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1.
J Environ Manage ; 356: 120446, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484595

RESUMO

There is a serious concern about the large amount of accumulated plastic waste all around the world. Synthetic polymers such as polyethylene terephthalate (PET), polypropylene (PP), and polyethylene (HDPE, LDPE) are substantially present in the plastic waste generated. There are various methods reported to minimise such plastics waste with certain limitations. To overcome such limitations the present study have been carried out in which thermal decomposition of plastic waste of PET, PP, HDPE, and LDPE studied using a novel plasma pyrolysis reactor. The major objective of this work is to investigate the viability of the continuous plasma pyrolysis process for the treatment of various plastic wastes with respect to waste volume reduction and production of combustible hydrogen-rich fuel gas. The effect of temperature and feed flow rate on product gas yield, product gas efficiency, solid residue yield, and H2/CO ratio has been evaluated. The experiments have been carried out at different temperatures within the range of 700-1000 °C. Plasma pyrolysis system exhibited combustible hydrogen-rich gas as a product and solid residue. Liquid products have not been observed during plasma pyrolysis, unlike conventional pyrolysis. The reaction mechanism of plastic cracking has been discussed based on literature and products obtained in the present work. The effects of feed flow rate and temperature on exergy efficiency were studied using the response surface method. The mass, energy, and exergy analyses have also been carried out for all the experiments, which are in the range of 0.95-0.99, 0.48 to 0.77, and 0.30 to 0.69, respectively.


Assuntos
Plásticos , Polietileno , Polietileno/química , Plásticos/química , Hidrogênio , Pirólise , Polipropilenos/química , Polietilenotereftalatos
2.
J Vasc Interv Radiol ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38342221

RESUMO

PURPOSE: To investigate if combination therapy with immune checkpoint inhibitor (ICI) and yttrium-90 (90Y) radioembolization results in superior outcomes than those yielded by tyrosine kinase inhibitor (TKI) therapy and 90Y for the treatment of intermediate- to advanced-stage hepatocellular carcinoma (HCC). METHODS: A retrospective review of patients presented at an institutional multidisciplinary liver tumor board between January 1, 2012 and August 1, 2023 was conducted. In total, 44 patients with HCC who underwent 90Y 4 weeks within initiation of ICI or TKI therapy were included. Propensity score matching was conducted to account for baseline demographic differences. Kaplan-Meier analysis was used to compare median progression-free survival (PFS) and overall survival (OS), and univariate statistics identified disease response and control rate differences. Duration of imaging response was defined as number of months between the first scan after therapy and the first scan showing progression as defined by modified Response Evaluation Criteria in Solid Tumors (mRECIST) or immune Response Evaluation Criteria in Solid Tumors (iRECIST). Adverse events were analyzed per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Patients in the 90Y+ICI therapy group had better objective response rates (ORRs) (89.5% vs 36.8%; P < .001) and disease control rates (DCRs) (94.7% vs 63.2%; P < .001) by mRECIST and iRECIST (ORR: 78.9% vs 36.8%; P < .001; DCR: 94.7% vs 63.2%; P < .001). Median PFS (8.3 vs 4.1 months; P = .37) and OS (15.8 vs 14.3 months; P = .52) were not statistically different. Twelve patients (63.1%) in the 90Y+TKI group did not complete systemic therapy owing to adverse effects compared with 1 patient (5.3%) in the 90Y+ICI group (P < .001). Grade 3/4 adverse events were not statistically different (90Y+TKI: 21.1%; 90Y+ICI: 5.3%; P = .150). CONCLUSIONS: Patients with HCC who received 90Y+ICI had better imaging response and fewer regimen-altering adverse events than those who received 90Y+TKI. No significant combination therapy adverse events were attributable to radioembolization.

