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1.
Pediatr Allergy Immunol ; 35(6): e14169, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38837464

RESUMO

BACKGROUND: Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in infants. RSV bronchiolitis is associated with an increased risk of subsequent wheezing. We aimed to document the parents' perception of the link between RSV infection and subsequent wheezing, wheezing-related healthcare and family resources use, and its impact on family daily life. METHODS: This cross-sectional online survey enrolled 1200 parents with at least one child ≤6y living in the United States, United Kingdom, Spain, and Italy. Children diagnosed with RSV bronchiolitis before age of 2 years were included in the RSV group, and those never diagnosed with RSV bronchiolitis in the Reference group. RESULTS: The odds of wheezing were 4.5-fold (95%CI 3.5-5.9) higher in the RSV than in the Reference group. The odds increased to 7.7-fold (95%CI 5.4-11.1) among children who were hospitalized, and 9-fold (95%CI 5.1-16.6) among those admitted to pediatric intensive care with RSV bronchiolitis. Similar trends were observed across all countries. In total, 57% of parents reported their child's wheezing to have moderate to severe impact on their emotional well-being, and 53% on their daily life activities and/or social life. 64% of parents reported moderate-severe impact of wheezing on child's quality of sleep and 49% and 46% reported a moderate-severe impact on their children's emotional well-being and physical activities. CONCLUSIONS: This survey suggests an association between RSV infection and subsequent wheezing in children across different countries. Wheezing, especially in association with RSV infection, was associated with increased healthcare utilization and costs, and significantly impacted parents' and children daily life.


Assuntos
Pais , Sons Respiratórios , Infecções por Vírus Respiratório Sincicial , Humanos , Estudos Transversais , Infecções por Vírus Respiratório Sincicial/epidemiologia , Pais/psicologia , Masculino , Feminino , Lactente , Pré-Escolar , Itália/epidemiologia , Inquéritos e Questionários , Espanha/epidemiologia , Reino Unido/epidemiologia , Estados Unidos/epidemiologia , Hospitalização/estatística & dados numéricos , Vírus Sincicial Respiratório Humano , Adulto , Criança , Efeitos Psicossociais da Doença
2.
J Diabetes Sci Technol ; : 19322968231179740, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37338104

RESUMO

BACKGROUND: Digital health solutions (DHS) are increasingly used to support people with diabetes (PwD) to help manage their diabetes and to gather and manage health and treatment data. There is a need for scientifically reliable and valid methods to measure the value and impact of DHS on outcomes that matter to PwD. Here, we describe the development of a survey questionnaire designed to assess the perceptions of PwD toward DHS and their prioritized outcomes for DHS evaluation. METHOD: We applied a structured process for engagement of a total of nine PwD and representatives of diabetes advocacy organizations. Questionnaire development consisted of a scoping literature review, individual interviews, workshops, asynchronous virtual collaboration, and cognitive debriefing interviews. RESULTS: We identified three overarching categories of DHS, which were meaningful to PwD and crucial for the identification of relevant outcomes: (1) online/digital tools for information, education, support, motivation; (2) personal health monitoring to support self-management; (3) digital and telehealth solutions for engaging with health professionals. Overall outcome domains identified to be important were diabetes-related quality of life, distress, treatment burden, and confidence in self-management. Additional positive and negative outcomes specific to DHS were identified and corresponding questions were incorporated into the survey questionnaire. CONCLUSION: We identified the need for self-reporting of quality of life, diabetes distress, treatment burden, and confidence in self-management, as well as specific positive and negative impacts of DHS. We designed a survey questionnaire to further assess the perceptions and perspectives of people with type 1 and 2 diabetes on outcomes relevant for DHS evaluations.

