RESUMEN
Antibodies at gastrointestinal mucosal membranes play a vital role in immunological protection against a range of pathogens, including helminths. Gastrointestinal health is central to efficient livestock production, and such infections cause significant losses. Fecal samples were taken from 114 cattle, across three beef farms, with matched blood samples taken from 22 of those animals. To achieve fecal antibody detection, a novel fecal supernatant was extracted. Fecal supernatant and serum samples were then analysed, using adapted enzyme-linked immunosorbent assay protocols, for levels of total immunoglobulin (Ig)A, IgG, IgM, and Teladorsagia circumcincta-specific IgA, IgG, IgM and IgE (in the absence of reagents for cattle-specific nematode species). Fecal nematode egg counts were conducted on all fecal samples. Assays performed successfully and showed that IgA was the predominant antibody in fecal samples, whereas IgG was predominant in serum. Total IgA in feces and serum correlated within individuals (0.581, P = 0.005), but other Ig types did not. Results support the hypothesis that the tested protocols are an effective method for the non-invasive assessment of cattle immunology. The method could be used as part of animal health assessments, although further work is required to interpret the relationship between results and levels of infection and immunity.
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Anticuerpos Antihelmínticos/análisis , Enfermedades de los Bovinos/parasitología , Enfermedades Gastrointestinales/veterinaria , Parasitosis Intestinales/veterinaria , Infecciones por Nematodos/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/inmunología , Granjas , Heces/parasitología , Enfermedades Gastrointestinales/inmunología , Enfermedades Gastrointestinales/parasitología , Parasitosis Intestinales/inmunología , Parasitosis Intestinales/parasitología , Infecciones por Nematodos/inmunología , Infecciones por Nematodos/parasitología , Carne Roja , Reino UnidoRESUMEN
We assessed evidence of exposure to viruses and bacteria in an unmanaged and long-isolated population of Soay sheep (Ovis aries) inhabiting Hirta, in the St Kilda archipelago, 65 km west of Benbecula in the Outer Hebrides of Scotland. The sheep harbour many metazoan and protozoan parasites but their exposure to viral and bacterial pathogens is unknown. We tested for herpes viral DNA in leucocytes and found that 21 of 42 tested sheep were infected with ovine herpesvirus 2 (OHV-2). We also tested 750 plasma samples collected between 1997 and 2010 for evidence of exposure to seven other viral and bacterial agents common in domestic Scottish sheep. We found evidence of exposure to Leptospira spp., with overall seroprevalence of 6·5%. However, serological evidence indicated that the population had not been exposed to border disease, parainfluenza, maedi-visna, or orf viruses, nor to Chlamydia abortus. Some sheep tested positive for antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) but, in the absence of retrospective faecal samples, the presence of this infection could not be confirmed. The roles of importation, the pathogen-host interaction, nematode co-infection and local transmission warrant future investigation, to elucidate the transmission ecology and fitness effects of the few viral and bacterial pathogens on Hirta.
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Bacterias/clasificación , Bacterias/aislamiento & purificación , Infecciones Bacterianas/veterinaria , Virosis/veterinaria , Virus/clasificación , Virus/aislamiento & purificación , Animales , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Femenino , Hébridas/epidemiología , Masculino , Estudios Seroepidemiológicos , Oveja Doméstica , Virosis/epidemiología , Virosis/virologíaRESUMEN
Issue addressed Primary healthcare settings are important providers of health promotion approaches. However, organisational challenges can affect their capacity to deliver these approaches. This review identified the common enablers and barriers health organisations faced and it aimed to explore the experiences health organisations, in particular Aboriginal organisations, had when increasing their health promotion capacity. Methods A systematic search of peer-reviewed literature was conducted. Articles published between 1990-2014 that focused on a health care-settings approach and discussed factors that facilitated or hindered an organisation's ability to increase health promotion capacity were included. Results Twenty-five articles met the inclusion criteria. Qualitative (n=18) and quantitative (n=7) study designs were included. Only one article described the experiences of an Aboriginal health organisation. Enablers included: management support, skilled staff, provision of external support to the organisation, committed staffing and financial resources, leadership and the availability of external partners to work with. Barriers included: lack of management support, lack of dedicated health promotion staff, staff lacking skills or confidence, competing priorities and a lack of time and resources allocated to health promotion activities. Conclusions While the literature highlighted the importance of health promotion work, barriers can limit the delivery of health promotion approaches within primary healthcare organisations. A gap in the literature exists about how Aboriginal health organisations face these challenges. So what? Primary healthcare organisations wanting to increase their health promotion capacity can pre-empt the common barriers and strengthen identified enablers through the shared learnings outlined in this review.