3.
Sci Rep ; 14(1): 4973, 2024 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424110

RESUMO

In China, circulating tumor DNA analysis is widely used and numerous assays are available. Systematic evaluation to help users make informed selections is needed. Nine circulating tumor DNA assays, including one benchmark assay, were evaluated using 23 contrived reference samples. There were two sample types (cell-free DNA and plasma samples), three circulating tumor DNA inputs (low, < 20 ng; medium, 20-50 ng; high, > 50 ng), two variant allele frequency ranges (low, 0.1-0.5%; intermediate, 0.5-2.5%), and four variant types (single nucleotide, insertion/deletion, structural, and copy number). Sensitivity, specificity, reproducibility, and all processes from cell-free DNA extraction to bioinformatics analysis were assessed. The test assays were generally comparable or superior to the benchmark assay, demonstrating high analytical sensitivity. Variations in circulating tumor DNA extraction and quantification efficiency, sensitivity, and reproducibility were observed, particularly at lower inputs. These findings will guide circulating tumor DNA assay choice for research and clinical studies, allowing consideration of multiple technical parameters.


Assuntos
Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias , Humanos , DNA Tumoral Circulante/genética , Reprodutibilidade dos Testes , Neoplasias/genética , DNA de Neoplasias/genética , Ácidos Nucleicos Livres/genética , Sequenciamento de Nucleotídeos em Larga Escala , Biomarcadores Tumorais/genética , Mutação
4.
Biomed Phys Eng Express ; 10(2)2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38277702

RESUMO

Background. Magnetocardiography (MCG) is a non-invasive and non-contact technique that measures weak magnetic fields generated by the heart. It is highly effective in the diagnosis of heart abnormalities. Multichannel MCG provides detailed spatio-temporal information of the measured magnetic fields. While multichannel MCG systems are costly, usage of the optimal number of measurement channels to characterize cardiac magnetic fields without any appreciable loss of signal information would be economically beneficial and promote the widespread use of MCG technology.Methods. An optimization method based on the sequential selection approach is used to choose channels containing the maximum signal information while avoiding redundancy. The study comprised 40 healthy individuals, along with two subjects having ischemic heart disease and one subject with premature ventricular contraction. MCG measured using a 37 channel MCG system. After revisiting the existing methods of optimization, the mean error and correlation of the optimal set of measurement channels with those of all 37 channels are evaluated for different sets, and it has been found that 18 channels are adequate.Results. The chosen 18 optimal channels exhibited a strong correlation (0.99 ± 0.006) between the original and reconstructed magnetic field maps for a cardiac cycle in healthy subjects. The root mean square error is 0.295 pT, indicating minimal deviation.Conclusion. This selection method provides an efficient approach for choosing MCG, which could be used for minimizing the number of channels as well as in practical unforeseen measurement conditions where few channels are noisy during the measurement.


Assuntos
Magnetocardiografia , Complexos Ventriculares Prematuros , Humanos , Magnetocardiografia/métodos , Análise Custo-Benefício , Coração , Eletrocardiografia
5.
Int J Toxicol ; 43(2): 184-195, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38108647

RESUMO

Electrocardiographic evaluation is performed in rhesus monkeys to establish the cardiovascular safety of candidate molecules before progressing to clinical trials. These animals are usually immobilized chemically by ketamine (KTM) and tiletamine-zolazepam (TZ) to obtain a steady-state heart rate and to ensure adequate human safety. The present study aimed to evaluate the effect of these anesthetic regimens on different electrocardiographic parameters. Statistically significant lower HR and higher P-wave duration, RR, QRS, and QT intervals were observed in the KTM-anesthetized group in comparison to TZ-anesthetized animals. No significant changes were noticed in the PR interval and p-wave amplitude. Sex-based significance amongst these parameters was observed in male and female animals of TZ- and KTM-anesthetized groups. Regression analysis of four QTc formulas in TZ-anesthetized rhesus monkeys revealed that QTcNAK (Nakayama) better corrected the QT interval than QTcHAS (Hassimoto), QTcBZT (Bazett), and QTcFRD (Fridericia) formulas. QTcNAK exhibited the least correlation with the RR interval (slope closest to zero and r = .01) and displayed no statistical significance between male and female animals. These data will prove useful in the selection of anesthetic regimens for chemical restraint of rhesus monkeys in nonclinical safety evaluation studies.


