Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.847
Filtrar
1.
Methods Mol Biol ; 2816: 53-67, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38977588

RESUMEN

This chapter conducts an in-depth exploration of the impact of musculoskeletal (MSK) disorders and injuries, with a specific emphasis on their consequences within the older population demographic. It underscores the escalating demand for innovative interventions in MSK tissue engineering. The chapter also highlights the fundamental role played by lipid signaling mediators (LSMs) in tissue regeneration, with relevance to bone and muscle recovery. Remarkably, Prostaglandin E2 (PGE2) emerges as a central orchestrator in these regenerative processes. Furthermore, the chapter investigates the complex interplay between bone and muscle tissues, explaining the important influence exerted by LSMs on their growth and differentiation. The targeted modulation of LSM pathways holds substantial promise as a beneficial way for addressing muscle disorders. In addition to these conceptual understandings, the chapter provides a comprehensive overview of methodologies employed in the identification of LSMs, with a specific focus on the Liquid Chromatography-Mass Spectrometry (LC-MS). Furthermore, it introduces a detailed LC MS/MS-based protocol tailored for the detection of PGE2, serving as an invaluable resource for researchers immersed in this dynamic field of study.


Asunto(s)
Dinoprostona , Lipidómica , Espectrometría de Masas en Tándem , Humanos , Lipidómica/métodos , Dinoprostona/metabolismo , Dinoprostona/análisis , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Enfermedades Musculoesqueléticas/diagnóstico , Metabolismo de los Lípidos , Lípidos/análisis
2.
Methods Mol Biol ; 2816: 151-159, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38977597

RESUMEN

Developing robust analytical techniques is a vital phase to facilitate understanding the roles and impacts of various omic profilings in cellular functions. The comprehensive analysis of various biological molecules within a biological system requires a precise sample preparation technique. Solid-Phase Extraction (SPE) has proven to be an indispensable method in lipidomic analysis, providing an uncomplicated and user-friendly technique for extraction and purification of lipid components from complex biological matrices. Of all the factors influencing the reliability and success of SPE, column or adsorbent materials, flow rate, and storage conditions are paramount in terms of their significance. In this chapter, we will discuss in detail the SPE steps for lipidomic analysis in biofluid samples (serum and plasma) and muscle tissues.


Asunto(s)
Lipidómica , Lípidos , Extracción en Fase Sólida , Extracción en Fase Sólida/métodos , Lipidómica/métodos , Lípidos/aislamiento & purificación , Lípidos/química , Humanos , Animales
4.
Methods Mol Biol ; 2816: 1-11, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38977583

RESUMEN

The intricate interplay between the muscle and bone tissues is a fundamental aspect of musculoskeletal physiology. Over the past decades, emerging research has highlighted the pivotal role of lipid signaling in mediating communication between these tissues. This chapter delves into the multifaceted mechanisms through which lipids, particularly phospholipids, sphingolipids, and eicosanoids, participate in orchestrating cellular responses and metabolic pathways in both muscle and bone. Additionally, we examine the clinical implications of disrupted lipid signaling in musculoskeletal disorders, offering insights into potential therapeutic avenues. This chapter aims to shed light on the complex lipid-driven interactions between the muscle and bone tissues, paving the way for a deeper understanding of musculoskeletal health and disease.


Asunto(s)
Metabolismo de los Lípidos , Enfermedades Musculoesqueléticas , Transducción de Señal , Animales , Humanos , Huesos/metabolismo , Eicosanoides/metabolismo , Músculo Esquelético/metabolismo , Enfermedades Musculoesqueléticas/metabolismo , Fosfolípidos/metabolismo , Esfingolípidos/metabolismo
5.
Methods Mol Biol ; 2816: 41-52, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38977587

