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1.
J Visc Surg ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38964939

RESUMO

BACKGROUND: With steep posterior anorectal angulation, transanal total mesorectal excision (taTME) may have a risk of dissection in the wrong plane or starting higher up, resulting in leaving distal mesorectum behind. Although the distal mesorectal margin can be assessed by preoperative MRI, it needs skilled radiologist and high-definition image for accurate evaluation. This study developed a deep neural network (DNN) to predict the optimal level of distal mesorectal margin. METHODS: A total of 182 pelvic MRI images extracted from the cancer image archive (TCIA) database were included. A DNN was developed using gender, the degree of anterior and posterior anorectal angles as input variables while the difference between anterior and posterior mesorectal distances from anal verge was selected as a target. The predictability power was assessed by regression values (R) which is the correlation between the predicted outputs and actual targets. RESULTS: The anterior angle was an obtuse angle while the posterior angle varied from acute to obtuse with mean angle difference 35.5°±14.6. The mean difference between the anterior and posterior mesorectal end distances was 18.6±6.6mm. The developed DNN had a very close correlation with the target during training, validation, and testing (R=0.99, 0.81, and 0.89, P<0.001). The predicted level of distal mesorectal margin was closely correlated with the actual optimal level (R=0.91, P<0.001). CONCLUSIONS: Artificial intelligence can assist in either making or confirming the preoperative decisions. Furthermore, the developed model can alert the surgeons for this potential risk and the necessity of re-positioning the proctectomy incision.

2.
BMC Plant Biol ; 24(1): 632, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970019

RESUMO

BACKGROUND: The myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress. RESULTS: In this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage. CONCLUSION: The results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.


Assuntos
Avena , Secas , Homeostase , Filogenia , Proteínas de Plantas , Espécies Reativas de Oxigênio , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Avena/genética , Avena/metabolismo , Regulação da Expressão Gênica de Plantas , Polietilenoglicóis/farmacologia , Família Multigênica , Estresse Fisiológico/genética , Estudo de Associação Genômica Ampla , Genoma de Planta
3.
Sci Rep ; 14(1): 15415, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965307

RESUMO

Sarcasm is a perplexing form of human expression that presents distinct challenges in understanding. The problem of sarcasm detection has centered around analyzing individual utterances in isolation which may not provide a comprehensive understanding of the speaker's sarcastic intent. Our work addresses this problem by exploring and understanding the specific contextual cues that contribute to sarcasm. In this paper, we propose an enhanced approach for sarcasm detection using contextual features. Our methodology involves employing pre-trained transformer models, RoBERTa and DistilBERT, and fine-tuning them on two datasets: the News Headlines and the Mustard datasets. Incorporating contextual information, the proposed approach yielded the best performance, achieving an impressive F1 score of 99% on News Headlines dataset and 90% on Mustard dataset. Moreover, we experimented summarizing the context into a concise short sentence. This enhancement reduced training time by 35.5% of the original time. We further validated the model trained on the News headlines dataset against the Reddit dataset, which resulted in 49% F1 score without context data. However, with the inclusion of context data, the F1 score surged to 75%. Proposed approach enhances the understanding of sarcasm in different contextual settings, enabling more accurate sentiment analysis and better decision-making in various applications.


Assuntos
Algoritmos , Senso de Humor e Humor como Assunto , Humanos
4.
Egypt Heart J ; 76(1): 89, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976090

