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1.
Environ Sci Technol ; 58(13): 5952-5962, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38506754

RESUMEN

The presence of oxyanions, such as nitrate (NO3-) and phosphate (PO43-), regulates the nucleation and growth of goethite (Gt) and hematite (Hm) during the transformation of ferrihydrite (Fh). Our previous studies showed that oxyanion surface complexes control the rate and pathway of Fh transformation to Gt and Hm. However, how oxyanion surface complexes control the mechanism of Gt and Hm nucleation and growth during the Fh transformation is still unclear. We used synchrotron scattering methods and cryogenic transmission electron microscopy to investigate the effects of NO3- outer-sphere complexes and PO43- inner-sphere complexes on the mechanism of Gt and Hm formation from Fh. Our TEM results indicated that Gt particles form through a two-step model in which Fh particles first transform to Gt nanoparticles and then crystallographically align and grow to larger particles by oriented attachment (OA). In contrast, for the formation of Hm, imaging shows that Fh particles first aggregate and then transform to Hm through interface nucleation. This is consistent with our X-ray scattering results, which demonstrate that NO3- outer-sphere and PO43- inner-sphere complexes promote the formation of Gt and Hm, respectively. These results have implications for understanding the coupled interactions of oxyanions and iron oxy-hydroxides in Earth-surface environments.


Asunto(s)
Compuestos Férricos , Compuestos de Hierro , Minerales , Adsorción
2.
Metabolomics ; 19(6): 53, 2023 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-37271779

RESUMEN

INTRODUCTION: A decrease in sperm cell count has been observed along the last several decades, especially in the most developed regions of the world. The use of metabolomics to study the composition of the seminal fluid is a promising approach to gain access to the molecular mechanisms underlying this fact. OBJECTIVES: In the present work, we aimed at relating metabolomic profiles of young healthy men to their semen quality parameters obtained from conventional microscopic analysis. METHODS: An untargeted metabolomics approach focusing on low- to mid-polarity compounds was used to analyze a subset of seminal fluid samples from a cohort of over 2700 young healthy men. RESULTS: Our results show that a broad metabolic profiling comprising several families of compounds (including acyl-carnitines, steroids, and other lipids) can contribute to effectively distinguish samples provided by individuals exhibiting low or high absolute sperm counts. CONCLUSION: A number of metabolites involved in sexual development and function, signaling, and energy metabolism were highlighted as being distinctive of samples coming from either group, proving untargeted metabolomics as a promising tool to better understand the pathophysiological processes responsible for male fertility impairment.


Asunto(s)
Análisis de Semen , Semen , Humanos , Masculino , Semen/metabolismo , Metabolómica/métodos , Espermatozoides/metabolismo , Recuento de Espermatozoides
3.
J Chem Inf Model ; 63(10): 3158-3170, 2023 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-37167566

RESUMEN

The accurate prediction of protein structures achieved by deep learning (DL) methods is a significant milestone and has deeply impacted structural biology. Shortly after its release, AlphaFold2 has been evaluated for predicting protein-peptide interactions and shown to significantly outperform RoseTTAfold as well as a conventional blind docking method: PIPER-FlexPepDock. Since then, new AlphaFold2 models, trained specifically to predict multimeric assemblies, have been released and a new ab initio folding model OmegaFold has become available. Here, we assess docking success rates for these new DL folding models and compare their performance with our state-of-the-art, focused peptide-docking software AutoDock CrankPep (ADCP). The evaluation is done using the same dataset and performance metric for all methods. We show that, for a set of 99 nonredundant protein-peptide complexes, the new AlphaFold2 model outperforms other Deep Learning approaches and achieves remarkable docking success rates for peptides. While the docking success rate of ADCP is more modest when considering the top-ranking solution only, it samples correct solutions for around 62% of the complexes. Interestingly, different methods succeed on different complexes, and we describe a consensus docking approach using ADCP and AlphaFold2, which achieves a remarkable 60% for the top-ranking results and 66% for the top 5 results for this set of 99 protein-peptide complexes.


