Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
1.
Cell Rep ; 41(7): 111651, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36384130

RESUMO

The immune system and placenta have a dynamic relationship across gestation to accommodate fetal growth and development. High-resolution characterization of this maternal-fetal interface is necessary to better understand the immunology of pregnancy and its complications. We developed a single-cell framework to simultaneously immuno-phenotype circulating, endovascular, and tissue-resident cells at the maternal-fetal interface throughout gestation, discriminating maternal and fetal contributions. Our data reveal distinct immune profiles across the endovascular and tissue compartments with tractable dynamics throughout gestation that respond to a systemic immune challenge in a gestationally dependent manner. We uncover a significant role for the innate immune system where phagocytes and neutrophils drive temporal organization of the placenta through remarkably diverse populations, including PD-L1+ subsets having compartmental and early gestational bias. Our approach and accompanying datasets provide a resource for additional investigations into gestational immunology and evoke a more significant role for the innate immune system in establishing the microenvironment of early pregnancy.


Assuntos
Feto , Placenta , Gravidez , Feminino , Humanos
2.
Epidemiol Infect ; 150: e125, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35641482

RESUMO

The increasing number of diversified small-scale farms (DSSF) that raise outdoor-based livestock in the USA reflects growing consumer demand for sustainably produced food. Diversified farms are small scale and raise a combination of multiple livestock species and numerous produce varieties. This 2015-2016 cross-sectional study aimed to describe the unique characteristics of DSSF in California, estimate the prevalence of Shiga toxin-producing Escherichia coli (STEC) in livestock and evaluate the association between risk factors and the presence of STEC in livestock, using generalised linear mixed models. STEC prevalence was 13.62% (76/558). Significant variables in the mixed-effect logistic regression model included daily maximum temperature (OR 0.95; CI95% 0.91-0.98), livestock sample source (cattle (OR 4.61; CI95% 1.64-12.96) and sheep (OR 5.29; CI95% 1.80-15.51)), multiple species sharing the same barn (OR 6.23; CI95% 1.84-21.15) and livestock having contact with wild areas (OR 3.63; CI95% 1.37-9.62). Identification of STEC serogroups of public health concern (e.g. O157:H7, O26, O103) in this study indicated the need for mitigation strategies to ensure food safety by evaluating risk factors and management practices that contribute to the spread and prevalence of foodborne pathogens in a pre-harvest environment on DSSF.


Assuntos
Infecções por Escherichia coli , Fazendas , Gado , Escherichia coli Shiga Toxigênica , Animais , California/epidemiologia , Bovinos/microbiologia , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/microbiologia , Estudos Transversais , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/veterinária , Gado/microbiologia , Fatores de Risco , Ovinos/microbiologia , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/microbiologia
3.
STAR Protoc ; 3(2): 101280, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35434655

RESUMO

Granulocytes encompass diverse roles, from fighting off pathogens to regulating inflammatory processes in allergies. These roles are represented by distinct cellular phenotypes that we captured with mass cytometry (CyTOF). Our protocol enables simultaneous evaluation of human basophils, eosinophils, and neutrophils under homeostasis and upon immune activation by anti-Immunoglobulin E (anti-IgE) or interleukin-3 (IL-3). Granulocyte integrity and detection of protein markers were optimized so that rare granulocyte populations could be deeply characterized by single cell mass cytometry. For complete details on the use and execution of this protocol, please refer to Vivanco Gonzalez et al. (2020).


Assuntos
Eosinófilos , Neutrófilos , Basófilos , Eosinófilos/metabolismo , Citometria de Fluxo/métodos , Humanos , Contagem de Leucócitos
4.
Ecol Appl ; 32(2): e2523, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34921463

RESUMO

Recent foodborne illness outbreaks have heightened pressures on growers to deter wildlife from farms, jeopardizing conservation efforts. However, it remains unclear which species, particularly birds, pose the greatest risk to food safety. Using >11,000 pathogen tests and 1565 bird surveys covering 139 bird species from across the western United States, we examined the importance of 11 traits in mediating wild bird risk to food safety. We tested whether traits associated with pathogen exposure (e.g., habitat associations, movement, and foraging strategy) and pace-of-life (clutch size and generation length) mediated foodborne pathogen prevalence and proclivities to enter farm fields and defecate on crops. Campylobacter spp. were the most prevalent enteric pathogen (8.0%), while Salmonella and Shiga-toxin producing Escherichia coli (STEC) were rare (0.46% and 0.22% prevalence, respectively). We found that several traits related to pathogen exposure predicted pathogen prevalence. Specifically, Campylobacter and STEC-associated virulence genes were more often detected in species associated with cattle feedlots and bird feeders, respectively. Campylobacter was also more prevalent in species that consumed plants and had longer generation lengths. We found that species associated with feedlots were more likely to enter fields and defecate on crops. Our results indicated that canopy-foraging insectivores were less likely to deposit foodborne pathogens on crops, suggesting growers may be able to promote pest-eating birds and birds of conservation concern (e.g., via nest boxes) without necessarily compromising food safety. As such, promoting insectivorous birds may represent a win-win-win for bird conservation, crop production, and food safety. Collectively, our results suggest that separating crop production from livestock farming may be the best way to lower food safety risks from birds. More broadly, our trait-based framework suggests a path forward for co-managing wildlife conservation and food safety risks in farmlands by providing a strategy for holistically evaluating the food safety risks of wild animals, including under-studied species.


