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In school-age children, the myelination of the auditory radiation thalamocortical pathway is associated with the latency of auditory evoked responses, with the myelination of thalamocortical axons facilitating the rapid propagation of acoustic information. Little is known regarding this auditory system function-structure association in infants and toddlers. The present study tested the hypothesis that maturation of auditory radiation white-matter microstructure (e.g., fractional anisotropy (FA); measured using diffusion-weighted MRI) is associated with the latency of the infant auditory response (P2m measured using magnetoencephalography, MEG) in a cross-sectional (2 to 24 months) as well as longitudinal cohort (2 to 29 months) of typically developing infants and toddlers. In the cross-sectional sample, non-linear maturation of P2m latency and auditory radiation diffusion measures were observed. After removing the variance associated with age in both P2m latency and auditory radiation diffusion measures, auditory radiation still accounted for significant variance in P2m latency. In the longitudinal sample, latency and FA associations could be observed at the level of a single child. Findings provide strong support for a contribution of auditory radiation white matter to rapid cortical auditory encoding processes in infants.
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AIM: To assess whether adults with diabetes on oral hypoglycaemic agents undergoing general endotracheal anaesthesia during nine common surgical procedures who are glucagon-like peptide-1 receptor agonist (GLP1-RA) users, compared with non-users, are at increased risk of six peri- and post-procedure complications. MATERIALS AND METHODS: A retrospective observational cohort analysis of over 130 million deidentified US adults with diabetes (defined as being on oral hypoglycaemic agents) from a nationally representative electronic health dataset between 1 January 2015 and 1 April 2023 was analysed. Cohorts were matched by high-dimensionality propensity scoring. We compared the odds of six peri- and postoperative complications in GLP1-RA users and non-users. A sensitivity analysis compared these odds in GLP1-RA users to non-users with diabetes and obesity. We measured the odds of (a) a composite outcome of postoperative decelerated gastric emptying, including antiemetic use, ileus within 7 days post-procedure, gastroparesis diagnosis, gastric emptying study; (b) postoperative aspiration or pneumonitis; (c) severe respiratory failure; (d) postoperative hypoglycaemia; (e) inpatient mortality; and (f) 30-day mortality. RESULTS: Among 13 361 adults with diabetes, 16.5% were treated with a GLP1-RA. In the high-dimensionality propensity score-matched cohort, GLP1-RA users had a lower risk of peri- and postoperative complications for decelerated gastric emptying and antiemetic use compared with non-users. The risk of ileus within 7 days, aspiration/pneumonitis, hypoglycaemia and 30-day mortality were not different. A sensitivity analysis showed similar findings in patients with diabetes and obesity. CONCLUSION: No increased risk of peri- and postoperative complications in GLP1-RA users undergoing surgery with general endotracheal anaesthesia was identified.
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Receptor del Péptido 1 Similar al Glucagón , Hipoglucemiantes , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Complicaciones Posoperatorias/epidemiología , Receptor del Péptido 1 Similar al Glucagón/agonistas , Persona de Mediana Edad , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/efectos adversos , Anciano , Adulto , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Hipoglucemia/inducido químicamente , Hipoglucemia/epidemiología , Factores de Riesgo , Complicaciones Intraoperatorias/inducido químicamente , Complicaciones Intraoperatorias/epidemiología , Estudios de Cohortes , Agonistas Receptor de Péptidos Similares al GlucagónRESUMEN
Mice engineered with a G12D versus Q61R mutation in Kras exhibited differences in tumorigenesis. Namely, the incidence or grade of oral or forestomach squamous epithelial lesions was more prevalent in the KrasG12D background while hematolymphopoietic disease was more prevalent in the KrasQ61R background. Loss of the Trp53 gene encoding the tumor suppressor p53 enhances the ability of oncogenic Kras to initiate tumorigenesis in carcinogen and genetic models of lung cancer. Conversley, an extra copy of Trp53 (Super p53) was recently shown to suppress Kras-induced tumorigenesis in a genetic model of this disease. Given this, we evaluated whether an extra copy of Trp53 would alter tumorigenesis upon global activation of a modified Kras allele engineered with either a G12D or Q61R mutation. We report that an increase in p53 dosage significantly reduced the incidence or grade of oral and forestomach squamous tumors induced by either G12D and Q61R-mutant Kras. The incidence of myeloproliferative disease was also significantly reduced with increased p53 dosage in the KrasQ61R background. Both the percentage of mice with lung tumors and total number of adenomas per animal were unchanged. However, the incidence and grade of peripheral atypical alveolar hyperplasia was significantly decreased in both backgrounds with increased p53 dosage. Finally, the number of foci of bronchioloalveolar hyperplasia per animal significantly increased with increased p53 dosage in the KrasG12D background. These results suggest that an extra copy of p53 can impede oncogenic Kras driven tumorigenesis in some tissues.
