Bovenschoolse Kenniswerkplaats Gezonde Leefstijl

Onderwijs, onderzoek en werkveld: samenwerking vanuit de bovenschoolse Kenniswerkplaats Gezonde Leefstijl   Achtergrond en doelstelling Het gezondheidsdomein verandert sterk en vraagt van nieuwe gezondheidsprofessionals dat zij in staat zijn om over de grenzen van hun eigen expertise heen te kijken. Binnen de Hanzehogeschool Groningen (HG) leent het speerpunt Healthy Ageing zich voor een multidisciplinaire aanpak van gezondheid: gezond opgroeien en gezond ouder worden vereisen preventieve benaderingen, interventies en begeleiding die gericht zijn op zowel lichaam als geest en waarbij diverse professionals betrokken zijn. Multidisciplinaire kenniswerkplaatsen (KWP’s) zijn een manier om deze samenwerking binnen de HG tot stand te brengen. In deze poster beschrijven we de opzet van de KWP Gezonde leefstijl.   Aanpak en methode van het project  In de KWP Gezonde Leefstijl  hebben docenten van de opleidingen Sport Gezondheid Management, Toegepaste Psychologie, Pabo, Verpleegkunde, Voeding en Diëtetiek en de Academie voor Lichamelijke Opvoeding zitting. Samen met studenten en werkveldpartners werken zij aan multidisciplinaire vraagstukken op het gebied van Gezonde Leefstijl. Dat wil zeggen: vraagstukken die vanuit verschillende vakgebieden bekeken en opgelost kunnen en moeten worden. Kernonderwerpen zijn: gecombineerde leefstijlinterventies, gedragsdeterminanten voor een gezonde leefstijl, en de implementatieprofessional.   Resultaten en opbrengsten Inmiddels is de KWP ruim twee jaar in de lucht. Met een aantal praktijkpartners vindt samenwerking plaats: de gemeente en provincie Groningen, GGD Groningen, Huis voor de Sport Groningen en de Hanzehogeschool zelf. Studenten van verschillende opleiding werken onder andere aan:  (1) de uitvoering van een duurzame inzetbaarheidsinterventie voor Hanze personeel, (2) het ondersteunen van scholen om een vignet Gezonde School aan te vragen en (3) Onderzoek naar Jongeren op Gezond Gewicht in een specifieke gemeente. De studenten komen bij elkaar Communities of Learners, waarin zij kennis en ervaring met elkaar en praktijkpartners uitdelen. Ook zijn diverse minoren gekoppeld aan de KWP.   Conclusies en aanbevelingen De bovenschoolse KWP Gezonde Leefstijl is een meerwaade in het opleiden van de toekomstige T-shaped professional. Ook de projecten hebben baat bij de multidisciplinaire invalshoek en de eerste ervaringen rondom de multidisciplinaire samenwerking in de CoL zijn positief. Toch vormt deze vorm van multidisciplinair samenwerken uitdagingen op organisatorisch vlak: de diversiteit aan opleidingskaders vormt het voornaamste struikelblok. De aaanjaagfunctie van de bovenschoolse KWP is een belangrijke voorwaarde voor samenwerking tussen opleidingen gebleken.    Visuele presentatie: Weergave van relaties tussen opleidingen, werkveldpartners en projecten en hoe deze binnen het onderwijs worden ingevuld

Towards integration of general practitioner posts and accident and emergency departments: a case study of two integrated emergency posts in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Accident and emergency (A&E) departments and general practitioner (GP) posts are often used inappropriately, leading to overcrowding. In the Netherlands, increasingly more integrated emergency posts (IEPs) are being created, integrating the care provided by GP posts and A&E departments, in order to improve the provision of the emergency care.</p> <p>Methods</p> <p>This explorative study compares the efficiency and patient and employee satisfaction in IEPs with those in two GP posts and two A&E departments. To this end, information was retrieved from hospital and GP patient records for the first quarter of the year before and of the year after the creation of IEPs. Patients and employees were sent a questionnaire to measure their satisfaction. Lastly, groups of hospital doctors, GPs, GP assistants, and nurses were interviewed.</p> <p>Results</p> <p>After the creation of IEPs, there was a shift of more than fifteen percent from secondary care to primary care for emergency consultations and waiting/consultation times were shortened by more than ten percent. Compared with the control settings, patients were more satisfied about telephone contact with an IEP, but professionals working at the IEP were less satisfied with several aspects of their work.</p> <p>Conclusion</p> <p>IEPs could be a promising innovation to organize emergency care more efficiently; however, it might take time to convince professionals of the possible advantages. Studies involving more IEPs and longer follow-up times are needed to determine whether such integration should be stimulated.</p