Assuntos
Animais Selvagens , Escherichia coli Shiga Toxigênica , Animais , Aves , Bovinos , Fazendas , Salmonella , Estados Unidos
5.
Res Sq ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33442675

RESUMO

Background: Latin America has now become the epicenter of the global coronavirus disease 2019 (COVID-19) pandemic. In the ongoing COVID -19 pandemic, a profound burden of SARS-COV-2 infection has been reported in Latin America. In the present study, we aim to determine the profiles that are associated with this disease in Latin America. We analyzed symptoms, morbidities and gastrointestinal (GI) manifestations by country. Methods: We analyzed data from SARS-CoV-2 positive patients evaluated at healthcare centers and hospitals of 8 Latin American countries including Brazil, Peru, Mexico, Argentina, Colombia, Venezuela, Ecuador, and Bolivia between March 1 and July 30, 2020. These countries consist of a total population that exceeds 519 million. Demographics, comorbidities and clinical symptoms were collected. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and lethality were performed. Results: A total of 728,282 patients tested positive for COVID-19 across all the 8 Latin American countries. Of these, 52.6% were female. The average age was 48.4 years. Peru had the oldest cohort with 56.8 years old and highest rate of females (56.8%) while Chile had the youngest cohort (39 years old). Venezuela had the highest male prevalence (56.7%). Most common symptoms were cough with 60.1% (Bolivia had the highest rate 78%), fatigue/tiredness with 52.0%, sore throat with 50.3%, and fever with 44.2%. Bolivia had fever as the top symptom (83.3%). GI symptoms including diarrhea (highest in Mexico with 22.9%), nausea, vomiting, and abdominal pain were not associated with higher mortality.Hypertension was among the top (12.1%) comorbidities followed by diabetes with 8.3% and obesity 4.5%. In multivariable analyses, the leading and significant comorbidities were hypertension (r=0.83, p=0.02), diabetes (r=0.91, p=0.01), and obesity (r=0.86, p=0.03). Asthma (r=0.37, p=0.54) and increasing age (0.13 p=0.81) were not independently associated with higher mortality. Lethality was highest in Mexico (16.6%) and lowest in Venezuela (0.9%) among the analyzed cohorts. Conclusion: Nearly, 10.5%-53% of patients with COVID-19 have GI manifestations. Differential clinical symptoms were associated with COVID-19 in Latin America countries. Metabolic syndrome components were the main comorbidities associated with poor outcome. Country-specific management and prevention plans are needed. Country-specific management and prevention plans can be established from this meta-analysis.

6.
Appl Environ Microbiol ; 87(2)2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158894

RESUMO

Flavobacterium psychrophilum affects salmonid health worldwide and causes economic losses. The genetic diversity of the pathogen must be considered to develop control methods. However, previous studies have reported both high and low levels of genetic diversity. The present longitudinal study aimed at assessing the genetic diversity of F. psychrophilum at a small temporal and geographic scale. Four farms located on the same watershed in France were studied. Rainbow trout (Oncorhynchus mykiss) batches were monitored, and apparently healthy individuals were sampled over 1 year. A total of 288 isolates were recovered from fish organs (gills and spleen) and eggs. Pulsed field gel electrophoresis revealed high genetic diversity. Multilocus sequence typing performed on a selection of 31 isolates provided congruent results, as follows: 18 sequence types (STs) were found, of which 13 were novel. The mean gene diversity (H = 0.8413) was much higher than that previously reported for this host species, although the sampling was restricted to a single watershed and 1 year. Seven isolates out of 31 were assigned to clonal complex ST10 (CC-ST10), which is the predominant clonal complex in the main salmonid production areas. A split decomposition tree reflected a panmictic population. This finding is important for aquaculture veterinarians in their diagnostic procedure, as the choice of adequate antibiotic treatment is conditioned by the correct identification of the causative agent. Furthermore, this study expands our knowledge on genetic diversity required for the development of an effective vaccine against F. psychrophilumIMPORTANCE The bacterium Flavobacterium psychrophilum is a serious pathogen in many fish species, especially salmonids, that is responsible for considerable economic losses worldwide. In order to treat infections and to develop vaccines, the genetic diversity of this bacterium needs to be known. We assessed the genetic diversity of F. psychrophilum isolates from apparently healthy rainbow trout raised in several fish farms in the same watershed in France. Two different genotyping methods revealed high diversity. The majority of isolates were unrelated to clonal complex sequence type 10 (CC-ST10), the clonal complex that is predominant worldwide and associated with disease in rainbow trout. In addition, we found 13 novel sequence types. These results suggest that a diverse subpopulation of F. psychrophilum may be harbored by rainbow trout.