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Creación de Capacidad , Promoción de la Salud , Atención Primaria de Salud , Humanos , LiderazgoRESUMEN
Determining risk for recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) is an important clinical need. We assessed consecutive patients who underwent LT for HCC following sequential transarterial chemoembolization (TACE). Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) categories: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Cox proportional hazard models were used to predict HCC recurrence. One hundred seventy-three patients underwent TACE and imaging to assess response prior to LT. TACE responses were: CR = 23.7%, PR = 24.3%, SD = 27.7% and PD = 24.3%. Five-year HCC recurrence rate was 5.3% in patients responding to TACE (CR/PR), versus 17.6%, among patients who did not respond (SD/PD, p = 0.014). In multivariate analysis, independent pre-LT predictors of recurrence were response to TACE and largest radiologic size of tumor (>3 cm vs. ≤3 cm). HCC recurrence rate for patients with tumor size >3 cm and no response to TACE was 35.8%, compared with 1.9% for patients with tumor size ≤3 cm and response to TACE (p = 0.0007). We conclude that mRECIST criteria and tumor size differentiate patients with high or low likelihood of HCC recurrence after LT. These findings raise the possibility of incorporating response to TACE and largest tumor size to identify patients at highest risk for HCC recurrence.
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Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica , Neoplasias Hepáticas/patología , Anciano , Carcinoma Hepatocelular/terapia , Femenino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , RecurrenciaRESUMEN
To identify genetic risks for obesity and diabetes postliver transplantation (LT), LT recipients underwent genotyping for IL28B rs12979860 (n = 295) and PNPLA3 rs738409 (n = 205) polymorphism in both donors and recipients. The development of obesity and diabetes/impaired fasting glucose (IFG) was determined 1-5 years post-LT. Recipient PNPLA-3 genotype was independently associated with obesity (BMI > 30) at 3 years posttransplant (genotype CC 33.7%, CG 48.3% and GG 82.4%, p = 0.002), with an odds ratio (OR 2.54, CI 1.38-4.66, p = 0.003), associated with the G allele. Diabetes/IFG diagnosed within 5 years posttransplant associated with PNPLA-3 non-CC genotype (HR 1.59, 1.12-2.26, p = 0.010), but not IL28B TT genotype (HR 1.46, 0.94-2.27, p = 0.092). No genotype variable was independently predictive of diabetes/IFG. The combination of PNPLA-3 non-CC and IL28B TT genotype was associated with increased risk of diabetes/IFG compared to PNPLA-3 CC, IL28B non-TT (HR 2.64, CI 1.30-5.39, p = 0.008). Donor genotypes were not associated with any of the outcomes analyzed. In conclusion, PNPLA-3 non-CC genotype is associated with posttransplant obesity but not independently with diabetes/IFG. The lack of donor related risk suggests a peripheral rather than central mechanism of insulin resistance in liver transplant recipients.
