Publications by authors named "Kumar A"

25,290 Publications

Use of machine learning to develop prediction models for mortality and stroke in patients undergoing balloon aortic valvuloplasty.

Cardiovasc Revasc Med 2022 Jul 30. Epub 2022 Jul 30.

Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, United States. Electronic address:

Objective: To develop an artificial intelligence, machine learning prediction model for estimating in-hospital mortality and stroke in patients undergoing balloon aortic valvuloplasty (BAV).

Methods: The National Inpatient Sample (NIS) database was used to identify patients who underwent BAV from 2005 to 2017. Outcomes analyzed were in-hospital all-cause mortality and stroke after BAV. Predictors of mortality and stroke were selected using LASSO regularization. A conventional logistic regression and a random forest machine learning algorithm were used to train the models for predicting outcomes. The performance of all the modeling algorithms for predicting in-hospital mortality and stroke was compared between models using c-statistic, F1 score, brier score loss, diagnostic accuracy, and Kolmogorov-Smirnov plots.

Results: A total of 6962 patients with severe aortic stenosis who underwent BAV were identified. The performance of random forest classifier was comparable with logistic regression for predicting in-hospital mortality for all measures of performance (F1 score 0.422 vs 0.409, ROC-AUC 0.822 [95 % CI 0.787-0.855] vs 0.815 [95 % CI 0.779-0.849], diagnostic accuracy 70.42 % vs 70.93 %, KS-statistic 0.513 vs 0.494 and brier score loss 0.295 vs 0.291). The random forest algorithm significantly outperformed logistic regression in predicting in-hospital stroke with respect to all performance metrics: F1 score 0.225 vs 0.095, AUC 0.767 [0.662-0.858] vs 0.637 [0.499-0.754], brier score loss [0.399 vs 0.407], and KS-statistic [0.465 vs 0.254].

Conclusions: The good discrimination of machine learning models reveal the potential of artificial intelligence to improve patient risk stratification for BAV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carrev.2022.07.024DOI Listing
July 2022

Into the future: A pilot study combining imaging with molecular profiling to predict resectability in ovarian cancer.

Gynecol Oncol 2022 Aug 2. Epub 2022 Aug 2.

Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, Rochester, MN, United States.

Objective: We sought to determine the predictive value of combining tumor molecular subtype and computerized tomography (CT) imaging for surgical outcomes after primary cytoreductive surgery in advanced stage high-grade serous ovarian cancer (HGSOC) patients.

Methods: We identified 129 HGSOC patients who underwent pre-operative CT imaging and post-operative tumor mRNA profiling. A continuous CT-score indicative of overall disease burden was defined based on six imaging measurements of anatomic involvement. Molecular subtypes were derived from mRNA profiling of chemo-naïve tumors and classified as mesenchymal (MES) subtype (36%) or non-MES subtype (64%). Fischer exact tests and multivariate logistic regression examined residual disease and surgical complexity.

Results: Women with higher CT-scores were more likely to have MES subtype tumors (p = 0.014). MES subtypes and a high CT-score were independently predictive of macroscopic disease and high surgical complexity. In multivariate models adjusting for age, stage and American Society of Anesthesiologists (ASA) score, patients with a MES subtype and high CT-score had significantly elevated risk of macroscopic disease (OR = 26.7, 95% CI = [6.42, 187]) and were more likely to undergo high complexity surgery (OR = 9.53, 95% CI = [2.76, 40.6], compared to patients with non-MES tumor and low CT-score.

Conclusion: Preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women unlikely to have resectable disease and likely to require high complexity surgery. Along with other clinical factors, these may refine predictive scores for resection and assist treatment planning. Investigating methods for pre-surgical molecular subtyping is an important next step.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2022.07.020DOI Listing
August 2022

Development of a predictive model for gravimetric powder feeding from an API-rich materials properties library.

Int J Pharm 2022 Aug 3;625:122071. Epub 2022 Aug 3.

Worldwide Research and Development, Pfizer Inc, Sandwich, Kent, UK.

A model was developed for predicting the feed factor profile of a powder, processed through a gravimetric feeder, as a function of material properties and process parameters. Predictive models proposed in existing literature have often used excipients and active pharmaceutical ingredients (APIs) with good powder flow characteristics in their development. In this work, a material properties library containing a large proportion of APIs, as well as excipients and co-processed blends, was used to build the model and enhance the prediction of feed factor profile for cohesive powders. Gravimetric feeder trials were performed at varying mass flow rates and screw geometries to determine the feed factor profiles. A semi-empirical exponential model, with parameters f, f, and β, was then used to fit the experimental feed factor profiles. Bayesian optimisation and Support Vector Regression (SVR) modelling techniques were utilised to optimise and predict the exponential model parameters as a function of material properties. The parameters found to strongly influence the model were particle size, bulk density, FFC and FT4 rheometer parameters. Results showed low prediction errors between the estimated and experimental data. The final model produces good estimations of the feed factor profile and requires minimal powder consumption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2022.122071DOI Listing
August 2022

Recent advances in the electrochemical applications of Ni-based metal organic frameworks (Ni-MOFs) and their derivatives.

Chemosphere 2022 Aug 2:135729. Epub 2022 Aug 2.

The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan,523808, China; Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Guangdong Medical University Key Laboratory of Research and Development of New Medical Materials, Dongguan, 523808, China. Electronic address:

Nickel-based metal-organic skeletal materials (Ni-MOFs) are a new class of inorganic materials that have aroused attention of investigators during past couple of years. They offer advantages such as high specific surface area, structural diversity, tunable framework etc. This assorted class of materials exhibited catalytic activity and electrochemical properties and display wide range of applications in the fields of electrochemical sensing, electrical energy storage and electrocatalysis. In this context, the presented review focuses on strategies to improve the electrochemical performance and stability of Ni-MOFs through the optimization of synthesis conditions, the construction of composite materials, and the preparation of derivatives of precursors. The review also presents the applications of Ni-MOFs and their derivatives as electrochemical sensors, energy storage devices, and electrocatalysts. In addition, the challenges and further electrochemical development prospects of Ni-MOFs have been discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2022.135729DOI Listing
August 2022

Japanese encephalitis virus induces vasodilation and severe lethality in adult and aged AG129 mice lacking alpha, beta and gamma interferon receptors.