RESUMEN

This chapter provides an overview of the diverse range of applications associated with nanoparticles. The application of nanoparticles in the medical field has garnered considerable attention due to their unique properties and versatile compositions. They have shown promise in the treatment of cancer, fungal and viral infections, and pain management. These systems provide numerous benefits, such as increased drug stability, improved bioavailability, and targeted delivery to specific tissues or cells. The objective of this chapter is to provide a brief analysis of the differences between nanoparticles and lipid particles, focusing particularly on the importance of nanoparticle size and composition in their interactions with lipids. Additionally, the applications of nanoparticles in lipid signaling will be discussed, considering the vital roles lipids play in cellular signaling pathways. Nanoparticles have shown immense potential in the regulation and control of medical pathways. In this case, we will focus on the manufacture of liposomes, a type of nanoparticle composed of lipids. The reason behind the extensive investigation into liposomes as drug delivery vehicles is their remarkable biocompatibility and adaptability. This section will provide insights into the methods and techniques employed for liposome formulation.


Asunto(s)
Lípidos , Liposomas , Nanopartículas , Transducción de Señal , Nanopartículas/química , Humanos , Liposomas/química , Lípidos/química , Animales , Sistemas de Liberación de Medicamentos/métodos , Metabolismo de los Lípidos
6.
Sci Rep ; 14(1): 15599, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971829

RESUMEN

Porous asphalt mixture is conventional hot mix asphalt (HMA) with substantially decreased fines, which produces an open-graded mixture that enables the water to flow through an interconnected void space. Porous asphalt is a permeable system that has a lot of benefits. However, because of its open structure, the durability of this mixture decreases, and both its stability and resilient modulus are much lower compared to the dense conventional asphalt mixtures. Also, the high void percentage may lead to an increase in the draindown proportion. Fibers (cellulose or mineral) and polymer-modified binders are recommended for porous asphalt mixtures, especially in hot and moderate climates. The objective of this study is to improve the porous asphalt mixture's performance by using ethylene-vinyl acetate (EVA) polymer-modified bitumen. Two types of fibers (cellulose fibers and glass wool fibers) were used, separately to determine the control mixture. Four different proportions of EVA polymer were added to the bitumen (1%, 2%, 3%, and 4%) and Scanning Electron Microscopy (SEM) was used for better investigating of the bitumen microstructure, then The Marshall mix design was used to determine the optimum EVA content (OEC) for the porous asphalt mixture. Several performance tests were conducted to investigate the characteristics of the porous asphalt mixture, such as the infiltration rate, binder draindown, the wheel track and the cantabro abrasion tests. The findings of the study conclude that the addition of EVA polymer to the porous asphalt mixtures enhances the performance as it increases stability by 20.8% and the infiltration rate by 20.6%. It decreases binder draindown proportion by 33.3%, cantabro abrasion loss by 25.1% and the rut depth at 5,000 cycles and 10,000 cycles by 29.8% and 19.7%, respectively.

7.
New Phytol ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953386

RESUMEN

C4 photosynthesis is a complex trait requiring multiple developmental and metabolic alterations. Despite this complexity, it has independently evolved over 60 times. However, our understanding of the transition to C4 is complicated by the fact that variation in photosynthetic type is usually segregated between species that diverged a long time ago. Here, we perform a genome-wide association study (GWAS) using the grass Alloteropsis semialata, the only known species to have C3, intermediate, and C4 accessions that recently diverged. We aimed to identify genomic regions associated with the strength of the C4 cycle (measured using δ13C), and the development of C4 leaf anatomy. Genomic regions correlated with δ13C include regulators of C4 decarboxylation enzymes (RIPK), nonphotochemical quenching (SOQ1), and the development of Kranz anatomy (SCARECROW-LIKE). Regions associated with the development of C4 leaf anatomy in the intermediate individuals contain additional leaf anatomy regulators, including those responsible for vein patterning (GSL8) and meristem determinacy (GIF1). The parallel recruitment of paralogous leaf anatomy regulators between A. semialata and other C4 lineages implies the co-option of these genes is context-dependent, which likely has implications for the engineering of the C4 trait into C3 species.