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Diabetes Mellitus/genética , Interleucinas/genética , Lipasa/genética , Trasplante de Hígado/efectos adversos , Proteínas de la Membrana/genética , Obesidad/genética , Adulto , Humanos , Resistencia a la Insulina/genética , Interferones , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Donantes de TejidosRESUMEN
Obesity is increasingly common before and after liver transplantation (LT), yet optimal management remains unclear. Our aim was to analyze the effectiveness of a multidisciplinary protocol for obese patients requiring LT, including a noninvasive pretransplant weight loss program, and a combined LT plus sleeve gastrectomy (SG) for obese patients who failed to lose weight prior to LT. Since 2006, all patients referred LT with a BMI > 35 were enrolled. There were 37 patients who achieved weight loss and underwent LT alone, and 7 who underwent LT combined with SG. In those who received LT alone, weight gain to BMI > 35 was seen in 21/34, post-LT diabetes (DM) in 12/34, steatosis in 7/34, with 3 deaths plus 3 grafts losses. In patients undergoing the combined procedure, there were no deaths or graft losses. One patient developed a leak from the gastric staple line, and one had excess weight loss. No patients developed post-LT DM or steatosis, and all had substantial weight loss (mean BMI = 29). Noninvasive pretransplant weight loss was achieved by a majority, though weight gain post-LT was common. Combined LT plus SG resulted in effective weight loss and was associated with fewer post-LT metabolic complications. Long-term follow-up is needed.
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Derivación Gástrica/métodos , Fallo Hepático/terapia , Trasplante de Hígado/métodos , Obesidad/cirugía , Adulto , Anciano , Índice de Masa Corporal , Endoscopía/métodos , Femenino , Gastrectomía/métodos , Humanos , Fallo Hepático/complicaciones , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Factores de Riesgo , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Identifying the genes underlying phenotypic variation in natural populations can provide novel insight into the evolutionary process. The candidate gene approach has been applied to studies of a number of traits in various species, in an attempt to elucidate their genetic basis. Here, we test the application of the candidate gene approach to identify the loci involved in variation in gastrointestinal parasite burden, a complex trait likely to be controlled by many loci, in a wild population of Soay sheep. A comprehensive literature review, Gene Ontology databases, and comparative genomics resources between cattle and sheep were used to generate a list of candidate genes. In a pilot study, these candidates, along with 50 random genes, were then sequenced in two pools of Soay sheep; one with low gastrointestinal nematode burden and the other high, using a NimbleGen sequence capture experiment. Further candidates were identified from single nucleotide polymorphisms (SNPs) that were highly differentiated between high- and low-resistance sheep breeds. A panel of 192 candidate and control SNPs were then typed in 960 individual Soay sheep to examine whether they individually explained variation in parasite burden, as measured as faecal egg count, as well as two immune measures (Teladorsagia circumcincta-specific antibodies and antinuclear antibodies). The cumulative effect of the candidate and control SNPs were estimated by fitting genetic relationship matrices (GRMs) as random effects in animal models of the three traits. No more significant SNPs were identified in the pilot sequencing experiment and association study than expected by chance. Furthermore, no significant difference was found between the proportions of candidate or control SNPs that were found to be significantly associated with parasite burden/immune measures. No significant effect of the candidate or control gene GRMs was found. There is thus little support for the candidate gene approach to the identification of loci explaining variation in parasitological and immunological traits in this population. However, a number of SNPs explained significant variation in multiple traits and significant correlations were found between the proportions of variance explained by individual SNPs across multiple traits. The significant SNPs identified in this study may still, therefore, merit further investigation.
