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1.
Methods ; 224: 63-70, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38367653

RESUMEN

Urinalysis is a useful test as an indicator of health or disease and as such, is a part of routine health screening. Urinalysis can be undertaken in many ways, one of which is reagent strips used in the general evaluation of health and to aid in the diagnosis and monitoring of kidney disease. To be effective, the test must be performed properly, and the results interpreted correctly. However, different light conditions and colour perception can vary between users leading to ambiguous readings. This has led to camera devices being used to capture and generate the estimated biomarker concentrations, but image colour can be affected by variations in illumination and inbuilt image processing. Therefore, a new portable device with embedded image processing techniques is presented in this study to provide quantitative measurements that are invariant to changes in illumination. The device includes a novel calibration process and uses the ratio of RGB values to compensate for variations in illumination across an image and improve the accuracy of quantitative measurements. Results show that the proposed calibration method gives consistent homogeneous illumination across the whole image. Comparisons against other existing methods and clinical results show good performance with a correlation to the clinical values. The proposed device can be used for point-of-care testing to provide reliable results consistent with clinical values.


Asunto(s)
Sistemas de Atención de Punto , Tiras Reactivas , Urinálisis/métodos , Procesamiento de Imagen Asistido por Computador
2.
Environ Res ; 246: 118052, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38163547

RESUMEN

The Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) have effectively kept lower antibiotic-resistant bacterial (ARB) pathogen rates than many other countries. However, in recent years, these five countries have encountered a rise in ARB cases and challenges in treating infections due to the growing prevalence of ARB pathogens. Wastewater-based surveillance (WBS) is a valuable supplement to clinical methods for ARB surveillance, but there is a lack of comprehensive understanding of WBS application for ARB in the Nordic countries. This review aims to compile the latest state-of-the-art developments in WBS for ARB monitoring in the Nordic countries and compare them with clinical surveillance practices. After reviewing 1480 papers from the primary search, 54 were found relevant, and 15 additional WBS-related papers were included. Among 69 studies analyzed, 42 dedicated clinical epidemiology, while 27 focused on wastewater monitoring. The PRISMA review of the literature revealed that Nordic countries focus on four major WBS objectives of ARB: assessing ARB in the human population, identifying ARB evading wastewater treatment, quantifying removal rates, and evaluating potential ARB evolution during the treatment process. In both clinical and wastewater contexts, the most studied targets were pathogens producing carbapenemase and extended-spectrum beta-lactamase (ESBL), primarily Escherichia coli and Klebsiella spp. However, vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) have received more attention in clinical epidemiology than in wastewater studies, probably due to their lower detection rates in wastewater. Clinical surveillance has mostly used culturing, antibiotic susceptibility testing, and genotyping, but WBS employed PCR-based and metagenomics alongside culture-based techniques. Imported cases resulting from international travel and hospitalization abroad appear to have frequently contributed to the rise in ARB pathogen cases in these countries. The many similarities between the Nordic countries (e.g., knowledge exchange practices, antibiotic usage patterns, and the current ARB landscape) could facilitate collaborative efforts in developing and implementing WBS for ARB in population-level screening.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Aguas Residuales , Humanos , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Antibacterianos/farmacología , Farmacorresistencia Microbiana , beta-Lactamasas , Escherichia coli , Países Escandinavos y Nórdicos/epidemiología
3.
Malar J ; 22(1): 125, 2023 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-37060041