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Carcinoma de Células Escamosas , Neoplasias Pulmonares , Ratones , Animales , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína p53 Supresora de Tumor/genética , Hiperplasia , Transformación Celular Neoplásica/genética , Carcinogénesis/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Modelos Animales de EnfermedadRESUMEN
Perfluorobutanesulfonic acid (PFBS) is a replacement for perfluorooctanesulfonic acid (PFOS) that is increasingly detected in drinking water and human serum. Higher PFBS exposure is associated with risk for preeclampsia, the leading cause of maternal and infant morbidity and mortality in the United States. This study investigated relevant maternal and fetal health outcomes after gestational exposure to PFBS in a New Zealand White rabbit model. Nulliparous female rabbits were supplied drinking water containing 0 mg/l (control), 10 mg/l (low), or 100 mg/l (high) PFBS. Maternal blood pressure, body weights, liver and kidney weights histopathology, clinical chemistry panels, and thyroid hormone levels were evaluated. Fetal endpoints evaluated at necropsy included viability, body weights, crown-rump length, and liver and kidney histopathology, whereas placenta endpoints included weight, morphology, histopathology, and full transcriptome RNA sequencing. PFBS-high dose dams exhibited significant changes in blood pressure markers, seen through increased pulse pressure and renal resistive index measures, as well as kidney histopathological changes. Fetuses from these dams showed decreased crown-rump length. Statistical analysis of placental weight via a mixed model statistical approach identified a significant interaction term between PFBS high dose and fetal sex, suggesting a sex-specific effect on placental weight. RNA sequencing identified the dysregulation of angiotensin (AGT) in PFBS high-dose placentas. These results suggest that PFBS exposure during gestation leads to adverse maternal outcomes, such as renal injury and hypertension, and fetal outcomes, including decreased growth parameters and adverse placenta function. These outcomes raise concerns about pregnant women's exposure to PFBS and pregnancy outcomes.
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Agua Potable , Fluorocarburos , Masculino , Humanos , Embarazo , Femenino , Conejos , Animales , Exposición Materna/efectos adversos , Placenta , Nueva Zelanda , Fluorocarburos/toxicidad , Peso CorporalRESUMEN
Irritable Bowel Syndrome (IBS), the most common gastrointestinal disorder, is diagnosed solely on symptoms. Potentially diagnostic alterations in the bacterial component of the gut microbiome (the bacteriome) are associated with IBS, but despite the known role of the virome (particularly bacteriophages), in shaping the gut bacteriome, few studies have investigated the virome in IBS. We performed metagenomic sequencing of fecal Virus-Like Particles (VLPs) from 55 patients with IBS and 51 control individuals. We detected significantly lower alpha diversity of viral clusters comprising both known and novel viruses (viral 'dark matter') in IBS and a significant difference in beta diversity compared to controls, but not between IBS symptom subtypes. The three most abundant bacteriophage clusters belonged to the Siphoviridae, Myoviridae, and Podoviridae families (Order Caudovirales). A core virome (defined as a cluster present in at least 50% of samples) of 5 and 12 viral clusters was identified in IBS and control subjects, respectively. We also identified a subset of viral clusters that showed differential abundance between IBS and controls. The virome did not co-vary significantly with the bacteriome, with IBS clinical subtype, or with Bile Acid Malabsorption status. However, differences in the virome could be related back to the bacteriome as analysis of CRISPR spacers indicated that the virome alterations were at least partially related to the alterations in the bacteriome. We found no evidence for a shift from lytic to lysogenic replication of core viral clusters, a phenomenon reported for the gut virome of patients with Inflammatory Bowel Disease. Collectively, our data show alterations in the virome of patients with IBS, regardless of clinical subtype, which may facilitate development of new microbiome-based therapeutics.