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Carga de Parásitos , Ovinos/genética , Ovinos/inmunología , Ovinos/parasitología , Tricostrongiloidiasis/veterinaria , Animales , Anticuerpos Antinucleares/sangre , Anticuerpos Antihelmínticos/sangre , Estudios de Asociación Genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Recuento de Huevos de Parásitos , Proyectos Piloto , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Análisis de Secuencia de ADN , Enfermedades de las Ovejas/genética , Enfermedades de las Ovejas/inmunología , Enfermedades de las Ovejas/parasitología , Trichostrongyloidea , Tricostrongiloidiasis/genética , Tricostrongiloidiasis/inmunologíaRESUMEN
The brain mechanisms that subserve music recognition remain unclear despite increasing interest in this process. Here we report the results of a magnetoencephalography experiment to determine the temporal dynamics and spatial distribution of brain regions activated during listening to a familiar and unfamiliar instrumental melody in control adults and adults with Down syndrome (DS). In the control group, listening to the familiar melody relative to the unfamiliar melody, revealed early and significant activations in the left primary auditory cortex, followed by activity in the limbic and sensory-motor regions and finally, activation in the motor related areas. In the DS group, listening to the familiar melody relative to the unfamiliar melody revealed increased significant activations in only three regions. Activity began in the left primary auditory cortex and the superior temporal gyrus and was followed by enhanced activity in the right precentral gyrus. These data suggest that familiar music is associated with auditory-motor coupling but does not activate brain areas involved in emotional processing in DS. These findings reveal new insights on the neural basis of music perception in DS as well as the temporal course of neural activity in control adults.
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Corteza Auditiva/fisiopatología , Percepción Auditiva/fisiología , Síndrome de Down/fisiopatología , Música/psicología , Reconocimiento en Psicología/fisiología , Adolescente , Adulto , Mapeo Encefálico , Síndrome de Down/psicología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Magnetoencefalografía , Masculino , Red Nerviosa/fisiopatologíaRESUMEN
IL28B polymorphisms are strongly associated with response to treatment for HCV infection. IL28B acts on interferon-stimulated genes via the JAK-STAT pathway, which has been implicated in development of insulin resistance. We investigated whether IL28B polymorphisms are associated with posttransplant diabetes mellitus (DM). Consecutive HCV patients who underwent liver transplantation between 1-1995 and 1-2011 were studied. Genotyping of the polymorphism rs12979860 was performed on DNA collected from donors and recipients. Posttransplant DM was screened for by fasting blood glucoses every 1-3 months. Of 221 included patients, 69 developed posttransplant DM (31%). Twenty-two patients with recipient IL28B genotype TT (48%), 25 with IL28B genotype CT (25%) and 22 with IL28B genotype CC (29%) developed posttransplant DM. TT genotype was statistically significantly associated with posttransplant DM over time (log rank p = 0.012 for TT vs. CT and p = 0.045 for TT vs. CC). Multivariate Cox regression analysis correcting for donor age, body mass index, baseline serum glucose, baseline serum cholesterol, recipient age and treated rejection, showed that recipient IL28B genotype TT was independently associated with posttransplant DM (hazard ratio 2.51; 95% confidence interval 1.17-5.40; p = 0.011). We conclude that the risk of developing posttransplant DM is significantly increased in recipients carrying the TT polymorphism of the IL28B gene.
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Diabetes Mellitus/etiología , Hepatitis C Crónica/complicaciones , Interleucinas/genética , Trasplante de Hígado/efectos adversos , Polimorfismo Genético/genética , Complicaciones Posoperatorias , Adulto , Diabetes Mellitus/diagnóstico , Femenino , Estudios de Seguimiento , Hepacivirus/patogenicidad , Hepatitis C Crónica/genética , Hepatitis C Crónica/cirugía , Humanos , Interferón gamma/metabolismo , Interferones , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , ARN Viral/genéticaRESUMEN
Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.