Assuntos
Anestésicos , Ketamina , Animais , Humanos , Masculino , Feminino , Ketamina/toxicidade , Tiletamina/toxicidade , Macaca mulatta , Zolazepam/toxicidade , Estudos Retrospectivos , Anestésicos/toxicidade , Frequência Cardíaca
6.
J Med Syst ; 48(1): 7, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38157145

RESUMO

Virtual assistants (VAs) are conversational agents that are able to provide cognitive aid. We developed a VA device for donning and doffing personal protective equipment (PPE) procedures and compared it to live human coaching to explore the feasibility of using VAs in the anesthesiology setting. An automated, scalable, voice-enabled VA was built using the Amazon Alexa device and Alexa Skills application. The device utilized voice-recognition technology to allow a touch-free interactive user experience. Audio and video step-by-step instructions for proper donning and doffing of PPE were programmed and displayed on an Echo Show device. The effectiveness of VA in aiding adherence to PPE protocols was compared to traditional human coaching in a randomized, controlled, single-blinded crossover design. 70 anesthesiologists, anesthesia assistants, respiratory therapists, and operating room nurses performed both donning and doffing procedures, once under step-by-step VA instructional guidance and once with human coaching. Performance was assessed using objective performance evaluation donning and doffing checklists. More participants in the VA group correctly performed the step of "Wash hands for 20 seconds" during both donning and doffing tests. Fewer participants in the VA group correctly performed the steps of "Put cap on and ensure covers hair and ears" and "Tie gown on back and around neck". The mean doffing total score was higher in the VA group; however, the donning score was similar in both groups. Our study demonstrates that it is feasible to use commercially available technology to create a voice-enabled VA that provides effective step-by-step instructions to healthcare professionals.


Assuntos
Anestesiologia , Humanos , Pessoal de Saúde , Equipamento de Proteção Individual , Roupa de Proteção , Estudos Cross-Over , Método Simples-Cego
7.
ACS Omega ; 8(36): 33069-33082, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37720740

RESUMO

The current research involves the synthesis of a new Schiff base through the reaction between 2-chlorobenzaldehyde and 3,3'-dimethyl-[1,1'-biphenyl]-4,4'-diamine by using a natural acid catalyst and a synthesized compound physicochemically characterized by X-ray diffraction, Fourier transform infrared spectroscopy, 1H- and 13C-nuclear magnetic resonance, and liquid chromatography-mass spectrometry. Thermal studies were conducted using thermogravimetric, differential thermal analysis, and differential thermogravimetric curves. These curves were obtained in an inert nitrogen environment from ambient temperature to 1263 K using heating rates of 10, 15, and 20 K·min-1. Using thermocurve data, model-free isoconversional techniques such as Kissinger-Akahira-Sunose, Flynn-Wall-Ozawa, and Friedman are used to determine kinetic parameters. These parameters include activation energy, phonon frequency factor, activation enthalpy, activation entropy, and Gibb's free energy change. All of the results have been thoroughly investigated. The molecule's anti-inflammatory and antidiabetic properties were also examined. To learn more about the potential of the Schiff base and how successfully it can suppress the amylase enzyme, a molecular docking experiment was also conducted. For in silico research, the Swiss Absorption, Distribution, Metabolism, Excretion, and Toxicity algorithms were used to calculate the theoretical pharmacokinetic properties, oral bioavailability, toxic effects, and biological activities of the synthesized molecule. Moreover, the cytotoxicity tests against a human lung cancer cell line (A549) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that the synthesized Schiff base exhibited significant anticancer properties.