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Microbioma Gastrointestinal , Síndrome del Colon Irritable/virología , Viroma , Adolescente , Adulto , Anciano , Bacteriófagos/clasificación , Bacteriófagos/genética , Bacteriófagos/aislamiento & purificación , Heces/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Virus/clasificación , Virus/genética , Virus/aislamiento & purificación , Adulto JovenRESUMEN
Alterations of the gut microbiota have been reported in various gastrointestinal disorders, but knowledge of the mycobiome is limited. We investigated the gut mycobiome of 80 patients with Irritable Bowel Syndrome (IBS) in comparison with 64 control subjects. The fungal-specific internal transcribed spacer 1 (ITS-1) amplicon was sequenced, and mycobiome zero-radius operational taxonomic units (zOTUs) were defined representing known and unknown species and strains. The fungal community was sparse and individual-specific in all (both IBS and control) subjects. Although beta-diversity differed significantly between IBS and controls, no difference was found among clinical subtypes of IBS or in comparison with the mycobiome of subjects with bile acid malabsorption (BAM), a condition which may overlap with IBS with diarrhoea. The mycobiome alterations co-varied significantly with the bacteriome and metabolome but were not linked with dietary habits. As a putative biomarker of IBS, the predictive power of the fecal mycobiome in machine learning models was significantly better than random but insufficient for clinical diagnosis. The mycobiome presents limited therapeutic and diagnostic potential for IBS, despite co-variation with bacterial components which do offer such potential.
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Bacterias/aislamiento & purificación , Heces/microbiología , Hongos/aislamiento & purificación , Microbioma Gastrointestinal , Síndrome del Colon Irritable/microbiología , Adulto , Anciano , Bacterias/clasificación , Bacterias/genética , Femenino , Hongos/clasificación , Hongos/genética , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
PURPOSE: To evaluate long-term outcomes of patients with hepatocellular carcinoma (HCC) who show a complete response (CR) vs non-CR on pretransplantation imaging studies or pathologic evaluation of liver explants after locoregional therapy (LRT) before liver transplantation. MATERIALS AND METHODS: Patients listed for liver transplantation for HCC (March 1998 to December 2010) undergoing LRT with available multiphase MR/CT imaging before transplantation were included. Pathologic response was evaluated based on liver explant pathology. A total of 108 patients (17 women; 16%) met the inclusion criteria. RESULTS: Radiologic CR was achieved in 65 patients (60%) vs non-CR in 43 (40%), and pathologic CR was achieved in 36 patients (33%) vs non-CR in 72 (67%). Mean 5-year overall survival (OS) from the time of listing and recurrence-free survival (RFS) after liver transplantation were significantly better for patients with pathologic CR vs non-CR on explant pathology (OS, 83.3% vs 65.2% [28% difference; P = .046]; RFS, 80.6% vs 62.5% [29% difference; P = .045]). Mean 5-y OS and RFS were not significantly different between patients with radiologic CR or non-CR on pretransplantation imaging (OS, 75.4% vs 65.1% [P = .12]; RFS, 74% vs 62.8% [P = .17]). CONCLUSIONS: Achievement of a pathologic CR vs non-CR in response to LRT before liver transplantation for HCC is associated with improved OS from time of listing and improved RFS after liver transplantation. However, current imaging paradigms fall short of accurate delineation of response to LRT, resulting in poor correlation of outcomes between pathologic and radiologic CR.
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Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Trasplante de Hígado , Ablación por Radiofrecuencia , Radiofármacos/administración & dosificación , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/mortalidad , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Imagen Multimodal , Recurrencia Local de Neoplasia , Supervivencia sin Progresión , Ablación por Radiofrecuencia/efectos adversos , Ablación por Radiofrecuencia/mortalidad , Radiofármacos/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Listas de EsperaRESUMEN
The COPD Genetic Epidemiology (COPDGene®) study provides a rich cross-sectional dataset of patients with substantial tobacco smoke exposure, varied by race, gender, chronic obstructive pulmonary disease (COPD) diagnosis, and disease. We aimed to determine the influence of race, gender and Global initiative for chronic Obstructive Lung Disease (GOLD) stage on prevalence of prior COPD diagnosis at COPDGene® enrollment. Data from the complete phase 1 cohort of 10,192 participants were analyzed. Participants were non-Hispanic white and African-American, ≥45 years of age with a minimum of 10 pack years of cigarette smoking. Characterization upon enrollment included spirometry, demographics and history of COPD diagnosis determined by questionnaire. We evaluated the effects of race and gender on the likelihood of prior diagnosis of COPD and the interaction of race and GOLD stage, and gender and GOLD stage, as determined at study enrollment, on likelihood of prior diagnosis of COPD. We evaluated the 3-way interaction of race, gender and GOLD stage on prior diagnosis. African-Americans had higher odds of not having a prior COPD diagnosis at all GOLD stages of airflow obstruction versus non-Hispanic whites (p<0.0001). Women had higher odds of having a prior COPD diagnosis at all GOLD stages versus men (p<0.0001). Three-way interaction of race, gender and GOLD stage was not significant. African-Americans were less likely to have prior COPD regardless of the severity of airflow obstruction determined at study enrollment. Women were more likely to have a prior COPD diagnosis regardless of the severity of measured airflow obstruction. Race and gender are associated with significant disparities in COPD diagnosis.
