The Active Recovery Triad (ART) model:A new approach in Dutch long-term mental health care

Unlike developments in short-term clinical and community care, the recovery movement has not yet gained foothold in long-term mental health services. In the Netherlands, approximately 21,000 people are dependent on long-term mental health care and support. To date, these people have benefited little from recovery-oriented care, rather traditional problem-oriented care has remained the dominant approach. Based on the view that recovery is within reach, also for people with complex needs, a new care model for long-term mental health care was developed, the active recovery triad (ART) model. In a period of 2.5 years, several meetings with a large group of stakeholders in the field of Dutch long-term mental health care took place in order to develop the ART model. Stakeholders involved in the development process were mental health workers, policy advisors, managers, directors, researchers, peer workers, and family representatives. The ART model combines an active role for professionals, service users, and significant others, with focus on recovery and cooperation between service users, family, and professionals in the triad. The principles of ART are translated into seven crucial steps in care and a model fidelity scale in order to provide practical guidelines for teams implementing the ART model in practice. The ART model provides guidance for tailored recovery-oriented care and support to this “low-volume high-need” group of service users in long-term mental health care, aiming to alter their perspective and take steps in the recovery process. Further research should investigate the effects of the ART model on quality of care, recovery, and autonomy of service users and cooperation in the triad

Afgraving Hellekens en hermeandering Kleine Nete. Een landschappelijk en archeologisch booronderzoek en een proefsleuvenonderzoek

Dit rapport werd ingediend bij het agentschap samen met een aantal afzonderlijke digitale bijlagen. Een aantal van deze bijlagen zijn niet inbegrepen in dit pdf document en zijn niet online beschikbaar. Sommige bijlagen (grondplannen, fotos, spoorbeschrijvingen, enz.) kunnen van belang zijn voor een betere lezing en interpretatie van dit rapport. Indien u deze bijlagen wenst te raadplegen kan u daarvoor contact opnemen met: [email protected]

Fc galactosylation promotes hexamerization of human IgG1, leading to enhanced classical complement activation

Human IgG contains one evolutionarily conserved N-linked glycan in its Fc region at position 297. This glycan is crucial for Fc-mediated functions, including its induction of the classical complement cascade. This is induced after target recognition through the IgG-Fab regions, allowing neighboring IgG-Fc tails to associate through Fc:Fc interaction, ultimately leading to hexamer formation. This hexamerization seems crucial for IgG to enable efficient interaction with the globular heads of the first complement component C1q and subsequent complement activation. In this study, we show that galactose incorporated in the IgG1-Fc enhances C1q binding, C4, C3 deposition, and complement-dependent cellular cytotoxicity in human erythrocytes and Raji cells. IgG1-Fc sialylation slightly enhanced binding of C1q, but had little effect on downstream complement activation. Using various mutations that decrease or increase hexamerization capacity of IgG1, we show that IgG1-Fc galactosylation has no intrinsic effect on C1q binding to IgG1, but enhances IgG1 hexamerization potential and, thereby, complement activation. These data suggest that the therapeutic potential of Abs can be amplified without introducing immunogenic mutations, by relatively simple glycoengineering.Proteomic

Employing the Gini coefficient to measure participation inequality in treatment-focused Digital Health Social Networks

Digital Health Social Networks (DHSNs) are common; however, there are few metrics that can be used to identify participation inequality. The objective of this study was to investigate whether the Gini coefficient, an economic measure of statistical dispersion traditionally used to measure income inequality, could be employed to measure DHSN inequality. Quarterly Gini coefficients were derived from four long-standing DHSNs. The combined data set included 625,736 posts that were generated from 15,181 actors over 18,671 days. The range of actors (8–2323), posts (29–28,684), and Gini coefficients (0.15–0.37) varied. Pearson correlations indicated statistically significant associations between number of actors and number of posts (0.527–0.835, p < .001), and Gini coefficients and number of posts (0.342–0.725, p < .001). However, the association between Gini coefficient and number of actors was only statistically significant for the addiction networks (0.619 and 0.276, p < .036). Linear regression models had positive but mixed R2 results (0.333–0.527). In all four regression models, the association between Gini coefficient and posts was statistically significant (t = 3.346–7.381, p < .002). However, unlike the Pearson correlations, the association between Gini coefficient and number of actors was only statistically significant in the two mental health networks (t = −4.305 and −5.934, p < .000). The Gini coefficient is helpful in measuring shifts in DHSN inequality. However, as a standalone metric, the Gini coefficient does not indicate optimal numbers or ratios of actors to posts, or effective network engagement. Further, mixed-methods research investigating quantitative performance metrics is required

Creating spatial synergies around food in cities

This paper focusses on the phenomenon of multifunctional urban food initiatives (MUFIs) and how, using food as a vehicle, they provide integrative solutions for a number of social, environmental and economic problems in European cities. Through an in-depth investigation of three MUFIs in the UK, Latvia and Belgium, the paper aims to increase understanding on how different activities are combined within MUFIs, leading to the creation and strengthening of synergies: both internal, between the different activities performed within MUFIs, and external synergies between the MUFI and the (peri-) urban environment in which it operates. The three cases illustrate that the dense and complex urban environment in which they are situated provides possibilities to create a wide, diverse network around food, leading to a high potential for synergies to occur. In this way, MUFIs can respond to specific urban needs, which are not addressed by the state, and therefore have an important signalling function. For the MUFIs themselves, although being multifunctional increases opportunities, it is also a challenge to find the right balance between the different functions and not to lose sight of the economic side of the business. Local governments can support MUFIs by providing space for them, room to experiment, adapting regulations to get MUFIs out of the “grey zones” of legislation, and by starting to strategically think about food in their city region

