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1.
Inorg Chem ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32378897

RESUMO

The three Co(II) complexes [Co(bbp)2][Co(NCS)4]·4DMF (1), [Co(bbp)(NCS)2(DMF)]·2DMF (2), and [Co(bbp)(NCS)2] (3) have been synthesized and characterized by single-crystal X-ray diffraction, magnetic, and various spectroscopic techniques. Complexes 1 and 3 are obtained by the reaction of Co(NCS)2 with 2,6-bis(1H-benzo[d]imidazol-2-yl)pyridine (bbp), and complex 1 undergoes a structural transformation to form complex 2. A single-crystal X-ray study revealed that complex 1 is comprised of two Co(II) centers, a cationic octahedral Co(II) unit and an anionic tetrahedral Co(II) unit, while the Co(II) ion is in a distorted-octahedral environment in 2. Moreover, in complex 3, the Co(II) ion is in a distorted-square-pyramidal geometry. The effect of coordination geometry on the magnetic properties was studied by both static and dynamic magnetic measurements. Direct current (dc) magnetic susceptibility measurements showed that all of the Co(II) ions are in high-spin state in these complexes. Alternating current (ac) magnetic susceptibility measurements indicated that complexes 2 and 3 display slow relaxation of magnetization in an external dc magnetic field, while complex 1 displayed no such property. EPR experiments and theoretical calculations were consistent with the above findings.

2.
Malar J ; 19(1): 179, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393251

RESUMO

BACKGROUND: Rapid diagnostic tests (RDTs) detecting the histidine-rich protein 2 (PfHRP2) have a central position for the management of Plasmodium falciparum infections. Yet, variable detection of certain targeted motifs, low parasitaemia, but also deletion of pfhrp2 gene or its homologue pfhrp3, may result in false-negative RDT leading to misdiagnosis and delayed treatment. This study aimed at investigating the prevalence, and understanding the possible causes, of P. falciparum RDT-negative infections at Montpellier Academic Hospital, France. METHODS: The prevalence of falsely-negative RDT results reported before and after the introduction of a loop-mediated isothermal amplification (LAMP) assay, as part as the malaria screening strategy in January 2017, was analysed. Negative P. falciparum RDT infections were screened for pfhrp2 or pfhrp3 deletion; and exons 2 were sequenced to show a putative genetic diversity impairing PfHRP2 detection. RESULTS: The overall prevalence of P. falciparum negative RDTs from January 2006 to December 2018 was low (3/446). Whereas no cases were reported from 2006 to 2016 (0/373), period during which the malaria diagnostic screen was based on microscopy and RDT, prevalence increased up to 4.1% (3/73) between 2017 and 2018, when molecular detection was implemented for primary screening. Neither pfhrp2/3 deletion nor major variation in the frequency of repetitive epitopes could explain these false-negative RDT results. CONCLUSION: This paper demonstrates the presence of pfhrp2 and pfhrp3 genes in three P. falciparum RDT-negative infections and reviews the possible reasons for non-detection of HRP2/3 antigens in a non-endemic setting. It highlights the emergence of falsely negative rapid diagnostic tests in a non-endemic setting and draws attention on the risk of missing malaria cases with low parasitaemia infections using the RDT plus microscopy-based strategy currently recommended by French authorities. The relevance of a novel diagnostic scheme based upon a LAMP assay is discussed.

3.
J Gynecol Obstet Hum Reprod ; : 101778, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32360485

RESUMO

INTRODUCTION: Sacrospinofixation is used for fundic vaginal vault's prolapse or to prevent mid-level or posterior prolapse. It can lead to complications such as dyspareunia, chronic pain, and quality of life impairment. Anchoring a posterior isthmic sling to the two sacrospinous ligaments is an alternative to classic Richter's sacrospinofixation. Objective of this study is to report the first cases of vaginal posterior isthmic slings. METHODS: This study is retrospective and unicentric. It includes women who had posterior isthmic sling at the time of a surgery with a mesh for anterior prolapse by vaginal way between 2010 and 2016 in the gynecologic department of a teaching hospital. Report of efficacy and tolerance was performed. RESULTS: Between 2010 and 2016, 53 women were included with a posterior isthmic sling and a mesh for an anterior prolapse. POP-Q evolution during the follow-up in the posterior isthmic sling group assess of a good efficacy of the sling. Four women (7.5%) required second surgery in 28 months following initial surgery (only 1 for excision). Four women (7.5%) had a prolapse recurrence in a mean time of 30 months without recurrent surgery. Women's satisfaction level was high (8.0/10 [7,1-8,8]). CONCLUSION: Efficacy and tolerance of the posterior isthmic sling seems good. It might then be an option for mid-level prolapses in case of vaginal surgery with mesh for anterior prolapse. A non-inferiority trial should be performed to be able to conclude on the place of this alternative to Richter's sacrospinofixation.