Assuntos
Flavobacterium/genética , Oncorhynchus mykiss/microbiologia , Animais , Aquicultura , Técnicas de Tipagem Bacteriana , Doenças dos Peixes/microbiologia , Infecções por Flavobacteriaceae/microbiologia , Infecções por Flavobacteriaceae/veterinária , Flavobacterium/isolamento & purificação , Variação Genética
7.
iScience ; 23(11): 101724, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33205028

RESUMO

Basophils, the rarest granulocyte, play critical roles in parasite- and allergen-induced inflammation. We applied mass cytometry (CyTOF) to simultaneously asses 44 proteins to phenotype and functionally characterize neutrophils, eosinophils, and basophils from 19 healthy donors. There was minimal heterogeneity seen in eosinophils and neutrophils, but data-driven analyses revealed four unique subpopulations within phenotypically basophilic granulocytes (PBG; CD45+HLA-DR-CD123+). Through CyTOF and fluorescence-activated cell sorting (FACS), we classified these four PBG subpopulations as (I) CD16lowFcεRIhighCD244high (88.5 ± 1.2%), (II) CD16highFcεRIhighCD244high (9.1 ± 0.4%), (III) CD16lowFcεRIlowCD244low (2.3 ± 1.3), and (IV) CD16highFcεRIlowCD244low (0.4 ± 0.1%). Prospective isolation confirmed basophilic-morphology of PBG I-III, but neutrophilic-morphology of PBG IV. Functional interrogation via IgE-crosslinking or IL-3 stimulation demonstrated that PBG I-II had significant increases in CD203c expression, whereas PBG III-IV remained unchanged compared with media-alone conditions. Thus, PBG III-IV could serve roles in non-IgE-mediated immunity. Our findings offer new perspectives in human basophil heterogeneity and the varying functional potential of these new subsets in health and disease.

8.
Acta bioquím. clín. latinoam ; 54(4): 407-414, jul. 2020. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1149030

RESUMO

Resumen La identificación inequívoca del antígeno D en medicina transfusional es de vital importancia para evitar reacciones postransfusionales y la enfermedad hemolítica del recién nacido. Es común el uso de reactivos serológicos monoclonales o tarjetas de gel y su interpretación está definida por cruces, de acuerdo con la reacción serológica. El propósito de este estudio fue determinar la frecuencia del factor Rh y las variantes del antígeno D en una población afroecuatoriana. Se trató de un estudio descriptivo, transversal con muestreo aleatorio simple de 541 pobladores. Para la tipificación del factor Rh se utilizó la metodología en tubo con antisueros monoclonales y para la detección de las variantes de D se utilizaron tarjetas de gel IDCoombs Anti-IgG. Las lecturas se verificaron mediante el análisis del índice kappa. Se aplicó estadística descriptiva y el análisis de Chi cuadrado para establecer la relación de las variables y su significación. Se identificó una frecuencia del 92% de individuos Rh(D) positivo y un 8% Rh(D) negativo. El 4,80% de los individuos presentaban la variante D débil y el 79% reacciones serológicas entre 2 y 3(+) indicativas de otras variantes del antígeno D. El fenotipo más común fue el R0/R0. Estos datos demuestran la necesidad de confirmar la existencia de variantes del antígeno D en esta población para un mejor manejo de la sangre. Una limitante constituye la disponibilidad de técnicas moleculares para la genotipificación de D; sin embargo, se podría implementar la fenotipificación RHCE como estrategia pretransfusional.