Virus Res 2022 Aug 3;319:198884. Epub 2022 Aug 3.

Translational Health Science & Technology Institute, NCR Biotech Science Cluster, Faridabad, Haryana 121001, India. Electronic address:

Japanese encephalitis virus (JEV) is a single-stranded positive-sense RNA virus belonging to the Flaviviridae family. The JEV is the leading cause of viral encephalitis in children and the elderly which is spread by mosquitoes. JEV infection has been established in different animal models such as mouse, hamster, guinea pig, swine, rat, monkey, rabbit by using the different routes of inoculations. Here, we have shown that the alpha/beta and gamma -receptor deficient AG129 mouse induces fatal encephalitis in both young and aged old mice, when challenged with high titer JEV Indian clinical isolate by both intraperitoneal and intradermal route. The JEV infected AG129 mouse have shown neurological symptoms, JEV-induced pathological features and supported high level viral replication. Additionally, administration of JEV in AG129 mice resulted in the induction of severe peripheral vascular permeability, which is a major hall mark of Dengue infection but not shown in JEV. Taken together, our results demonstrate interferon α/β and γ receptors knock out AG129 mouse does not need adaptation of JEV clinical isolates and could be is a promising JEV challenge mouse model by mimicking the natural intradermal route of administration for rapid screening of novel antivirals and vaccines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virusres.2022.198884DOI Listing
August 2022

DPP-4 inhibition mediated antidiabetic potential of phytoconstituents of an aqueous fruit extract of (Stocks) Dunal: , and assessments.

J Biomol Struct Dyn 2022 Aug 5:1-23. Epub 2022 Aug 5.

Centre for System Biology and Bioinformatics, Panjab University, Chandigarh, India.

The DPP-4 inhibition is an interesting target for the development of antidiabetic agents which promotes the longevity of GPL-1(Glucagon-like peptide 1). The current study was intended to assess DPP-4(Dipeptidyl Peptidase-4) inhibition mediated antidiabetic effect of phytocompounds of an aqueous fruit extract of (Stocks) Dunal by , and approaches. The phytoconstituents screening was executed by LCMS (Liquid Chromatography with tandem mass spectrometry). The and , DPP-4 assays were performed by using available kits. The DPP-4 activity was inhibited up to 68.3% by the test extract. Accordingly, determinations of molecular docking, molecular dynamics and pharmacokinetics were performed between the target enzyme DPP-4 and leading phytocompounds. The molecular dynamics authenticated the molecular docking data by crucial parameters of cytosolic milieu by the potential energy, RSMD (Root Mean Square Deviation), RSMF (Root Mean Square Fluctuation), system density, NVT (Number of particles at fixed volume, ensemble) and NPT (Number of particles at fixed pressure, ensemble). Accordingly, ADMET predictions assessed the druggability profile. Subsequently, the course of the test extract and the sitagliptin (positive control), instigated significant ( ≤ 0.001) ameliorations in HOMA indices and the equal of antioxidants in nicotinamide-streptozotocin induced type 2 diabetic animal model. Compassionately, the histopathology represented increased pancreatic cellular mass which caused in restoration of histoarchitectures. It has been concluded that phytoconstituents in aqueous fruit extract can regulate DPP-4, resulting in improved glucose homeostasis and enhanced endocrinal pancreatic cellular mass.Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2022.2103029DOI Listing
August 2022

Identification of novel genes by targeted exome sequencing in Retinoblastoma.

Ophthalmic Genet 2022 Aug 5:1-18. Epub 2022 Aug 5.

Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.

Background: Retinoblastoma (RB) is initiated by mutation in both alleles of gene. However, few cases may occur even in the absence of mutation suggesting the role of genes other than .

Methodology: The current study was planned to utilize targeted exome sequencing in Indian RB patients affected with unilateral non-familial RB. 75 unilateral RB patients below 5 years of age were enrolled. Genomic DNA was extracted from blood and tumor tissue. From peripheral blood DNA, all coding and exon/intron regions were amplified using PCR and direct sequencing. Cases which did not harbor pathogenic variants in peripheral blood DNA were further screened for mutations in their tumor tissue DNA using targeted exome sequencing. Three pathogenicity prediction tools (Mutation Taster, SIFT, and PolyPhen-2) were used to determine the pathogenicity of non-synonymous variations. An in-house bioinformatics pipeline was devised for the mutation screening by targeted exome sequencing. Protein modeling studies were also done to predict the effect of the mutations on the protein structure and function.

Results: Using the mentioned approach, we found two novel variants (g.69673_69674insT and g.48373314C>A) in gene in peripheral blood DNA. We also found novel variants in eight genes (, , , , , , , and ) that may be associated with RB pathogenesis.

Conclusion: The present study expands our current knowledge regarding the genomic landscape of RB and also highlights the importance of NGS technologies to detect genes and novel variants that may play an important role in cancer initiation, progression, and prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13816810.2022.2106497DOI Listing
August 2022

A biomechanical evaluation on Cubic, Octet, and TPMS gyroid Ti6Al4V lattice structures fabricated by selective laser melting and the effects of their debris on human osteoblast-like cells.

Biomater Adv 2022 Jun 28;137:212829. Epub 2022 Apr 28.

