•Forensic psychiatric patients with ASD and/or ID are willing to use biocueing.•Biocueing may help to recognize changes in arousal (both stress and calmness).•The ability to personalize biocueing ...settings to the patients’ needs is important.•There is a need for embedding biocueing interventions within treatment.•Simple and direct explanations on what biocueing can(not) do must be provided.
Autism spectrum disorder (ASD) and intellectual disability (ID) are prevalent in forensic psychiatric samples. People with ASD and/or ID often experience difficulties in emotion processing which can lead to aggressive or self-harming behavior. The use of biocueing (using wearable technology to constantly monitor and provide feedback on bodily changes) shows promise for improving emotion processing and, thus, potentially reducing aggressive behavior in this population. Both qualitative and quantitative methods were used to examine the feasibility and acceptance of Sense-IT, a biocueing application, in a sample of forensic psychiatric patients with ASD and/or ID and their forensic psychiatric nurses. To our knowledge, the current study is the first to examine first-person experiences with biocueing in forensic psychiatric patients with ASD and/or ID. Results show that, in general, participants experienced the biocueing application as positive and are willing to use biocueing. This is an important finding since forensic patients are often unmotivated to engage with therapeutic techniques. An exploration of trends in aggression and self-harm prior to and during the use of biocueing showed no significant changes. Future research should focus on the way biocueing can be implemented in clinical practice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
Patients with autism spectrum disorder (ASD) are overrepresented in forensic samples. However, research on risk assessment in forensic patients with ASD is scarce. The purpose of this paper ...was to examine the prevalence of short-term inpatient aggression and explore the risk and protective factors for aggression in forensic psychiatric patients with ASD (N = 32).
Design/methodology/approach
The association between two commonly used violence risk assessment instruments (HKT-R and SAPROF) and physical aggression during ten weeks of inpatient stay was examined in a Dutch forensic psychiatric hospital.
Findings
Results showed no significant association between HKT-R and SAPROF and incidents of physical aggression. This suggests that the commonly used assessment instruments may be of limited use for assessing the risk of short-term inpatient aggression in patients with ASD.
Research limitations/implications
Limitations to the current study include the relatively small sample size and the lack of information on index offenses. Further research with a larger, more homogeneous sample and longer follow-up is indicated to confirm the results of this study. Future research should also include the possible association between aggressive behavior of people with ASD and other factors that might be relevant, such as social cognition deficits, cognitive and sensory impairments, deficient empathy and emotion regulation problems.
Originality/value
To the authors’ knowledge, this is the first study to directly examine the prevalence of inpatient aggression of forensic psychiatric patients with ASD and its association with risk and protective factors.
•Deep hypothermia leads to a higher microglial activation than mild hypothermia.•Mild hypothermia induces the expression of cold-shock proteins.•Mild hypothermia may have advantages over deep ...hypothermia during CPB.
Targeted temperature management (TTM) is considered to be a neuroprotective strategy during cardiopulmonary bypass (CPB) assisted procedures, possibly through the activation of cold shock proteins. We therefore investigated the effects of mild compared with deep hypothermia on the neuroinflammatory response and cold shock protein expression after CPB in rats.
Wistar rats were subjected to 1 hr of mild (33 °C) or deep (18 °C) hypothermia during CPB or sham procedure. PET scan analyses using TSPO ligand 11CPBR28 were performed on day 1 (short-term) or day 3 and 7 post-procedure (long-term) to assess neuroinflammation. Hippocampal and cortical samples were obtained at day 1 in the short-term group and at day 7 in the long-term group. mRNA expression of M1 and M2 microglia associated cytokines was analysed with RT-PCR. Cold shock protein RNA-binding motive 3 (RBM3) and tyrosine receptor kinase B (TrkB) receptor protein expression were determined with Western Blot and quantified.