RESUMEN

BACKGROUND: Although pro-inflammatory cytokines are involved in the clearance of Plasmodium falciparum during the early stages of the infection, increased levels of these cytokines have been implicated in the pathogenesis of severe malaria. Amongst various parasite-derived inducers of inflammation, the malarial pigment haemozoin (Hz), which accumulates in monocytes, macrophages and other immune cells during infection, has been shown to significantly contribute to dysregulation of the normal inflammatory cascades. METHODS: The direct effect of Hz-loading on cytokine production by monocytes and the indirect effect of Hz on cytokine production by myeloid cells was investigated during acute malaria and convalescence using archived plasma samples from studies investigating P. falciparum malaria pathogenesis in Malawian subjects. Further, the possible inhibitory effect of IL-10 on Hz-loaded cells was examined, and the proportion of cytokine-producing T-cells and monocytes during acute malaria and in convalescence was characterized. RESULTS: Hz contributed towards an increase in the production of inflammatory cytokines, such as Interferon Gamma (IFN-γ), Tumor Necrosis Factor (TNF) and Interleukin 2 (IL-2) by various cells. In contrast, the cytokine IL-10 was observed to have a dose-dependent suppressive effect on the production of TNF among other cytokines. Cerebral malaria (CM) was characterized by impaired monocyte functions, which normalized in convalescence. CM was also characterized by reduced levels of IFN-γ-producing T cell subsets, and reduced expression of immune recognition receptors HLA-DR and CD 86, which also normalized in convalescence. However, CM and other clinical malaria groups were characterized by significantly higher plasma levels of pro-inflammatory cytokines than healthy controls, implicating anti-inflammatory cytokines in balancing the immune response. CONCLUSIONS: Acute CM was characterized by elevated plasma levels of pro-inflammatory cytokines and chemokines but lower proportions of cytokine-producing T-cells and monocytes that normalize during convalescence. IL-10 is also shown to have the potential to indirectly prevent excessive inflammation. Cytokine production dysregulated by the accumulation of Hz appears to impair the balance of the immune response to malaria and exacerbates pathology.


Asunto(s)
Malaria Cerebral , Malaria Falciparum , Humanos , Interleucina-10 , Convalecencia , Citocinas , Factor de Necrosis Tumoral alfa , Interferón gamma , Plasmodium falciparum , Macrófagos/metabolismo , Inflamación
4.
Can J Microbiol ; 69(9): 339-350, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37267627

RESUMEN

The goal of this study was to (a) determine the minimum selection concentrations of tetracycline family antibiotics necessary to maintain plasmids carrying tetracycline-resistant genes and (b) correlate these results to environmental hotspot concentrations reported in previous studies. This study used two plasmids (pT295A and pT413A) originating from dairy manure in a surrogate Escherichia coli host CV601. The minimum selection concentrations of antibiotics tested in nutrient-rich medium were determined as follows: 0.1 mg/L for oxytetracycline, 0.45 mg/L for chlortetracycline, and 0.13-0.25 mg/L for tetracycline. Mixing oxytetracycline and chlortetracycline had minimum selection concentration values increased 2-fold compared to those in single antibiotic tests. Minimum selection concentrations found in this study were lower than reported environmental hotspot concentrations, suggesting that tetracycline family antibiotics were likely to be the driver for the selection and maintenance of these plasmids. Relatively high plasmid loss rates (>90%) were observed when culturing a strain carrying a tetracycline-resistant plasmid in antibiotic-free nutrient-rich and nutrient-defined media. Overall, results suggested that these plasmids can be maintained at concentrations environmentally relevant in wastewater treatment plants, sewage, manure, and manured soil; however, they are unstable and easily lost in the absence of antibiotics.


Asunto(s)
Clortetraciclina , Oxitetraciclina , Clortetraciclina/farmacología , Oxitetraciclina/farmacología , Estiércol , Antibacterianos/farmacología , Tetraciclina/farmacología , Plásmidos/genética , Escherichia coli/genética
5.
BMC Med Educ ; 23(1): 724, 2023 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-37789373

RESUMEN

BACKGROUND: The incidence and mortality rates of cancer are rapidly increasing worldwide. This study aimed to assess the knowledge of common cancers among new-entry health science students in Japan and Vietnam, thereby providing insights for implementing appropriate medical educational interventions. METHODS: This cross-sectional study was conducted among new-entry health science students at Hiroshima University, Japan, and the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam. A printed predesigned questionnaire consisting of eleven questions was distributed to the participants during the freshmen health screening at the beginning of the academic year to assess their knowledge of cancer. RESULTS: A total of 2,748 new-entry health science students participated in the study, including 394 (14.3%) Japanese students and 2,354 (85.7%) Vietnamese students. Most cancer knowledge levels in Japanese students were significantly higher than those in Vietnamese students (p < 0.001), except for human papillomavirus (HPV) infection awareness. For this understanding, only 14.8% of Japanese students selected the correct answer, which was significantly lower than the 22.4% of Vietnamese students (p = 0.001). Both the Japanese and Vietnamese students had limited knowledge regarding the connection between HPV infection and cancer and the link between estrogen-progestogen menopausal therapy and breast cancer. Additionally, female students had better knowledge about breast, skin, and endometrial cancers than male students. CONCLUSIONS: Japanese students generally exhibited higher levels of cancer knowledge than Vietnamese students, except for HPV infection recognition. Both groups had limited knowledge regarding the connection between HPV infection and cancer and the relationship between estrogen-progestogen menopausal therapy and breast cancer.