Department of Mechanical Engineering, 9 Engineering Drive 1, #07-08 Block EA, National University of Singapore, 117575, Singapore. Electronic address:

Lattice structures are widely used in orthopedic implants due to their unique features, such as high strength-to-weight ratios and adjustable biomechanical properties. Based on the type of unit cell geometry, lattice structures may be classified into two types: strut-based structures and sheet-based structures. In this study, strut-based structures (Cubic & Octet) and sheet-based structure (triply periodic minimal surface (TPMS) gyroid) were investigated. The biomechanical properties of the three different Ti6Al4V lattice structures fabricated by selective laser melting (SLM) were investigated using room temperature compression testing. Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) were used to check the 3D printing quality with regards to defects and quantitative compositional information of 3D printed parts. Experimental results indicated that TPMS gyroid has superior biomechanical properties when compared to Cubic and Octet. Also, TPMS gyroid was found to be less affected by the variations in relative density. The biocompatibility of Ti6Al4V lattice structures was validated through the cytotoxicity test with human osteoblast-like SAOS2 cells. The debris generated during the degradation process in the form of particles and ions is among the primary causes of implant failure over time. In this study, Ti6Al4V particles with spherical and irregular shapes having average particle sizes of 36.5 μm and 28.8 μm, respectively, were used to mimic the actual Ti6Al4V particles to understand their harmful effects better. Also, the effects and amount of Ti6Al4V ions released after immersion within the cell culture media were investigated using the indirect cytotoxicity test and ion release test.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioadv.2022.212829DOI Listing
June 2022

Evidence-based surgical guidelines for treating children with Wilms tumor in low-resource settings.

Pediatr Blood Cancer 2022 Aug 5:e29906. Epub 2022 Aug 5.

Department of Pediatric Surgery, Pediatric Oncology Institute - GRAACC - Federal University of São Paulo, São Paulo, Brazil.

Background: Survival of Wilms tumor (WT) is > 90% in high-resource settings but < 30% in low-resource settings. Adapting a standardized surgical approach to WT is challenging in low-resource settings, but a local control strategy is crucial to improving outcomes.

Objective: Provide resource-sensitive recommendations for the surgical management of WT.

Methods: We performed a systematic review of PubMed and EMBASE through July 7, 2020, and used the GRADE approach to assess evidence and recommendations.

Recommendations: Initiation of treatment should be expedited, and surgery should be done in a high-volume setting. Cross-sectional imaging should be done to optimize preoperative planning. For patients with typical clinical features of WT, biopsy should not be done before chemotherapy, and neoadjuvant chemotherapy should precede surgical resection. Also, resection should include a large transperitoneal laparotomy, adequate lymph node sampling, and documentation of staging findings. For WT with tumor thrombus in the inferior vena cava, neoadjuvant chemotherapy should be given before en bloc resection of the tumor and thrombus and evaluation for viable tumor thrombus. For those with bilateral WT, neoadjuvant chemotherapy should be given for 6-12 weeks. Neither routine use of complex hilar control techniques during nephron-sparing surgery nor nephron-sparing resection for unilateral WT with a normal contralateral kidney is recommended. When indicated, postoperative radiotherapy should be administered within 14 days of surgery. Post-chemotherapy pulmonary oligometastasis should be resected when feasible, if local protocols allow omission of whole-lung irradiation in patients with nonanaplastic histology stage IV WT with pulmonary metastasis without evidence of extrapulmonary metastasis.

Conclusion: We provide evidence-based recommendations for the surgical management of WT, considering the benefits/risks associated with limited-resource settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.29906DOI Listing
August 2022

Nerve changes associated with post thoracotomy pain syndrome.

Histol Histopathol 2022 Aug 5:18515. Epub 2022 Aug 5.

First Discipline of Surgical Semiology, First Department of Surgery, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania.

Background: Chronic post-thoracotomy pain (PTPS) is a frequent complication of thoracic operations. Sometimes the pain is excruciating enough to impair activities of daily living (ADL). All thoracic procedures have the potential to cause trauma to the intercostal nerves due to retractor use, chest closure techniques, and or wound healing. In our study, we analyzed the microscopic aspects of the nerves involved in the healing process, to better understand the histopathology of chronic pain.

Material And Methods: 29 patients with PTPS underwent intercostal neurectomy to alleviate the symptoms. Microscopic specimens harvested during the surgeries were sent to our pathology unit for evaluation. The following data regarding the surgical procedures was collected: surgical approach, chest closure type, number of excised nerves, and time interval from previous surgery to neurectomy.

Results: A mean of 2.34±1.11 nerves were excised. Microscopy of the specimens revealed: fibrosis, hyalinization of the epineurium and perineurium, intense hyperemia of the blood capillaries, and interstitial edema. 7 cases presented with myxoid degeneration of epineurium and perineurium. In all the cases, endoneurium, myelin sheaths, and axons were interrupted. The endoneurium showed the presence of hyperemic dilated capillaries. The segmental cytoplasmic vacuolization of Schwann's cells with the total disappearance of axons was also noted. 60% of the examined specimens had intraneural myxoid degeneration, with highly dense irregular connective tissue around nerve fibers.

Conclusions: The pathologic findings in the structure of the intercostal nerves obtained from the patients are indicative of the involvement of the wound healing mechanisms in PTPS. The negative impact of wound healing could be considered a key component in the development of intense chronic pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14670/HH-18-515DOI Listing
August 2022

Risk Prediction of Injury Among Recreational Badminton Players in India.

Indian J Orthop 2022 Aug 7;56(8):1378-1384. Epub 2022 Jun 7.

Department of Orthopaedics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background/purpose: Since badminton has emerged as a frequently played non-contact recreational sport in India, it is essential to document the injury patterns and incidence. However, there is no existing literature on this topic among Indian players.

Materials And Methods: A web-based questionnaire was circulated among recreational badminton players across North India, enquiring about demographic details, injury characteristics, and factors associated with an injury like BMI, warm-up practice, and physical training.

