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1.
BMC Geriatr ; 24(1): 334, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609852

RESUMEN

BACKGROUND: Outcomes following proximal humeral fracture (PHF) may be impacted by a range of clinical, fracture and premorbid factors. The aim of this study was to examine factors impacting hospital admission; length of stay (LOS) and new discharge destination for patients presenting to hospital with PHF. METHODS: Retrospective audit conducted at a tertiary health service. Data was collected from adult patients presenting to hospital with a PHF over a 54-month period. Fractures that were pathological or sustained during admission were excluded. Univariable and multivariable logistic and negative binomial regression were used to explore factors associated with hospital admission, LOS and new discharge destination. RESULTS: Data were analyzed from 701 participants (age 70 years (IQR 60, 81); 72.8% female); 276 (39.4%) participants required a hospital admission. New discharge destination was required for 109 (15.5%) participants, of whom 49 (45%) changed from home alone to home with family/friend(s). Greater comorbidities, as indicated by the Charlson Comorbidity Index score, were associated with hospital admission, longer LOS and new discharge destination. Premorbid living situations of home with family/friend(s) or from an external care facility were associated with a decreased likelihood of hospital admission, shorter LOS and reduced risk of a new discharge destination. Surgical treatment was associated with shorter LOS. Older age and dementia diagnosis were associated with a new discharge destination. CONCLUSIONS: Many factors potentially impact on the likelihood or risk of hospitalization, LOS and new discharge destination post PHF. Patients with greater comorbidities are more likely to have negative outcomes, while patients who had premorbid living situations of home with family/friend(s) or from an external care facility are more likely to have positive outcomes. Early identification of factors that may impact patient outcomes may assist timely decision making in hospital settings. Further research should focus on developing tools to predict hospital outcomes in the PHF population.


Asunto(s)
Alta del Paciente , Fracturas del Hombro , Humanos , Femenino , Anciano , Masculino , Tiempo de Internación , Estudios Retrospectivos , Hospitalización , Fracturas del Hombro/epidemiología , Fracturas del Hombro/terapia , Hospitales
2.
Phys Chem Chem Phys ; 26(17): 13316-13326, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38639914

RESUMEN

In this article we present a quantitative analysis of the second positive system of molecular nitrogen and the first negative system of the molecular nitrogen cation excited in the presence of ionizing radiation. Optical emission spectra of atmospheric air and nitrogen surrounding 210Po sources were measured from 250 to 400 nm. Multi-Boltzmann and non-Boltzmann vibrational distribution spectral models were used to determine the vibrational temperature and vibrational distribution function of the emitting N2(C3Πu) and N2+(B2Σ+u) states. A zero-dimensional kinetic model, based on the electron energy distribution function (EEDF) and steady-state excitation and de-excitation of N2(X1Σ+g), N2+(B2Σ+u), N2+(X2Σ+g), N4+, O2+, and N2(C3Πu, v), was developed for the prediction of the relative spectral intensity of both the N2+(B2Σ+u → X2Σ+g) emission band and the vibrational bands of N2(C3Πu → B3Πg) for comparison with the experimental data.

5.
Breast Cancer Res Treat ; 190(2): 287-293, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34515905

RESUMEN

PURPOSE: Older cancer survivors required medical care during the COVID-19 pandemic, but there are limited data on medical care in this age group. METHODS: We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors aged 60-98 from five US regions (n = 321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included interruptions in seeing or speaking to doctors, receiving medical treatment or supportive therapies, or filling prescriptions since the pandemic began. Logistic regression models evaluated associations between care disruptions and education, medical, psychosocial, and COVID-19-related factors. Multivariate models included age, county COVID-19 death rates, comorbidity, and post-diagnosis time. RESULTS: There was a high response rate (n = 262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were higher with each year of education (OR 1.22, 95% CI 1.08-1.37, p = < 0.001) and increased depression by CES-D score (OR 1.04, CI 1.003-1.08, p = 0.033) while increased tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99, p = 0.012). There was a trend between disruptions and comorbidities (unadjusted OR 1.13 per comorbidity, 95% CI 0.99-1.29, p = 0.07). Adjusting for covariates, higher education years (OR1.23, 95% CI 1.09-1.39, p = 0.001) and tangible social support (OR 0.98 95% CI 0.97-1.00, p = 0.006) remained significantly associated with having care disruptions. CONCLUSION: Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions. CLINICALTRIALS. GOV IDENTIFIER: NCT03451383.