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Proteínas Adaptadoras Transductoras de Señales/genética , Adiposidad/genética , Ácidos Grasos/metabolismo , Enfermedades Metabólicas/genética , Músculo Esquelético/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Regulación de la Expresión Génica , Resistencia a la Insulina/genética , Masculino , Enfermedades Metabólicas/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/genética , Obesidad/metabolismo , Oxidación-Reducción , Interferencia de ARN , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Proteínas Señalizadoras YAPRESUMEN
Although mortality rates following liver transplantation (LT) are well described, there is a lack of detailed, prospective studies determining patterns of and risk factors for long-term mortality. We analyzed the multicenter, prospectively obtained The National Institute of Diabetes and Digestive and Kidney Diseases LT Database of 798 transplant recipients from 1990 to 1994 (follow-up 2003). Overall, 327 recipients died. Causes of death >1 year: 28% hepatic, 22% malignancy, 11% cardiovascular, 9% infection, 6% renal failure. Renal-related death increased dramatically over time. Risk factors for death >1 year (univariate): male gender, age/decade, pre-LT diabetes, post-LT diabetes, post-LT hypertension, post-LT renal insufficiency, retransplantation >1 year, pre-LT malignancy, alcoholic disease (ALD) and metabolic liver disease, with similar risks noted for death >5 years. Hepatitis C, retransplantation, post-LT diabetes, hypertension and renal insufficiency were significant risk factors for liver-related death. Cardiac deaths associated with age, male gender, ALD, cryptogenic disease, pre-LT hypertension and post-LT renal insufficiency. In summary, the leading causes of late deaths after transplant were graft failure, malignancy, cardiovascular disease and renal failure. Older age, diabetes and renal insufficiency identified patients at highest risk of poor survival overall. Diligent management of modifiable post-LT factors including diabetes, hypertension and renal insufficiency may impact long-term mortality.
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Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Alcohólicos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus/inducido químicamente , Diabetes Mellitus/etiología , Diabetes Mellitus/mortalidad , Femenino , Estudios de Seguimiento , Hepatitis C/inducido químicamente , Hepatitis C/etiología , Hepatitis C/mortalidad , Humanos , Hipertensión/inducido químicamente , Hipertensión/etiología , Hipertensión/mortalidad , Riñón , Trasplante de Riñón/mortalidad , Hígado , Hepatopatías/etiología , Hepatopatías/mortalidad , Estudios Longitudinales , Masculino , Persona de Mediana Edad , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) , Estudios Prospectivos , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/etiología , Insuficiencia Renal/mortalidad , Factores de Riesgo , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Measuring the perception of friendship in adults with Down syndrome (DS) has long been a research challenge. While there have been studies investigating the number of friends children with DS have in, the study of how adults with DS view the concept of friendship has been relatively unexplored. The aim of this study was to evaluate the perception of friendship in adults with DS using a visually based scale. METHODS: Sixty-six individuals participated in this study: 22 adults with DS, 22 typical mental age (MA) matched children and 22 typical adults matched for chronological age (CA). We administered a visually based Friendship scale made up of photographs depicting social interactions between individuals or groups. The scale was composed of two parts. In Part 1 participants were shown two photographs and asked to select the photograph that best depicted friends. In Part 2 participants were asked to view one photograph and asked, 'Is it okay for friends to do this?' RESULTS: Adults with DS scored lower on the Friendship scale in comparison with the CA and MA matched groups. Adults with DS made more errors in identifying 'friends' from 'non-friends' but were equally able to distinguish friendly behaviours and actions from non-friendly behaviours as their CA and MA matched peers. Individuals with DS were more likely to incorrectly identify photographs depicting a teacher, or a mother with a child as friends. Actions or behaviours that depicted subtle negative emotions were also incorrectly identified. CONCLUSIONS: These results are an important first step in understanding the perception of friendship and social behaviours related to friendship in adults with DS.
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Síndrome de Down/psicología , Amigos/psicología , Ajuste Social , Conducta Social , Adulto , Cognición , Humanos , Pruebas Psicológicas , Valores Sociales , Adulto JovenRESUMEN
Hepatitis C-associated liver failure is the most common indication for liver transplantation, with virological recurrence near ubiquitous. Approximately 30% of HCV-infected recipients will die or lose their allograft or develop cirrhosis secondary to hepatitis C recurrence by the fifth postoperative year, with the proportion increasing with duration of follow-up. Strategies for minimizing the frequency of severe HCV recurrence include avoidance of older donors, early diagnosis/treatment of CMV and minimization of immunosuppression, particularly T-cell depleting therapies and pulsed corticosteroid treatment of acute cellular rejection. Patients should be offered treatment with peginterferon and ribavirin before LT if MELD = 17 or as soon as histological evidence of recurrence of HCV is apparent post-LT. Because of the high frequency of hemotoxicity and renal insufficiency, ribavirin should be dosed according to renal function.