Results: Data of 237 eligible participants revealed an injury incidence rate of 57.1%. The ankle and dominant-side shoulder were the most common anatomical regions affected. The most common injury types were ligament sprain and muscle/tendon strain. Factors like age, frequency, duration of play, type of footwear, BMI, prior warm-up, court surface, and physical training were significantly associated with injury incidence on univariate logistic regression analysis. On multivariate logistic regression analysis, we found male gender, a lack of prior warm-up, inadequate physical training, and age group between 26 and 30 years to be four independent risk factors for injury.

Conclusion: The recreational badminton player of India had a relatively higher incidence of injury compared with the limited published data from other countries. Modifiable factors like a proper warm-up before the game, regular physical fitness training, and injury awareness programs can reduce the injury rates.

Supplementary Information: The online version contains supplementary material available at 10.1007/s43465-022-00663-y.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43465-022-00663-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9283613PMC
August 2022

Uterine Sarcoma: Retrospective Study From A Single institute.

J Obstet Gynaecol India 2022 Aug 23;72(Suppl 1):306-312. Epub 2022 Feb 23.

Division of Radiation Oncology, Regional Cancer Centre, Thiruvananthapuram, Kerala India.

Abstract: Uterine sarcomas are heterogeneous group of tumours comprising 1% of gynaecological malignancies. There is lack of concences on optimal treatment of uterine sarcomas. This is because of lack of randomised controlled trials due to rarity of these tumours. Surgical management without spill remains the standard primary treatment. Most of the times uterine sarcomas are diagnosed postoperatively from histopathology report of either myomectomy or hysterectomy. This retrospective study analysed the clinico pathological characteristics, prognostic factors, treatment details and survival outcome of different types of uterine sarcomas.

Materials And Methods: This is a retrospective analysis of 59 patients of uterine sarcomas. All patients underwent surgery. Adjuvant chemotherapy or radiation treatment were given according to histopathological report and FIGO stage. Patients were followed up every three months for first two years and then every six months. Disease free survival (DFS) and Overall survival (OS) were calculated.

Statistical Analysis: The data were summarized using descriptive statistics as mean, percent and range. Survival probabilities were estimated using Kaplan-Meier method and the significance of difference between the survival curves were calculate using log-rank test.

Results: Uterine sarcomas are rare and aggressive tumours of uterus. Majority of these tumours present in early stage. Surgery remains the main treatment modality. Role of adjuvant radiation treatment remains controversial. Tumour stage is the most important prognostic factor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13224-021-01612-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343530PMC
August 2022

Five years of a comprehensive ST-elevation myocardial infarction protocol and its association with sex disparities.

Eur Heart J Open 2021 Nov 20;1(3):oeab011. Epub 2021 Aug 20.

Cleveland Clinic Heart, Vascular, & Thoracic Institute, Cleveland, OH, USA.

Aims: To determine whether a comprehensive ST-elevation myocardial infarction (STEMI) protocol is associated with reduced sex disparities over 5 years.

Methods And Results: This was an observational cohort study of 1833 consecutive STEMI patients treated with percutaneous coronary intervention (PCI) before (1 January 2011-14 July 2014, control group) and after (15 July 2014-15 July 2019, protocol group) implementation of a protocol for early guideline-directed medical therapy (GDMT), rapid door to balloon time (D2BT), and use of trans-radial PCI. In the control group, females had less GDMT (77.1% vs. 68.1%, = 0.03), similarly low trans-radial PCI (19.0% vs. 17.6%, = 0.73), and longer D2BT [104 min (79, 133) vs. 112 min (85, 147), = 0.02] corresponding to higher in-hospital mortality [4.5% vs. 10.3%, odds ratio (OR) 2.44 (1.34-4.46), = 0.004], major adverse cardiac and cerebrovascular events [MACCE, 9.8% vs. 16.3%, OR 1.79 (1.14-2.84), = 0.01], and net adverse clinical events [NACE, 16.1% vs. 28.3%, OR 2.06 (1.42-2.99), < 0.001]. In the protocol group, no significant sex differences were observed in GDMT (87.2% vs. 86.4%, = 0.81) or D2BT [85 min (64-106) vs. 89 min (65-111), = 0.06], but trans-radial PCI was used less in females (77.6% vs. 71.2%, = 0.03). In-hospital mortality [2.5% vs. 4.4%, OR 1.78 (0.91-3.51), = 0.09] and MACCE [9.0% vs. 11.1%, OR 1.27 (0.83-1.92), = 0.26] were similar between sexes, but higher NACE in females approached significance [14.8% vs. 19.4%, OR 1.38 (0.99-1.92), = 0.05] due to higher bleeding risk [7.2% vs. 11.1%, OR 1.60 (1.04-2.46), = 0.03].

Conclusions: A comprehensive STEMI protocol was associated with sustained reductions for in-hospital ischaemic outcomes over 5 years, but higher bleeding rates in females persisted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ehjopen/oeab011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242076PMC
November 2021

Appraising the Phytochemical and Therapeutic Perspectives of Bryonia laciniosa: A Literature Metasynthesis.

Comb Chem High Throughput Screen 2022 Aug 4. Epub 2022 Aug 4.

Department of Pharmacology, KIET School of Pharmacy, KIET Group of Institutions, Ghaziabad, Uttar Pradesh, India.

Background: Nature has bestowed mother Earth with an array of herbals utilized as therapeutics for various human ailments since the origin of life. Bryonia laciniosa (family: Cucurbitaceae) is one such herb which finds its mention in various traditional systems of medicine and has attracted the current researchers due to its significant therapeutic value.

Objective: The current article aims to present a literature metasynthesis on Bryonia laciniosa.

Method: The authors performed the scholarly searches for peer-reviewed findings on Bryonia laciniosa and incorporated all the data related to the phytochemical and therapeutic profile of the drug.

