Pregnancy outcomes of forced migrants in the Netherlands: A national registry-based study.

Background: The rise of global forced migration urges healthcare systems to respond to the needs of forced migrants (FM) during pregnancy and childbirth. Yet, comprehensive data on the health outcomes of pregnant FM in destination countries remain scarce. This study aimed to describe the characteristics and maternal and perinatal outcomes of pregnancy in this specific migrant population on a national scale in the Netherlands and to explore differences from other populations. Methods: The Dutch perinatal registry was linked to national migration data to analyze pregnancy outcomes in FM (2014-2019), using non-migrants (NM) and resident migrants (RM) as reference populations. We reported outcome rates (% [95 % CI]) for a range of primary and secondary pregnancy outcomes. Primary outcomes included perinatal mortality, small for gestational age infants (SGA), preterm birth, and emergency cesarean section (CS), for which we also calculated the crude relative risk (RR [95 % CI]) of FM compared to NM and RM. In addition, we conducted binary logistic regression analyses on primary outcomes to report adjusted odds ratios (aORs [95 % CIs]) while controlling for multiple births, maternal age and parity. Findings: Compared to the NM group, the FM group had increased risks of perinatal mortality (RR 1.50 [95 % CI 1.20-1.88]), SGA (1.65 [1.59-1.71], and emergency CS (1.19 [1.13-1.25]). Compared to RM, FM still had elevated risks of SGA (1.17 [1.13-1.22]). In contrast, the risk of preterm birth was lower in FM than in NM (0.81 [0.76-0.86]) and RM (0.83 [0.77-0.88]). These differences were confirmed in the adjusted analysis. Differences in secondary outcomes included higher rates of late antenatal care in FM (29.4 % [28.5-30.3]) than in NM (6.7 % [6.6-6.9]) and RM (15.5 % [15.1-15.9]). Rates of planned CS were similarly elevated (14.3 % [95 % CI 13.7-14.8] versus 7.·8 % [7.7-7.8] and 9.6 % [9.5-9.7]), while FM had lower rates of postpartum hemorrhage (3.9 % [3.6-4.2]) versus 6.8 % [6.8-6.9] and 5.7 % [5.6-5.9]). Conclusion: This first Dutch registry-based study demonstrated increased risks of multiple, though not all, adverse pregnancy outcomes in forced migrants. Our results emphasize the imperative to further unravel and address migration-related disparities, dismantle structural barriers to health among forced migrants, and improve the inclusivity of data systems. Collaborative policy, clinical practice, and research efforts are essential to ensure equitable care for every individual, regardless of migration status.

The cellular Potts model on disordered lattices.

The cellular Potts model, also known as the Glazier-Graner-Hogeweg model, is a lattice-based approach by which biological tissues at the level of individual cells can be numerically studied. Traditionally, a square or hexagonal underlying lattice structure is assumed for two-dimensional systems, and this is known to introduce artifacts in the structure and dynamics of the model tissues. That is, on regular lattices, cells can assume shapes that are dictated by the symmetries of the underlying lattice. Here, we developed a variant of this method that can be applied to a broad class of (ir)regular lattices. We show that on an irregular lattice deriving from a fluid-like configuration, two types of artifacts can be removed. We further report on the transition between a fluid-like disordered and a solid-like hexagonally ordered phase present for monodisperse confluent cells as a function of their surface tension. This transition shows the hallmarks of a first-order phase transition and is different from the glass/jamming transitions commonly reported for the vertex and active Voronoi models. We emphasize this by analyzing the distribution of shape parameters found in our state space. Our analysis provides a useful reference for the future study of epithelia using the (ir)regular cellular Potts model.

Inhibiting the NADase CD38 improves cytomegalovirus-specific CD8+ T cell functionality and metabolism.

Cytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in people who are immunocompromised, such as kidney transplant recipients (KTRs). The exact mechanisms underlying the disability of cytotoxic T cells to provide sufficient protection against CMV in people who are immunosuppressed have not been identified yet. Here, we performed in-depth metabolic profiling of CMV-specific CD8+ T cells in patients who are immunocompromised and show the development of metabolic dysregulation at the transcriptional, protein, and functional level of CMV-specific CD8+ T cells in KTRs with noncontrolled CMV infection. These dysregulations comprise impaired glycolysis and increased mitochondrial stress, which is associated with an intensified expression of the nicotinamide adenine dinucleotide nucleotidase (NADase) CD38. Inhibiting NADase activity of CD38 reinvigorated the metabolism and improved cytokine production of CMV-specific CD8+ T cells. These findings were corroborated in a mouse model of CMV infection under conditions of immunosuppression. Thus, dysregulated metabolic states of CD8+ T cells could be targeted by inhibiting CD38 to reverse hyporesponsiveness in individuals who fail to control chronic viral infection.

Exploring patients' experience using PROMs within routine post-discharge follow-up assessment after stroke: a mixed methods approach.

BACKGROUND: Patient Reported Outcomes Measures (PROMs) are being used increasingly to measure health problems in stroke clinical practice. However, the implementation of these PROMs in routine stroke care is still in its infancy. To understand the value of PROMs used in ischemic stroke care, we explored the patients' experience with PROMs and with the consultation at routine post-discharge follow-up after stroke. METHODS: In this prospective mixed methods study, patients with ischemic stroke completed an evaluation questionnaire about the use of PROMs and about their consultation in two Dutch hospitals. Additionally, telephone interviews were held to gain in-depth information about their experience with PROMs. RESULTS: In total, 63 patients completed the evaluation questionnaire of which 10 patients were also interviewed. Most patients (82.2-96.6%) found completing the PROMs to be feasible and relevant. Half the patients (49.2-51.6%) considered the PROMs useful for the consultation and most patients (87.3-96.8%) reported the consultation as a positive experience. Completing the PROMs provided 51.6% of the patients with insight into their stroke-related problems. Almost 75% of the patients found the PROMs useful in giving the healthcare provider greater insight, and 60% reported discussing the PROM results during the consultation. Interviewed patients reported the added value of PROMs, particularly when arranging further care, in gaining a broader insight into the problems, and in ensuring all important topics were discussed during the consultation. CONCLUSIONS: Completing PROMs appears to be feasible for patients with stroke attending post-discharge consultation; the vast majority of patients experienced added value for themselves or the healthcare provider. We recommend that healthcare providers discuss the PROM results with their patients to improve the value of PROMs for the patient. This could also improve the willingness to complete PROMs in the future.

Delayed vaccine-induced CD8+ T cell expansion by topoisomerase I inhibition mediates enhanced CD70-dependent tumor eradication.

BACKGROUND: The survival of patients with cervical cancer who are treated with cisplatin in conjunction with the topoisomerase I inhibitor topotecan is enhanced when compared with patients treated with only one of these chemotherapeutics. Moreover, cisplatin-based and T cell-based immunotherapy have been shown to synergize, resulting in stronger antitumor responses. Here, we interrogated whether topotecan could further enhance the synergy of cisplatin with T cell-based cancer immunotherapy. METHODS: Mice bearing human papilloma virus 16 (HPV16) E6/E7-expressing TC-1 tumors were vaccinated with HPV16 E7 long peptides and additionally received chemotherapy consisting of cisplatin and topotecan. We performed an in-depth study of this combinatorial chemoimmunotherapy on the effector function and expansion/contraction kinetics of vaccine-induced CD8+ T cells in the peripheral blood and tumor microenvironment (TME). In addition, we interrogated the particular role of chemotherapy-induced upregulation of costimulatory ligands by tumor-infiltrated myeloid cells on T cell proliferation and survival. RESULTS: We show that E7 long peptide vaccination combined with cisplatin and topotecan, results in CD8+ T cell-dependent durable rejection of established tumors and 94% long-term survival. Although topotecan initially repressed the expansion of vaccine-induced CD8+ T cells, these cells eventually expanded vigorously, which was followed by delayed contraction. These effects associated with the induction of the proliferation marker Ki-67 and the antiapoptosis molecule Bcl-2 by intratumoral tumor-specific CD8+ T cells, which was regulated by topotecan-mediated upregulation of the costimulatory ligand CD70 on myeloid cells in the TME. CONCLUSIONS: Taken together, our data show that although treatment with cisplatin, topotecan and vaccination initially delays T cell expansion, this combinatorial therapy results eventually in a more robust T cell-mediated tumor eradication due to enhancement of costimulatory molecules in the TME.