8.
Sci Rep ; 14(1): 15221, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956104

RESUMEN

Municipal wastewater treatment systems use the chemical oxygen demand test (COD) to identify organic contaminants in industrial effluents that impede treatment due to their high concentration. This study reduced the COD levels in tannery wastewater using a multistage treatment process that included Fenton oxidation, chemical coagulation, and nanotechnology based on a synthetic soluble COD standard solution. At an acidic pH of 5, Fenton oxidation reduces the COD concentration by approximately 79%. It achieves this by combining 10 mL/L of H2O2 and 0.1 g/L of FeCl2. Furthermore, the author selected the FeCl3 coagulant for the coagulation process based on the best results of comparisons between different coagulants. At pH 8.5, the coagulation dose of 0.15 g/L achieved the maximum COD removal efficiency of approximately 56.7%. Finally, nano bimetallic Fe/Cu was used to complete the degradation and adsorption of the remaining organic pollutants. The XRD, SEM, and EDX analyses proved the formation of Fe/Cu nanoparticles. A dose of 0.09 g/L Fe/Cu NPs, 30 min of contact time, and a stirring rate of 200 rpm achieve a maximum removal efficiency of about 93% of COD at pH 7.5. The kinetics studies were analyzed using pseudo-first-order P.F.O., pseudo-second-order P.S.O., and intraparticle diffusion models. The P.S.O. showed the best fit among the kinetic models, with an R2 of 0.998. Finally, the authors recommended that technique for highly contaminated industrial effluents treatment for agriculture or industrial purposes.

9.
Cureus ; 16(5): e61335, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38947709

RESUMEN

Alzheimer's and Parkinson's diseases are among the most prevalent neurodegenerative conditions affecting aging populations globally, presenting significant challenges in early diagnosis and management. This narrative review explores the pivotal role of advanced neuroimaging techniques in detecting and managing these diseases at early stages, potentially slowing their progression through timely interventions. Recent advancements in MRI, such as ultra-high-field systems and functional MRI, have enhanced the sensitivity for detecting subtle structural and functional changes. Additionally, the development of novel amyloid-beta tracers and other emerging modalities like optical imaging and transcranial ultrasonography have improved the diagnostic accuracy and capability of existing methods. This review highlights the clinical applications of these technologies in Alzheimer's and Parkinson's diseases, where they have shown improved diagnostic performance, enabling earlier intervention and better prognostic outcomes. Moreover, the integration of artificial intelligence (AI) and longitudinal research is emerging as a promising enhancement to refine early detection strategies further. However, this review also addresses the technical, ethical, and accessibility challenges in the field, advocating for the more extensive use of advanced imaging technologies to overcome these barriers. Finally, we emphasize the need for a holistic approach that incorporates both neurological and psychiatric perspectives, which is crucial for optimizing patient care and outcomes in the management of neurodegenerative diseases.

10.
BMJ Open ; 14(6): e085506, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950989

RESUMEN

OBJECTIVES: Hepatitis C virus (HCV) infection poses a global health challenge. By the end of 2021, the WHO estimated that less than a quarter of global HCV infections had been diagnosed. There is a need for a public health tool that can facilitate the identification of people with HCV infection and link them to testing and treatment, and that can be customised for each country. METHODS: We derived and validated a risk score to identify people with HCV in Egypt and demonstrated its utility. Using data from the 2008 and 2014 Egypt Demographic and Health Surveys, two risk scores were constructed through multivariable logistic regression analysis. A range of diagnostic metrics was then calculated to evaluate the performance of these scores. RESULTS: The 2008 and 2014 risk scores exhibited similar dependencies on sex, age and type of place of residence. Both risk scores demonstrated high and similar areas under the curve of 0.77 (95% CI: 0.76 to 0.78) and 0.78 (95% CI: 0.77 to 0.80), respectively. For the 2008 risk score, sensitivity was 73.7% (95% CI: 71.5% to 75.9%), specificity was 68.5% (95% CI: 67.5% to 69.4%), positive predictive value (PPV) was 27.8% (95% CI: 26.4% to 29.2%) and negative predictive value (NPV) was 94.1% (95% CI: 93.5% to 94.6%). For the 2014 risk score, sensitivity was 64.0% (95% CI: 61.5% to 66.6%), specificity was 78.2% (95% CI: 77.5% to 78.9%), PPV was 22.2% (95% CI: 20.9% to 23.5%) and NPV was 95.7% (95% CI: 95.4% to 96.1%). Each score was validated by applying it to a different survey database than the one used to derive it. CONCLUSIONS: Implementation of HCV risk scores is an effective strategy to identify carriers of HCV infection and to link them to testing and treatment at low cost to national programmes.


