Publications by authors named "Jacques Amar"

80 Publications

Intracellular detection of singlet oxygen using fluorescent nanosensors.

Analyst 2021 May 13. Epub 2021 May 13.

Department of Physics and Astronomy, University of Toledo, Toledo, Ohio, USA.

Detection of singlet oxygen is of great importance for a range of therapeutic applications, particularly photodynamic therapy, plasma therapy and also during photo-endosomolytic activity. Here we present a novel method of intracellular detection of singlet oxygen using biocompatible polymeric nanosensors, encapsulating the organic fluorescent dye, Singlet Oxygen Sensor Green (SOSG) within its hydrophobic core. The singlet oxygen detection efficiency of the nanosensors was quantified experimentally by treating them with a plasma source and these results were further validated by using Monte Carlo simulations. The change in fluorescence intensity of the nanosensors serves as a metric to detect singlet oxygen in the local micro-environment inside mammalian cancer cells. We used these nanosensors for monitoring singlet oxygen inside endosomes and lysosomes of cancer cells, during cold plasma therapy, using a room-temperature Helium plasma jet.
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http://dx.doi.org/10.1039/d1an00456eDOI Listing
May 2021

Visit-to-visit blood pressure variability and incident frailty in older adults.

J Gerontol A Biol Sci Med Sci 2021 Apr 12. Epub 2021 Apr 12.

Gérontopôle de Toulouse, Institut du Vieillissement, CHU de Toulouse, France.

To determine whether visit-to-visit blood pressure (BP) variability (BPV) is associated with incident frailty. We included 1,394 non-frail community-dwelling participants aged ≥ 70 years from the Multidomain Alzheimer Preventive Trial (MAPT) who underwent repeated clinical examinations, including BP and frailty, over a 5-year follow-up period. Systolic BPV (SBPV), diastolic BPV (DBPV), mean arterial pressure variability (MAPV) and pulse pressure variability (PPV) were evaluated using standard deviation, coefficient of variation (CV), average real variability, successive variation, variation independent of mean and residual standard deviation. Incident frailty was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses. Higher SBPV was significantly associated with greater risk of frailty (1-sd increase of CV: HR = 1.18, 95% CI [1.02-1.36]) after adjustment for demographics, systolic BP, antihypertensive drugs, body mass index, diabetes, ischemic heart disease, congestive heart failure, stroke, atrial fibrillation, MAPT randomization group and frailty status. Similar results were observed with all indicators of variability. Higher PPV was associated with a greater risk of developing frailty over time (1-sd increase of CV: HR = 1.17, 95% CI [1.01-1.35]). DBPV and MAPV were not significantly associated with incident frailty. Higher SBPV and PPV were associated with greater risk of incident frailty. Our findings support the concept of BP physiological dysregulation underlying the frail state and suggest that BP instability could be an early marker of frailty.
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http://dx.doi.org/10.1093/gerona/glab112DOI Listing
April 2021

Interactions between hypertension and inflammatory tone and the effect on blood pressure and outcomes in patients with COVID-19.

J Clin Hypertens (Greenwich) 2021 02 24;23(2):238-244. Epub 2021 Jan 24.

Department of Arterial Hypertension, Toulouse University III, Toulouse, France.

Arterial hypertension represented one of the most common comorbidities in patients with COVID-19. However, the impact of hypertension on outcome in COVID-19 patients is not clear. Close connections between inflammation and blood pressure (BP) have been described, and inflammation plays a key role in the outcome for patients with COVID-19. Whether hypertension impairs the relationship between inflammation, BP, and outcomes in this context is not known. The aim of this study was to examine the effects of the interactions between inflammation and hypertension status on BP and clinical outcome in patients hospitalized with COVID-19. We designed a retrospective study in 129 patients hospitalized with COVID-19 at Toulouse University Hospital. The hospital outcome was admission to the intensive care unit or death. The inflammatory markers were blood C-reactive protein level (CRP), neutrophil to lymphocyte, and platelet to lymphocyte ratios. We identified strong correlations between CRP (P < .01) and the other inflammatory markers recorded on admission (P < .001) with mean BP within 3 days after admission in normotensive patients, whereas these correlations were absent in patients with hypertension. Also, we observed after multivariate adjustment (P < .05) that CRP level predicted a worse prognosis in hypertensive patients (relative risk 2.52; 95% confidence intervals [1.03- 6.17]; P = .04), whereas CRP was not predictive of outcome in patients without hypertension. In conclusion, the study revealed that in COVID-19 patients, hypertension impairs the relationship between inflammation and BP and interacts with inflammation to affect prognosis. These findings provide insights that could explain the relationship between hypertension and outcomes in COVID-19 patients.
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http://dx.doi.org/10.1111/jch.14137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013547PMC
February 2021

Severe hypertensive flare-up after intravitreal injection of ranibizumab for retinal venous branch occlusion.