Asunto(s)
Benchmarking , Aprendizaje Profundo , Simulación del Acoplamiento Molecular , Proteínas/química , Péptidos/química , Programas Informáticos , Unión Proteica , Conformación Proteica
4.
An Acad Bras Cienc ; 95(4): e20190509, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37585878

RESUMEN

The aim of this study was to evaluate the body yield and quality of fresh and post-freezing filet of male and female fish of inbred and non-inbred AquaAmérica genetic group and the hybrid between the AquaAmérica and Tilamax varieties. Forty fish (20 males and 20 females) of each genetic group were housed in four 48-m3 hapa net cages, getting 120 fish per cage. The fish were housed at 51 days of age and farmed for 269 days. Pre-slaughter weight was higher (P<0.05) in the AquaAmérica × Tilamax males (0.805±0.204 kg) than in the inbred AquaAmérica male (0.643±0.115 kg). Filet yield percentage was higher (P<0.05) in the AquaAmérica × Tilamax males (32.14±4.72%) than in the inbred AquaAmérica (28.15±2.67%) and non-inbred AquaAmérica (29.06±2.80%) males. Head and viscera yield percentages, pH, color values (L*, a* and b*), shear force, drip loss and cooking loss did not differ significantly between the genetic groups and sexes. Alterations in meat quality were observed after freezing. In conclusion, inbreeding in the AquaAmérica variety resulted in reduced slaughter weight for males; AquaAmérica × Tilamax males have a higher filet yield; and filet quality is not influenced by crossing, inbreeding, or sex, but is changed after freezing.


Asunto(s)
Tilapia , Tilapia/genética , Regulación de la Expresión Génica , Congelación , Masculino , Femenino , Animales , Alimentos Marinos
5.
Health Promot Pract ; 24(1): 153-159, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-34628969

RESUMEN

This article focuses on examining the implementation of evidence-based teen pregnancy prevention programming in a select school district. Results are presented based on the following implementation drivers: (1) actions taken by leadership to make decisions, provide guidance, and support how the school site and community-based organizations are functioning in support of implementation; (2) actions taken to ensure competent staff delivery of the curricula; and (3) actions taken to create and sustain a hospitable context in order to implement the interventions at the school site. The need for adolescent sexual health education is evident in this geographic location where Hispanic or Latino teens consistently have higher birth rates among race and ethnicities that are routinely reported. For 2018, when this project started, those rates were 40 births per 1,000 females aged 15 to 19 years. For 2018, the birth rates for African Americans was 31 and for Whites was 17 per 1,000 females aged 15 to 19 years. The project goals were to reduce teen birth rates by (1) providing evidence-based teen pregnancy prevention curricula to youth aged 11 to 19 years over the course of the 5-year project period, (2) training school staff and community members in the curricula, and (3) generating community support of youth access to reproductive health care and education. Despite a funding interruption to implementation of the project and the impact of COVD-19, educational programming was provided to 9,616 youth. The article details the key implementation strategies and solutions so that other practitioners can consider application of these implementation drivers in their own adolescent health education programming.


Asunto(s)
Embarazo en Adolescencia , Embarazo , Adolescente , Femenino , Humanos , Embarazo en Adolescencia/prevención & control , Educación Sexual , Curriculum , Educación en Salud , Etnicidad
6.
Prog Urol ; 33(11): 547-554, 2023 Sep.
Artículo en Francés | MEDLINE | ID: mdl-37666743

RESUMEN

AIM: To determine the surgical indication and results of bladder augmentation (BA) during the last decade in a neurourology center in the era of intradetrusor botulinum toxin injection. MATERIAL: We conducted a retrospective study that included patients with BA between January 1, 2012 and December 31, 2022 in our centre. We collected pre-operative demographic, clinical, and urodynamic data, BA indication, and associated procedures. We analyzed early and late complications as well as continence and postoperative voiding mode in patients with first BA in a neurological pathology context. RESULTS: We performed 77 BA over the study period. The main indication was neurogenic overactive bladder, which was secondarily resistant to botulinum toxin. The main associated procedure was continent cutaneous diversion (n=31, 57.4%). Among patients who had a first BA for neurogenic bladder, 34 patients had early complications (50%) including 12 patients with≥Clavien 3 complications (17.6%). After a median follow-up of 33 [14; 55] months, 23 patients had late complications (33.8%) and 59 patients had complete continence (86.8%). CONCLUSION: In the era of botulinum toxin, the main indication of BA is the secondary failure of botulinum toxin for overactive neurogenic bladder. The BA provided continence in 86.8% of patients. It remains however an intervention with a significant rate of severe complications whose indication must be discussed by a multidisciplinary team. LEVEL OF EVIDENCE: Weak.


