Investigation of PNPLA3 and IL28B genotypes on diabetes and obesity after liver transplantation: insight into mechanisms of disease.

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.

MiR-1 and miR-200 inhibit EMT via Slug-dependent and tumorigenesis via Slug-independent mechanisms.

Epithelial-mesenchymal transition (EMT) is a developmental program of signaling pathways that determine commitment to epithelial and mesenchymal phenotypes. In the prostate, EMT processes have been implicated in benign prostatic hyperplasia and prostate cancer progression. In a model of Pten- and TP53-null prostate adenocarcinoma that progresses via transforming growth factor ß-induced EMT, mesenchymal transformation is characterized by plasticity, leading to various mesenchymal lineages and the production of bone. Here we show that SLUG is a major regulator of mesenchymal differentiation. As microRNAs (miRs) are pleiotropic regulators of differentiation and tumorigenesis, we evaluated miR expression associated with tumorigenesis and EMT. Mir-1 and miR-200 were reduced with progression of prostate adenocarcinoma, and we identify Slug as one of the phylogenetically conserved targets of these miRs. We demonstrate that SLUG is a direct repressor of miR-1 and miR-200 transcription. Thus, SLUG and miR-1/miR-200 act in a self-reinforcing regulatory loop, leading to amplification of EMT. Depletion of Slug inhibited EMT during tumorigenesis, whereas forced expression of miR-1 or miR-200 inhibited both EMT and tumorigenesis in human and mouse model systems. Various miR targets were analyzed, and our findings suggest that miR-1 has roles in regulating EMT and mesenchymal differentiation through Slug and functions in tumor-suppressive programs by regulating additional targets.

Lamivudine therapy in chronic delta hepatitis: a multicentre randomized-controlled pilot study.

BACKGROUND: Delta virus (HDV)-related chronic hepatitis is difficult to treat. AIMS: To evaluate the efficacy of lamivudine 100 mg daily on serum HDV-RNA, hepatitis D virus antibodies and alanine aminotransferase levels, liver histology, and on hepatitis B surface antigen seroconversion. METHODS: Thirty-one hepatitis B surface antigen-positive, HDV-RNA-positive patients with ALT > or = 1.5 upper normal level and compensated liver disease were randomized (1:2 ratio) to placebo (group A, n = 11) or lamivudine (group B, n = 20) for 52 weeks; thereafter, all patients were given lamivudine for 52 weeks and followed up for 16 weeks. RESULTS: Twenty-five patients (81%) completed the study. No patient was HDV-RNA-negative at week 52; three patients (11%) were negative at week 104. Two of them remained HDV-RNA-negative at week 120, and one lost the hepatitis B surface antigen without seroconversion. Paired pre-treatment and week 104 liver biopsies were available from 19 patients: of which three of seven (43%) from group A and two of 12 patients (17%) from group B had a > or =2 point decrease in the Ishak necroinflammatory score. CONCLUSION: A sustained complete response was achieved in 8% of hepatitis D virus-infected patients treated with lamivudine and a partial histological response in 26% of them. Hepatitis D virus viraemia was unaffected, even in patients when hepatitis B virus replication was lowered by lamivudine therapy.

Environmental turbulence: staff nurse perspectives.

The purpose of this qualitative study was to explore staff nurses' perceptions of how turbulence in the internal environment affected their ability to provide patient care. The themes that emerged from the data point toward multiple factors impinging on a staff nurse's ability to provide quality care in today's healthcare environment. The authors discuss these factors, the consequences for staff nurses, patients, and the organization, and the implications for nursing administrators and their colleagues in hospital administration.

Plasma cholesteryl ester transfer in patients with non-insulin dependent diabetes mellitus.

Plasma newly synthesised cholesteryl ester transfer (NCET) rates from high density lipoproteins (HDL) to very low density lipoproteins (VLDL) and low density lipoproteins lipoproteins (LDL) were measured in 26 patients with non-insulin dependent diabetes mellitus (NIDDM), 26 healthy subjects with closely matching plasma triglyceride (TG) levels and 10 normolipidaemic healthy individuals. In addition, insulin mediated glucose uptake was measured in the NIDDM patients and the normolipidaemic subjects. Rates of NCET were significantly (P < 0.05) elevated in NIDDM patients compared with healthy normolipidaemic individuals but were similar to rates in healthy subjects with closely matching TG levels. In all groups of subjects plasma NCET was significantly (P < 0.001) correlated with plasma TG concentration. In NIDDM patients correlations between NCET and plasma glucose (r = 0.489, P = 0.011) independently of plasma TG levels, and glycated haemoglobin levels (r = 0.430, P = 0.028) were also recorded. Insulin mediated glucose uptake was unrelated to plasma NCET rates in the study. These data suggest that in NIDDM patients under good diabetic control elevated plasma NCET rates are mainly due to hypertriglyceridaemia and a specific and possibly stimulatory effect of diabetes on these rates may be seen only in patients with poorly controlled diabetes.

The effect of acute hyperinsulinemia on plasma cholesteryl ester transfer protein activity in patients with non-insulin-dependent diabetes mellitus and healthy subjects.