Fundam Clin Pharmacol 2020 Nov 23. Epub 2020 Nov 23.

Service d'Hypertension Artérielle et Thérapeutique, Pôle Cardiovasculaire et Métabolique, Centre Hospitalier Universitaire Rangueil, Toulouse, 31059, France.

Vascular endothelial growth factor (VEGF) proteins are involved in the regulation of angiogenesis. Systemic adverse effects of some anti-VEGF include hypertension, proteinuria and cardiovascular complications which could involve lower systemic VEGF levels. However, the question regarding intravitreal administration of anti-VEGF remains controversial given that the patients receiving these drugs are often elderly and present cardiac risk factors such as arterial hypertension or atrial fibrillation. We report a case of hypertensive flare-up following intravitreal injection of ranibizumab for retinal vein occlusion. The outcome was favourable after adapted antihypertensive treatment. This case report adds to the growing body of evidence suggesting that intravitreal administration of anti-VEGF, regardless of agents, may result in hypertensive episodes in some predisposed patients. Listing this adverse effect should help to minimize risks by heightening clinician and patient awareness and to improve blood pressure monitoring following the intravitreal administration of anti-VEGF agents.
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http://dx.doi.org/10.1111/fcp.12632DOI Listing
November 2020

Spécificités du traitement médicamenteux antihypertenseur chez la femme.

Presse Med 2019 Nov 14;48(11 Pt 1):1261-1264. Epub 2019 Nov 14.

CHU de Toulouse, fédération de cardiologie, service d'HTA, avenue Jean-Pouhles, Toulouse, France.

The impact of antihypertensive drugs on blood pressure does not differ according to the sex. There are women-specific conditions or medical conditions encountered more frequently among womens that guide the selection of therapy such as a desire to become pregnant, a pregnancy, a polycystic ovarian syndrome, breast cancer, osteoporosis or migraine.
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http://dx.doi.org/10.1016/j.lpm.2019.07.028DOI Listing
November 2019

Blood Microbiota Modification After Myocardial Infarction Depends Upon Low-Density Lipoprotein Cholesterol Levels.

J Am Heart Assoc 2019 10 28;8(19):e011797. Epub 2019 Sep 28.

Metabolic and Cardiovascular Diseases Department Rangueil Hospital CHU Toulouse Toulouse France.

Background The role of bacteria on the onset of cardiovascular disease has been suggested. Reciprocally, increased intestinal bacterial translocation and bloodstream infection are common comorbidities associated with heart failure and myocardial infarction (MI). In this context, the aim of this study was to analyze the blood microbiome in patients shortly after acute myocardial infarction. Methods and Results We carried out a case control study comparing 103 patients at high cardiovascular risk but free of coronary disease and 99 patients who had an MI. The blood microbiome was analyzed both quantitatively by 16S quantitative polymerase chain reaction and qualitatively by 16S targeted metagenomic sequencing specifically optimized for blood samples. A significant increase in blood bacterial 16S rDNA concentration was observed in patients admitted for MI. This increase in blood bacterial DNA concentration was independent of post-MI left ventricular function and was more marked in patients with low-density lipoprotein cholesterol ≥1 g/L. In addition, differences in the proportion of numerous bacterial taxa in blood were significantly modified with the onset of MI, thus defining a blood microbiota signature of MI. Among the bacterial taxa whose proportions are decreased in patients with MI, at least 6 are known to include species able to metabolize cholesterol. Conclusions These results could provide the basis for the identification of blood microbiome-based biomarkers for the stratification of MI patients. Furthermore, these findings should provide insight into the mechanism underlying the negative correlation reported between low-density lipoprotein cholesterol concentration and the prognosis at the acute onset of MI and mortality. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02405468.
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http://dx.doi.org/10.1161/JAHA.118.011797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806051PMC
October 2019

Breast cancer and spironolactone: an observational postmarketing study.

Eur J Clin Pharmacol 2019 Nov 15;75(11):1593-1598. Epub 2019 Aug 15.

Service de Pharmacologie Médicale et Clinique, Centre de PharmacoVigilance, de Pharmaco-épidémiologie et d'Informations sur le Médicament, CIC INSERM 1436, UMR INSERM 1027, Faculté de Médecine - Centre Hospitalier Universitaire, Toulouse, France.

Introduction: Recent studies have discussed the risk of breast cancer with antihypertensive drugs. For spironolactone, data are conflicting. The present paper investigates this potential signal in VigiBase, the World Health Organization Global Individual Case Safety Report (ICSR) database.

Methods: In VigiBase, we performed a case/non-case study using data registered from 1981 (spironolactone's marketing authorization) to December 31, 2017. Among women ≥ 50 years, we measured the risk of reporting "Breast malignant tumors" compared with all other adverse drug reactions (as a crude and adjusted (a) reporting odds ratio (ROR 95% CI)) for spironolactone compared with first, all other drugs and second, pseudo aldosterone antagonists (amiloride, triamterene). ROR were adjusted for age, year of report, continent of report, number of drug prescribed, and completeness score. Sensitivity analyses were performed after exclusion of drug competitors (i.e., drugs like estroprogestative therapy and progestogens that could mask a putative signal) and reports from health professionals.