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

Polymersomes have the potential to encapsulate and deliver chemotherapeutic drugs into tumor cells, reducing off-target toxicity that often compromises anticancer treatment. Here, we assess the ability of the pH-sensitive poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC)- poly 2-(diisopropylamino)ethyl methacrylate (PDPA) polymersomes to encapsulate chemotherapeutic agents for effective combinational anticancer therapy. Polymersome uptake and ability to deliver encapsulated drugs into healthy normal oral cells and oral head and neck squamous cell carcinoma (HNSCC) cells was measured in two and three-dimensional culture systems. PMPC-PDPA polymersomes were more rapidly internalized by HNSCC cells compared to normal oral cells. Polymersome cellular uptake was found to be mediated by class B scavenger receptors. We also observed that these receptors are more highly expressed by cancer cells compared to normal oral cells, enabling polymersome-mediated targeting. Doxorubicin and paclitaxel were encapsulated into pH-sensitive PMPC-PDPA polymersomes with high efficiencies either in isolation or as a dual-load for both singular and combinational delivery. In monolayer culture, only a short exposure to drug-loaded polymersomes was required to elicit a strong cytotoxic effect. When delivered to three-dimensional tumor models, PMPC-PDPA polymersomes were able to penetrate deep into the center of the spheroid resulting in extensive cell damage when loaded with both singular and dual-loaded chemotherapeutics. PMPC-PDPA polymersomes offer a novel system for the effective delivery of chemotherapeutics for the treatment of HNSCC. Moreover, the preferential internalization of PMPC polymersomes by exploiting elevated scavenger receptor expression on cancer cells opens up the opportunity to target polymersomes to tumors

Selective blockade of interferon-α and -β reveals their non-redundant functions in a mouse model of West Nile virus infection

Although type I interferons (IFNs) were first described almost 60 years ago, the ability to monitor and modulate the functional activities of the individual IFN subtypes that comprise this family has been hindered by a lack of reagents. The major type I IFNs, IFN-β and the multiple subtypes of IFN-α, are expressed widely and induce their effects on cells by interacting with a shared heterodimeric receptor (IFNAR). In the mouse, the physiologic actions of IFN-α and IFN-β have been defined using polyclonal anti-type I IFN sera, by targeting IFNAR using monoclonal antibodies or knockout mice, or using Ifnb-/- mice. However, the corresponding analysis of IFN-α has been difficult because of its polygenic nature. Herein, we describe two monoclonal antibodies (mAbs) that differentially neutralize murine IFN-β or multiple subtypes of murine IFN-α. Using these mAbs, we distinguish specific contributions of IFN-β versus IFN-α in restricting viral pathogenesis and identify IFN-α as the key mediator of the antiviral response in mice infected with West Nile virus. This study thus suggests the utility of these new reagents in dissecting the antiviral and immunomodulatory roles of IFN-β versus IFN-α in murine models of infection, immunity, and autoimmunity

A Comparison Of The Microleakage Of Direct Composite Resin Restorations And Composite Resin Inlays - In Vitro

OBJECTIVES: Autoinflammatory disorders are disorders of the innate immune system. Standard genetic testing provided no correct diagnosis in a female patient from a non-consanguineous family of British descent with a colchicine-responsive autosomal dominant periodic fever syndrome. We aimed to unravel the genetic cause of the symptoms. METHODS: Whole exome sequencing was used to screen for novel sequence variants, which were validated by direct Sanger sequencing. Ex vivo stimulation with peripheral blood mononuclear cells was performed to study the functional consequences of the mutation. mRNA and cytokine levels were measured by quantitative PCR and ELISA, respectively. RESULTS: Whole exome sequencing revealed a novel missense sequence variant, not seen in around 6800 controls, mapping to exon 8 of the MEFV gene (c.1730C>A; p.T577N), co-segregating perfectly with disease in this family. Other mutations at the same amino acid (c.1730C>G; p.T577S and c.1729A>T; p.T577S) were found in a family of Turkish descent, with autosomal dominant inheritance of familial Mediterranean fever (FMF)-like phenotype, and a Dutch patient, respectively. Moreover, a mutation (c.1729A>G; p.T577A) was detected in two Dutch siblings, who had episodes of inflammation of varying severity not resembling FMF. Peripheral blood mononuclear cells from one patient of the index family showed increased basal interleukin 1β mRNA levels and cytokine responses after lipopolysaccharide stimulation. Responses normalised with colchicine treatment. CONCLUSIONS: Heterozygous mutations at amino acid position 577 of pyrin can induce an autosomal dominant autoinflammatory syndrome. This suggests that T577, located in front of the C-terminal B30.2/SPRY domain, is crucial for pyrin function

