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JNJ-42165279 is a selective inhibitor of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of fatty acid amides (FAA) including anandamide (AEA), palmitoylethanolamide (PEA), and N-oleoylethanolamide (OEA). We assessed the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of treatment with JNJ-42165279 in subjects with social anxiety disorder (SAD). This was a multicenter, double-blind, placebo-controlled study randomizing subjects to 12 weeks of treatment with either JNJ-42165279 (25 mg daily) or placebo (PBO). The primary endpoint was the change in the Liebowitz Social Anxiety Scale (LSAS) total score from baseline to end of study. Secondary endpoints included the Hamilton Anxiety Scale (HAM-A), Hamilton Depression Rating Scale (HDRS17), and the Clinical Global Impression-Improvement (CGI-I). Samples were collected for plasma concentration of AEA, PEA, OEA, and JNJ-42165279. A total of 149 subjects were enrolled with a mean baseline LSAS total score of 102.6 (SD 16.84). The mean change from baseline (SD) in LSAS total score at week 12 was numerically greater for JNJ-42165279: −29.4 (27.47) compared to PBO: −22.4 (23.57) but not significant. The percentage of subjects with ≥30% improvement from baseline in the LSAS total score was significantly higher for JNJ-42165279 (42.4%) compared to PBO (23.6%) (p value = 0.04). The percentage of subjects with a CGI-I score of much or very much improved was also significantly higher for JNJ-42165279 (44.1%) than for PBO (23.6%) (p value = 0.02). The drug was well tolerated. JNJ-42165279 appears to elicit an anxiolytic effect in subjects with SAD although trough concentrations with 25 mg once daily appeared to be insufficient to completely inhibit FAAH activity which may have led to suboptimal efficacy. ClinicalTrials.gov Identifier: NCT02432703.

Attachment insecurity and difficulty with mentalization are common in patients with eating disorders and might be related to their symptoms and lack of autonomy.br/AIM: To investigate the role of attachment and mentalization in the course of anorexia nervosa (AN) and bulimia nervosa (BN).br/METHOD: Patients with AN and BN were assessed at the start of treatment, and after 1 year and 1.5 years concerning attachment security and mentalization in relation to eating disorder and co-morbid symptoms and autonomy. The results at the start of treatment were compared to those of controls without an eating disorder.br/RESULTS: Attachment insecurity and low level of mentalization were more prevalent in patients than in controls, and associated with borderline personality disorder and/or self-injurious behaviour. Attachment security increased after 1 year of treatment. Recovery from eating disorder after 1 year was related to higher level of mentalization and improvement of autonomy. Low pre-treatment level of mentalization predicted persistence of eating disorder until 1.5 years of follow-up.br/CONCLUSION: Good mentalization is associated with recovery from eating disorder. More research on the effect of mentalization based treatment for patients with eating disorders, with or without borderline personality disorder, is recommended.

The zoonotic pathogen Streptococcus suis can cause septicemia and meningitis in humans. We report five complete genomes of Streptococcus suis serotype 2 and serotype 9, covering the complete phylogeny of serotype 9 Dutch porcine isolates and zoonotic isolates. The isolates include the model strain S10 and the Dutch emerging zoonotic lineage.