Asunto(s)
Hepatitis C , Humanos , Egipto/epidemiología , Femenino , Masculino , Estudios Transversales , Adulto , Persona de Mediana Edad , Hepatitis C/epidemiología , Hepatitis C/diagnóstico , Adulto Joven , Medición de Riesgo/métodos , Adolescente , Factores de Riesgo , Modelos Logísticos , Anciano , Sensibilidad y Especificidad
12.
ASAIO J ; 70(7): 602-608, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949774

RESUMEN

We report the largest pediatric multicenter experience with Impella pump use and peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. Utilizing the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) collaborative database, we conducted a retrospective, multicenter study of all patients with cardiogenic shock requiring VA-ECMO support with subsequent Impella implant between October 2014 and December 2021. The primary outcome was defined as death while on Impella support. Secondary outcomes were recovery, transplantation, and transition to durable ventricular assist device (VAD) at the time of Impella explantation. Adverse events were defined according to the ACTION registry criteria. Twenty subjects were supported with Impella; Impella 2.5 (n = 3), CP (n = 12), 5.0/5.5 (n = 5). The median Interquartile range (IQR) age, weight, and body surface area at implantation were 15.6 years (IQR = 13.9-17.2), 65.7 kg (IQR = 53.1-80.7), and 1.74 m2 (IQR = 1.58-1.98). Primary cardiac diagnoses were dilated cardiomyopathy/myocarditis in nine (45%), congenital heart disease in four (20%), graft failure/rejection in four (20%), and three (15%) others. Most common adverse events included hemolysis (50%) and bleeding (20%). There were two deaths (10%) in the cohort. Nine patients (45%) were explanted for recovery, eight (40%) were transitioned to a durable VAD, and one (5%) underwent heart transplantation. Impella percutaneous pump support should be considered in the older pediatric population supported with peripheral VA-ECMO, as a means of left heart decompression, and a strategy to come off ECMO to achieve endpoints of myocardial recovery, transition to a durable VAD, or transplantation.


Asunto(s)
Oxigenación por Membrana Extracorpórea , Corazón Auxiliar , Choque Cardiogénico , Humanos , Oxigenación por Membrana Extracorpórea/métodos , Oxigenación por Membrana Extracorpórea/efectos adversos , Corazón Auxiliar/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Adolescente , Choque Cardiogénico/terapia , Niño , Preescolar , Resultado del Tratamiento
13.
Healthcare (Basel) ; 12(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38998835

RESUMEN

BACKGROUND: Early mobility (EM) is vital in the intensive care unit (ICU) to counteract immobility-related effects. A multidisciplinary approach is key, as it requires precise initiation knowledge. However, physicians' understanding of EM in adult ICU settings remains unexplored. This study was conducted to investigate the knowledge and clinical competency of physicians working in adult ICUs toward EM. METHODS: This cross-sectional study enrolled 236 physicians to assess their knowledge of EM. A rigorously designed survey comprising 30 questions across the demographic, theoretical, and clinical domains was employed. The criteria for knowledge and competency were aligned with the minimum passing score (70%) stipulated for physician licensure by the medical regulatory authority in Saudi Arabia. RESULTS: Nearly 40% of the respondents had more than 5 years of experience. One-third of the respondents received theoretical knowledge about EM as part of their residency training, and only 4% of the respondents attended formal courses to enhance their knowledge. Almost all the respondents (95%) stated their awareness of EM benefits and its indications and contraindications and considered it safe to mobilize patients on mechanical ventilators. However, 62.3% of the respondents did not support EM for critically ill patients on mechanical ventilators until weaning. In contrast, 51.7% of respondents advised EM for agitated patients with RASS > 2. Only 113 (47.9%) physicians were competent in determining the suitability of ICU patients for EM. For critically ill patients who should be mobilized, nearly 60% of physicians refused to initiate EM. CONCLUSIONS: This study underscores insufficient practical knowledge of ICU physicians about EM criteria, which leads to suboptimal decisions, particularly in complex ICU cases. These findings emphasize the need for enhanced training and education of physicians working in adult ICU settings to optimize patient care and outcomes in critical care settings.