Results: During the study period, 125 ICSRs reported spironolactone exposure and breast malignant cancer in women ≥ 50 years. We failed to find a positive association between spironolactone exposure and breast cancer in comparison with exposure to other drugs (aROR = 0.63 95% CI [0.52-0.75]) or pseudo aldosterone antagonists (amiloride, triamterene) (0.56 [0.44-0.72]). Similar trends were found after exclusion of drug competitors and/or reports from health professionals.

Conclusion: This study did not find evidence for breast cancer associated with spironolactone.
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http://dx.doi.org/10.1007/s00228-019-02740-yDOI Listing
November 2019

Microbiota-Host Crosstalk: A Bridge Between Cardiovascular Risk Factors, Diet, and Cardiovascular Disease.

Authors:
Jacques Amar

Am J Hypertens 2018 07;31(8):941-944

Toulouse teaching hospital, Department of arterial Hypertension, CARDIOMET Institute, Toulouse, France.

Cardiovascular disease is the leading cause of death and is also a major cause of disability worldwide. Indeed, even in well-treated patients for hypertension or dyslipidemia, there is still a high cardiovascular risk called residual risk. It is of utmost importance to identify the pathway leading from risk factors to cardiovascular disease to further improve stroke and myocardial infarction prevention. In this review, we presented some of experimental and epidemiological evidences suggesting that microbiota-host crosstalk is involved in this pathway and bridges the gap between cardiovascular risk factors, diet, and cardiovascular residual risk. We considered the 3 participants in this dialogue: the gut microbiota, the intestinal barrier, and bacterial translocation. We analyzed their relations with cardiovascular risk factors and cardiovascular diseases. Also, we presented some of therapeutic strategies aiming to control microbiota to further prevent cardiovascular disease and the take home messages that can be drawn for clinical practice.
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http://dx.doi.org/10.1093/ajh/hpy067DOI Listing
July 2018

[Host-microbiota crosstalk and cardiovascular diseases].

Authors:
Jacques Amar

Presse Med 2018 Sep 13;47(9):775-779. Epub 2018 Jun 13.

CHU de Toulouse, ESH excellence center, fédération de cardiologie, service d'hypertension artérielle, 1, avenue du Professeur-Jean-Poulhès, TSA 50032, 31059 Toulouse cedex 9, France. Electronic address:

When analyzing the microbiota-host crosstalk, we have to consider three participants in this dialogue: the gut microbiota, the intestinal barrier and bacterial translocation. Experimental data demonstrate that host microbiota crosstalk plays a causal on the regulation of blood pressure, glucose metabolism and the development of atherosclerosis. Host microbiota crosstalk is associated in humans with main cardiovascular risk factors notably hypertension and type 2 diabetes. Host microbiota crosstalk is associated in humans with the onset of cardiovascular diseases. The Mediterranean diet has proven as proven to be an effective strategy in improving cardiovascular prognosis and in changing gut microbiota.
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http://dx.doi.org/10.1016/j.lpm.2018.03.016DOI Listing
September 2018

Arterial stiffness evaluated by pulse wave velocity is not predictive of the improvement in hypertension after adrenal surgery for primary aldosteronism: A multicentre study from the French European Society of Hypertension Excellence Centres.

Arch Cardiovasc Dis 2018 Oct 16;111(10):564-572. Epub 2018 Mar 16.

Department of Therapeutics and Hypertension, Rangueil University Hospital, 31059 Toulouse, France.

Background: Predictive factors associated with normal blood pressure (BP) after unilateral adrenalectomy for primary aldosteronism (PA) are not clearly identified.

Aims: To evaluate the predictive value of arterial stiffness before surgery on BP after surgery.

Methods: During 2009-2013, 96 patients with PA due to unilateral adrenal adenoma who underwent surgery were enrolled in a multicentre open-label, prospective study. Aortic pulse wave velocity (PWV) was assessed before surgery. Patients underwent ambulatory blood pressure monitoring (ABPM) before surgery and 6 and 12months after surgery. Twenty-four h SBP/DBP values were compared in subjects with PWV
Results: BP and PWV were available for 82 patients (mean age 49±12years). Mean 24-hour systolic/diastolic BP (SBP/DBP) values decreased from 144±15/91±9 before surgery to 131±15/84±11mmHg 6months after surgery. At 6months, mean 24-hour SBP did not differ significantly between high versus low PWV groups (SBP-0.8mmHg, 95% confidence interval-6.9 to 5.2, P=0.79). A total of 42.3% of women versus 20.0% of men had 24-hour SBP/DBP<130/80mmHg at 6months (P=0.07) and 57.9% vs. 23.8% at 12months (P=0.03). Higher SBP/DBP was recorded for men versus women after 6months (P=0.01/0.001) and 1year (P=0.04/0.05).