3.
Sci Rep ; 13(1): 1163, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670157

RESUMO

Biofilms represent a major concern in the food industry and healthcare. The use of probiotic bacteria and their derivatives as an alternative to conventional treatments to fight biofilm development is a promising option that has provided convincing results in the last decades. Recently, membrane vesicles (MVs) produced by probiotics have generated considerable interest due to the diversity of roles they have been associated with. However, the antimicrobial activity of probiotic MVs remains to be studied. In this work, we showed that membrane vesicles produced by Lacticaseibacillus casei BL23 (LC-MVs) exhibited strong antibiofilm activity against Salmonella enterica serovar Enteritidis (S. Enteritidis) without affecting bacterial growth. Furthermore, we found that LC-MVs affected the early stages of S. Enteritidis biofilm development and prevented attachment of bacteria to polystyrene surfaces. Importantly, LC-MVs did not impact the biomass of already established biofilms. We also demonstrated that the antibiofilm activity depended on the proteins associated with the LC-MV fraction. Finally, two peptidoglycan hydrolases (PGHs) were found to be associated with the antibiofilm activity of LC-MVs. Overall, this work allowed to identify the antibiofilm properties of LC-MVs and paved the way for the use of probiotic MVs against the development of negative biofilms.


Assuntos
Lacticaseibacillus casei , Salmonella enteritidis , Lacticaseibacillus , Biofilmes
4.
Front Psychol ; 12: 674110, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531783

RESUMO

Recent research has shown that the reported participation of employees in voluntary safety activities is related to the prevention of accidents and injuries. Encouraging such participation, then, is beneficial to organizations. A key question, therefore, is why employees should choose to report that they engage in such activities: what is their motivation given such activities are not compulsory? We used social exchange theory (SET) and organizational support theory (OST) to develop a model linking perceived organizational support to reports of safety participation. SET postulates that the benefits given (by an organization) are reciprocated with potential benefits to the giver as a result. OST emphasizes that feeling obliged is a key part of why people reciprocate the perceived support they get from their organization. Voluntary safety activities have the potential to benefit an organization, so for the first time, we test whether there is a link between perceived organizational support and the reported participation of employees in such activities, and whether the relationship is mediated by felt obligation. We also test whether another key SET motivation to reciprocate, the anticipated reward, is involved in mediating the relationship. A structural equation model with a sample of 536 workers from a Belgian public company, involved in the production and distribution of safe drinking water and in waste water treatment, supported the hypotheses of the authors. The model showed that felt obligation mediated the relationship between perceived organizational support and safety participation reports, and that the anticipatory reward, in the form of perceptions that management was committed to safety, also mediated the relationship between perceived organizational support and safety participation reports. These processes were shown to be separable from employee job engagement and employee perspectives on whether or not voluntary safety activities were part of their job. The findings add to the understanding of why employees choose reported participation in voluntary safety behaviors and also, add to the literature on OST by demonstrating for the first time the involvement of felt obligation and perceived management commitment to safety as mediators between outcomes and perceived organizational support.

5.
Methods Mol Biol ; 2229: 189-203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33405223

RESUMO

Cell-free synthetic biology offers an approach to building and testing gene circuits in a simplified environment free from the complexity of a living cell. Recent advances in microfluidic devices allowed cell-free reactions to run under nonequilibrium, steady-state conditions enabling the implementation of dynamic gene regulatory circuits in vitro. In this chapter, we present a detailed protocol to fabricate a microfluidic chemostat device which enables such an operation, detailing essential steps in photolithography, soft lithography, and hardware setup.


Assuntos
Redes Reguladoras de Genes , Técnicas Analíticas Microfluídicas/instrumentação , Biologia Sintética/métodos , Sistema Livre de Células , Expressão Gênica , Humanos , Software
6.
Nat Food ; 2(7): 485-493, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37117674

RESUMO

In semi-arid regions, water stress during seed germination and early seedling growth is the highest cause of crop loss. In nature, some seeds (for example, chia and basil) produce a mucilage-based hydrogel that creates a germination-promoting microenvironment by retaining water, regulating nutrient entry and facilitating interactions with beneficial microorganisms. Inspired by this strategy, a two-layered biopolymer-based seed coating has been developed to increase germination and water-stress tolerance in semi-arid, sandy soils. Seeds are coated with a silk/trehalose inner layer containing rhizobacteria and a pectin/carboxymethylcellulose outer layer that reswells upon sowing and acts as a water jacket. Using Phaseolus vulgaris (common bean) cultured under water-stress conditions in an experimental farm in Ben Guerir, Morocco, the proposed seed coating effectively delivered rhizobacteria to form root nodules, resulted in plants with better health and mitigated water stress in drought-prone marginal lands. A programmable seed coating technology has the potential to increase seed germination and water-stress tolerance in semi-arid, sandy soils.