Neurological phenotype of ADA2 deficient patients:a cohort study

BACKGROUND: Patients with adenosine deaminase 2 (ADA2) deficiency can present with various neurological manifestations due to vasculopathies and autoinflammation. These include ischemic and hemorrhagic stroke, but less clearly defined neurological symptoms have also been reported.METHODS: In this cohort study, we included patients with confirmed ADA2 deficiency from seven university hospitals in the Netherlands. We analyzed the frequency and recurrence rates of neurological manifestations before and after initiation of TNF-α inhibiting therapy.RESULTS: We included 29 patients with a median age at presentation of 5 years (IQR: 1-17). Neurological manifestations occurred in 19/29 (66%) patients and were the presenting symptom in 9/29 (31%) patients. TIA/ischemic stroke occurred in 12/29 (41%) patients and was the presenting symptom in 8/29 (28%) patients. In total, 25 TIAs/ischemic strokes occurred in 12 patients; one after initiation of TNF-α inhibiting therapy and one while switching between TNF-α inhibitors. None were large-vessel occlusion strokes. Two hemorrhagic strokes occurred: one aneurysmatic subarachnoid hemorrhage and one spontaneous intracerebral hemorrhage. Most neurological symptoms, including cranial nerve deficits, vertigo, ataxia and seizures, were caused by TIAs/ischemic strokes and seldom recurred after initiation of TNF-α inhibiting therapy.CONCLUSIONS: Neurological manifestations, especially TIA/ischemic stroke, are common in patients with ADA2 deficiency and frequently are the presenting symptom. Because it is a treatable cause of young stroke, for which antiplatelet and anticoagulant therapy are considered contraindicated, awareness among neurologists and pediatricians is important. Screening for ADA2 deficiency in young patients with small-vessel ischemic stroke without an identified cause should be considered.</p

Clinical Symptoms, Laboratory Parameters and Long-Term Follow-up in a National DADA2 Cohort

Deficiency of adenosine deaminase-2 (DADA2) is an autosomal recessive autoinflammatory disease with an extremely variable disease presentation. This paper provides a comprehensive overview of the Dutch DADA2 cohort. We performed a retrospective cohort study in 29 ADA2-deficient patients from 23 families with a median age at inclusion of 26 years. All patients had biallelic pathogenic variants in the ADA2 gene. The most common clinical findings included cutaneous involvement (79.3%), (hepato)splenomegaly (70.8%) and recurrent infections (58.6%). Stroke was observed in 41.4% of the patients. The main laboratory abnormalities were hypogammaglobulinemia and various cytopenias. Patients presented most often with a mixed phenotype involving vasculopathy, immunodeficiency and hematologic manifestations (62.1%). In this cohort, malignancies were reported in eight patients (27.6%), of whom five presented with a hematologic malignancy and two with a basal cell carcinoma. Four patients developed hemophagocytic lymphohistiocytosis (HLH) or an HLH-like episode, of whom three passed away during or shortly after the occurrence of HLH. TNF-inhibitors (TNFi) were effective in treating vasculopathy-associated symptoms and preventing stroke, but were hardly effective in the treatment of hematologic manifestations. Three patients underwent hematopoietic cell transplantation and two of them are doing well with complete resolution of DADA2-related symptoms. The overall mortality in this cohort was 17.2%. In conclusion, this cohort describes the clinical, genetic and laboratory findings of 29 Dutch DADA2 patients. We describe the occurrence of HLH as a life-threatening disease complication and report a relatively high incidence of malignancies and mortality

Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer: Results of a Retrospective, Single-Institution Study

OBJECTIVE: Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome “resistance” in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting. METHODS: Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively. RESULTS: Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses. CONCLUSIONS: Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after first-line platinum-taxane treatment