RESUMO

BACKGROUND: Persistent Atrial Fibrillation (PeAF) is a challenging case for rhythm control modalities. Catheter ablation is the mainstay in PeAF management; however, data regarding the comparative safety and efficacy of cryoballoon ablation (CBA) versus radiofrequency ablation (RFA) for PeAF is still limited. We aim to compare the safety and efficacy of CBA versus RFA for PeAF ablation. METHODS: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane through October 2023. RevMan version 5.4 software was used to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: CRD42023480314. RESULTS: Three RCTs with 400 patients were included. There was no significant difference between RFA and CBA regarding AF recurrence (RR: 0.77, 95% CI [0.50, 1.20], P = 0.25), atrial tachycardia or atrial flutter recurrence (RR: 0.54, 95% CI [0.11, 2.76], P = 0.46), and any arrhythmia recurrence (RR: 0.96, 95% CI [0.70, 1.31], P = 0.80). CBA was significantly associated with decreased total procedure duration (MD: - 45.34, 95% CI [- 62.68, - 28.00], P < 0.00001), with no significant difference in fluoroscopy duration (MD: 3.59, 95% CI [- 5.13, 12.31], P = 0.42). Safety parameters were similar in both groups, including the incidence of any complications, phrenic nerve palsy (RR: 2.91 with 95% CI [0.31, 27.54], P = 0.35), access site complications (RR: 0.33 with 95% CI [0.05, 2.03], P = 0.23), and pericardial effusion. CONCLUSIONS: In PeAF catheter ablation, CBA is comparable to RFA in terms of safety and efficacy. Also, CBA is associated with a shorter total procedure duration.

5.
J Exp Bot ; 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39031128

RESUMO

The plant cuticle is a complex extracellular lipid barrier that has multiple protective functions. We investigated cuticle deposition by integrating metabolomics and transcriptomics data gathered from six different maize seedling organs of four genotypes, the inbred lines B73 and Mo17, and their reciprocal hybrids. These datasets captured the developmental transition of the seedling from heterotrophic skotomorphogenic growth to autotrophic photomorphogenic growth, which is a transition that is highly vulnerable to environmental stresses. Statistical interrogation of these data reveals that the predominant determinant of cuticle composition is seedling organ type, whereas the seedling genotype has a smaller effect on this phenotype. Gene-to-metabolite associations assessed by integrated statistical analyses identified three gene networks connected with the deposition of different elements of the cuticle: a) cuticular waxes; b) monomers of lipidized cell wall biopolymers, including cutin and suberin; and c) both of these elements. These gene networks reveal three metabolic programs that appear to support cuticle deposition, including processes of chloroplast biogenesis, lipid metabolism, and molecular regulation (e.g., transcription factors, post-translational regulators and phytohormones). This study demonstrates the wider physiological metabolic context that can determine cuticle deposition and lays the groundwork for new targets for modulating properties of this protective barrier.

6.
Alcohol ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39009173

RESUMO

Yearly adult per capita consumption of alcohol in China between 2016 and 2019 decreased by 2.4 litres of pure alcohol, or 33%. According to the World Health Organization, this decrease in consumption was accompanied by reductions in alcohol-attributable mortality of 23% between 2015 and 2019. This paper examines the contribution of alcohol control policies in China to these public health gains. A systematic search of the literature was conducted on alcohol control policies and their effectiveness in China as part of a larger search of all countries in WHO Western Pacific Region. In addition to articles on empirical evidence on the impact of such alcohol control policies, we also searched for reviews. The plausibility of changes of traditional alcohol control policies (taxation increases, availability restrictions, restriction on advertisement and marketing, drink-driving laws, screening and brief interventions) in explaining reductions of consumption levels and attributable mortality rates was explored. There was some progress in the successful implementation of strict drink-driving policies, which could explain reductions in traffic injuries, including fatalities. Other traditional alcohol control policies seem to have played a minimal role in reducing alcohol consumption and attributable harms during the time period 2016-2019. However, an anti-corruption campaign was extensive enough to have substantially contributed to these reductions. The campaign prohibited the consumption of alcoholic beverages in everyday life of government officials and thus contributed to a de-normalization of alcohol. While this anti-corruption campaign was the only policy to potentially explain marked decreases in levels of alcohol consumption and attributable mortality, more detailed research is required to determine exactly how the campaign achieved these decreases.