Results: This compilation comprises of Phytochemical and Pharmacological profile of Bryonia laciniosa elaborating its traditional significance and recent researches related to its biological activities. The plant exhibits its potential as antimicrobial, anti-inflammatory, analgesic, antipyretic, anticonvulsant, anti-asthamatic, anticancer, antioxidant, antidiabetic and aphrodiasiac agent. Also displays its benefits in wound healing and ulcerative colitis.

Conclusion: The presence of flavonoids, saponins, terpenoids, anthocyanins, coumarins, alkaloids, polyphenols, tannins and emodins in this plant is responsible for its various pharmacological activities. The retrospective study provides direction for existing research as well as future studies to support the domain of pharmaceutical and medical sciences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1386207325666220804113744DOI Listing
August 2022

Thrombocytopenia in a child with polyarthritis: A pointer to gray platelet syndrome.

Pediatr Blood Cancer 2022 Aug 4:e29916. Epub 2022 Aug 4.

Pediatric Allergy Immunology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.29916DOI Listing
August 2022

Microscopic Insights into the Mechanism of White Light Generation by Disruptive Interaction between Human Serum Albumin Amyloid Fibrils and Surfactant-AIEgen Nanorods.

J Phys Chem Lett 2022 Aug 4:7355-7362. Epub 2022 Aug 4.

Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

Dimethyl-2,5-bis[4-(methoxyphenyl)amino] terephthalate (DBMPT) exhibits aggregation-induced enhancement of emission with Tween 40 and formation of nanorods with strong orange fluorescence. These nanorods disrupt fibrils of human serum albumin and lead to partial refolding of the protein, as monitored by circular dichroism and thioflavin T (ThT) fluorescence. The resultant milieu emits white light, the mechanism of which is explored in this study. It is established that direct excitation of the acceptor plays a significant role, even though Förster resonance energy transfer (FRET) is found to be operative to some extent. A decrease in the fluorescence intensity and lifetime of ThT with progressive addition of DBMPT, which is often used as the sole indicator of FRET, is ascribed to the disruption of the fibrils by the nanorods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpclett.2c01599DOI Listing
August 2022

Feature Extraction Approach for Speaker Verification to Support Healthcare System Using Blockchain Security for Data Privacy.

Comput Math Methods Med 2022 25;2022:8717263. Epub 2022 Jul 25.

Department of Electrical and Electronics Engineering, Faculty of Engineering, BoluAbantIzzetBaysal University, Bolu, Turkey.

Speech is one form of biometric that combines both physiological and behavioral features. It is beneficial for remote-access transactions over telecommunication networks. Presently, this task is the most challenging one for researchers. People's mental status in the form of emotions is quite complex, and its complexity depends upon internal behavior. Emotion and facial behavior are essential characteristics through which human internal thought can be predicted. Speech is one of the mechanisms through which human's various internal reflections can be expected and extracted by focusing on the vocal track, the flow of voice, voice frequency, etc. Human voice specimens of different ages can be emotions that can be predicted through a deep learning approach using feature removal behavior prediction that will help build a step intelligent healthcare system strong and provide data to various doctors of medical institutes and hospitals to understand the physiological behavior of humans. Healthcare is a clinical area with data concentrated where many details are accessed, generated, and circulated periodically. Healthcare systems with many existing approaches like tracing and tracking continuously disclose the system's constraints in controlling patient data privacy and security. In the healthcare system, majority of the work involves swapping or using decisively confidential and personal data. A key issue is the modeling of approaches that guarantee the value of health-related data while protecting privacy and observing high behavioral standards. This will encourage large-scale perception, especially as healthcare information collection is expected to continue far off this current ongoing pandemic. So, the research section is looking for a privacy-preserving, secure, and sustainable system by using a technology called Blockchain. Data related to healthcare and distribution among institutions is a very challenging task. Storage of facts in the centralized form is a targeted choice for cyber hackers and initiates an accordant sight of patients' facts which will cause a problem in sharing information over a network. So, this research paper's approach based on Blockchain for sharing sufferer data in a secured manner is presented. Finally, the proposed model for extracting optimum value in error rate and accuracy was analyzed using different feature removal approaches to determine which feature removal performs better with different voice specimen variations. The proposed method increases the rate of correct evidence collection and minimizes the loss and authentication issues and using feature extraction based on text validation increases the sustainability of the healthcare system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/8717263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343193PMC
August 2022

Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set.

Crit Care 2022 Aug 3;26(1):236. Epub 2022 Aug 3.

Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium.

Background: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.

Methods: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method.

Results: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.

Conclusions: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-022-04108-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347163PMC
August 2022

Novel alantolactone derivative AL-04 exhibits potential anti-inflammatory activity via modulation of iNOS, COX-2 and NF-κB.

Cytokine 2022 Jul 31;158:155978. Epub 2022 Jul 31.

Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, Jammu and Kashmir 180001, India. Electronic address:

Natural compounds and their synthesized analogues continue to be valuable sources in the discovery and development of novel anti-inflammatory agents. AL-04 is a thiol analogue derived from a natural sesquiterpene alantolactone, that demonstrated potential anti-inflammatory activity in vitro in comparison to its parent compound. However, the anti-inflammatory mechanism of action of AL-04 has not been elucidated. In this context, we investigated the signaling pathway that primarily mediate the anti-inflammatory activity of AL-04 and its effect on principal inflammatory mediators including iNOS, COX-2 and ROS. Furthermore, the anti-inflammatory activity was investigated in vivo in carrageenan induced paw oedema model in addition to the exploration of anti-nociceptive activity and acute toxicity. The results suggested that treatment with AL-04 significantly decreased the LPS-induced upregulation of pro-inflammatory cytokines and mediators in addition to the downregulated transcription of TNF-α and IL-6 in RAW 264.7 cell line. Furthermore, mRNA and the protein expression of COX-2 and iNOS were also significantly attenuated with AL-04 at a concentration of 10 µM. Western blot studies further suggested that AL-04 downregulated LPS-stimulated NF-κB p65 expression. In addition to this the anti-inflammatory activity of AL-04 was demonstrated in carrageenan induced paw oedema model with significant inhibition of oedema in a dose-dependent manner. The anti-inflammatory activity of AL-04 was further demonstrated in balb/c mice by inhibition of leukocyte migration and vascular permeability. Besides, AL-04 also inhibited thermally and chemically induced pain in tail-flick and acetic acid induced writing assays respectively in balb/c mice suggesting the analgesic potential of the compound. Acute toxicity studies further suggested the appreciable safety of AL-04 at high dose of 2000 mg/kg with no indications of toxicity or changes in biochemical and haematological parameters. Overall, the study insinuates the anti-inflammatory potential of AL-04 and paves way for further exploration of the compound as a safer therapeutic anti-inflammatory agent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2022.155978DOI Listing
July 2022

