Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 350
Filtrar
Más filtros

Bases de datos
Tipo del documento
Intervalo de año de publicación
1.
J Am Chem Soc ; 146(12): 7915-7921, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38488295

RESUMEN

A new alkylthiolate-ligated nonheme iron complex, FeII(BNPAMe2S)Br (1), is reported. Reaction of 1 with O2 at -40 °C, or reaction of the ferric form with O2•- at -80 °C, gives a rare iron(III)-superoxide intermediate, [FeIII(O2)(BNPAMe2S)]+ (2), characterized by UV-vis, 57Fe Mössbauer, ATR-FTIR, EPR, and CSIMS. Metastable 2 then converts to an S-oxygenated FeII(sulfinate) product via a sequential O atom transfer mechanism involving an iron-sulfenate intermediate. These results provide evidence for the feasibility of proposed intermediates in thiol dioxygenases.


Asunto(s)
Hierro , Superóxidos , Compuestos Ferrosos , Oxígeno
2.
Rev Neurol (Paris) ; 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38553272

RESUMEN

Amyotrophic lateral sclerosis (ALS) diagnosis relies on signs of progressive damage to both lower motoneuron (LMN), given by clinical examination and electromyography (EMG), and upper motoneuron (UMN), given by clinical examination only. Recognition of UMN involvement, however, is still difficult, so that diagnostic delay often remains too long. Shortening the time to clinical and genetic diagnosis is essential in order to provide accurate information to patients and families, avoid time-consuming investigations and for appropriate care management. This study investigates whether combined patellar tendon reflex recording with motor-evoked potentials to the lower limbs (T-MEP-LL) is relevant to assess corticospinal function in ALS, so that it might serve as a tool improving diagnosis. T-MEP-LL were recorded in 135 patients with suspected motor neuron disease (MND) from February 2010 to March 2021. The sensitivity, specificity, and ability to improve diagnosis when added to Awaji and Gold Coast criteria were determined. The main finding of the study is that T-MEP-LL can detect UMN dysfunction with a 70% sensitivity and 63% specificity when UMN clinical signs are lacking. The sensitivity reaches 82% when considering all MND patients. Moreover, at first evaluation, using T-MEP-LL to quantify reflex briskness and to measure central conduction time, can improve the diagnostic accuracy. T-MEP-LL is easy to perform and does not need any electrical stimulation, making the test rapid, and painless. By the simultaneous quantification of both UMN and LMN system, it could also help to identify different phenotype with more accuracy than clinical examination in this broad-spectrum pathology. The question whether T-MEP-LL could further be a real biomarker need further prospective studies.

3.
Biochemistry ; 62(9): 1484-1496, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-37014173

RESUMEN

The nematode Caenorhabditis elegans contains genes for two types of ferritin (ftn-1 and ftn-2) that express FTN-1 and FTN-2. We have expressed and purified both proteins and characterized them by X-ray crystallography, cryo-electron microscopy, transmission electron microscopy, dynamic light scattering, and kinetically by oxygen electrode and UV-vis spectroscopy. Both show ferroxidase activity, but although they have identical ferroxidase active sites, FTN-2 is shown to react approximately 10 times faster than FTN-1, with L-type ferritin character over longer time periods. We hypothesize that the large variation in rate may be due to differences in the three- and four-fold channels into the interior of the protein 24-mer. FTN-2 is shown to have a wider entrance into the three-fold channel than FTN-1. Additionally, the charge gradient through the channel of FTN-2 is more pronounced, with Asn and Gln residues in FTN-1 replaced by Asp and Glu residues in FTN-2. Both FTN-1 and FTN-2 have an Asn residue near the ferroxidase active site that is a Val in most other species, including human H ferritin. This Asn residue has been observed before in ferritin from the marine pennate diatom Pseudo-mitzchia multiseries. By replacing this Asn residue with a Val in FTN-2, we show that the reactivity decreases over long time scales. We therefore propose that Asn106 is involved in iron transport from the ferroxidase active site to the central cavity of the protein.