Immunophenotyping beyond the limits of time.

Immunophenotyping is a powerful approach for deciphering responses of the immune system to drug screening and immunotherapy. In this issue of Cell Report Methods, Liechti et al. have advanced this approach by developing a pipeline, which allows high-throughput but still accurate single-cell immunophenotyping in time.

Hydrodynamic lubrication in colloidal gels.

Colloidal gels are elasto-plastic materials composed of an out-of-equilibrium, self-assembled network of micron-sized (solid) particles suspended in a fluid. Recent work has shown that far-field hydrodynamic interactions do not change gel structure, only the rate at which the network forms and ages. However, during gel formation, the interplay between short-ranged attractions leading to gelation and equally short-ranged hydrodynamic lubrication interactions remains poorly understood. Here, we therefore study gelation using a range of hydrodynamic descriptions: from single-body (Brownian Dynamics), to pairwise (Rotne-Prager-Yamakawa), to (non-)lubrication-corrected many-body (Stokesian Dynamics). We confirm the current understanding informed by simulations accurate in the far-field. Yet, we find that accounting for lubrication can strongly impact structure at low colloid volume fraction. Counterintuitively, strongly dissipative lubrication interactions also accelerate the aging of a gel, irrespective of colloid volume fraction. Both elements can be explained by lubrication forces facilitating collective dynamics and therefore phase-separation. Our findings indicate that despite the computational cost, lubricated hydrodynamic modeling with many-body far-field interactions is needed to accurately capture the evolution of the gel structure.

Acquired hypothalamic dysfunction in childhood: 'what do patients need?' - an Endo-ERN survey.

Objective: Hypothalamic dysfunction is a rare condition and can be encountered in patients who have been diagnosed or treated for a suprasellar brain tumor. Due to its rarity, the signs and symptoms of hypothalamic dysfunction may be difficult to recognize, leading to delayed diagnosis of the suprasellar brain tumor or to difficulties in finding the health-care expertise for hypothalamic dysfunction after tumor treatment. To improve the care and outcome of patients with acquired hypothalamic dysfunction, professionals are required to understand the patient's needs. Design: A worldwide online survey was distributed from April 2022 to October 2022 to patients with childhood-onset hypothalamic dysfunction (as reported by the patient) following a brain tumor. Methods: Patients were notified about the survey through patient advocacy groups, the SIOPe craniopharyngioma working group and the Endo-ERN platform. Results: In total, 353 patients with hypothalamic dysfunction following craniopharyngioma (82.2%), low-grade glioma (3.1%) or a pituitary tumor (8.2%) or caregivers responded to the survey. Sixty-two percent had panhypopituitarism. Obesity (50.7%) and fatigue (48.2%) were considered the most important health problems. Unmet needs were reported for help with diet, exercise and psychosocial issues. Patients' suggestions for future research include new treatments for hypothalamic obesity and alternative ways for hormone administration. Conclusions: According to the patient's perspective, care for acquired hypothalamic dysfunction can be improved if delivered by experts with a holistic view of the patient in a multidisciplinary setting with a focus on quality of life. Future care and research on hypothalamic dysfunction must integrate the patients' unmet needs. Significance statement: Patients with hypothalamic dysfunction may experience a variety of symptoms, which are not always adequately recognized or addressed. In previous papers, the perspective of caregivers of children with craniopharyngioma has been reported (Klages et al. 2022, Craven et al. 2022). Now we address the patients' perspective on acquired hypothalamic dysfunction using an Endo-ERN global survey. According to the patients' perspective, care can be improved, with needs for improvement in the domains of obesity, fatigue and lifestyle. Research may focus on ways to improve hypothalamic obesity and alternative ways for hormone administration. Ideally, care should be delivered by doctors who have a holistic view of the patient in a multidisciplinary expert team. The results of this study can be used to formulate best practices for clinical care and to design future research proposals.