Asunto(s)
Toxinas Botulínicas , Vejiga Urinaria Neurogénica , Humanos , Estudios Retrospectivos , Vejiga Urinaria/cirugía , Vejiga Urinaria Neurogénica/tratamiento farmacológico , Vejiga Urinaria Neurogénica/cirugía , Procedimientos Quirúrgicos Urológicos
7.
Environ Sci Technol ; 56(22): 15672-15684, 2022 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-36219790

RESUMEN

The rate and pathway of ferrihydrite (Fh) transformation at oxic conditions to more stable products is controlled largely by temperature, pH, and the presence of other ions in the system such as nitrate (NO3-), sulfate (SO42-), and arsenate (AsO43-). Although the mechanism of Fh transformation and oxyanion complexation have been separately studied, the effect of surface complex type and strength on the rate and pathway remains only partly understood. We have developed a kinetic model that describes the effects of surface complex type and strength on Fh transformation to goethite (Gt) and hematite (Hm). Two sets of oxyanion-adsorbed Fh samples were prepared, nonbuffered and buffered, aged at 70 ± 1.5 °C, and then characterized using synchrotron X-ray scattering methods and wet chemical analysis. Kinetic modeling showed a significant decrease in the rate of Fh transformation for oxyanion surface complexes dominated by strong inner-sphere (SO42- and AsO43-) versus weak outer-sphere (NO3-) bonding and the control. The results also showed that the Fh transformation pathway is influenced by the type of surface complex such that with increasing strength of bonding, a smaller fraction of Gt forms compared with Hm. These findings are important for understanding and predicting the role of Fh in controlling the transport and fate of metal and metalloid oxyanions in natural and applied systems.


Asunto(s)
Compuestos Férricos , Minerales , Cinética , Adsorción , Compuestos Férricos/química , Minerales/química
8.
Environ Sci Technol ; 56(23): 16831-16837, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36394535

RESUMEN

Nanosized zinc sulfides (nano-ZnS) have size-dependent and tunable physical and chemical properties that make them useful for a variety of technological applications. For example, structural changes, especially caused by strain, are pronounced in nano-ZnS < 5 nm in size, the size range typical of incidental nano-ZnS that form in the environment. Previous research has shown how natural organic matter impacts the physical properties of nano-ZnS but was mostly focused on their aggregation state. However, the specific organic molecules and the type of functional groups that are most important for controlling the nano-ZnS size and strain remain unclear. This study examined the size-dependent strain of nano-ZnS synthesized in the presence of serine, cysteine, glutathione, histidine, and acetate. Synchrotron total scattering pair distribution function analysis was used to determine the average crystallite size and strain. Among the different organic molecules tested, those containing a thiol group were shown to affect the particle size and size-induced strain most strongly when added during synthesis but significantly reduced the particle strain when added to as-formed nano-ZnS. The same effects are useful to understand the properties and behavior of natural nano-ZnS formed as products of microbial activity, for example, in reducing environments, or of incidental nano-ZnS formed in organic wastes.


Asunto(s)
Nanopartículas , Compuestos de Zinc , Compuestos de Zinc/análisis , Compuestos de Zinc/química , Sulfuros/química , Nanopartículas/química , Tamaño de la Partícula
9.
Ann Vasc Surg ; 83: 240-250, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34933108

RESUMEN

BACKGROUND: For surgical treatment of primary aortic infection and aortic graft infection, in situ reconstruction with autologous vein(s) has the lowest rates of re-infection and of graft thrombosis. In this study, we have assessed the outcome after autologous femoral vein reconstruction in patients with aortic (graft) infection and we provide insights into the specific technical surgical considerations of the procedure. METHODS: In this retrospective single-center study, all patients who underwent autologous femoral vein reconstruction because of primary aortic infection or aortic graft infection between January 2012 and January 2020 were included. The primary outcome parameter was 30-day mortality. RESULTS: Twenty-nine patients with autologous femoral vein reconstruction for a primary aortic infection (n = 3) or aortic graft infection (n = 26) were included. An aorto-enteral fistula was detected in 13 patients (49%). Venous reconstruction of the aorta was performed with a single femoral vein in 17 patients (59%), and two femoral veins in 12 patients (41%). Thirty-day mortality was 17%. Relapse of infection occurred in two patients (7%) and no amputations were needed. One year after surgery, only three patients (10%) still needed stockings and after 2 years none of the patients used stockings. CONCLUSIONS: Central aortic reconstruction with femoral veins is a durable solution for primary aortic and aortoiliac graft infections with a low incidence of reinfections, amputations, and venous hypertension.