Asunto(s)
Neoplasias de la Mama , Infecciones por Papillomavirus , Humanos , Masculino , Femenino , Vietnam/epidemiología , Japón/epidemiología , Infecciones por Papillomavirus/prevención & control , Estudios Transversales , Progestinas , Conocimientos, Actitudes y Práctica en Salud , Estudiantes , Encuestas y Cuestionarios , Estrógenos
6.
Int J Mol Sci ; 24(12)2023 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-37373352

RESUMEN

Pseudomonas aeruginosa forms stable biofilms, providing a major barrier for multiple classes of antibiotics and severely impairing treatment of infected patients. The biofilm matrix of this Gram-negative bacterium is primarily composed of three major exopolysaccharides: alginate, Psl, and Pel. Here, we studied the antibiofilm properties of sponge-derived natural products ianthelliformisamines A-C and their combinations with clinically used antibiotics. Wild-type P. aeruginosa strain and its isogenic exopolysaccharide-deficient mutants were employed to determine the interference of the compounds with biofilm matrix components. We identified that ianthelliformisamines A and B worked synergistically with ciprofloxacin to kill planktonic and biofilm cells. Ianthelliformisamines A and B reduced the minimum inhibitory concentration (MIC) of ciprofloxacin to 1/3 and 1/4 MICs, respectively. In contrast, ianthelliformisamine C (MIC = 53.1 µg/mL) alone exhibited bactericidal effects dose-dependently on both free-living and biofilm populations of wild-type PAO1, PAO1ΔpslA (Psl deficient), PDO300 (alginate overproducing and mimicking clinical isolates), and PDO300Δalg8 (alginate deficient). Interestingly, the biofilm of the clinically relevant mucoid variant PDO300 was more susceptible to ianthelliformisamine C than strains with impaired polysaccharide synthesis. Ianthelliformisamines exhibited low cytotoxicity towards HEK293 cells in the resazurin viability assay. Mechanism of action studies showed that ianthelliformisamine C inhibited the efflux pump of P. aeruginosa. Metabolic stability analyses indicated that ianthelliformisamine C is stable and ianthelliformisamines A and B are rapidly degraded. Overall, these findings suggest that the ianthelliformisamine chemotype could be a promising candidate for the treatment of P. aeruginosa biofilms.


Asunto(s)
Poríferos , Pseudomonas aeruginosa , Animales , Humanos , Células HEK293 , Biopelículas , Antibacterianos/farmacología , Antibacterianos/metabolismo , Ciprofloxacina/farmacología , Ciprofloxacina/metabolismo , Alginatos/farmacología , Alginatos/metabolismo
7.
Molecules ; 28(7)2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-37050007

RESUMEN

Hydrogels have various promising prospects as a successful platform for detecting biomarkers, and human serum albumin (HSA) is an important biomarker in the diagnosis of kidney diseases. However, the difficult-to-control passive diffusion kinetics of hydrogels is a major factor affecting detection performance. This study focuses on using hydrogels embedded with aggregation-induced emission (AIE) fluorescent probe TC426 to detect HSA in real time. The vortex fluidic device (VFD) technology is used as a rotation strategy to control the reaction kinetics and micromixing during measurement. The results show that the introduction of VFD could significantly accelerate its fluorescence response and effectively improve the diffusion coefficient, while VFD processing could regulate passive diffusion into active diffusion, offering a new method for future sensing research.


Asunto(s)
Colorantes Fluorescentes , Albúmina Sérica Humana , Humanos , Espectrometría de Fluorescencia/métodos , Hidrogeles
8.
Plant J ; 106(4): 953-964, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33619818