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Lipoproteins are complex molecular assemblies that are key participants in the intricate cascade of extracellular lipid metabolism with important consequences in the formation of atherosclerotic lesions and the development of cardiovascular disease. Multiplexed mass spectrometry (MS) techniques have substantially improved the ability to characterize the composition of lipoproteins. However, these advanced MS techniques are limited by traditional pre-analytical fractionation techniques that compromise the structural integrity of lipoprotein particles during separation from serum or plasma. In this work, we applied a highly effective and gentle hydrodynamic size based fractionation technique, asymmetric flow field-flow fractionation (AF4), and integrated it into a comprehensive tandem mass spectrometry based workflow that was used for the measurement of apolipoproteins (apos A-I, A-II, A-IV, B, C-I, C-II, C-III and E), free cholesterol (FC), cholesterol esters (CE), triglycerides (TG), and phospholipids (PL) (phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and lysophosphatidylcholine (LPC)). Hydrodynamic size in each of 40 size fractions separated by AF4 was measured by dynamic light scattering. Measuring all major lipids and apolipoproteins in each size fraction and in the whole serum, using total of 0.1 ml, allowed the volumetric calculation of lipoprotein particle numbers and expression of composition in molar analyte per particle number ratios. Measurements in 110 serum samples showed substantive differences between size fractions of HDL and LDL. Lipoprotein composition within size fractions was expressed in molar ratios of analytes (A-I/A-II, C-II/C-I, C-II/C-III. E/C-III, FC/PL, SM/PL, PE/PL, and PI/PL), showing differences in sample categories with combinations of normal and high levels of Total-C and/or Total-TG. The agreement with previous studies indirectly validates the AF4-LC-MS/MS approach and demonstrates the potential of this workflow for characterization of lipoprotein composition in clinical studies using small volumes of archived frozen samples.
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Apolipoproteínas/sangre , Cromatografía Liquida/métodos , Fraccionamiento de Campo-Flujo/métodos , Lípidos/sangre , Lipoproteínas/sangre , Espectrometría de Masas en Tándem/métodos , Apolipoproteína A-I/metabolismo , Apolipoproteína B-100/metabolismo , Análisis Químico de la Sangre/métodos , Calibración , Colesterol/química , Humanos , Luz , Modelos Estadísticos , Tamaño de la Partícula , Control de Calidad , Dispersión de Radiación , Flujo de TrabajoRESUMEN
OBJECTIVE: Venous thromboembolism (VTE) is a potentially preventable complication following surgery. There is variation with regard to the most effective mode of prophylaxis. We sought to determine if an aggressive approach to VTE prophylaxis would reduce VTE rates on the inpatient vascular surgical service. METHODS: Vascular inpatients from a single institution from July 2010 to March 2013 were included in the analysis. A protocol for VTE prophylaxis was implemented on the inpatient vascular surgical service in November 2011. This included subcutaneous (SQ) heparin initiation within 24 h of admission unless deemed inappropriate by the attending, as well as intermittent compression devices (ICD) and compression stockings (CS). The rate of VTE was compared prior to and following the intervention. Patients were compared using AHRQ comorbidity categories, APR-DRG severity of illness, insurance status, and principle procedure. T-tests were used to compare continuous variables and chi-square analysis used to compare categorical variables. RESULTS: There were 1483 vascular patients in the pre-intervention group and 1652 patients in the post-intervention group. The rate of pharmacologic prophylaxis was 52.57% pre-intervention compared to 69.33% post-intervention (p < 0.001). The rate of pharmacologic or mechanical prophylaxis was 91.76% pre-intervention compared to 93.10% post-intervention (p = 0.54). The overall rate of VTE prior to the intervention was 1.49% compared to after intervention which was 0.38% (p = 0.033). The DVT rate prior to intervention was 1.09% vs 0.189% after intervention (p = 0.0214). The rate of pulmonary embolism trended towards a significant reduction with the intervention (0.681% vs 0.189%, p = 0.095). There were no statistically significant differences in patient groups based on gender, comorbidity category, severity of illness, or insurance type. CONCLUSIONS: The overall rate of VTE was reduced by 75% after the initiation of a standard protocol for pharmacologic VTE prophylaxis. These findings justify an aggressive approach to VTE prophylaxis in vascular surgery patients.
