g-Egen NPs was found to be 18.70 ± 0.416 mV and 12.45 ± 0.574 mV, respectively. The morphological analysis demonstrated that all NPs were spherical in shape and had a smooth surface. An in vitro cytotoxicity assay was performed in estrogen receptor (ER)-expressing MCF7 cells and T47D cells, which suggested that targeted NPs were 57.34- and 30.32-fold more cytotoxic compared to the pure PLB, respectively. Additionally, cell cycle analysis confirmed that cell cycle progression from the G1 into S phase was blocked more efficiently by targeted NPs compared to nontargeted NPs and PLB in MCF7 cells. In vivo pharmacokinetic studies demonstrated that entrapment of the PLB in the NPs improved the half-life and bioavailability by ∼2-3-fold. Further, ultrasound and photoacoustic imaging of DMBA induced breast cancer in the Sprague-Dawley (SD) rat showed that targeted NPs completely vanished breast tumor, reduced hypoxic tumor volume, and suppressed tumor angiogenesis more efficiently compared to the nontargeted NPs and free PLB. Further, in vitro hemocompatibility and histopathology studies suggested that NPs were biocompatible and safe for clinical use.

Therapeutic Potential of Dillenia indica L. in Attenuating Hyperglycemia-Induced Oxidative Stress and Apoptosis in Alloxan-Administered Diabetic Mice.

BACKGROUND: Hyperglycemia-induced oxidative stress accelerates the process of apoptosis in tissues. Dilleniaindica (DI) is a medicinal plant, and its fruit contains many therapeutic properties. The therapeutic activity of the Methanolic Fruit Extract (MFE) of DI in attenuating oxidative stress and apoptosis in the liver and kidney tissues of alloxan-induced diabetic mice was analyzed in the present study. METHODS: High-Performance Thin Layer Chromatography (HPTLC) profiling of MFE was conducted. GLUT4 protein expression analysis and lipid peroxidation assays were conducted to check for MFE effect by administering in diabetic mice. An ultrastructural study was conducted for both the tissues. In apoptotic studies, the TUNEL assay and apoptotic protein expression analysis was conducted. RESULTS: High-Performance Thin Layer Chromatography (HPTLC) profiling of MFE showed the presence of two crucial antioxidants, ascorbic acid, and naringenin. In GLUT-4 protein expression analysis, MFE suppresses hyperglycemia by upregulating GLUT4 protein expression. Lipid peroxidation assay showed a decrease in malondialdehyde (MDA) upon MFE administration in diabetic mice. An ultrastructural study was conducted, and MFE was found to restore cellular alterations in diabetic tissues. In apoptotic studies, the TUNEL assay shows that MFE treatment showed fewer apoptotic cells than the diabetic group. The study also observed decreased caspase 3 protein expression and increased Bcl-2 protein expression. CONCLUSIONS: Therefore, it is inferred from the study that MFE can exert a protective effect by suppressing hyperglycemia and modulating oxidative stress and apoptosis in alloxan-administered diabetic mice.

Assessment of the dual role of Lyonia ovalifolia (Wall.) Drude in inhibiting AGEs and enhancing GLUT4 translocation through LC-ESI-QTOF-MS/MS determination and in silico studies.

Introduction: Diabetes mellitus (DM) is a metabolic disorder that results in glucose accumulation in the blood, accompanied by the production of advanced glycation end products (AGEs) through glycation of cellular proteins. These AGEs interfere with insulin signaling and prevent GLUT4 membrane translocation, thereby promoting the accumulation of more glucose in the blood and causing post-diabetic complications. Methods: In this study, we examine the anti-diabetic potential of Lyonia ovalifolia (Wall.) Drude, a well-known ethnomedicinal plant of the Indian Himalayas. Considering its various medicinal properties, we analyzed its ethanolic extract and various solvent fractions for in vitro antiglycation activity and antidiabetic potential, i.e., stimulation of GLUT4 translocation. Result and Discussions: The results showed that the extract and fractions exhibited increased antiglycation activity and an increased level of GLUT4 translocation. Analysis of a further 12 bioactive compounds of ethanolic extract, identified through LC-ESI-QTOF-MS/MS, revealed the presence of three new compounds: leucothol B, rhodoterpenoids A, and leucothol A. Moreover, we performed molecular docking of identified compounds against key proteins of diabetes mellitus: the sirtuin family of NAD (+)-dependent protein deacetylases 6 (SIRT6), aldose reductase (AR), and tyrosine kinase (TK). The results showed that flavonoid luteolin showed the best binding affinity ((-12.3 kcal/mol), followed by eriodictyol, astilbin, and syringaresinol. An ADMET study showed that luteolin, eriodictyol, astilbin, and syringaresinol may be promising drug candidates belonging to the flavonoid class of compounds, with no harmful effects and complying with all the drug-likeness guidelines. Furthermore, molecular dynamics (MD) simulations on a 50 ns timescale revealed that AR protein was most stable with luteolin throughout the simulation period. Therefore, this study reveals for the first time that L. ovalifolia plays an important role in insulin homeostasis, as shown in in vitro and in silico studies.