Asunto(s)
Caenorhabditis elegans , Ferritinas , Animales , Humanos , Ferritinas/química , Caenorhabditis elegans/metabolismo , Hierro/química , Ceruloplasmina/metabolismo , Microscopía por Crioelectrón
4.
Malar J ; 22(1): 14, 2023 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-36635720

RESUMEN

BACKGROUND: Entomological surveillance provides critical information on vectors for appropriate malaria vector control and strategic decision-making. The widely documented insecticide resistance of malaria vectors in Côte d'Ivoire requires that any vector control intervention deployment be driven by entomological data to optimize its effectiveness and appropriate resource allocations. To achieve this goal, this study documents the results of monthly vector surveillance and insecticide susceptibility tests conducted in 2019 and a review of all previous entomological monitoring data used to guide vector control decision making. Furthermore, susceptibility to pirimiphos-methyl and clothianidin was assessed in addition to chlorfenapyr and pyrethroids (intensity and piperonyl butoxide (PBO) synergism) tests previously reported. Vector bionomic data were conducted monthly in four sites (Sakassou, Béoumi, Dabakala and Nassian) that were selected based on their reported high malaria incidence. Adult mosquitoes were collected using human landing catches (HLCs), pyrethrum spray catches (PSCs), and human-baited CDC light traps to assess vector density, behaviour, species composition and sporozoite infectivity. RESULTS: Pirimiphos-methyl and clothianidin susceptibility was observed in 8 and 10 sites, respectively, while previous data reported chlorfenapyr (200 µg/bottle) susceptibility in 13 of the sites, high pyrethroid resistance intensity and increased mortality with PBO pre-exposure at all 17 tested sites. Anopheles gambiae sensu lato was the predominant malaria vector collected in all four bionomic sites. Vector density was relatively higher in Sakassou throughout the year with mean biting rates of 278.2 bites per person per night (b/p/n) compared to Béoumi, Dabakala and Nassian (mean of 48.5, 81.4 and 26.6 b/p/n, respectively). The mean entomological inoculation rate (EIR) was 4.44 infective bites per person per night (ib/p/n) in Sakassou, 0.34 ib/p/n in Beoumi, 1.17 ib/p/n in Dabakala and 1.02 ib/p/n in Nassian. The highest EIRs were recorded in October in Béoumi (1.71 ib/p/n) and Nassian (3.22 ib/p/n), in July in Dabakala (4.46 ib/p/n) and in May in Sakassou (15.6 ib/p/n). CONCLUSION: Based on all results and data review, the National Malaria Control Programme developed and implemented a stratified insecticide-treated net (ITN) mass distribution in 2021 considering new generation ITNs. These results also supported the selection of clothianidin-based products and an optimal spraying time for the first indoor residual spraying (IRS) campaign in Sakassou and Nassian in 2020.


Asunto(s)
Anopheles , Insecticidas , Malaria , Humanos , Animales , Insecticidas/farmacología , Malaria/epidemiología , Control de Mosquitos/métodos , Côte d'Ivoire/epidemiología , Mosquitos Vectores , Resistencia a los Insecticidas
5.
Inorg Chem ; 62(38): 15719-15735, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37691232

RESUMEN

Spin crossover (SCO) complexes can reversibly switch between low spin (LS) and high spin (HS) states, affording possible applications in sensing, displays, and molecular electronics. Dinuclear SCO complexes with access to [LS-LS], [LS-HS], and [HS-HS] states may offer increased levels of functionality. The nature of the SCO interconversion in dinuclear complexes is influenced by the local electronic environment. We report the synthesis and characterization of [{FeIII(tpa)}2spiro](PF6)2 (1), [{FeIII(tpa)}2Br4spiro](PF6)2 (2), and [{FeIII(tpa)}2thea](PF6)2 (3) (tpa = tris(2-pyridylmethyl)amine, spiroH4 = 3,3,3',3'-tetramethyl-1,1'-spirobi(indan)-5,5',6,6'-tetraol, Br4spiroH4 = 3,3,3',3'-tetramethyl-1,1'-spirobi(indan)-4,4',7,7'-tetrabromo-5,5',6,6'-tetraol, theaH4 = 2,3,6,7-tetrahydroxy-9,10-dimethyl-9,10-dihydro-9,10-ethanoanthracene), utilizing non-conjugated bis(catecholate) bridging ligands. In the solid state, magnetic and structural analysis shows that 1 remains in the [HS-HS] state, while 2 and 3 undergo a partial SCO interconversion upon cooling from room temperature involving the mixed [LS-HS] state. In solution, all complexes undergo SCO from [HS-HS] at room temperature, via [LS-HS] to mixtures including [LS-LS] at 77 K, with the extent of SCO increasing in the order 1 < 2 < 3. Gas phase density functional theory calculations suggest a [LS-LS] ground state for all complexes, with the [LS-HS] and [HS-HS] states successively destabilized. The relative energy separations indicate that ligand field strength increases following spiro4- < Br4spiro4- < thea4-, consistent with solid-state magnetic and EPR behavior. All three complexes show stabilization of the [LS-HS] state in relation to the midpoint energy between [LS-LS] and [HS-HS]. The relative stability of the [LS-HS] state increases with increasing ligand field strength of the bis(catecholate) bridging ligand in the order 1 < 2 < 3. The bromo substituents of Br4spiro4- increase the ligand field strength relative to spiro4-, while the stronger ligand field provided by thea4- arises from extension of the overlapping π-orbital system across the two catecholate units. This study highlights how SCO behavior in dinuclear complexes can be modulated by the bridging ligand, providing useful insights for the design of molecules that can be interconverted between more than two states.

