Development and implementation of a lifestyle intervention to promote physical activity and healthy diet in the Dutch general practice setting: the BeweegKuur programme

<p>Abstract</p> <p>Background</p> <p>The number of patients with diabetes is increasing. BeweegKuur (Dutch for 'Exercise Therapy') is a Dutch lifestyle intervention which aims to effectively and feasibly promote physical activity and better dietary behaviour in primary health care to prevent diabetes.</p> <p>Methods</p> <p>The goal of this paper is to present the development process and the contents of the intervention, using a model of systematic health promotion planning. The intervention consists of a 1-year programme for diabetic and prediabetic patients. Patients are referred by their general practitioner (GP) to a lifestyle advisor (LSA), usually the practice nurse or a physiotherapist. Based on specific inclusion criteria and in close collaboration with the patient, an individual exercise programme is designed and supervised by the LSA. This programme can be attended at existing local exercise facilities or (temporarily) under the supervision of a specialized exercise coach or physiotherapist. All participants are also referred to a dietician and receive diet-related group education. In the first pilot year (2008), the BeweegKuur programme was implemented in 7 regions in the Netherlands (19 GP practices and health centres), while 14 regions (41 GP practices and health centres) participated during the second year. The aim is to implement BeweegKuur in all regions of the Netherlands by 2012.</p> <p>Discussion</p> <p>The BeweegKuur programme was systematically developed in an evidence- and practice-based process. Formative monitoring studies and (controlled) effectiveness studies are needed to examine the diffusion process and the effectiveness and cost-effectiveness of the intervention.</p

Not your average job: Measuring farm labor in Tanzania

Understanding the constraints to agricultural growth in Africa relies on the accurate measurement of smallholder labor. Yet, serious weaknesses in these statistics persist. The extent of bias in smallholder labor data is examined by conducting a randomized survey experiment among farming households in rural Tanzania. Agricultural labor estimates obtained through weekly surveys are compared with the results of reporting in a single end-of-season recall survey. The findings show strong evidence of recall bias: people in traditional recall-style modules reported working up to four times as many hours per person-plot as those reporting labor on a weekly basis. Recall bias manifests both in the intensive and extensive margins of labor reporting: while hours are over-reported in recall, the number of people and plots active in agricultural work are under-reported. The evidence suggests that this recall bias is driven not only by failures in memory, but also by the mental burdens of reporting on highly variable agricultural work patterns to provide a typical estimate. All things equal, studies suffering from this bias would understate agricultural labor productivity

De novo backbone and sequence design of an idealized α/β-barrel protein: evidence of stable tertiary structure

We have designed, synthesized, and characterized a 216 amino acid residue sequence encoding a putative idealized α/β-barrel protein. The design was elaborated in two steps. First, the idealized backbone was defined with geometric parameters representing our target fold: a central eight parallel-stranded β-sheet surrounded by eight parallel α-helices, connected together with short structural turns on both sides of the barrel. An automated sequence selection algorithm, based on the dead-end elimination theorem, was used to find the optimal amino acid sequence fitting the target structure. A synthetic gene coding for the designed sequence was constructed and the recombinant artificial protein was expressed in bacteria, purified and characterized. Far-UV CD spectra with prominent bands at 222 nm and 208 nm revealed the presence of α-helix secondary structures (50%) in fairly good agreement with the model. A pronounced absorption band in the near-UV CD region, arising from immobilized aromatic side-chains, showed that the artificial protein is folded in solution. Chemical unfolding monitored by tryptophan fluorescence revealed a conformational stability (ΔGH_2O) of 35 kJ/mol. Thermal unfolding monitored by near-UV CD revealed a cooperative transition with an apparent T_m of 65 °C. Moreover, the artificial protein did not exhibit any affinity for the hydrophobic fluorescent probe 1-anilinonaphthalene-8-sulfonic acid (ANS), providing additional evidence that the artificial barrel is not in the molten globule state, contrary to previously designed artificial a/ b-barrels. Finally, ^1H NMR spectra of the folded and unfolded proteins provided evidence for specific interactions in the folded protein. Taken together, the results indicate that the de novo designed α/β-barrel protein adopts a stable three-dimensional structure in solution. These encouraging results show that de novo design of an idealized protein structure of more than 200 amino acid residues is now possible, from construction of a particular backbone conformation to determination of an amino acid sequence with an automated sequence selection algorithm