In both groups target temperature was reached within an hour. Standard uptake values (SUV) of 11CPBR28 in CPB rats at 1 day and 3 days were similar to that of sham animals. At 7 days after CPB the SUV was significantly higher in amygdala and hippocampal regions of the CPB 18 °C group as compared to the CPB 33 °C group. No differences were observed in the expression of M1 and M2 microglia-related cytokines between TTM 18 °C and 33 °C. RBM3 protein levels in cortex and hippocampus were significantly higher in CPB 33 °C compared to CPB 18 °C and sham 33 °C, at day 1 and day 7, respectively.
TTM at 18 °C increased the neuroinflammatory response in amygdala and hippocampus compared to TTM at 33 °C in rats undergoing a CPB procedure. Additionally, TTM at 33 °C induced increased expression of TrkB and RBM3 in cortex and hippocampus of rats on CPB compared to TTM at 18 °C. Together, these data indicate that neuroinflammation is alleviated by TTM at 33 °C, possibly by recruiting protective mechanisms through cold shock protein induction.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Anaesthetic agents are likely to alter circulating cytokine concentrations. Because preceding studies have not been able to exclude the contribution of surgical trauma, perioperative stress, or both ...to circulating cytokine concentrations, the effects of anaesthesia remain unclear. The aim of this study was to quantify serum cytokines in healthy volunteers administered i.v. anaesthetic agents in the absence of surgical trauma and perioperative stress.
Serum samples obtained during previous standardised studies from healthy volunteers were compared before and 6–8 h after induction of anaesthesia with propofol (n=31), propofol/remifentanil (n=30), dexmedetomidine (n=17) or dexmedetomidine/remifentanil (n=15). Anaesthetic regimens were standardised and volunteers did not undergo any surgical intervention. Serum concentrations of interleukin (IL)2, IL4, IL6, IL10, IL17, IL18, IL21, IL22, IL23, C-X-C motif ligand 8, interferon gamma, E-selectin, L-selectin, major histocompatibility complex class I chain-polypeptide-related sequence (MIC)A, MICB, Granzyme A, and Granzyme B were quantified using a multiplexed antibody-based assay (Luminex).
Samples were obtained from volunteers of either sex aged 18–70 yr. After anaesthesia with propofol alone, concentrations of IL4 (P=0.012), IL6 (P=0.027), IL21 (P=0.035), IL22 (P=0.002), C-X-C motif ligand 8 (P=0.004), MICB (P=0.046), and Granzyme A (P=0.045) increased. After anaesthesia with propofol and remifentanil, IL17 (P=0.013), interferon gamma (P=0.003), and MICA (P=0.001) decreased, but IL6 (P=0.006) and L-selectin (P=0.001) increased. After dexmedetomidine alone, IL18 (P=0.002), L-selectin (P=0.017), E-selectin (P=0.002), and Granzyme B (P=0.023) decreased. After dexmedetomidine with remifentanil no changes were observed.
In healthy volunteers not undergoing surgery, different i.v. anaesthesia regimens were associated with differential effects on circulating cytokines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IntroductionThe importance of cardiovascular health in relation to pregnancy outcome is increasingly acknowledged. Women who develop certain pregnancy complications, in particular preeclampsia, are ...at higher risk for future cardiovascular disease. Independent of its outcome, pregnancy requires a substantial adaptive response of the maternal cardiovascular system. In the Hemodynamic Adaptation to Pregnancy and Placenta-related Outcome (HAPPO) study, we aim to examine longitudinal maternal haemodynamic adaptation to pregnancy from the preconception period onwards. We hypothesise that women who will develop adverse pregnancy outcomes have impaired cardiovascular health before conception, leading to haemodynamic maladaptation to pregnancy and diminished uteroplacental vascular development.Methods and analysisIn this prospective cohort study embedded in the Rotterdam periconception cohort, 200 women with a history of placenta-related pregnancy complications (high-risk group) and 100 women with an uncomplicated obstetric history (low-risk group) will be included. At five moments (preconception, first, second and third trimester and postdelivery), women will undergo an extensive examination of the macrocirculatory and microcirculatory system and uteroplacental vascular development. The main outcome measures are differences in maternal haemodynamic adaptation to pregnancy between women with and without placenta-related pregnancy complications. In a multivariate linear mixed model, the relationship between maternal haemodynamic adaptive parameters, (utero)placental vascularisation indices and clinical outcomes (occurrence of pregnancy complications, embryonic and fetal growth trajectories, miscarriage rate, gestational age at delivery, birth weight) will be studied. Subgroup analysis will be performed to study baseline and trajectory differences between high-risk and low-risk women, independent of subsequent pregnancy outcome.Ethics and disseminationThis study protocol was approved by the Medical Ethics Committee of the Erasmus MC, Rotterdam, the Netherlands (MEC 2018–150). Results will be disseminated to the medical community by publications in peer-reviewed journals and presentations at scientific congresses. Also, patient associations will be informed and the public will be informed by dissemination through (social) media.Trial registration numberNL7394 (www.trialregister.nl)