6.
Rev Neurol (Paris) ; 179(9): 1020-1029, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37735015

RESUMEN

Relationships between genes and amyotrophic lateral sclerosis (ALS) have been widely accepted since the first studies highlighting pathogenic mutations in the SOD1 gene 30years ago. Over the last three decades, scientific literature has clearly highlighted the central role played by genetic factors in the disease, in both clinics and pathophysiology, as well as in therapeutics. This implies that health professionals who care for patients with ALS are increasingly faced with patients and relatives eager to have answers to questions related to the role of genetic factors in the occurrence of the disease and the risk for their relatives to develop ALS. In order to address these public health issues, the French ALS network FILSLAN proposed to the Haute Autorité de santé (HAS) the drafting of a French National Protocol (PNDS) on ALS genetics. This PNDS was developed according to the "method for developing a national diagnosis and care protocol for rare diseases" published by the HAS in 2012 (methodological guide for PNDS available on the HAS website: http://www.has-sante.fr/). This document aims to provide the most recent data on the role of genes in ALS and to detail the implications for diagnosis and care.


Asunto(s)
Esclerosis Amiotrófica Lateral , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/genética , Mutación
7.
Am J Transplant ; 22(7): 1901-1908, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35182000

RESUMEN

Liver allocation policy was changed to reduce variance in median MELD scores at transplant (MMaT) in February 2020. "Acuity circles" replaced local allocation. Understanding the impact of policy change on donor utilization is important. Ideal (I), standard (S), and non-ideal (NI) donors were defined. NI donors include older, higher BMI donors with elevated transaminases or bilirubin, history of hepatitis B or C, and all DCD donors. Utilization of I, S, and NI donors was established before and after allocation change and compared between low MELD (LM) centers (MMaT ≤ 28 before allocation change) and high MELD (HM) centers (MMaT > 28). Following reallocation, transplant volume increased nationally (67 transplants/center/year pre, 74 post, p .0006) and increased for both HM and LM centers. LM centers significantly increased use of NI donors and HM centers significantly increased use of I and S donors. Centers further stratify based on donor utilization phenotype. A subset of centers increased transplant volume despite rising MMaT by broadening organ acceptance criteria, increasing use of all donor types including DCD donors (98% increase), increasing living donation, and transplanting more frequently for alcohol associated liver disease. Variance in donor utilization can undermine intended effects of allocation policy change.


Asunto(s)
Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Obtención de Tejidos y Órganos , Enfermedad Hepática en Estado Terminal/cirugía , Humanos , Políticas , Donantes de Tejidos , Listas de Espera
8.
Psychosom Med ; 84(2): 215-223, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34629425

RESUMEN

OBJECTIVE: Lung cancer remains the number one cause of cancer-related mortality worldwide, but less known is that lung cancer patients are among the most psychologically disabled of all cancer groups. Patients with stage IV non-small cell lung cancer (NSCLC) were studied to test the hypothesis that trajectories of depression and/or anxiety symptoms after diagnosis would show an adverse relationship with survival, beyond relevant controls. METHODS: Patients with stage IV NSCLC (n = 157) were enrolled (ClinicalTrials.gov Identifier: NCT03199651) at diagnosis and completed validated measures for depressive symptoms (Patient Health Questionnaire-9) and anxiety symptoms (Generalized Anxiety Disorder-7). Patients were reassessed every 1 to 2 months through 24 months (16 assessments; 80% average completion rate) and survival monitored. Joint statistical models provided simultaneous modeling of longitudinal (psychological) and time-to-event (survival) processes. Control variables were age, sex, marital status, education, smoking status, cancer type, and treatment received. RESULTS: Depression and anxiety symptoms significantly decreased with time since diagnosis. The 2-year trajectory of depressive symptoms was significantly associated with cancer survival after adjustment for covariates (hazard ratio = 1.09 per unit increase in the Patient Health Questionnaire-9, 95% confidence interval = 1.03-1.15, p = .002). Anxiety was marginally significant in the unadjusted (p = .053) but not the adjusted (p = .39) model. CONCLUSIONS: For the first time, joint model analyses test the interaction of a longitudinal trajectory of psychological symptoms, assessed from diagnosis to 24 months, and cancer survival. New data show the continuation of depressive and anxiety symptoms through treatment and thereafter. Immunotherapy and targeted therapies have dramatically improved survival for patients with advanced NSCLC; however, novel data suggest their benefit may be constrained by depressive symptoms.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Ansiedad/epidemiología , Trastornos de Ansiedad/terapia , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Depresión/etiología , Humanos , Modelos de Riesgos Proporcionales
9.
Br J Surg ; 110(1): 34-42, 2022 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-36346716