Asunto(s)
Neoplasias de la Mama , COVID-19 , Supervivientes de Cáncer , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Femenino , Humanos , Persona de Mediana Edad , Pandemias , SARS-CoV-2
6.
Fungal Syst Evol ; 7: 67-98, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34124618

RESUMEN

The taxonomy of Oculimacula, Rhynchosporium and Spermospora is re-evaluated, along with that of phylogenetically related genera. Isolates are identified using comparisons of DNA sequences of the internal transcribed spacer ribosomal RNA locus (ITS), partial translation elongation factor 1-alpha (tef1), actin (act), DNA-directed RNA polymerase II largest (rpb1) and second largest subunit (rpb2) genes, and the nuclear ribosomal large subunit (LSU), combined with their morphological characteristics. Oculimacula is restricted to two species, O. acuformis and O. yallundae, with O. aestiva placed in Cyphellophora, and O. anguioides accommodated in a new genus, Helgardiomyces. Rhynchosporium s. str. is restricted to species with 1-septate conidia and hooked apical beaks, while Rhynchobrunnera is introduced for species with 1-3-septate, straight conidia, lacking any apical beak. Rhynchosporium graminicola is proposed to replace the name R. commune applied to the barley scald pathogen based on nomenclatural priority. Spermospora is shown to be paraphyletic, representing Spermospora (type: S. subulata), with three new species, S. arrhenatheri, S. loliiphila and S. zeae, and Neospermospora gen. nov. (type: N. avenae). Ypsilina (type: Y. graminea), is shown to be monophyletic, but appears to be of minor importance on cereals. Finally, Vanderaaea gen. nov. (type: V. ammophilae), is introduced as a new coelomycetous fungus occurring on dead leaves of Ammophila arenaria. Citation: Crous PW, Braun U, McDonald BA, Lennox CL, Edwards J, Mann RC, Zaveri A, Linde CC, Dyer PS, Groenewald JZ (2020). Redefining genera of cereal pathogens: Oculimacula, Rhynchosporium and Spermospora. Fungal Systematics and Evolution 7: 67-98. doi: 10.3114/fuse.2021.07.04.

7.
Res Sq ; 2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33880464

RESUMEN

PurposeOlder cancer survivors required medical care during the COVID-19 pandemic despite infection risks, but there are limited data on medical care in this age group. METHODS: We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors ages 60-98 from five US regions (n=321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included self-reported interruptions in ability to see doctors, receive treatment or supportive therapies, or fill prescriptions. Logistic regression models evaluated bivariate and multivariate associations between care disruptions and education, medical, psychosocial and COVID-19-related factors. Multivariate models included age, county COVID-19 rates, comorbidity and post-diagnosis time. RESULTS: There was a high response rate (n=262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were significantly higher with more education (OR 1.23 per one-year increase, 95% CI 1.09-1.39, p =0.001) and greater depression (OR 1.04 per one-point increase in CES-D score, CI 1.003-1.08, p=0.033); tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99 per one-point increase, p=0.012). There was a trend for associations between disruptions and comorbidity (unadjusted OR 1.13 per 1 added comorbidity, 95% CI 0.99-1.29, p=0.07). Adjusting for covariates, only higher education (p=0.001) and tangible social support (p=0.006) remained significantly associated with having care disruptions. CONCLUSIONS: Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions.

8.
Environ Pollut ; 274: 116547, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33548672

RESUMEN

Wetland snakes, as top predators, are becoming globally recognised as bioindicators of wetland contamination. Livers are the traditional test organ for contaminant exposure in organisms, but research is moving towards a preference for non-lethal tissue sampling. Snake scales can be used as an indicator of exposure, as many metals bind to the keratin. We used laser ablation with inductively coupled plasma-atomic emission spectroscopy and mass spectrometry (LA-ICP-MS) to quantify the concentrations of 19 metals and metalloids (collectively referred to 'metals' hereafter) in Western tiger snake (Notechis scutatus occidentalis) scales from four wetlands along an urban gradient, and compared them to concentrations measured in captive tiger snake scales. We conducted repeat measures to determine the concentration accuracy of each metal using LA-ICP-MS. Concentrations in wild Western tiger snake scales were significantly higher than in reference tiger snake scales for most metals analysed, suggesting accumulation from environmental exposure. We compared the scale concentrations to sediment concentrations of sampled wetlands, and found inter-site differences between mean concentrations of metals in scales parallel patterns recorded from sediment. Four metals (Mn, As, Se, Sb) had strong positive correlations with liver tissue contents suggesting scale concentrations can be used to infer internal concentrations. By screening for a larger suite of metals than we could using traditional digestive methods, we identified additional metals (Ti, V, Sr, Cs, Tl, Th, U) that may be accumulating to levels of concern in tiger snakes in Perth, Western Australia. This research has progressed the use of LA-ICP-MS for quantifying a suite of metals available in snake scales, and highlights the significance of using wetland snake scales as a non-lethal indicator of environmental contamination.