Asunto(s)
Implantación de Prótesis Vascular , Infecciones Relacionadas con Prótesis , Aorta/diagnóstico por imagen , Aorta/cirugía , Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Vena Femoral/cirugía , Vena Femoral/trasplante , Humanos , Infecciones Relacionadas con Prótesis/diagnóstico por imagen , Infecciones Relacionadas con Prótesis/etiología , Infecciones Relacionadas con Prótesis/cirugía , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento
10.
BMC Pediatr ; 22(1): 137, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-35291967

RESUMEN

BACKGROUND: In neonatology, parents play a central role as guarantors of the new-born's autonomy. Notifying parents about their infant's status in neonatal critical care is an integral part of the care. However, conveying this information can be very difficult for physicians and the neonatal medical team. The objective of this work is to assess the dimensions and dynamic processes of critical care communications in neonatal intensive care in order to enhance the development of theoretical and applied knowledge of these discussions. METHODS: This qualitative, descriptive study was conducted on critical care new-borns less than 28 days-old who were hospitalized in a neonatal intensive care unit. Verbatim communications with the parents were recorded using a dictaphone. RESULTS: The verbatim information had five themes: (a) critical care, (b) establishing the doctor-patient relationship, (c) assistance in decision making, (d) Socio-affective and (e) socio-symbolic dimensions. Our recordings underscored both the necessity of communication skills and the obligation to communicate effectively. Analysis of the dynamics of the communication process, according to the categories of delivering difficult information, showed few significant differences. CONCLUSION: Physician training needs to include how to effectively communicate to parents to optimize their participation and cooperation in managing their care.


Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Relaciones Médico-Paciente , Comunicación , Humanos , Lactante , Recién Nacido , Cuidado Intensivo Neonatal/psicología , Padres/psicología , Investigación Cualitativa
11.
Prog Urol ; 32(17): 1531-1542, 2022 Dec.
Artículo en Francés | MEDLINE | ID: mdl-35961806

RESUMEN

INTRODUCTION: Urine flowmetry (UF) is a key non-invasive urodynamic test for the evaluation of the voiding phase in patients with lower urinary tract symptoms (LUTS). Traditional free urodynamic testing (FUT) performed on a one-time basis in the office is limited by difficulty in capturing normal voiding and high intrapatient variability in urine flow parameters. Home measurement of urine flow by the patient could be a way to obtain multiple data in real-life conditions, addressing its limitations. The objective of this article was to review the literature on the different techniques of home uroflowmetry (HUF) and their clinical interest in comparison with FUT. MATERIAL AND METHODS: A search on the PubMed database using the key words "Urodynamics, Uroflowmetry, non-invasive urodynamics, Ambulatory urodynamics, bladder outlet obstruction, male LUTS" was performed to find articles in English or French that had been published with no time limit and March 2022. The sorting by reading the abstract allowed the selection of all articles describing and/or evaluating a HUF technique that were read entirely according to the same collection grid to propose a narrative synthesis. RESULTS: Thirty-one articles were identified, selected, and analyzed. Simple and inexpensive techniques by timing or use of funnels reliably and reproducibly estimate the average and maximum urine flow in relation to the FUT, without providing a complete flow curve. More sophisticated electronic or sonometric methods, some using connected mobile applications, present results that are more consistent with ICS recommendations for flow measurement. With the possibility of studying the average of several values of the maximum urinary flow (Qmax) captured during micturition in physiological conditions, some studies suggest a gain in diagnostic value in the evaluation of the emptying phase and lower urinary tract symptoms in men. However, the literature is sparse, old and the clinical benefits are not yet proven. CONCLUSION: There is a wide range of techniques for measuring urine flow in the patient's home, all of which aim to fill the gaps in conventional urine flow measurement. Further studies are needed to demonstrate the acceptability of this type of measurement by patients, the existence of a real clinical benefit, to assess the cost/benefit balance and finally to define a possible place for home uroflowmetry in daily practice, compared with traditional free flowmetry and invasive urodynamics (pressure-flow test).