4.
Alzheimers Res Ther ; 12(1): 66, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460855

RESUMO

BACKGROUND: There is growing interest in identifying sensitive composite cognitive tests to serve as primary endpoints in preclinical Alzheimer's disease (AD) treatment trials. We reported previously a composite cognitive test score sensitive to tracking preclinical AD decline up to 5 years prior to clinical diagnosis. Here we expand upon and refine this work, empirically deriving a composite cognitive test score sensitive to tracking preclinical AD decline up to 11 years prior to diagnosis and suitable for use as a primary endpoint in a preclinical AD trial. METHODS: This study used a longitudinal approach to maximize sensitivity to tracking progressive cognitive decline in people who progressed to the clinical stages of AD (n = 868) compared to those who remained cognitively unimpaired during the same time period (n = 989), thereby correcting for normal aging and practice effects. Specifically, we developed the Alzheimer's Prevention Initiative Preclinical Composite Cognitive test (APCC) to measure very early longitudinal cognitive decline in older adults with preclinical AD. Data from three cohorts from Rush University were analyzed using a partial least squares (PLS) regression model to identify optimal composites within different time periods prior to diagnosis, up to 11 years prior to diagnosis. The mean-to-standard deviation ratio (MSDRs) is an indicator of sensitivity to change and was used to inform the final calculation of the composite score. RESULTS: The optimal composite, the APCC, is calculated: 0.26*Symbol Digit Modalities + 2.24*MMSE Orientation to Time + 2.14*MMSE Orientation to Place + 0.53*Logical Memory Delayed Recall + 1.36* Word List-Delayed Recall + 0.68*Judgment of Line Orientation + 1.39*Raven's Progressive Matrices Matrices (subset of 9 items from A and B). The MSDR of the APCC in a population of preclinical AD individuals who eventually progress to cognitive impairment, compared to those who remained cognitively unimpaired during the same time period, was - 1.10 over 1 year. CONCLUSIONS: The APCC is an empirically derived composite cognitive test score with high face validity that is sensitive to preclinical AD decline up to 11 years prior to diagnosis of the clinical stages of AD. The components of the APCC are supported by theoretical understanding of cognitive decline that occurs during preclinical AD. The APCC was used as a primary outcome in the API Generation Program trials.

5.
Eur Radiol ; 30(7): 3960-3967, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32100088

RESUMO

OBJECTIVES: In the ascending aorta, calcification density was independently and inversely associated with cardiovascular disease (CVD) risk prediction. Until now, the density of thoracic aorta calcium (TAC) was estimated as the Agatston score divided by the calcium area (DAG). We thought to analyze TAC density in a full Hounsfield unit (HU) range and to study its association with TAC volume, traditional risk factors, and CVD events. METHODS: Non-enhanced CT images of 1426 patients at intermediate risk were retrospectively reviewed. A calcium density score was estimated as the average of the maximum HU attenuation in all calcified plaques of the entire thoracic aorta (DAV). RESULTS: During a mean 4.0 years follow-up, there were 26 events for a total of 674 patients with TAC > 0. TAC volume and DAV were positively correlated (R = 0.72). The median DAV value was 457 HU (IQ 323-603 HU) and was exponentially related to DAG (R = 0.86). DAV was inversely associated with systolic pressure (p < 0.05), pulse pressure (p < 0.01), hypertension (p < 0.05), and 10-year FRS (p < 0.001) after adjusting for TAC volume. When TAC volume and DAV were included in a logistic model, a significant improvement was shown in CVD risk estimation beyond coronary artery calcium (CAC) (AUC = 0.768 vs 0.814, p < 0.05). In multivariable Cox models, TAC volume and DAV showed an independent association with CVD. CONCLUSIONS: In intermediate risk patients, TAC density was inversely associated with several risk factors after adjustment for TAC volume. A significant improvement was observed over CAC when TAC volume and density were added into the risk prediction model. KEY POINTS: • Calcifications in the aorta can be non-invasively assessed using CT images • A higher calcium score is associated with a higher cardiovascular risk • Measuring the calcifications size and the density separately can improve the risk prediction.