Non-native hydrophobic interactions detected in unfolded apoflavodoxin by paramagnetic relaxation enhancement

Transient structures in unfolded proteins are important in elucidating the molecular details of initiation of protein folding. Recently, native and non-native secondary structure have been discovered in unfolded A. vinelandii flavodoxin. These structured elements transiently interact and subsequently form the ordered core of an off-pathway folding intermediate, which is extensively formed during folding of this α–β parallel protein. Here, site-directed spin-labelling and paramagnetic relaxation enhancement are used to investigate long-range interactions in unfolded apoflavodoxin. For this purpose, glutamine-48, which resides in a non-native α-helix of unfolded apoflavodoxin, is replaced by cysteine. This replacement enables covalent attachment of nitroxide spin-labels MTSL and CMTSL. Substitution of Gln-48 by Cys-48 destabilises native apoflavodoxin and reduces flexibility of the ordered regions in unfolded apoflavodoxin in 3.4 M GuHCl, because of increased hydrophobic interactions in the unfolded protein. Here, we report that in the study of the conformational and dynamic properties of unfolded proteins interpretation of spin-label data can be complicated. The covalently attached spin-label to Cys-48 (or Cys-69 of wild-type apoflavodoxin) perturbs the unfolded protein, because hydrophobic interactions occur between the label and hydrophobic patches of unfolded apoflavodoxin. Concomitant hydrophobic free energy changes of the unfolded protein (and possibly of the off-pathway intermediate) reduce the stability of native spin-labelled protein against unfolding. In addition, attachment of MTSL or CMTSL to Cys-48 induces the presence of distinct states in unfolded apoflavodoxin. Despite these difficulties, the spin-label data obtained here show that non-native contacts exist between transiently ordered structured elements in unfolded apoflavodoxin

Twelve-Month Follow-up Results from a Randomized Controlled Trial of a Brief Personalized Feedback Intervention for Problem Drinkers

Aims: To examine the impact of a web-based personalized feedback intervention, the Check Your Drinking (CYD; www.CheckYourDrinking.net) screener at 12-month follow-up

Dysregulation of synaptic pruning as a possible link between intestinal microbiota dysbiosis and neuropsychiatric disorders

The prenatal and early postnatal stages represent a critical time window for human brain development. Interestingly, this window partly overlaps with the maturation of the intestinal flora (microbiota) that play a critical role in the bidirectional communication between the central and the enteric nervous systems (microbiota-gut-brain axis). The microbial composition has important influences on general health and the development of several organ systems, such as the gastrointestinal tract, the immune system, and also the brain. Clinical studies have shown that microbiota alterations are associated with a wide range of neuropsychiatric disorders including autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. In this review, we dissect the link between these neuropsychiatric disorders and the intestinal microbiota by focusing on their effect on synaptic pruning, a vital process in the maturation and establishing efficient functioning of the brain. We discuss in detail how synaptic pruning is dysregulated differently in the aforementioned neuropsychiatric disorders and how it can be influenced by dysbiosis and/or changes in the intestinal microbiota composition. We also review that the improvement in the intestinal microbiota composition by a change in diet, probiotics, prebiotics, or fecal microbiota transplantation may play a role in improving neuropsychiatric functioning, which can be at least partly explained via the optimization of synaptic pruning and neuronal connections. Altogether, the demonstration of the microbiota's influence on brain function via microglial-induced synaptic pruning addresses the possibility that the manipulation of microbiota-immune crosstalk represents a promising strategy for treating neuropsychiatric disorders

Increased Th22 cell numbers in a general pediatric population with filaggrin haploinsufficiency: the Generation R Study

Background Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated whether school-aged children with and without FLG mutations have differences in T- and B-cell subsets.Methods This study was embedded in a population-based prospective cohort study, the Generation R Study, and included 523 children of European genetic ancestry aged 10 years. The most common FLG mutations in the European population (R501X, S1085CfsX36, R2447X, and S3247X) were genotyped. Additionally, 11-color flow cytometry was performed on peripheral blood samples to determine helper T (Th), regulatory T (Treg), and CD27(+) and CD27(-) memory B cells. Subset analysis was performed in 358 non-AD and 102 AD cases, assessed by parental questionnaires.Results FLG mutations were observed in 8.4% of the total population and in 15.7% of the AD cases. Children with any FLG mutation had higher Th22 cell numbers compared to FLG wild-type children in the general and non-AD population. Children with and without FLG mutations had no difference in Th1, Th2, Th17, Treg, or memory B-cell numbers. Furthermore, in children with AD, FLG mutation carriership was not associated with differences in T- and B-cell subsets.Conclusions School-aged children of a general population with FLG mutations have higher Th22 cell numbers, which reflects the immunological response to the skin barrier dysfunction. FLG mutations did not otherwise affect the composition of the adaptive immunity in this general pediatric population.Prevention, Population and Disease management (PrePoD)Public Health and primary car

CD40-targeted adenoviral GM-CSF gene transfer enhances and prolongs the maturation of human CML-derived dendritic cells upon cytokine deprivation

Vaccination with autologous leukaemia-derived dendritic cells (DC) presents an adjuvant treatment option for chronic myeloid leukaemia (CML). Here, we show that high-efficiency CD40-targeted adenoviral gene transfer of GM-CSF to CML-derived DC induces long-lived maturation in the absence of exogenous cytokines and may thus ensure protracted stimulation of CML-specific T cells upon vaccination