7.
NPJ Biofilms Microbiomes ; 6(1): 44, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116127

RESUMO

In this study, we show that calcium pectinate beads (CPB) allow the formation of 20 µm spherical microcolonies of the probiotic bacteria Lacticaseibacillus paracasei (formerly designated as Lactobacillus paracasei) ATCC334 with a high cell density, reaching more than 10 log (CFU/g). The bacteria within these microcolonies are well structured and adhere to a three-dimensional network made of calcium-pectinate through the synthesis of extracellular polymeric substances (EPS) and thus display a biofilm-like phenotype, an attractive property for their use as probiotics. During bacterial development in the CPB, a coalescence phenomenon arises between neighboring microcolonies accompanied by their peripheral spatialization within the bead. Moreover, the cells of L. paracasei ATCC334 encased in these pectinate beads exhibit increased resistance to acidic stress (pH 1.5), osmotic stress (4.5 M NaCl), the freeze-drying process and combined stresses, simulating the harsh conditions encountered in the gastrointestinal (GI) tract. In vivo, the oral administration of CPB-formulated L. paracasei ATCC334 in mice demonstrated that biofilm-like microcolonies are successfully released from the CPB matrix in the colonic environment. In addition, these CPB-formulated probiotic bacteria display the ability to reduce the severity of a DSS-induced colitis mouse model, with a decrease in colonic mucosal injuries, less inflammation, and reduced weight loss compared to DSS control mice. To conclude, this work paves the way for a new form of probiotic administration in the form of biofilm-like microcolonies with enhanced functionalities.


Assuntos
Biofilmes/crescimento & desenvolvimento , Colite/dietoterapia , Lacticaseibacillus paracasei/fisiologia , Pectinas/química , Probióticos/administração & dosagem , Animais , Cápsulas , Colite/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Composição de Medicamentos , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Liofilização , Masculino , Camundongos , Pressão Osmótica , Probióticos/farmacologia , Resultado do Tratamento
8.
Int J Mol Sci ; 21(15)2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32751457

RESUMO

Bacterial strains of the Lactobacillaceae family are widely used as probiotics for their multifaceted potential beneficial properties. However, no official recommendations for their clinical use exist since, in many cases, oral administrations of these bacteria displayed limited beneficial effects in human. Additional research is thus needed to improve the efficiency of existing strains with strong potential. In this context, we assess in vitro the effects of nine polyphenols to stimulate biofilm formation by lactobacilli, a feature enhancing their functionalities. Among these polyphenols, we identify trans-Resveratrol (referred to hereafter as Resveratrol) as a potent inducer of biofilm formation by Lacticaseibacillus paracasei (formerly designated as Lactobacillus paracasei) ATCC334 strain. This effect is strain-dependent and relies on the enhancement of L. paracasei adhesion to abiotic and biotic surfaces, including intestinal epithelial cells. Mechanistically, Resveratrol modify physico-chemical properties of the bacterial surface and thereby enhances L. paracasei aggregation, subsequently facilitating adhesion and biofilm development. Together, our in vitro data demonstrate that Resveratrol might be used to modulate the behavior of Lactobacilli with probiotic properties. Combination of probiotics and polyphenols could be considered to enhance the probiotic functionalities in further in vivo studies.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Lacticaseibacillus paracasei , Probióticos/metabolismo , Resveratrol/farmacologia , Células HCT116 , Células HT29 , Humanos , Lacticaseibacillus paracasei/efeitos dos fármacos , Lacticaseibacillus paracasei/crescimento & desenvolvimento
9.
Heliyon ; 6(1): e03201, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31970304

