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[Display omitted] The decades-long effort to deliver peptide drugs orally has resulted in several clinically successful formulations. These formulations are enabled by the inclusion of permeation enhancers that facilitate the intestinal absorption of peptides. Thus far, these oral peptide drugs have been limited to peptides less than 5 kDa, and it is unclear whether there is an upper bound of protein size that can be delivered with permeation enhancers. In this work, we examined two permeation enhancers, 1-phenylpiperazine (PPZ) and sodium deoxycholate (SDC), for their ability to increase intestinal transport of a model macromolecule (FITC-Dextran) as a function of its size. Specifically, the permeability of dextrans with molecular weights of 4, 10, 40, and 70 kDa was assessed in an in vitro and in vivo model of the intestine. In Caco-2 monolayers, both PPZ and SDC significantly increased the permeability of only FD4 and FD10. However, in mice, PPZ and SDC behaved differently. While SDC improved the absorption of all tested sizes of dextrans, PPZ was effective only for FD4 and FD10. This work is the first report of PPZ as a permeation enhancer in vivo , and it highlights the ability of permeation enhancers to improve the absorption of macromolecules across a broad range of sizes relevant for protein drugs. [ABSTRACT FROM AUTHOR]

[Display omitted] The vast majority of drugs are not designed or developed for pediatric and infant populations. Peptide drugs, which have become increasingly relevant in the past several decades, are no exception. Unfortunately, nearly all of the 60+ approved peptide drugs are formulated for injection, a particularly unfriendly mode of administration for infants. Although three peptide drugs were recently approved for oral formulations, this major advance in peptide drug delivery is available only for adults. In this review, we consider the current challenges and opportunities for the oral formulation of peptide therapeutics, specifically for infant populations. We describe the strategies that enable oral protein delivery and the potential impact of infant physiology on those strategies. We also detail the limited but encouraging progress towards 1) adapting conventional drug development and delivery approaches to infants and 2) designing novel infant-centric formulations. Together, these efforts underscore the feasibility of oral peptide delivery in infants and provide motivation to increase attention paid to this underserved area of drug delivery and formulation. [ABSTRACT FROM AUTHOR]

Oral drug delivery systems have multiple goals, assessing and enabling intestinal absorption at efficacious doses being one of them. Here we highlight the in vitro advances in modeling drug absorption, which more faithfully reflect human intestinal physiology and reduce the reliance on animal models. [ABSTRACT FROM AUTHOR]

The tripeptides, Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP), inhibit angiotensin-converting enzyme (ACE) resulting in lowered blood pressure. Our hypothesis was that the medium chain fatty acid permeation enhancer, sodium caprate (C 10 ), may prevent the decrease in permeability of the tripeptides when PepT1 is inhibited by glycyl-sarcosine (Gly-Sar), a situation that may occur in the presence of food hydrolysates. Using Caco-2 monolayers and isolated rat jejunal tissue, the apparent permeability coefficients (P app ) of [ 3 H]-IPP and [ 3 H]-LKP were assessed in the presence of Gly-Sar with and without C 10 . Gly-Sar decreased the P app of both tripeptides across monolayers and isolated jejunal tissue, but C 10 restored it. C 10 likely increased the paracellular permeability of the tripeptides, as indicated by immunofluorescence changes in tight junction proteins in Caco-2 monolayers accompanied by a concentration-dependent decrease in transepithelial electrical resistance (TEER). [ 3 H]-IPP and [ 3 H]-LKP were orally-gavaged to normal rats with Gly-Sar, C 10 , or with a mixture. Plasma levels of both peptides were reduced by Gly-Sar to less than half that of the levels detected in its absence, but were restored when C 10 was co-administered. In spontaneously hypertensive rats (SHRs), unlabelled IPP and LKP lowered blood pressure when delivered either by i.v. or oral routes. Oral gavage of Gly-Sar reduced the hypotensive action of peptides in SHRs, but the effect was restored in the presence of C 10 . In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C 10 may circumvent this by enhancing paracellular permeability. [ABSTRACT FROM AUTHOR]

Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP) are food-derived antihypertensive peptides which inhibit angiotensin-converting enzyme (ACE) and may have potential to attenuate hypertension. There is debate over their mechanism of uptake across small intestinal epithelia, but paracellular and PepT1 carrier-mediated uptake are thought to be important routes. The aim of this study was to determine their routes of intestinal permeability using in vitro , ex vivo and in vivo intestinal models. The presence of an apical side pH of 6.5 (mimicking the intestinal acidic microclimate) and of Gly-Sar (a high affinity competitive inhibitor and substrate for PepT1) were tested on the transepithelial apical to basolateral (A to B) transport of [ 3 H]-IPP and [ 3 H]-LKP across filter-grown Caco-2 monolayers in vitro and rat jejunal mucosae ex vivo . A buffer pH of 6.5 on the apical side enabled Gly-Sar to reduce the apparent permeability (P app ) of [ 3 H]-IPP and [ 3 H]-LKP, but this inhibition was not evident at an apical buffer pH of 7.4. Gly-Sar reduced the P app across isolated jejunal mucosae and the area under the curve (AUC) in intra-jejunal instillations when the apical/luminal buffer pH was either 7.4 or 6.5. However, the jejunal surface acidic pH was maintained in rat jejunal tissue even when the apical side buffer pH was 7.4 due to the presence of the microclimate which is not present in monolayers. PepT1 expression was confirmed by immunofluorescence on monolayers and brush border of rat jejunal tissue. This data suggest that IPP and LKP are highly permeable and cross small intestinal epithelia in part by the PepT1 transporter, with an additional contribution from the paracellular route. [ABSTRACT FROM AUTHOR]

Background Lifestyle issues contribute to the development of obesity, type 2 diabetes, and cardiovascular disease. Together with appropriate diet and exercise, nutraceuticals may contribute to managing prevention at an early stage prior to therapeutic intervention. However, many useful food-derived bioactive compounds will not sufficiently permeate the small intestine to yield efficacy without appropriate oral delivery technology. The pharmaceutical industry uses commercialised approaches for oral delivery including solubilizing technologies for small molecules, which could be applied to selected nutraceuticals with solubility issues. Systems currently being studied for labile and poorly permeable hydrophilic peptides and macromolecules include nanoparticles, intestinal permeation enhancers (PE) and mucolytics. These may also have potential for application to nutraceuticals with similar sub-optimal physicochemical characteristics. Scope and approach We introduce factors which effect oral delivery of four types of nutraceuticals, namely fatty acids, bioactive peptides, micronutrients, and phytochemicals. Factors preventing oral absorption can arise from molecule physicochemical characteristics, which influence solubility, stability, and epithelial permeability in the gastrointestinal tract (GIT). We highlight the potential of selected delivery strategies to improve oral bioavailability of different types of nutraceuticals. Key findings and conclusions There is an opportunity for the nutraceutical industry to leverage the pharmaceutical industry's progress in oral drug delivery. The use of delivery approaches using formulation with excipients or substances with a history of use in man has potential to improve solubility, stability, or permeability of nutraceuticals, leading to improved oral bioavailability. Leveraging oral delivery formulation approaches across nutraceutical and pharmaceutical molecules will lead to synergies for both fields. [ABSTRACT FROM AUTHOR]

Introduction Identification of a suitable treatment for osteochondral repair presents a major challenge due to existing limitations and an urgent clinical need remains for an off-the-shelf, low cost, one-step approach. A biomimetic approach, where the biomaterial itself encourages cellular infiltration from the underlying bone marrow and provides physical and chemical cues to direct these cells to regenerate the damaged tissue, provides a potential solution. To meet this need, a multi-layer collagen-based osteochondral defect repair scaffold has been developed in our group. Aim The objective of this study was to assess the in vivo response to this scaffold and determine its ability to direct regenerative responses in each layer in order to repair osteochondral tissue in a critical-sized defect in a rabbit knee. Methods Multi-layer scaffolds, consisting of a bone layer composed of type I collagen (bovine source) and hydroxyapatite (HA), an intermediate layer composed of type I and type II collagen and HA; and a superficial layer composed of type I and type II collagen (porcine source) and hyaluronic acid (HyA), were implanted into critical size (3 × 5 mm) osteochondral defects created in the medial femoral condyle of the knee joint of New Zealand white rabbits and compared to an empty control group. Repair was assessed macroscopically, histologically and using micro-CT analysis at 12 weeks post implantation. Results Analysis of repair tissue demonstrated an enhanced macroscopic appearance in the multi-layer scaffold group compared to the empty group. In addition, diffuse host cellular infiltration in the scaffold group resulted in tissue regeneration with a zonal organisation, with repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark. Conclusion These results demonstrate the potential of this biomimetic multi-layered scaffold to support and guide the host reparative response in the treatment of osteochondral defects. Statement of Significance Osteochondral defects, involving cartilage and the underlying subchondral bone, frequently occur in young active patients due to disease or injury. While some treatment options are available, success is limited and patients often eventually require joint replacement. To address this clinical need, a multi-layer collagen-based osteochondral defect repair scaffold designed to direct host-stem cell mediated tissue formation within each region, has been developed in our group. The present study investigates the in vivo response to this scaffold in a critical-sized defect in a rabbit knee. Results shows the scaffolds ability to guide the host reparative response leading to tissue regeneration with a zonal organisation, repair of the subchondral bone, formation of an overlying cartilaginous layer and evidence of an intermediate tidemark. [ABSTRACT FROM AUTHOR]