8.
Front Plant Sci ; 14: 1220339, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711311

RESUMO

Aedes mosquitoes are the major cause of several vector-borne diseases in tropical and subtropical regions. Synthetic pesticides against these mosquitoes have certain limitations; hence, natural, eco-friendly, and safe larvicides obtained from plant resources are used to overcome these. In the present study, the larvicidal efficiency of Commiphora wightii against the fourth instar stage of the dengue fever mosquito Aedes aegypti (Linnaeus, 1762) was studied. The gum resin of C. wightii was collected using the borehole tapping method, and hexane extracts in different concentrations were prepared. The fourth-instar larvae were exposed to the extracts, and percent mortality, as well as LC20, LC50, and LC90, was calculated. Volatile compounds of the hexane gum extract were analyzed by Headspace GC/MS, and the sequence of the acetylcholine, Gamma-aminobutyric acid (GABA) receptor, and octopamine receptor subunit of A. aegypti was obtained. It was found that the hexane gum extract was toxic and lethal for larvae at different concentrations. Minimum mortality was observed at 164 µg mL-1 (10%/h), while maximum mortality was at 276 µg mL-1 (50%/h). The lethal concentrations LC20, LC50, and LC90 were 197.38 µg mL-1, 294.13 µg mL-1, and 540.15 µg mL-1, respectively. The GC/MS analysis confirmed the presence of diterpenes, monoterpenes, monoterpene alcohol, and sesquiterpenes in the gum samples, which are lethal for larvae due to their inhibitory activity on the acetylcholinesterase enzyme, GABA receptor, and octopamine receptor subunit. The use of commonly occurring plant gum for the control of mosquitoes was explored, and it was found that the gum of C. wightii had larvicidal activities and could be potentially insecticidal.

9.
Microorganisms ; 11(8)2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37630590

RESUMO

Cholera, a disease caused by the Vibrio cholerae bacteria, threatens public health worldwide. The organism mentioned above has a significant historical record of being identified as a prominent aquatic environmental pollutant capable of adapting its phenotypic and genotypic traits to react to host patients effectively. This study aims to elucidate the heterogeneity of the sporadic clinical strain of V. cholerae VC01 among patients residing in Silvasa. The study involved conducting whole-genome sequencing of the isolate obtained from patients exhibiting symptoms, including those not commonly observed in clinical practice. The strain was initially identified through a combination of biochemical analysis, microscopy, and 16s rRNA-based identification, followed by type strain-based identification. The investigation demonstrated the existence of various genetic alterations and resistance profiles against multiple drugs, particularly chloramphenicol (catB9), florfenicol (floR), oxytetracycline (tet(34)), sulfonamide (sul2), and Trimethoprim (dfrA1). The pan-genomic analysis indicated that 1099 distinct clusters were detected within the genome sequences of recent isolates worldwide. The present study helps to establish a correlation between the mutation and the coexistence of antimicrobial resistance toward current treatment.

10.
Am J Physiol Gastrointest Liver Physiol ; 325(4): G334-G346, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37489865