Using the Endsley Model to Evaluate Simulation-Based Situation Awareness Training for Medical and Nursing Students in India: A Qualitative Analysis.

Simul Healthc 2022 Aug 5. Epub 2022 Aug 5.

From the Royal Children's Hospital (M.R.B.); Department of Paediatrics (A.M.), Monash University, Melbourne, Australia; Hind Institute of Medical Sciences (A.M., U.B., J.V.S., A.K.); Lucknow, India; and Department of Obstetrics and Gynaecology (A.K.), Monash University, Melbourne, Australia.

Introduction: Situation awareness (SA) training is a vital part of healthcare training, and opportunities to provide SA training to healthcare workers are limited in low- and middle-income countries. We aimed to analyze undergraduate medical and nursing students' perception of their understanding of SA through an interprofessional obstetric neonatal emergency simulation workshop (ONE-Sim) and subsequently evaluate their perceived changes in SA understanding using the Endsley model ( Hum Factors 1995;37(1):32-64).

Methods: Feedback on SA before and after the workshop was collected through questionnaire-based surveys. Thematic analysis was performed, with themes emerging from an inductive analysis followed by a deductive analysis using the Endsley model.

Results: The themes emerging from the inductive analysis included environmental awareness, evolving knowledge, skill development, and applicability to practice. These aligned with the 3 levels of SA in the Endsley model in the deductive analysis suggesting that participants transformed their perception, comprehension, and projection of SA after the workshop.

Conclusion: Simulation-based education enhanced SA perception in obstetric and neonatal emergencies for medical and nursing students in a low- and middle-income country, and the Endsley model is a feasible framework to measure learner perceived changes in SA understanding through simulation-based education.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SIH.0000000000000677DOI Listing
August 2022

Design, synthesis, extra-precision docking, and molecular dynamics simulation studies of pyrrolidin-2-one derivatives as potential acetylcholinesterase inhibitors.

J Biomol Struct Dyn 2022 Aug 3:1-13. Epub 2022 Aug 3.

Department of Pharmacy ,Banasthali Vidyapith, Newai, Rajasthan, India.

Inhibition of acetylcholinesterase (AChE) has been widely explored to develop novel molecules for management of Alzheimer's disease. In past research finding reported molecule 3-(4-(4-fluorobenzoyl)piperidin-1-yl)-1-(4-methoxybenzyl)pyrrolidin-2-one displayed a spectrum of anti-Alzheimer's properties herein, we report a library of 18 novel molecules that were rationally designed and synthesized employing known literature to mimic and explore the novel chemical space around the lead compound and donepezil. All the compounds were docked in extra-precision mode with AChE (PDB ID 4EY7) using the Glide module. Molecular dynamics (MD) simulation studies were carried out for 100 ns along with MM-PBSA studies of the trajectory frames generated post-MD simulations. Docking and MD simulation studies suggested that the synthesized compounds showed a good binding affinity with AChE. and might form stable complexes. 3-(4-(benzyl(methyl)amino)piperidin-1-yl)-1-(3,4-dimethoxybenzyl)pyrrolidin-2-one (; docking score: -18.59) and 1-(3,4-dimethoxybenzyl)-3-(4-(methyl(thiazol-2-ylmethyl)amino)piperidin-1-yl)pyrrolidin-2-one (; docking score: -18.057) showed higher docking score than donepezil (docking score: -17.257) while most of the compounds had docking score >-10.0. ADMET study predicted these compounds to be CNS active and most of the compounds were drug-like molecules with no HERG blockade and good to excellent oral absorption. We developed an atom-based 3 D-QSAR model with R^2 and Q^2 values of 0.9639 and 0.8779 to predict the activity of the synthesized compounds. The model predicted these compounds to be potent AChE inhibitors with IC values in the lower micromolar range. Based on the findings, we report these newly synthesized compounds 3-(4-(benzyl(methyl)amino)piperidin-1-yl)-1-(3,4-dimethoxybenzyl)pyrrolidin-2-one and 7-(2,6-difluorobenzyl)-2-(4-methoxybenzyl)-2,7-diazaspiro[4.5]decan-1-one () as potential AChE inhibitors.Communicated by Ramaswamy H. Sarma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07391102.2022.2106515DOI Listing
August 2022

Introduction of cadmium chloride additive to improve the performance and stability of perovskite solar cells.

RSC Adv 2022 Jul 15;12(32):20461-20470. Epub 2022 Jul 15.

Laboratory for Biomaterials and Bioengineering (CRC-I), Department of Min-Met-Materials Engineering, Laval University Quebec City QC G1V0A6 Canada.