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Anticoagulantes/administración & dosificación , Heparina/administración & dosificación , Aparatos de Compresión Neumática Intermitente , Embolia Pulmonar/prevención & control , Medias de Compresión , Procedimientos Quirúrgicos Vasculares/efectos adversos , Tromboembolia Venosa/prevención & control , Trombosis de la Vena/prevención & control , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Distribución de Chi-Cuadrado , Femenino , Heparina/efectos adversos , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Philadelphia , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/etiología , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Tromboembolia Venosa/diagnóstico por imagen , Tromboembolia Venosa/etiología , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/etiologíaRESUMEN
With modern medicine and an awareness of healthy lifestyle practices, people are living longer and generally healthier lives than their ancestors. These successes of modern medicine have resulted in an increasing proportion of elderly in society. Research groups around the world have investigated the contribution of gut microbial communities to human health and well-being. It was established that the microbiota composition of the human gut is modulated by lifestyle factors, especially diet. The microbiota composition and function, acting in concert with direct and indirect effects of habitual diet, is of great importance in remaining healthy and active. This is not a new concept, but until now the scale of the potential microbiota contribution was not appreciated. There are an estimated ten times more bacteria in an individual than human cells. The bacterial population is relatively stable in adults, but the age-related changes that occur later in life can have a negative impact on host health. This loss of the adult-associated microbiota correlates with measures of markers of inflammation, frailty, co-morbidity and nutritional status. This effect may be greater than that of diet or in some cases genetics alone. Collectively, the recent studies show the importance of the microbiota and associated metabolites in healthy aging and the importance of diet in its modulation.
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Envejecimiento/fisiología , Dieta , Conducta Alimentaria , Tracto Gastrointestinal/microbiología , Microbiota , Adulto , Anciano , Salud , HumanosRESUMEN
OBJECTIVES: To assess the dietary intakes of Irish community-dwelling elderly individuals, participating in the ELDERMET project. DESIGN: Cross-sectional study. SETTING: Cork city and county region of southern Ireland. PARTICIPANTS: Two hundred and eight (94 males, 114 females) community-dwelling subjects aged 64-93 yrs. MEASUREMENTS: Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire (FFQ). Anthropometric data were recorded. Nutritional status was assessed using the Mini Nutritional Assessment (MNA). RESULTS: A high rate of overweight/obesity was observed in this population group. Consumption of energy-dense, low-nutrient foods was excessive among this population group. Older elderly subjects (≥75 yrs) consumed significantly (P<0.01) more desserts/sweets than younger elderly (64-74 yrs). Intakes of dietary fat and saturated fat were high while dairy food consumption was inadequate in both males and females. Elderly females typically had a more nutrient-dense diet than males. A considerable proportion of subjects, particularly males, had inadequate intakes of calcium, magnesium, vitamin D, folate, zinc and vitamin C. CONCLUSION: The data indicate that the diet of Irish community-dwelling elderly individuals is sub-optimal with respect to nutrient intake, and excessive in terms of fat intake, with implications for the health status of this population group. Reductions in dietary fat and increased low fat dairy food intakes are recommended for the prevention of diet-related disease in older persons. In addition, strategies to improve a number of sub-optimal micronutrient intakes need to be developed and implemented, particularly among elderly males.