ACHTERGROND Onveilige gehechtheid en moeite met mentaliseren komen vaak voor bij patiënten met een eetstoornis, en hangen mogelijk samen met hun symptomen en gebrek aan autonomie. DOEL Zicht krijgen op de rol van gehechtheid en mentaliseren in het beloop van anorexia (AN) en bulimia nervosa (BN). METHODE Patiënten met AN en BN werden bij de start van behandeling, 1 jaar later en 1,5 jaar later, onderzocht op gehechtheid en mentaliserend vermogen in relatie tot eetstoornissymptomen, comorbiditeit en autonomie. De metingen bij de start werden vergeleken met die van personen zonder eetstoornis. RESULTATEN Onveilige gehechtheid en een laag mentaliserend vermogen kwamen meer voor bij patiënten dan bij controlepersonen, en hingen samen met een borderlinepersoonlijkheidsstoornis en/of zelfverwondend gedrag. Veilige gehechtheid nam toe in 1 jaar van behandeling. Herstel van de eetstoornis na 1 jaar ging gepaard met een hoger mentaliserend vermogen en toegenomen autonomie. Een laag mentaliserend vermogen bij aanvang van de behandeling bleek het voortduren van de eetstoornis 1,5 jaar later te voorspellen. CONCLUSIE Goed mentaliseren hangt samen met verbetering van een eetstoornis. Onderzoek naar het effect van mentalization-based treatment bij patiënten met een eetstoornis, met of zonder comorbide borderlinepersoonlijkheidsstoornis, wordt aanbevolen.

Background When patients receiving palliative care are transferred between care settings, adequate collaboration and information exchange between health care professionals is necessary to ensure continuity, efficiency and safety of care. Several studies identified deficits in communication and information exchange between care settings. Aim of this study was to get insight in the quality of collaboration and information exchange in palliative care from the perspectives of nurses. Methods We performed a cross-sectional regional survey study among nurses working in different care settings. Nurses were approached via professional networks and media. Respondents were asked questions about collaboration in palliative care in general and about their last deceased patient. Potential associations between quality scores for collaboration and information handovers and characteristics of respondents or patients were tested with Pearson’s chi-square test. Results A total of 933 nurses filled in the questionnaire. Nurses working in nursing homes were least positive about inter-organizational collaboration. Forty-six per cent of all nurses had actively searched for such collaboration in the last year. For their last deceased patient, 10% of all nurses had not received the information handover in time, 33% missed information they needed. An adequate information handover was positively associated with timeliness and completeness of the information and the patient being well-informed, not with procedural characteristics. Conclusion Nurses report that collaboration between care settings and information exchange in palliative care is suboptimal. This study suggests that health care organizations should give more attention to shared professionalization towards inter-organizational collaboration among nurses in order to facilitate high-quality palliative care.

Respondents may use satisficing (i.e., nonoptimal) strategies when responding to self-report questionnaires. These satisficing strategies become more likely with decreasing motivation and/or cognitive ability (Krosnick, 1991). Considering that cognitive deficits are characteristic of depressive and anxiety disorders, depressed and anxious patients may be prone to satisficing. Using data from the Netherland’s Study of Depression and Anxiety ( N = 2,945), we studied the relationship between depression and anxiety, cognitive symptoms, and satisficing strategies on the NEO Five-Factor Inventory. Results showed that respondents with either an anxiety disorder or a comorbid anxiety and depression disorder used satisficing strategies substantially more often than healthy respondents. Cognitive symptom severity partly mediated the effect of anxiety disorder and comorbid anxiety disorder on satisficing. The results suggest that depressed and anxious patients produce relatively low-quality self-report data—partly due to cognitive symptoms. Future research should investigate the degree of satisficing across different mental health care assessment contexts.

