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Keratins are epithelial intermediate filament proteins that play a crucial role in cellular stress protection, with K8 being the most abundant in the colon. The intestinal epithelial-specific K8-deficient mouse model (K8flox/flox;Villin-Cre) exhibits characteristics of inflammatory bowel disease, including diarrhea, crypt erosion, hyperproliferation, and decreased barrier function. Nevertheless, the order in which these events occur and whether they are a direct cause of K8 loss or a consequence of one event inducing another remains unexplored. Increased knowledge about early events in the disruption of colon epithelial integrity would help to understand the early pathology of inflammatory and functional colon disorders and develop preclinical models and diagnostics of colonic diseases. Here, we aimed to characterize the order of physiological events after Krt8 loss by utilizing K8flox/flox;Villin-CreERt2 mice with tamoxifen-inducible Krt8 deletion in intestinal epithelial cells, and assess stool analysis as a noninvasive method to monitor real-time gene expression changes following Krt8 loss. K8 protein was significantly decreased within a day after induction, followed by its binding partners, K18 and K19 from day 4 onward. The sequential colonic K8 downregulation in adult mice leads to immediate diarrhea and crypt elongation with activation of proliferation signaling, followed by crypt loss and increased neutrophil activity within 6-8 days, highlighting impaired water balance and crypt elongation as the earliest colonic changes upon Krt8 loss. Furthermore, epithelial gene expression patterns were comparable between colon tissue and stool samples, demonstrating the feasibility of noninvasive monitoring of gut epithelia in preclinical research utilizing Cre-LoxP-based intestinal disease models. NEW & NOTEWORTHY: Understanding the order in which physiological and molecular events occur helps to recognize the onset of diseases and improve their preclinical models. We utilized Cre-Lox-based inducible keratin 8 deletion in mouse intestinal epithelium to characterize the earliest events after keratin 8 loss leading to colitis. These include diarrhea and crypt elongation, followed by erosion and neutrophil activity. Our results also support noninvasive methodology for monitoring colon diseases in preclinical models. [ABSTRACT FROM AUTHOR]

The diagnosis of inflammatory bowel diseases (IBD) may be challenging and their clinical course, characterized by relapses and spontaneous or drug-induced remissions, is difficult to predict. Novel prognostic biomarkers are needed. Keratin 7 (K7) is a cytoskeletal intermediate filament protein which is not normally expressed in the colonic epithelium. It was recently shown that K7 expression in the colonic epithelium is associated with ulcerative colitis and Crohn's disease, the two main subtypes of IBD. Here we investigated IBD associated K7 neo-expression in different regions of colon and terminal ileum. The correlation of the K7 expression with the inflammatory activity of the epithelium was analyzed in each region. The prognostic value of K7 was estimated by comparing the clinical disease activity after 3 years with the K7 expression at the time of enrollment. Our data shows that the level of K7 expression in inflamed epithelium varies depending on the anatomical region and it is the most pronounced in ascending and descending colon, but it did not predict the severity of IBD for the following 3 years. These results warrant future studies focusing on the biological role of K7 in colon and its utilization as potential IBD biomarker. [ABSTRACT FROM AUTHOR]

The clinical course of IBD, characterized by relapses and remissions, is difficult to predict. Initial diagnosis can be challenging, and novel disease markers are needed. Keratin 7 (K7) is a cytoskeletal intermediate filament protein not expressed in the colonic epithelium but has been reported in IBD-associated colorectal tumors. Our aim was to analyze whether K7 is expressed in chronic colonic inflammatory diseases and evaluate its potential as a novel biomarker. K7 was analyzed in two patient cohorts using immunohistochemistry-stained colon samples and single-cell quantitative digital pathology methods. K7 was correlated to pathological changes and clinical patient characteristics. Our data shows that K7 is expressed de novo in the colonic epithelium of ulcerative colitis and Crohn's disease IBD patients, but not in collagenous or lymphocytic colitis. K7 mRNA expression was significantly increased in colons of IBD patients compared to controls when assessed in publicly available datasets. While K7 increased in areas with inflammatory activity, it was not expressed in specific crypt compartments and did not correlate with neutrophils or stool calprotectin. K7 was increased in areas proximal to pathological alterations and was most pronounced in drug-resistant ulcerative colitis. In conclusion, colonic epithelial K7 is neo-expressed selectively in IBD patients and could be investigated for its potential as a disease biomarker. [ABSTRACT FROM AUTHOR]