RESUMEN

Acetyl-triacylglycerols (acetyl-TAG) contain an acetate group in the sn-3 position instead of the long-chain fatty acid present in regular triacylglycerol (TAG). The acetate group confers unique physical properties such as reduced viscosity and a lower freezing point to acetyl-TAG, providing advantages for use as emulsifiers, lubricants, and 'drop-in' biofuels. Previously, the synthesis of acetyl-TAG in the seeds of the oilseed crop camelina (Camelina sativa) was achieved through the heterologous expression of the diacylglycerol acetyltransferase gene EaDAcT, isolated from Euonymus alatus seeds that naturally accumulate high levels of acetyl-TAG. Subsequent work identified a similar acetyltransferase, EfDAcT, in the seeds of Euonymus fortunei, that possesses higher in vitro activity compared to EaDAcT. In this study, the seed-specific expression of EfDAcT in camelina led to a 20 mol% increase in acetyl-TAG levels over that of EaDAcT. Coupling EfDAcT expression with suppression of the endogenous competing enzyme DGAT1 further enhanced acetyl-TAG accumulation, up to 90 mol% in the best transgenic lines. Accumulation of high levels of acetyl-TAG was stable over multiple generations, with minimal effect on seed size, weight, and fatty acid content. Slight delays in germination were noted in transgenic seeds compared to the wild type. EfDAcT transcript and protein levels were correlated during seed development with a limited window of EfDAcT protein accumulation. In high acetyl-TAG producing lines, EfDAcT protein expression in developing seeds did not reflect the eventual acetyl-TAG levels in mature seeds, suggesting that other factors limit acetyl-TAG accumulation.


Asunto(s)
Acetiltransferasas/metabolismo , Camellia/enzimología , Euonymus/enzimología , Aceites de Plantas/química , Triglicéridos/metabolismo , Acetiltransferasas/genética , Biocombustibles , Camellia/química , Camellia/genética , Diglicéridos/metabolismo , Euonymus/genética , Ácidos Grasos/metabolismo , Germinación , Metabolismo de los Lípidos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Semillas/química , Semillas/enzimología , Semillas/genética
9.
Metab Eng ; 72: 391-402, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35598886

RESUMEN

Biologically produced wax esters can fulfil different industrial purposes. These functionalities almost drove the sperm whale to extinction from hunting. After the ban on hunting, there is a niche in the global market for biolubricants with properties similar to spermaceti. Wax esters can also serve as a mechanism for producing insect sex pheromone fatty alcohols. Pheromone-based mating disruption strategies are in high demand to replace the toxic pesticides in agriculture and manage insect plagues threatening our food and fiber reserves. In this study we set out to investigate the possibilities of in planta assembly of wax esters, for specific applications, through transient expression of various mix-and-match combinations of genes in Nicotiana benthamiana leaves. Our synthetic biology designs were outlined in order to pivot plant lipid metabolism into producing wax esters with targeted fatty acyl and fatty alcohols moieties. Through this approach we managed to obtain industrially important spermaceti-like wax esters enriched in medium-chain fatty acyl and/or fatty alcohol moieties of wax esters. Via employment of plant codon-optimized moth acyl-CoA desaturases we also managed to capture unusual, unsaturated fatty alcohol and fatty acyl moieties, structurally similar to moth pheromone compounds, in plant-accumulated wax esters. Comparison between outcomes of different experimental designs identified targets for stable transformation to accumulate specialized wax esters and helped us to recognize possible bottlenecks of such accumulation.


Asunto(s)
Ésteres , Alcoholes Grasos , Ésteres/metabolismo , Alcoholes Grasos/metabolismo , Feromonas/metabolismo , Hojas de la Planta/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Ceras/metabolismo
10.
Nature ; 535(7611): 252-7, 2016 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-27338790

RESUMEN

Immunomodulatory drugs bind to cereblon (CRBN) to confer differentiated substrate specificity on the CRL4(CRBN) E3 ubiquitin ligase. Here we report the identification of a new cereblon modulator, CC-885, with potent anti-tumour activity. The anti-tumour activity of CC-885 is mediated through the cereblon-dependent ubiquitination and degradation of the translation termination factor GSPT1. Patient-derived acute myeloid leukaemia tumour cells exhibit high sensitivity to CC-885, indicating the clinical potential of this mechanism. Crystallographic studies of the CRBN-DDB1-CC-885-GSPT1 complex reveal that GSPT1 binds to cereblon through a surface turn containing a glycine residue at a key position, interacting with both CC-885 and a 'hotspot' on the cereblon surface. Although GSPT1 possesses no obvious structural, sequence or functional homology to previously known cereblon substrates, mutational analysis and modelling indicate that the cereblon substrate Ikaros uses a similar structural feature to bind cereblon, suggesting a common motif for substrate recruitment. These findings define a structural degron underlying cereblon 'neosubstrate' selectivity, and identify an anti-tumour target rendered druggable by cereblon modulation.