Dit onderzoek, dat gefinancierd is door NRO, heeft tot doel om meer inzicht te verkrijgen in de vraag hoe lerarenopleidingen de intake van nieuwe studenten voor de lerarenopleidingen vormgeven en hoe die intake bijdraagt aan en voorspellend is voor het succes van studenten binnen de lerarenopleidingen. De uitkomsten van het onderzoek kunnen opleidingen helpen om hun intakeprocedures te verbeteren, zodat zij aankomende studenten beter ondersteunen bij het proces van zelfselectie. De volgende onderzoeksvragen staan centraal: 1. Welke doelen, criteria en instrumenten hanteren de lerarenopleidingen tijdens de intake- en selectieprocedure? 2. In hoeverre ondersteunen die procedures bij het proces van zelfselectie ten aanzien van de vraag: a. Kan ik succesvol studeren? b. Kan ik als leraar succesvol zijn? c. Wil ik leraar worden en wat voor leraar dan? 3. In welke mate hebben de gehanteerde criteria en instrumenten een voorspellende waarde voor studiesucces en handelen in de beroepspraktijk? 4. Hoe ervaren studenten de intakeprocedures? 5. Welke mechanismen spelen een rol bij intake en zelfselectie en wat is de betekenis daarvan voor de praktijk van de opleidingen? Op nbasis van de uitkomsten van het onderzoek bevelen de onderzoekers aan om bij de inrichting van intakeprocedures meer systematisch aandacht te besteden aan de drie zelfselectievragen: - Kan ik succesvol aan deze opleiding studeren? - Kan ik een succesvolle leraar worden? - Wil ik leraar worden en zo ja, wat voor leraar? Intakes bij lerarenopleidingen worden hiermee nadrukkelijker een zelfselectie-instrument, bedoeld om de kandidaat-student, de opleiding en het toekomstige beroep van leraar te matchen. Intakeprocedures zouden studenten moeten uitdagen om echt een inspanning te leveren en persoonlijk betrokken te raken. Dit zou meerdere keren over een langere periode moeten gebeuren. In een zelfselectieproces vraagt dit meer van de verantwoordelijkheid van de toekomstige student om inspanningen te leveren, zodat het realistisch uitvoerbaar is voor de opleiding om de intake vorm te geven.

Nucleotide skew analysis is a versatile method to study the nucleotide composition of RNA/DNA molecules, in particular to reveal characteristic sequence signatures. For instance, skew analysis of the nucleotide bias of several viral RNA genomes indicated that it is enriched in the unpaired, single-stranded genome regions, thus creating an even more striking virus-specific signature. The comparison of skew graphs for many virus isolates or families is difficult, time-consuming, and nonquantitative. Here, we present a procedure for a more simple identification of similarities and dissimilarities between nucleotide skew data of coronavirus, flavivirus, picornavirus, and HIV-1 RNA genomes. Window and step sizes were normalized to correct for differences in length of the viral genome. Cumulative skew data are converted into pairwise Euclidean distance matrices, which can be presented as neighbor-joining trees. We present skew value trees for the four virus families and show that closely related viruses are placed in small clusters. Importantly, the skew value trees are similar to the trees constructed by a “classical” model of evolutionary nucleotide substitution. Thus, we conclude that the simple calculation of Euclidean distances between nucleotide skew data allows an easy and quantitative comparison of characteristic sequence signatures of virus genomes. These results indicate that the Euclidean distance analysis of nucleotide skew data forms a nice addition to the virology toolbox.

Background Detection of pathological tau aggregates could facilitate clinical diagnosis of Alzheimer's disease (AD) and monitor drug effects in clinical trials. S-[18F]THK-5117 could be a potential tracer to detect pathological tau deposits in brain. However, no previous study have correlated S-[18F]THK-5117 uptake in PET with brain biopsy verified tau pathology in vivo. Objective Here we aim to evaluate the association between cerebrospinal fluid (CSF) AD biomarkers, S-[18F]THK-5117, and [11C]PIB PET against tau and amyloid lesions in brain biopsy. Methods Fourteen patients with idiopathic normal pressure hydrocephalus (iNPH) with previous shunt surgery including right frontal cortical brain biopsy and CSF Aβ1 - 42, total tau, and P-tau181 measures, underwent brain MRI, [11C]PIB PET, and S-[18F]THK-5117 PET imaging. Results Seven patients had amyloid-β (Aβ, 4G8) plaques, two both Aβ and phosphorylated tau (Pτ, AT8) and one only Pτ in biopsy. As expected, increased brain biopsy Aβ was well associated with higher [11C]PIB uptake in PET. However, S-[18F]THK-5117 uptake did not show any statistically significant correlation with either brain biopsy Pτ or CSF P-tau181 or total tau. Conclusions S-[18F]THK-5117 lacked clear association with neuropathologically verified tau pathology in brain biopsy probably, at least partially, due to off-target binding. Further studies with larger samples of patients with different tau tracers are urgently needed. The detection of simultaneous Aβ and tau pathology in iNPH is important since that may indicate poorer and especially shorter response for CSF shunt surgery compared with no pathology.

