Proteomics-on-a-chip for Biomarker discovery

In proteomics research still two-dimensional gel electrophoresis (2D-GE) is currently used for biomarker discovery. We applied free flow electrophoresis (FFE) separation technology combined with biomolecular interaction sensing using Surface Plasmon Resonance (SPR) imaging in an integrated proteomics-on-a-chip device as a proof of concept for biomarker discovery

Placental transfer of a hydroxylated polychlorinated biphenyl and effects on fetal and maternal thyroid hormone homeostasis in the rat

Earlier studies at our laboratory indicated that several hydroxylated polychlorinated biphenyls (OH-PCBs) detected in human blood could specifically inhibit thyroxine (T4) transport by competitive binding to the thyroid hormone transport protein transthyretin (TTR) in vitro. In the present study we investigated the effects of prenatal exposure to 5 mg/kg body weight of [14C]-labeled or unlabeled 4-OH-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107), one of the major metabolites of PCBs detected in human blood, from gestation days (GD) 10 to 16 on thyroid hormone status and metabolism in pregnant rats and their fetuses at GD 17 and GD 20. 4-OH-CB107 is a metabolite of both 2,3,3',4,4'-pentachlorobiphenyl (CB-105) and 2,3',4,4',5-pentachlorobiphenyl (CB-118). We were able to show the accumulation of 4-OH-CB107 in the fetal compartment. The fetal/maternal ratios at GD 20 in liver, cerebellum, and plasma were 11.0, 2.6, and 1.2, respectively. The 14C-4-OH-CB107-derived radioactivity in plasma was bound to TTR in both dams and fetuses. Fetal plasma TT4 and FT4 levels were significantly decreased at GD 17 and GD 20 (89 and 41␛espectively at GD 20). Fetal thyroid stimulating hormone levels were increased by 124 at GD 20. The T4 concentrations in fetal forebrain homogenates at GD20 were reduced by 35°but no effects could be detected on brain T3 concentrations. The deiodination of T4 to T3 was significantly increased in fetal forebrain homogenates at GD 17, and unaltered at GD 20. In addition, no alterations were observed in maternal and fetal hepatic T4-UDP-glucuronosyltransferase activity, type I deiodinase activity, and EROD activity. In conclusion, exposure of pregnant rats to 4-OH-CB107 results in the distribution of the compound in the maternal and fetal compartment, which is probably caused by the binding of the PCB metabolite to TTR. Consequently, TT4 levels in fetal plasma and brain samples were reduced. Despite reductions in fetal brain T4 levels, the active hormone (T3) in fetal brains remained unaffected

Health–economic Benefits of Treating Trauma in Psychosis

Background: Co-occurrence of posttraumatic stress disorder (PTSD) in psychosis (estimated as 12%) raises personal suffering and societal costs. Health–economic studies on PTSD treatments in patients with a diagnosis of a psychotic disorder have not yet been conducted, but are needed for guideline development and implementation. This study aims to analyse the cost-effectiveness of guideline PTSD therapies in patients with a psychotic disorder. Methods: This health–economic evaluation alongside a randomized controlled trial included 155 patients with a psychotic disorder in care as usual (CAU), with comorbid PTSD. Participants received eye movement desensitization and reprocessing (EMDR) (n = 55), prolonged exposure (PE) (n = 53) or waiting list (WL) (n = 47) with masked assessments at baseline (T0) and at the two-month (post-treatment, T2) and six-month follow-up (T6). Costs were calculated using the TiC-P interview for assessing healthcare consumption and productivity losses. Incremental cost-effectiveness ratios and economic acceptability were calculated for quality-adjusted life years (EQ-5D-3L-based QALYs) and PTSD ‘Loss of diagnosis’ (LoD, CAPS). Results: Compared to WL, costs were lower in EMDR (-€1410) and PE (-€501) per patient per six months. In addition, EMDR (robust SE 0.024, t = 2.14, p = .035) and PE (robust SE 0.024, t = 2.14, p = .035) yielded a 0.052 and 0.051 incremental QALY gain, respectively, as well as 26% greater probability for LoD following EMDR (robust SE = 0.096, z = 2.66, p = .008) and 22% following PE (robust SE 0.098, z = 2.28, p = .023). Acceptability curves indicate high probabilities of PTSD treatments being the better economic choice. Sensitivity analyses corroborated these outcomes. Conclusion: Adding PTSD treatment to CAU for individuals with psychosis and PTSD seem to yield better health and less PTSD at lower costs, which argues for implementation

An intergenerational family study on the impact of experienced and perpetrated child maltreatment on neural face processing