RESUMO

Carbamoyl phosphate synthetase 1 (CPS1) is the most abundant hepatocyte mitochondrial matrix protein. Hypoosmotic stress increases CPS1 release in isolated mouse hepatocytes without cell death. We hypothesized that increased CPS1 release during hypoosmosis is selective and associates with altered mitochondrial morphology. Both ex vivo and in vivo models were assessed. Mouse hepatocytes and livers were challenged with isotonic or hypoosmotic (35 mosM) buffer. Mice were injected intraperitoneally with water (10% body weight) with or without an antidiuretic. Mitochondrial and cytosolic fractions were isolated using differential centrifugation, then analyzed by immunoblotting to assess subcellular redistribution of four mitochondrial proteins: CPS1, ornithine transcarbamylase (OTC), pyrroline-5-carboxylate reductase 1 (PYCR1), and cytochrome c. Mitochondrial morphology alterations were examined using electron microscopy. Hypoosmotic treatment of whole livers or hepatocytes led to preferential or increased mitochondrial release, respectively, of CPS1 as compared with two mitochondrial matrix proteins (OTC/PYCR1) and with the intermembrane space protein, cytochrome c. Mitochondrial apoptosis-induced channel opening using staurosporine in hepatocytes led to preferential CPS1 and cytochrome c release. The CPS1-selective changes were accompanied by dramatic alterations in ultrastructural mitochondrial morphology. In mice, hypoosmosis/hyponatremia led to increased liver vascular congestion and increased CPS1 in bile but not blood, coupled with mitochondrial structural alterations. In contrast, isotonic increase of intravascular volume led to a decrease in mitochondrial size with limited change in bile CPS1 compared with hypoosmotic conditions and absence of the hypoosmosis-associated histological alterations. Taken together, hepatocyte CPS1 is selectively released in response to hypoosmosis/hyponatremia and provides a unique biomarker of mitochondrial injury.NEW & NOTEWORTHY Exposure of isolated mouse livers, primary cultured hepatocytes, or mice to hypoosmosis/hyponatremia conditions induces significant mitochondrial shape alterations accompanied by preferential release of the mitochondrial matrix protein CPS1, a urea cycle enzyme. In contrast, the intermembrane space protein, cytochrome c, and two other matrix proteins, including the urea cycle enzyme ornithine transcarbamylase, remain preferentially retained in mitochondria. Therefore, hepatocyte CPS1 manifests unique mitochondrial stress response compartmentalization and is a sensitive sensor of mitochondrial hypoosmotic/hyponatremic injury.


Assuntos
Hiponatremia , Hepatopatias , Animais , Camundongos , Carbamoil-Fosfato/metabolismo , Ornitina Carbamoiltransferase/metabolismo , Citocromos c/metabolismo , Hiponatremia/metabolismo , Hiponatremia/patologia , Hepatócitos/metabolismo , Carbamoil-Fosfato Sintase (Amônia)/metabolismo , Hepatopatias/metabolismo , Mitocôndrias/metabolismo , Ureia/metabolismo
11.
J Environ Manage ; 344: 118335, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37329581

RESUMO

Energy security and waste management are gaining global attention. The modern world is producing a large amount of liquid and solid waste as a result of the increasing population and industrialization. A circular economy encourages the conversion of waste to energy and other value-added products. Waste processing requires a sustainable route for a healthy society and clean environment. One of the emerging solutions for waste treatment is plasma technology. It converts waste into syngas, oil, and char/slag depending on the thermal/non-thermal processes. Most of all the types of carbonaceous wastes can be treated by plasma processes. The addition of a catalyst to the plasma process is a developing field as plasma processes are energy intensive. This paper covers the detailed concept of plasma and catalysis. It comprises various types of plasma (non-thermal and thermal) and catalysts (zeolites, oxides, and salts) which have been used for waste treatment. Catalyst addition improves gas yield and hydrogen selectivity at moderate temperatures. Depending on the properties of the catalyst and type of plasma, comprehensive points are listed for the selection of the right catalyst for a plasma process. This review offers an in-depth analysis of the research in the field of waste-to-energy using plasma-catalytic processes.


Assuntos
Resíduos Sólidos , Gerenciamento de Resíduos , Resíduos Sólidos/análise , Tecnologia , Catálise , Conservação dos Recursos Naturais
12.
Environ Monit Assess ; 195(6): 649, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37160469