Conclusion: Preoperative arterial stiffness does not predict a beneficial effect of adrenalectomy on BP values.
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http://dx.doi.org/10.1016/j.acvd.2018.01.004DOI Listing
October 2018

Identification by highly sensitive 16S metagenomic sequencing of an unusual case of polymicrobial bacteremia.

J Infect 2017 09 20;75(3):278-280. Epub 2017 May 20.

Vaiomer SAS, Labège, 31670, France; CHU de Toulouse, Rangueil Hospital, 31400, Toulouse, France.

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http://dx.doi.org/10.1016/j.jinf.2017.05.005DOI Listing
September 2017

Island nucleation and growth with anomalous diffusion in one-dimension.

J Chem Phys 2017 Feb;146(7):074702

Department of Physics and Astronomy, University of Toledo, Toledo, Ohio 43606, USA.

Recently a general rate-equation (RE) theory of submonolayer island nucleation and growth was developed [J. G. Amar and M. Semaan, Phys. Rev. E 93, 062805 (2016)] which takes into account the critical island-size i, island fractal dimension d, substrate dimension d, and diffusion exponent μ, and good agreement with simulations was found for the case of irreversible growth corresponding to a critical island-size i=1 with d = 2. Here we present the results of simulations carried out in 1D (corresponding to d = 1) of island nucleation and growth with anomalous diffusion which were carried out for both the case of superdiffusion (μ>1) and subdiffusion (μ<1). Excellent agreement is found with the general RE theory for both irreversible growth (i=1) and reversible growth with i=2 for all 0≤μ≤2.
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http://dx.doi.org/10.1063/1.4976137DOI Listing
February 2017

Reply.

Hepatology 2017 05 30;65(5):1776-1777. Epub 2017 Mar 30.

Vaiomer SAS, Labège, France.

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http://dx.doi.org/10.1002/hep.28986DOI Listing
May 2017

Hypertension and pregnancy: expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology.

Fundam Clin Pharmacol 2017 Feb 21;31(1):83-103. Epub 2016 Dec 21.

French Society of Hypertension, 5 rue des Colonnes du Trône, 75012, Paris, France.

High blood pressure in pregnancy remains, by its complications, the leading cause of morbidity as well as maternal and fetal mortality. The frequency (5-10% of pregnancies) and the potential severity of this disease, for both mother and child, encourage to standardize and to optimize our medical practices. If the short-term complications for the mother and child are well known, long-term ones for the mother are beginning to be better identified. The onset of hypertension during pregnancy disrupts the classic organization of health care and requires the intervention of the general practitioner and/or an obstetrician, a gynecologist, a midwife, a cardiologist, a nephrologist. There is not always a care coordinator, and decisions are sometimes taken with delay. This is what drove the French Society of Hypertension, in partnership with the French National College of Gynecologists-Obstetricians, to develop a consensus proposing easy-to-use guidelines. Educating women and all health professionals to hypertension and its management, in line with current scientific data, is one of the major challenges of this consensus.
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http://dx.doi.org/10.1111/fcp.12254DOI Listing
February 2017

Changes in blood microbiota profiles associated with liver fibrosis in obese patients: A pilot analysis.

Hepatology 2016 12;64(6):2015-2027

Vaiomer SAS, Labège, France.

The early detection of liver fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) is an important clinical need. In view of the suggested role played by bacterial translocation in liver disease and obesity, we sought to investigate the relationship between blood microbiota and liver fibrosis (LF) in European cohorts of patients with severe obesity. We carried out a cross-sectional study of obese patients, well characterized with respect to the severity of the NAFLD, in the cohort FLORINASH. This cohort has been divided into a discovery cohort comprising 50 Spanish patients and then in a validation cohort of 71 Italian patients. Blood bacterial DNA was analyzed both quantitatively by 16S ribosomal DNA (rDNA) quantitative polymerase chain reaction and qualitatively by 16S rDNA targeted metagenomic sequencing and functional metagenome prediction. Spanish plasma bile acid contents were analyzed by liquid chromatography/mass spectrometry. The 16S rDNA concentration was significantly higher in patients of the discovery cohort with LF. By 16S sequencing, we found specific differences in the proportion of several bacterial taxa in both blood and feces that correlate with the presence of LF, thus defining a specific signature of the liver disease. Several secondary/primary bile acid ratios were also decreased with LF in the discovery cohort. We confirmed, in the validation cohort, the correlation between blood 16S rDNA concentration and LF, whereas we did not confirm the specific bacterial taxa signature, despite a similar trend in patients with more-severe fibrosis.

Conclusion: Changes in blood microbiota are associated with LF in obese patients. Blood microbiota analysis provides potential biomarkers for the detection of LF in this population. (Hepatology 2016;64:2015-2027).
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http://dx.doi.org/10.1002/hep.28829DOI Listing
December 2016

[Management of arterial hypertension before 20weeks gestation in pregnant women].