Altered processing of emotional faces due to childhood maltreatment has repeatedly been reported, and may be a key process underlying the intergenerational transmission of maltreatment. The current study is the first to examine the role of neural reactivity to emotional and neutral faces in the transmission of maltreatment, using a multi-generational family design including 171 participants of 51 families of two generations with a large age range (8–69 years). The impact of experienced and perpetrated maltreatment (abuse and neglect) on face processing was examined in association with activation in the amygdala, hippocampus, inferior frontal gyrus (IFG) and insula in response to angry, fearful, happy and neutral faces. Results showed enhanced bilateral amygdala activation in response to fearful faces in older neglected individuals, whereas reduced amygdala activation was found in response to these faces in younger neglected individuals. Furthermore, while experienced abuse was associated with lower IFG activation in younger individuals, experience of neglect was associated with higher IFG activation in this age group, pointing to potentially differential effects of abuse and neglect and significant age effects. Perpetrated abusive and neglectful behavior were not related to neural activation in any of these regions. Hence, no indications for a role of neural reactivity to emotional faces in the intergenerational transmission of maltreatment were found.Stress and Psychopatholog

23 Questions of fluency in Australian languages revitalisation

Changes in endothelial glycocalyx are one of the earliest changes in development of cardiovascular disease. The endothelial glycocalyx is both an important biological modifier of interactions between flowing blood and the vessel wall, and a determinant of organ perfusion. We hypothesize that deeper penetration of erythrocytes into the glycocalyx is associated with reduced microvascular perfusion. The population-based prospective cohort study (the Netherlands Epidemiology of Obesity [NEO] study) includes 6,673 middle-aged individuals (oversampling of overweight and obese individuals). Within this cohort, we have imaged the sublingual microvasculature of 915 participants using sidestream darkfield (SDF) imaging together with a recently developed automated acquisition and analysis approach. Presence of RBC (as a marker of microvascular perfusion) and perfused boundary region (PBR), a marker for endothelial glycocalyx barrier properties for RBC accessibility, were assessed in vessels between 5 and 25 µm RBC column width. A wide range of variability in PBR measurements, with a mean PBR of 2.14 µm (range: 1.43-2.86 µm), was observed. Linear regression analysis showed a marked association between PBR and microvascular perfusion, reflected by RBC filling percentage (regression coefficient β: -0.034; 95% confidence interval: -0.037 to -0.031). We conclude that microvascular beds with a thick ("healthy") glycocalyx (low PBR), reflects efficient perfusion of the microvascular bed. In contrast, a thin ("risk") glycocalyx (high PBR) is associated with a less efficient and defective microvascular perfusion

A multi-site single blind clinical study to compare the effects of prolonged exposure, eye movement desensitization and reprocessing and waiting list on patients with a current diagnosis of psychosis and co morbid post traumatic stress disorder: study protocol for the randomized controlled trial Treating Trauma in Psychosis

Contains fulltext : 116518.pdf (publisher's version ) (Open Access)Background: Trauma contributes to psychosis and in psychotic disorders post-traumatic stress disorder (PTSD) is often a comorbid disorder. A problem is that PTSD is underdiagnosed and undertreated in people with psychotic disorders. This study's primary goal is to examine the efficacy and safety of prolonged exposure and eye movement desensitization and reprocessing (EMDR) for PTSD in patients with both psychotic disorders and PTSD, as compared to a waiting list. Secondly, the effects of both treatments are determined on (a) symptoms of psychosis, in particular verbal hallucinations, (b) depression and social performance, and (c) economic costs. Thirdly, goals concern links between trauma exposure and psychotic symptomatology and the prevalence of exposure to traumatic events, and of PTSD. Fourthly predictors, moderators, and mediators for treatment success will be explored. These include cognitions and experiences concerning treatment harm, credibility and burden in both participants and therapists. Methods/Design: A short PTSD-screener assesses the possible presence of PTSD in adult patients (21- to 65-years old) with psychotic disorders, while the Clinician Administered PTSD Scale interview will be used for the diagnosis of current PTSD. The M.I.N.I. Plus interview will be used for diagnosing lifetime psychotic disorders and mood disorders with psychotic features. The purpose is to include consenting participants (N = 240) in a multi-site single blind randomized clinical trial. Patients will be allocated to one of three treatment conditions (N = 80 each): prolonged exposure or EMDR (both consisting of eight weekly sessions of 90 minutes each) or a six-month waiting list. All participants are subjected to blind assessments at pre-treatment, twomonths post treatment, and six monthspost treatment. In addition, participants in the experimental conditions will have assessments at mid treatment and at 12 months follow-up. Discussion: The results from the post treatment measurement can be considered strong empirical indicators of the safety and effectiveness of prolonged exposure and EMDR. The six-month and twelve-month follow-up data have the potential of reliably providing documentation of the long-term effects of both treatments on the various outcome variables. Data from pre-treatment and midtreatment can be used to reveal possible pathways of change.19 p

Droplet microreactor for reaction monitoring at elevated temperatures and pressure

Recording reaction kinetics in detail and at various reaction conditions can be a time-consuming process. Microdroplets form ideal reaction chambers, suitable for high-throughput studies [1]. We report the fabrication of a microfluidic droplet-based microreactor operating at elevated temperatures (up to 130 °C) and pressures (up to 0.7 MPa), to rapidly study reaction kinetics. As proof-of-principle, the temperature-dependent fluorescence of Rhodamine B in ethanol is monitored [2]. Time-resolved information is obtained by measuring at multiple spots in the microreacto