Objective: Despite early dietary treatment phenylketonuria patients have lower IQ and poorer executive functions compared to healthy controls. Cognitive problems in phenylketonuria have often been ...associated with phenylalanine levels. The present study examined the cognitive profile and mental health in adult phenylketonuria, in relation to phenylalanine levels and tetrahydrobiopterin treatment. Method: Fifty-seven early treated adult patients with phenylketonuria and 57 healthy matched controls (18-40 years) performed IQ subtests and executive function tests from the Amsterdam Neuropsychological Tasks. They also completed the Adult Self-Report on mental health problems. Analyses of variance were performed to examine group differences. Results: Patients with phenylketonuria had normal IQs although lower than controls. They performed poorer on working memory, inhibitory control, and sustained attention tasks. Patients reported Depressive and Avoidant Personality problems more frequently. Specifically, patients with childhood and lifetime phenylalanine ≥360 μmol/L had poorer cognitive and mental health outcomes than controls. In a subset of patients, comparisons between patients on and off tetrahydrobiopterin showed that nontetrahydrobiopterin users (matched for childhood, pretreatment phenylalanine) were slower (on number of tasks) and reported more mental health problems. Conclusions: Adult patients had lower IQ and poorer executive functions than controls, resembling problems observed in younger patients with phenylketonuria, as well as more internalizing problems. Group differences and phenylalanine-outcome associations were smaller than those observed in younger populations. A subset of nontetrahydrobiopterin users, matched for childhood phenylalanine level, had a poorer outcome on some tests than tetrahydrobiopterin users, which might indicate an impact of tetrahydrobiopterin treatment beyond lowering phenylalanine. However, clinical relevance needs further investigation.
General Scientific Summary
This study examined the cognitive profile and mental health in adult phenylketonuria, in relation to phenylalanine levels and tetrahydrobiopterin treatment. Adult patients had lower IQ and poorer executive functions than controls, resembling problems observed in younger patients with phenylketonuria, as well as more internalizing problems. A subset of nontetrahydrobiopterin users had a poorer outcome on some tests than tetrahydrobiopterin users, which might indicate an impact of tetrahydrobiopterin treatment beyond lowering phenylalanine.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
As cancer is a multifactorial disease, the multimodal action of microRNAs makes them an attractive tool for novel therapeutic approaches. The tumor suppressive miR-7-5p has been shown to act on many ...aspects of oncogenesis, including cell proliferation, migration and angiogenesis, by targeting a spectrum of key genes. We developed a synthetic chemically modified miR-7-5p mimic, 5A2, and performed a comprehensive functional characterization in a panel of human cancer cell lines. 5A2 reduced cell proliferation in most cell lines by inducing cell cycle arrest. To enable systemic delivery of 5A2 to tumors, it was formulated in a novel lipid nanoparticle (INT-5A2) and we demonstrated the anti-tumor activity of INT-5A2 in an experimental human liver tumor-bearing mouse model. Next, RNA-sequencing was used to gain more insight into the molecular mechanism of action of 5A2 and demonstrated a broad repression of target mRNAs. Interestingly, Ingenuity Pathway Analysis revealed a new role for 5A2 in metabolic pathways. Validation experiments
in vitro
showed that 5A2 reduced the expression of key glycolysis and glutaminolysis enzymes, leading to a decrease in glycolysis, lactate secretion and intracellular glutamate availability. Taken together, these data strongly suggest that miR-7-5p/5A2 is a potent tumor suppressor that targets various key cellular pathways across cancer types. Therefore, 5A2 may represent a promising novel treatment strategy in oncology.