Asunto(s)
Síntomas del Sistema Urinario Inferior , Obstrucción del Cuello de la Vejiga Urinaria , Humanos , Masculino , Urodinámica/fisiología , Obstrucción del Cuello de la Vejiga Urinaria/diagnóstico , Síntomas del Sistema Urinario Inferior/diagnóstico , Micción/fisiología , Vejiga Urinaria
12.
Endoscopy ; 53(2): 196-202, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33412590

RESUMEN

The European Society of Gastrointestinal Endoscopy (ESGE) has developed performance measures and established a framework for quality assessment for gastrointestinal endoscopy in Europe. Most national societies actively undertake initiatives to implement and explicitly endorse these quality indicators. Given this, ESGE proposes that, at a national level, strong leadership should exist to disseminate and implement quality parameters. Thus, understanding the potential barriers that may vary locally is of paramount importance. ESGE suggests that each national society should prioritize quality and standards of care in gastrointestinal endoscopy in their activities and should survey/understand which measures are a local priority to their members and make measuring quality intrinsic to daily endoscopy practice.


Asunto(s)
Gastroenterología , Endoscopía Gastrointestinal , Europa (Continente) , Humanos , Indicadores de Calidad de la Atención de Salud , Sociedades Médicas
13.
Med Mycol ; 59(10): 1006-1014, 2021 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-34021564

RESUMEN

This study aimed to assess the species distribution and antifungal susceptibility patterns of 200 strains of Aspergillus isolated from clinical specimens (n = 146) and soil samples (n = 54) in Mexico. ITS, ß-tubulin, and calmodulin DNA sequencing was performed for species identification. Broth microdilution susceptibility testing for amphotericin B, voriconazole, posaconazole, itraconazole, isavuconazole, anidulafungin, caspofungin, and micafungin was done according to CLSI for all strains. A. fumigatus was most frequently recovered from clinical specimens, while A. niger was commonly encountered in soil, both followed by A. flavus in the second place. A total of 60 (30%) cryptic species were identified, with A. tubingensis and A. tamarii being the most commonly found. The decreased susceptibility to amphotericin B and azoles was 32% for both, and were mainly led by A. fumigatus, whereas this percentage decreased to 9% for caspofungin, particularly in A. terreus. More than 75% of cryptic species were susceptible in vitro to all antifungals. Multi-azole decreased susceptibility was detected only in seven isolates. Given that antifungal resistance in Aspergillus spp. is an increasing worldwide threat that causes major challenges in the clinical management of aspergillosis, these data highlight the need for continuous epidemiological surveillance of these pathogens for the implementation of locally adequate treatment strategies. LAY SUMMARY: This is an epidemiological study in Mexico. A. fumigatus was most frequent in clinical specimens and A. niger in soil samples. A. tubingensis and A. tamarii were the most common cryptic species. Resistance to amphotericin B and azoles was 32% each, and 9% for caspofungin.


Asunto(s)
Antifúngicos , Aspergillus , Animales , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , México/epidemiología , Pruebas de Sensibilidad Microbiana/veterinaria , Suelo , Voriconazol
14.
Infection ; 49(3): 523-525, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32960418

RESUMEN

A 58-year-old woman was diagnosed with severe endometriosis and had multiple gastrointestinal tract complications for many years. Candida auris and C. parapsilosis were isolated from the bloodstream. Identification of C. auris was confirmed by amplification and sequencing of the internal transcriber spacer and the D1/D2 domain of the large rRNA gene subunit. Antifungal susceptibility was tested in both isolates using the Clinical Laboratory Standards Institute protocol M27-A3/S4. The patient evolved favorably with systemic antifungal therapy consisting of caspofungin and liposomal amphotericin B.