7.
Int J Mol Sci ; 25(13)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-39000565

RESUMO

The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, drug resistance, and treatment. This review investigates the potential of autophagy inhibition as a therapeutic strategy for cancer. A systematic search was conducted on Embase, PubMed, and Google Scholar databases from 1967 to 2024 to identify studies on autophagy inhibitors and their mechanisms in cancer therapy. The review includes original articles utilizing in vitro and in vivo experimental methods, literature reviews, and clinical trials. Key terms used were "Autophagy", "Inhibitors", "Molecular mechanism", "Cancer therapy", and "Clinical trials". Autophagy inhibitors such as chloroquine (CQ) and hydroxychloroquine (HCQ) have shown promise in preclinical studies by inhibiting lysosomal acidification and preventing autophagosome degradation. Other inhibitors like wortmannin and SAR405 target specific components of the autophagy pathway. Combining these inhibitors with chemotherapy has demonstrated enhanced efficacy, making cancer cells more susceptible to cytotoxic agents. Clinical trials involving CQ and HCQ have shown encouraging results, although further investigation is needed to optimize their use in cancer therapy. Autophagy exhibits a dual role in cancer, functioning as both a survival mechanism and a cell death pathway. Targeting autophagy presents a viable strategy for cancer therapy, particularly when integrated with existing treatments. However, the complexity of autophagy regulation and the potential side effects necessitate further research to develop precise and context-specific therapeutic approaches.


Assuntos
Antineoplásicos , Autofagia , Neoplasias , Humanos , Autofagia/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Hidroxicloroquina/farmacologia
8.
Bioorg Med Chem ; 110: 117826, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39004050

RESUMO

Design, synthesis, and biological evaluation of two series of O4'-benzyl-hispidol derivatives and the analogous corresponding O3'-benzyl derivatives aiming to develop selective monoamine oxidase-B inhibitors endowed with anti-neuroinflammatory activity is reported herein. The first O4'-benzyl-hispidol derivatives series afforded several more potentially active and MAO-B inhibitors than the O3'-benzyl derivatives series. The most potential compound 2e of O4'-benzyl derivatives elicited sub-micromolar MAO-B IC50 of 0.38 µM with a selectivity index >264 whereas most potential compound 3b of O3'-benzyl derivatives showed only 0.95 MAO-B IC50 and a selectivity index >105. Advancement of the most active compounds showing sub-micromolar activities to further cellular evaluations of viability and induced production of pro-neuroinflammatory mediators confirmed compound 2e as a potential lead compound inhibiting the production of the neuroinflammatory mediator nitric oxide significantly by microglial BV2 cells at 3 µM concentration without significant cytotoxicity up to 30 µM. In silico molecular docking study predicted plausible binding modes with MAO enzymes and provided insights at the molecular level. Overall, this report presents compound 2e as a potential lead compound to develop potential multifunctional compounds.

9.
Luminescence ; 39(7): e4824, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39004773

RESUMO

Dabigatran (DBG), marketed as Pradaxa, is an anticoagulant medication prescribed for the treatment and mitigation of blood clots and to lower the risk of stroke in individuals with the heart condition known as atrial fibrillation. This medication is specifically indicated for preventing blood clots post hip or knee replacement surgeries and in patients with a prior history of clots. Compared to warfarin, dabigatran serves as a viable alternative that does not necessitate routine blood monitoring tests. The complimentary benefits associated with SALL (salting-out assisted liquid-liquid extraction) and the fluorogenic capabilities of benzofurazan. These methods were combined to provide an affordable and sensitive DBG assaying method. The spectral strength of the yellow luminous product was examined at 533.8 nm and by adjustment of a wavelength of 474.7 nm for excitation. To assess its linearity, the calibration chart was tested across a DBG concentration range of 30-500 ng/ml. Via accurate computation based on ICH, the detection limit (LD) was determined to be 9.5 ng/ml, and the strategy can quantify the DBG to a limit of 28 ng/ml. To ensure success, various crucial parameters for method implementation have been extensively studied and adapted. The validation of the strategy adhered to the policies outlined by ICH, affirming its precision in quantifying DBG in capsules. Furthermore, the inclusion of SALLE steps facilitated accurate monitoring of DBG in plasma samples, introducing a unique and advanced methodology for analyzing this compound in biological samples.