The industrially important genus Kaempferia: An ethnopharmacological review.

Kaempferia, a genus of the family Zingiberaceae, is widely distributed with more than 50 species which are mostly found throughout Southeast Asia. These plants have important ethnobotanical significance as many species are used in Ayurvedic and other traditional medicine preparations. This genus has received a lot of scholarly attention recently as a result of the numerous health advantages it possesses. In this review, we have compiled the scientific information regarding the relevance, distribution, industrial applications, phytochemistry, ethnopharmacology, tissue culture and conservation initiative of the Kaempferia genus along with the commercial realities and limitations of the research as well as missing industrial linkages followed by an exploration of some of the likely future promising clinical potential. The current review provides a richer and deeper understanding of Kaempferia, which can be applied in areas like phytopharmacology, molecular research, and industrial biology. The knowledge from this study can be further implemented for the establishment of new conservation strategies.

The unique N-terminal region of Mycobacterium tuberculosis sigma factor A plays a dominant role in the essential function of this protein.

SigA (σA) is an essential protein and the primary sigma factor in Mycobacterium tuberculosis (Mtb). However, due to the absence of genetic tools, our understanding of the role and regulation of σA activity and its molecular attributes that help modulate Mtb survival is scant. Here, we generated a conditional gene replacement of σA in Mtb and showed that its depletion results in a severe survival defect in vitro, ex vivo, and in vivo in a murine infection model. Our RNA-seq analysis suggests that σA either directly or indirectly regulates ∼57% of the Mtb transcriptome, including ∼28% of essential genes. Surprisingly, we note that despite having ∼64% similarity with σA, overexpression of the primary-like σ factor SigB (σB) fails to compensate for the absence of σA, suggesting minimal functional redundancy. RNA-seq analysis of the Mtb σB deletion mutant revealed that 433 genes are regulated by σB, of which 283 overlap with the σA transcriptome. Additionally, surface plasmon resonance, in vitro transcription, and functional complementation experiments reveal that σA residues between 132-179 that are disordered and missing from all experimentally determined σA-RNAP structural models are imperative for σA function. Moreover, phosphorylation of σA in the intrinsically disordered N-terminal region plays a regulatory role in modulating its activity. Collectively, these observations and analysis provide a rationale for the centrality of σA for the survival and pathogenicity of this bacillus.

Fatty acid oxidation fuels agonist-induced platelet activation and thrombus formation: Targeting ß-oxidation of fatty acids as an effective anti-platelet strategy.

Platelet mitochondria possess remarkable plasticity for oxidation of energy substrates, where metabolic dependency on glucose or fatty acids is higher than glutamine. Since platelets metabolize nearly the entire pool of glucose to lactate rather than fluxing through mitochondrial tricarboxylic acid cycle, we posit that majority of mitochondrial ATP, which is essential for platelet granule secretion and thrombus formation, is sourced from oxidation of fatty acids. We performed a comprehensive analysis of bioenergetics and function of stimulated platelets in the presence of etomoxir, trimetazidine and oxfenicine, three pharmacologically distinct inhibitors of ß-oxidation. Each of them significantly impaired oxidative phosphorylation in unstimulated as well as thrombin-stimulated platelets leading to a small but consistent drop in ATP level in activated cells due to a lack of compensation from glycolytic ATP. Trimetazidine and oxfenicine attenuated platelet aggregation, P-selectin externalization and integrin αIIb ß3 activation. Both etomoxir and trimetazidine impeded agonist-induced dense granule release and platelet thrombus formation on collagen under arterial shear. The effect of inhibitors on platelet aggregation and dense granule release was dose- and incubation time- dependent with significant inhibition at higher doses and prolonged incubation times. Neither of the inhibitors could protect mice from collagen-epinephrine-induced pulmonary embolism or prolong mouse tail bleeding times. However, mice pre-administered with etomoxir, trimetazidine and oxfenicine were protected from ferric chloride-induced mesenteric thrombosis. In conclusion, ß-oxidation of fatty acids sustains ATP level in stimulated platelets and is therefore essential for energy-intensive agonist-induced platelet responses. Thus, fatty acid oxidation may constitute an attractive therapeutic target for novel antiplatelet agents.