Abstract The unequivocal identification of D antigen in transfusion medicine is of vital importance to avoid post-transfusion reactions and hemolytic disease of the newborn. The use of monoclonal serological reagents or gel cards is common and their interpretation is defined according to the serological reaction by crosses. The purpose of this study was to determine the frequency of Rh factor and D antigen variants in the Afro-Ecuadorian population. This was a descriptive, cross-sectional study with simple random sampling of 541 residents. Tube typing with monoclonal antisera was used to typify Rh factor and ID-Coombs Anti-IgG gel cards were used to detect D variants, and the readings were verified by analysis of the kappa index. Descriptive statistics and Chi-square analysis were applied for the relationship of the variables and their significance. A frequency of 92% of Rh(D) positive individuals and 8% Rh(D) negative individuals were identified. Almost 5% (4.80%) of the individuals presented the weak D variant and 79% serological reactions between 2-3(+) indicative of other D antigen variants, the most common phenotype being R0/R0. These data demonstrate the need to confirm the existence of D antigen variants in this population for better management and availability of blood. A limitation is the availability of molecular techniques for D genotyping, however, RHCE phenotyping could be implemented as a pretransfusion strategy.


Resumo A identificação inequívoca do antígeno D na medicina transfusional é de vital importância para evitar reações pós-transfusionais e a doença hemolítica do recém-nascido. É comum o uso de reagentes sorológicos monoclonais ou cartões de gel e sua interpretação é definida por cruzamentos de acordo com a reação sorológica. O objetivo deste estudo foi determinar a frequência do fator Rh e as variantes do antígeno D numa população afro-equatoriana. Foi um estudo descritivo, transversal, com amostragem aleatória simples de 541 residentes. Para a tipagem do fator Rh foi utilizada a metodologia em tubo com anti-soros monoclonais e para a detecção das variantes de D, os cartões de gel ID-Coombs Anti-IgG. As leituras foram verificadas por análise do índice kappa. Foi aplicada estatística descritiva e para estabelecer a relação das variáveis e sua significação se utilizou a análise do qui-quadrado. Identificando uma frequência de 92% dos indivíduos Rh (D) positivos e 8% Rh (D) negativos. 4,80% dos indivíduos apresentavam a variante D fraca e 79% reações sorológicas entre 2 e 3(+) indicativas de outras variantes do antígeno D, sendo o fenótipo mais comum o R0/R0. Esses dados demonstram a necessidade de confirmar a existência de variantes do antígeno D nessa população para melhor gerenciamento e disponibilidade de sangue. Uma limitação é a disponibilidade de técnicas moleculares para a genotipagem de D, no entanto, a fenotipagem de RHCE poderia ser implementada como uma estratégia de pré-transfusão.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Sistema do Grupo Sanguíneo Rh-Hr/análise , Sistema do Grupo Sanguíneo Rh-Hr/sangue , Antígenos/análise , População , Sistema do Grupo Sanguíneo Rh-Hr , Sangue , Recém-Nascido , Estudos Transversais , Medicina Transfusional , Indicadores e Reagentes , Doenças do Recém-Nascido/prevenção & controle , Antígenos
9.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1390191

RESUMO

RESUMEN Introducción: la comorbilidad es la presencia de enfermedades coexistentes o adicionales en relación al diagnóstico inicial o enfermedad guía. Es más frecuente en ancianos y contribuye a la aparición de eventos adversos de salud como mayor duración de la internación y mortalidad hospitalaria. Objetivo: determinar el efecto de las comorbilidades en la duración de la internación y en la mortalidad intrahospitalaria de los pacientes ingresados en el Servicio de Clínica Médica del Hospital Nacional (Itauguá, Paraguay) y del Hospital Militar Central (Asunción, Paraguay) entre marzo y julio del 2019. Materiales y métodos: se aplicó diseño de cohortes prospectivas en base al índice de comorbilidad de Charlson con punto de corte en 3 puntos. Ingresaron al estudio todos los varones y mujeres, mayores de 16 años, ingresados al Servicio de Clínica Médica del Hospital Nacional (Itauguá, Paraguay) y del Hospital Militar Central (Asunción, Paraguay) entre marzo y julio 2019. Se aplicó muestreo no probabilístico de casos consecutivos. Se midieron dos variables dependientes: duración de la hospitalización y mortalidad intrahospitalaria. Se calculó RR (IC 95%) y se consideró significativa toda p<0,05. El estudio respetó las normas éticas. Resultados: se incluyeron 543 sujetos, con predominio del sexo masculino (56%). La edad media fue 52±20 años. La mediana del índice de Charlson fue 2 puntos. No se detectó asociación estadísticamente significativa entre la severidad de este índice y la duración de la internación pero la mortalidad intrahospitalaria fue mayor con índice de Charlson ≥4: 6,5% vs 14,5% (p 0,005). Conclusiones: la mediana del índice de Charlson en dos Servicios de Clínica Médica fue 2. Se halló asociación estadísticamente significativa entre este índice y la mortalidad hospitalaria.