Reliability is usually estimated for a test score, but it can also be estimated for item scores. Item-score reliability can be useful to assess the item’s contribution to the test score’s reliability, for identifying unreliable scores in aberrant item-score patterns in person-fit analysis, and for selecting the most reliable item from a test to use as a single-item measure. Four methods were discussed for estimating item-score reliability: the Molenaar–Sijtsma method (method MS), Guttman’s method [Formula: see text], the latent class reliability coefficient (method LCRC), and the correction for attenuation (method CA). A simulation study was used to compare the methods with respect to median bias, variability (interquartile range [IQR]), and percentage of outliers. The simulation study consisted of six conditions: standard, polytomous items, unequal [Formula: see text] parameters, two-dimensional data, long test, and small sample size. Methods MS and CA were the most accurate. Method LCRC showed almost unbiased results, but large variability. Method [Formula: see text] consistently underestimated item-score reliabilty, but showed a smaller IQR than the other methods.

Inhibition of fatty acid amide hydrolase (FAAH) potentiates endocannabinoid activity and is hypothesized to have therapeutic potential for mood and anxiety disorders and pain. The clinical profile of JNJ-42165279, an oral selective FAAH inhibitor, was assessed by investigating the pharmacokinetics, pharmacodynamics, safety, and binding to FAAH in the brain of healthy human volunteers. Concentrations of JNJ-42165279 (plasma, cerebrospinal fluid (CSF), urine) and fatty acid amides (FAA; plasma, CSF), and FAAH activity in leukocytes was determined in a phase I multiple ascending dose study. A positron emission tomography study with the FAAH tracer [11 C]MK3168 was conducted to determine brain FAAH occupancy after single and multiple doses of JNJ-42165279. JNJ-42165279 administration resulted in an increase in plasma and CSF FAA. Significant blocking of brain FAAH binding of [11 C]MK3168 was observed after pretreatment with JNJ-42165279. JNJ-42165279 produces potent central and peripheral FAAH inhibition. Saturation of brain FAAH occupancy occurred with doses ≥10 mg of JNJ-42165279. No safety concerns were identified.

We propose a general cognitive diagnosis model framework to diagnose mental disorders using item scores obtained from clinical measurement instruments. This framework can be used to validate the extent to which the items measure the specific disorders. The method is illustrated using data obtained with the Dutch version of Millon Clinical Multiaxial Inventory-III.

The abundance of the human intestinal symbiont Akkermansia muciniphila has found to be inversely correlated with several diseases, including metabolic syndrome and obesity. A.muciniphila is known to use mucin as sole carbon and nitrogen source. To study the physiology and the potential for therapeutic applications of this bacterium, we designed a defined minimal medium. The composition of the medium was based on the genome-scale metabolic model of A.muciniphila and the composition of mucin. Our results indicate that A.muciniphila does not code for GlmS, the enzyme that mediates the conversion of fructose-6-phosphate (Fru6P) to glucosamine-6-phosphate (GlcN6P), which is essential in peptidoglycan formation. The only annotated enzyme that could mediate this conversion is Amuc-NagB on locus Amuc_1822. We found that Amuc-NagB was unable to form GlcN6P from Fru6P at physiological conditions, while it efficiently catalyzed the reverse reaction. To overcome this inability, N-acetylglucosamine needs to be present in the medium for A.muciniphila growth. With these findings, the genome-scale metabolic model was updated and used to accurately predict growth of A.muciniphila on synthetic media. The finding that A.muciniphila has a necessity for GlcNAc, which is present in mucin further prompts the adaptation to its mucosal niche.