SARS-CoV-2 Variant Delta Potently Suppresses Innate Immune Response and Evades Interferon-Activated Antiviral Responses in Human Colon Epithelial Cells.

The Delta variant of SARS-CoV-2 has caused more severe infections than its previous variants. We studied the host innate immune response to Delta, Alpha, and two earlier variants to map the evolution of the recent ones. Our biochemical and transcriptomic studies in human colon epithelial cell line Caco2 reveal that Alpha and Delta have progressively evolved over the ancestral variants by silencing the innate immune response, thereby limiting cytokine and chemokine production. Though Alpha silenced the retinoic acid-inducible gene (RIG)-I-like receptor (RLR) pathway just like Delta did, it failed to persistently silence the innate immune response, unlike Delta. Both Alpha and Delta have evolved to resist interferon (IFN) treatment, while they are still susceptible to RLR activation, further highlighting the importance of RLR-mediated, IFN-independent mechanisms in restricting SARS-CoV-2. Our studies reveal that SARS-CoV-2 Delta has integrated multiple mechanisms to silence the host innate immune response and evade the IFN response. We speculate that Delta's silent replication and sustained suppression of the host innate immune response, thereby resulting in delayed or reduced intervention by the adaptive immune response, could have potentially contributed to the severe symptoms and poor recovery index associated with it. It is likely that this altered association with the host would play an important role in the coevolution of SARS-CoV-2 with humans. IMPORTANCE Viruses generally learn to coexist with the host during the process of evolution. It is expected that SARS-CoV-2 would also evolve to coexist in humans by trading off its virulence for longer persistence, causing milder disease. Clinically, the fatality associated with COVID-19 has been declining due to vaccination and preinfections, but the Delta variant caused the most severe disease and fatality across several parts of the world. Our study identified an evolving trend of SARS-CoV-2 variants where the variants that emerged during early parts of the pandemic caused a more robust innate immune response, while the later emerging variant Delta showed features of suppression of the response. The features that Delta has acquired could have strongly influenced the distinct pathophysiology associated with its infection. How these changed associations with the host influence the long-term evolution of the virus and the disease outcome should be closely studied to understand the process of viral evolution.

A Comparative Study of Baseline Heart Rate Variability, Sleep Quality, and Oxidative Stress Levels in Hypertensive Versus Normotensive Subjects: A Cross-Sectional Study.

OBJECTIVES: To understand sleep quality, oxidative stress levels, and heart rate variability (HRV) in subjects with hypertension. This study aims to create baseline data in hypertensive subjects to research the possibility of further estimating the risk of developing cardiovascular mortality and morbidity in a patient with hypertension. DESIGN AND METHODS: This analytical cross-sectional study, encompassing 128 study subjects of both genders, with 64 hypertensive subjects, analyse the co-relation of sleep quality, malondialdehyde, and heart rate variability in hypertensive and normotensive subjects. The study was done in a tertiary teaching institute in northern India for 14 months. Descriptive statistics were used, and the independent t-test, Mann-Whitney U test, and Chi-square were used to find the association among the variables. Linear regression was used to estimate the effect of blood pressure on malondialdehyde levels. RESULTS: Subjects with hypertension were found to have poor sleep quality (Global PSQI score ≥5, p=0.0001) and an increased malondialdehyde level (0.30303±0.17193 µM/L, p=0.0001). The hypertensive subjects were found to have lower parasympathetic activity as indicated by low high frequency (2.79463±473.220280; p=0.0001) and increased sympathetic activity; low frequency/high frequency (2.29823±2.792441; p=0.0001). Multivariate linear regression predicts that with one unit increase in systolic blood pressure, the malondialdehyde level increases by 0.006 units (p=0.002; 95% CI). CONCLUSION: Among the hypertensive group, there is significantly increased oxidative stress level, poor quality of sleep, and increased sympathetic activity, thereby predisposing the subjects to increased risk of cardiac morbidity and mortality.

Investigation of the Utility of Features in a Clinical De-identification Model: A Demonstration Using EHR Pathology Reports for Advanced NSCLC Patients.