Two food-derived ACE inhibitory peptides, Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP), may have potential as alternative treatments for treatment of mild- or pre-hypertension. Lack of stability to secretory and intracellular peptidases and poor permeability across intestinal epithelia are typical limiting factors of oral delivery of peptides. The stability of IPP and LKP was confirmed in vitro in rat intestinal washes, and intestinal and liver homogenates over 60 min. A positive protein control for peptidases, insulin, was significantly digested in each format over the same period. Neither tripeptide showed cytotoxic activity on Caco-2 and Hep G2 cells using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, even after chronic exposure. The basal P app of fluorescein isothiocyanate (FITC)-labeled IPP and FITC-LKP across isolated rat jejunal and colonic mucosae were low, but were significantly increased in each tissue type by the medium chain fatty acids (MCFA) permeation enhancers, sodium caprate (C 10 ) and the sodium salt of 10-undecylenic acid (uC 11 ). IPP and LKP were therefore stable against intestinal and liver peptidases and were non-cytotoxic; their P app values across rat intestinal mucosae were low, but could be increased by MCFA. There is potential to make on oral dosage form once in vivo pharmacology is confirmed. [ABSTRACT FROM AUTHOR]

Objectives We sought to review empirical studies of psychological factors accounting for distress in caregivers of young people with early psychosis. Method Following the PRISMA guidelines, we included studies that empirically tested psychological models of caregiver distress in early psychosis by searching the following databases up until March 2014: PsycINFO, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL). This was followed by additional manual searches of reference lists and relevant journals. Results The search identified 15 papers describing 13 studies together comprising 1056 caregivers of persons with early psychosis. The mean age of caregivers was 47.2 years (SD = 9.8), of whom 71.5% were female and 74.4% were parents. Nine different psychological variables were examined in the included studies, which were categorised in the following non-mutually exclusive groups: coping, appraisal/attribution and interpersonal response. There was considerable data to support the link between distress and psychological factors such as avoidant coping, appraisal and emotional over-involvement. However, the possibilities of drawing conclusions were limited by a number of methodological issues, including cross-sectional data, small sample sizes, confounding variables not being accounted for, and a wide variation in outcome measures. Discussion The strengths of the review were the systematic approach, the exclusion of non-empirical papers and the rating of methodological quality by two independent raters. Limitations were that we excluded studies published in languages other than English, that data extraction forms were developed for this study and hence not tested for validity, and that there was a potential publication bias in favour of significant findings. Conclusion and implications A better grasp of the psychological factors accounting for caregiver distress early in the course of illness may help us understand the trajectory of distress. This is an important step in preventing long-term distress in caregivers and supporting recovery in the whole family. [ABSTRACT FROM AUTHOR]

Facebook is an environment in which adolescents can experiment with self-presentation. Unfortunately, Facebook can also be an environment in which cyberbullying occurs. The aim of the current study was to investigate whether specific self-presentation behaviours in Facebook were associated with cyberbullying victimisation for adolescents. The contents of 147 adolescent (15–24 years) Facebook profile pages were recorded and used to predict cyberbullying victimisation. Coded contents included the presence or absence of Facebook profile features (e.g., relationship status) and the specific content of certain features (e.g., type and valence of wall posts). Participants completed measures of cyberbullying victimisation and traditional bullying victimisation and perpetration. More than three out of four participants reported experiencing at least one victimisation experience on Facebook in the preceding 6 months. A series of Facebook features and experiences of traditional bullying victimisation/perpetration were found to be associated with an increased risk of cyberbullying victimisation. Number of Facebook friends and traditional bullying victimisation were also significant predictors of cyberbullying victimisation. These results support the hypothesis that self-presentation on Facebook can increase the likelihood of eliciting negative attention from potential perpetrators. This has important implications for the development of cyberbullying prevention and education programs that teach adolescents about measures they may take to decrease their risk for cyberbullying victimisation within social networking sites like Facebook. [ABSTRACT FROM AUTHOR]