Community midwives' perspectives on perinatal care for asylum seekers and refugees in the Netherlands: A survey study.

BACKGROUND: The rise of forced migration worldwide compels birth care systems and professionals to respond to the needs of women giving birth in these vulnerable situations. However, little is known about the perspective of midwifery professionals on providing perinatal care for forcibly displaced women. This study aimed to identify challenges and target areas for improvement of community midwifery care for asylum seekers (AS) and refugees with a residence permit (RRP) in the Netherlands. METHODS: For this cross-sectional study, data were collected through a survey aimed at community care midwives who currently work or who have worked with AS and RRP. We evaluated challenges identified through an inductive thematic analysis of respondents' responses to open-ended questions. Quantitative data from close-ended questions were analyzed descriptively and included aspects related to the quality and organization of perinatal care for these groups. RESULTS: Respondents generally considered care for AS and RRP to be of lower quality, or at best, equal quality compared to care for the Dutch population, while the workload for midwives caring for these groups was considered higher. The challenges identified were categorized into five main themes, including: 1) interdisciplinary collaboration; 2) communication with clients; 3) continuity of care; 4) psychosocial care; and 5) vulnerabilities among AS and RRP. CONCLUSIONS: Findings suggest that there is considerable opportunity for improvement in perinatal care for AS and RRP, while also providing direction for future research and interventions. Several concerns raised, especially the availability of professional interpreters and relocations of AS during pregnancy, require urgent consideration at legislative, policy, and practice levels.

Structuring colloidal gels via micro-bubble oscillations.

Locally (re)structuring colloidal gels - micron-sized particles forming a connected network with arrested dynamics - can enable precise tuning of the micromechanical and -rheological properties of the system. A recent experimental study [B. Saint-Michel, G. Petekidis, and V. Garbin, Soft Matter, 2022, 18, 2092] showed that local ordering can be rapidly induced by acoustically modulating an embedded microbubble. Here, we perform Brownian dynamics simulations to understand the mechanical effect of an oscillating microbubble on the next-to-bubble structure of the embedding colloidal gel. Our simulations reveal hexagonal-close-packed structures over a range that is comparable to the amplitude of the oscillations. However, we were unable to reproduce the unexpectedly long-ranged modification of the gel structure - dozens of amplitudes - observed in experiment. This suggests including long-ranged effects, such as fluid flow, should be considered in future computational work.

Complexity and interplay of faced adversities and perceived health and well-being in highly vulnerable pregnant women-the Mothers of Rotterdam program.

BACKGROUND: Living in socially disadvantaged circumstances has a widespread impact on one's physical and mental health. That is why individuals living in this situation are often considered vulnerable. When pregnant, not only the woman's health is affected, but also that of her (unborn) child. It is well accepted that vulnerable populations experience worse (perinatal) health, however, little is known about the lived adversities and health of these vulnerable individuals. OBJECTIVES: With this article, insights into this group of highly vulnerable pregnant women are provided by describing the adversities these women face and their experienced well-being. METHODS: Highly vulnerable women were recruited when referred to tailored social care during pregnancy. Being highly vulnerable was defined as facing at least three different adversities divided over two or more life-domains. The heat map method was used to assess the interplay between adversities from the different life domains. Demographics and results from the baseline questionnaires on self-sufficiency and perceived health and well-being were presented. RESULTS: Nine hundred nineteen pregnant women were referred to social care (2016-2020). Overall, women had a median of six adversities, distributed over four life-domains. The heat map revealed a large variety in lived adversities, which originated from two parental clusters, one dominated by financial adversities and the other by a the combination of a broad range of adversities. The perceived health was moderate, and 25-34% experienced moderate to severe levels of depression, anxiety or stress. This did not differ between the two parental clusters. CONCLUSIONS: This study shows that highly vulnerable pregnant women deal with multiple adversities affecting not only their social and economic position but also their health and well-being.

Adaptability and learning Intraprofessional collaboration of residents during the COVID-19 pandemic.