6.
Chem Sci ; 10(38): 8855-8871, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31803460

RESUMO

The concurrent effects of single-ion anisotropy and exchange interactions on the electronic structure and magnetization dynamics have been analyzed for a cobalt(ii)-semiquinonate complex. Analogs containing diamagnetic catecholate and tropolonate ligands were employed for comparison of the magnetic behavior and zinc congeners assisted with the spectroscopic characterization and assessment of intermolecular interactions in the cobalt(ii) compounds. Low temperature X-band (ν ≈ 9.4 GHz) and W-Band (ν ≈ 94 GHz) electron paramagnetic resonance spectroscopy and static and dynamic magnetic measurements have been used to elucidate the electronic structure of the high spin cobalt(ii) ion in [Co(Me3tpa)(Br4cat)] (1; Me3tpa = tris[(6-methyl-2-pyridyl)methyl]amine, Br4cat2- = tetrabromocatecholate) and [Co(Me3tpa)(trop)](PF6) (2(PF6); trop- = tropolonate), which show slow relaxation of the magnetization in applied field. The cobalt(ii)-semiquinonate exchange interaction in [Co(Me3tpa)(dbsq)](PF6)·tol (3(PF6)·tol; dbsq- = 3,5-di-tert-butylsemiquinonate, tol = toluene) has been determined using an anisotropic exchange Hamiltonian in conjunction with multistate restricted active space self-consistent field ab initio modeling and wavefunction analysis, with comparison to magnetic and inelastic neutron scattering data. Our results demonstrate dominant ferromagnetic exchange for 3+ that is of similar magnitude to the anisotropy parameters of the cobalt(ii) ion and contains a significant contribution from spin-orbit coupling. The nature of the exchange coupling between octahedral high spin cobalt(ii) and semiquinonate ligands is a longstanding question; answering this question for the specific case of 3+ has confirmed the considerable sensitivity of the exchange to the molecular structure. The methodology employed will be generally applicable for elucidating exchange coupling between orbitally-degenerate metal ions and radical ligands and relevant to the development of bistable molecules and their integration into devices.

7.
Rev Prat ; 69(4): e111-e115, 2019 Apr.
Artigo em Francês | MEDLINE | ID: mdl-31626508
8.
PLoS One ; 14(9): e0219276, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31560697

RESUMO

PCR inhibition is frequent in medical microbiology routine practice and may lead to false-negative results; however there is no consensus on how to detect it. Pathogen-specific and human gene amplifications are widely used to detect PCR inhibition. We aimed at comparing the value of PCR inhibitor detection using these two methods. We analysed Cp shifts (ΔCp) obtained from qPCRs targeting either the albumin gene or the pathogen-specific sequence used in two laboratory-developed microbiological qPCR assays. 3152 samples including various matrixes were included. Pathogen-specific amplification and albumin qPCR identified 62/3152 samples (2.0%), and 409/3152 (13.0%) samples, respectively, as inhibited. Only 16 samples were detected using both methods. In addition, the use of the Youden's index failed to determine adequate Cp thresholds for albumin qPCR, even when we distinguished among the different sample matrixes. qPCR targeting the albumin gene therefore appears not adequate to identify the presence of PCR inhibitors in microbiological PCR assays. Our data may be extrapolated to other heterologous targets and should discourage their use to assess the presence of PCR inhibition in microbiological PCR assays.