BACKGROUND: Electronic health record (EHR) systems contain a large volume of texts, including visit notes, discharge summaries, and various reports. To protect the confidentiality of patients, these records often need to be fully de-identified before circulating for secondary use. Machine learning (ML) based named entity recognition (NER) model has emerged as a popular technique of automatic de-identification. OBJECTIVE: The performance of a machine learning model highly depends on the selection of appropriate features. The objective of this study was to investigate the usability of multiple features in building a conditional random field (CRF) based clinical de-identification NER model. METHODS: Using open-source natural language processing (NLP) toolkits, we annotated protected health information (PHI) in 1,500 pathology reports and built supervised NER models using multiple features and their combinations. We further investigated the dependency of a model's performance on the size of training data. RESULTS: Among the 10 feature extractors explored in this study, n-gram, prefix-suffix, word embedding, and word shape performed the best. A model using combination of these four feature sets yielded precision, recall, and F1-score for each PHI as follows: NAME (0.80; 0.79; 0.80), LOCATION (0.85; 0.83; 0.84), DATE (0.86; 0.79; 0.82), HOSPITAL (0.96; 0.93; 0.95), ID (0.99; 0.82; 0.90), and INITIALS (0.97; 0.49; 0.65). We also found that the model's performance becomes saturated when the training data size is beyond 200. CONCLUSION: Manual de-identification of large-scale data is an impractical procedure since it is time-consuming and subject to human errors. Analysis of the NER model's performance in this study sheds light on a semi-automatic clinical de-identification pipeline for enterprise-wide data warehousing.

Epidemiological and Clinical Characteristics of Adults with Coronavirus Disease 2019 Complicated with Pneumothorax.

Background: The major brunt of coronavirus disease-2019 (COVID-2019) is borne by the lungs. The major cause of morbidity and mortality in COVID-19 patients is a compromise of the respiratory system. Pneumothorax is noted as an insignificant proportion of patients suffering from COVID-19, but it jeopardizes the clinical recovery significantly. We, in the case series of 10 patients, will be summarizing the epidemiological, demographic, and clinical characteristics of COVID-19 patients who also developed pneumothorax. Patients and methods: All the confirmed cases of COVID-19 pneumonia diagnosed between May 1, 2020 and August 30, 2020, admitted at our center meeting the inclusion criteria and whose clinical course was complicated by pneumothorax were made part of our study. Their clinical records were studied, and epidemiological, demographic, and clinical data of these patients were collected and compiled in this case series. Results: All the patients in our study required ICU care, and 60% received non-invasive mechanical ventilation, while 40% of the patients progressed to intubation and invasive mechanical ventilation. A total of 70% of the patients in our study had a successful outcome, while 30% succumbed to the disease and expired. Conclusion: Epidemiological, demographic, and clinical characteristics of COVID-19 patients complicated with pneumothorax were evaluated. Our study showed that pneumothorax also developed in some patients who had not received mechanical ventilation, indicating that pneumothorax could be a secondary complication of SARS-CoV-2 infection. Our study also emphasizes the fact that even the majority of patients whose clinical course was complicated by pneumothorax had a successful outcome emphasizing the need for timely and adequate intervention in such cases. How to cite this article: Singh NK. Epidemiological and Clinical Characteristics of Adults with Coronavirus Disease 2019 Complicated with Pneumothorax. Indian J Crit Care Med 2022;26(7):833-835.

Sequence and structural similarities of ACCase protein of Phalaris minor and wheat: An insight to explain herbicide selectivity.

Uncontrolled growth of Phalaris minor in the wheat (Triticum aestivum) crop has remained a problem, leading to a massive reduction in wheat grain production. Herbicides have been used to control the weed, which leads to the development of frequent resistance in P. minor and mutant biotypes were also reported (Trp2027Cys and Ile2041Asn). Development of resistance enforced agro researchers to analyses the action of herbicide on P. minor. In this study, the sequence and structure of P. minor and T. aestivum Acetyl CoA Carboxylase (ACCase) have been analysed to locate the differences in their sequence and structure and to formulate a plausible explanation of the selectivity of herbicides which may help in the rationale discovery of noble herbicides. The sequence and 3D structure analysis of weed and wheat ACCase indicate minute differences in the distantly located amino acid residues. However, proteins are conserved at the binding site of herbicides with no mutation at the catalytic site. Analysis indicates that herbicides selectively target P. minor ACCase might be due to unknown other reasons, but not due to differences in their protein sequence and structure.