ABSTRACT Introduction: Comorbidity is the presence of coexisting or additional diseases in relation to the initial diagnosis or guiding disease. It is more frequent in the elderly and contributes to the occurrence of adverse health events such as longer hospitalization and hospital mortality. Objective: To determine the effect of comorbidities on the length of hospitalization and in-hospital mortality of patients admitted to the Medical Clinic Services of the National Hospital (Itauguá, Paraguay) and the Central Military Hospital (Asunción, Paraguay) between March and July 2019 Materials and methods: Prospective cohort design was applied based on the Charlson comorbidity index with a 3-point cut-off point. All men and women, older than 16 years who were admitted to the Medical Clinic Services of the National Hospital (Itauguá, Paraguay) and the Central Military Hospital (Asunción, Paraguay) between March and July 2019, entered into the study. Non-probabilistic sampling of consecutive cases was applied. Two dependent variables were measured: length of hospitalization and in-hospital mortality. RR (95% CI) was calculated and all p<0.05 was considered significant. The study respected ethical standards. Results: Five hundred forty-three subjects were included, and there was male predominance (56%). The mean age was 52 ± 20 years. The median Charlson index was 2 points. No statistically significant association was detected between the severity of this index and the length of hospitalization, but in-hospital mortality was higher with a Charlson index ≥4: 6.5% vs. 14.5% (p 0.005). Conclusion: The median Charlson index in two Medical Clinic Services was 2. A statistically significant association was found between this index and in-hospital mortality.

10.
J Dairy Sci ; 102(10): 9117-9137, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31378491

RESUMO

Mycobacterium avium ssp. paratuberculosis (MAP) is the etiological agent of paratuberculosis, a disease that affects ruminants worldwide. Despite global interest in the control of this disease, gaps exist in our knowledge of fecal shedding patterns and concurrent serological patterns. This longitudinal study in dairy cattle herds with high MAP seroprevalence in France aimed at accurately describing fecal shedding patterns over 1 year; relating those shedding patterns to individual animal characteristics (age, breed, parity); and exploring the association between fecal shedding patterns and serological patterns. To describe temporal fecal shedding patterns and continuity of shedding, along with the standard quantitative PCR (qPCR) threshold cycle we used a cutoff value that related to low or nonculturable fecal shedding. We also defined a threshold cycle indicative of shedding in high quantities to describe infection progression patterns. Twenty-one herds completed the study, and 782 cows were tested 4 times each. We obtained 4 sets of paired fecal qPCR and serum ELISA results from 757 cows. Although we targeted highly likely infectious animals, we found a large diversity of shedding patterns, as well as high variability between herds in the proportion of animals showing a given pattern. The fecal qPCR results of almost 20% of the final study sample were positioned at least once in the range that indicated low or nonculturable fecal shedding (between the adjusted and the standard cutoff value). Although these animals would typically be classified as non-shedders, they could be important to infection dynamics on the farm. Animals that shed at least twice consecutively and animals that shed in high quantities rarely reverted to negativity. Repeated fecal qPCR can be used to detect temporal fecal shedding traits, and the decision to cull an animal could practically be based on temporal, semiquantitative results. Overall, we found a mismatch between fecal shedding and ELISA seropositivity (637 animals were ELISA-negative 4 times, but only 13% of those animals were qPCR-negative 4 times). We found that having more than 2 ELISA-positive samples was strongly related to persistent and continuous shedding. We suggest that although serological testing is much less sensitive than qPCR, it can also be used, particularly over the course of multiple testing events, to identify animals that are most likely to contribute to the contamination of the farm environment.


Assuntos
Derrame de Bactérias , Doenças dos Bovinos/microbiologia , Mycobacterium avium subsp. paratuberculosis , Paratuberculose/microbiologia , Animais , Bovinos , Ensaio de Imunoadsorção Enzimática/veterinária , Fezes/microbiologia , Feminino , França , Estudos Longitudinais , Mycobacterium avium subsp. paratuberculosis/imunologia , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Estudos Soroepidemiológicos
11.
Cancer Causes Control ; 30(4): 375-384, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30830494

