Fatty acid ethanolamide levels are altered in borderline personality and complex posttraumatic stress disorders

Borderline personality (BPD) and complex posttraumatic stress disorders (PTSD) are both powerfully associated with the experience of interpersonal violence during childhood and adolescence. The disorders frequently co-occur and often result in pervasive problems in, e.g., emotion regulation and altered pain perception, where the endocannabinoid system is deeply involved. We hypothesize an endocannabinoid role in both disorders. We investigated serum levels of the endocannabinoids anandamide and 2-arachidonoylglycerol and related fatty acid ethanolamides (FAEs) in BPD, PTSD, and controls. Significant alterations were found for both endocannabinoids in BPD and for the FAE oleoylethanolamide in PTSD suggesting a respective link to both disorders.     

TIDAL WAVES: Network mechanisms in the neuroendocrine control of prolactin release

Neuroendocrine tuberoinfundibular dopamine (TIDA) neurons tonically inhibit pituitary release of the hormone, prolactin. Through the powerful actions of prolactin in promoting lactation and maternal behaviour while suppressing sexual drive and fertility, TIDA neurons play a key role in reproduction. We summarize insights from recent in vitro studies into the membrane properties and network behaviour of TIDA neurons including the observations that TIDA neurons exhibit a robust oscillation that is synchronized between cells and depends on intact gap junction communication. Comparisons are made with phasic firing patterns in other neuronal populations. Modulators involved in the control of lactation – including serotonin, thyrotropin-releasing hormone and prolactin itself – have been shown to change the electrical behaviour of TIDA cells. We propose that TIDA discharge mode may play a central role in tuning the amount of dopamine delivered to the pituitary and hence circulating prolactin concentrations in different reproductive states and pathological conditions.     

Emotional variability during mother–adolescent conflict interactions: Longitudinal links to adolescent disclosure and maternal control

The aim of this study was to examine relations of emotional variability during mother–adolescent conflict interactions in early adolescence with adolescent disclosure and maternal control in early and late adolescence. Data were used from 92 mother–adolescent dyads (M age T1 = 13.05; 65.20% boys) that were videotaped at T1 while discussing a conflict. Emotional variability was derived from these conflict interactions. Mothers also completed questionnaires at the start of the study (T1) and five years later (T6) on adolescent disclosure and maternal control. Path analysis showed that more emotional variability during conflict interactions in early adolescence was associated with higher levels of adolescent disclosure in early adolescence and with relative decreases in maternal control from early to late adolescence. More emotional variability of mother–adolescent dyads serves an important function in adaptively dealing with relational challenges that arise during adolescence.     

Target-mediated clearance and bio-distribution of a monoclonal antibody against the Kunitz–type protease inhibitor 2 domain of Tissue Factor Pathway Inhibitor

Introduction

A humanised monoclonal antibody, concizumab, that binds with high affinity to the Kunitz-type protease inhibitor (KPI) 2 domain of human tissue factor pathway inhibitor (TFPI) is in clinical development. It promotes coagulation by neutralising the inhibitory function of TFPI and may provide a subcutaneous prophylaxis option for patients with haemophilia. We aimed to study biodistribution and pharmacokinetics (PK) of concizumab.

Materials and Methods

Blockage of cellular TFPI by concizumab was measured by tissue factor/Factor VIIa-mediated Factor X activation on human EA.hy926 cells. Biodistribution of concizumab was analysed in rabbits by immunohistology, and the PK was measured in rabbits and rats.

Results and Conclusions

Concizumab bound to cell surface TFPI on EA.hy926 cells and neutralised TFPI inhibition of Factor X activation. The antibody cross-reacted with rabbit TFPI, but not with rat TFPI, allowing for comparative PK studies. PK data in rats described a log-linear profile typical for a non-binding antibody, whereas PK data in rabbits revealed a non-linear, dose-dependent profile, consistent with a target-mediated clearance mechanism. Immunohistology in rabbits during target-saturation showed localisation of the antibody on the endothelium of the microvasculature in several organs. We observed a marked co-localisation with endogenous rabbit TFPI, but a negligible sub-endothelial build-up. Concizumab binds and neutralises the inhibitory effect of cell surface-bound TFPI. The PK profile observed in rabbits is consistent with a TFPI-mediated drug disposition. Double immunofluorescence shows co-localisation of the antibody with TFPI on the endothelium of the microvasculature and points to this TFPI as a putative target involved in the clearance mechanism.     

Pediatric Healthcare Professionals’ Views on Autism Spectrum Disorder Screening at 12–18 Months

This study explored North Carolina pediatric healthcare professional’s (PHP) perceptions of screening 12–18 month old infants for Autism Spectrum Disorder (ASD). Eight focus groups (66 PHPs) were conducted across practice settings. The purpose was to explore PHP’s perspectives to: inform development of ASD screening tools and ultimately impact their use in PHP settings. PHPs reported concerns, barriers, and the need for research to support early ASD screening. Additionally, they expressed the need for: (a) clear “red flags” of ASD for 12–18 month olds; (b) socioculturally sensitive and effective screening tools; (c) effective early interventions; (d) systems to handle potential increases in referrals; and (e) continuing education. PHPs also demonstrated preferences about screening tool characteristics and processes for enhancing screening efforts.     

Inflammatory infratentorial progressive multifocal leukoencephalopathy in a patient with rheumatoid arthritis

An 84–year‐old man with rheumatoid arthritis (RA) treated with methotrexate, developed progressive confusion and cerebellar symptoms, and died approximately 2 months later. Neuropathological examination revealed progressive multifocal leukoencephalopathy (PML) involving the cerebellum and brainstem. The affected tissues displayed intense infiltrations by CD8+ T‐cells and microglia. JC virus was localized in oligodendroglia and cerebellar granule cells. This case illustrates unusual localization of inflammatory PML in a patient with RA treated with methotrexate.     

Fewer intensive care unit refusals and a higher capacity utilization by using a cyclic surgical case schedule

PURPOSE: Mounting health care costs force hospital managers to maximize utilization of scarce resources and simultaneously improve access to hospital services. This article assesses the benefits of a cyclic case scheduling approach that exploits a master surgical schedule (MSS). An MSS maximizes operating room (OR) capacity and simultaneously levels the outflow of patients toward the intensive care unit (ICU) to reduce surgery cancellation. MATERIALS AND METHODS: Relevant data for Erasmus MC have been electronically collected since 1994. These data are used to construct an MSS that consisted of a set of surgical case types scheduled for a period or cycle. This cycle was executed repetitively. During such a cycle, surgical cases for each surgical department were scheduled on a specific day and OR. The experiments were performed for the Erasmus University Medical Center and for a virtual hospital. RESULTS: Unused OR capacity can be reduced by up to 6.3% for a cycle length of 4 weeks, with simultaneous optimal leveling of the ICU workload. CONCLUSIONS: Our findings show that the proposed cyclic OR planning policy may benefit OR utilization and reduce surgical case cancellation and peak demands on the ICU.