RESUMEN

BACKGROUND: Neoadjuvant therapy is increasingly being used before surgery for localized pancreatic cancer. Given the importance of completing multimodal therapy, the aim of this study was to characterize surgical resection rates after neoadjuvant therapy as well as the reasons for, and long-term prognostic impact of, not undergoing resection. METHODS: A systematic review and meta-analysis of prospective trials and high-quality retrospective studies since 2010 was performed to calculate pooled resection rates using a generalized random-effects model for potentially resectable, borderline resectable, and locally advanced pancreatic cancer. Median survival times were calculated using random-effects models for patients who did and did not undergo resection. RESULTS: In 125 studies that met the inclusion criteria, neoadjuvant therapy consisted of chemotherapy (36.8 per cent), chemoradiation (15.2 per cent), or chemotherapy and radiation (48.0 per cent). Among 11 713 patients, the pooled resection rates were 77.4 (95 per cent c.i. 71.3 to 82.5), 60.6 (54.8 to 66.1), and 22.2 (16.7 to 29.0) per cent for potentially resectable, borderline resectable, and locally advanced pancreatic cancer respectively. The most common reasons for not undergoing resection were distant progression for resectable and borderline resectable cancers, and local unresectability for locally advanced disease. Among 42 studies with survival data available, achieving surgical resection after neoadjuvant therapy was associated with improved survival for patients with potentially resectable (median 38.5 versus 13.3 months), borderline resectable (32.3 versus 13.9 months), and locally advanced (30.0 versus 14.6 months) pancreatic cancer (P < 0.001 for all). CONCLUSION: Although rates of surgical resection after neoadjuvant therapy vary based on anatomical stage, surgery is associated with improved survival for all patients with localized pancreatic cancer. These pooled resection and survival rates may inform patient-provider decision-making and serve as important benchmarks for future prospective trials.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Terapia Neoadyuvante , Pancreatectomía/efectos adversos , Estudios Retrospectivos , Carcinoma Ductal Pancreático/cirugía , Carcinoma Ductal Pancreático/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/cirugía , Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas
10.
Int J Legal Med ; 136(5): 1321-1339, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35488928

RESUMEN

The accumulation of ßAPP caused by axonal injury is an active energy-dependent process thought to require blood circulation; therefore, it is closely related to the post-injury survival time. Currently, the earliest reported time at which axonal injury can be detected in post-mortem traumatic brain injury (TBI) tissue by ßAPP (Beta Amyloid Precursor Protein) immunohistochemistry is 35 min. The aim of this study is to investigate whether ßAPP staining for axonal injury can be detected in patients who died rapidly after TBI in road traffic collision (RTC), in a period of less than 30 min.We retrospectively studied thirty-seven patients (group 1) died very rapidly at the scene; evidenced by forensic assessment of injuries short survival, four patients died after a survival period of between 31 min and 12 h (group 2) and eight patients between 2 and 31 days (group 3). The brains were comprehensively examined and sampled at the time of the autopsy, and ßAPP immunohistochemistry carried out on sections from a number of brain areas.ßAPP immunoreactivity was demonstrated in 35/37 brains in group 1, albeit with a low frequency and in a variable pattern, and with more intensity and frequency in all brains of group 2 and 7/8 brains from group 3, compared with no similar ßAPP immunoreactivity in the control group. The results suggest axonal injury can be detected in those who died rapidly after RTC in a period of less than 30 min, which can help in the diagnosis of severe TBI with short survival time.