The effectiveness of peer health coaching in improving glycemic control among low-income patients with diabetes: protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Although self-management support improves diabetes outcomes, it is not consistently provided in health care settings strained for time and resources. One proposed solution to personnel and funding shortages is to utilize peer coaches, patients trained to provide diabetes education and support to other patients. Coaches share similar experiences about living with diabetes and are able to reach patients within and beyond the health care setting. Given the limited body of evidence that demonstrates peer coaching significantly improves chronic disease care, this present study examines the impact of peer coaching delivered in a primary care setting on diabetes outcomes.</p> <p>Methods/Design</p> <p>The aim of this multicenter, randomized control trial is to evaluate the effectiveness of utilizing peer coaches to improve clinical outcomes and self-management skills in low-income patients with poorly controlled diabetes. A total of 400 patients from six primary health centers based in San Francisco that serve primarily low-income populations will be randomized to receive peer coaching (n = 200) or usual care (n = 200) over 6 months. Patients in the peer coach group receive coaching from patients with diabetes who are trained and mentored as peer coaches. The primary outcome is change in HbA1c. Secondary outcomes include change in: systolic blood pressure, body mass index (BMI), LDL cholesterol, diabetes self-care activities, medication adherence, diabetes-related quality of life, diabetes self-efficacy, and depression. Clinical values (HbA1c, LDL cholesterol and blood pressure) and self-reported diabetes self-efficacy and self-care activities are measured at baseline and after 6 months for patients and coaches. Peer coaches are also assessed at 12 months.</p> <p>Discussion</p> <p>Patients with diabetes, who are trained as peer health coaches, are uniquely poised to provide diabetes self management support and education to patients. This study is designed to investigate the impact of peer health coaching in patients with poorly controlled diabetes. Additionally, we will assess disease outcomes in patients with well controlled diabetes who are trained and work as peer health coaches.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01040806">NCT01040806</a></p

Prophylactic platelet transfusion prior to central venous catheter placement in patients with thrombocytopenia:study protocol for a randomised controlled trial

Background Severe thrombocytopenia should be corrected by prophylactic platelet transfusion prior to central venous catheter (CVC) insertion, according to national and international guidelines. Even though correction is thought to prevent bleeding complications, evidence supporting the routine administration of prophylactic platelets is absent. Furthermore, platelet transfusion bears inherent risk. Since the introduction of ultrasound-guided CVC placement, bleeding complication rates have decreased. The objective of the current trial is, therefore, to demonstrate that omitting prophylactic platelet transfusion prior to CVC placement in severely thrombocytopenic patients is non-inferior compared to prophylactic platelet transfusion. Methods/design The PACER trial is an investigator-initiated, national, multicentre, single-blinded, randomised controlled, non-inferior, two-arm trial in haematologic and/or intensive care patients with a platelet count of between 10 and 50 × 109/L and an indication for CVC placement. Consecutive patients are randomly assigned to either receive 1 unit of platelet concentrate, or receive no prophylactic platelet transfusion prior to CVC insertion. The primary endpoint is WHO grades 2–4 bleeding. Secondary endpoints are any bleeding complication, costs, length of intensive care and hospital stay and transfusion requirements. Discussion This is the first prospective, randomised controlled trial powered to test the hypothesis of whether omitting forgoing platelet transfusion prior to central venous cannulation leads to an equal occurrence of clinical relevant bleeding complications in critically ill and haematologic patients with thrombocytopenia

Bortezomib maintenance after R-CHOP, cytarabine and autologous stem cell transplantation in newly diagnosed patients with mantle cell lymphoma, results of a randomised phase II HOVON trial

Rituximab-containing induction followed by autologous stem cell transplantation (ASCT) is the standard first-line treatment for young mantle cell lymphoma patients. However, most patients relapse after ASCT. We investigated in a randomised phase II study the outcome of a chemo-immuno regimen and ASCT with or without maintenance therapy with bortezomib. Induction consisted of three cycles R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles high-dose cytarabine, BEAM (carmustine, etoposide, cytarabine, melphalan) and ASCT. Patients responding were randomised between bortezomib maintenance (1·3 mg/m2 intravenously once every 2 weeks, for 2 years) and observation. Of 135 eligible patients, 115 (85%) proceeded to ASCT, 60 (44%) were randomised. With a median follow-up of 77·5 months for patients still alive, 5-year event-free survival (EFS) was 51% (95% CI 42–59%); 5-year overall survival (OS) was 73% (95% CI 65–80%). The median follow-up of randomised patients still alive was 71·5 months. Patients with bortezomib maintenance had a 5-year EFS of 63% (95% CI 44–78%) and 5-year OS of 90% (95% CI 72–97%). The patients randomised to observation had 5-year PFS of 60% (95% CI, 40–75%) and OS of 90% (95% CI 72–97%). In conclusion, in this phase II study we found no indication of a positive effect of bortezomib maintenance after ASCT