CONTEXT: The COVID-19 pandemic created a worldwide public health emergency, in which hospitals created new COVID departments and doctors from different disciplines had to work together. In the Netherlands, a large proportion of doctors in these departments were residents. With knowledge of the disease developing only gradually, the influx of COVID-19 patients called for adaptability, innovative work behavior, and intraprofessional collaboration (intraPC) between residents and between residents and medical specialists. RESEARCH GOAL: This study investigates how the delivery of COVID-19 care in hospital settings altered the way residents develop their sense of adaptability and intraPC during their training. METHODS: Sixteen semi-structured interviews were conducted with residents and medical specialists from various disciplines who worked at a COVID department or Intensive Care Unit (ICU) during the COVID pandemic in the Netherlands, focusing on adaptability and intraPC learning. Transcripts were analyzed using (thematic) template analysis. RESULTS: Four themes that influenced learning during COVID care were identified: collective uncertainty, social cohesion and a sense of safety, the need for adaptive performance and intraPC learning. During the first wave, collective uncertainty about the unknown disease and the continuation of the crisis urged residents to adapt in order to take care of patients with a disease that was as yet unknown. The combination of collective uncertainty, social cohesion and a sense of safety, and the presence of different disciplines in one department promoted residents' intraPC learning. However, intraPC learning was not always the matter of course due to the scope of the crisis and the huge numbers of new patients. CONCLUSION: Collective uncertainty affected the residents' adaptability. The combination of collective uncertainty, social cohesion, and the presence of different disciplines in one department promoted the residents' intraPC learning. An important facilitating factor for both adaptability and intraPC learning is a high level of social cohesion and safety. The physical and psychological proximity of supervisors is an important factor contributing to a safe learning environment. This study provides implications for practice for learning during postgraduate training in non-crisis settings.

Understanding enhanced rotational dynamics of active probes in rod suspensions.

Active Brownian particles (APs) have recently been shown to exhibit enhanced rotational diffusion (ERD) in complex fluids. Here, we experimentally observe ERD and numerically corroborate its microscopic origin for a quasi-two-dimensional suspension of colloidal rods. At high density, the rods form small rafts, wherein they perform small-amplitude, high-frequency longitudinal displacements. Activity couples AP-rod contacts to reorientation, with the variance therein leading to ERD. This is captured by a local, rather than a global relaxation time, as used in previous phenomenological modeling. Our result should prove relevant to the microrheological characterization of complex fluids and furthering our understanding of the dynamics of microorganisms in such media.

Comparison between intratumoral and intravenously administered oncolytic virus therapy with Newcastle disease virus in a xenograft murine model for pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor clinical prognosis and is usually a metastatic disease. In the last decades, oncolytic viro-immunotherapy has shown a promise as treatment strategy with encouraging results for a variety of tumors. Newcastle Disease Virus (NDV) is an oncolytic virus which selectively infects and damages tumors either by directly killing tumor cells or by promoting an anti-tumor immune response. Several studies have demonstrated that NDV strains with a multi-basic cleavage site (MBCS) in the fusion protein (F) have increased anti-tumor efficacy upon intratumoral injection in murine tumor models. However, intravenous injections, in which the oncolytic virus spreads systemically, could be more beneficial to treat metastasized PDAC in addition to the primary tumor. In this study, we compared the oncolytic efficacy and safety of intratumoral and intravenous injections with NDV containing an MBCS in F (NDV F3aa) in an immune deficient murine xenograft (BxPC3) model for PDAC. In this model, both intratumoral and intravenous injections with NDV F3aa induced anti-tumor efficacy as measured at 10 days after the first injection. Upon intravenous injection virus was detected in some of the tumors, indicating the systemic spread of the virus. Upon both treatments, mice did not display weight loss or abnormalities and treated mice did not secrete virus to the environment. These data demonstrate that intravenous injections of NDV F3aa can be applicable to treat metastasized cancers in immune deficient hosts without inflicting adverse effects.

A tailored intervention does not reduce low value MRI's and arthroscopies in degenerative knee disease when the secular time trend is taken into account: a difference-in-difference analysis.