RESUMO

Safety citizenship behaviors (SCB) have never been classified following the intended beneficiary of these behaviors. The first aim of this study was to examine Hofmann et al. (2003)'s SCB items in an attempt to identify two dimensions: SCB oriented towards individuals (SCB-I) and SCB oriented towards the organization (SCB-O). Further, by drawing on Christian et al. (2009)'s model of safety performance, we examined how distal (i.e. personality) and proximal (i.e. safety motivation and knowledge) person-related factors are associated with these behaviors. Structural equation modelling realized on a sample of 290 workers from a Belgian pharmaceutical company showed that the broader conscientiousness trait was related to both SCB-I and SCB-O, indirectly through safety motivation and knowledge, as would be predicted by Christian et al. In contrast, the altruism facet was directly related to SCB-I only. Results are discussed and practical implications considered.

10.
Int J Food Microbiol ; 318: 108464, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-31816527

RESUMO

The wine spoilage yeast Brettanomyces bruxellensis can be found at several steps in the winemaking process due to its resistance to multiple stress conditions. The ability to form biofilm is a potential resistance strategy, although it has been given little attention so far for this yeast. In this work, the capacity to form biofilm and its structure were explored in YPD medium and in wine. Using microsatellite analysis, 65 isolates were discriminated into 5 different genetic groups from which 12 strains were selected. All 12 strains were able to form biofilm in YPD medium on a polystyrene surface. The presence of microcolonies, filamentous cells and extracellular polymeric substances, constituting the structure of the biofilm despite a small thickness, were highlighted using confocal and electronic microscopy. Moreover, different cell morphologies according to genetic groups were highlighted. The capacity to form biofilm in wine was also revealed for two selected strains. The impact of wine on biofilms was demonstrated with firstly considerable biofilm cell release and secondly growth of these released biofilm cells, both in a strain dependent manner. Finally, B. bruxellensis has been newly described as a producer of chlamydospore-like structures in wine, for both planktonic and biofilm lifestyles.


Assuntos
Biofilmes/crescimento & desenvolvimento , Brettanomyces/fisiologia , Vinho/microbiologia , Brettanomyces/citologia , Brettanomyces/genética , Microbiologia de Alimentos , Vinho/análise
11.
J Biomed Mater Res B Appl Biomater ; 107(2): 324-331, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29717817

RESUMO

Esophageal diseases may require resectioning of the damaged portion. The current standard of care requires the replacement of the esophagus with the stomach or the intestine. Such procedures have high rates of mortality and morbidity; therefore, the use of alternative conduits is needed. A tissue engineering approach that allows for the regeneration of esophageal tissues would have significant clinical application. A cell-seeded synthetic scaffold could replace the resected part of the esophagus and elicit tissue regrowth. In order to ideally recreate a functioning esophagus, its two crucial tissue layers should be induced: an epithelium on the luminal surface and a muscle layer on the exterior surface. To create a bioengineered esophagus with both tissue layers, a multilayer (ML) tubular scaffold design was considered. Luminal and exterior layers were electrospun with broad pore size to promote penetration and proliferation of mesenchymal stem cells on the lumen and smooth muscle cells on the external. These two layers would be separated by a thin layer with substantially narrower pore size intended to act as a barrier for the two cell types. This ML scaffold design was achieved via electrospinning by tuning the solution and the process parameters. Analysis of the scaffold demonstrated that this tuning enabled the production of three integrated layers with distinguishable microstructures and good mechanical integrity. In vitro validation was conducted on the separated unilayer components of the ML scaffold. The resultant proof-of-concept ML scaffold design could possibly support the spatial arrangement of cells needed to promote esophageal tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 324-331, 2019.