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Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Trasplante de Hígado/efectos adversos , Hepatitis C/epidemiología , Humanos , Inmunosupresores/uso terapéutico , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Trasplante de Hígado/inmunología , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes , Ribavirina/uso terapéutico , Factores de RiesgoRESUMEN
In the nontransplant setting diabetes mellitus is a risk factor for disease progression in patients with chronic hepatitis C virus (HCV) infection. The impact of early insulin resistance on the development of advanced fibrosis, even in the absence of clinically apparent diabetes mellitus, is not known. Our aim was to determine whether the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) can be used to identify insulin-resistant patients at risk for rapid fibrosis progression. Cohort study including patients transplanted for chronic HCV between January 1, 1995 and January 1, 2005. One hundred sixty patients were included; 25 patients (16%) were treated for diabetes mellitus and 36 patients (23%) were prediabetic, defined as HOMA-IR >2.5. Multivariate Cox regression analysis showed that insulin resistance (hazard ratio (HR) 2.07; confidence interval (CI) 1.10-3.91, p = 0.024), donor age (HR 1.33;CI 1.08-1.63, p = 0.007) and aspartate aminotransferase (HR 1.03;CI 1.01-1.05, p < 0.001) were significantly associated with a higher probability of developing advanced fibrosis, i.e. Knodell fibrosis stage 3 or 4, whereas steatosis (HR 0.94;CI 0.46-1.92, p = 0.87) and acute cellular rejection (HR 1.72;CI 0.88-3.36, p = 0.111) were not. In conclusion, posttransplant insulin resistance is strongly associated with more severe recurrence of HCV infection. HOMA-IR is an important tool for the identification of insulin resistance among patients at risk for rapid fibrosis progression after liver transplantation for HCV.
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Adipoquinas/sangre , Hepatitis C Crónica/complicaciones , Resistencia a la Insulina , Cirrosis Hepática/complicaciones , Trasplante de Hígado , Adulto , Estudios de Cohortes , Complicaciones de la Diabetes , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Leptina/sangre , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , Estado Prediabético/fisiopatología , Análisis de Regresión , RiesgoRESUMEN
The ras p21 GTPase-activating protein (GAP) was purified from human placental tissue. Internal amino acid sequence was obtained from this 120,000-dalton protein and, by means of this sequence, two types of complementary DNA clones were isolated and characterized. One type encoded GAP with a predicted molecular mass of 116,000 daltons and 96% identity with bovine GAP. The messenger RNA of this GAP was detected in human lung, brain, liver, leukocytes, and placenta. The second type appeared to be generated by a differential splicing mechanism and encoded a novel form of GAP with a predicted molecular mass of 100,400 daltons. This protein lacks the hydrophobic amino terminus characteristic of the larger species, but retains GAP activity. The messenger RNA of this type was abundantly expressed in placenta and in several human cell lines, but not in adult tissues.