Abstract: An emerging paradigm in orthopedics is that a bone-healing outcome is the product of the anabolic (bone-forming) and catabolic (bone-resorbing) outcomes. Recently, surgical and tissue engineering strategies have emerged that combine recombinant human bone morphogenetic proteins (rhBMPs) and bisphosphonates (BPs) in order to maximize anabolism and minimize catabolism. Collagen-based scaffolds that are the current surgical standard can bind rhBMPs, but not BPs. We hypothesized that a biomimetic collagen–hydroxyapatite (CHA) scaffold would bind both agents and produce superior in vivo outcomes. Consistent with this concept, in vitro elution studies utilizing rhBMP-2 ELISA assays and scintillation counting of 14C-radiolabeled zoledronic acid (ZA) confirmed delayed release of both agents from the CHA scaffold. Next, scaffolds were tested for their capacity to form ectopic bone after surgical implantation into the rat hind limb. Using CHA, a significant 6-fold increase in bone volume was seen in rhBMP-2/ZA groups compared to rhBMP-2 alone, confirming the ability of ZA to enhance rhBMP-2 bone formation. CHA scaffolds were found to be capable of generating mineralized tissue in the absence of rhBMP-2. This study has implications for future clinical treatments of critical bone defects. It demonstrates the relative advantages of co-delivering anabolic and anti-catabolic agents using a multicomponent scaffold system. [Copyright &y& Elsevier]

Abstract: Cartilage and osteochondral defects pose a significant challenge in orthopedics. Tissue engineering has shown promise as a potential method for the treatment of such defects; however, a long-lasting repair strategy has yet to be realized. This study focuses on the development of a layered construct for osteochondral repair, fabricated through a novel “iterative layering” freeze-drying technique. The process involved repeated steps of layer addition followed by freeze-drying, enabling control over material composition, pore size and substrate stiffness in each region of the construct, while also achieving a seamlessly integrated layer structure. The novel construct developed mimics the inherent gradient structure of healthy osteochondral tissue: a bone layer composed of type I collagen and hydroxyapatite (HA), an intermediate layer composed of type I collagen, type II collagen and HA and a cartilaginous region composed of type I collagen, type II collagen and hyaluronic acid. The material properties were designed to provide the biological cues required to encourage infiltration of host cells from the bone marrow while the biomechanical properties were designed to provide an environment optimized to promote differentiation of these cells towards the required lineage in each region. This novel osteochondral graft was shown to have a seamlessly integrated layer structure, high levels of porosity (>97%), a homogeneous pore structure and a high degree of pore interconnectivity. Moreover, homogeneous cellular distribution throughout the entire construct was evident following in vitro culture, demonstrating the potential of this multi-layered scaffold as an advanced strategy for osteochondral defect repair. [Copyright &y& Elsevier]

Abstract: The response of mesenchymal stem cells (MSCs) to a matrix largely depends on the composition as well as the extrinsic mechanical and morphological properties of the substrate to which they adhere to. Collagen–glycosaminoglycan (CG) scaffolds have been extensively used in a range of tissue engineering applications with great success. This is due in part to the presence of the glycosaminoglycans (GAGs) in complementing the biofunctionality of collagen. In this context, the overall goal of this study was to investigate the effect of two GAG types: chondroitin sulphate (CS) and hyaluronic acid (HyA) on the mechanical and morphological characteristics of collagen-based scaffolds and subsequently on the differentiation of rat MSCs in vitro. Morphological characterisation revealed that the incorporation of HyA resulted in a significant reduction in scaffold mean pore size (m) relative to collagen–CS (CCS) scaffolds (m). In addition, the collagen–HyA (CHyA) scaffolds exhibited greater levels of MSC infiltration in comparison to the CCS scaffolds. Moreover, these CHyA scaffolds showed significant acceleration of early stage gene expression of SOX-9 (approximately 60-fold higher, ) and collagen type II (approximately 35-fold higher, ) as well as cartilage matrix production (7-fold higher sGAG content) in comparison to CCS scaffolds by day 14. Combining their ability to stimulate MSC migration and chondrogenesis in vitro, these CHyA scaffolds show great potential as appropriate matrices for promoting cartilage tissue repair. [Copyright &y& Elsevier]