RESUMO

INTRODUCTION: The purpose of this study was to assess effects of three different educational intervention arms on knowledge of and intention to receive Pap testing and HPV co-testing. METHODS: Three active educational intervention arms were developed: a fotonovela, a radionovela, and a digital story. A pilot randomized controlled trial of 160 Latinas was conducted to assess the effectiveness of the intervention arms in increasing knowledge of cervical cancer and HPV and intention to be screened for cervical cancer compared to an attention control group (flu vaccination). RESULTS: Women in all three treatment arms significantly increased knowledge about cervical cancer compared to control arm (p = 0.02). Knowledge about cervical cancer screening also increased in the active arms compared to control (p = 0.0003). Knowledge of HPV risk also increased relative to the control (p = 0.0001). There were no significant differences between the intervention arms in increased knowledge of cervical cancer or cervical cancer screening (p = 0.57 and 0.16, respectively). DISCUSSION: This study supported the use of small media interventions in narrative education form as effective in increasing knowledge and intention to be screened for cervical cancer. The three culturally relevant interventions, built on qualitative data, were all successful in increasing knowledge.


Assuntos
Hispânico ou Latino , Infecções por Papillomavirus/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Adulto , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Projetos Piloto , Vacinação , Esfregaço Vaginal , Adulto Jovem
12.
Nat Biotechnol ; 37(3): 259-266, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30742126

RESUMO

Selective differentiation of naive T cells into multipotent T cells is of great interest clinically for the generation of cell-based cancer immunotherapies. Cellular differentiation depends crucially on division state and time. Here we adapt a dye dilution assay for tracking cell proliferative history through mass cytometry and uncouple division, time and regulatory protein expression in single naive human T cells during their activation and expansion in a complex ex vivo milieu. Using 23 markers, we defined groups of proteins controlled predominantly by division state or time and found that undivided cells account for the majority of phenotypic diversity. We next built a map of cell state changes during naive T-cell expansion. By examining cell signaling on this map, we rationally selected ibrutinib, a BTK and ITK inhibitor, and administered it before T cell activation to direct differentiation toward a T stem cell memory (TSCM)-like phenotype. This method for tracing cell fate across division states and time can be broadly applied for directing cellular differentiation.


Assuntos
Diferenciação Celular/genética , Proliferação de Células/genética , Ativação Linfocitária/genética , Células-Tronco Multipotentes/citologia , Rastreamento de Células/métodos , Humanos , Análise de Célula Única/métodos , Linfócitos T/citologia
13.
Zoonoses Public Health ; 65(7): 887-896, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29998551

RESUMO

Mixed crop-livestock farms (MCLF) integrate livestock and crops using their animals to graze crop residues and/or cover crops. MCLF are considered sustainable because grazing and the manure deposited by livestock enhance soil fertility and recycles farm nutrients. However, livestock manure may introduce enteric foodborne pathogens to the soil, which could contaminate fresh produce. Organic farmers in the United States follow the USDA National Organic Program (NOP) standards, which require 90 or 120 days between incorporating raw manure into the soil and harvest. Although not specifically addressed in NOP, organic farmers using grazing within production fields may also use this standard. The objectives of this study were to generate preharvest data to assess the die-off of generic Escherichia coli (E. coli) in the soil, after cover crops were grazed by sheep; and assess the genetic relatedness of generic E. coli isolates between soil and sheep faecal samples. We conducted a repeated observational study to evaluate the persistence of generic E. coli, as an indicator of faecal contamination and surrogate for STEC, in the soil of two fields (A and B) on an organic MCLF. Results showed a 3.70 log10 reduction in mean generic E. coli concentration MPN in the soil of field A from the highest of 3.70 log10 MPN/g on 48 day postsheep grazing (DPS) to -0.70 log10 MPN/g on 139 DPS. Field B showed a 3.51 log10 reduction in mean generic E. coli concentration in the soil from the highest mean of 3.51 log10 MPN/g on 14 DPS to the lowest mean -0.35 log10 MPN/g on 112 DPS. STEC prevalence in the sheep flock was 4.17% (1/24). Closely related generic E. coli strains were found between soil and faecal samples. Developing research-based waiting periods between grazing and harvest is important to inform best practices for farmers and food safety regulators.


