Early life Adversity,functional connectivity and cognitive performance in Schizophrenia: The mediating role of IL-6

ObjectiveExposure to childhood trauma (CT) is associated with cognitive impairment in schizophrenia, and deficits in social cognition in particular. Here, we sought to test whether IL-6 mediated the association between CT and social cognition both directly, and sequentially via altered default mode network (DMN) connectivity.MethodsThree-hundred-and-eleven participants (104 patients and 207 healthy participants) were included, with MRI data acquired in a subset of n = 147. CT was measured using the childhood trauma questionnaire (CTQ). IL-6 was measured in both plasma and in toll like receptor (TLR) stimulated whole blood. The CANTAB emotion recognition task (ERT) was administered to assess social cognition, and cortical connectivity was assessed based on resting DMN connectivity.ResultsHigher IL-6 levels, measured both in plasma and in toll-like receptor (TLR-2) stimulated blood, were significantly correlated with higher CTQ scores and lower cognitive and social cognitive function. Plasma IL-6 was further observed to partly mediate the association between higher CT scores and lower emotion recognition performance (CTQ total: β_indirect −0.0234, 95% CI: −0.0573 to −0.0074; CTQ physical neglect: β_indirect = −0.0316, 95% CI: −0.0741 to −0.0049). Finally, sequential mediation was observed between plasma IL-6 levels and DMN connectivity in mediating the effects of higher CTQ on lower social cognitive function (β_indirect = −0.0618, 95% CI: −0.1523 to −0.285).ConclusionThis work suggests that previous associations between CT and social cognition may be partly mediated via an increased inflammatory response. IL-6′s association with changes in DMN activity further suggest at least one cortical network via which CT related effects on cognition may be transmitted.     

Accuracy of two midsagittal planes in three-dimensional analysis and their measurement in patients with skeletal mandibular deviation: a comparative study

Our aim was to evaluate the accuracy of two midsagittal planes (MSP) to provide a better reference plane for studying the 3-dimensional structural symmetry in patients with skeletal mandibular deviation. Thirty adult patients with facial asymmetry were admitted to the Department of Orthodontics, Hospital of Stomatology, between January 2015 and 2017. The DICOM data were collected and reconstructed using ProPlan CMF^® 2.0 (Materialise). Two sets of reference planes were set up. In the orbital margin plane group, the plane crossing the nasion (N) point and perpendicular to the frontozygomatic (FZ) suture line was used as the MSP. In the skull base plane group, the MSP was established using the sella turcica (S), N, and basion (Ba). The distances from the craniofacial skeletal and soft tissue midline landmarks to the two MSP were separately measured, and the significance of differences between measurements corresponding to two reference planes were assessed using the paired t test. Except for the posterior nasal spine (PNS)-MSP, the distances from other soft and hard tissue landmarks to the MSP in the orbital margin plane group were significantly shorter than those in the skull base plane group. In the 3-dimensional measurement analysis, the skeletal and soft tissue anatomical midline landmarks were closer to the MSP in the orbital margin plane group. The MSP crossing point N, perpendicular to the FZ suture line, was more accurate and suitable.     

Influence of unfused cranial bones on magnetoencephalography signals in human infants

ObjectiveTo clarify the effects of unfused cranial bones on magnetoencephalography (MEG) signals during early development.MethodsIn a simulation study, we compared the MEG signals over a spherical head model with a circular hole mimicking the anterior fontanel to those over the same head model without the fontanel for different head and fontanel sizes with varying skull thickness and conductivity.ResultsThe fontanel had small effects according to three indices. The sum of differences in signal over a sensor array due to a fontanel, for example, was < 6% of the sum without the fontanel. However, the fontanel effects were extensive for dipole sources deep in the brain or outside the fontanel for larger fontanels. The effects were comparable in magnitude for tangential and radial sources. Skull thickness significantly increased the effect, while skull conductivity had minor effects.ConclusionMEG signal is weakly affected by a fontanel. However, the effects can be extensive and significant for radial sources, thicker skull and large fontanels. The fontanel effects can be intuitively explained by the concept of secondary sources at the fontanel wall.SignificanceThe minor influence of unfused cranial bones simplifies MEG analysis, but it should be considered for quantitative analysis.     

Psycho-sexual disorders and their treatment. Part III: Sexual deviation

Summary

In this third and final part of a review of psycho-sexual disorders the author considers the problem of sexual deviation. The various theories of the aetiology of homosexuality and other deviations are discussed and the different methods of treatment used by investigators in this field are reviewed, including recent drugs such as the anti-androgen, cyproterone acetate.     

Risk factors for bleeding after dental extractions in patients over 60 years of age who are taking antiplatelet drugs

The aim of this retrospective, single-centre study was to identify the risk factors for bleeding after dental extractions in patients aged over 60 who were being treated with antiplatelet drugs. A total of 338 patients who fulfilled the inclusion criteria were enrolled, and their personal and clinical details, and complications with bleeding after extraction, were retrieved and recorded. There were 182 men and 156 women (mean (SD) age 72 (8) years). A total of 469 teeth were extracted, with a mean (SD) of 1.4 (0.6) teeth/patient. Seventy-seven patients (23%) developed mild, and 55 (16%) severe, bleeding postoperatively. No patient developed a major cardiovascular or cerebrovascular event. We calculated the significance of the association of different variables with the occurrence of postoperative haemorrhage using a multivariate stepwise logistic regression model. The presence of three or more coexisting conditions, a complicated tooth extraction, and the use of two antiplatelet drugs were independent risk factors, while discontinuation of antiplatelet treatment four or more days before the tooth was extracted was a protective factor. This suggests that clinicians should assess the thrombotic risk associated with the interruption of antiplatelet drugs as well as the risk of bleeding for each patient before dental extraction. Strong and effective measures for haemostasis may be preferred over blind discontinuation of antiplatelet drugs. This study is registered in the Chinese Clinical Trial Registry (No. ChiCTR1800014355).     

Influence of MCC II fraction and storage conditions on pellet properties

Microcrystalline cellulose II (MCC II) – a polymorph of commonly used MCC I – was introduced as new pelletization aid in wet-extrusion/spheronization leading to fast disintegrating pellets. Previous investigations suggested that pellet properties were influenced by the fraction of MCC II. Furthermore, it is unknown whether the storage conditions can affect the disintegration behavior. Therefore, the effects of MCC II fraction and the storage conditions on several pellet properties were investigated.MCC II-based pellets were prepared of pure MCC II or binary mixtures containing 10–50% (steps of 10%) MCC II as pelletization aid and theophylline, chloramphenicol or lactose. The pellets were characterized by their aspect ratio, equivalent diameter, water content, tensile strength, porosity as well as shrinking, and disintegration behavior and drug release according to their MCC II fraction. Furthermore, the pellets were stored at different relative humidities (0–97%rh), and the influence on their disintegration and drug release was investigated.With increasing MCC II fraction, the pellets became lager in size, decreased their porosity, and required higher water contents for spheronization. Moreover, the disintegration time increased and the disintegration itself was incomplete. Furthermore, the storage conditions had an impact on the disintegration properties of MCC II-based pellets. The disintegrating was affected irreversibly after storage at high humidity (80–97%rh) resulting in a slow drug release. Therefore, MCC II-based pellets need to be stored below 80%rh to secure a fast disintegration.A better knowledge of the properties of MCC II-based pellets was obtained providing a basis for a successful manufacturing and adequate storage of MCC II-based pellets prepared by extrusion/spheronization.