Assuntos
Proliferação de Células , Esôfago/metabolismo , Teste de Materiais , Células-Tronco Mesenquimais/metabolismo , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Esôfago/citologia , Células-Tronco Mesenquimais/citologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Porosidade , Suínos
12.
Toxicol Sci ; 168(2): 315-338, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30535037

RESUMO

The GMO90+ project was designed to identify biomarkers of exposure or health effects in Wistar Han RCC rats exposed in their diet to 2 genetically modified plants (GMP) and assess additional information with the use of metabolomic and transcriptomic techniques. Rats were fed for 6-months with 8 maize-based diets at 33% that comprised either MON810 (11% and 33%) or NK603 grains (11% and 33% with or without glyphosate treatment) or their corresponding near-isogenic controls. Extensive chemical and targeted analyses undertaken to assess each diet demonstrated that they could be used for the feeding trial. Rats were necropsied after 3 and 6 months. Based on the Organization for Economic Cooperation and Development test guideline 408, the parameters tested showed a limited number of significant differences in pairwise comparisons, very few concerning GMP versus non-GMP. In such cases, no biological relevance could be established owing to the absence of difference in biologically linked variables, dose-response effects, or clinical disorders. No alteration of the reproduction function and kidney physiology was found. Metabolomics analyses on fluids (blood, urine) were performed after 3, 4.5, and 6 months. Transcriptomics analyses on organs (liver, kidney) were performed after 3 and 6 months. Again, among the significant differences in pairwise comparisons, no GMP effect was observed in contrast to that of maize variety and culture site. Indeed, based on transcriptomic and metabolomic data, we could differentiate MON- to NK-based diets. In conclusion, using this experimental design, no biomarkers of adverse health effect could be attributed to the consumption of GMP diets in comparison with the consumption of their near-isogenic non-GMP controls.


Assuntos
Ração Animal/toxicidade , Grão Comestível/química , Alimentos Geneticamente Modificados/toxicidade , Plantas Geneticamente Modificadas/química , Zea mays/genética , Ração Animal/normas , Animais , Qualidade de Produtos para o Consumidor , Grão Comestível/genética , Feminino , Alimentos Geneticamente Modificados/normas , Masculino , Plantas Geneticamente Modificadas/genética , Ratos , Ratos Wistar , Testes de Toxicidade/métodos , Zea mays/química
13.
Transplant Direct ; 4(4): e357, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29707628

RESUMO

BACKGROUND: End-stage renal failure occurs in a substantial number of patients having received a nonrenal transplantation (NRT), for whom a kidney transplantation is needed. The medical strategy regarding the use of immunosuppression (IS) for a kidney graft in patients after an NRT is not well established. The prekidney grafts long-term IS advocates for a mild induction, such as using anti-IL-2R antibodies, whereas addition of new incompatibilities and anti-HLA preimmunization may suggest using stronger IS such as induction by polyclonal antithymocyte globulins (ATG). METHODS: We performed Cox multivariate and propensity score analysis of our validated transplant database to study the impact of the type of induction therapy on kidney graft survival of recipients of a kidney graft after NRT. RESULTS: We report here that kidney transplantation after NRT treated with an ATG induction has a poorer outcome (kidney and recipient survival) than that with an anti-IL-2R induction. After accounting for potential baseline differences with a multivariate Cox model, or by adjusting on a propensity score, we found that despite patients having received ATG cumulate more risk factors, ATG appears independently involved. As animal-derived biotherapeutics induce antiglycan antibodies and particularly anti-N-glycolylneuraminic acid (Neu5Gc) IgGs which may activate endothelial cells in patients and grafts, we also investigated the magnitude and the nature of the anti-Neu5Gc elicited by the induction and showed that induction was associated with a shift in anti-Neu5Gc IgG repertoire. Possible reasons and mechanisms of a deleterious ATG usage in these patients are discussed. CONCLUSIONS: Our study suggests that ATG induction after a kidney transplantation in recipients already under maintenance IS for a NRT should be used cautiously.