Assuntos
Anticoagulantes , Cápsulas , Dabigatrana , Dabigatrana/sangue , Dabigatrana/química , Dabigatrana/farmacologia , Humanos , Anticoagulantes/química , Anticoagulantes/sangue , Anticoagulantes/farmacologia , Corantes Fluorescentes/química , Extração Líquido-Líquido , Espectrometria de Fluorescência , Limite de Detecção , 4-Cloro-7-nitrobenzofurazano
10.
BMC Med Educ ; 24(1): 754, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997722

RESUMO

INTRODUCTION: Achieving integration in medical curricula without redundancy in basic medical sciences disciplines is a substantial challenge. Introducing co-teaching in such curricula with active inter-disciplinary participation is believed to best utilize the teaching and learning time for instructors and students, to motivate the students, and to provide a more robust base for bridging the gap between basic and clinical medical sciences in medical schools. Additionally, including more than one student-centered activity in one session is expected to increase the students' involvement and improve the retention of knowledge. Our study aims at minimizing redundancy and improving the students' motivation in learning the topic "insulin-glucose regulation" during the Endocrine and Metabolism module taught to year three students at Galala University, Faculty of Medicine in Egypt. METHODS: The authors designed a 3-hr co-teaching integrated session with 3 basic medical sciences aimed to explain the clinical terms including online accessed pre/post-tests, small student groups-created pre/post-session MCQ, with co-sharing of students in the introduction of scientific materials. RESULTS: The students' scores in the post-test showed that they gained more knowledge compared to before. Interestingly, there was only an improvement in the students' performance in generating questions before and after the session, as well as in the integrated question in the end-of-semester exam, we suggest implementing this approach in other topics and modules in medical schools. It would also be favorable to follow up with the students taught using this approach and those taught differently to assess the effectiveness of this approach in a controlled manner. CONCLUSION: Integrated sessions effectively increase student awareness of medical concepts and reduce redundancy in basic medical sciences. This approach exposes students to a more comprehensive understanding of the subject matter, improving their comprehension and retention. It is a valuable method for educators and instructors seeking to enhance their students' learning experience in the field of medical sciences.


Assuntos
Currículo , Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Egito , Estudantes de Medicina/psicologia , Avaliação Educacional , Ensino , Faculdades de Medicina
11.
Transplant Direct ; 10(8): e1665, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38988689

RESUMO

Background: The clinical success of liver transplantation has led to increased demand, requiring further expansion of the donor pool. Therapeutic interventions to optimize organs from donation after circulatory death (DCD) have significant potential to mitigate the organ shortage. Dysfunction in DCD liver grafts is mediated by microvascular thrombosis during the warm ischemic period, and strategies that reduce this thrombotic burden may improve graft function. We hypothesized that the administration of the fibrinolytic enzyme plasmin to the donor organ during the cold storage period would reduce the thrombotic burden and improve DCD liver graft function. Methods: In 2 separate cohorts, 32 syngeneic orthotopic rat liver transplants were performed in Lewis rats. Livers were procured from donors with 45 min of warm ischemic injury. Liver grafts were flushed with histidine-tryptophan-ketoglutarate preservation solution mixed with either plasmin (experimental group) or albumin (control group). All investigators were blinded to treatment group. After preparing the liver for implant using a modified cuff technique, the liver was stored for 1 h by static cold storage at 4 °C. Immediately before implantation, the liver graft was flushed, and this effluent was analyzed for fibrin degradation products to determine graft clot burden. Twenty-four hours following transplantation, animals were euthanized, and samples were collected. Results: Recipient survival was significantly higher for DCD liver grafts treated with plasmin compared with control. Moreover, histology of liver graft tissue immediately before implant reflected significantly reduced congestion in plasmin-treated livers (score, mean ± SD: 0.73 ±â€…0.59 versus 1.12 ±â€…0.48; P = 0.0456). The concentration of fibrin degradation products in the final flush before implantation was significantly reduced in plasmin-treated livers (743 ±â€…136 versus 10 919 ±â€…4642 pg/mL; P = 0.0001), reflecting decreased clot burden in the graft. Conclusions: The present study demonstrates that plasmin improves survival and may reduce thrombotic burden in DCD liver grafts with prolonged warm ischemic injury, meriting further study.