Asunto(s)
Lesiones Traumáticas del Encéfalo , Traumatismos Craneocerebrales , Accidentes de Tránsito , Precursor de Proteína beta-Amiloide/metabolismo , Axones/metabolismo , Encéfalo/metabolismo , Humanos , Inmunohistoquímica , Estudios Retrospectivos
11.
Int J Legal Med ; 136(6): 1865-1881, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35960370

RESUMEN

Cases of suicidal hanging are a common death referred for medico-legal autopsy throughout the world. Although some advocate using postmortem computed tomography (PMCT) without traditional invasive autopsy (TIA) to investigate such deaths, others reject this approach. There is currently limited evidence to guide practice. In this context, the TIA reports and PMCT images of 50 cases of suspected suicidal hanging during an 11-month period were reviewed. The reviewers were blinded to the findings of the other modality. A Cohen's Kappa coefficient (K) was calculated to assess agreement between TIA and PMCT across a range of pertinent findings. This analysis demonstrated perfect agreement for identification of a ligature (K = 1.00) and a strong level of agreement for identification of a ligature suspension point (K = 0.832) but only a minimal level of agreement for overall ligature mark (K = 0.223). PMCT demonstrated a weak level of agreement for fractures of hyoid bone (K = 0.555) and thyroid cartilage (K = 0.538). Three probable fractures not identified at TIA were identified on PMCT. TIA was shown to be superior in the identification of intramuscular and laryngeal fracture-related haemorrhage/bruising whereas PMCT was superior to TIA in identifying body gas deposition. There was overall good correlation between the natural disease and trauma identified elsewhere in the body during the TIA and PMCT. The study demonstrates that PMCT can assist the investigation of suspected suicidal hangings. However, the accuracy of many findings is limited, and if it is used as an alternative to the TIA, potentially pertinent findings, such as fractures of the laryngeal cartilages, could be missed.


Asunto(s)
Fracturas Óseas , Traumatismos del Cuello , Autopsia/métodos , Patologia Forense , Hemorragia/diagnóstico por imagen , Humanos , Hueso Hioides/diagnóstico por imagen , Hueso Hioides/lesiones , Traumatismos del Cuello/diagnóstico por imagen , Ideación Suicida , Tomografía Computarizada por Rayos X
12.
Environ Res ; 214(Pt 3): 114005, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35944620

RESUMEN

BACKGROUND: When coal is burned for energy, coal ash, a hazardous waste product, is generated. Throughout the world, over 1 billion tons of coal ash is produced yearly. In the United States, over 78 million tons of coal ash was produced in 2019. Fly ash, the main component of coal ash contains neurotoxic metal (loid)s that may affect children's neurodevelopment and mental health. The objective of this study was to investigate the association between fly ash and depressive problems in children aged 6-14 years old. METHODS: Children and their parents/guardians were recruited from 2015 to 2020. Tobit regression and logistic regression were used to assess the association between coal fly ash and depressive problems. To determine fly ash presence, Scanning Electron Microscopy was conducted on polycarbonate filters containing PM10 from the homes of the study participants. Depressive problems in children were measured using the Depressive Problems DSM and withdrawn/depressed syndromic problem scales of the Child Behavior Checklist. RESULTS: In covariate-adjusted Tobit regression models, children with fly ash on the filter had higher scores on the DSM Depressive Problems (3.13 points; 95% CI = 0.39, 5.88) compared with children who did not have fly ash on the filter. Logistic regression supported these findings. CONCLUSION: Coal ash is one of the largest waste streams in the U.S, but it is not classified as a hazardous waste by the Environmental Protection Agency. To our knowledge, no studies have assessed the impact of coal ash on children's mental health. This study highlights the need for further research into the effects of coal ash exposure on children's mental health, and improved regulations on release and storage of coal ash.


Asunto(s)
Ceniza del Carbón , Depresión , Carbón Mineral , Ceniza del Carbón/toxicidad , Depresión/inducido químicamente , Depresión/epidemiología , Residuos Peligrosos , Humanos , Centrales Eléctricas
13.
Biochem J ; 478(3): 669-684, 2021 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-33480393