Presse Med 2016 Jul-Aug;45(7-8 Pt 1):627-30. Epub 2016 Aug 21.

CHU de Toulouse, université Paul-Sabatier, service d'hypertension artérielle et de thérapeutique, 31059 Toulouse, France. Electronic address:

In the first 6 months of pregnancy, the primary goal of antihypertensive treatment is to prevent the complications of severe hypertension. Initiation of antihypertensive drug treatment is recommended in pregnant women with severe hypertension (blood pressure>160/110mmHg). Initiation of antihypertensive drug treatment should also be considered in pregnant women at high cardiovascular risk (diabetes, chronic kidney disease, personal history of cardiovascular disease) with moderate hypertension (blood pressure between 140-159/90-109mmHg). A systolic blood pressure goal<160 and a diastolic blood pressure goal between 85 and 100mmHg is recommended in pregnancy. Labetalol, nifedipine, nicardipine and alphamethyldopa should be considered preferential antihypertensive drugs in pregnancy. Salt restriction, physical exercise and weight loss have not demonstrated any effect in the prevention of preeclampsia and serious maternal complications of hypertension.
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http://dx.doi.org/10.1016/j.lpm.2016.06.008DOI Listing
February 2017

Island nucleation and growth with anomalous diffusion.

Phys Rev E 2016 Jun 29;93(6):062805. Epub 2016 Jun 29.

Department of Physics & Astronomy, University of Toledo, Toledo, Ohio 43606, USA.

While most studies of submonolayer island nucleation and growth have been based on the assumption of ordinary monomer diffusion corresponding to diffusion exponent μ=1, in some cases either subdiffusive (μ<1) or superdiffusive (μ>1) behavior may occur. Here we present general expressions for the exponents describing the flux dependence of the island and monomer densities as a function of the critical island size i, substrate dimension d, island fractal dimension d_{f}, and diffusion exponent μ, where 0≤μ≤2. Our results are compared with kinetic Monte Carlo simulations for the case of irreversible island growth (i=1) with 0≤μ≤2 and d=2 as well as simulation results for d=1, 3, and 4, and excellent agreement is found.
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http://dx.doi.org/10.1103/PhysRevE.93.062805DOI Listing
June 2016

[Hypertension and pregnancy. Expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology].

Presse Med 2016 Jul-Aug;45(7-8 Pt 1):682-99. Epub 2016 Jul 9.

Société française d'hypertension artérielle, 5, rue des Colonnes du Trône, 75012 Paris, France.

High blood pressure in pregnancy remains, by its complications, the leading cause of morbidity and maternal and fetal mortality. The frequency (5 to 10% of pregnancies) and the potential severity of this disease, both for mother and child, encourage to standardize and to optimize our medical practices. This is the main objective of this work. If the short-term complications for the mother and child are well known, long-term ones for the mother beginning to be better identified (in particular, the risk of recurrence in a subsequent pregnancy, the risk of chronic hypertension and the increased risk of cardiovascular events). The occurrence of hypertension during pregnancy disturbs the "classic" organization of care. Several health professionals are involved, the general practitioner, obstetrician, gynecologist, midwife, cardiologist, nephrologist… There is not always a care coordinator and decisions are sometimes taken with delay. These data encouraged the French Society of Hypertension to write a consensus offering easy and efficient recommendations. Educate women and all health professionals to hypertension and its management, in line with current scientific data, is one of the major challenges of this consensus.
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http://dx.doi.org/10.1016/j.lpm.2016.05.012DOI Listing
February 2017

Improved scaling of temperature-accelerated dynamics using localization.

J Chem Phys 2016 Jul;145(1):014105

Department of Physics and Astronomy, University of Toledo, Toledo, Ohio 43606, USA.

While temperature-accelerated dynamics (TAD) is a powerful method for carrying out non-equilibrium simulations of systems over extended time scales, the computational cost of serial TAD increases approximately as N(3) where N is the number of atoms. In addition, although a parallel TAD method based on domain decomposition [Y. Shim et al., Phys. Rev. B 76, 205439 (2007)] has been shown to provide significantly improved scaling, the dynamics in such an approach is only approximate while the size of activated events is limited by the spatial decomposition size. Accordingly, it is of interest to develop methods to improve the scaling of serial TAD. As a first step in understanding the factors which determine the scaling behavior, we first present results for the overall scaling of serial TAD and its components, which were obtained from simulations of Ag/Ag(100) growth and Ag/Ag(100) annealing, and compare with theoretical predictions. We then discuss two methods based on localization which may be used to address two of the primary "bottlenecks" to the scaling of serial TAD with system size. By implementing both of these methods, we find that for intermediate system-sizes, the scaling is improved by almost a factor of N(1/2). Some additional possible methods to improve the scaling of TAD are also discussed.
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http://dx.doi.org/10.1063/1.4954996DOI Listing
July 2016

Triggering the adaptive immune system with commensal gut bacteria protects against insulin resistance and dysglycemia.