A flexible coupling approach to multi-agent planning under incomplete information

The final publication is available at Springer via http://dx.doi.org/10.1007/s10115-012-0569-7Multi-agent planning (MAP) approaches are typically oriented at solving loosely coupled problems, being ineffective to deal with more complex, strongly related problems. In most cases, agents work under complete information, building complete knowledge bases. The present article introduces a general-purpose MAP framework designed to tackle problems of any coupling levels under incomplete information. Agents in our MAP model are partially unaware of the information managed by the rest of agents and share only the critical information that affects other agents, thus maintaining a distributed vision of the task. Agents solve MAP tasks through the adoption of an iterative refinement planning procedure that uses single-agent planning technology. In particular, agents will devise refinements through the partial-order planning paradigm, a flexible framework to build refinement plans leaving unsolved details that will be gradually completed by means of new refinements. Our proposal is supported with the implementation of a fully operative MAP system and we show various experiments when running our system over different types of MAP problems, from the most strongly related to the most loosely coupled.This work has been partly supported by the Spanish MICINN under projects Consolider Ingenio 2010 CSD2007-00022 and TIN2011-27652-C03-01, and the Valencian Prometeo project 2008/051.Torreño Lerma, A.; Onaindia De La Rivaherrera, E.; Sapena Vercher, O. (2014). A flexible coupling approach to multi-agent planning under incomplete information. 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Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 1

Polo-like kinase-1 (Plk1) has a pivotal role in cell proliferation and is considered a potential target for anticancer therapy. The noncatalytic polo-box domain (PBD) of Plk1 forms a phosphoepitope binding module for protein-protein interaction. Here, we report the identification of minimal phosphopeptides that specifically interact with the PBD of human PLK1, but not those of the closely related PLK2 and PLK3. Comparative binding studies and analyses of crystal structures of the PLK1 PBD in complex with the minimal phosphopeptides revealed that the C-terminal SpT dipeptide functions as a high-affinity anchor, whereas the N-terminal residues are crucial for providing specificity and affinity to the interaction. Inhibition of the PLK1 PBD by phosphothreonine mimetic peptides was sufficient to induce mitotic arrest and apoptotic cell death. The mode of interaction between the minimal peptide and PBD may provide a template for designing therapeutic agents that target PLK1.National Institutes of Health (U.S.) (Grant R01 GM60594)National Cancer Institute (U.S.)National Institutes of Health (U.S.) (Contract N01-CO-12400)National Institutes of Health (U.S.) (HHSN261200800001E

Serendipitous alkylation of a Plk1 ligand uncovers a new binding channel

We obtained unanticipated synthetic byproducts from alkylation of the δ[superscript 1] nitrogen (N3) of the histidine imidazole ring of the polo-like kinase-1 (Plk1) polo-box domain (PBD)-binding peptide PLHSpT. For the highest-affinity byproduct, bearing a C[subscript 6]H[subscript 5](CH[subscript 2])[subscript 8]– group, a Plk1 PBD cocrystal structure revealed a new binding channel that had previously been occluded. An N-terminal PEGylated version of this peptide containing a hydrolytically stable phosphothreonyl residue (pT) bound the Plk1 PBD with affinity equal to that of the non-PEGylated parent but showed markedly less interaction with the PBDs of the two closely related proteins Plk2 and Plk3. Treatment of cultured cells with this PEGylated peptide resulted in delocalization of Plk1 from centrosomes and kinetochores and in chromosome misalignment that effectively induced mitotic block and apoptotic cell death. This work provides insights that might advance efforts to develop Plk1 PBD-binding inhibitors as potential Plk1-specific anticancer agents.National Institutes of Health (U.S.) (Grant GM60594)National Institutes of Health (U.S.) (Grant GM68762)National Institutes of Health (U.S.) (Grant CA112967