14.
Sci Rep ; 14(1): 15397, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965274

RESUMEN

This article presents a novel approach for parameters estimation of photovoltaic cells/modules using a recent optimization algorithm called quadratic interpolation optimization algorithm (QIOA). The proposed formula is dependent on variable voltage resistances (VVR) implementation of the series and shunt resistances. The variable resistances reduced from the effect of the electric field on the semiconductor conductivity should be included to get more accurate representation. Minimizing the mean root square error (MRSE) between the measured (I-V) dataset and the extracted (V-I) curve from the proposed electrical model is the main goal of the current optimization problem. The unknown parameters of the proposed PV models under the considered operating conditions are identified and optimally extracted using the proposed QIOA. Two distinct PV types are employed with normal and low radiation conditions. The VVR TDM is proposed for (R.T.C. France) silicon PV operating at normal radiation, and eleven unknown parameters are optimized. Additionally, twelve unknown parameters are optimized for a Q6-1380 multi-crystalline silicon (MCS) (area 7.7 cm2) operating under low radiation. The efficacy of the QIOA is demonstrated through comparison with four established optimizers: Grey Wolf Optimization (GWO), Particle Swarm Optimization (PSO), Salp Swarm Algorithm (SSA), and Sine Cosine Algorithm (SCA). The proposed QIO method achieves the lowest absolute current error values in both cases, highlighting its superiority and efficiency in extracting optimal parameters for both Single-Crystalline Silicon (SCS) and MCS cells under varying irradiance levels. Furthermore, simulation results emphasize the effectiveness of QIO compared to other algorithms in terms of convergence speed and robustness, making it a promising tool for accurate and efficient PV parameter estimation.

15.
Anal Sci ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38971934

RESUMEN

Contamination of college campus dust with heavy metals and the calculation of their ecological and health risks to the students and staff did not receive much attention except in recent years. This study aims to assess the ecological and human health risks of Cd, Cr, Cu, Pb, and Zn in interior dust of College of Science/University campus. An atomic absorption spectrophotometer was utilized to estimate the samples that were collected from 46 locations of the college campus including: classrooms, offices, and laboratories. The Pb, Cu, Cr and Zn metals in the interior dust of the College of Science pose low potential ecological risk, whereas Cd generates medium potential ecological risk. The gained results showed that the student and staff of the College are exposed to low non-cancerous health risks (HI < 1) caused by Cd, Cr, Cu, Pb, and Zn in interior dust. The total lifetime carcinogenic risks (TLCR) of Cd, Cr, and Pb are within the acceptable safe limit (10-6-10-4). The low non-carcinogenic health risks of Cd, Cr, Cu, Pb, and Zn and that the carcinogenic health risks of Cd, Cr and Pb fall within acceptable safe limits, measured in the interior dust of the campus of the College of Science, does not mean neglecting the continuous assessment of those risks.

16.
Pediatr Crit Care Med ; 25(7): 643-675, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38959353

RESUMEN

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference. DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill children. DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements. CONCLUSIONS: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials.