Mol Metab 2016 Jun 28;5(6):392-403. Epub 2016 Mar 28.

Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse, France; Université Paul Sabatier (UPS), Unité Mixte de Recherche (UMR) 1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Team 2: « Intestinal Risk Factors, Diabetes, Dyslipidemia », 1 avenue Jean Poulhès, BP 84225, F-31432 Toulouse Cedex 4, France. Electronic address:

Objective: To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk.

Methods: We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naïve mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease.

Results: Subcutaneous injection (immunization procedure) of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD.

Conclusions: Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet.
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http://dx.doi.org/10.1016/j.molmet.2016.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877664PMC
June 2016

Comprehensive description of blood microbiome from healthy donors assessed by 16S targeted metagenomic sequencing.

Transfusion 2016 05 10;56(5):1138-47. Epub 2016 Feb 10.

Vaiomer SAS, Labège.

Background: Recent studies have revealed that the blood of healthy humans is not as sterile as previously supposed. The objective of this study was to provide a comprehensive description of the microbiome present in different fractions of the blood of healthy individuals.

Study Design And Methods: The study was conducted in 30 healthy blood donors to the French national blood collection center (Établissement Français du Sang). We have set up a 16S rDNA quantitative polymerase chain reaction assay as well as a 16S targeted metagenomics sequencing pipeline specifically designed to analyze the blood microbiome, which we have used on whole blood as well as on different blood fractions (buffy coat [BC], red blood cells [RBCs], and plasma).

Results: Most of the blood bacterial DNA is located in the BC (93.74%), and RBCs contain more bacterial DNA (6.23%) than the plasma (0.03%). The distribution of 16S DNA is different for each fraction and spreads over a relatively broad range among donors. At the phylum level, blood fractions contain bacterial DNA mostly from the Proteobacteria phylum (more than 80%) but also from Actinobacteria, Firmicutes, and Bacteroidetes. At deeper taxonomic levels, there are striking differences between the bacterial profiles of the different blood fractions.

Conclusion: We demonstrate that a diversified microbiome exists in healthy blood. This microbiome has most likely an important physiologic role and could be implicated in certain transfusion-transmitted bacterial infections. In this regard, the amount of 16S bacterial DNA or the microbiome profile could be monitored to improve the safety of the blood supply.
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http://dx.doi.org/10.1111/trf.13477DOI Listing
May 2016

The Characterization of Novel Tissue Microbiota Using an Optimized 16S Metagenomic Sequencing Pipeline.

PLoS One 2015 6;10(11):e0142334. Epub 2015 Nov 6.

Vaiomer SAS, Labège, France.

Background: Substantial progress in high-throughput metagenomic sequencing methodologies has enabled the characterisation of bacteria from various origins (for example gut and skin). However, the recently-discovered bacterial microbiota present within animal internal tissues has remained unexplored due to technical difficulties associated with these challenging samples.

Results: We have optimized a specific 16S rDNA-targeted metagenomics sequencing (16S metabarcoding) pipeline based on the Illumina MiSeq technology for the analysis of bacterial DNA in human and animal tissues. This was successfully achieved in various mouse tissues despite the high abundance of eukaryotic DNA and PCR inhibitors in these samples. We extensively tested this pipeline on mock communities, negative controls, positive controls and tissues and demonstrated the presence of novel tissue specific bacterial DNA profiles in a variety of organs (including brain, muscle, adipose tissue, liver and heart).

Conclusion: The high throughput and excellent reproducibility of the method ensured exhaustive and precise coverage of the 16S rDNA bacterial variants present in mouse tissues. This optimized 16S metagenomic sequencing pipeline will allow the scientific community to catalogue the bacterial DNA profiles of different tissues and will provide a database to analyse host/bacterial interactions in relation to homeostasis and disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142334PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636327PMC
June 2016

The Gut Microbiota Regulates Intestinal CD4 T Cells Expressing RORγt and Controls Metabolic Disease.

Cell Metab 2015 Jul;22(1):100-12

Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048 F-31432 Toulouse, France; Université Paul Sabatier, F-31432 Toulouse, France. Electronic address:

A high-fat diet (HFD) induces metabolic disease and low-grade metabolic inflammation in response to changes in the intestinal microbiota through as-yet-unknown mechanisms. Here, we show that a HFD-derived ileum microbiota is responsible for a decrease in Th17 cells of the lamina propria in axenic colonized mice. The HFD also changed the expression profiles of intestinal antigen-presenting cells and their ability to generate Th17 cells in vitro. Consistent with these data, the metabolic phenotype was mimicked in RORγt-deficient mice, which lack IL17 and IL22 function, and in the adoptive transfer experiment of T cells from RORγt-deficient mice into Rag1-deficient mice. We conclude that the microbiota of the ileum regulates Th17 cell homeostasis in the small intestine and determines the outcome of metabolic disease.
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http://dx.doi.org/10.1016/j.cmet.2015.06.001DOI Listing
July 2015

Diabetes: Antibiotics or prodiabetics?