Assuntos
Criação de Animais Domésticos/métodos , Escherichia coli/isolamento & purificação , Ovinos , Microbiologia do Solo , Verduras , Animais , Fazendas , Fezes/microbiologia , Estados Unidos
14.
Cancer Epidemiol Biomarkers Prev ; 27(11): 1283-1288, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29871884

RESUMO

Background: Disparities in colorectal cancer incidence and mortality rates exist among racial/ethnic minorities, especially those living in rural areas. There is an urgent need to implement interventions to improve colorectal cancer screening behaviors among such groups, particularly those living in rural areas in the United States.Methods: From a rural community of Hispanics, we recruited participants to attend home-based promotor(a)-led "home health parties" in which participants were taught about colorectal cancer screening; participants ages 50 and older were given a free fecal occult blood test (FOBT) kit to complete on their own. A pre- and posttest design was used to assess changes in colorectal cancer awareness, knowledge, and screening at baseline and at 1-month follow-up after the intervention.Results: We observed a statistically significant increase in colorectal cancer screening awareness and knowledge among participants. Colorectal cancer screening rates with FOBT increased from 51.0% to 80%. There was also a statistically significant increase in social engagement, that is, the intent to speak to friends and relatives about colorectal cancer screening.Conclusions: Findings indicate that culturally tailored colorectal cancer education facilitated by promotores in a rural environment, coupled with free stool-based test for colorectal cancer screening, is an effective way to increase colorectal cancer screening awareness, knowledge, and screening among Hispanics living in a rural area in Washington State. Impact: Culturally tailored home health interventions have the potential to achieve Healthy People 2020 colorectal cancer screening goals in Hispanic rural communities. Cancer Epidemiol Biomarkers Prev; 27(11); 1283-8. ©2018 AACR.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Neoplasias Colorretais/patologia , Feminino , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural
15.
Conserv Physiol ; 5(1): cox052, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28948023

RESUMO

Muskoxen (Ovibos moschatus) are increasingly subject to multiple new stressors associated with unprecedented climate change and increased anthropogenic activities across much of their range. Hair may provide a measurement of stress hormones (glucocorticoids) over periods of weeks to months. We developed a reliable method to quantify cortisol in the qiviut (wooly undercoat) of muskoxen using liquid chromatography coupled to tandem mass spectrometry. We then applied this technique to determine the natural variability in qiviut cortisol levels among 150 wild muskoxen, and to assess differences between sexes, seasons and years of collection. Qiviut samples were collected from the rump of adult muskoxen by subsistence and sport hunters in seven different locations in Nunavut and the Northwest Territories between 2013 and 2016. Results showed a high inter-individual variability in qiviut cortisol concentrations, with levels ranging from 3.5 to 48.9 pg/mg (median 11.7 pg/mg). Qiviut cortisol levels were significantly higher in males than females, and varied seasonally (summer levels were significantly lower than in fall and winter), and by year (levels significantly increased from 2013 to 2015). These differences may reflect distinct environmental conditions and the diverse stressors experienced, as well as physiological and/or behavioural characteristics. Quantification of qiviut cortisol may serve as a valuable tool for monitoring health and informing conservation and management efforts.

16.
Sci Rep ; 7(1): 5692, 2017 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-28720834

RESUMO

Candida albicans is an opportunistic pathogen, typically found as a benign commensal yeast living on skin and mucosa, but poised to invade injured tissue to cause local infections. In debilitated and immunocompromised individuals, C. albicans may spread to cause life-threatening systemic infections. Upon contact with serum and at body temperature, C. albicans performs a regulated switch to filamentous morphology, characterized by emergence of a germ tube from the yeast cell followed by mold-like growth of branching hyphae. The ability to switch between growth morphologies is an important virulence factor of C. albicans. To identify compounds able to inhibit hyphal morphogenesis, we screened libraries of existing drugs for inhibition of the hyphal switch under stringent conditions. Several compounds that specifically inhibited hyphal morphogenesis were identified. Chemogenomic analysis suggested an interaction with the endocytic pathway, which was confirmed by direct measurement of fluid-phase endocytosis in the presence of these compounds. These results suggest that the activity of the endocytic pathway, which is known to be particularly important for hyphal growth, represents an effective target for hyphae-inhibiting drugs.


Assuntos
Candida albicans/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Hifas/efeitos dos fármacos , Animais , Biofilmes/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Bovinos , Reposicionamento de Medicamentos , Hifas/crescimento & desenvolvimento , Morfogênese/efeitos dos fármacos , Soro , Fatores de Virulência
18.
Cancer ; 123(4): 666-674, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-27787893