Asunto(s)
Monitoreo del Ambiente , Metales , Animales , Metales/análisis , Serpientes , Australia Occidental , Humedales
9.
Persoonia ; 46: 116-128, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35935891

RESUMEN

Several plant pathogenic Parastagonospora species have been identified infecting wheat and other cereals over the past 50 years. As new lineages were discovered, naming conventions grew unwieldy and the relationships with previously recognized species remained unclear. We used genome sequencing to clarify relationships among these species and provided new names for most of these species. Six of the nine described Parastagonospora species were recovered from wheat, with five of these species coming from Iran. Genome sequences revealed that three strains thought to be hybrids between P. nodorum and P. pseudonodorum were not actually hybrids, but rather represented rare gene introgressions between those species. Our data are consistent with the hypothesis that P. nodorum originated as a pathogen of wild grasses in the Fertile Crescent, then emerged as a wheat pathogen via host-tracking during the domestication of wheat in the same region. The discovery of a diverse array of Parastagonospora species infecting wheat in Iran suggests that new wheat pathogens could emerge from this region in the future. Citation: Croll D, Crous PW, Pereira D, et al. 2021. Genome-scale phylogenies reveal relationships among Parastagonospora species infecting domesticated and wild grasses. Persoonia 46: 116-128. https://doi.org/10.3767/persoonia.2021.46.04.

11.
Genes (Basel) ; 11(1)2019 12 26.
Artículo en Inglés | MEDLINE | ID: mdl-31888105

RESUMEN

Maize lethal necrosis (MLN) occurs when maize chlorotic mottle virus (MCMV) and sugarcane mosaic virus (SCMV) co-infect maize plant. Yield loss of up to 100% can be experienced under severe infections. Identification and validation of genomic regions and their flanking markers can facilitate marker assisted breeding for resistance to MLN. To understand the status of previously identified quantitative trait loci (QTL)in diverse genetic background, F3 progenies derived from seven bi-parental populations were genotyped using 500 selected kompetitive allele specific PCR (KASP) SNPs. The F3 progenies were evaluated under artificial MLN inoculation for three seasons. Phenotypic analyses revealed significant variability (P ≤ 0.01) among genotypes for responses to MLN infections, with high heritability estimates (0.62 to 0.82) for MLN disease severity and AUDPC values. Linkage mapping and joint linkage association mapping revealed at least seven major QTL (qMLN3_130 and qMLN3_142, qMLN5_190 and qMLN5_202, qMLN6_85 and qMLN6_157qMLN8_10 and qMLN9_142) spread across the 7-biparetal populations, for resistance to MLN infections and were consistent with those reported previously. The seven QTL appeared to be stable across genetic backgrounds and across environments. Therefore, these QTL could be useful for marker assisted breeding for resistance to MLN.


Asunto(s)
Mapeo Cromosómico/métodos , Resistencia a la Enfermedad , Sitios de Carácter Cuantitativo , Zea mays/crecimiento & desarrollo , Fenotipo , Fitomejoramiento , Potyvirus/patogenicidad , Análisis de Componente Principal , Tombusviridae/patogenicidad , Zea mays/genética , Zea mays/virología
12.
Semin Thorac Cardiovasc Surg ; 31(1): 21-31, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30012367