RESUMO

Diversity lifts the productivity of any ecosystem as all the species have a vital role to play that is present within the ecosystem. The characterization is essential to delve into the ecological functions of microbial communities and discover the type of microorganisms present within the ecosystem. As microbial diversity in ecosystems responds to environmental disturbances, it functions as a marker to indicate the change in such ecosystems. Mine ecology differs significantly from other habitats due to the presence of acidic runoff. This paper provides insight into the diversity of cultivable bacteria isolated from lignite mines located in south Gujarat. A total of 67 heterotrophic isolates were successfully cultivated from the collected solid and water samples of the Rajpardi and Tadkeshwar Lignite mine sites. The isolates were characterized morphologically and biochemically, and intra- and extracellular enzyme synthesis were studied. Moreover, the relative density and frequency of cultivated isolates from the samples were calculated. The similarity and evenness of the heterotrophic isolated were studied by calculating diversity indices such as Shannon and Simpson. Alpha diversity was calculated in PAST software to analyse the similarity between the selected two mine sites. This research also explored the relationship between the variance in heterotrophic microbial diversity and substrate utilization richness of the studied lignite mines of Gujarat.


Assuntos
Monitoramento Ambiental , Microbiota , Bactérias , Software
13.
Front Genet ; 14: 1119740, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37197021

RESUMO

A major part of any biological system on earth involves microorganisms, of which the majority are yet to be cultured. The conventional methods of culturing microbes have given fruitful outcomes yet have limitations. The curiosity for better understanding has led to the development of culture-independent molecular methods that help push aside the roadblocks of earlier methods. Metagenomics unifies the scientific community in search of a better understanding of the functioning of the ecosystem and its component organisms. This approach has opened a new paradigm in advanced research. It has brought to light the vast diversity and novelty among microbial communities and their genomes. This review focuses on the development of this field over time, the techniques and analysis of data generated through sequencing platforms, and its prominent interpretation and representation.

14.
Int J Biol Macromol ; 238: 124051, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-36933597

RESUMO

Non-aqueous enzymology has always drawn attention due to the wide range of unique possibilities in biocatalysis. In general, the enzymes do not or insignificantly catalyze substrate in the presence of solvents. This is due to the interfering interactions of the solvents between enzyme and water molecules at the interface. Therefore, information about solvent-stable enzymes is scarce. Yet, solvent-stable enzymes prove quite valuable in the present day biotechnology. The enzymatic hydrolysis of the substrates in solvents synthesizes commercially valuable products, such as peptides, esters, and other transesterification products. Extremophiles, the most valuable yet not extensively explored candidates, can be an excellent source to investigate this avenue. Due to inherent structural attributes, many extremozymes can catalyze and maintain stability in organic solvents. In the present review, we aim to consolidate information about the solvent-stable enzymes from various extremophilic microorganisms. Further, it would be interesting to learn about the mechanism adapted by these microorganisms to sustain solvent stress. Various approaches to protein engineering are used to enhance catalytic flexibility and stability and broaden biocatalysis's prospects under non-aqueous conditions. It also describes strategies to achieve optimal immobilization with minimum inhibition of the catalysis. The proposed review would significantly aid our understanding of non-aqueous enzymology.


Assuntos
Extremófilos , Solventes/química , Extremófilos/metabolismo , Biotecnologia , Engenharia de Proteínas , Biocatálise , Enzimas/metabolismo
15.
Am J Perinatol ; 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36858070

RESUMO

OBJECTIVE: This study aimed to investigate pregnancy rate, pregnancy outcomes, and resumption of menses after transcatheter arterial embolization (TAE) for obstetric hemorrhage (OH). STUDY DESIGN: Sixty-seven patients who underwent TAE for OH from 2006 to 2020 within an urban, multihospital health care system were identified retrospectively. Selected patients were interviewed by phone to complete a survey with a primary outcome of self-reported pregnancy in those seeking pregnancy. Secondary outcomes included pregnancy outcomes and resumption of menses. Univariate testing of association of pregnancy and miscarriage rate with embolic agent was performed using Fisher's exact test. RESULTS: Thirty-three of 50 patients (66%) meeting the inclusion criteria completed the survey on fertility, a median of 47 (range, 13-123) months after TAE for OH. Of the 13 patients who attempted pregnancy, there was a pregnancy rate of 77% and miscarriage rate of 38%. Those who delivered live newborns conceived spontaneously, carried to term, and delivered a healthy newborn via cesarean section at a weight appropriate for gestational age. Thirty (91%) patients resumed menstruation, and the majority with unchanged frequency. Most patients underwent bilateral uterine artery embolization with radial artery access (54%). The most common embolic agents used were gelfoam only (30%) and glue only (24%). There was no statistically significant association between embolic agent and pregnancy or miscarriage rate. CONCLUSION: Spontaneous pregnancy with live birth and resumption of menses can occur in a majority of patients after TAE for OH. KEY POINTS: · Most patients who attempted pregnancy after TAE for OH achieved pregnancy.. · Most patients who became pregnant conceived spontaneously and delivered healthy newborns at term.. · Most patients resumed menstruation after TAE for OH.. · There was no significant association between type of embolic and pregnancy or miscarriage rate..