With the increase in the importance of using green energy sources to meet the world's energy demands, attempts have been made to push perovskite solar cell technology toward industrialization all around the world. Improving the properties of perovskite materials as the heart of PSCs is one of the methods to fabricate favorable photovoltaic (PV) solar cells based on perovskites. Here, cadmium chloride (CdCl) was used as an additive source for the perovskite precursor to improve its PV properties. Results indicated CdCl improves the perovskite growth and tailors its crystalline properties, suggesting boosted charge transport processes in the bulk and interfaces of the perovskite layer with electron-hole transport layers. Overall, by incorporation of 1.0% into the MAPbI layer, a maximum power conversion efficiency of 15.28% was recorded for perovskite-based solar cells, higher than the 12.17% for the control devices. The developed method not only improved the PV performance of devices but also boosted the stability behavior of solar cells due to the passivated domain boundaries and enhanced hydrophobicity in the CdCl-based devices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d2ra03776aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284664PMC
July 2022

Parks 3-step test.

Authors:
Annapurna Kumar

Indian J Ophthalmol 2022 Aug;70(8):3167

Ophthalmology Educator, Puducherry, India.

Background: The Parks 3-step test is an important test in the diagnosis of a single cyclovertical muscle palsy.

Purpose: This video is presented to provide a simplified and easy understanding of the Parks 3-step test for post-graduate residents.

Synopsis: The video contains a description of the steps to perform a 3-step test, the results of the test in a case of superior oblique palsy, the conditions that mimic a positive 3-step test, and how to identify these mimicking conditions.

Highlights: This is a simple demonstration of a classic clinical diagnostic procedure.

Online Video Link: https://youtu.be/1wpjwe19c0E.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijo.IJO_714_22DOI Listing
August 2022

CAF08 adjuvant enables single dose protection against respiratory syncytial virus infection in murine newborns.

Nat Commun 2022 Aug 2;13(1):4234. Epub 2022 Aug 2.

Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.

Respiratory syncytial virus is a leading cause of morbidity and mortality in children, due in part to their distinct immune system, characterized by impaired induction of Th 1 immunity. Here we show application of cationic adjuvant formulation CAF08, a liposomal vaccine formulation tailored to induce Th 1 immunity in early life via synergistic engagement of Toll-like Receptor 7/8 and the C-type lectin receptor Mincle. We apply quantitative phosphoproteomics to human dendritic cells and reveal a role for Protein Kinase C-δ for enhanced Th1 cytokine production in neonatal dendritic cells and identify signaling events resulting in antigen cross-presentation. In a murine in vivo model a single immunization at birth with CAF08-adjuvanted RSV pre-fusion antigen protects newborn mice from RSV infection by induction of antigen-specific CD8 T-cells and Th1 cells. Overall, we describe a pediatric adjuvant formulation and characterize its mechanism of action providing a promising avenue for development of early life vaccines against RSV and other respiratory viral pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-022-31709-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346114PMC
August 2022

Response to: Correspondence on 'Delayed collapse of flow diverter due to acute severe vasospasm: another concern for flow diversion in ruptured aneurysms' by Kumar .

J Neurointerv Surg 2022 Aug 2. Epub 2022 Aug 2.

Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnis-2022-019420DOI Listing
August 2022

A green approach towards sorption of CO on waste derived biochar.

Environ Res 2022 Jul 30;214(Pt 2):113954. Epub 2022 Jul 30.

CSIR-National Environmental Engineering Research Institute, Nagpur, 440 020, Maharashtra, India. Electronic address:

Carbon capture technologies have advanced in recent years to meet the ever-increasing quest to minimize excessive anthropogenic CO emissions. The most promising option for CO control has been identified as carbon capture and storage. Among the numerous sorbents, char generated from biomass thermal conversion has shown to be an efficient CO adsorbent. This study examines various characteristics that can be used to increase the yield of biochar suited for carbon sequestration. This review gives recent research progress in the area, stressing the variations and consequences of various preparation processes on textural features such as surface area, pore size and sorption performance with respect to CO's sorption capacity. The adjoining gaps discovered in this field have also been highlighted herewith, which will serve as future work possibility. It aims to analyse and describe the possibilities and potential of employing pristine and modified biochar as a medium of CO capture. It also examines the parameters that influence biochar's CO adsorption ability and pertinent challenges regarding the production of biochar-based CO sorbent materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envres.2022.113954DOI Listing
July 2022

Comparative Effectiveness of Pre-Identified Homeopathic Medicines in Asymptomatic COVID-19 Individuals Receiving Standard Care-An Open-Label, Randomized, Controlled Exploratory Trial.

Homeopathy 2022 Aug 2. Epub 2022 Aug 2.

Department of Clinical Research, Central Council for Research in Homoeopathy (CCRH), New Delhi, India.

Background And Objectives:  Asymptomatic COVID-19 subjects can transmit the infection for as many as 14 days and are regarded as a significant factor in the rapid spread of the COVID-19 pandemic. This exploratory study aimed to determine any additional benefits of selected homeopathic medicines compared with placebo in asymptomatic COVID-19 individuals receiving standard care.

Methods:  This open-label, randomized, placebo-controlled, exploratory trial was undertaken at a COVID Care Centre (CCC) in Madhya Pradesh, India. Patients ( = 200, 18-65 years, both sexes) having a positive RT-PCR and asymptomatic during admission were enrolled. They were randomly assigned to one of four groups (each  = 50): 30C (), 1M (.), 30C and placebo (.). All the patients were given standard care. The primary outcome was the number of patients becoming RT-PCR negative for SARS-CoV-2 at days 5, 10 and 15.

Results:  In total, 200 asymptomatic COVID-19 patients were enrolled. One hundred and seventy-seven patients became RT-PCR negative by day 15; 88%, 80%, 98% and 88% from and respectively. A Chi-square test of association for the total patients who became RT-PCR negative for SARS-Cov-2 in each group showed a marginal statistical significance (Chi-square: 8.1,  = 0.04). A two-proportion -test comparing each pre-identified homeopathic medicine with placebo showed marginal statistical significance ( = 0.05) for only. Median time in days to RT-PCR negative (Kaplan Meier analysis) was 10 days in each of the groups.

