Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study

High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The -308A allele of the TNF-alpha gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05-3.09; P = 0.034). Subjects with both the A allele of the TNF-alpha gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02-4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the -308A allele of the promoter polymorphism (G-308A) of the TNF-alpha gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene.     

Oncologic,Functional, and Complications Outcomes of Robot-assisted Radical Cystectomy with Totally Intracorporeal Neobladder Diversion

Background

Robot-assisted radical cystectomy (RARC) with totally intracorporeal neobladder diversion is a complex procedure that has been reported with good outcomes in small series.

Objective

To present complications and oncologic and functional outcomes of this procedure.

Design, setting, and participants

Between 2003 and 2012 in a tertiary referral center, 70 patients were operated on by two experienced robotic surgeons. Data were collected prospectively and reviewed retrospectively.

Intervention

RARC with totally intracorporeal modified Studer ileal neobladder formation.

Outcome measurements and statistical analysis

The overall outcome of RARC with a totally intracorporeal neobladder was presented by assessing (1) surgical margins, (2) recurrence or cancer-specific death at 24 mo, (3) 30-d and 90-d complications graded according to the modified Clavien-Dindo system, (4) daytime and nighttime continence (no or one pad per day) at 6 and 12 mo, and (5) satisfactory sexual activity or potency at 6 mo and 12 mo. Survival rates were estimated by Kaplan-Meier plots.

Results and limitations

Median follow-up of the cohort was 30.3 mo (interquartile range: 12.7–35.6). We recorded negative margins in 69 of 70 patients (98.6%). Clavien 3–5 complications occurred in 22 of 70 patients (31.4%) at 30 d and 13 of 70 (18.6%) at >30 d. At 90 d, the overall complication rate was 58.5%. Clavien <3 and Clavien ≥3 complications were recorded in 15 of 70 patients (21.4%) and 26 of 70 (37.1%), respectively. Kaplan-Meier estimates for recurrence-free, cancer-specific, and overall survival at 24 mo were 80.7%, 88.9%, and 88.9%, respectively. Daytime continence and satisfactory sexual function or potency at 12 mo ranged between 70% and 90% in both men and women. Limitations of this study include its retrospective design, selection bias due to the learning curve phase, and missing data.

Conclusions

In this expert center for RARC, outcomes after RARC with totally intracorporeal neobladder diversion appear satisfactory and in line with contemporary open series.     

Association between Disability,Cognition, Fatigue,EQ-5D-3L Domains,and Utilities Estimated with Different Western European Value Sets in Patients with Multiple Sclerosis

Objectives

To assess the association between fatigue, cognition, domains of the EuroQol five-dimensional questionnaire (EQ-5D-3L), disability, and utilities estimated with several Western European value sets in patients with multiple sclerosis (MS).

Occupational therapists’ perceptions of implementing a client-centered intervention in close collaboration with researchers: A mixed methods study

Abstract

Background: Integration of research-based knowledge in health care is challenging. Occupational therapists (OTs) need to implement new research-based interventions in clinical practice. Therefore it is crucial to recognize and understand the factors of specific barriers and facilitators affecting the implementation process.

Aim: To identify the key factors important for OTs during the implementation process of a complex intervention.

Materials and methods: A cross-sectional study with a combination of qualitative and quantitative data in a mixed method design. Forty-one OTs and 23 managers from three county councils in Sweden, responded to a questionnaire one year after the OTs participation in a workshop to prepare for implementation of a client-centered activity of daily living intervention for persons with stroke.

Results: Over 70% of the OTs benefitted from reading and discussing articles in the workshop; 60% had faith in the intervention; 69% reported usability of the intervention. High level of support from managers was reported, but less from team members. The therapists’ interaction, perceptions of own efforts and contextual influence affected the implementation process.

Conclusion: The workshop context with facilitation and access to evidence, supportive organizations and teams, sufficient interaction with researchers and satisfying self-image were successful key factors when involved in research.     

Evaluation of aldehyde dehydrogenase 1 promoter polymorphisms identified in human populations

BACKGROUND: Cytosolic aldehyde dehydrogenase, or ALDH1A1, functions in ethanol detoxification, metabolism of neurotransmitters, and synthesis of retinoic acid. Because the promoter region of a gene can influence gene expression, the ALDH1A1 promoter regions were studied to identify polymorphism, to assess their functional significance, and to determine whether they were associated with a risk for developing alcoholism. METHODS: Sequence analysis was performed in the promoter region by using Asian, Caucasian, and African American subjects. The resulting polymorphisms were assessed for frequency in Asian, Caucasian, Jewish, and African American populations and tested for associations with alcohol dependence in Asian and African American populations of alcoholics and controls. The functional significance of each polymorphism was determined through in vitro expression analysis by using HeLa and HepG2 cells. RESULTS: Two polymorphisms, a 17 base pair (bp) deletion (-416/-432) and a 3 bp insertion (-524), were discovered in the ALDH1A1 promoter region: ALDH1A1*2 and ALDH1A1*3, respectively. ALDH1A1*2 was observed at frequencies of 0.035, 0.023, 0.023, and 0.012 in the Asian, Caucasian, Jewish, and African American populations, respectively. ALDH1A1*3 was observed only in the African American population, at a frequency of 0.029. By using HeLa and HepG2 cells for in vitro expression, the activity of the luciferase reporter gene was significantly decreased after transient transfection of ALDH1A1*3-luciferase compared with the wild-type construct ALDH1A1*1-luciferase. In an African American population, a trend for higher frequencies of the ALDH1A1*2 and ALDH1A1*3 alleles was observed in a population of alcoholics (p = 0.03 and f = 0.12, respectively) compared with the control population. CONCLUSIONS: ALDH1A1*2 and ALDH1A1*3 may influence ALDH1A1 gene expression. Both ALDH1A1*2 and ALDH1A1*3 produce a trend in an African American population that may be indicative of an association with alcoholism; however, more samples are required to validate this observation. The underlying mechanisms contributing to these trends are still unknown.     

Interactions between peroxisome proliferator-activated receptor-gamma 2 gene polymorphisms and size at birth on blood pressure and the use of antihypertensive medication

OBJECTIVE: The combination of small birth size and the Pro12Pro variant of the peroxisome proliferator-activated receptor-gamma 2 (PPAR-gamma 2) gene has been shown to be associated with insulin resistance, which is linked to hypertension. We examined whether the association between small body size at birth and adult blood pressure is modulated by PPAR-gamma 2 gene polymorphism, and whether the use of any class of antihypertensive medication is related to birth size. DESIGN AND METHODS: A total of 500 subjects from an original epidemiological cohort of 7086 men and women aged 65-75 years attended a clinical study. Two hundred and eight of them (73 men and 135 women) were taking antihypertensive medication and are included in this study. The Pro12Ala polymorphism of the PPAR-gamma 2 gene was determined using the polymerase chain reaction single-strand conformation polymorphism method. RESULTS AND CONCLUSIONS: Hypertensive subjects with low birth weight or short length at birth and the Pro12Pro variant had raised systolic blood pressure. We suggest that insulin resistance enhances the regulatory responses of the renin-angiotensin system, leading to raised blood pressure levels. Those hypertensive subjects who had small birth size and the Pro12Pro variant tended to use angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers (ACEI/ARB). This could be because insulin resistance interacts with the renin-angiotensin system in ways that make ACEI/ARB an effective therapy. Alternative explanations include more severe and treatment resistant hypertension, leading to application of ACEI/ARB, or co-morbid conditions, such as myocardial infarction and type 2 diabetes, known to be linked to low birth weight.