12.
J Family Med Prim Care ; 13(5): 1620-1627, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38948636

RESUMO

Diabetic ketoacidosis (DKA) is a life-threatening condition affecting individuals with diabetes characterised by hyperglycaemia, metabolic acidosis and ketonemia. The incidence and financial burden of DKA is still high. Thiamine deficiency is well documented in patients with DKA and could be associated with cardiac dysfunction in those patients. Thiamine deficiency leads to cardiac dysfunction, neuronal death and worsens the prognosis of DKA. There is an existing metabolic relationship between thiamine deficiency in diabetes, obesity and bariatric surgery. Careful monitoring of thiamine, along with other vitamins, is essential for diabetic patients, obese individuals and postbariatric surgery. Further research and clinical studies are urgently needed to assess the following: (1) Whether diabetes, obesity and bariatric surgery make individuals more prone to have DKA related to thiamine deficiency and (2) Whether supplementation of thiamine can protect diabetic patients, obese subjects and individuals undergoing bariatric surgery from DKA. This review summarises the biochemistry of thiamine and the existing metabolic relationships between thiamine deficiency in DKA, diabetes, obesity and bariatric surgery. Primary and family physicians have an important role in ensuring adequate replacement of thiamine in individuals with diabetes, obesity and bariatric surgery.

13.
Egypt J Immunol ; 31(3): 15-27, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38985531

RESUMO

The interleukin 13 (IL-13) gene single nucleotide polymorphisms (SNPs) are frequently linked to increased vulnerability to allergic asthma. Forkhead box protein P3 (FOXP3) is an important molecule in the formation of regulatory T cells (Treg). The genetic variants that alter FOXP3 function may have a role in the development of asthma and other allergic disorders. We aimed to determine the association of IL-13 rs20541, FOXP3 rs3761548 genes SNPs and serum levels of IL-13 with allergic asthma patients. In this case-control study, 41 Egyptian patients with allergic asthma were included. Age and gender matched. 41 normal volunteers were considered the controls. All subjects were examined for IL-13 rs20541 and FOXP3 rs3761548 SNPs by the polymerase chain reaction /restriction fragment length polymorphism technique. The serum level of IL-13 was assessed by the enzyme linked immunosorbent assay (ELISA). AA genotype at IL-13 rs20541 SNP was statistically significantly different between the studied groups (p= 0.042). Also, a statistically significant difference was detected when compared AA genotype to GG genotype as AA genotype was three times at risk for asthma (p1=0.031) (OR=3.95) and A allele increased the risk of asthma by about 3 times (OR=3.2). AA genotype at FOXP3 rs3761548 SNP was statistically significantly different between the studied groups (p=0.013). Also, a statistically significant difference was detected when compared AA genotype to CC genotype as AA genotype was 7 times at risk for asthma (p1=0.003) (OR=7.04) and A allele increased the risk of asthma by about 3 times (p<0.001) (OR=3.07). The serum level of IL-13 was statistically significant different between both groups (p<0.001). We can conclude that IL-13 could be a useful tool for predicting allergic asthma. Patients with AA genotype of IL-13 rs20541 and AA genotype of FOXP3 rs3761548 have a higher risk for developing allergic asthma.


Assuntos
Asma , Fatores de Transcrição Forkhead , Predisposição Genética para Doença , Genótipo , Interleucina-13 , Polimorfismo de Nucleotídeo Único , Humanos , Interleucina-13/genética , Interleucina-13/sangue , Asma/genética , Asma/sangue , Fatores de Transcrição Forkhead/genética , Masculino , Feminino , Egito , Estudos de Casos e Controles , Predisposição Genética para Doença/genética , Adulto , Alelos , Adolescente , Frequência do Gene , Adulto Jovem
15.
Egypt Heart J ; 76(1): 76, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888761