16.
Toxicol Mech Methods ; 33(6): 490-501, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36879461

RESUMO

Rhesus monkeys are a non-rodent species employed in the preclinical safety evaluation of pharmaceuticals and biologics. These nonhuman primate species have been increasingly used in biomedical research because of the similarity in their ionic mechanisms of repolarization with humans. Heart rate and QT interval are two primary endpoints in determining the pro-arrhythmic risk of drugs. As heart rate and QT interval have an inverse relationship, any change in heart rate causes a subsequent change in QT interval. This warrants for calculation of a corrected QT interval. This study aimed to identify an appropriate formula that best corrected QT for change in heart rate. We employed seven formulas based on source-species type, clinical relevance, and requirements of various international regulatory guidelines. Data showed that corrected QT interval values varied drastically for different correction formulas. Equations were compared on their slope values based on QTc versus RR plots. The rank order of the slope for different formulas was (closest to farthest from zero) QTcNAK, QTcHAS, QTcBZT, QTcFRD, QTcVDW, QTcHDG, and QTcFRM. QTcNAK emerged to be the best correcting formula in this study. It showed the least correlation with the RR interval (r = -0.01) and displayed no significant difference amongst the sexes. As there is no universally recognized formula for preclinical use, the authors recommend developing a best-case scenario model for specific study designs and individual organizations. The data from this research will be helpful in deciding an appropriate QT correction formula for the safety assessment of new pharmaceuticals and biologics.


Assuntos
Ketamina , Síndrome do QT Longo , Animais , Humanos , Eletrocardiografia , Macaca mulatta , Ketamina/toxicidade , Frequência Cardíaca , Preparações Farmacêuticas , Síndrome do QT Longo/induzido quimicamente
17.
Clin Imaging ; 96: 26-30, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36738667

RESUMO

PURPOSE: To evaluate medical student engagement with Interventional Radiology (IR) before and after a virtual elective course. METHODS: The elective was nine, one-hour lectures over ten weeks. An anonymous pre and post-course survey was administered to students. The hypothesis was that this course would increase student engagement with IR. Respondents answered nine questions to score their interest in, exposure to, familiarity with, and understanding of IR using a five-point Likert scale. Demographics were reported for the pre-course group only. A Wilcoxon signed-ranked test was performed to assess for significant mean change in pre and post-course responses. Among the 276 registered students, there were 144 individual, complete responses for the pre-course survey, and 60 paired responses for both surveys. RESULTS: Thirty-seven percent of respondents were first or second year medical students. Thirty percent of participants were enrolled at an institution outside of the United States, 26% are the first in their family to attend college, and 41% identified as female. Thirty-six percent reported this virtual course was one of their earliest experiences with IR. There was a significant increase in student exposure to IR generally, familiarity with IR compared to other specialties, familiarity with the IR training pathway(s), understanding of what an Interventional Radiologist does, understanding of the difference between IR and Diagnostic Radiology, and understanding of when to consult IR for patient care after completion of the course. CONCLUSION: A virtual IR elective is an effective means to increase exposure to, familiarity with, and understanding of IR.