RESUMEN

Cardiac surgery patients with a prolonged ICU length of stay (prICULOS) have lower rates of functional survival following their procedure, however detailed information on their health related quality of life (HRQoL) is lacking. We sought to investigate the potential need for intervention in these high-risk patients through comprehensive HRQoL assessments in the months to year following their surgery. A prospective, observational pilot study was undertaken and cardiac surgery patients with a prICULOS (ICU length of stay of ≥5 days) were recruited. A control group was obtained through recruitment of cardiac surgery patients with an ICU length of stay of <5 days. In-person clinical or telephone survey HRQoL assessments were completed at 3-6 months and 1-year time points after their procedure. The standardized mean difference (SMD) was calculated for all study variable comparisons to quantify the standardized effect size observed between non-prICULOS and prICULOS patients. 789 cardiac procedures were performed during the study period and 89 patients experienced a prICULOS (10.7%). Of these 89 patients, 35 prICULOS patients were recruited along with 35 controls. 29 out of 35 prICULOS patients completed the study (83%). At the 3-6 month follow up the prICULOS patients had higher levels of weight loss, fear of falling, and driving deficits. At 1-year, prICULOS patients had persistent difficulties with activities of daily living and required more family and external support. This study demonstrates the need for closer follow up and intervention for cardiac surgery patients with a prICULOS who were found to have poorer mid and long-term HRQoL.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/efectos adversos , Unidades de Cuidados Coronarios , Tiempo de Internación , Calidad de Vida , Actividades Cotidianas , Anciano , Estudios de Casos y Controles , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Recuperación de la Función , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
14.
Clin Exp Dermatol ; 42(7): 771-773, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28597964

RESUMEN

Inflammatory bowel disease (IBD) can be divided into Crohn disease, ulcerative colitis and inflammatory bowel disease unclassified (IBDU). In most patients, these disorders present in adolescence or early adulthood. Patients with infantile IBD can have an associated underlying immunodeficiency disorder caused by a mutation in interleukin (IL)-10 or its receptor. We describe a child presenting with intractable bloody diarrhoea since 2 weeks of age and with severe nappy ulceration, who was ultimately diagnosed as having inflammatory bowel disease (IBD) due to an immunodeficiency in the IL-10 receptor. This report highlights the importance of considering this rare immunodeficiency in patients with infantile IBD presenting with severe perianal disease to a dermatologist.


Asunto(s)
Enfermedades Inflamatorias del Intestino/genética , Interleucina-10/genética , Mutación , Úlcera Cutánea/genética , Resultado Fatal , Trasplante de Células Madre Hematopoyéticas , Humanos , Lactante , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/terapia , Masculino , Úlcera Cutánea/complicaciones , Úlcera Cutánea/terapia
15.
J Intellect Disabil Res ; 61(2): 181-195, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27561217

RESUMEN

BACKGROUND: Executive function (EF) plays a critical role in academic outcomes in typically developing children, but the contribution of EF to academic performance in Down syndrome (DS) is less well understood. This study evaluated differences in early academic foundations between primary school aged children with DS and non-verbal mental-age matched typically developing (TD) children. Additionally, the contribution of EF domains to academic outcomes was evaluated in each group. METHOD: Participants with DS (n = 29) and mental-age matched TD participants (n = 23) were administered the Woodcock Johnson- III NU Tests of Academic Achievement, as well as a laboratory-based EF battery, including measures of working memory, shifting, inhibition and object-planning. RESULTS: Findings indicated a difference in early academic foundations profile between children with DS and mental-age matched TD children. Patterns of EF contributions towards academic outcomes were also observed across groups. CONCLUSIONS: Aspects of EF are critical to academic achievement in DS but differentially so relative to typical development. Implications for educational instruction are discussed.


Asunto(s)
Éxito Académico , Síndrome de Down/fisiopatología , Función Ejecutiva/fisiología , Niño , Preescolar , Femenino , Humanos , Masculino
16.
Matern Child Nutr ; 13(3)2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-27460693