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Clonación Molecular , ADN/genética , Placenta/análisis , Proteínas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Química Encefálica , ADN/aislamiento & purificación , Femenino , Proteínas Activadoras de GTPasa , Regulación de la Expresión Génica , Humanos , Leucocitos/análisis , Hígado/análisis , Pulmón/análisis , Datos de Secuencia Molecular , Peso Molecular , Hibridación de Ácido Nucleico , Sondas de Oligonucleótidos , Embarazo , Proteínas/aislamiento & purificación , ARN Mensajero/análisis , ARN Mensajero/genética , Homología de Secuencia de Ácido Nucleico , Proteínas Activadoras de ras GTPasaRESUMEN
A strain of Saccharomyces cerevisiae capable of simultaneous hydrolysis and fermentation of highly polymerized starch oligosaccharides was constructed. The Aspergillus awamori glucoamylase enzyme, form GAI, was expressed in Saccharomyces cerevisiae by means of the promoter and termination regions from a yeast enolase gene. Yeast transformed with plasmids containing an intron-free recombinant glucoamylase gene efficiently secreted glucoamylase into the medium, permitting growth of the transformants on starch as the sole carbon source. The natural leader sequence of the precursor of glucoamylase (preglucoamylase) was processed correctly by yeast, and the secreted enzyme was glycosylated through both N- and O-linkages at levels comparable to the native Aspergillus enzyme. The data provide evidence for the utility of yeast as an organism for the production, glycosylation, and secretion of heterologous proteins.
RESUMEN
Our understanding of the deterioration in immune function in old age-immunosenescence-derives principally from studies of modern human populations and laboratory animals. The generality and significance of this process for systems experiencing complex, natural infections and environmental challenges are unknown. Here, we show that late-life declines in an important immune marker of resistance to helminth parasites in wild Soay sheep predict overwinter mortality. We found senescence in circulating antibody levels against a highly prevalent nematode worm, which was associated with reduced adult survival probability, independent of changes in body weight. These findings establish a role for immunosenescence in the ecology and evolution of natural populations.
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Envejecimiento/inmunología , Resistencia a la Enfermedad/inmunología , Helmintiasis Animal/inmunología , Inmunosenescencia , Ovinos/inmunología , Ovinos/parasitología , Animales , Anticuerpos Antihelmínticos/sangre , Peso Corporal , Femenino , Inmunoglobulina G/sangre , Modelos Lineales , Masculino , Recuento de Huevos de Parásitos , Carga de Parásitos , Escocia , Enfermedades de las Ovejas/inmunología , Enfermedades de las Ovejas/parasitología , Análisis de SupervivenciaRESUMEN
BACKGROUND: Liver arteriovenous malformations (AVM) in hereditary hemorrhagic telangiectasia (HHT) can necessitate liver transplantation. There is limited data on HHT patients undergoing liver transplantation (LT) in the United States. METHODS: Two sources of data were used: (1) Scientific Registry of Transplant Recipients (SRTR) database (1998-2016) (2) Single center liver transplant database (Mayo Clinic Rochester, MN). The aims of this study were (1) to determine trends in LT for HHT-related liver involvement in the United States using the SRTR database; (2) to identify clinical characteristics, indications, and outcomes for LT in HHT. RESULTS: Thirty-nine HHT patients were listed for LT in the SRTR database from 1998-2016 to 1998-2001 (n = 1); 2002-2005 (n = 4); 2006-2010 (n = 10), and 2011-2016 (n = 24). Twenty-four underwent LT at a median age of 47.5 years (interquartile range, 37.0-58.5 years). Median calculated MELD score at time of LT was 8.0 (interquartile range, 7.0-9.5), and 75% received an exception MELD score. Two status-1 patients died during transplant surgery. Nineteen (86%) patients were alive after a median post-LT follow-up of 48 months, whereas 2 patients were lost to follow-up. Five of the aforementioned HHT patients underwent LT at Mayo Clinic, 4 with high output cardiac failure, and 1 with biliary ischemia. All 5 were alive at the time of last follow-up with good graft function and resolution of heart failure. CONCLUSIONS: Outcomes after LT for HHT patients are excellent with 86% survival after a median follow-up of 48 months and resolution of heart failure. LT listing for HHT has increased in substantially in more recent eras.
