Tetracycline-regulated expression of VEGF-A in beta cells induces angiogenesis: improvement of engraftment following transplantation.

Early revascularization of pancreatic islet cells after transplantation is crucial for engraftment, and it has been suggested that vascular endothelial growth factor-A (VEGF-A) plays a significant role in this process. Although VEGF gene therapy can improve angiogenesis, uncontrolled VEGF secretion can lead to vascular tumor formation. Here we have explored the role of temporal VEGF expression, controlled by a tetracycline (TC)-regulated promoter, on revascularization and engraftment of genetically modified beta cells following transplantation. To this end, we modified the CDM3D beta cell line using a lentiviral vector to promote secretion of VEGF-A either in a TC-regulated (TET cells) or a constitutive (PGK cells) manner. VEGF secretion, angiogenesis, cell proliferation, and stimulated insulin secretion were assessed in vitro. VEGF secretion was increased in TET and PGK cells, and VEGF delivery resulted in angiogenesis, whereas addition of TC inhibited these processes. Insulin secretion by the three cell types was similar. We used a syngeneic mouse model of transplantation to assess the effects of this controlled VEGF expression in vivo. Time to normoglycemia, intraperitoneal glucose tolerance test, graft vascular density, and cellular mass were evaluated. Increased expression of VEGF resulted in significantly better revascularization and engraftment after transplantation when compared to control cells. In vivo, there was a significant increase in vascular density in grafted TET and PGK cells versus control cells. Moreover, the time for diabetic mice to return to normoglycemia and the stimulated plasma glucose clearance were also significantly accelerated in mice transplanted with TET and PGK cells when compared to control cells. VEGF was only needed during the first 2-3 weeks after transplantation; when removed, normoglycemia and graft vascularization were maintained. TC-treated mice grafted with TC-treated cells failed to restore normoglycemia. This approach allowed us to switch off VEGF secretion when the desired effects had been achieved. TC-regulated temporal expression of VEGF using a gene therapy approach presents a novel way to improve early revascularization and engraftment after islet cell transplantation.

Education, disease prevalence and health service utilization in the Swiss National Health Survey "SOMIPOPS".

The relation among education, disease prevalence, and frequency of health service utilization was analyzed using data from the Swiss National Health Survey SOMIPOPS, conducted in 1981-1983 on a randomly selected sample of 4,255 individuals, representative of the entire Swiss population. The prevalence of several important cardiovascular, respiratory, digestive, osteoarticular, and psychiatric disorders was higher among less educated individuals; only allergic conditions were directly associated with indicators of social class. More educated individuals reported lower frequencies of general practitioner visits, but higher frequencies of specialized consultations. These findings confirm that education is an important determinant not only of mortality but also of morbidity and health-care utilization and require careful consideration in terms of the planning and evaluation of health services.

Treatment and Early Intervention in Psychosis Program (TIPP-Lausanne): implementation of an early intervention programme for psychosis in Switzerland.

AIM: In a survey conducted in the Lausanne catchment area in 2000, we could estimate on the basis of file assessment that first-episode psychosis (FEP) patients had psychotic symptoms for more than 2 years before treatment and that 50% did not attend any outpatient appointment after discharge from hospital. In this paper, we describe the implementation of a specialized programme aimed at improving engagement and quality of treatment for early psychosis patients in the Lausanne catchment area in Switzerland. METHOD: The Treatment and Early Intervention in Psychosis Program-Lausanne is a comprehensive 3-year programme composed of (i) an outpatient clinic based on assertive case management; (ii) a specialized inpatient unit; and (iii) an intensive mobile team, connected for research to the Center for Psychiatric Neuroscience. RESULTS: Eight years after implementation, the programme has included 350 patients with a disengagement rate of 9% over 3 years of treatment. All patients have been assessed prospectively and 90 participated in neurobiological research. Based on this experience, the Health Department funded the implementation of similar programmes in other parts of the state, covering a total population of 540 000 people. CONCLUSION: Programmes for early intervention in psychosis have a major impact on patients' engagement into treatment. While development of mobile teams and assertive case management with specific training are crucial, they do not necessitate massive financial support to be started. Inclusion of a research component is important as well, in terms of service planning and improvement of both quality of care and impact of early intervention strategies.

Brain dynamics underlying training-induced improvement in suppressing inappropriate action.

Inhibitory control, a core component of executive functions, refers to our ability to suppress intended or ongoing cognitive or motor processes. Mostly based on Go/NoGo paradigms, a considerable amount of literature reports that inhibitory control of responses to "NoGo" stimuli is mediated by top-down mechanisms manifesting ∼200 ms after stimulus onset within frontoparietal networks. However, whether inhibitory functions in humans can be trained and the supporting neurophysiological mechanisms remain unresolved. We addressed these issues by contrasting auditory evoked potentials (AEPs) to left-lateralized "Go" and right NoGo stimuli recorded at the beginning versus the end of 30 min of active auditory spatial Go/NoGo training, as well as during passive listening of the same stimuli before versus after the training session, generating two separate 2 × 2 within-subject designs. Training improved Go/NoGo proficiency. Response times to Go stimuli decreased. During active training, AEPs to NoGo, but not Go, stimuli modulated topographically with training 61-104 ms after stimulus onset, indicative of changes in the underlying brain network. Source estimations revealed that this modulation followed from decreased activity within left parietal cortices, which in turn predicted the extent of behavioral improvement. During passive listening, in contrast, effects were limited to topographic modulations of AEPs in response to Go stimuli over the 31-81 ms interval, mediated by decreased right anterior temporoparietal activity. We discuss our results in terms of the development of an automatic and bottom-up form of inhibitory control with training and a differential effect of Go/NoGo training during active executive control versus passive listening conditions.

Inpatient diabetes care in a Swiss multi-site hospital: is there room for improvement?

Background and objective: Optimal care of diabetic patients (DPs) decreases the risk of complications. Close blood glucose monitoring can improve patient outcomes and shorten hospital stay. The objective of this pilot study was to evaluate the treatment of hospitalized DPs according to the current standards, including their diabetic treatment and drugs to prevent diabetes related complications [=guardian drugs: angiotensin converting enzyme inhibitors (ACEI) or Angiotensin II Receptor Blockers (ARB), antiplatelet drugs, statins]. Guidelines of the American Diabetes Association (ADA) [1] were used as reference as they were the most recent and exhaustive for hospital care. Design: Observational pilot study: analysis of the medical records of all DPs seen by the clinical pharmacists during medical rounds in different hospital units. An assessment was made by assigning points for fulfilling the different criteria according to ADA and then by dividing the total by the maximum achievable points (scale 0-1; 1 = all criteria fulfilled). Setting: Different Internal Medicine and Geriatric Units of the (multi-site) Ho^pital du Valais. Main outcome measures: - Completeness of diabetes-related information: type of diabetes, medical history, weight, albuminuria status, renal function, blood pressure, (recent) lipid profile. - Management of blood glucose: Hb1Ac, glycemic control, plan for treating hyper-/hypoglycaemia. - Presence of guardian drugs if indicated. Results: Medical records of 42 patients in 10 different units were analysed (18 women, 24 men, mean age 75.4 ± 11 years). 41 had type 2 diabetes. - Completeness of diabetes-related information: 0.8 ± 0.1. Information often missing: insulin-dependence (43%) and lipid profile (86%). - Management of blood glucose: 0.5 ± 0.2. 15 patients had suboptimal glycemic balance (target glycaemia 7.2-11.2 mmol/ l, with values[11.2 or\3.8 mmol/l, or Hb1Ac[7%), 10 patients had a deregulated balance (more than 10 values[11.2 mmol/l or \3.8 mmol/l and even values[15 mmol/l). - Presence of guardian drugs if indicated: ACEI/ARB: 19 of 23 patients (82.6%), statin: 16 of 40 patients (40%), antiplatelet drug: 16 of 39 patients (41%). Conclusions: Blood glucose control was insufficient in many DPs and prescription of statins and antiplatelet drugs was often missing. If confirmed by a larger study, these two points need to be optimised. As it is not always possible and appropriate to make those changes during hospital stay, a further project should assess and optimise diabetes care across both inpatient and outpatient settings.

Resigned but satisfied: The negative impact of public service motivation and red tape on work satisfaction

This article examines the relationship between red tape, Public Service Motivation (PSM) and a particular work outcome labelled 'resigned satisfaction'. Using data from a national survey of over 3754 public servants working at the municipal level in Switzerland, this study shows the importance of looking more closely at the concept of work satisfaction and, furthermore, of thoroughly investigating the impact of the different PSM dimensions on work outcomes. Unsurprisingly, research findings show that red tape is the most important predictor of resignation. Nevertheless, when PSM dimensions are analysed separately, results demonstrate that 'commitment to public interest/civic duty' and, to a lesser extent, 'attraction to policy-making' decrease resignation, whereas 'compassion' and 'self-sacrifice' increase it. This study thus highlights some of the negative (or undesirable) effects of PSM that have not been previously addressed in PSM literature.

Policy Environment and Public Service Motivation

This article analyzes whether and to what extent the policy environment of civil servants has an impact on their level of Public Service Motivation (PSM). It hypothesizes that public employees working in different policy domains and stages of the policy cycle are diversely motivated by four PSM orientations (Compassion, Commitment to the public interest, Self-sacrifice and Attraction to politics). The empirical results are based on a survey of 6885 Swiss civil servants. They show that those in charge of Welfare State policies are inclined to have higher levels of 'Compassion', whereas those performing core state functions report lower levels. Furthermore, employees whose main tasks are related to policy formulation display high levels of the 'Attraction to politics' dimension of PSM. This study questions the generalization of previous findings on PSM that are based on heterogeneous survey populations.