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Encuestas sobre Dietas , Dieta/estadística & datos numéricos , Conducta Alimentaria , Estado Nutricional , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas , Calcio de la Dieta/administración & dosificación , Estudios Transversales , Productos Lácteos , Carbohidratos de la Dieta/administración & dosificación , Grasas de la Dieta/administración & dosificación , Femenino , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Sobrepeso/epidemiología , Características de la Residencia , Riesgo , Encuestas y Cuestionarios , Vitaminas/administración & dosificación , Población BlancaRESUMEN
Lymph nodes in differentiated thyroid cancer have many different histomorphologic features. The current AJCC staging system does not distinguish between different lymph node characteristics and is based entirely on the presence of metastatic disease to upstage pN0 to pN1. However, clinicians involved in the management of thyroid cancer recognize that there is a difference in the clinical significance of finding macroscopic versus microscopic nodes. There appears to be a difference in disease biology that allows lymph nodes to reach different sizes and to manifest disease extension outside the capsule, which has led clinicians, and even clinical practice guidelines, to stratify nodal metastases on the basis of these features. The inherent presumption is that all lymph node metastases in differentiated thyroid cancer do not have the same clinical significance with respect to the risk of recurrence and the risk of death. However, the College of American Pathology (CAP) has not mandated that pathologists include these findings as part of their standard reporting protocol in thyroid cancer. In order to arm clinicians with the tools to design clinical trials and to make important patient management decisions in the presence of lymph node metastases, it is imperative that the CAP adopt a strategy for more detailed reporting that is similar to the protocol currently utilized in breast cancer pathologic reporting.
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Ganglios Linfáticos/patología , Metástasis Linfática/patología , Recurrencia Local de Neoplasia/patología , Patología/normas , Neoplasias de la Tiroides/patología , Humanos , Estadificación de NeoplasiasRESUMEN
AIM: To investigate whether patients with metabolic syndrome (MetS) undergoing total hip or knee replacement have an increased risk for pulmonary embolism (PE). METHODS: We studied patients undergoing total hip or total knee replacement from January 2001 to April 2006. The diagnosis of PE was based on a positive finding with a chest CT or a lung scan. Components of MetS were defined as 1) BMI≥30 kg/m(2) , 2) non-fasting preadmission glucose ≥11.1 mmol/L or diagnosis of diabetes, 3) hypertension, and 4) dyslipidemia. MetS was diagnosed if at least three of these components were present. RESULTS: Of 7282 patients, 107 (1.47%) were diagnosed with PE. The incidence of PE in patients with 0, 1, 2, 3, and 4 MetS components was respectively 0.85% (16/1888; 95% confidence interval [CI] 0.5%-1.4%), 1.24% (31/2500; 95% CI 0.9%-1.8%), 1.76% (34/1936; 95% CI 1.2%-2.5%), 2.64% (21/796; 95% CI 1.7%-4.1%), and 3.09% (5/162; 95% CI 1.1%-7.4%). The independent risk factors for PE were age ≥70, knee as opposite to hip replacement, bilateral knee surgery, congestive heart failure, and MetS or the number of MetS components. The odds of PE independently increased 1.6 times (95% CI 1.01-2.56; P=0.043) for patients with MetS and 1.23 times (95% CI 1.02-1.48; P=0.028) per each additional MetS component. CONCLUSION: Patients with MetS are at increased risk for PE after total joint arthroplasty. The increasing number of MetS components significantly increased the incidence of PE.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Síndrome Metabólico/complicaciones , Embolia Pulmonar/etiología , Adulto , Femenino , Articulación de la Cadera/cirugía , Humanos , Incidencia , Articulación de la Rodilla/cirugía , Masculino , Síndrome Metabólico/cirugía , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico por imagen , Factores de Riesgo , Tomografía Computarizada por Rayos XRESUMEN
UNLABELLED: In this study, we characterized the gut microbiota in six healthy Irish thoroughbred racehorses and showed it to be dominated by the phyla Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobia, Actinobacteria, Euryarchaeota, Fibrobacteres and Spirochaetes. Moreover, all the horses harboured Clostridium, Fibrobacter, Faecalibacterium, Ruminococcus, Eubacterium, Oscillospira, Blautia Anaerotruncus, Coprococcus, Treponema and Lactobacillus spp. Notwithstanding the sample size, it was noteworthy that the core microbiota species assignments identified Fibrobacter succinogenes, Eubacterium coprostanoligenes, Eubacterium hallii, Eubacterium ruminantium, Oscillospira guillermondii, Sporobacter termiditis, Lactobacillus equicursoris, Treponema parvum and Treponema porcinum in all the horses. This is the first study of the faecal microbiota in the Irish thoroughbred racehorse, a significant competitor in the global bloodstock industry. The information gathered in this pilot study provides a foundation for veterinarians and other equine health-associated professionals to begin to analyse the microbiome of performance of racehorses. This study and subsequent work may lead to alternate dietary approaches aimed at minimizing the risk of microbiota-related dysbiosis in these performance animals. SIGNIFICANCE AND IMPACT OF THE STUDY: Although Irish thoroughbreds are used nationally and internationally as performance animals, very little is known about the core faecal microbiota of these animals. This is the first study to characterize the bacterial microbiota present in the Irish thoroughbred racehorse faeces and elucidate a core microbiome irrespective of diet, animal management and geographical location.