The effect of acute hyperinsulinemia on plasma cholesteryl ester (CE) transfer protein (CETP) activity was determined in 11 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 10 healthy subjects. Plasma CETP activity was reduced significantly in NIDDM patients (-37 +/- 59 nmol/mL/h, P < .05) but not in healthy subjects (-7 +/- 37 nmol/mL/h) during insulin infusion. Saline infusion did not alter plasma CETP activity significantly. The change in plasma CETP activity was correlated significantly with the baseline plasma triglyceride (TG) concentration (r = -.523, n = 21, P = .01) and marginally with the concomitant decrease in these levels with acute hyperinsulinemia (r = .413, n = 21, P = .06) in NIDDM patients and healthy subjects combined. These data indicate that acute hyperinsulinemia reduces plasma CETP activity and probably plasma CETP concentration in NIDDM patients, and suggest coordinated regulation of CETP levels and TG metabolism by insulin.

The response of plasma lipoprotein (a) concentration to acute hyperinsulinemia in patients with non-insulin dependent diabetes and in healthy subjects.

The effect of acute hyperinsulinemia on plasma lipoprotein a [Lp(a)] concentration in 25 patients with non-insulin dependent diabetes mellitus (NIDDM) and in 10 healthy subjects was examined. Insulin was infused into the subjects for 2 hours while baseline plasma glucose concentrations were maintained. Plasma Lp(a) levels showed a small but significant mean (+/- SD) increase in NIDDM patients (12 +/- 26 U/l, p < 0.01) but did not vary significantly in healthy subjects (3 +/- 15 U/l) when insulin was infused. There was considerable individual variation (-35 to 98 U/l) in the response of Lp(a) to acute hyperinsulinemia and the response was correlated significantly with baseline Lp(a) levels (r = 0.399, p < 0.05). These data suggest that acute hyperinsulinemia at constant baseline glucose levels may raise plasma Lp(a) levels in NIDDM patients more particularly in those with high initial Lp(a) concentrations.

Biennial survey of physician clinical-nutrition training programs.

This is the fourth survey of physician clinical-nutrition training programs. As in previous reports, current fellowship training programs were identified, descriptive information obtained, and program content surveyed. In addition, a questionnaire developed by the American Board of Nutrition Committee on Fellowship Training Programs was used to determine the degree of emphasis given to content in the areas of basic nutrition science, clinical applications, and research training. Among the 38 programs identified, uniform ratings of importance were found in all major topic areas. There was also uniformity in most subtopics, with minor exceptions. As expected, in the area of nutrition in the life cycle, pediatric training programs emphasized infancy and childhood whereas medical-surgical programs emphasized adulthood and aging. Alcoholism was emphasized in medical-surgical training programs whereas cystic fibrosis and inborn errors of metabolism were emphasized in pediatric programs. Nutrition in burn patients received minor emphasis in all programs. The overall uniformity of curricular content in training programs confirms the contention that clinical nutrition has a defined clinical scope and should be considered for establishment as a recognized subspecialty in American medicine.

Nursing research priorities for the care of the naval hospital patient: a Delphi survey.

The purpose of this study was to identify priorities for nursing research in a naval hospital using the Delphi technique. A general objective was to provide empirically based information to guide the development of a nursing research program at a regional medical treatment facility. Via a three-round Delphi survey, priority research questions were identified for the nursing department of a naval regional medical treatment facility. A serendipitous result was the identification of nursing research priorities within a deployed naval fleet hospital.

Enhancing the level of nutrition education at Tufts University's Medical and Dental Schools.

The current medical and dental curricula at Tufts were evaluated to ascertain the breadth and depth of their nutrition programs. The program, which both schools plan to initiate, to enhance the level of nutrition education involves (1) development of nutrition units for the first and second year, (2) expansion of required nutrition courses in the second year, (3) diet lunches in the third year introducing the role of nutrition in the clinical setting, and (4) nutrition rounds in the fourth year. A combined medical-dental seminar will be presented each year. At the end of the five-year funding period, it is anticipated that a manual will be available to all medical and dental schools that includes (1) nutrition units, (2) methods of dietary assessment in medical-dental practices, (3) nutrition interaction for the prevention of chronic disease in medical-dental practices, and (4) nutrition support for chronic disease and cancer, and case studies on nutrition and disease. The success of this program will be evaluated on the basis of goals and a national nutritional literacy exam.

Tuberous sclerosis.

Tuberous sclerosis (epiloia, Bourneville-Pringle syndrome) is an inherited disease with an autosomal pattern. Both sexes are affected equally with varied expression in successive generations. Two cases of this unusual disorder in siblings are reported. They illustrate heredofamilial nature, dissimilar expression, mutations, and oral manifestations.

Oral health services for adult rehabilitation patients: three illustrative cases.

Recent research has shown that the actual capability of physical medicine and rehabilitation units to provide oral health services is less than the need as perceived by rehabilitation administrators. Three cases have been selected to illustrate the nature and diversity of health benefits that can be provided by a complete oral health service which focuses on rehabilitation patients. The advantages of offering a comprehensive oral health service include not only improvement of the oral health of the patient but also often directly aids the patients' achievement of overall rehabilitation goals. Furthermore, by synergistic interaction with the other rehabilitation disciplines, an oral health service can appreciably enhance the quality and the scope of the rehabilitation program itself. Additionally, a new adaptive device for oral grasping, designed for use by patients who lack the use of their upper extremities, is illustrated. The device is intended to provide the patient with a range of functions including recreational participation in board games as well as vocational activities which require the lifting or grasping of objects.