Assuntos
Amplificação de Genes , Técnicas Microbiológicas , Reação em Cadeia da Polimerase em Tempo Real , Humanos , Técnicas Microbiológicas/métodos , Técnicas Microbiológicas/normas , Pneumocystis/classificação , Pneumocystis/genética , Infecções por Pneumocystis/diagnóstico , Infecções por Pneumocystis/microbiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/normas , Estudos Retrospectivos , Sensibilidade e Especificidade , Toxoplasma/classificação , Toxoplasma/genética , Toxoplasmose/diagnóstico , Toxoplasmose/microbiologia
9.
Drug Test Anal ; 11(11-12): 1698-1713, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31301268

RESUMO

The combination of growth hormone (GH) and recombinant erythropoietin (rEPO) is thought to be used particularly in endurance sports. Our objective was to reproduce a 2-week administration of rEPO microdoses alone or in combination with GH microdoses (three times a week) on healthy and athletic male subjects and to evaluate if GH had any additional effects compared to EPO treatment alone. The effects of the treatments on hematological parameters and VO2max were studied as well as the detection of GH in serum. While the rEPO microdose regimen was associated with a significant increase in reticulocytes, no clear elevation in hemoglobin concentration (HGB) was observed. Using a correction by plasma volume did not reveal more effects of EPO on HGB. Our results did not show any additional effect when the GH microdoses were co-administered. In addition, no clear increase in VO2max was observed after treatment, with an elevation in only half the subjects in both groups (EPO and EPO+GH). A clear effect of GH on insulin-like growth factor I (IGF-I) was seen but it was lower on procollagen III amino-terminal propeptide (P-III-NP). GH detection using the direct isoform test identified only one subject 24 hours after receiving GH. The GH biomarker test combining IGF-I and P-III-NP was not able to detect the GH administration. However, a longitudinal follow-up of the intraindividual variations showed a significant increase in IGF-I 24 and 48 hours after GH administration in most subjects, while the effect of GH microdoses on P-III-NP was less straightforward.


Assuntos
Eritropoetina/sangue , Eritropoetina/farmacologia , Hormônio do Crescimento/sangue , Hormônio do Crescimento/farmacologia , Doping nos Esportes , Relação Dose-Resposta a Droga , Contagem de Eritrócitos , Eritropoetina/administração & dosagem , Hormônio do Crescimento/administração & dosagem , Humanos , Masculino , Oxigênio/metabolismo , Reticulócitos/citologia , Reticulócitos/efeitos dos fármacos , Detecção do Abuso de Substâncias/métodos
10.
Sante Publique ; Vol. 31(1): 83-92, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31210521

RESUMO

OBJECTIVE: The goal of this review is to present online social support interventions described in recent scientific literature, in order to (i) guide organizations wishing to develop such an intervention or to improve an existing program, and (ii) to identify future research directions and recommendations for practitioners. METHODS AND RESULTS: 59 peer-reviewed articles presenting online social support interventions (2006-2016) were analyzed by using a thematic grid focusing on theoretical perspectives on social support, the online platforms used and their functionalities, the process of intervention development and evaluation, the modalities of participation and the facilitation methods, the documented impacts of interventions, and finally future research directions and recommendations for practitioners. A narrative methodology was used to identify challenges in intervention development and implementation, in order to provide guidance to organizations who want to develop or improve their online social support services. CONCLUSIONS: Several research directions and recommendations for the development of online social support interventions are suggested, including the need to develop theoretical models of online social support and enrich traditional models of social support, the need to understand the benefits associated with different levels of participation, the importance of needs assessment in the development of interventions, and the contribution of qualitative methods to the evaluation of interventions.


Assuntos
Promoção da Saúde/métodos , Internet , Rede Social , Apoio Social , Humanos , Motivação , Pesquisa/tendências , Grupos de Autoajuda
11.
Alzheimers Dement (N Y) ; 5: 216-227, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31211217