Asunto(s)
Fallo Hepático/cirugía , Trasplante de Hígado/tendencias , Evaluación de Procesos y Resultados en Atención de Salud/tendencias , Telangiectasia Hemorrágica Hereditaria/cirugía , Adulto , Anciano , Gasto Cardíaco Elevado/epidemiología , Gasto Cardíaco Elevado/fisiopatología , Bases de Datos Factuales , Femenino , Supervivencia de Injerto , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Humanos , Fallo Hepático/diagnóstico , Fallo Hepático/mortalidad , Fallo Hepático/fisiopatología , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Recuperación de la Función , Sistema de Registros , Estudios Retrospectivos , Telangiectasia Hemorrágica Hereditaria/diagnóstico , Telangiectasia Hemorrágica Hereditaria/mortalidad , Telangiectasia Hemorrágica Hereditaria/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Función Ventricular IzquierdaRESUMEN
The impact of obesity on outcomes following liver transplantation has been difficult to determine, in part due to the confounding effects of ascites on BMI. We evaluated the impact of pretransplant recipient obesity on outcomes following liver transplantation using the NIDDK Liver Transplantation Database. Pretransplant BMI, corrected for ascites, was categorized as underweight (BMI <18 kg/m(2)), normal weight (BMI 18-25 kg/m(2)), overweight (BMI 25.1-30 kg/m(2)), Class I obese (BMI 30.1-35 kg/m(2)), Class II obese (BMI 35.1-40 kg/m(2)) and Class III obese (BMI >40 kg/m(2)). Primary outcomes were patient and graft survival. Secondary outcomes included days in hospital and days in ICU. Data from 704 adult liver transplant recipients from the NIDDK LTD and a further 609 patients from the Mayo Clinic were analyzed. Early and late patient and graft survival was similar across all BMI categories. Correcting for ascites volume resulted in 11-20% of patients moving into a lower BMI classification. The relative risk for mortality increased by 7% for each liter of ascites removed. We conclude that corrected BMI is not independently predictive of patient or graft survival. Obesity, within the ranges observed in this study, should not be considered to be a contraindication to liver transplantation in the absence of other relative contraindications.
Asunto(s)
Supervivencia de Injerto , Trasplante de Hígado/mortalidad , Obesidad/complicaciones , Ascitis/diagnóstico , Ascitis/patología , Índice de Masa Corporal , Peso Corporal , Contraindicaciones , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) , Tasa de Supervivencia , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
Recurrent hepatitis C virus (HCV) infection is a major cause of morbidity and mortality after liver transplantation for HCV-related end stage liver disease. Although previous studies have shown a short-term effect of interferon-based treatment on fibrosis progression, it is unclear whether this translates to improved graft survival. We evaluated whether treatment of recurrent HCV leads to an improved graft survival. Cohort study included consecutive HCV patients who underwent liver transplantation between 1 January 1995 and 1 January 2005 in the Mayo Clinic, Rochester, MN. Two hundred and fifteen patients were included in the study. During a median follow-up of 4.4 years (interquartile range 2.2-6.6), 165 patients (77%) had biopsy-proven recurrent HCV infection confirmed by serum HCV RNA testing. Seventy-eight patients were treated. There were no differences in MELD-score, fibrosis stage or time towards HCV recurrence between treated and untreated patients at time of recurrence. There was a trend for greater frequency of acute cellular rejection among untreated patients. The incidence of graft failure was lower for patients treated within 6 months of recurrence compared to patients not treated within this time-period (log rank p = 0.002). Time-dependent multivariate Cox regression analysis showed that treatment of recurrent HCV infection was statistically significantly associated with a decreased risk of overall graft failure (hazard ratio 0.34; CI 0.15-0.77, p = 0.009) and a decreased risk of graft failure due to recurrent HCV (hazard ratio 0.24; CI 0.08-0.69, p = 0.008). In conclusion, although a cause and effect relationship cannot be established, treatment of recurrent HCV infection after liver transplantation is associated with a reduced risk of graft failure.