RESUMEN

Vitamin D deficiency has adverse health effects in young children. Our aims were to determine predictors of vitamin D status and then to use these factors to develop a practical tool to predict low 25(OH)D concentrations in preschool New Zealand children. A cross-sectional sample of 1329 children aged 2 to <5 years were enrolled from throughout New Zealand in late-winter to spring 2012. 25-Hydroxyvitamin D (25(OH)D) was measured on dried blood spot (DBS) samples collected using finger-prick sampling. Caregivers completed a questionnaire. Mean (SD) DBS 25(OH)D concentration was 52(19)nmol/L. 25(OH)D < 25 nmol/L was present in 86(7%), 25(OH)D < 50 nmol/L in 642(48%), 25(OH)D 50- < 75 nmol/L in 541(41%) and 25(OH)D > 75 nmol/L in 146(11%) of children. Factors independently associated with the risk of 25(OH)D < 25 nmol/L were female gender (OR 1.92,95%CI 1.17-3.14), other non-European ethnicities (not including Maori or Pacific) (3.51,1.89-6.50), had olive-dark skin colour (4.52,2.22-9.16), did not take vitamin D supplements (2.56,1.06-6.18), had mothers with less than secondary-school qualifications (5.00,2.44-10.21) and lived in more deprived households (1.27,1.06-1.53). Children who drank toddler milk (vitamin D fortified cow's milk formula marketed to young children) had a zero risk of 25(OH)D < 25 nmol/L. The predictive tool identified children at risk of 25(OH)D < 25 nmol/L with sensitivity 42%, specificity 97% and ROC area-under-curve 0.76(95%CI 0.67-0.86, p < 0.001). Predictors of low vitamin D status were consistent with those identified in previous studies of New Zealand children. The tool had insufficient predictive ability for use in clinical situations, and suggests a need to promote safe, inexpensive testing to determine vitamin D status in preschool children.


Asunto(s)
Alimentos Fortificados , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/epidemiología , Vitamina D/administración & dosificación , Vitamina D/sangre , Animales , Preescolar , Estudios Transversales , Suplementos Dietéticos , Femenino , Humanos , Masculino , Leche/química , Nueva Zelanda/epidemiología , Estado Nutricional , Instituciones Académicas , Estaciones del Año , Pigmentación de la Piel
17.
Environ Entomol ; 45(6): 1415-1423, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-28028088

RESUMEN

Subterranean termites need to minimize potentially pathogenic and competitive fungi in their environment in order to maintain colony health. We examined the ability of Actinobacteria isolated from termite guts in suppressing microorganisms commonly encountered in a subterranean environment. Guts from two subterranean termite species, Reticulitermes flavipes (Kollar) and Reticulitermes tibialis Banks, were extracted and plated on selective chitin media. A total of 38 Actinobacteria isolates were selected for in vitro growth inhibition assays. Target microbes included three strains of Serratia marcescens Bizio, two mold fungi (Trichoderma sp. and Metarhizium sp.), a yeast fungus (Candida albicans (C.P. Robin) Berkhout), and four basidiomycete fungi (Gloeophyllum trabeum (Persoon) Murrill, Tyromyces palustris (Berkeley & M.A. Curtis) Murrill, Irpex lacteus (Fries) Fries, and Trametes versicolor (L.) Lloyd). Results showed both broad and narrow ranges of antimicrobial activity against the mold fungi, yeast fungus, and S. marcescens isolates by the Actinobacteria selected. This suggests that termite gut-associated Actinobacteria produce secondary antimicrobial compounds that may be important for pathogen inhibition in termites. Basidiomycete fungi were strongly inhibited by the selected Actinobacteria isolates, with G. trabeum and T. versicolor being most inhibited, followed by I. lacteus and T. palustris The degree of inhibition was correlated with shifts in pH caused by the Actinobacteria. Nearly all Actinobacteria isolates raised pH of the growth medium to basic levels (i.e. pH ∼8.0-9.5). We summarize antimicrobial activity of these termite gut-associated Actinobacteria and examine the implications of these pH shifts.


Asunto(s)
Actinobacteria/fisiología , Antiinfecciosos/farmacología , Microbioma Gastrointestinal , Isópteros/microbiología , Actinobacteria/genética , Animales , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Análisis de Secuencia de ARN
18.
Handb Clin Neurol ; 138: 297-309, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27637965

RESUMEN

Cancer and treatment-related neurocognitive dysfunction (CRND) - impairments in aspects of cognition commonly including attention and memory, information-processing speed, and executive functioning - can negatively affect patients' and survivors' participation in routine activities of daily living and overall quality of life. CRND can be enduring, and varies in severity level. The epidemiology of CRND is not yet clearly established; reported incidence has ranged from 17% to 75% among patients and survivors of noncentral nervous system malignancies, including breast, prostate, cervical, and colorectal cancers. Progress in the development of strategies for assessing and treating CRND has been delayed by limitations in the knowledge of the precise etiology of this adverse condition, as well as the lack of sufficiently sensitive and reliable methods to determine its presence and quantify its severity. In this chapter, we present a brief description of the concept of CRND and its clinical presentation, and discuss the descriptive epidemiology, pathophysiology, risk factors, and availability of treatment interventions. This neuroepidemiologic perspective provides a framework for characterizing CRND, determining its etiology, and understanding its negative effects on routine activities of daily living, to help support the development and testing of reliable interventions to treat this deleterious condition for patients and survivors.