Asunto(s)
Candidiasis , Endometriosis , Enfermedades Gastrointestinales , Antifúngicos/uso terapéutico , Candida/genética , Candidiasis/diagnóstico , Candidiasis/tratamiento farmacológico , Femenino , Enfermedades Gastrointestinales/diagnóstico , Humanos , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad
15.
J Chem Inf Model ; 61(6): 3074-3090, 2021 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-34124893

RESUMEN

In recent years, therapeutic peptides have gained a lot interest as demonstrated by the 60 peptides approved as drugs in major markets and 150+ peptides currently in clinical trials. However, while small molecule docking is routinely used in rational drug design efforts, docking peptides has proven challenging partly because docking scoring functions, developed and calibrated for small molecules, perform poorly for these molecules. Here, we present random forest classifiers trained to discriminate correctly docked peptides. We show that, for a testing set of 47 protein-peptide complexes, structurally dissimilar from the training set and previously used to benchmark AutoDock Vina's ability to dock short peptides, these random forest classifiers improve docking power from ∼25% for AutoDock scoring functions to an average of ∼70%. These results pave the way for peptide-docking success rates comparable to those of small molecule docking. To develop these classifiers, we compiled the ProptPep37_2021 data set, a curated, high-quality set of 322 crystallographic protein-peptides complexes annotated with structural similarity information. The data set also provides a collection of high-quality putative poses with a range of deviations from the crystallographic pose, providing correct and incorrect poses (i.e., decoys) of the peptide for each entry. The ProptPep37_2021 data set as well as the classifiers presented here are freely available.


Asunto(s)
Péptidos , Proteínas , Benchmarking , Diseño de Fármacos , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Péptidos/metabolismo , Unión Proteica , Proteínas/metabolismo
16.
J Chem Inf Model ; 61(6): 3015-3026, 2021 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-34000187

RESUMEN

Under-expression or overexpression of protein kinases has been shown to be associated with unregulated cell signal transduction in cancer cells. Therefore, there is major interest in designing protein kinase inhibitors as anticancer agents. We have previously reported [WR]5, a peptide containing alternative arginine (R) and tryptophan (W) residues as a non-competitive c-Src tyrosine kinase inhibitor. A number of larger cyclic peptides containing alternative hydrophobic and positively charged residues [WR]x (x = 6-9) and hybrid cyclic-linear peptides, [R6K]W6 and [R5K]W7, containing R and W residues were evaluated for their protein kinase inhibitory potency. Among all the peptides, cyclic peptide [WR]9 was found to be the most potent tyrosine kinase inhibitor. [WR]9 showed higher inhibitory activity (IC50 = 0.21 µM) than [WR]5, [WR]6, [WR]7, and [WR]8 with IC50 values of 0.81, 0.57, 0.35, and 0.33 µM, respectively, against c-Src kinase as determined by a radioactive assay using [γ-33P]ATP. Consistent with the result above, [WR]9 inhibited other protein kinases such as Abl kinase activity with an IC50 value of 0.35 µM, showing 2.2-fold higher inhibition than [WR]5 (IC50 = 0.79 µM). [WR]9 also inhibited PKCa kinase activity with an IC50 value of 2.86 µM, approximately threefold higher inhibition than [WR]5 (IC50 = 8.52 µM). A similar pattern was observed against Braf, c-Src, Cdk2/cyclin A1, and Lck. [WR]9 exhibited IC50 values of <0.25 µM against Akt1, Alk, and Btk. These data suggest that [WR]9 is consistently more potent than other cyclic peptides with a smaller ring size and hybrid cyclic-linear peptides [R6K]W6 and [R5K]W7 against selected protein kinases. Thus, the presence of R and W residues in the ring, ring size, and the number of amino acids in the structure of the cyclic peptide were found to be critical in protein kinase inhibitory potency. We identified three putative binding pockets through automated blind docking of cyclic peptides [WR](5-9). The most populated pocket is located between the SH2, SH3, and N-lobe domains on the opposite side of the ATP binding site. The second putative pocket is formed by the same domains and located on the ATP binding site side of the protein. Finally, a third pocket was identified between the SH2 and SH3 domains. These results are consistent with the non-competitive nature of the inhibition displayed by these molecules. Molecular dynamics simulations of the protein-peptide complexes indicate that the presence of either [WR]5 or [WR]9 affects the plasticity of the protein and in particular the volume of the ATP binding site pocket in different ways. These results suggest that the second pocket is most likely the site where these peptides bind and offer a plausible rationale for the increased affinity of [WR]9.