Abstract: In stem cell biology, focus has recently turned to the influence of the intrinsic properties of the extracellular matrix (ECM), such as structural, composition and elasticity, on stem cell differentiation. Utilising collagen–glycosaminoglycan (CG) scaffolds as an analogue of the ECM, this study set out to determine the effect of scaffold stiffness and composition on naive mesenchymal stem cell (MSC) differentiation in the absence of differentiation supplements. Dehydrothermal (DHT) and 1-ethyl-3-3-dimethyl aminopropyl carbodiimide (EDAC) crosslinking treatments were used to produce three homogeneous CG scaffolds with the same composition but different stiffness values: 0.5, 1 and 1.5 kPa. In addition, the effect of scaffold composition on MSC differentiation was investigated by utilising two glycosaminoglycan (GAG) types: chondroitin sulphate (CS) and hyaluronic acid (HyA). Results demonstrated that scaffolds with the lowest stiffness (0.5 kPa) facilitated a significant up-regulation in SOX9 expression indicating that MSCs are directed towards a chondrogenic lineage in more compliant scaffolds. In contrast, the greatest level of RUNX2 expression was found in the stiffest scaffolds (1.5 kPa) indicating that MSCs are directed towards an osteogenic lineage in stiffer scaffolds. Furthermore, results demonstrated that the level of up-regulation of SOX9 was higher within the CHyA scaffolds in comparison to the CCS scaffolds indicating that hyaluronic acid further influences chondrogenic differentiation. In contrast, enhanced RUNX2 expression was observed in the CCS scaffolds in comparison to the CHyA scaffolds suggesting an osteogenic influence of chondroitin sulphate on MSC differentiation. In summary, this study demonstrates that, even in the absence of differentiation supplements, scaffold stiffness can direct the fate of MSCs, an effect that is further enhanced by the GAG type used within the CG scaffolds. These results have significant implications for the therapeutic uses of stem cells and enhance our understanding of the physical effects of the in vivo microenvironment on stem cell behaviour. [Copyright &y& Elsevier]

Oral delivery of macromolecular drugs is the most patient-preferred route of administration because it is painless and convenient. Over the past 30 years, significant attention has been paid to oral protein delivery in adults. Unfortunately, there is an outstanding need for similar efforts in infants, a patient population with distinct intestinal physiology and treatment needs. Here, we assess the intestinal permeability of neonatal and infant mice to determine the feasibility of orally delivering peptide and protein drugs without permeation enhancers or other assistance. Using the non-everted gut sac model, we found that macromolecular permeability depended on molecular size, mouse age, and intestinal tissue type using model dextrans. For example, the apparent permeability of 70 kDa FITC-Dextran (FD70) in infant small intestinal tissue was 2-5-fold higher than in adult tissue. As mice aged, the expression of barrier-forming and pore-forming tight junction proteins increased and decreased, respectively. The in vivo oral absorption of 4 kDa FITC-Dextran (FD4) and FD70 was significantly higher in younger mice, and there was a fourfold increase in oral absorption of the 80 kDa protein lactoferrin compared to adults. Oral gavage of insulin (5 IU/kg) reduced blood glucose levels in infants by >20% at 2 and 3 h but had no effect in adults. Oral insulin had 35% and <1% of the pharmacodynamic effect of a 1 IU/kg subcutaneous dose in infants and adults, as measured by area above the curve. These data indicate that the uniquely leaky nature of the infantile intestine may support the oral delivery of biologics without the need for traditional oral delivery technology. [ABSTRACT FROM AUTHOR]

Abstract: The aims of this study were to validate a computerised method to detect muscle activity from surface electromyography (SEMG) signals in gait in patients with cervical spondylotic myelopathy (CSM), and to evaluate the test–retest reliability of the activation times designated by this method. SEMG signals were recorded from rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and medial gastrocnemius (MG), during gait in 12 participants with CSM on two separate test days. Four computerised activity detection methods, based on the Teager–Kaiser Energy Operator (TKEO), were applied to a subset of signals and compared to visual interpretation of muscle activation. The most accurate method was then applied to all signals for evaluation of test–retest reliability. A detection method based on a combined slope and amplitude threshold showed the highest agreement (87.5%) with visual interpretation. With respect to reliability, the standard error of measurement (SEM) of the timing of RF, TA and MG between test days was 5.5% stride duration or less, while the SEM of BF was 9.4%. The timing parameters of RF, TA and MG designated by this method were considered sufficiently reliable for use in clinical practice, however the reliability of BF was questionable. [Copyright &y& Elsevier]