14.
Int J Food Microbiol ; 247: 18-23, 2017 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-27318622

RESUMO

Lactococcus lactis is a lactic acid bacterium widely used in cheese and fermented milk production. During fermentation, L. lactis is subjected to acid stress that impairs its growth. The small heat shock protein (sHsp) Lo18 from the acidophilic species Oenococcus oeni was expressed in L. lactis. This sHsp is known to play an important role in protein protection and membrane stabilization in O. oeni. The role of this sHsp could be studied in L. lactis, since no gene encoding for sHsp has been detected in this species. L. lactis subsp. cremoris strain MG1363 was transformed with the pDLhsp18 plasmid, which is derived from pDL278 and contains the hsp18 gene (encoding Lo18) and its own promoter sequence. The production of Lo18 during stress conditions was checked by immunoblotting and the cellular distribution of Lo18 in L. lactis cells after heat shock was determined. Our results clearly indicated a role for Lo18 in cytoplasmic protein protection and membrane stabilization during stress. The production of sHsp in L. lactis improved tolerance to heat and acid conditions in this species. Finally, the improvement of the L. lactis survival in milk medium thanks to Lo18 was highlighted, suggesting an interesting role of this sHsp. These findings suggest that the expression of a sHsp by a L. lactis strain results in greater resistance to stress, and, can consequently enhance the performances of industrial strains.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Choque Térmico Pequenas/genética , Proteínas de Choque Térmico Pequenas/metabolismo , Lactococcus lactis/fisiologia , Oenococcus/genética , Fermentação , Temperatura Alta , Lactococcus lactis/genética , Oenococcus/metabolismo , Estresse Fisiológico
15.
Appl Environ Microbiol ; 82(21): 6483-6489, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27663024

RESUMO

Fusarium oxysporum is typically a soilborne fungus but can also be found in aquatic environments. In hospitals, water distribution systems may be reservoirs for the fungi responsible for nosocomial infections. F. oxysporum was previously detected in the water distribution systems of five French hospitals. Sixty-eight isolates from water representative of all hospital units that were previously sampled and characterized by translation elongation factor 1α sequence typing were subjected to microsatellite analysis and full-length ribosomal intergenic spacer (IGS) sequence typing. All but three isolates shared common microsatellite loci and a common two-locus sequence type (ST). This ST has an international geographical distribution in both the water networks of hospitals and among clinical isolates. The ST dominant in water was not detected among 300 isolates of F. oxysporum that originated from surrounding soils. Further characterization of 15 isolates by vegetative compatibility testing allowed us to conclude that a clonal lineage of F. oxysporum circulates in the tap water of the different hospitals. IMPORTANCE: We demonstrated that a clonal lineage of Fusarium oxysporum inhabits the water distribution systems of several French hospitals. This clonal lineage, which appears to be particularly adapted to water networks, represents a potential risk for human infection and raises questions about its worldwide distribution.


Assuntos
Água Potável/microbiologia , Fusarium/genética , Fusarium/isolamento & purificação , Hospitais , DNA Fúngico/isolamento & purificação , DNA Intergênico , França/epidemiologia , Fusariose/epidemiologia , Fusariose/etiologia , Fusariose/microbiologia , Fusarium/classificação , Humanos , Repetições de Microssatélites , Fator 1 de Elongação de Peptídeos/genética , Filogenia , Análise de Sequência de DNA
16.
Hum Immunol ; 77(11): 1024-1029, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27262455

RESUMO

Modern clinical research takes advantage of multicentric cohorts to increase sample size and gain in statistical power. However, combining individuals from different recruitment centers provides heterogeneity in the dataset that needs to be accounted for to obtain robust results. Sophisticated statistical multivariate models adjusting for center effect can be implemented, but they can become unstable and can be complex to interpret with the increasing number of covariates to consider. Here, we present a multidimensional reduction technique to identify heterogeneity in a French multicentric cohort of hematopoietic stem cell transplantations and characterize a homogeneous subgroup prior to performing simple statistical univariate analyses. The exclusion of outliers allowed the identification of two genetic factors associated with post-transplantation overall survival. We therefore provide proof-of-concept that a sample size reduction method can efficiently account for heterogeneity and center effect in multicentric cohorts while increasing statistical power and robustness for discovery of new association signals.