Asunto(s)
Anticoagulantes , Enfermedad Crítica , Oxigenación por Membrana Extracorpórea , Oxigenación por Membrana Extracorpórea/métodos , Humanos , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Niño , Enfermedad Crítica/terapia , Recién Nacido , Lactante , Preescolar
17.
Pediatr Crit Care Med ; 25(7 Suppl 1): e1-e6, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38959354

RESUMEN

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding the influence of extracorporeal membrane oxygenation (ECMO) circuit components on anticoagulation practices for pediatric ECMO for the Pediatric ECMO Anticoagulation CollaborativE. DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. STUDY SELECTION: Management of ECMO anticoagulation in the setting of different ECMO circuit components. DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twenty-nine references were used for data extraction and informed recommendations, evidence-based consensus statements, and good practice statements. Evidence tables were constructed using a standardized data extraction form. DATA SYNTHESIS: Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements or good practice statements for the influence of ECMO circuit and components on anticoagulation management. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One good practice statement, 2 weak recommendations, and 2 consensus statements are presented. CONCLUSIONS: The incorporation of new component technologies into clinical practice has outpaced clinical investigations of anticoagulation strategies for pediatric ECMO. Future investigations should leverage academic and industrial collaborations, translational platforms, and modern biostatistical methods to improve patient outcomes.


Asunto(s)
Anticoagulantes , Técnica Delphi , Oxigenación por Membrana Extracorpórea , Oxigenación por Membrana Extracorpórea/métodos , Humanos , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Niño , Consenso
18.
Eur J Med Chem ; 276: 116685, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39042991

RESUMEN

Pseudomonas aeruginosa causes life-threatening infections especially in hospitalized patients and shows an increasing resistance to established antibiotics. A process known as quorum sensing (QS) enables the pathogen to collectively adapt to various environmental conditions. Disrupting this cell-to-cell communication machinery by small-molecular entities leads to a blockade of bacterial pathogenicity. We aim to devise QS inhibitors acting on the PA-specific PQS QS system via the signal-molecule receptor and transcriptional regulator PqsR (MvfR). In this manuscript, we describe the further optimization of PqsR inverse agonists by broadening the structural space of a previously described triazole-bearing lead compound and arriving at highly potent thiazole derivatives with activities against P. aeruginosa virulence factor pyocyanin in the nanomolar range. All new derivatives were profiled regarding biological activity as well as in vitro ADMET parameters. Additionally, we assessed safety-pharmacology characteristics of the two most promising compounds both bearing a 3-chloro-4-isopropoxyphenyl motive. Demonstrating an overall favorable profile, our new PqsR inverse agonists represent a valuable addition as optimized lead compounds, enabling preclinical development of P. aeruginosa-specific pathoblockers.

19.
Sleep Med Rev ; 77: 101979, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39043056
20.
Can Urol Assoc J ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39037506

RESUMEN

INTRODUCTION: We aimed to investigate the factors impacting stone clearance following retrograde intrarenal surgery (RIRS) for lower pole kidney stones and to determine whether there is a significant relationship between the infundibular pelvic angle (IPA) of the kidney's lower pole and stone fragment clearance. METHODS: We retrospectively reviewed patients who underwent flexible ureteroscopy (f-URS) for lower pole renal calculi between December 2020 and July 2023 at our institution. Patient demographics and stone parameters were recorded, including stone size, number, volume, density, and IPA. Intraoperative data, including total operative time, lasing time, type of laser used, and stone composition, were collected and analyzed. All patients underwent a computed tomography (CT) scan at three months followup. We recorded the presence of residual stones and the percentage of stone volume reduction. Patients with a stone size ≤3 mm were deemed stone-free. All patients were discharged home on the same operative day. RESULTS: A total of 123 patients were included in the study: 71 in the stone-free group (group 1) and 52 in the residual stones group (group 2). On univariate analysis, there were significant differences between the two groups in terms of stone size, IPA, and the type of ureteroscopy used. At three months followup, 96% (24/25) of patients with an IPA <30° had residual stones, compared to 28.6% (28/98) of patients with an IPA >30° (p<0.001). There was no significant difference in the intraoperative or postoperative complications between the two groups. On multivariate analysis, IPA and stone size were the only predictive factors for the presence of residual stones. Twelve patients (23.1%) from group 2 required retreatment. CONCLUSIONS: RIRS is an effective treatment option for the management of lower pole kidney stones. IPA, in conjunction with stone size, appears to dictate the stone clearance rates of RIRS for lower pole stones.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...