RESUMO

Introduction: Alzheimer's disease (AD) pathology, including the accumulation of amyloid beta (Aß) species and tau pathology, begins decades before the onset of cognitive impairment. This long preclinical period provides an opportunity for clinical trials designed to prevent or delay the onset of cognitive impairment due to AD. Under the umbrella of the Alzheimer's Prevention Initiative Generation Program, therapies targeting Aß, including CNP520 (umibecestat), a ß-site-amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibitor, and CAD106, an active Aß immunotherapy, are in clinical development in preclinical AD. Methods: The Alzheimer's Prevention Initiative Generation Program comprises two pivotal (phase 2/3) studies that assess the efficacy and safety of umibecestat and CAD106 in cognitively unimpaired individuals with high risk for developing symptoms of AD based on their age (60-75 years), APOE4 genotype, and, for heterozygotes (APOE ε2/ε4 or ε3/ε4), elevated brain amyloid. Approximately, 3500 individuals will be enrolled in either Generation Study 1 (randomized to cohort 1 [CAD106 injection or placebo, 5:3] or cohort 2 [oral umibecestat 50 mg or placebo, 3:2]) or Generation Study 2 (randomized to oral umibecestat 50 mg and 15 mg, or placebo [2:1:2]). Participants receive treatment for at least 60 months and up to a maximum of 96 months. Primary outcomes include time to event, with event defined as diagnosis of mild cognitive impairment due to AD and/or dementia due to AD, and the Alzheimer's Prevention Initiative preclinical composite cognitive test battery. Secondary endpoints include the Clinical Dementia Rating Sum of Boxes, Repeatable Battery for the Assessment of Neuropsychological Status total score, Everyday Cognition Scale, biomarkers, and brain imaging. Discussion: The Generation Program is designed to assess the efficacy, safety, and biomarker effects of the two treatments in individuals at high risk for AD. It may also provide a plausible test of the amyloid hypothesis and further accelerate the evaluation of AD prevention therapies.

12.
Chemosphere ; 234: 242-251, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31226506

RESUMO

The development of methods to automatically determine the chemical nature of microplastics by FTIR-ATR spectra is an important challenge. A machine learning method, named k-nearest neighbors classification, has been applied on spectra of microplastics collected during Tara Expedition in the Mediterranean Sea (2014). To realize these tests, a learning database composed of 969 microplastic spectra has been created. Results show that the machine learning process is very efficient to identify spectra of classical polymers such as poly(ethylene), but also that the learning database must be enhanced with less common microplastic spectra. Finally, this method has been applied on more than 4000 spectra of unidentified microplastics. The verification protocol showed less than 10% difference in the results between the proposed automated method and a human expertise, 75% of which can be very easily corrected.


Assuntos
Algoritmos , Aprendizado de Máquina , Plásticos/análise , Plásticos/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Monitoramento Ambiental/métodos , Humanos , Mar Mediterrâneo
13.
Tissue Eng Part A ; 25(23-24): 1667-1676, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31062647

RESUMO

Although skeletal muscle is capable of complete recovery after an injury, specific situations require support or acceleration of this process, such as in the elderly and athletes, respectively. Skeletal muscle regeneration is due to muscle stem cells (MuSCs) that undergo adult myogenesis, a process sustained by MuSC environment. Although recognized as important, extracellular matrix (ECM) has been overlooked in this process. Matrix-based therapy aims at improving ECM remodeling to support tissue repair. In this context, we investigated the properties of a single injection of the clinical grade glycosaminoglycan mimetics RGTA® (ReGeneraTing Agents) on skeletal muscle regeneration in a context compatible with a clinical application, that is, 3 days after the injury. Our results show that RGTA-treated muscles showed an increase of the number of myonuclei in regenerating myofibers and an increase of the capillarization of the new myofibers. In vitro experiments showed that RGTA directly acts on MuSCs by stimulating their fusion into myotubes and on endothelial cells by stimulating the formation and maturation of vessels in a 3D culture setup. These results indicate that a single administration of RGTA in regenerating muscle stimulated both myogenesis and angiogenesis, thus accelerating skeletal muscle regeneration. Impact Statement Although highly powerful in normal condition, postinjury skeletal muscle regeneration is less efficient in some situations, such as obese, elderly, or resting people. In other context, such as high-performance sport, skeletal muscle regeneration must be shortened but in a way ensuring a full functional recovery. In this context, our results show that a single injection of the clinical grade glycosaminoglycan mimetics RGTA® (ReGeneraTing Agents), in a context compatible with a clinical application, that is, 3 days after the injury, is beneficial for skeletal muscle regeneration, through the stimulation of both myogenesis and angiogenesis.