Asunto(s)
Antineoplásicos/farmacología , Péptido Hidrolasas/metabolismo , Factores de Terminación de Péptidos/metabolismo , Compuestos de Fenilurea/farmacología , Talidomida/análogos & derivados , Proteínas Adaptadoras Transductoras de Señales , Secuencias de Aminoácidos , Antineoplásicos/química , Sitios de Unión , Cristalografía por Rayos X , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Humanos , Factor de Transcripción Ikaros/química , Factor de Transcripción Ikaros/metabolismo , Modelos Moleculares , Complejos Multiproteicos/química , Complejos Multiproteicos/metabolismo , Péptido Hidrolasas/química , Factores de Terminación de Péptidos/química , Factores de Terminación de Péptidos/deficiencia , Compuestos de Fenilurea/química , Unión Proteica , Proteolisis/efectos de los fármacos , Especificidad por Sustrato , Talidomida/química , Talidomida/farmacología , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/metabolismo
11.
Appl Environ Microbiol ; 87(14): e0298020, 2021 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-33931422

RESUMEN

The present study investigated the impact of on-farm anaerobic digestion on the abundance of enteric bacteria, antibiotic resistance-associated gene targets, and the horizontal transfer potential of extended-spectrum ß-lactamase (ESBL) genes. Samples of raw and digested manure were obtained from six commercial dairy farms in Ontario, Canada. Digestion significantly abated populations of viable coliforms in all six farms. Conjugative transfer of plasmids carrying ß-lactamase genes from manure bacteria enriched overnight with buffered peptone containing 4 mg/liter cefotaxime into a ß-lactam-sensitive green fluorescent protein (GFP)-labeled Escherichia coli recipient strain was evaluated in patch matings. Digestion significantly decreased the frequency of the horizontal transfer of ESBL genes. Twenty-five transconjugants were sequenced, revealing six distinct plasmids, ranging in size from 40 to 180 kb. A variety of ESBL genes were identified: blaCTX-M-1, blaCTX-M-14, blaCTX-M-15, blaCTX-M-27, blaCTX-M-55, and blaPER-1. blaCTX-M-15 was the most prevalent ESBL gene detected on plasmids harbored by transconjugants. Various mobile genetic elements were found located proximal to resistance genes. Ten gene targets, including sul1, str(A), str(B), erm(B), erm(F), intI1, aadA, incW, blaPSE, and blaOXA-20, were quantified by quantitative PCR on a subset of 18 raw and 18 digested samples. Most targets were significantly more abundant in raw manure; however, erm(B) and erm(F) targets were more abundant in digested samples. Overall, on-farm digestion of dairy manure abated coliform bacteria, a number of antibiotic resistance-associated gene targets, and the potential for in vitro conjugation of plasmids conferring resistance to extended-spectrum ß-lactams and other classes of antibiotics into E. coli CV601. IMPORTANCE Using livestock manure for fertilization can entrain antibiotic-resistant bacteria into soil. Manure on some dairy farms is anaerobically digested before being land applied. Recommending the widespread implementation of the practice should be founded on understanding the impact of this treatment on various endpoints of human health concern. Although lab-scale anaerobic treatments have shown potential for reducing the abundance of antibiotic resistance genes, there are very few data from commercial farms. Anaerobic digestion of manure on six dairy farms efficiently abated coliform bacteria, E. coli, and a majority of antibiotic resistance-associated gene targets. In addition, the conjugation potential of plasmids carrying ESBL genes into introduced E. coli strain CV601 was reduced. Overall, anaerobic digestion abated coliform bacteria, the genes that they carry, and the potential for ESBL-carrying plasmid transfer.


Asunto(s)
Farmacorresistencia Microbiana/genética , Estiércol , Anaerobiosis , Animales , Bacterias/genética , Bovinos , ADN Bacteriano/genética , Granjas , Femenino , Transferencia de Gen Horizontal , Genes Bacterianos , Genotipo , Estiércol/microbiología , Fenotipo , Plásmidos
12.
Plasmid ; 117: 102598, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34499918

RESUMEN

Promoter engineering has been employed as a strategy to enhance and optimize the production of bio-products. Availability of promoters with predictable activities is needed for downstream application. However, whether promoter activity remains the same in different gene contexts remains unknown. Six consecutive promoters that have previously been determined to have different activity levels were used to construct six different versions of plasmid backbone pTH1227, followed by inserted genes encoding two polymer-producing enzymes. In some cases, promoter activity in the presence of inserted genes did not correspond to the reported activity levels in a previous study. After removing the inserted genes, the activity of these promoters returned to their previously reported level. These changes were further confirmed to occur at the transcriptional level. Polymer production using our newly constructed plasmids showed polymer accumulation levels corresponding to the promoter activity reported in our study. Our study demonstrated the importance of re-assessing promoter activity levels with regard to gene context, which could influence promoter activity, leading to different outcomes in downstream applications.