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Bacterias/clasificación , Bacterias/aislamiento & purificación , Heces/microbiología , Tracto Gastrointestinal/microbiología , Caballos/microbiología , Microbiota , Animales , Bacterias/genética , Femenino , Masculino , MetagenomaRESUMEN
BACKGROUND: Differences in interlaboratory research protocols contribute to the conflicting data in the literature regarding engineered nanomaterial (ENM) bioactivity. OBJECTIVES: Grantees of a National Institute of Health Sciences (NIEHS)-funded consortium program performed two phases of in vitro testing with selected ENMs in an effort to identify and minimize sources of variability. METHODS: Consortium program participants (CPPs) conducted ENM bioactivity evaluations on zinc oxide (ZnO), three forms of titanium dioxide (TiO2), and three forms of multiwalled carbon nanotubes (MWCNTs). In addition, CPPs performed bioassays using three mammalian cell lines (BEAS-2B, RLE-6TN, and THP-1) selected in order to cover two different species (rat and human), two different lung epithelial cells (alveolar type II and bronchial epithelial cells), and two different cell types (epithelial cells and macrophages). CPPs also measured cytotoxicity in all cell types while measuring inflammasome activation [interleukin-1ß (IL-1ß) release] using only THP-1 cells. RESULTS: The overall in vitro toxicity profiles of ENM were as follows: ZnO was cytotoxic to all cell types at ≥ 50 µg/mL, but did not induce IL-1ß. TiO2 was not cytotoxic except for the nanobelt form, which was cytotoxic and induced significant IL-1ß production in THP-1 cells. MWCNTs did not produce cytotoxicity, but stimulated lower levels of IL-1ß production in THP-1 cells, with the original MWCNT producing the most IL-1ß. CONCLUSIONS: The results provide justification for the inclusion of mechanism-linked bioactivity assays along with traditional cytotoxicity assays for in vitro screening. In addition, the results suggest that conducting studies with multiple relevant cell types to avoid false-negative outcomes is critical for accurate evaluation of ENM bioactivity.
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Inflamación/inducido químicamente , Nanopartículas/toxicidad , Nanotubos de Carbono/toxicidad , Titanio/toxicidad , Óxido de Zinc/toxicidad , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Humanos , Interleucina-1beta/biosíntesis , Nanopartículas/química , Nanotubos de Carbono/química , National Institute of Environmental Health Sciences (U.S.) , Ratas , Titanio/química , Estados UnidosRESUMEN
BACKGROUND: Cerium dioxide (CeO(2)) nanoparticles have potential therapeutic applications and are widely used for industrial purposes. However, the effects of these nanoparticles on primary human cells are largely unknown. The ability of nanoparticles to exacerbate pre-existing inflammatory disorders is not well documented for engineered nanoparticles, and is certainly lacking for CeO(2) nanoparticles. We investigated the inflammation-modulating effects of CeO(2) nanoparticles at noncytotoxic concentrations in human peripheral blood monocytes. METHODS: CD14(+) cells were isolated from peripheral blood samples of human volunteers. Cells were exposed to either 0.5 or 1 µg/mL of CeO(2) nanoparticles over a period of 24 or 48 hours with or without lipopolysaccharide (10 ng/mL) prestimulation. Modulation of the inflammatory response was studied by measuring secreted tumor necrosis factor-alpha, interleukin-1beta, macrophage chemotactic protein-1, interferon-gamma, and interferon gamma-induced protein 10. RESULTS: CeO(2) nanoparticle suspensions were thoroughly characterized using dynamic light scattering analysis (194 nm hydrodynamic diameter), zeta potential analysis (-14 mV), and transmission electron microscopy (irregular-shaped particles). Transmission electron microscopy of CD14(+) cells exposed to CeO(2) nanoparticles revealed that these nanoparticles were efficiently internalized by monocytes and were found either in vesicles or free in the cytoplasm. However, no significant differences in secreted cytokine profiles were observed between CeO(2) nanoparticle-treated cells and control cells at noncytotoxic doses. No significant effects of CeO(2) nanoparticle exposure subsequent to lipopolysaccharide priming was observed on cytokine secretion. Moreover, no significant difference in lipopolysaccharide-induced cytokine production was observed after exposure to CeO(2) nanoparticles followed by lipopolysaccharide exposure. CONCLUSION: CeO(2) nanoparticles at noncytotoxic concentrations neither modulate pre-existing inflammation nor prime for subsequent exposure to lipopolysaccharides in human monocytes from healthy subjects.