14.
Clin Hemorheol Microcirc ; 71(4): 379-385, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31006675

RESUMO

 The ideal hematocrit is the hematocrit (Hct) value resulting in the highest value of Hct/viscosity (h/η) ratio and can thus be predicted from viscometric measurements with the use of equations such as Quemada's one which yield the determination of the bell-shaped curve of h/η as a function of Hct. In a series of recent papers we applied this approach to various populations, using viscometry at high shear rate (1000 s-1). However the shape of this curve has been reported to be dependent on the shear rate, resulting in a right-shift in this top value when Hct increase. We present here in 11 young recreative athletes the evolution of the predicted top of the h/η curve and optimal theoretical Hct and the discrepancy between theoretical and optimal values over the range of shear rates 1 to 6000 s-1. Results show that the predicted optimal value of both h/η and Hct increases when shear rate increases and that the discrepancy between predicted laquooptimalraquo and actual values decreases and becomes almost asymptotic at very high shear (500 s-1). It is minimal at 2720 s-1. The correlation between predicted laquooptimalraquo and actual values of both parameters describes the same evolution. Therefore, it is better for assessing h/η and its agreement with theoretical values, and for determining the theoretical ideal hematocrit, to measure blood viscosity at shear rates equal or superior to 500 s-1.


Assuntos
Viscosidade Sanguínea/fisiologia , Hematócrito/métodos , Hemorreologia/fisiologia , Humanos
15.
Clin Hemorheol Microcirc ; 71(4): 387-396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31006676

RESUMO

Physiological modifications of blood rheology during pregnancy and their alterations in pregnant hypertensive women have been extensively studied in the 1980's. Since vascular resistance is higher in hypertensive pregnant women whose newborns are small-for gestational-age (SGA), we investigated in a personal database if growth retardation of newborns is related to the oxygen delivery index (ratio hematocrit/blood viscosity) and to the difference between hematocrit (Hct) and the prediction of its optimal valued based on Quemada's equation. A sample of 38 hypertensive pregnant women (age 29 yr±1) was compared with 64 controls matched for age and gestational age, studied at 35±1 weeks gestation, extracted from a larger series of 162 pregnant women. On the whole the hypertensive group gave birth to smaller children (p = 0.014). Plasma viscosity correlated with blood pressure (BP) only in hypertensive women (r = 0.403 p < 0.05). The bell-shaped curve of predicted optimal Hct of non hypertensive pregnant women was similar to that of non-pregnant women, but in hypertensive women it was shifted toward higher values (p = 0.07), and the predicted optimal Hct (but not the actual one) was correlated with systolic blood pressure (SBP) (r = 0.349 p < 0.001) and diastolic blood pressure (DBP) (r = 0.218 p < 0.05). The predicted optimal Hct/viscosity (h/η) ratio was higher in hypertensive women whose newborns exhibited a low birth weight (p = 0.03), resulting in a higher discrepancy between actual and model-predicted «ideal¼ values of h/η ratio (p = 0.03) and Hct (p = 0.02) compared with the subgroup with no growth retardation. Therefore, in hypertensive women whose newborns exhibited a low birth weight, hemorheological parameters predicting oxygen supply are shifted to lower values than predicted by the model.


Assuntos
Pressão Sanguínea/fisiologia , Viscosidade Sanguínea/fisiologia , Retardo do Crescimento Fetal/fisiopatologia , Hematócrito/métodos , Hemorreologia/fisiologia , Hipertensão/fisiopatologia , Oxigênio/fisiologia , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez
16.
Clin Hemorheol Microcirc ; 71(4): 397-402, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31006677

RESUMO

 We previously reported that whole body bioelectrical impedance analysis (BIA) measurements are correlated to some hemorheologic factors, suggesting a relationship between viscosity factors and electric properties of flowing blood not only in vitro but also in vivo. Recently we reported that with segmental BIA (analyzing the body considered as composed of 5 cylinders) predictive equations for various determinants of blood viscosity were closer than for the wole body. Another widely used BIA technique uses leg-to-leg impedance measurements so that two cylinders (the two legs) are analyzed. We investigated whether impedance measured with this technique (Tanita TBF-300) is also a predictor of blood viscosity factors. From viscometric measurements performed on venous blood drawn in recreative athletes over the range of shear rates 1 to 6000 s-1 (RHEOMETRE Anton Paar CP 50-1), we found a correlation between leg-leg resistance at 50 kHz (Rx[50 kHz]) and blood viscosity at 1000 s-1 (η1000= 0.0051 Rx[50 kHz] + 1.3265; r = 0.521 p = 0.028 yielding a prediction of η1000 (Bland Altman plot: bias 0.05 [RANGE - 0.24; 0.34]. Neither plasma viscosity nor the red cell rheology index «k¼ of Quemada's model are correlated with Rx[50 kHz], but hematocrit (Hct) does (Hct (%) = 0.0217 Rx[50 kHz] + 33.783; r = 0.480 p = 0.044) yielding a prediction of Hct (Bland Altman plot: bias - 0.11, [range - 1.67; 1.45]. The discrepancy between actual and predicted Hct is also correlated with resistance at 50 kHz (r = 0.575 p = 0.031) as does the discrepancy between actual and predicted Hct/viscosity ratio (r = -0.651 p = 0.006). Therefore, as other previously studied methods, leg to leg BIA predicts viscosity, suggesting that blood rheology may influence the passage of an electric current in the legs.