Background Three out of four first-episode psychosis (FEP) patients achieve clinical remission following treatment. Unfortunately, functional recovery lags behind symptomatic remission, and many individuals with FEP remain socially isolated with poor functional outcomes. Aims To systematically compile and analyse predictors of functional recovery in FEP. Method Systematic review and meta-analysis of peer-reviewed, longitudinal studies reporting predictors of functioning, with a minimum 12-month follow-up and at least 80% of participants diagnosed with FEP. Results Out of 2205 citations, 274 articles were retrieved for detailed evaluation resulting in 50 eligible studies ( N = 6669). Sociodemographic, clinical, physical and neuroimaging variables had little impact on long-term functioning. Conversely duration of untreated psychosis (DUP), most cognitive variables, and concurrent remission of positive and negative symptoms were independently related to functional recovery. Conclusions These findings strongly support the rationale for early intervention in FEP. Novel treatments targeting cognitive deficits may improve functional outcomes in FEP. [ABSTRACT FROM AUTHOR]

Developing repair strategies for osteochondral tissue presents complex challenges due to its interfacial nature and complex zonal structure, consisting of subchondral bone, intermediate calcified cartilage and the superficial cartilage regions. In this study, the long term ability of a multi-layered biomimetic collagen-based scaffold to repair osteochondral defects is investigated in a large animal model: namely critical sized lateral trochlear ridge (TR) and medial femoral condyle (MC) defects in the caprine stifle joint. The study thus presents the first data in a clinically applicable large animal model. Scaffold fixation and early integration was demonstrated at 2 weeks post implantation. Macroscopic analysis demonstrated improved healing in the multi-layered scaffold group compared to empty defects and a market approved synthetic polymer osteochondral scaffold groups at 6 and 12 months post implantation. Radiological analysis demonstrated superior subchondral bone formation in both defect sites in the multi-layered scaffold group as early as 3 months, with complete regeneration of subchondral bone by 12 months. Histological analysis confirmed the formation of well-structured subchondral trabecular bone and hyaline-like cartilage tissue in the multi-layered scaffold group by 12 months with restoration of the anatomical tidemark. Demonstration of improved healing following treatment with this natural polymer scaffold, through the recruitment of host cells with no requirement for pre-culture, shows the potential of this device for the treatment of patients presenting with osteochondal lesions. [ABSTRACT FROM AUTHOR]

Abstract: Aims: The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) is a brief, easily administered, valid and reliable screening instrument for all psychoactive substances in drug treatment and primary care settings. This study aims to determine the reliability and validity of the ASSIST for detecting substance use disorders in first-episode psychosis. Participants: Participants were 214 first-episode psychosis patients attending the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne, Australia. Measurements: Participants were administered the ASSIST, Alcohol Use Disorders Identification Test (AUDIT), the Severity of Dependence Scale (SDS) and the Brief Psychiatric Rating Scale (BPRS). Presence of DSM-IV substance abuse and dependence disorders in the previous 12 months was assessed using the Structured Clinical Interview for DSM-IV (SCID-IV). Findings: The ASSIST total substance involvement (TSI) score and specific substance involvement (SSI) scores for cannabis, alcohol and amphetamine use demonstrated high levels of internal consistency and acceptable levels of concurrent and discriminative validity. Individuals with cutoff scores of ≥2, 4 and 1 on the ASSIST cannabis, alcohol and amphetamine SSI scores were 5 to 6 times more likely to meet the diagnostic criteria for these substance use disorders. Conclusions: The ASSIST is a psychometrically sound measure of cannabis, alcohol and amphetamine use disorders in first-episode psychosis. [Copyright &y& Elsevier]

Abstract: Semantic processing deficits may underlie thought disorder in schizophrenia. Cognitive Disorganisation (CD) in schizotypy is a thought disorder analogue. This study established CD was related to abnormal strategic semantic processing on an indirect semantic priming task. There were no gender differences. It also confirms the importance of replicating underpowered studies. [Copyright &y& Elsevier]