Asunto(s)
Plásmidos , Plásmidos/genética , Regiones Promotoras Genéticas
13.
J Cogn Neurosci ; 32(9): 1813-1822, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32427069

RESUMEN

Healthy aging is associated with a multitude of structural changes in the brain. These physical age-related changes are accompanied by increased variability in neural activity of all kinds, and this increased variability, collectively referred to as "neural noise," is argued to contribute to age-related cognitive decline. In this study, we examine the relationship between two particular types of neural noise in aging. We recorded scalp EEG from younger (20-30 years old) and older (60-70 years old) adults performing a spatial visual discrimination task. First, we used the 1/f-like exponent of the EEG power spectrum, a putative marker of neural noise, to assess baseline shifts toward a noisier state in aging. Next, we examined age-related decreases in the trial-by-trial consistency of visual stimulus processing. Finally, we examined to what extent these two age-related noise markers are related, hypothesizing that greater baseline noise would increase the variability of stimulus-evoked responses. We found that visual cortical baseline noise was higher in older adults, and the consistency of older adults' oscillatory alpha (8-12 Hz) phase responses to visual targets was also lower than that of younger adults. Crucially, older adults with the highest levels of baseline noise also had the least consistent alpha phase responses, whereas younger adults with more consistent phase responses achieved better behavioral performance. These results establish a link between tonic neural noise and stimulus-associated neural variability in aging. Moreover, they suggest that tonic age-related increases in baseline noise might diminish sensory processing and, as a result, subsequent cognitive performance.


Asunto(s)
Disfunción Cognitiva , Ruido , Adulto , Anciano , Envejecimiento , Encéfalo , Electroencefalografía , Humanos , Persona de Mediana Edad , Ruido/efectos adversos , Adulto Joven
14.
FASEB J ; 33(7): 8221-8231, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30958695

RESUMEN

Apolipoprotein E (APOE) genotype is the strongest prevalent genetic risk factor for Alzheimer's disease (AD). Numerous studies have provided insights into the pathologic mechanisms. However, a comprehensive understanding of the impact of APOE genotype on microflora speciation and metabolism is completely lacking. In this study, we investigated the association between APOE genotype and the gut microbiome composition in human and APOE-targeted replacement (TR) transgenic mice. Fecal microbiota amplicon sequencing from matched individuals with different APOE genotypes revealed no significant differences in overall microbiota diversity in group-aggregated human APOE genotypes. However, several bacterial taxa showed significantly different relative abundance between APOE genotypes. Notably, we detected an association of Prevotellaceae and Ruminococcaceae and several butyrate-producing genera abundances with APOE genotypes. These findings were confirmed by comparing the gut microbiota of APOE-TR mice. Furthermore, metabolomic analysis of murine fecal water detected significant differences in microbe-associated amino acids and short-chain fatty acids between APOE genotypes. Together, these findings indicate that APOE genotype is associated with specific gut microbiome profiles in both humans and APOE-TR mice. This suggests that the gut microbiome is worth further investigation as a potential target to mitigate the deleterious impact of the APOE4 allele on cognitive decline and the prevention of AD.-Tran, T. T. T., Corsini, S., Kellingray, L., Hegarty, C., Le Gall, G., Narbad, A., Müller, M., Tejera, N., O'Toole, P. W., Minihane, A.-M., Vauzour, D. APOE genotype influences the gut microbiome structure and function in humans and mice: relevance for Alzheimer's disease pathophysiology.