Conclusion:  There was some evidence that, compared with . or , was associated with an increased number of patients who became RT-PCR negative for COVID-19 by day 15. The possible effect exerted needs to be investigated in additional research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0042-1745754DOI Listing
August 2022

Evaluating chemicals of emerging concern in the Ganga River at the two major cities Prayagraj and Varanasi through validated analytical approaches.

Environ Sci Pollut Res Int 2022 Aug 2. Epub 2022 Aug 2.

Analytical and Structural Chemistry Department, CSIR-Indian Institute of Chemical Technology, Tarnaka, Uppal Road, Hyderabad, 500 007, Telangana, India.

Evaluating environmental water quality means to assess and protect the environment against unfriendly impacts from various organic impurities emerging from industrial emissions and those released during harvesting. Potential risks related with release of polycyclic aromatic hydrocarbons (PAHs), pesticides and pharmaceuticals (PhAcs), and personal care products (PCPs) into the environment have turned into an increasingly serious issue in ecological safety. Monitoring helps in control of chemicals and ecological status compliance to safeguard specific water uses, for example, drinking water abstraction. A longitudinal review was carried out for 55 different persistent organic pollutants (POPs) for the Ganga River which passes through the urban areas of Prayagraj and Varanasi, India, through validated analytical approaches and measurement uncertainty (MU) estimation to assess their potential use for routine analysis. Furthermore, environmental risk assessment (ERA) carried out in the present study has revealed risk quotient (RQ) higher than 1 in a portion of the aquatic bodies. Using a conservative RQ strategy, POPs were assessed for having extensive risks under acute and chronic exposure, proposing that there is currently critical ecological risk identified with these compounds present in the Ganga River. In general, these outcomes demonstrate a significant contribution for focusing on measures and feasible techniques to minimize the unfavorable effects of contaminants on the aquatic environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-022-22226-2DOI Listing
August 2022

Indole Sensing Regulator (IsrR) Promotes Virulence Gene Expression in Enteric Pathogens.

mBio 2022 Aug 2:e0193922. Epub 2022 Aug 2.

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Enteric pathogens such as enterohemorrhagic E. coli (EHEC) and its surrogate murine model Citrobacter rodentium sense indole levels within the gut to navigate its biogeography and modulate virulence gene expression. Indole is a microbiota-derived signal that is more abundant in the intestinal lumen, with its concentration decreasing at the epithelial lining where it is absorbed. E. coli, but not C. rodentium, produces endogenous indole because it harbors the gene. Microbiota-derived exogenous indole is sensed by the CpxAR two-component system, where CpxA is a membrane-bound histidine-sensor-kinase (HK) and CpxR is a response regulator (RR). Indole inhibits CpxAR function leading to decreased expression of the locus of enterocyte effacement (LEE) pathogenicity island, which is essential for these pathogens to form lesions on enterocytes. In our transcriptome studies comparing wild-type (WT) EHEC and Δ ± indole, one of the most upregulated genes by indole is , which is a predicted orphan RR. Because of the role YgeV plays in the indole signaling cascade, we renamed this gene indole sensing regulator (). In the absence of endogenous indole, IsrR activates LEE gene expression. IsrR only responds to endogenous indole, with exogenous indole still blocking virulence gene expression independently from IsrR. Notably, a C. rodentium mutant is attenuated for murine infection, depicting delayed death, lower intestinal colonization, and LEE gene expression. IsrR aids in discriminating between microbiota-derived (exogenous) and endogenous self-produced indole in fine-tuning virulence gene expression by enteric pathogens in the intestine. Enteric pathogens sense the complex intestinal chemistry to find a suitable colonization niche. The microbiota plays an important part in shaping this chemistry. Here we show that the abundant microbiota-derived exogenous signal indole impacts host-pathogen interactions by allowing enteric pathogens to discriminate between the luminal environment, where expression of virulence genes is an unnecessary energy burden, from the epithelial surface, where this gene expression is needed for host colonization. We describe a new signaling node through the regulator IsrR that allows for this shift. These findings establish a mechanism through which pathogens discriminate from self- and microbiota-derived signaling to establish infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mbio.01939-22DOI Listing
August 2022

Genetically Engineered Viral Vectors and Organic-based Non-viral Nanocarriers for Drug Delivery Applications.

Adv Healthc Mater 2022 Aug 2:e2201583. Epub 2022 Aug 2.

Istituto Italiano di Tecnologia, Centre for Materials Interface, viale Rinaldo Piaggio 34, Pontedera, Pisa, 56025, Italy.

Conventional drug delivery systems are challenged by concerns related to systemic toxicity, repetitive doses, drug concentrations fluctuation, and adverse effects. Various drug delivery systems have been developed to overcome these limitations. Nanomaterials are employed in a variety of biomedical applications such as therapeutics delivery, cancer therapy, and tissue engineering. Physiochemical nanoparticle assembly techniques involve the application of solvents and potentially harmful chemicals, commonly at high temperatures. Genetically engineered organisms have the potential to be used as promising candidates for greener, efficient, and more adaptable platforms for the synthesis and assembly of nanomaterials. Genetically engineered carriers are precisely designed and constructed in shape and size, enabling precise control over drug attachment sites. The high accuracy of these novel advanced materials, biocompatibility, and stimuli-responsiveness, elucidate their emerging application in controlled drug delivery. The current article represents the research progress in developing various genetically engineered carriers. Organic-based nanoparticles including cellulose, collagen, silk-like polymers (SLP), elastin-like protein (ELP), silk-like elastane (SELP), and inorganic-based nanoparticles are discussed in detail. Afterwards, viral-based carriers are classified, and their potential for targeted therapeutics delivery is highlighted. Finally, the challenges and prospects of these delivery systems are concluded. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202201583DOI Listing
August 2022
-->