Tetramethoxystilbene-loaded liposomes restore reactive-oxygen-species-mediated attenuation of dilator responses in rat aortic vessels Ex vivo

The methylated analogue of the polyphenol resveratrol (RV), 2,3',4,5'-tetramethoxystilbene (TMS) displays potent antioxidant properties and is an effective cytochrome P450 (CYP) 1B1 inhibitor. The bioavailability of TMS is low. Therefore, the use of liposomes for the encapsulation of TMS is a promising delivery modality for enhanced uptake into tissues. We examined the effect of delivery of TMS in liposomes on the restoration of vasodilator responses of isolated aortic vessels after acute tension elevation ex vivo. Aortic vessels from young male Wistar rats were isolated, and endothelial-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) responses assessed. Acute tension elevation (1 h) significantly reduced ACh dilator responses, which were restored following incubation with superoxide dismutase or apocynin (an NADPH oxidase inhibitor). Incubation with TMS-loaded liposomes (mean diameter 157 ± 6 nm; PDI 0.097) significantly improved the attenuated dilator responses following tension elevation, which was sustained over a longer period (4 h) when compared to TMS solution. Endothelial denudation or co-incubation with L-NNA (Nω-nitro-l-arginine; nitric oxide synthase inhibitor) resulted in loss of dilator function. Our findings suggest that TMS-loaded liposomes can restore attenuated endothelial-dependent dilator responses induced by an oxidative environment by reducing NADPH-oxidase-derived ROS and potentiating the release of the vasodilator nitric oxide. TMS-loaded liposomes may be a promising therapeutic strategy to restore vasodilator function in vascular disease

An anatomy-based lumped parameter model of cerebrospinal venous circulation: can an extracranial anatomical change impact intracranial hemodynamics?

Background The relationship between extracranial venous system abnormalities and central nervous system disorders has been recently theorized. In this paper we delve into this hypothesis by modeling the venous drainage in brain and spinal column areas and simulating the intracranial flow changes due to extracranial morphological stenoses. Methods A lumped parameter model of the cerebro-spinal venous drainage was created based on anatomical knowledge and vessels diameters and lengths taken from literature. Each vein was modeled as a hydraulic resistance, calculated through Poiseuille’s law. The inputs of the model were arterial flow rates of the intracranial, vertebral and lumbar districts. The effects of the obstruction of the main venous outflows were simulated. A database comprising 112 Multiple Sclerosis patients (Male/Female = 42/70; median age ± standard deviation = 43.7 ± 10.5 years) was retrospectively analyzed. Results The flow rate of the main veins estimated with the model was similar to the measures of 21 healthy controls (Male/Female = 10/11; mean age ± standard deviation = 31 ± 11 years), obtained with a 1.5 T Magnetic Resonance scanner. The intracranial reflux topography predicted with the model in cases of internal jugular vein diameter reduction was similar to those observed in the patients with internal jugular vein obstacles. Conclusions The proposed model can predict physiological and pathological behaviors with good fidelity. Despite the simplifications introduced in cerebrospinal venous circulation modeling, the key anatomical feature of the lumped parameter model allowed for a detailed analysis of the consequences of extracranial venous impairments on intracranial pressure and hemodynamics

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders

A review of non-linear structural control techniques

In this articles the authors present a review of non-linear structural control techniques. This is an area of growing importance in a range of engineering applications, where non-linear behaviour is encountered. Structural control is usually divided into three main areas: (a) passive (b) semi-active, and (c) active control. This article follows this convention, and highlights in each section the relevant state of the art for non-linear systems, with additional references to related linear approaches

The relationship between ingroup identity and Paranoid ideation among people from African and African Caribbean backgrounds.

OBJECTIVES: People from ethnic minority groups experience higher rates of paranoid delusions compared with people from ethnic majority groups. Identifying with social groups has been shown to protect against mental health symptoms; however, no studies have investigated the relationship between social identification and paranoia in ethnic minority populations. Here, we investigated the association between British identification and paranoia in a sample of people from African and African Caribbean backgrounds living in the United Kingdom. We also assessed the role of potential mediating (self-esteem and locus of control) and moderating (contact with White British people) factors. DESIGN: Cross-sectional quantitative survey design. METHODS: We recruited 335 people from African and African Caribbean backgrounds who completed online self-report measures of identification with Great Britain, self-esteem, locus of control, positive and negative contact with White British people, and paranoia. RESULTS: A parallel moderated mediation model indicated that British identification was associated with lower paranoia when participants experienced primarily positive contact with White British people. British identification was associated with higher paranoia when participants had primarily negative contact with White British people. Both effects were mediated by changes in locus of control, but self-esteem was not implicated in either pathway. CONCLUSIONS: Identification with the majority culture is associated both positively and negatively with paranoid beliefs depending on the types of social interactions people experience. The findings have implications for preventative social prescribing initiatives and for understanding the causes of the high rates of psychosis in ethnic minority populations. PRACTITIONER POINTS: People from African and African Caribbean backgrounds experience high rates of paranoia, which may stem from social causes such as lack of belonging and negative social experiences. Among people from African backgrounds living in the UK, British identification is associated with lower paranoia when people's social experiences with White British people are positive and higher paranoia when their social experiences with White British people are negative. It is recommended that social interventions designed to reduce paranoia in vulnerable groups foster positive social contact and community belonging, which should enhance feelings of personal control. Understanding the complex interplay between social identity and social contact in the development of paranoia may help therapists and researchers better understand the phenomenology and risk factors of paranoid symptomology

The relationship between genetic liability, childhood maltreatment, and IQ: findings from the EU-GEI multicentric case–control study

This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). Controlling for FH and SZ-PRS did not attenuate the association between childhood maltreatment and IQ in cases or controls. Findings suggest that these expressions of genetic liability cannot account for the lower levels of cognition found among adults maltreated in childhood

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study

Abstract: Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03–0.33) and positive (B = 0.19; 95%CI 0.03–0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11–0.52) and in controls (B = 0.26; 95%CI 0.06–0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders

engineering vibration analysis with application to control systems

Most machines and structures are required to operate with low levels of vibration as smooth running leads to reduced stresses and fatigue and little noise. This book provides a thorough explanation of the principles and methods used to analyse the vibrations of engineering systems, combined with a description of how these techniques and results can be applied to the study of control system dynamics. Numerous worked examples are included, as well as problems with worked solutions, and particular attention is paid to the mathematical modelling of dynamic systems and the derivation of the equations of motion. All engineers, practising and student, should have a good understanding of the methods of analysis available for predicting the vibration response of a system and how it can be modified to produce acceptable results. This text provides an invaluable insight into both.Most machines and structures are required to operate with low levels of vibration as smooth running leads to reduced stresses and fatigue and little noise. This book provides a thorough explanation of the principles and methods used to analyse the vibrations of engineering systems, combined with a description of how these techniques and results can be applied to the study of control system dynamics. Numerous worked examples are included, as well as problems with worked solutions, and particular attention is paid to the mathematical modelling of dynamic systems and the derivation of the equations of motion. All engineers, practising and student, should have a good understanding of the methods of analysis available for predicting the vibration response of a system and how it can be modified to produce acceptable results. This text provides an invaluable insight into both.General notation * Introduction * The vibrations of systems having one degree of freedom * The vibrations of systems having more than one degree of freedom * The vibrations of systems with mass and elasticity * Automatic control systems * Problems * Answers and solutions to selected problems * Bibliography * Index.Includes bibliographical references (pages 419-421) and index.Print version record.Elsevie