PURPOSE: To evaluate the effectiveness of a tailored intervention to reduce low value MRIs and arthroscopies among patients ≥ 50 years with degenerative knee disease in 13 Dutch orthopaedic centers (intervention group) compared with all other Dutch orthopaedic centers (control group). METHODS: All patients with degenerative knee disease ≥ 50 years admitted to Dutch orthopaedic centers from January 2016 to December 2018 were included. The tailored intervention included participation of clinical champions, education on the Dutch Choosing Wisely recommendation for MRI's and arthroscopies in degenerative knee disease, training of orthopaedic surgeons to manage patient expectations, performance feedback, and provision of a patient brochure. A difference-in-difference analysis was used to compare the time trend before (admitted January 2016-June 2017) and after introduction of the intervention (July 2017-December 2018) between intervention and control hospitals. Primary outcome was the monthly percentage of patients receiving a MRI or knee arthroscopy, weighted by type of hospital. RESULTS: 136,446 patients were included, of whom 32,163 were treated in the intervention hospitals. The weighted percentage of patients receiving a MRI on average declined by 0.15% per month (ß = - 0.15, P < 0.001) and by 0.19% per month for arthroscopy (ß = - 0.19, P < 0.001). However, these changes over time did not differ between intervention and control hospitals, neither for MRI (ß = - 0.74, P = 0.228) nor arthroscopy (ß = 0.13, P = 0.688). CONCLUSIONS: The extent to which patients ≥ 50 years with degenerative knee disease received a MRI or arthroscopy declined significantly over time, but could not be attributed to the tailored intervention. This secular downward time trend may reflect anoverall focus of reducing low value care in The Netherlands. LEVEL OF EVIDENCE: III.

Assessment of the virulence for chickens of Newcastle Disease virus with an engineered multi-basic cleavage site in the fusion protein and disrupted V protein gene.

Newcastle Disease virus (NDV) has shown promise as an oncolytic virus for treatment of a wide range of tumours. NDV with a multi-basic cleavage site (MBCS) in the fusion (F) protein (NDV F3aa) has increased oncolytic efficacy in several tumour models, but also increased virulence in chickens compared to non-virulent NDV F0, raising potential environmental safety issues. Previously, we generated a variant of NDV F3aa with a disrupted V protein gene and a substitution of phenylalanine to serine at position 117 of the F protein (NDV F3aa-S-STOPV). Compared to NDV F3aa this virus had decreased virulence in embryonated chicken eggs. In this study, the virulence of the virus was evaluated upon inoculation of six-week-old chickens through a natural infection route and by determination of the intracerebral pathogenicity index (ICPI). Based on these data NDV F3aa-S-STOPV classified as a non-virulent virus. Although NDV F3aa was classified as a virulent virus based on the ICPI, the virus was also less pathogenic than NDV F0 upon inoculation of six-week-old chickens. These data indicate that NDV with a MBCS is not necessarily pathogenic in chickens. In addition, these data show that F3aa-S-STOPV is safe to use in viro-immunotherapies without posing a threat for chickens upon accidental exposure.

Optimizing environmental safety and cell-killing potential of oncolytic Newcastle Disease virus with modifications of the V, F and HN genes.

Newcastle Disease Virus (NDV) is an avian RNA virus, which was shown to be effective and safe for use in oncolytic viral therapy for several tumour malignancies. The presence of a multi basic cleavage site (MBCS) in the fusion protein improved its oncolytic efficacy in vitro and in vivo. However, NDV with a MBCS can be virulent in poultry. We aimed to develop an NDV with a MBCS but with reduced virulence for poultry while remaining effective in killing human tumour cells. To this end, the open reading frame of the V protein, an avian specific type I interferon antagonist, was disrupted by introducing multiple mutations. NDV with a mutated V gene was attenuated in avian cells and chicken and duck eggs. Although this virus still killed tumour cells, the efficacy was reduced compared to the virulent NDV. Introduction of various mutations in the fusion (F) and hemagglutinin-neuraminidase (HN) genes slightly improved this efficacy. Taken together, these data demonstrated that NDV with a MBCS but with abrogation of the V protein ORF and mutations in the F and HN genes can be safe for evaluation in oncolytic viral therapy.