RESUMO

BACKGROUND: In heart failure with reduced ejection fraction (HFrEF), sodium-glucose co-transporter inhibitors (SGLT-2i) have persistently shown cardiovascular benefits through different trials. However, their impact on ventricular remodeling and cardiac hemodynamics has not been sufficiently studied. This study aimed to study how SGLT-2i initiation affects invasive hemodynamics and cardiac magnetic resonance imaging (CMR)-derived ventricular volumes, function, and fraction of the extracellular volume (ECV) in HFrEF patients with non-ischemic dilated cardiomyopathy (NIDCM). RESULTS: In this study, 23 patients with HFrEF and a mean age of 42, including 82.6% males, all have NIDCM and underwent right heart catheterization and CMR at the initiation of dapagliflozin and at 6-month follow-up. The addition of dapagliflozin resulted in significant reductions in the following invasive hemodynamic parameters compared to baseline: left ventricular end-diastolic pressure (23.4 vs 19.7 mmHg, p = 0.003), mean pulmonary artery pressure (31.3 vs 27.7 mmHg, p = 0.03), and systemic vascular resistance (18 vs 15 Wood units, p = 0.047). Among the studied CMR-derived measurements, only the percentage of extracellular volume fraction was significantly less at follow-up (33.7 vs 32.16%, p = 0.001). Additionally, functional class showed significant improvement with a notable reduction of the NT-proBNP level and a considerable decrease in diuretic dose (median: 40 vs 80 mg, p = 0.01). CONCLUSION: Adding dapagliflozin to patients with HFrEF due to NIDCM improved invasively measured hemodynamics and significantly reduced left ventricular extracellular volume fraction measured by CMR, with no significant change in ventricular volumes or ejection fraction.

17.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124596, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-38850823

RESUMO

People frequently administer Tizanidine (TIZ) to treat spasticity resulting from diseases like multiple sclerosis or spinal cord injuries. It also helps prevent muscle spasms. It helps to relax and release tense and stiff muscles by inhibiting specific nerve signals in the brain and spinal cord. The technique employed in this study made use of the unique ability of benzofurazan to confer fluorescent character when reacted with TIZ at specific conditions. This fluorogenic property was harnessed to evolve a remarkably sensitive, affordable, and selective method to quantify TIZ. The resulting yellow fluorescent product was observedat a wavelength beam of 532.9 nm, and an excitation wavelength beam of 474.9 nm was applied. By looking at the response across the TIZ concentration, the calibration chart's linearity was assessed in the range of 40-500 ng/mL. By computation, the approach's detection level (LOD) was determined to be 11.9 ng/mL, while the quantitation level was approximated to be 36 ng/mL. All pertinent factors impacting the strategy's efficacy were thoroughly inspected and adjusted accordingly. The proposed strategy was validated following the guidelines outlined by the ICH. The outcomes confirmed the method's capability for the accurate quantifying of TIZ in tablets, spiked plasma, and pharmaceutical assessing content uniformity.


Assuntos
Benzoxazóis , Clonidina , Limite de Detecção , Espectrometria de Fluorescência , Comprimidos , Clonidina/análogos & derivados , Clonidina/análise , Clonidina/sangue , Espectrometria de Fluorescência/métodos , Humanos , Benzoxazóis/química , Corantes Fluorescentes/química , Reprodutibilidade dos Testes , Calibragem , Concentração de Íons de Hidrogênio
18.
Sci Rep ; 14(1): 13014, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844777

RESUMO

Centrifugal water pumps account for more than 20% of energy use all over the world. Even a little increase in centrifugal pump operating efficiency may result in billions of dollars in savings each year and help reduce carbon dioxide emissions. This study creates a design tool that integrates one-dimensional equations and computational fluid dynamics (CFD) simulations to design centrifugal pump impellers. This examines different combinations of design factors by utilizing both the powerful numerical tools that allow the modeling of numerous scenarios and the large number of empirical equations and coefficients that represent the significant knowledge accumulated in this field. The design tool runs through a series of equations to select the beginning candidates for the different impeller design variables. After that, a design space is established by generating upper and lower bounds for each design variable. The CFD tool executes numerous scenarios inside the design space in order to find the best candidates with the maximum operating efficiency and meet the design objectives. A low specific speed centrifugal pump with a semi-open impeller is used as a case study. The design tool is successful in designing it, fulfilling the design requirement, and increasing operational efficiency when compared to a simple single-arc comparable impeller.