Assuntos
Viscosidade Sanguínea/fisiologia , Impedância Elétrica/uso terapêutico , Hematócrito/métodos , Hemorreologia/fisiologia , Perna (Membro)/irrigação sanguínea , Adulto , Feminino , Humanos , Masculino , Viscosidade
17.
J Gynecol Obstet Hum Reprod ; 48(6): 391-394, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30905851

RESUMO

OBJECTIVE: Cervical cerclage is the principal treatment for women with a cervical insufficiency, which is a predominant factor in second trimester loss and preterm birth. A cervico-isthmic cerclage is recommended in case of a previous failure of McDonald cerclage or in case of an absent portio vaginalis of the cervix. In women who have prolapsed membranes at or beyond a dilated external cervical os before 24 weeks of gestation, an emergency cerclage can sometimes be performed. The aim of this study is to report our experience with emergency transvaginal cervico-isthmic cerclage. STUDY DESIGN: This is a retrospective, single-centre study conducted between 2009 and 2017 of women who received a transvaginal cervico-isthmic emergency cerclage. Emergency cerclage was defined as cerclage performed on women who had prolapsed membranes at or beyong a dilated external cervical os before 24 weeks of gestation. The exclusion criteria were twin pregnancy, preterm rupture of membranes, and clinical or biological signs of infection. RESULTS: Three women were included. One woman had a history of failure of emergency McDonald cerclage during her previous pregnancy. The two other women had a failure of McDonald cerclage during index pregnancy. All women presented prolapsed membranes at or beyond a dilated external cervical os as defined for an emergency cerclage. The emergency cerclage was performed at a mean gestational age of 21.5 weeks of gestation. The average gestational age of delivery was 38.5 weeks of gestation by caesarean section. CONCLUSION: Despite the small number of women, this study shows that this type of cerclage was effective in pregnancy prolongation for women at high risk of preterm birth in case of McDonald cerclage failure. Nevertheless, this technique requires a trained surgical team. A randomised trial should be performed to evaluate the need for emergency vaginal cervico-isthmic cerclage.


Assuntos
Cerclagem Cervical/métodos , Vagina , Adulto , Colo do Útero/cirurgia , Cesárea , Tratamento de Emergência , Feminino , Idade Gestacional , Humanos , Primeira Fase do Trabalho de Parto , Gravidez , Nascimento Prematuro/prevenção & controle , Estudos Retrospectivos , Falha de Tratamento , Incompetência do Colo do Útero/cirurgia
18.
Inorg Chem ; 58(7): 4230-4243, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30892028

RESUMO

The family of complexes of general formula [Co(Me ntpa)(Xdiox)]+ (tpa = tris(2-pyridylmethyl)amine, n = 0-3 corresponds to successive methylation of the 6-position of the pyridine rings; X = Br4, Cl4, H4, 3,5-Me2, 3,5- tBu2; diox = dioxolene) was investigated by density functional theory (DFT) calculations to predict the likelihood of valence tautomerism (VT). The OPBE functional with relativistic and solvent corrections allowed accurate reproduction of trends in spin-state energetics, affording the prediction of VT in complex [Co(Me3tpa)(Br4diox)]+ (1+). One-electron oxidation of neutral precursor [CoII(Me3tpa)(Br4cat)] (1) enabled isolation of target compounds 1(PF6) and 1(BPh4). Solution variable-temperature UV-vis absorption and Evans method magnetic susceptibility data confirm DFT predictions that 1+ exists in a temperature-dependent valence tautomeric equilibrium between low-spin Co(III)-catecholate and high-spin Co(II)-semiquinonate forms. The solution VT transition temperature of 1+ is solvent-tunable with critical temperatures in the range of 291-359 K for the solvents measured. Solid-state magnetic susceptibility measurements of 1(PF6) and 1(BPh4) reveal the onset of VT transitions above room temperature.