Asunto(s)
Cerio/farmacología , Nanopartículas del Metal/química , Monocitos/efectos de los fármacos , Análisis de Varianza , Supervivencia Celular , Células Cultivadas , Cerio/química , Cerio/farmacocinética , Citocinas/metabolismo , Histocitoquímica , Humanos , Inflamación/inducido químicamente , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Lipopolisacáridos/efectos adversos , Monocitos/inmunología , Monocitos/patología , Nanomedicina , FagocitosisRESUMEN
Transcranial Doppler-detected high-intensity transient signals (HITS) during cardiopulmonary bypass (CPB) surgery have been associated with postoperative neurocognitive dysfunction, suggesting microemboli in the brain could be a contributing factor. HITS occur despite administration of unfractionated heparin (UFH). This study was done to determine whether antithrombin-heparin covalent complex (ATH), a more potent anticoagulant than heparin, can reduce HITS during CPB. In a pig CPB model, ATH, UFH, or UFH + antithrombin (AT) was intravenously administered to female Yorkshire pigs after sternotomy. Twenty minutes later, hypothermic CPB was initiated and continued for 1.25 hours, then normothermia was re-established for 45 minutes. Protamine sulfate was given to neutralize the anticoagulants, and pigs were allowed to recover. HITS were monitored using an arterial flow probe placed over the carotid artery. Compared with UFH (300 or 1000 U/kg), ATH reduced the number of HITS during CPB in a dose-dependent manner. AT (3 mg/kg) + UFH (300 U/kg) resulted in an intermediate HITS rate between UFH and ATH (2 mg/kg in terms of AT). Examination of brain sections for emboli formation confirmed that, similar to HITS, number of thrombi decreased in direct proportion to ATH dosage. These results support the hypotheses that the majority of HITS represent thromboemboli and that ATH reduces emboli formation during CPB.
Asunto(s)
Anticoagulantes/uso terapéutico , Antitrombinas/uso terapéutico , Puente Cardiopulmonar/efectos adversos , Embolia Aérea/prevención & control , Heparina/uso terapéutico , Ultrasonografía Doppler Transcraneal , Animales , Coagulación Sanguínea/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Embolia Aérea/diagnóstico , Femenino , Sus scrofaRESUMEN
We investigate whether preadmission hyperglycemia is a risk factor for developing in-hospital symptomatic pulmonary embolism after major orthopedic surgery. Medical records of patients undergoing total hip or total knee arthroplasty from January 2001 to April 2006 were reviewed. The incidence of PE was 1.47% (107/7282 patients). Multivariate analysis showed that preadmission blood glucose (BG) of at least 200 mg/dL independently increased the risk of pulmonary embolism by 3.19 times (P = .015), when compared with patients with BG of less than 110 mg/dL. Other significant risks factors were age (>or=70 years old), body mass index of more than 30 kg/m(2), and congestive heart failure. Total knee had 2.19 times (P = .002) more risk than total hip arthroplasty and bilateral procedure increased the risk by 2.13 times (P = .015). Sex, American Society of Anesthesiologists status, duration of surgery, malignancy, pulmonary disease, hypertension, diabetes mellitus, dyslipidemia, sleep apnea, and stroke were not found to be significant risk factors for pulmonary embolism.