Asunto(s)
Péptidos Cíclicos , Inhibidores de Proteínas Quinasas , Secuencia de Aminoácidos , Humanos , Simulación de Dinámica Molecular , Péptidos Cíclicos/farmacología , Unión Proteica , Inhibidores de Proteínas Quinasas/farmacología , Relación Estructura-Actividad , Dominios Homologos src
17.
Paediatr Anaesth ; 31(11): 1150-1160, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34379843

RESUMEN

Living-donor kidney transplantation is the first choice therapy for children with end-stage renal disease and shows good long-term outcome. Etiology of renal failure, co-morbidities, and hemodynamic effects, due to donor-recipient size mismatch, differs significantly from those in adult patients. Despite the complexities related to both patient and surgery, there is a lack of evidence-based anesthesia guidelines for pediatric kidney transplantation. This educational review summarizes the pathophysiological changes to consider and suggests recommendations for perioperative anesthesia care, based on recent research papers.


Asunto(s)
Anestesia , Fallo Renal Crónico , Trasplante de Riñón , Niño , Humanos , Riñón , Donadores Vivos , Atención Perioperativa
18.
PLoS Genet ; 14(5): e1007381, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29742103

RESUMEN

Chromosome segregation errors during meiosis result in the formation of aneuploid gametes and are the leading cause of pregnancy loss and birth defects in humans. Proper chromosome segregation requires pairwise associations of maternal and paternal homologous chromosomes. Chiasmata, which are the cytological manifestations of crossovers (COs), provide a physical link that holds the homologs together as a pair, facilitating their orientation on the spindle at meiosis I. Although CO-promoting activities ensure a balanced number and position of COs, their identity and mechanism of action in mammals remain understudied. Previous work in yeast and Arabidopsis has shown that Zip2 and Shoc1 are ortholog proteins with an important role in promoting the formation of COs. Our work is the first study in mammals showing the in vivo and in vitro function of mouse and human SHOC1. We show that purified recombinant human SHOC1, an XPF/MUS81 family member, preferentially binds branched DNA molecules but apparently lacks in vitro endonuclease activity, despite its conserved ERCC4-(HhH)2 core structure. Cytological observations suggest that initial steps of recombination are normal in a majority of spermatocytes from SHOC1 hypomorphic mice. However, late stages of recombination appear abnormal, as chromosomal localization of MLH1 is reduced. In agreement, chiasma formation is reduced, and cells arrest at metaphase I with a few lagging chromosomes and subsequent apoptosis. This analysis of SHOC1-deficient mice and the selective localization of SHOC1 to a subset of recombination sites show that SHOC1 acts at key mid-stage steps of the CO formation process. The formation of chromosome axial elements and homologous pairing are apparently normal, but synapsis is altered with SYCP1 frequently failing to extend the full length of the chromosome axes. Finally, we describe that SHOC1 interacts with TEX11, another protein important for the formation of COs, connecting SHOC1 to chromosome axis and structure.


Asunto(s)
Intercambio Genético , Proteínas de Unión al ADN/metabolismo , Endonucleasas/metabolismo , Meiosis/genética , Animales , Emparejamiento Cromosómico/genética , Segregación Cromosómica/genética , Proteínas de Unión al ADN/genética , Endonucleasas/genética , Femenino , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Recombinación Genética , Espermatocitos/metabolismo
19.
Gac Med Mex ; 157(5): 478-483, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35104274

RESUMEN

OBJECTIVES: To evaluate the effect of azithromycin (AZM) on biofilm formation and composition in multidrug resistant (MDR) Acinetobacter baumannii. MATERIAL AND METHODS: Ninety-six A. baumannii isolates were studied. Antimicrobial susceptibility and sub-minimum inhibitory concentration (sub-MIC) were determined by the broth microdilution method. Carbapenemase genes were detected by polymerase chain reaction and clonal diversity by pulsed-field gel electrophoresis (PFGE). Biofilm formation without AZM and AZM sub-MIC were determined by crystal violet staining. AZM-free biofilm composition and AZM sub-MIC were determined by detachment assays. RESULTS: The selected A. baumannii were MDR; 93.8% were carbapenem-resistant and 24 were OXA-24-positive. PFGE showed predominance of clones A (53%), B (34.7%) and C (12.5%). Biofilm production at AZM sub-MICs decreased in 53.1%, increased in 34.7% and showed no differences in 12.5% of isolates, in comparison with biofilm production without AZM. CONCLUSION: AZM sub-MIC can reduce biofilm production in A. baumannii MDR isolates with decreased protein and DNA in the biofilm. Our results may be useful in synergy studies for new therapeutic alternatives.