19.
J Virol ; 93(10)2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30842319

RESUMO

Recent emergence of direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) proteins has considerably enhanced the success of antiviral therapy. However, the appearance of DAA-resistant-associated variants is a cause of treatment failure, and the high cost of DAAs renders the therapy not accessible in countries with inadequate medical infrastructures. Therefore, the search for new inhibitors with a lower cost of production should be pursued. In this context, the crude extract of Juncus maritimus Lam. was shown to exhibit high antiviral activity against HCV in cell culture. Bio-guided fractionation allowed the isolation and identification of the active compound, dehydrojuncusol. A time-of-addition assay showed that dehydrojuncusol significantly inhibited HCV infection when added after virus inoculation of HCV genotype 2a (50% effective concentration [EC50] = 1.35 µM). This antiviral activity was confirmed with an HCV subgenomic replicon, and no effect on HCV pseudoparticle entry was observed. Antiviral activity of dehydrojuncusol was also demonstrated in primary human hepatocytes. No in vitro toxicity was observed at active concentrations. Dehydrojuncusol is also efficient on HCV genotype 3a and can be used in combination with sofosbuvir. Interestingly, dehydrojuncusol was able to inhibit RNA replication of two frequent daclatasvir-resistant mutants (L31M or Y93H in NS5A). Finally, mutants resistant to dehydrojuncusol were obtained and showed that the HCV NS5A protein is the target of the molecule. In conclusion, dehydrojuncusol, a natural compound extracted from J. maritimus, inhibits infection of different HCV genotypes by targeting the NS5A protein and is active against resistant HCV variants frequently found in patients with treatment failure.IMPORTANCE Tens of millions of people are infected with hepatitis C virus (HCV) worldwide. Recently marketed direct-acting antivirals (DAAs) targeting HCV proteins have enhanced the efficacy of treatment. However, due to its high cost, this new therapy is not accessible to the vast majority of infected patients. Furthermore, treatment failures have also been reported due to the appearance of viral resistance. Here, we report on the identification of a new HCV inhibitor, dehydrojuncusol, that targets HCV NS5A and is able to inhibit RNA replication of replicons harboring resistance mutations to anti-NS5A DAAs used in current therapy. Dehydrojuncusol is a natural compound isolated from Juncus maritimus, a halophilic plant species that is very common in coastlines worldwide. This molecule might serve as a lead for the development of a new therapy that is more accessible to hepatitis C patients in the future.


Assuntos
Hepacivirus/efeitos dos fármacos , Fenantrenos/farmacologia , Replicação Viral/efeitos dos fármacos , Antivirais/farmacologia , Linhagem Celular , Farmacorresistência Viral/genética , Genótipo , Células HEK293 , Hepacivirus/genética , Hepatite C/genética , Hepatite C/virologia , Hepatite C Crônica/virologia , Hepatócitos/virologia , Humanos , Fenantrenos/metabolismo , Fenetilaminas/farmacologia , Extratos Vegetais/farmacologia , Inibidores de Proteases/farmacologia , Replicon/efeitos dos fármacos , Rizoma
20.
PLoS One ; 14(2): e0212088, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30742663

RESUMO

The study of microplastic pollution involves multidisciplinary analyses on a large number of microplastics. Therefore, providing an overview of plastic pollution is time consuming and, despite high throughput analyses, remains a major challenge. The objective of this study is to propose a protocol to determine how many microplastics must be analyzed to give a representative view of the particle size distribution and chemical nature, and calculate the associated margin error. Based on microplastic data from Tara Mediterranean campaign, this approach is explained through different examples. In this particular case, the results show that only 3% of the collected microplastics need to be analyzed to give a precise view on the scale of the North West Mediterranean Basin (error <5%), and 17.7% to give an overview manta per manta (error <10%). This approach could be an important practical contribution to microplastic studies.


Assuntos
Poluição Ambiental/análise , Plásticos/análise , Água do Mar/análise , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Mar Mediterrâneo , Tamanho da Partícula , Reprodutibilidade dos Testes , Espectrofotometria , Espectroscopia de Infravermelho com Transformada de Fourier
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