Assuntos
Sobrevivência de Enxerto/genética , Transplante de Células-Tronco Hematopoéticas , Modelos Estatísticos , Adulto , Estudos de Coortes , Feminino , França , Heterogeneidade Genética , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho da Amostra , Análise de Sobrevida , Adulto Jovem
17.
J Hepatol ; 64(2): 427-432, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26334577

RESUMO

BACKGROUND & AIMS: 30-40% of portal vein thrombosis (PVT) remains of unknown origin. An association between metabolic syndrome (MetS) and peripheral vein thrombosis has been reported but not with PVT, to date. The aim of this study was to investigate the association between MetS and PVT. METHODS: Between 2003 and 2014, all consecutive patients with non-cirrhotic PVT were prospectively included. Patient's characteristics and risks factors were recorded at the time of inclusion. Controls were selected by random in the general population and were matched 1/1 according to age and sex. RESULTS: Seventy-nine patients with PVT were included: 40 present with at least one risk factor for PVT (SPVT) and 39 were found to be idiopathic (IPVT). The prevalence of MetS was 25.6% in SPVT group vs. 47.4% in IPVT group and 17.9% in controls from the general population (C-IPVT: p=0.01). The waist circumference and body mass index were higher in the IPVT group than in the SPVT group (105 vs. 93cm, p=0.004 and 29.4 vs. 25.0kg/m(2), p=0.004) and in the C-IPVT group (105 vs. 92cm, p=0.001 and 29.4 vs. 25.8kg/m(2), p=0.003). Overweight was observed in 82.0% of patients in the IPVT group vs. 44% in the SPVT group (p=0.002) and 51% in the C-IPVT group (p=0.01). The mean visceral fat area was higher in IPVT than in SPVT (18,223mm(2)vs. 12,690mm(2), p=0.02). In multivariate analyses, an increase in waist circumference was the strongest parameter associated with idiopathic PVT. CONCLUSION: Central obesity is associated with PVT and could become one of the main risk factors for digestive thromboses.


Assuntos
Obesidade Abdominal , Veia Porta , Trombose Venosa , Adulto , Estudos de Casos e Controles , Anticoncepcionais Orais/uso terapêutico , Feminino , França/epidemiologia , Humanos , Testes de Função Hepática/métodos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/epidemiologia , Prevalência , Fatores de Risco , Estatística como Assunto , Trombose Venosa/diagnóstico , Trombose Venosa/epidemiologia , Circunferência da Cintura
18.
Environ Health Perspect ; 124(3): 388-95, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26080391

RESUMO

BACKGROUND: Drinking water is recognized as a source of lead (Pb) exposure. However, questions remain about the impact of chronic exposure to lead-contaminated water on internal dose. OBJECTIVE: Our goal was to estimate the relation between a cumulative water Pb exposure index (CWLEI) and blood Pb levels (BPb) in children 1-5 years of ages. METHODS: Between 10 September 2009 and 27 March 2010, individual characteristics and water consumption data were obtained from 298 children. Venous blood samples were collected (one per child) and a total of five 1-L samples of water per home were drawn from the kitchen tap. A second round of water collection was performed between 22 June 2011 and 6 September 2011 on a subsample of houses. Pb analyses used inductively coupled plasma mass spectroscopy. Multiple linear regressions were used to estimate the association between CWLEI and BPb. RESULTS: Each 1-unit increase in CWLEI multiplies the expected value of BPb by 1.10 (95% CI: 1.06, 1.15) after adjustment for confounders. Mean BPb was significantly higher in children in the upper third and fourth quartiles of CWLEI (0.7-1.9 and ≥ 1.9 µg/kg of body weight) compared with the first (< 0.2 µg/kg) after adjusting for confounders (19%; 95% CI: 0, 42% and 39%; 95% CI: 15, 67%, respectively). The trends analysis yielded a p-value < 0.0001 after adjusting for confounders suggesting a dose-response relationship between percentiles of CWLEI and BPb. CONCLUSIONS: In children 1-5 years of age, BPb was significantly associated with water lead concentration with an increase starting at a cumulative lead exposure of ≥ 0.7 µg Pb/kg of body weight. In this age group, an increase of 1 µg/L in water lead would result in an increase of 35% of BPb after 150 days of exposure.