Still, projects in the construction sector are delivered with time delays and cost overruns. One of the reasons for poor performance was assigned to project complexity. A combination of lean ...construction and agile project management are hypothesized as a possible solution to cope with project complexity. In this paper we aim to understand if the implicit usage of lean and agile help coping with complexity. The research was done by means of correlation analysis on data gathered from a structured questionnaire (67 responses). In total, 51 significant correlations among 255 possible relations were found. To reduce the number of variables, factor analysis was performed. Correlation analysis on the defined factors showed 8 significant correlations among 25 relations. Several lean and agile elements were shown to significantly correlate to either reducing complexity or managing complexity. It was therefore concluded that these are promising to cope with complexity and improve project performance, which is to be confirmed in subsequent research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
Early treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still show cognitive and mood problems. In this study, it was investigated whether ET-PKU-patients ...have specific phenylalanine (Phe-)related problems with respect to social-cognitive functioning and social skills.
Methods
Ninety five PKU-patients (mean age 21.6 ± 10.2 years) and 95 healthy controls (mean age 19.6 ± 8.7 years) were compared on performance of computerized and paper-and-pencil tasks measuring social-cognitive abilities and on parent- and self-reported social skills, using multivariate analyses of variance, and controlling for general cognitive ability (IQ-estimate). Further comparisons were made between patients using tetrahydrobiopterin (BH4,
N
= 30) and patients not using BH4. Associations with Phe-levels on the day of testing, during childhood, during adolescence and throughout life were examined.
Results
PKU-patients showed poorer social-cognitive functioning and reportedly had poorer social skills than controls (regardless of general cognitive abilities). Quality of social-cognitive functioning was negatively related to recent Phe-levels and Phe-levels between 8 and 12 years for adolescents with PKU. Quality of social skills was negatively related to lifetime phenylalanine levels in adult patients, and specifically to Phe-levels between 0 and 7, and between 8 and 12 years. There were no differences with respect to social outcome measures between the BH
4
and non-BH
4
groups.
Conclusion
PKU-patients have Phe-related difficulties with social-cognitive functioning and social skills. Problems seem to be more evident among adolescents and adults with PKU. High Phe-levels during childhood and early adolescence seem to be of greater influence than current and recent Phe-levels for these patients.
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FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
Cognitive and mental health problems in individuals with the inherited metabolic disorder phenylketonuria (PKU) have often been associated with metabolic control and its history. For the present ...study executive functioning (EF) was assessed in 21 PKU patients during childhood (T1, mean age 10.4 years, SD = 2.0) and again in adulthood (T2, mean age 25.8 years, SD = 2.3). At T2 additional assessments of EF in daily life and mental health were performed. Childhood (i.e. 0–12 years) blood phenylalanine was significantly related to cognitive flexibility, executive motor control, EF in daily life and mental health in adulthood (i.e. at T2). Patients with a greater increase in phenylalanine levels after the age of 12 performed more poorly on EF-tasks at T2. Group-based analyses showed that patients with phenylalanine <360 µmol/L in childhood and phenylalanine ≥360 µmol/L from age 13 onwards (n = 11) had better cognitive flexibility and executive motor control than those who had phenylalanine ≥360 µmol/L throughout life (n = 7), supporting the notion that phenylalanine should be below the recommended upper treatment target of 360 µmol/L during childhood for better outcome in adulthood. Despite some results indicating additional influence of phenylalanine levels between 13 and 17 years of age, evidence for a continued influence of phenylalanine levels after childhood on adult outcomes was largely lacking. This may be explained by the fact that the patients in the present study had relatively low phenylalanine levels during childhood (mean: 330 µmol/L, range: 219–581 µmol/L) and thereafter (mean Index of Dietary Control at T2: 464 µmol/L, range: 276–743 µmol/L), which may have buffered against transitory periods of poor metabolic control during adolescence and early adulthood.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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