RESUMEN

Mutation of cytochrome c in humans causes mild autosomal dominant thrombocytopenia. The role of cytochrome c in platelet formation, and the molecular mechanism underlying the association of cytochrome c mutations with thrombocytopenia remains unknown, although a gain-of-function is most likely. Cytochrome c contributes to several cellular processes, with an exchange between conformational states proposed to regulate changes in function. Here, we use experimental and computational approaches to determine whether pathogenic variants share changes in structure and function, and to understand how these changes might occur. Three pathogenic variants (G41S, Y48H, A51V) cause an increase in apoptosome activation and peroxidase activity. Molecular dynamics simulations of these variants, and two non-naturally occurring variants (G41A, G41T), indicate that increased apoptosome activation correlates with the increased overall flexibility of cytochrome c, particularly movement of the Ω loops. Crystal structures of Y48H and G41T complement these studies which overall suggest that the binding of cytochrome c to apoptotic protease activating factor-1 (Apaf-1) may involve an 'induced fit' mechanism which is enhanced in the more conformationally mobile variants. In contrast, peroxidase activity did not significantly correlate with protein dynamics. Thus, the mechanism by which the variants increase peroxidase activity is not related to the conformational dynamics of the native hexacoordinate state of cytochrome c. Recent molecular dynamics data proposing conformational mobility of specific cytochrome c regions underpins changes in reduction potential and alkaline transition pK was not fully supported. These data highlight that conformational dynamics of cytochrome c drive some but not all of its properties and activities.


Asunto(s)
Apoptosis/fisiología , Citocromos c/química , Mutación Missense , Mutación Puntual , Sustitución de Aminoácidos , Apoptosomas , Cristalografía por Rayos X , Citocromos c/genética , Citocromos c/aislamiento & purificación , Citocromos c/metabolismo , Humanos , Enlace de Hidrógeno , Peróxido de Hidrógeno/metabolismo , Concentración de Iones de Hidrógeno , Modelos Moleculares , Simulación de Dinámica Molecular , Mutagénesis Sitio-Dirigida , Oxidación-Reducción , Conformación Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Relación Estructura-Actividad , Células U937
14.
Chemistry ; 27(55): 13793-13806, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34310770

RESUMEN

Thiol dioxygenases are important enzymes for human health; they are involved in the detoxification and catabolism of toxic thiol-containing natural products such as cysteine. As such, these enzymes have relevance to the development of Alzheimer's and Parkinson's diseases in the brain. Recent crystal structure coordinates of cysteine and 3-mercaptopropionate dioxygenase (CDO and MDO) showed major differences in the second-coordination spheres of the two enzymes. To understand the difference in activity between these two analogous enzymes, we created large, active-site cluster models. We show that CDO and MDO have different iron(III)-superoxo-bound structures due to differences in ligand coordination. Furthermore, our studies show that the differences in the second-coordination sphere and particularly the position of a positively charged Arg residue results in changes in substrate positioning, mobility and enzymatic turnover. Furthermore, the substrate scope of MDO is explored with cysteinate and 2-mercaptosuccinic acid and their reactivity is predicted.


Asunto(s)
Dioxigenasas , Dominio Catalítico , Cisteína , Cisteína-Dioxigenasa/metabolismo , Compuestos Férricos , Humanos
15.
Environ Sci Technol ; 55(13): 9074-9086, 2021 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-34132542

RESUMEN

Children who live near coal-fired power plants are exposed to coal fly ash, which is stored in landfills and surface impoundments near residential communities. Fly ash has the potential to be released as fugitive dust. Using data collected from 263 children living within 10 miles of coal ash storage facilities in Jefferson and Bullitt Counties, Kentucky, USA, we quantified the elements found in nail samples. Furthermore, using principal component analysis (PCA), we investigated whether metal(loid)s that are predominately found in fly ash loaded together to indicate potential exposure to fly ash. Concentrations of several neurotoxic metal(loid)s, such as chromium, manganese, and zinc, were higher than concentrations reported in other studies of both healthy and environmentally exposed children. From PCA, it was determined that iron, aluminum, and silicon in fly ash were found to load together in the nails of children living near coal ash storage facilities. These metal(loid)s were also highly correlated with each other. Last, results of geospatial analyses partially validated our hypothesis that children's proximity to power plants was associated with elevated levels of concentrations of fly ash metal(loid)s in nails. Taken together, nail samples may be a powerful tool in detecting exposure to fly ash.