Assuntos
Educação a Distância , Estudantes de Medicina , Humanos , Feminino , Radiologia Intervencionista/educação , Currículo , Inquéritos e Questionários
18.
Foods ; 12(3)2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36766059

RESUMO

Several commercially important botanicals have a lack of diagnostic testing options that can quickly and unambiguously identify materials of different matrices. Real-time PCR can be a useful, orthogonal approach to identification for its exceptional specificity and sensitivity. Carica papaya L. is a species with a lack of available identification methods, and one which features two distinct commercially relevant matrices: fresh fruit and powdered fruit extract. In this study, we demonstrate the successful design and validation of a real-time PCR assay for detection of papaya DNA extracted from the two matrices. We also propose a technique that can be used during exclusivity panel construction, when genuine botanical samples are not available for certain species: substitution with synthetic DNA. We demonstrate the use of this material to complete a comprehensive specificity evaluation and confidently determine suitable Ct cutoff values. Further, we demonstrate how ddPCR can be used to determine the copy number of the target sequence in a set amount of genomic DNA, to which synthetic DNA samples can be corrected, and how it can verify specificity of the primers and probe. Through the presentation of successful assay validation for papaya detection, this work serves as a guideline for how to approach specificity evaluation when non-target botanical samples are difficult to obtain and otherwise may not have been included in the exclusivity panel.

19.
iScience ; 26(1): 105821, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36632058

RESUMO

The hybrid renewable energy system (HRES) can overcome the problem of the mismatch of supply of variable renewable energies and demand. The optimal sizing of the HRES methodology is implemented by employing the generalized reduced gradient (GRG) method. A case study of HRES with solar, bio, and hydro sources for tribal areas in a hilly region of India is demonstrated. Both the grid-connected scenario and the standalone scenario in island mode are simulated. The optimal LCOE of 0.106-0.053 $/kWh is achieved in standalone mode for 100%-70% reliability. The grid-connected scenario is simulated with two different rates of payment for the electric energy delivered to the grid and a range of grid purchase prices. The LCOE results to around 0.06 $/kWh for the prospective grid-connected mode cases. The sensitivity analysis and validation of the work are also performed.

20.
J Biomol Struct Dyn ; 41(7): 3089-3109, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35220906

RESUMO

Prostate cancer has been recently considered the most diagnosed cancer in male. DLL3 is overexpressed in CRPC-NE but not in localised prostate cancer or BPH. There are no effective treatments for neuroendocrine differentiated prostate cancer due to a lack of understanding of DLL3 structure and function. The structure of DLL3 is not yet determined using any experimental techniques. Hence, the structure-based drug discovery approach against prostate cancer has not shown great success. In present study, molecular modelling techniques were employed to generate three-dimensional structure of DLL3 and performed its thorough structural analysis. Further, all-atom molecular dynamics simulation was performed to obtain energetically favourable conformation. Further, we used a virtual screening using a library of >13800 phytochemicals from the IMPPAT database and other literature to select the best possible phytochemical inhibitor for DLL3 and identified the top five compounds. Relative binding affinity was calculated using the MM-PBSA approach. ADMET properties of the screened compounds reveal the toxic effect of Gnemonol C. We believe these studied physicochemical properties, functional domain identification, and binding site identification would be very useful to gain more structural and functional insights of DLL3; also, it can be used to infer their pharmacodynamics properties of DLL3 which was recently reported as an important prostate cancer target. The current study also proposes that Ergosterol Peroxide, Dioslupecin A, Mulberrofuran K, and Caracurine V have strong affinities and could serve as plausible inhibitors against DLL3. We believe this study would further help develop better drug candidates against neuroendocrine prostate cancer.Communicated by Ramaswamy H. Sarma.


Assuntos
Simulação de Dinâmica Molecular , Neoplasias da Próstata , Masculino , Humanos , Simulação de Acoplamento Molecular , Sítios de Ligação , Descoberta de Drogas , Proteínas de Membrana/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular
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