Assuntos
Água Potável/química , Exposição Ambiental/análise , Chumbo/sangue , Poluentes Químicos da Água/sangue , Pré-Escolar , Humanos , Lactente , Modelos Lineares , Quebeque
19.
Stem Cells Transl Med ; 4(5): 413-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25926330

RESUMO

The development of a California-based induced pluripotent stem cell (iPSC) bank based on human leukocyte antigen (HLA) haplotype matching represents a significant challenge and a valuable opportunity for the advancement of regenerative medicine. However, previously published models of iPSC banks have neither addressed the admixed nature of populations like that of California nor evaluated the benefit to the population as a whole. We developed a new model for evaluating an iPSC haplobank based on demographic and immunogenetic characteristics reflecting California. The model evaluates haplolines or cell lines from donors homozygous for a single HLA-A, HLA-B, HLA-DRB1 haplotype. We generated estimates of the percentage of the population matched under various combinations of haplolines derived from six ancestries (black/African American, American Indian, Asian/Pacific Islander, Hispanic, and white/not Hispanic) and data available from the U.S. Census Bureau, the California Institute for Regenerative Medicine, and the National Marrow Donor Program. The model included both cis (haplotype-level) and trans (genotype-level) matching between a modeled iPSC haplobank and the recipient population following resampling simulations. We showed that serving a majority (>50%) of a simulated California population through cis matching would require the creation, redundant storage, and maintenance of almost 207 different haplolines representing the top 60 most frequent haplotypes from each ancestry group. Allowances for trans matching reduced the haplobank to fewer than 141 haplolines found among the top 40 most frequent haplotypes. Finally, we showed that a model optimized, custom haplobank was able to serve a majority of the California population with fewer than 80 haplolines.


Assuntos
Genética Populacional , Antígenos HLA/genética , Haplótipos/genética , Células-Tronco Pluripotentes Induzidas/citologia , California , Linhagem Celular , Etnicidade/genética , Genótipo , Teste de Histocompatibilidade , Homozigoto , Humanos , Pesquisa com Células-Tronco , Doadores de Tecidos
20.
Water Res ; 76: 53-65, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25792434

RESUMO

Members of the Fusarium group were recently detected in water distribution systems of several hospitals in the world. An epidemiological investigation was conducted over 2 years in hospital buildings in Dijon and Nancy (France) and in non-hospital buildings in Dijon. The fungi were detected only within the water distribution systems of the hospital buildings and also, but at very low concentrations, in the urban water network of Nancy. All fungi were identified as Fusarium oxysporum species complex (FOSC) and Fusarium dimerum species complex (FDSC) by sequencing part of the translation elongation factor 1-alpha (TEF-1α) gene. Very low diversity was found in each complex, suggesting the existence of a clonal population for each. Density and heterogeneous distributions according to buildings and variability over time were explained by episodic detachments of parts of the colony from biofilms in the pipes. Isolates of these waterborne populations as well as soilborne isolates were tested for their ability to grow in liquid medium in the presence of increasing concentrations of sodium hypochlorite, copper sulfate, anti-corrosion pipe coating, at various temperatures (4°-42 °C) and on agar medium with amphotericin B and voriconazole. The waterborne isolates tolerated higher sodium hypochlorite and copper sulfate concentrations and temperatures than did soilborne isolates but did not show any specific resistance to fungicides. In addition, unlike waterborne isolates, soilborne isolates did not survive in water even supplemented with glucose, while the former developed in the soil as well as soilborne isolates. We concluded the existence of homogeneous populations of FOSC and FDSC common to all contaminated hospital sites. These populations are present at very low densities in natural waters, making them difficult to detect, but they are adapted to the specific conditions offered by the complex water systems of public hospitals in Dijon and Nancy and probably other localities in the world.


Assuntos
Água Potável/microbiologia , Fusarium/isolamento & purificação , Microbiologia da Água , Abastecimento de Água , Aclimatação , Antifúngicos/farmacologia , Biofilmes , Sulfato de Cobre/farmacologia , França , Fusarium/genética , Fusarium/crescimento & desenvolvimento , Hospitais , Fator 1 de Elongação de Peptídeos/genética , Compostos de Fósforo/farmacologia , Dióxido de Silício/farmacologia , Hipoclorito de Sódio/farmacologia , Microbiologia do Solo , Temperatura
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