Asunto(s)
Ceniza del Carbón , Centrales Eléctricas , Niño , Carbón Mineral , Ceniza del Carbón/análisis , Polvo/análisis , Humanos , Metales
16.
Forensic Sci Med Pathol ; 17(3): 498-500, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33939115

RESUMEN

During the Corona Virus Disease-19 (COVID-19) pandemic, there is still a requirement for post-mortems to continue, including those examinations performed in the context of medico-legal investigations. Currently, very little is known about how long this coronavirus can survive in deceased human bodies or whether un-embalmed human cadavers can be contagious to people who handle them. Therefore, it would appear to be prudent to consider implementation of additional safety measures for all necessary post-mortem procedures. During the post-mortem examination of babies and young children, it is important to open the calvarium to enable visualization of the brain and its coverings, particularly in cases where a head injury is likely to have occurred. Since October 2013, the use of neurosurgical equipment to open the calvarium during infant and young child autopsies has become routine practice in our unit. Both the neurosurgical craniotome and a standard oscillating mortuary saw produce particulate matter consisting of bone and body fluids (including blood) which can become aerosolized. Within this paper, we discuss the use of a transparent plastic tent whilst opening the calvarium during pediatric post-mortems, to reduce the spread of aerosols into the mortuary environment.


Asunto(s)
COVID-19 , Traumatismos Craneocerebrales , Aerosoles , Autopsia , Niño , Preescolar , Traumatismos Craneocerebrales/prevención & control , Humanos , Lactante , Pandemias , SARS-CoV-2
17.
Pediatr Res ; 87(1): 81-87, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31330530

RESUMEN

BACKGROUND: Pulmonary hypertension (PH) in patients with bronchopulmonary dysplasia (BPD) results from vasoconstriction and/or vascular remodeling, which can be regulated by mitogen-activated protein kinases (MAPKs). MAPKs are deactivated by dual-specificity phosphatases (DUSPs). We hypothesized that single-nucleotide polymorphisms (SNPs) in DUSP genes could be used to predict PH in BPD. METHODS: Preterm infants diagnosed with BPD (n = 188) were studied. PH was defined by echocardiographic criteria. Genomic DNA isolated from patient blood samples was analyzed for 31 SNPs in DUSP genes. Clinical characteristics and minor allele frequencies were compared between BPD-PH (cases) and BPD-without PH (control) groups. Biomarker models to predict PH in BPD using clinical and SNP data were tested by calculations of area under the ROC curve. RESULTS: In our BPD cohort, 32% (n = 61) had PH. Of the DUSP SNPs evaluated, DUSP1 SNP rs322351 was less common, and DUSP5 SNPs rs1042606 and rs3793892 were more common in cases than in controls. The best fit biomarker model combines clinical and DUSP genetic data with an area under the ROC curve of 0.76. CONCLUSION: We identified three DUSP SNPs as potential BPD-PH biomarkers. Combining clinical and DUSP genetic data yields the most robust predictor for PH in BPD.


Asunto(s)
Displasia Broncopulmonar/genética , Fosfatasa 1 de Especificidad Dual/genética , Fosfatasas de Especificidad Dual/genética , Hipertensión Pulmonar/genética , Polimorfismo de Nucleótido Simple , Displasia Broncopulmonar/complicaciones , Displasia Broncopulmonar/diagnóstico , Displasia Broncopulmonar/enzimología , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/enzimología , Lactante , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Masculino , Fenotipo , Medición de Riesgo , Factores de Riesgo
18.
Clin Transplant ; 34(3): e13822, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32037573

RESUMEN

BACKGROUND: Hospital readmission (HR) after surgery is considered a quality metric. METHODS: Data on 2371 first-time adult kidney transplant (KT) recipients were collected to analyze the "early" (≤30 days) and "late" (31-365 days) HR patterns after KT at a single center over a 12-year time span (2002-2013). RESULTS: 30-day, 90-day, and 1-year HR were 31%, 41%, and 53%, respectively. Risk factors for HR included age >50, female sex, black race, BMI >30, transplant LOS >5 days, and pre-transplant time on dialysis >765 days. Indications for early (n = 749) and late (n = 508) HR were similar. Early HR (OR: 3.80, P = .007) and black race (OR: 2.38, P = .009) were associated with higher odds of 1-year graft failure while frequency (1-2, 3-4, 5+) of HR (ORs: 4.68, 8.36, 9.44, P < .001) and age > 50 (OR: 2.11, P = .007) were associated with higher odds of 1-year mortality. Transplant LOS > 5 days increased both odds of 1-year graft failure (OR: 3.51, P = .001) and mortality (OR: 2.05, P = .006). One-year graft and recipient survival were 96.7% and 94.8%, respectively. CONCLUSIONS: Hospital readmission was associated with reduced graft and patient survival; however, despite a relatively high and consistent HR rate after KT, overall 1-year graft and patient survival was high.