Asunto(s)
Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/etiología , Neoplasias/complicaciones , Sobrevivientes/psicología , Edad de Inicio , Antineoplásicos/efectos adversos , Humanos , Incidencia , Neoplasias/tratamiento farmacológico
19.
PLoS One ; 11(7): e0159524, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27454866

RESUMEN

Non-alcoholic fatty liver disease has become the leading liver disease in North America and is associated with the progressive inflammatory liver disease non-alcoholic steatohepatitis (NASH). Considerable effort has been made to understand the role of resident and recruited macrophage populations in NASH however numerous questions remain. Our goal was to characterize the dynamic changes in liver macrophages during the initiation of NASH in a murine model. Using the methionine-choline deficient diet we found that liver-resident macrophages, Kupffer cells were lost early in disease onset followed by a robust infiltration of Ly-6C+ monocyte-derived macrophages that retained a dynamic phenotype. Genetic profiling revealed distinct patterns of inflammatory gene expression between macrophage subsets. Only early depletion of liver macrophages using liposomal clodronate prevented the development of NASH in mice suggesting that Kupffer cells are critical for the orchestration of inflammation during experimental NASH. Increased understanding of these dynamics may allow us to target potentially harmful populations whilst promoting anti-inflammatory or restorative populations to ultimately guide the development of effective treatment strategies.


Asunto(s)
Macrófagos del Hígado/metabolismo , Hígado/metabolismo , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Inmunidad Adaptativa , Animales , Biomarcadores , Quimiotaxis de Leucocito/inmunología , Análisis por Conglomerados , Dieta , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Inmunidad Innata , Macrófagos del Hígado/patología , Pruebas de Función Hepática , Subgrupos Linfocitarios/inmunología , Subgrupos Linfocitarios/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Monocitos/metabolismo , Monocitos/patología , Enfermedad del Hígado Graso no Alcohólico/patología , Transcriptoma
20.
Biochim Biophys Acta ; 1862(7): 1337-44, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27085070

RESUMEN

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease is now the leading liver disease in North America. The progression of non-alcoholic fatty liver disease to the inflammatory condition, non-alcoholic steatohepatitis is complex and currently not well understood. Intestinal microbial dysbiosis has been implicated in the development of non-alcoholic fatty liver disease and progression of non-alcoholic steatohepatitis. Volatile organic compounds are byproducts of microbial metabolism in the gut that may enter portal circulation and have hepatotoxic effects contributing to the pathogenesis of non-alcoholic steatohepatitis. To test this hypothesis, we measured volatile organic compounds in cecal luminal contents and portal venous blood in a mouse model of non-alcoholic steatohepatitis. METHODS: Gas chromatography-mass spectrometry analysis was conducted on cecal content and portal vein blood for volatile organic compound detection from mice fed a methionine and choline deficient diet, which induces non-alcoholic steatohepatitis. The colonic microbiome was studied by 16S rRNA gene amplification using the Illumina MiSeq platform. RESULTS: Sixty-eight volatile organic compounds were detected in cecal luminal content, a subset of which was also present in portal venous blood. Importantly, differences in portal venous volatile organic compounds were associated with diet-induced steatohepatitis establishing a biochemical link between gut microbiota-derived volatile organic compounds and increased susceptibility to non-alcoholic steatohepatitis. CONCLUSION: Our model creates a novel tool to further study the role of gut-derived volatile organic compounds in the pathogenesis of non-alcoholic steatohepatitis.


Asunto(s)
Inflamación/microbiología , Hígado/irrigación sanguínea , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/microbiología , Vena Porta/microbiología , Compuestos Orgánicos Volátiles/análisis , Animales , Bacterias/aislamiento & purificación , Células Cultivadas , Modelos Animales de Enfermedad , Inflamación/patología , Mediadores de Inflamación/análisis , Hígado/microbiología , Hígado/patología , Macrófagos/microbiología , Macrófagos/patología , Masculino , Ratones Endogámicos C57BL , Microbiota , Enfermedad del Hígado Graso no Alcohólico/patología , Vena Porta/patología
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