Nat Rev Endocrinol 2015 Jul 19;11(7):385-6. Epub 2015 May 19.

Institut des Maladies Métaboliques et Cardiovasculaires, INSERM U1048, 1 Avenue Jean Poulhès, F-31432 Toulouse, France.

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http://dx.doi.org/10.1038/nrendo.2015.75DOI Listing
July 2015

Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance.

EMBO Mol Med 2015 Mar;7(3):259-74

Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada

Pattern recognition receptors link metabolite and bacteria-derived inflammation to insulin resistance during obesity. We demonstrate that NOD2 detection of bacterial cell wall peptidoglycan (PGN) regulates metabolic inflammation and insulin sensitivity. An obesity-promoting high-fat diet (HFD) increased NOD2 in hepatocytes and adipocytes, and NOD2(-/-) mice have increased adipose tissue and liver inflammation and exacerbated insulin resistance during a HFD. This effect is independent of altered adiposity or NOD2 in hematopoietic-derived immune cells. Instead, increased metabolic inflammation and insulin resistance in NOD2(-/-) mice is associated with increased commensal bacterial translocation from the gut into adipose tissue and liver. An intact PGN-NOD2 sensing system regulated gut mucosal bacterial colonization and a metabolic tissue dysbiosis that is a potential trigger for increased metabolic inflammation and insulin resistance. Gut dysbiosis in HFD-fed NOD2(-/-) mice is an independent and transmissible factor that contributes to metabolic inflammation and insulin resistance when transferred to WT, germ-free mice. These findings warrant scrutiny of bacterial component detection, dysbiosis, and protective immune responses in the links between inflammatory gut and metabolic diseases, including diabetes.
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http://dx.doi.org/10.15252/emmm.201404169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364944PMC
March 2015

Critical island-size, stability, and morphology of 2D colloidal Au nanoparticle islands.

J Chem Phys 2015 Jan;142(2):024709

Department of Physics and Astronomy, University of Toledo, Toledo, Ohio 43606, USA.

The critical island-size, stability, and morphology of 2D colloidal Au nanoparticle islands formed during drop-drying are studied using an empirical potential which takes into account core-core, ligand-ligand, and ligand-solvent interactions. Good agreement with experiment is obtained for the dependence of the critical island-size on nanoparticle diameter. Our results for the critical length-scale for smoothing via edge-diffusion are also consistent with the limited facet size and island-relaxation observed in experiments. In addition, the relatively high rate of monomer diffusion on an island as well as the low barrier for interlayer diffusion are consistent with experimental observations that second-layer growth does not occur until after the first layer is complete.
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http://dx.doi.org/10.1063/1.4905144DOI Listing
January 2015

Critical island size, scaling, and ordering in colloidal nanoparticle self-assembly.

Phys Rev E Stat Nonlin Soft Matter Phys 2014 Sep 29;90(3):032406. Epub 2014 Sep 29.

Department of Physics & Astronomy, University of Toledo, Toledo, Ohio 43606, USA.

In order to obtain a better understanding of short-range (SR) and long-range (LR) nanoparticle (NP) interactions during the self-assembly of dodecanethiol-coated Au NPs in toluene via drop drying, we have investigated the dependence of the island density, scaled island-size distribution (ISD), and scaled capture-zone distribution (CZD) on coverage, deposition flux, and NP size. Our results indicate that, while the critical island size is larger than 1 for all NP sizes studied, due to the increase in the strength of the SR attraction between NPs with increasing NP size, both the exponent describing the dependence of the island density on deposition flux and the critical island-size decrease with increasing NP size. We also find that, despite the existence of significant cluster diffusion and coalescence, the ISD is sharply peaked as in epitaxial growth. In particular, for large NP size, we find good agreement between the scaled ISD and epitaxial growth models as well as good agreement between the scaled CZD and scaled ISD. However, for smaller NPs the scaled ISD is less sharply peaked despite the fact that the critical island size is larger. This latter result suggests that in this case additional effects such as enhanced island coalescence or NP detachment from large islands may play an important role. Results for the ordering of NP islands are also presented which indicate the existence of LR repulsive interactions. One possible mechanism for such an interaction is the existence of a small dipole moment on each NP which arises as a result of an asymmetry, driven by surface tension, in the thiol distribution for NPs adsorbed at the toluene-air interface. Consistent with this mechanism, we find good agreement between experimental results for the nearest-neighbor island-distance distribution and simulations which include dipole repulsion.
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http://dx.doi.org/10.1103/PhysRevE.90.032406DOI Listing
September 2014

Adsorption and diffusion of colloidal Au nanoparticles at a liquid-vapor interface.

