Metabolic syndrome: is immunosuppression to blame?

1. Metabolic syndrome (MS) is common after liver transplantation and has been associated with increased risks of cardiovascular disease, cardiovascular death, liver-related death, and overall mortality. 2.

Autoimmune hepatitis: a review of current diagnosis and treatment.

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by periportal inflammation, elevated immunoglobulins, autoantibodies, and a dramatic response to immunosuppression. An environmental agent is hypothesized to trigger an immune-mediated attack directed against liver antigens in genetically predisposed individuals. A plethora of clinical presentations can be seen ranging from chronic indolent disease to fulminant hepatic failure, and diagnosis requires exclusion of other causes of liver disease.

Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States.

Background & Aims: The relative frequency of nonalcoholic steatohepatitis (NASH) as an indication for liver transplantation and comparative outcomes following transplantation are poorly understood.

Methods: We analyzed the Scientific Registry of Transplant Recipients for primary adult liver transplant recipients from 2001 to 2009.

Results: From 2001 to 2009, 35,781 patients underwent a primary liver transplant, including 1959 for who NASH was the primary or secondary indication.

Noninvasive diagnosis of acute cellular rejection in liver transplant recipients: a proteomic signature validated by enzyme-linked immunosorbent assay.

The diagnosis of acute cellular rejection (ACR) requires liver biopsy with its attendant expense and risk. Our first aim was to prospectively determine in an exploratory analysis whether there is a serum proteome signature associated with histologically confirmed ACR. Our second aim was to use simpler and faster enzyme-linked immunosorbent assay (ELISA)-based assays for proteins identified as differentially abundant in the proteomic analysis to identify patients with ACR in a separate validation cohort.

Somatic mutagenesis with a Sleeping Beauty transposon system leads to solid tumor formation in zebrafish.

Large-scale sequencing of human cancer genomes and mouse transposon-induced tumors has identified a vast number of genes mutated in different cancers. One of the outstanding challenges in this field is to determine which genes, when mutated, contribute to cellular transformation and tumor progression. To identify new and conserved genes that drive tumorigenesis we have developed a novel cancer model in a distantly related vertebrate species, the zebrafish, Danio rerio.

Pediatric cardiovascular drug dosing in critically ill children and extracorporeal membrane oxygenation.

Cardiovascular disease in children is common and results in significant morbidity and mortality. The sickest children with cardiovascular disease may require support with extracorporeal membrane oxygenation (ECMO), which provides life-saving assistance for children with refractory cardiorespiratory failure. Many classes of cardiovascular drugs are used in children, but very few of these agents have been well studied in children.

Paediatric low speed vehicle run-over fatalities in Queensland.

Introduction: Child pedestrian fatalities associated with motor vehicles reversing or moving at low speed are difficult to identify in surveillance data. This study aims to determine the incidence of fatalities associated with what is thought to be an under-reported and preventable fatal injury mechanism.

Methods: The term low speed vehicle run-over (LSVRO) incidents encompasses pedestrian fatalities where vehicles run-over a child at low speed.

Pharmacokinetics of antifungal agents in children.

Invasive fungal infections in immunocompromised children are common and often fatal. The first antifungal agents such as amphotericin B and fluconazole offered effective treatment, but their use was often limited by toxicity and resistance. Numerous new antifungal agents have since been developed and appear to be as effective.

Predictors of cardiovascular events after liver transplantation: a role for pretransplant serum troponin levels.

Cardiovascular complications are major causes of morbidity and mortality after liver transplantation. Identifying candidates at highest risk of postoperative complications is a cornerstone of optimizing outcomes and utility. Using traditional cardiac risk factors in addition to C-reactive protein (CRP) levels, troponin levels, and echocardiographic parameters before transplantation, we sought to define cardiac risk so that we could predict cardiovascular events after transplantation.

Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection.

Unlabelled: Polymorphism in the interleukin-28B (IL28B) gene region, encoding interferon (IFN)-λ3, is strongly predictive of response to antiviral treatment in the nontransplant setting. We sought to determine the prevalence and impact on clinical outcomes of donor and recipient IL28B genotypes among liver transplant recipients. The cohort study included 189 consecutive patients infected with hepatitis C virus (HCV) who underwent liver transplantation between January 1, 1995, and January 1, 2005, at the Mayo Clinic, Rochester, MN.

Planning volunteer responses to low-volume mass gatherings: do event characteristics predict patient workload?

Introduction: Workforce planning for first aid and medical coverage of mass gatherings is hampered by limited research. In particular, the characteristics and likely presentation patterns of low-volume mass gatherings of between several hundred to several thousand people are poorly described in the existing literature.

Objectives: This study was conducted to: 1.

The perception of friendship in adults with Down syndrome.

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.

Fitness correlates of heritable variation in antibody responsiveness in a wild mammal.

A functional immune system is important for survival in natural environments, where individuals are frequently exposed to parasites. Yet strong immune responses may have fitness costs if they deplete limited energetic resources or cause autoimmune disease. We have found associations between fitness and heritable self-reactive antibody responsiveness in a wild population of Soay sheep.

Regulation of the androgen receptor by SET9-mediated methylation.

The androgen receptor (AR) is a member of the nuclear hormone receptor family of transcription factors that plays a critical role in regulating expression of genes involved in prostate development and transformation. Upon hormone binding, the AR associates with numerous co-regulator proteins that regulate the activation status of target genes via flux to the post-translational modification status of histones and the receptor. Here we show that the AR interacts with and is directly methylated by the histone methyltransferase enzyme SET9.

NAFLD and insulin resistance do not increase the risk of postoperative complications among patients undergoing bariatric surgery--a prospective analysis.

Background: Nonalcoholic fatty liver disease (NAFLD) and insulin resistance are common consequences of obesity and are highly prevalent among patients undergoing bariatric surgery. Insulin resistance and NAFLD have been reported to be associated with postoperative complications following major surgery.

Methods: We prospectively evaluated complications in a cohort of 437 consecutive patients undergoing bariatric surgery.

Changing epidemiology of serious bacterial infections in febrile infants without localizing signs.

Objective: Historically, management of infants with fever without localizing signs (FWLS) has generated much controversy, with attempts to risk stratify based on several criteria. Advances in medical practice may have altered the epidemiology of serious bacterial infections (SBIs) in this population. We conducted this study to test the hypothesis that the rate of SBIs in this patient population has changed over time.

Conformation of the mineralocorticoid receptor N-terminal domain: evidence for induced and stable structure.

The mineralocorticoid receptor (MR) binds the steroid hormones aldosterone and cortisol and has an important physiological role in the control of salt homeostasis. Regions of the protein important for gene regulation have been mapped to the amino-terminal domain (NTD) and termed activation function (AF)1a, AF1b, and middle domain (MD). In the present study, we used a combination of biophysical and biochemical techniques to investigate the folding and function of the MR-NTD transactivation functions.

Pretransplant serum troponin levels are highly predictive of patient and graft survival following liver transplantation.

Optimizing the utility of liver transplantation requires the identification of factors that confer increased risk of posttransplant mortality. Elevated serum troponin (TN) levels are strongly predictive of posttransplant mortality after kidney transplantation. We sought to determine whether pretransplant TN levels were predictive of mortality and graft loss after liver transplantation in 236 liver transplant recipients from 1998 to 2001 with 8.

Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor.

Castration-recurrent prostate cancer (CRPC) is suspected to depend on androgen receptor (AR). The AF-1 region in the amino-terminal domain (NTD) of AR contains most, if not all, of the transcriptional activity. Here we identify EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors.

Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study.

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.

Metabolic syndrome and liver transplantation: a review and guide to management.

Metabolic syndrome is common among liver transplant recipients before and after transplantation. The components of metabolic syndrome are often exacerbated in the post-transplant period by transplant specific factors, such as immunosuppression, and are strong predictors of patient morbidity and mortality. Many aspects of the metabolic syndrome are modifiable.

Anticipated behaviors of emergency prehospital medical care providers during an influenza pandemic.

Introduction: Emergency prehospital medical care providers are frontline health workers during emergencies. However, little is known about their attitudes, perceptions, and likely behaviors during emergency conditions. Understanding these attitudes and behaviors is crucial to mitigating the psychological and operational effects of biohazard events such as pandemic influenza, and will support the business continuity of essential prehospital services.

Attitudes to living and working in pandemic conditions among emergency prehospital medical care personnel.

Introduction: Little is known about the risk perceptions and attitudes of healthcare personnel, especially of emergency prehospital medical care personnel, regarding the possibility of an outbreak or epidemic event.

Problem: This study was designed to investigate pre-event knowledge and attitudes of a national sample of the emergency prehospital medical care providers in relation to a potential human influenza pandemic, and to determine predictors of these attitudes.

Methods: Surveys were distributed to a random, cross-sectional sample of 20% of the Australian emergency prehospital medical care workforce (n = 2,929), stratified by the nine services operating in Australia, as well as by gender and location.

Pain management in the cirrhotic patient: the clinical challenge.

Pain management in patients with cirrhosis is a difficult clinical challenge for health care professionals, and few prospective studies have offered an evidence-based approach. In patients with end-stage liver disease, adverse events from analgesics are frequent, potentially fatal, and often avoidable. Severe complications from analgesia in these patients include hepatic encephalopathy, hepatorenal syndrome, and gastrointestinal bleeding, which can result in substantial morbidity and even death.

Yap is a novel regulator of C2C12 myogenesis.

The expression, regulation and function of mammalian Hippo pathway members in skeletal muscle is largely unknown. The aim of this study was thus to test the hypothesis that core members of the mammalian Hippo pathway are expressed in skeletal muscle and that the transcriptional co-factor Yap, a core member of the Hippo pathway, regulates C2C12 myogenesis. We found that the major components of the mammalian Hippo pathway including Yap are all expressed in skeletal muscles, C2C12 myoblasts and myotubes.