19.
PLoS One ; 19(6): e0304147, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861564

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a cancer type that is thought to be influenced by human papillomaviruses (HPVs) and human polyomaviruses (HPyVs). In Egypt, CRC ranks as the 7th most common cancer, accounting for 3.47% of male cancers and 3% of female cancers. However, there is currently a lack of information regarding the presence of PyVs and HPVs co-infection specifically in CRC cases in Egypt. Therefore, the aim of this study was to investigate the occurrence of HPVs and HPyVs (JCPyV, BKPyV, and SV40) infections, as well as co-infections, among CRC patients in Egypt. Additionally, the study aimed to assess any potential association between these viral infections and tumor stages. METHODS: In the present study, we analyzed a total of 51 tissue samples obtained from Egyptian CRC patients, along with 19 polyps' samples. Our investigation focused on the detection and genotyping of HPyVs using Real-Time PCR. Additionally, we employed real-time PCR for the detection of HPVs, and for their genotyping, we utilized a combination of PCR amplification followed by sequencing. RESULTS: In our study, we found evidence of HPyVs infection in the CRC patients, specifically SV40 (25.5%) and BKPyV (19.6%). However, JCPyV was not detected in the samples that were examined. Additionally, we discovered that HPV was present in 43.1% of the CRC patients. When considering viral co-infections, 19.6% of the CRC samples showed coexistence of multiple viruses, while no co-infections were found in the polyps samples. Importantly, we observed a significant correlation between the presence of HPVs and advanced colorectal tumor grades B2 and D. CONCLUSION: Our findings provide valuable data for the detection of oncogenic viruses in colorectal cancer (CRC) and underscore the association of viral co-infections with advanced tumor stages. However, further research with larger cohorts is necessary to validate these findings and strengthen their significance in the field of CRC.


Assuntos
Neoplasias Colorretais , Papillomaviridae , Infecções por Papillomavirus , Infecções por Polyomavirus , Polyomavirus , Humanos , Neoplasias Colorretais/virologia , Egito/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/virologia , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/complicações , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Polyomavirus/isolamento & purificação , Polyomavirus/genética , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Estudos de Casos e Controles , Coinfecção/virologia , Coinfecção/epidemiologia , Idoso , Adulto , Infecções Tumorais por Vírus/virologia , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/complicações , Genótipo
20.
JACC Adv ; 3(2): 100811, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38939382

RESUMO

Background: Systemic right ventricle (RV) dysfunction is associated with lower transplant-free survival (TFS) in hypoplastic left heart syndrome (HLHS), but the likelihood of functional improvement and utility of heart failure (HF) medications is not understood. Objectives: The authors aimed to describe TFS, HF medication use, and surgical interventions in HLHS patients with RV dysfunction with and without subsequent improvement in function. Methods: The SickKids HF Database is a retrospective cohort that includes all pediatric HLHS patients with RV dysfunction lasting >30 days. We compared TFS, HF medications, and surgical interventions in HLHS patients with and without functional normalization. Results: Of 99 patients with HLHS and RV dysfunction, 52% had normalized function for ≥30 days. TFS at 2 years after dysfunction onset was lower in those without normalization (14% vs 78%, P < 0.001). Patients without normalization were less likely to reach target dosing (TD) of HF medications (27% vs 47% on 1 medication at TD, P < 0.001) and undergo Fontan completion (7% vs 53%, P < 0.001). Clinical factors associated with improved TFS were normalization of function for ≥30 days, onset of dysfunction after bidirectional Glenn, and exposure to ACE inhibition. Conclusions: Our cohort of HLHS patients with systemic RV dysfunction demonstrated a novel finding of improved TFS in those with functional normalization for ≥30 days. Achieving TD of HF medications was associated with improved outcomes. This may reflect patient stability and tolerance for HF medication more than its therapeutic effect, but it can help inform decisions to proceed with surgical palliation or list for transplant.

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