Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis.

BACKGROUND: Nonselective beta-adrenergic blockers decrease portal pressure and prevent variceal hemorrhage. Their effectiveness in preventing varices is unknown. METHODS: We randomly assigned 213 patients with cirrhosis and portal hypertension (minimal hepatic venous pressure gradient [HVPG] of 6 mm Hg) to receive timolol, a nonselective beta-blocker (108 patients), or placebo (105 patients). The primary end point was the development of gastroesophageal varices or variceal hemorrhage. Endoscopy and HVPG measurements were repeated yearly. RESULTS: During a median follow-up of 54.9 months, the rate of the primary end point did not differ significantly between the timolol group and the placebo group (39 percent and 40 percent, respectively; P=0.89), nor were there significant differences in the rates of ascites, encephalopathy, liver transplantation, or death. Serious adverse events were more common among patients in the timolol group than among those in the placebo group (18 percent vs. 6 percent, P=0.006). Varices developed less frequently among patients with a baseline HVPG of less than 10 mm Hg and among those in whom the HVPG decreased by more than 10 percent at one year and more frequently among those in whom the HVPG increased by more than 10 percent at one year. CONCLUSIONS: Nonselective beta-blockers are ineffective in preventing varices in unselected patients with cirrhosis and portal hypertension and are associated with an increased number of adverse events. (ClinicalTrials.gov number, NCT00006398.

An investigation to assess ankle mobility in healthy individuals from the application of multi-component compression bandages and compression hosiery

Background An investigation was undertaken to compare the effect of multi-component compression bandages and compression hosiery kits on individuals’ range of ankle motion whilst wearing typical and medical footwear, and barefoot. Methods A convenience sample of 30 healthy individuals recruited from the staff and student population at the University of Huddersfield, UK. Plantarflexion/dorsiflexion range of ankle motion (ROAM) was measured in participants over 6 steps in every combination of typical, medical and no footwear; and multi-component bandages, compression hosiery and no garments. Results Controlling for age, gender and garments, the use of typical footwear was associated with a mean increase in ROAM of 2.54° at best estimate compared with barefoot; the use of medical footwear was associated with a mean decrease in ROAM of 1.12° at best estimate compared with barefoot. Controlling for age, gender and footwear, the use of bandaging was associated with a mean decrease in ROAM of 2.51° at best estimate compared with no garments. Controlling for age, gender and footwear, the use of hosiery was not associated with a significant change in ROAM compared with no garments. Conclusions Bandages appear to restrict ROAM more than hosiery when used in conjunction with a variety of footwear types

The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis

Chronic diarrhea associated with persistent norovirus excretion in patients with chronic lymphocytic leukemia: report of two cases

BACKGROUND: Chronic diarrhea in patients treated with immunosuppressive agents or suffering from immunosuppressive disease can represent a diagnostic and therapeutic challenge to the clinician. Norovirus infection, a major cause of acute epidemic diarrhea, has been described as a cause of chronic diarrhea in patients who are immunosuppressed, including transplant recipients and the very young. CASE PRESENTATIONS: We describe two patients, a 64 year-old man and a 59 year-old woman, both suffering from chronic lymphocytic leukemia and hypogammaglobulinemia, who developed chronic diarrhea resistant to therapy. In both cases, after months of symptoms, persistent norovirus infection--documented by repeatedly-positive high-sensitivity stool enzyme immunoassay--was found to be the cause. Both patients died with active diarrheal symptoms. CONCLUSIONS: We describe the first cases of advanced chronic lymphocytic leukemia to suffer from chronic symptomatic norovirus infection. Clinicians caring for such patients, particularly those with concomitant hypogammaglobulinema, who have chronic unexplained diarrhea, should consider norovirus infection in the differential diagnosis

Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach

BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions. METHODS: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs. Overall, 17 women shared their experiences of diabetes, pregnancy, and health services in group discussions and 28 women gave individual narrative interviews, facilitated by multilingual researchers, audiotaped, translated, and transcribed. Data were analysed using the constant comparative method, drawing on sociological and narrative theories. RESULTS: Key storylines (over-arching narratives) recurred across all ethnic groups studied. Short-term storylines depicted the experience of diabetic pregnancy as stressful, difficult to control, and associated with negative symptoms, especially tiredness. Taking exercise and restricting diet often worsened these symptoms and conflicted with advice from relatives and peers. Many women believed that exercise in pregnancy would damage the fetus and drain the mother's strength, and that eating would be strength-giving for mother and fetus. These short-term storylines were nested within medium-term storylines about family life, especially the cultural, practical, and material constraints of the traditional South Asian wife and mother role and past experiences of illness and healthcare, and within longer-term storylines about genetic, cultural, and material heritage - including migration, acculturation, and family memories of food insecurity. While peer advice was familiar, meaningful, and morally resonant, health education advice from clinicians was usually unfamiliar and devoid of cultural meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and managing diabetes in South Asian women before and during pregnancy are likely to be ineffective if delivered in a socio-cultural vacuum. Individual education should be supplemented with community-level interventions to address the socio-material constraints and cultural frames within which behavioural 'choices' are made

A smartphone intervention for adolescent obesity: study protocol for a randomised controlled non-inferiority trial

Background There are few evidence-based mobile health solutions for treating adolescent obesity. The primary aim of this parallel non-inferiority trial is to assess the effectiveness of an experimental smartphone application in reducing obesity at 12 months, compared to the Temple Street W82GO Healthy Lifestyles intervention. Methods/design The primary outcome measure is change in body mass index standardised deviation score at 12 months. The secondary aim is to compare the effect of treatment on secondary outcomes, including waist circumference, insulin sensitivity, quality of life, physical activity and psychosocial health. Adolescents with a body mass index at or above the 98th percentile (12 to 17 years) will be recruited from the Obesity clinic at Temple Street Children’s University Hospital in Dublin, Ireland. W82GO is a family-based lifestyle change intervention delivered in two phases over 12 months. In the current study, participants will be randomised for phase two of treatment to either usual care or care delivered via smartphone application. One hundred and thirty-four participants will be randomised between the two study arms. An intention-to-treat analysis will be used to compare treatment differences between the groups at 12 months. Discussion The results of this study will be disseminated via open access publication and will provide important information for clinicians, patients and policy makers regarding the use of mobile health interventions in the management of adolescent obesity. Trial registration Clinicaltrials.gov NCT01804855

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Psychometric Properties of an Assessment for Mental Health Recovery Programs

The concept of recovery can be operationalized from either the point of view of the consumer, or from the perspective of the agency providing services. The Milestones of Recovery Scale (MORS) was created to capture aspects of recovery from the agency perspective. Evidence establishing the psychometric properties of the MORS was obtained in three efforts: Inter-rater reliability using staff at The Village, a multi-service organization serving the homeless mentally ill in Long Beach, California; inter-rater reliability was also obtained from Vinfen Corporation, a large provider of housing services to mentally ill persons in Boston, Massachusetts. A test–retest reliability study was conducted using staff rating of clients at The Village, and evidence for validity was obtained using the Level of Care Utilization System (LOCUS) as a validity measure. The intra-class correlation coefficient for the inter-rater reliability study was r = .85 (CI .81, .89) for The Village and r = .86 (CI .80, .90) for Vinfen Corporation; test–retest reliability was r = .85 (CI .81, .87); and validity coefficients for the LOCUS were at or above r = .49 for all subscales except one. There is sufficient evidence for the reliability and validity of the MORS

Transcriptome Responses of Insect Fat Body Cells to Tissue Culture Environment

Tissue culture is performed to maintain isolated portions of multicellular organisms in an artificial milieu that is outside the individual organism and for considerable periods of time; cells derived from cultured explants are, in general, different from cells of the corresponding tissue in a living organism. The changes in cultured tissues that precede and often explain the subsequent cell proliferation of explant-derived cells have been partially studied, but little is known about the molecular and genomic basis of these changes. Comparative transcriptomics of intact and cultured (90 hours in MGM-450 insect medium) Bombyx mori tissues revealed that fewer genes represented a larger portion of the transcriptome of intact fat body tissues than of cultured fat body tissues. This analysis also indicated that expression of genes encoding sugar transporters and immune response proteins increased during culture and that expression of genes encoding lipoproteins and cuticle proteins decreased during culture. These results provide support for hypotheses that cultured tissues respond immunologically to surgery, adapt to the medium by accelerating sugar uptake, and terminate their identity as part of an intact organism by becoming independent of that organism