Asunto(s)
Trasplante de Riñón , Adulto , Femenino , Supervivencia de Injerto , Humanos , Readmisión del Paciente , Diálisis Renal , Factores de Riesgo , Receptores de Trasplantes
19.
J Vasc Interv Radiol ; 31(6): 978-985, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32414572

RESUMEN

PURPOSE: This study evaluated the long-term outcomes of the Misago peripheral stent trial (Terumo) for atherosclerotic lesions in the superficial femoral artery (SFA) in patients with claudication. MATERIALS AND METHODS: This was a prospective multicenter, single-arm, clinical trial of primary stent placement for de novo cases of SFA disease conducted in the United States and Asia. The primary endpoint was freedom from clinically driven target lesion revascularization (CD-TLR) at 36 months. Secondary outcomes were ankle-brachial index (ABI), Rutherford score, Walking Impairment Questionnaire (WIQ), a quality of life survey, and rate of device fracture. RESULTS: A total of 276 patients (64.4% male; mean age, 69.3 ± 10.1 years) were enrolled. Freedom from CD-TLR was 78.5% (95% confidence interval [CI], 73.0%-83.0%) at 24 months and 75.4% (95% CI, 69.6%-80.2%) at 36 months. Baseline ABI was 0.7 ± 0.1 and 0.98 ± 0.20 (P < .001) at 30 days after the procedure. Baseline Rutherford score was 3.6 ± 0.6 and 1.6 ± 1.0 30 at 30 days after the procedure (P < .001). Mean (and changed) ABI and Rutherford score at 36 months compared to day 30 after the procedure were, respectively, 0.91 (-0.1 ± 0.2) and 1.5 (-0.2 ± 1.1). WIQ score at baseline was 21.49 ± 26.30 and 50.51 ± 38.49 at 30 days after the procedure ( P < .001). The mean WIQ score at 2 years was 46.65 ± 37.31 (P = .12). Stent fracture rate at 36 months was 2.0% (4 of 202 patients). CONCLUSIONS: OSPREY (Occlusive-Stenotic Peripheral Artery Revascularization Study) 36-month data demonstrated persistent freedom from CD-TLR and sustained improvement in ABI and Rutherford score with primary stent placement for SFA lesions.


Asunto(s)
Procedimientos Endovasculares/instrumentación , Arteria Femoral , Claudicación Intermitente/terapia , Enfermedad Arterial Periférica/terapia , Stents Metálicos Autoexpandibles , Anciano , Anciano de 80 o más Años , Índice Tobillo Braquial , Asia , Procedimientos Endovasculares/efectos adversos , Femenino , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/fisiopatología , Humanos , Claudicación Intermitente/diagnóstico , Claudicación Intermitente/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/fisiopatología , Estudios Prospectivos , Diseño de Prótesis , Falla de Prótesis , Calidad de Vida , Recuperación de la Función , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Grado de Desobstrucción Vascular
20.
Int J Legal Med ; 134(2): 637-643, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31250083

RESUMEN

On 14 June 2017 at 00:54 h, the worst residential fire since the conclusion of the Second World War broke out in Flat 16, 4th floor of the 24-storey residential Grenfell Tower Block of flats, North Kensington, West London, UK. Seventy-one adults and children died, including one stillbirth. All victims of the Grenfell Tower disaster who died at the scene underwent post-mortem computed tomography (PMCT) imaging using a mortuary-sited mobile computed tomography scanner. For the first time, to the authors' knowledge, the disaster victim identification (DVI) radiology reporting was undertaken remote to the mortuary scanning. Over an 11-week period, 119 scans were undertaken on 16 days, with up to 18 scans a day. These were delivered to a remote reporting centre at Leicester on 13 days with between 2 and 20 scans arriving each day. Using a disaster-specific process pathway, a team of 4 reporters, with 3 support staff members, trialled a prototype INTERPOL DVI radiology reporting form and produced full radiology reports and supporting image datasets such that they were able to provide 96% of prototype DVI forms, 99% of image datasets and 86% of preliminary reports to the DVI teams in London within one working day of image receipt. This paper describes the first use of remote radiology reporting for DVI and exemplifies how remote PMCT reporting can be used to support a DVI process of this scale.


Asunto(s)
Restos Mortales/diagnóstico por imagen , Víctimas de Desastres , Documentación , Antropología Forense/instrumentación , Tomógrafos Computarizados por Rayos X , Tomografía Computarizada por Rayos X/métodos , Incendios , Humanos , Reino Unido
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA