The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR) study (NCT00237913)

<p>Abstract</p> <p>Background</p> <p>The aim of this paper is to evaluate the effect of antipsychotics for the treatment of schizophrenia in a community based study on sexual function and prolactin levels comparing the use of aripiprazole and standard of care (SOC), which was a limited choice of three widely used and available antipsychotics (olanzapine, quetiapine or risperidone) (The Schizophrenia Trial of Aripiprazole [STAR] study [NCT00237913]).</p> <p>Method</p> <p>This open-label, 26-week, multi-centre, randomised study compared aripiprazole to SOC (olanzapine, quetiapine or risperidone) in patients with schizophrenia (DSM-IV-TR criteria). The primary effectiveness variable was the mean total score of the Investigator Assessment Questionnaire (IAQ) at Week 26. The outcome research variables included the Arizona Sexual Experience scale (ASEX). This along with the data collected on serum prolactin levels at week 4, 8, 12, 18 and 26 will be the focus of this paper.</p> <p>Results</p> <p>A total of 555 patients were randomised to receive aripiprazole (n = 284) or SOC (n = 271). Both treatment groups experienced improvements in sexual function from baseline ASEX assessments. However at 8 weeks the aripiprazole treatment group reported significantly greater improvement compared with the SOC group (p = 0.007; OC). Although baseline mean serum prolactin levels were similar in the two treatment groups (43.4 mg/dL in the aripiprazole group and 42.3 mg/dL in the SOC group, p = NS) at Week 26 OC, mean decreases in serum prolactin were 34.2 mg/dL in the aripiprazole group, compared with 13.3 mg/dL in the SOC group (p < 0.001).</p> <p>Conclusion</p> <p>The study findings suggest that aripiprazole has the potential to reduce sexual dysfunction, which in turn might improve patient compliance.</p

Design of a decision support tool for visualising E. coli risks on agricultural land using a stakeholder-driven approach

Enabling knowledge exchange between scientists and decision-makers is becoming increasingly necessary to promote the development of effective decision-support tools (DSTs) for environmental management. Participation of stakeholders in the design process beyond a basic level of consultation is essential for promoting trust in modelled outputs and accelerating eventual uptake of resulting tools and models by end-user communities. This study outlines the development of a DST to visualise and communicate the spatial and temporal patterns ofE. coli(a faecal indicator organism) on agricultural land, as a first step in managing microbial pollution risks to the wider environment. A participatory approach was used to engage regulators, catchment managers, environmental scientists, farmers and farm advisors, researchers in geospatial technologies and water industry staff in the co-design of a novel, user-friendly and accessible DST for guiding on-farm microbial risk assessment. Recommendations for maximising the benefits of a participatory process to DST design are discussed with reference to a series of opportunities and limitations identified by our stakeholder cohort during the development of the Visualising Pathogen &amp; Environmental Risk (ViPER) DST. The resulting toolkit provides environmental managers and farm advisors with one of the first freely-available DSTs for visualising patterns ofE. coliinputs to pasture in space and time, and begins to address the lack of advisory tools currently available for informing decision-making with respect to managing microbial risks in agricultural systems

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

The WaterProtect governance guide: experiences from seven agricultural and drinking water production catchments across Europe

Although collaborative, multi-level and adaptive governance is put forward as the right approach to manage water resources, it remains a challenge for local water managers to engage with multiple understandings and perspectives and to move towards more transdisciplinary approaches in water governance. In this research, we address this need by proposing a practical guide for water governance assessment and improvement, existing of three successive steps, i.e. (1) an assessment of water governance, (2) the implementation of a multi-actor process and (3) an evaluation of achievements. This guide is tested in the seven action labs of the WaterProtect project, which have in common that they are drinking water catchments suffering from agricultural pollution throughout Europe. By implementing the guide in the different action labs, we find that water managers appreciated the integrated approach of the guide, helping them in the efficient organization of the water governance process while taking into account the human dimension. Furthermore action lab leaders evaluated the governance guide as being hands-on and practical, allowing them to redirect and open up the governance process. Despite this, they welcomed the presence of a facilitator, who boosted the local action lab leaders\u2019 confidence and motivation to put things into motion. Looking at the results, we find that over the different action labs a lot of progress has been made towards intermediary goals, however that an improvement of the water quality cannot be expected in the short time frame of a project. We therefore recommend to improve the design of the guide with insights from transition management, which will allow local water managers to better address change at different time-scale levels

Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity

Steviol glycosides (SGs), such as stevioside and rebaudioside A, are natural, non-caloric sweet-tasting organic molecules, present in extracts of the scrub plant Stevia rebaudiana, which are widely used as sweeteners in consumer foods and beverages. TRPM5 is a Ca2+-activated cation channel expressed in type II taste receptor cells and pancreatic β-cells. Here we show that stevioside, rebaudioside A and their aglycon steviol potentiate the activity of TRPM5. We find that SGs potentiate perception of bitter, sweet and umami taste, and enhance glucose-induced insulin secretion in a Trpm5-dependent manner. Daily consumption of stevioside prevents development of high-fat-diet-induced diabetic hyperglycaemia in wild-type mice, but not in Trpm5−/− mice. These results elucidate a molecular mechanism of action of SGs and identify TRPM5 as a potential target to prevent and treat type 2 diabetes

Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity

Steviol glycosides (SGs), such as stevioside and rebaudioside A, are natural, non-caloric sweet-tasting organic molecules, present in extracts of the scrub plant Stevia rebaudiana, which are widely used as sweeteners in consumer foods and beverages. TRPM5 is a Ca(2+)-activated cation channel expressed in type II taste receptor cells and pancreatic β-cells. Here we show that stevioside, rebaudioside A and their aglycon steviol potentiate the activity of TRPM5. We find that SGs potentiate perception of bitter, sweet and umami taste, and enhance glucose-induced insulin secretion in a Trpm5-dependent manner. Daily consumption of stevioside prevents development of high-fat-diet-induced diabetic hyperglycaemia in wild-type mice, but not in Trpm5(-/-) mice. These results elucidate a molecular mechanism of action of SGs and identify TRPM5 as a potential target to prevent and treat type 2 diabetes

Context matters-using an agent-based model to investigate the influence of market context on the supply of local biomass for anaerobic digestion

Biogas plant managers often face difficulties in obtaining feedstock at stable and affordable prices. The context in which the biogas plant manager needs to purchase the feedstock could be important when the biomass is also used in valorization trajectories besides anaerobic digestion. Using a combination of qualitative research and agent-based modelling, we investigated the effect of market context on the purchase of local biomass for anaerobic digestion. This paper details the institutional arrangements of our case study, the silage maize market in Flanders and the results of a scenario analysis, simulating nine different market contexts. Silage maize is an interesting case study, as it is both used for feed by farmers and as an input in biogas plants. The results show that mainly the time of entry into the market explains the difficulties in obtaining a stable supply of silage maize to biogas plants. Furthermore, we found a silage maize price increase for farmers in competition with a biogas plant, especially in case of a silage maize deficit in the market. The different institutional arrangements used have no significant effect. Our findings may guide biogas plant managers in assessing and reducing the consequences of the establishment of a biogas plant, competing for local biomass resources