RESUMO

BACKGROUND: Latinas have the highest rates of cervical cancer in the United States and the second highest rate of cervical cancer mortality. One factor in the disparity is the relatively low rate of screening for cervical cancer in this population. METHODS: Eligible women who were out of adherence with cervical cancer screening (>3 years since their last Papanicolaou [Pap] test) were identified via medical record review by a federally qualified local health center. The effects of a low-intensity intervention (video delivered to participants' homes; n = 150) and a high-intensity intervention (video plus a home-based educational session; n = 146) on cervical cancer screening uptake in comparison with a control arm (usual care; n = 147) were investigated. A cost-effectiveness analysis of the interventions was conducted: all intervention costs were calculated, and the incremental cost-effectiveness ratio was computed. Finally, women with positive Pap tests were provided navigation by a community health educator to ensure that they received follow-up care. RESULTS: A total of 443 Latinas participated. Seven months after randomization, significantly more women in the high-intensity arm received a Pap test (53.4%) in comparison with the low-intensity arm (38.7%; P < .001) and the usual-care arm (34.0%; P < .01). The incremental cost-effectiveness ratio for high-intensity women versus the control group amounted to $4.24. Twelve women had positive Pap tests, which encompassed diagnoses ranging from atypical squamous cells of unknown significance to invasive cancer; these women received navigation for follow-up care. CONCLUSIONS: A culturally appropriate, in-home, promotora-led educational intervention was successful in increasing cervical cancer screening among Latinas. Cancer 2017;123:666-674. © 2016 American Cancer Society.


Assuntos
Detecção Precoce de Câncer , Programas de Rastreamento , Neoplasias do Colo do Útero/diagnóstico , Adolescente , Adulto , Análise Custo-Benefício , Feminino , Hispânico ou Latino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , População Rural , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia
19.
PLoS One ; 11(9): e0163971, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27682987

RESUMO

Reactive oxygen and nitrogen species (ROS-RNS) are important defence substances involved in the immune response against pathogens. An excessive increase in ROS-RNS, however, can damage the organism causing oxidative stress (OS). The organism is able to neutralise OS by the production of antioxidant enzymes (AE); hence, tissue damage is the result of an imbalance between oxidant and antioxidant status. Though some work has been carried out in humans, there is a lack of information about the oxidant/antioxidant status in the presence of tuberculosis (TB) in wild reservoirs. In the Mediterranean Basin, wild boar (Sus scrofa) is the main reservoir of TB. Wild boar showing severe TB have an increased risk to Mycobacterium spp. shedding, leading to pathogen spreading and persistence. If OS is greater in these individuals, oxidant/antioxidant balance in TB-affected boars could be used as a biomarker of disease severity. The present work had a two-fold objective: i) to study the effects of bovine TB on different OS biomarkers (namely superoxide dismutase (SOD), catalasa (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and thiobarbituric acid reactive substances (TBARS)) in wild boar experimentally challenged with Mycobacterium bovis, and ii) to explore the role of body weight, sex, population and season in explaining the observed variability of OS indicators in two populations of free-ranging wild boar where TB is common. For the first objective, a partial least squares regression (PLSR) approach was used whereas, recursive partitioning with regression tree models (RTM) were applied for the second. A negative relationship between antioxidant enzymes and bovine TB (the more severe lesions, the lower the concentration of antioxidant biomarkers) was observed in experimentally infected animals. The final PLSR model retained the GPX, SOD and GR biomarkers and showed that 17.6% of the observed variability of antioxidant capacity was significantly correlated with the PLSR X's component represented by both disease status and the age of boars. In the samples from free-ranging wild boar, however, the environmental factors were more relevant to the observed variability of the OS biomarkers than the TB itself. For each OS biomarker, each RTM was defined as a maximum by one node due to the population effect. Along the same lines, the ad hoc tree regression on boars from the population with a higher prevalence of severe TB confirmed that disease status was not the main factor explaining the observed variability in OS biomarkers. It was concluded that oxidative damage caused by TB is significant, but can only be detected in the absence of environmental variation in wild boar.

20.
Vet Parasitol ; 209(1-2): 133-7, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25725547

RESUMO

The most widely used technique to assess helminth infection in both domestic and wild mammals is the faecal egg count (FEC). Most efforts to test the reliability of FEC as a proxy for parasite load are in small ruminant studies and limited work has evaluated the use of FEC in pigs. The aim of this study was to explore whether FEC is a reliable indicator of helminth load, and to evaluate the effects of sample storage on FEC accuracy in 59 wild boars. Though FEC was useful for assessing most helminth infections (e.g., Metastrongylus spp., Ascaris suum, Trichuris suis), stomach nematodes were often missed. The accuracy of FEC decreased over time, and thus it is recommended that samples be processed within 5 days of collection.


Assuntos
Fezes/parasitologia , Contagem de Ovos de Parasitas/veterinária , Doenças Parasitárias em Animais/parasitologia , Sus scrofa , Doenças dos Suínos/parasitologia , Animais , Contagem de Ovos de Parasitas/métodos , Doenças Parasitárias em Animais/diagnóstico , Suínos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...