Asunto(s)
Enfermedad de Alzheimer , Apolipoproteínas E , Disfunción Cognitiva , Microbioma Gastrointestinal , Genotipo , Anciano , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/microbiología , Enfermedad de Alzheimer/patología , Animales , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Ácido Butírico/metabolismo , Disfunción Cognitiva/genética , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/microbiología , Disfunción Cognitiva/patología , Femenino , Humanos , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Estudios Retrospectivos
15.
J Org Chem ; 85(4): 1991-2009, 2020 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-31928002

RESUMEN

Benzimidazoles are common in nature, medicines, and materials. Numerous strategies for preparing 2-arylbenzimidazoles exist. In this work, 1,2-disubstituted benzimidazoles were prepared from various mono- and disubstituted ortho-phenylenediamines (OPD) by iron-catalyzed oxidative coupling. Specifically, O2 and FeCl3·6H2O catalyzed the cross-dehydrogenative coupling and aromatization of diarylmethyl and dialkyl benzimidazole precursors. N,N'-Disubstituted-OPD substrates were significantly more reactive than their N,N-disubstituted isomers, which appears to be relative to their propensity for complexation and charge transfer with Fe3+. The reaction also converted N-monosubstituted OPD substrates to 2-substituted benzimidazoles; however, electron-poor substrates produce 1,2-disubstituted benzimidazoles by intermolecular imino-transfer. Kinetic, reagent, and spectroscopic (UV-vis and EPR) studies suggest a mechanism involving metal-substrate complexation, charge transfer, and aerobic turnover, involving high-valent Fe(IV) intermediates. Overall, comparative strategies for the relatively sustainable and efficient synthesis of 1,2-disubstituted benzimidazoles are demonstrated.

16.
J Community Health ; 45(6): 1178-1186, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33026553

RESUMEN

Colorectal cancer (CRC) is the second and fourth most common cancer in Vietnamese American women and men, respectively. Recent research has highlighted the importance of modifiable lifestyle behaviors such as smoking, alcohol use, dietary behaviors, and physical activities in CRC prevention for the general population. However, it is not well understood how well Vietnamese Americans knew about CRC prevention and risk factors, and whether there were any disparities in knowledge within this vulnerable population. This study examined whether comprehensive measures of acculturation and knowledge of CRC risk are associated with different health behaviors, specifically physical activity, protective dietary behaviors, and risky dietary behaviors in Vietnamese Americans. We recruited 374 Vietnamese Americans aged 50 or above from community-based organizations in the Vietnamese American communities in the greater Philadelphia metropolitan area. Through a cross-sectional survey, we collected data on their knowledge of CRC prevention and risk factors, acculturation-related factors, and sociodemographic characteristics. We found limited knowledge of CRC prevention and risk factors, and suboptimal physical activity and healthy dietary behaviors in the Vietnamese Americans. We also found that higher levels of knowledge about CRC and risk factors were associated with less unhealthy diets but not with more protective diets or physical activity. Acculturation was not significantly associated with overall dietary behaviors in our study. Our findings addressed gaps in current literature concerning the impact of knowledge about CRC risk factors and acculturation on different dimensions of dietary behaviors as well as physical activity. Research and practical implications were discussed.


Asunto(s)
Aculturación , Neoplasias del Colon/prevención & control , Neoplasias Colorrectales/prevención & control , Conductas Relacionadas con la Salud , Estilo de Vida , Adulto , Anciano , Asiático/estadística & datos numéricos , Neoplasias del Colon/psicología , Neoplasias Colorrectales/psicología , Estudios Transversales , Femenino , Estado de Salud , Estilo de Vida Saludable , Humanos , Masculino , Persona de Mediana Edad , Philadelphia , Pobreza , Factores de Riesgo , Asunción de Riesgos , Fumar
17.
J Pak Med Assoc ; 69(Suppl 2)(6): S2-S9, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31369528

RESUMEN

OBJECTIVES: To estimate the economic burden of asthma treatment by quantifying direct medical expenditures at one of Southern Vietnam's public hospitals base on the hospital perspective. METHODS: A retrospective, prevalence-based, cost-of-illness analysis was developed using the hospital's electronic medical record data to calculate the economic burden of asthma (ICD-10 code J45, J46) through direct medical costs from January 2014 to December 2017. All costs were converted to US dollars and to the year 2018. Data were analyzed using descriptive statistics. The potential correlations between variables were evaluated using the chisquare test and bootstrap difference. RESULTS: The average direct medical cost of asthma was estimated to range from $34.7 to $55.3 per - outpatient and $45.1 to $107.2 per - inpatient annually. The total economic burdens for 4 years from 2014 to 2017 were $110,387.4 from outpatients and $13,413.8 from inpatients. The most influential component was medication cost. CONCLUSIONS: Asthma places a high economic burden on individuals and the healthcare system in Vietnam. The findings of this study provide health administrators with important evidence to enhance surveillance of the disease and to allow suitable drafting of national health policy.