OBJETIVOS: Evaluar el efecto de la azitromicina (AZM) en la formación y composición de biopelículas en Acinetobacter baumannii resistente a múltiples fármacos (MDR). MATERIAL Y MÉTODOS: Se estudiaron 96 aislamientos de A. baumannii. La susceptibilidad antimicrobiana y la concentración inhibitoria submínima (sub-MIC) se determinaron por el método de microdilución del caldo. Los genes carbapenemasa fueron detectados por reacción en cadena de la polimerasa y la diversidad clonal por electroforesis en gel de campos pulsados (PFGE). La formación de biopelículas sin AZM y la sub-MIC de AZM por tinción de cristal violeta. La composición de la biopelícula sin AZM y la sub-MIC de AZM se determinaron mediante ensayos de desprendimiento. RESULTADOS: Los A. baumannii seleccionados fueron MDR; el 93.8% resistentes al carbapenem y 24 OXA-24 positivos. El PFGE demostró predominancia en los clones A (53%), B (34.7%) y C (12.5%). La producción de biopelículas en sub-MIC de AZM disminuyó en un 53.1%, aumentó en un 34.7% y no mostró diferencias en un 12.5% de los aislamientos, comparado con la producción de biopelículas sin AZM. CONCLUSIÓN: La sub-MIC de AZM puede reducir la producción de biopelículas en aislamientos de A. baumannii MDR con disminución de proteínas y el ADN en la biopelícula. Nuestros resultados pueden ser útiles en estudios de sinergia para nuevas alternativas terapéuticas.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter baumannii/genética , Azitromicina/farmacología , Biopelículas , Carbapenémicos , Humanos
20.
Prog Urol ; 31(7): 430-438, 2021 Jun.
Artículo en Francés | MEDLINE | ID: mdl-33579624

RESUMEN

INTRODUCTION: During idiopathic Parkinson's disease (IPD), lower urinary tract symptoms and dysfunctions are frequent, dominated by overactive bladder and detrusor overactivity (OAB, DO). Intradetrusor Injection (IDI) of Botulinum Toxin A (BTA) is recommended as second-line treatment for neurogenic urinary incontinence related to DO in multiple sclerosis or spinal cord injury patients. However, there is little data on BTA IDI to treat incontinence owing to OAB and DO during idiopathic Parkinson's disease. The objective of this study is to evaluate efficacy and tolerance of BTA IDI in patients suffering IPD. PATIENTS AND METHODS: We conducted a retrospective study in IPD patients treated with BTA IDI from 2012 to 2018. For each patient we compared patient clinical and urodynamic data at baseline before the first injection and 8 weeks following the injection. We defined 3 levels of effects (perfect, improved, failure), corresponding to 3-dimension composite criteria: clinical, quality of life (Likert scale), urodynamics. RESULTS: Sixteen patients were included from 2012 to 2018. The median age was 73 (70-78.25). The median number of micturition/day before and after TBA was 13 (10-16) and 9 (6.75-13.25) (p=0.022). The median number of pad used/day before and after BTA was 5.4 (2-5) and 1 (0-5) (p=0.035). Median USP scores for OAB was 15.5 (11.75-20) and 14 (6.75-15.25). Median score on the Likert scale was 1 (0-1.5) meaning "slight improvement" felt by the patient. The median maximum cystometric capacity raised from 130cm3 (41.25-187.75) to 217cm3 (165-376.75) (p=0,013). Among the patients, 20% had a perfect result, 40% were significantly improved and in 40% TBA injections failed. After TBA 4/14 patients (28%) needed intermittent self-catheterization. No severe side effect was observed. CONCLUSION: In this retrospective study we observe some short-term efficacy of TBA IDI to treat urinary incontinence owing to OAB/DO in patients with IPD in 60% of patients. These results are consistent with findings from previous retrospective studies. Prospective data coming from larger cohorts are now tremendously needed to clarify the best patient responders profiles, the actual TBA dose, and eventually to define TBA IDI place in the therapeutic algorithm of IPD patients' incontinence. LEVEL OF EVIDENCE: 4.


Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Fármacos Neuromusculares/administración & dosificación , Enfermedad de Parkinson/complicaciones , Vejiga Urinaria Hiperactiva/etiología , Incontinencia Urinaria/tratamiento farmacológico , Administración Intravesical , Anciano , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
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