J Chem Phys 2014 Jun;140(24):244702

Department of Physics and Astronomy, University of Toledo, Toledo, Ohio 43606, USA.

Motivated by recent drop-drying experiments of Au nanoparticle (NP) island self-assembly, we investigate the structure, diffusion, and binding of dodecanethiol-coated Au NPs adsorbed at the toluene-vapor interface using molecular dynamics (MD) simulations as well as analytical calculations. For a 6 nm core diameter NP our results indicate the existence of significant intermixing between the ligands and the solvent. As a result, the NP lies primarily below the interface with only a portion of the ligands sticking out, while the toluene-vapor interface is significantly higher in the region above the NP core than away from the NP. These results are consistent with a competition between the negative free energy of mixing of toluene and the dodecanethiol ligands, which tends to keep the NP below the interface, and the effects of surface tension which keeps the NP near the interface. Consistent with this result, we find that the coefficient for nanoparticle diffusion along the interface is close to the Stokes-Einstein prediction for three-dimensional bulk diffusion. An analysis of the ligand arrangement surrounding the NP also indicates that there is relatively little asymmetry in the ligand-coating. We then consider the effects of van der Waals interactions on the adsorption energy. In particular, we derive an analytical expression for the van der Waals interaction energy between a coated nanoparticle and the surrounding solvent along with a closed-form expression for the van der Waals corrections to the binding energy at the interface due to the long-range core-solvent interaction. Using these results along with the results of our MD simulations, we then estimate the van der Waals corrections to the adsorption energy for dodecanethiol-coated Au nanoparticles at the toluene-vapor interface as well as for decanethiol-coated nanoparticles at the water-vapor interface. In both cases, we find that the long-range core-solvent interaction may significantly reduce the binding energy. Based on these results, we conclude that in many cases, the core-solvent van der Waals interaction is likely to have a significant effect on the binding energy and interface position of Au NPs. Our results also indicate that the competition between the van der Waals interaction and the short-range attraction to the interface leads to the existence of well-defined activation barriers for nanoparticle adsorption from the solvent as well as for interfacial desorption.
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http://dx.doi.org/10.1063/1.4884022DOI Listing
June 2014

Metagenome and metabolism: the tissue microbiota hypothesis.

Diabetes Obes Metab 2013 Sep;15 Suppl 3:61-70

Institut National de Santé et de Recherche Médicale (INSERM), U1048, Toulouse, France.

Over the last decade, the research community has revealed the role of a new organ: the intestinal microbiota. It is considered as a symbiont that is part of our organism since, at birth, it educates the immune system and contributes to the development of the intestinal vasculature and most probably the nervous system. With the advent of new generation sequencing techniques, a catalogue of genes that belong to this microbiome has been established that lists more than 5 million non-redundant genes called the metagenome. Using germ free mice colonized with the microbiota from different origins, it has been formally demonstrated that the intestinal microbiota causes the onset of metabolic diseases. Further to the role of point mutations in our genome, the microbiota can explain the on-going worldwide pandemic of obesity and diabetes, its dissemination and family inheritance, as well as the diversity of the associated metabolic phenotypes. More recently, the discovery of bacterial DNA within host tissues, such as the liver, the adipose tissue and the blood, which establishes a tissue microbiota, introduces new opportunities to identify targets and predictive biomarkers based on the host to microbiota interaction, as well as to define new strategies for pharmacological, immunomodulatory vaccines and nutritional applications.
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http://dx.doi.org/10.1111/dom.12157DOI Listing
September 2013

[Intestinal microbiota and novel therapeutic perspectives for the treatment of metabolic diseases].

Med Sci (Paris) 2013 Aug-Sep;29(8-9):800-6. Epub 2013 Sep 5.

Institut des maladies métaboliques et cardiovasculaires, hôpital Rangueil, Toulouse Cedex, France.

A new organ has emerged over the course of the last century: the intestinal microbiota. It is characterized by numerous functions provided by several billions of bacteria inhabiting and living in harmony in the lumen and in the mucosal layer of the intestinal epithelium. More than 4 million genes composed by more than 1 500 species interact with each other, with the host and the environment to set up a mutualistic ecological group. A nutritional stress will modify the terms of the symbiosis between the host and the microbiota for the control of energy homeostasis. It is now thought that the pandemic of diabetes and obesity, not being due to the sole variations of our genome, would be due to changes in our metagenome: our intestinal bacteria. This organ which genomic varies on an everyday basis is inherited from our mother and the closed environment at birth. The corresponding diversity, the rapid evolution of gene expression, its influence on metabolism, as well as the very recent discovery of the existence of an tissue microbiota within the host, open new therapeutic pharmacological and nutritional opportunities as well as the identification of very accurate biomarkers constituting a personalized metagenomic identity card. Hence, individualized medicine foresees its origin within the metagenome.
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http://dx.doi.org/10.1051/medsci/2013298021DOI Listing
November 2013