Asunto(s)
Atención Ambulatoria/economía , Antiasmáticos/economía , Asma/economía , Costo de Enfermedad , Gastos en Salud , Hospitalización/economía , Adolescente , Adulto , Antiasmáticos/uso terapéutico , Asma/terapia , Niño , Costos de los Medicamentos , Femenino , Costos de Hospital , Hospitales Públicos , Humanos , Seguro de Salud , Masculino , Estudios Retrospectivos , Espirometría/economía , Vietnam , Adulto Joven
18.
Plant J ; 92(1): 82-94, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28715115

RESUMEN

Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) catalyzes the transfer of an acetyl group from acetyl-CoA to the sn-3 position of diacylglycerol to form 3-acetyl-1,2-diacyl-sn-glycerol (acetyl-TAG). EaDAcT belongs to a small, plant-specific subfamily of the membrane bound O-acyltransferases (MBOAT) that acylate different lipid substrates. Sucrose gradient density centrifugation revealed that EaDAcT colocalizes to the same fractions as an endoplasmic reticulum (ER)-specific marker. By mapping the membrane topology of EaDAcT, we obtained an experimentally determined topology model for a plant MBOAT. The EaDAcT model contains four transmembrane domains (TMDs), with both the N- and C-termini orientated toward the lumen of the ER. In addition, there is a large cytoplasmic loop between the first and second TMDs, with the MBOAT signature region of the protein embedded in the third TMD close to the interface between the membrane and the cytoplasm. During topology mapping, we discovered two cysteine residues (C187 and C293) located on opposite sides of the membrane that are important for enzyme activity. In order to identify additional amino acid residues important for acetyltransferase activity, we isolated and characterized acetyltransferases from other acetyl-TAG-producing plants. Among them, the acetyltransferase from Euonymus fortunei possessed the highest activity in vivo and in vitro. Mutagenesis of conserved amino acids revealed that S253, H257, D258 and V263 are essential for EaDAcT activity. Alteration of residues unique to the acetyltransferases did not alter the unique acyl donor specificity of EaDAcT, suggesting that multiple amino acids are important for substrate recognition.


Asunto(s)
Diacilglicerol O-Acetiltransferasa/metabolismo , Euonymus/enzimología , Acetilcoenzima A/metabolismo , Diacilglicerol O-Acetiltransferasa/química , Diacilglicerol O-Acetiltransferasa/genética , Diglicéridos/metabolismo , Retículo Endoplásmico/metabolismo , Euonymus/genética , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Especificidad por Sustrato
20.
Am J Public Health ; 107(3): 433-440, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28103075

RESUMEN

OBJECTIVES: To evaluate the effectiveness of a community-based liver cancer prevention program on hepatitis B virus (HBV) screening among low-income, underserved Vietnamese Americans at high risk. METHODS: We conducted a cluster randomized trial involving 36 Vietnamese community-based organizations and 2337 participants in Pennsylvania, New Jersey, and New York City between 2009 and 2014. We randomly assigned 18 community-based organizations to a community-based multilevel HBV screening intervention (n = 1131). We randomly assigned the remaining 18 community-based organizations to a general cancer education program (n = 1206), which included information about HBV-related liver cancer prevention. We assessed HBV screening rates at 6-month follow-up. RESULTS: Intervention participants were significantly more likely to have undergone HBV screening (88.1%) than were control group participants (4.6%). In a Cochran-Mantel-Haenszel analysis, the intervention effect on screening outcomes remained statistically significant after adjustment for demographic and health care access variables, including income, having health insurance, having a regular health provider, and English proficiency. CONCLUSIONS: A community-based, culturally appropriate, multilevel HBV screening intervention effectively increases screening rates in a high-risk, hard-to-reach Vietnamese American population.


Asunto(s)
Hepatitis B/etnología , Neoplasias Hepáticas/etnología , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/virología , Tamizaje Masivo , Adulto , Asiático , Femenino , Humanos , Masculino , Persona de Mediana Edad , New Jersey/epidemiología , Ciudad de Nueva York/epidemiología , Educación del Paciente como Asunto , Pennsylvania/epidemiología , Prevalencia , Vietnam/etnología
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