Development of a Blueprint for Integrated Care for Vulnerable Pregnant Women.

PURPOSE: There has been increasing awareness of perinatal health and organisation of maternal and child health care in the Netherlands as a result of poor perinatal outcomes. Vulnerable women have a higher risk of these poor perinatal outcomes and also have a higher chance of receiving less adequate care. Therefore, within a consortium, embracing 100 organisations among professionals, educators, researchers, and policymakers, a joint aim was defined to support maternal and child health care professionals and social care professionals in providing adequate, integrated care for vulnerable pregnant women. DESCRIPTION: Within the consortium, vulnerability is defined as the presence of psychopathology, psychosocial problems, and/or substance use, combined with a lack of individual and/or social resources. Three studies focussing on population characteristics, organisation of care and knowledge, skills, and attitudes of professionals regarding vulnerable pregnant women, were carried out. Outcomes were discussed in three field consultations. ASSESSMENT: The outcomes of the studies, followed by the field consultations, resulted in a blueprint that was subsequently adapted to local operational care pathways in seven obstetric collaborations (organisational structures that consist of obstetricians of a single hospital and collaborating midwifery practices) and their collaborative partners. We conducted 12 interviews to evaluate the adaptation of the blueprint to local operational care pathways and its' embedding into the obstetric collaborations. CONCLUSION: Practice-based research resulted in a blueprint tailored to the needs of maternal and child health care professionals and social care professionals and providing structure and uniformity to integrated care provision for vulnerable pregnant women.

The influence of psychological factors and mood on the course of participation up to four years after stroke.

PURPOSE: (1) To explore the course of participation from two months up to four years after stroke, and (2) to examine if adaptive and maladaptive psychological factors and mood measured at two months after stroke are determinants of the course of participation during this period. MATERIALS AND METHODS: Prospective cohort study in which 369 individuals with stroke were assessed at stroke onset, two months, six months, one year, two years and three to four years after stroke. The Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-Participation) restrictions subscale was used to measure participation. Psychological factors were clustered into adaptive (proactive coping, self-efficacy, extraversion and optimism) and maladaptive (passive coping, neuroticism and pessimism) psychological factors. The Hospital Anxiety and Depression Scale was used to assess mood. RESULTS: Although improvements in participation were observed up to one year after stroke, considerable long-term restrictions in social and physical domains persisted. More mood problems and less adaptive psychological factors were independent determinants of worse participation up to four years after stroke. CONCLUSIONS: Participation improves in the first 12 months after stroke and stabilizes afterwards. Mood problems and less adaptive psychological factors negatively influence the course of participation over time up to four years after stroke.Implications for rehabilitationFollow-up assessments after stroke should not only focus on cognitive and motor impairment, but also encompass screening on mood problems and adaptive psychological factors.Implementation of a routine follow-up assessment one year after stroke can be beneficial as restrictions in participation are unlikely to diminish spontaneously from then onwards.

Identification of a novel conserved signaling motif in CD200 receptor required for its inhibitory function.

The inhibitory signaling of CD200 receptor 1 (CD200R) has been attributed to its NPxY signaling motif. However, NPxY-motifs are present in multiple protein families and are mostly known to mediate protein trafficking between subcellular locations rather than signaling. Therefore, we investigated whether additional motifs specify the inhibitory function of CD200R. We performed phylogenetic analysis of the intracellular domain of CD200R in mammals, birds, bony fish, amphibians and reptiles. Indeed, the tyrosine of the NPxY-motif is fully conserved across species, in line with its central role in CD200R signaling. In contrast, P295 of the NPxY-motif is not conserved. Instead, a conserved stretch of negatively charged amino acids, EEDE279, and two conserved residues P285 and K292 in the flanking region prior to the NPxY-motif are required for CD200R mediated inhibition of p-Erk, p-Akt308, p-Akt473, p-rpS6 and LPS-induced IL-8 secretion. Altogether, we show that instead of the more common NPxY-motif, CD200R signaling can be assigned to a unique signaling motif in mammals defined by: EEDExxPYxxYxxKxNxxY.