Introduction: Despite the established finding that migrants are at higher risk of developing a first-episode psychosis, they are under-represented in cohorts of young people identified as being at ultra-high risk for psychosis (UHR). Therefore, in order to determine the reasons for these conflicting findings, this study examined the pathways to care and clinical presentation of migrants attending an At-Risk Mental State clinic.Methodology: This study included consecutive UHR cases identified over five years attending the PACE clinic in Melbourne, Australia. The CAARMS was used to assess the severity of attenuated psychotic symptoms. Depressive symptoms and functioning were measured using the PHQ9 and GAF, respectively.Results: Over the five-year study period, 461 UHR young people attended the PACE clinic and 13.7% were first-generation migrants. A higher proportion of migrants were referred by community health services, such as general practitioners, than other referral sources. Australian born UHR patients were more likely to be referred via another mental health service. There was no difference in the type or severity of attenuated psychotic symptoms based on migrant status, except that there was a trend for young African migrants to have more severe unusual thought content. Depressive symptoms and poor functioning were highly prevalent across the total cohort and did not differ according to migrant status.Conclusions: It is not yet understood why migrants are under-represented in UHR cohorts. Qualitative interviews of migrants, who are not typically identified in the UHR stage, could provide insights into the barriers to accessing care. [ABSTRACT FROM AUTHOR]

Keratin (K) intermediate filaments are attached to desmosomes and constitute the orchestrators of epithelial cell and tissue architecture. While their relevance in the epidermis is well recognized, our review focuses on their emerging importance in internal epithelia. The significance of keratin-desmosome scaffolds (KDSs) in the intestine is highlighted by transgenic mouse models and individuals with inflammatory bowel disease who display profound KDS alterations. In lung, high K8 expression defines a transitional cell subset during regeneration, and K8 variants are associated with idiopathic pulmonary fibrosis. Inherited variants in desmosomal proteins are overrepresented in idiopathic lung fibrosis, and familiar eosinophilic esophagitis. K18 serum fragments are established hepatocellular injury markers that correlate with the extent of histological inflammation. K17 expression is modified in multiple tumors, and K17 levels might be of prognostic relevance. These data should spur further studies on biological roles of these versatile tissue protectors and efforts on their therapeutic targeting. [ABSTRACT FROM AUTHOR]

Objective: Language used in psychiatry is important because it provides an understandable and accurate way of describing clinical and theoretical concepts. The use of labels in psychiatry has often been associated with stigma and reduced engagement with clinical services. This studys aims were to generate new terms for the 'at-risk mental state' (ARMS) concept and to investigate what young people, their caregivers and clinicians thought about them as well as terms commonly used in early intervention clinics. Another aim was to understand participants preference related to the best timing to introduce the at-risk concept and the extent and context of the information presented.Methods: New terms illustrating the at-risk concept have been generated by a youth reference group with lived experience of mental illness: 'pre-diagnosis stage' (PDS), potential of developing a mental illness (PDMI) and disposition for developing a mental illness (DDMI). A specifically designed questionnaire was administered to 46 patients with ARMS, 24 caregivers and 52 clinicians to obtain their feedback on newly proposed terms and on the terms already used in clinical practice and research.Results: The preferred terms were PDS, PDMI and ARMS. The least favoured terms were Ultra High Risk and Attenuated Psychosis Syndrome, which were thought to be associated with the most stigma. Most participants agreed that disclosure about diagnosis should be delivered early by the key clinician.Conclusions: Patients generated terms such as PDS, PDMI, alongside ARMS should be considered to be used in clinical practice. They present with low stigma and are illustrative of young peoples difficulties. [ABSTRACT FROM AUTHOR]

Aim: Several prediction models have been introduced to identify young people at greatest risk of transitioning to psychosis. To date, none has examined the possibility of developing a clinical prediction model of outcomes other than transition. The aims of this study were to examine the association between baseline clinical predictors and outcomes including, but not limited to, transition to psychosis in young people at risk for psychosis, and to develop a prediction model for these outcomes. Methods: Several evidence‐based variables previously associated with transition to psychosis and some important clinical comorbidities experienced by ultra‐high risk (UHR) individuals were identified in 202 UHR individuals. Secondary analysis of the Neurapro clinical trial were conducted to investigate the associations between these variables and favourable (remission and recovery) or unfavourable (transition to psychosis, no remission, any recurrence and relapse) clinical outcomes. Logistic regression, best subset selection, Akaike Information Criterion and receiver operating characteristic curves were used to seek the best prediction model for clinical outcomes from all combinations of possible predictors. Results: When considered individually, only higher general psychopathology levels (P =.023) was associated with the unfavourable outcomes. Prediction models suggest that general psychopathology and functioning are predictive of unfavourable outcomes. Conclusion: The predictive performance of the resulting models was modest and further research is needed. Nonetheless, when designing early intervention centres aiming to support individuals in the early phases of a mental disorder, the proper assessment of general psychopathology and functioning should be considered in order to inform interventions and length of care provided. [ABSTRACT FROM AUTHOR]

The impact of cultivar, harvest time, and crop season on olive fruit characteristics and olive oil quality and minor components composition is assessed for super‐high‐density "Arbequina", "Arbosana", and "Koroneiki" in California, United States, during 2016, 2017, and 2018. Fruit oil content reaches a plateau in November for "Arbequina" and "Arbosana," while the accumulation rate keeps constant until early December for "Koroneiki." Free fatty acids, diacylglycerols, pyropheophytins, and ΔK are not affected by any of the considered factors. Peroxide value, K232, and K270 decreases with harvest time. Chlorophylls content decreases with harvest time, more rapidly in "Arbequina" and "Arbosana" than in "Koroneiki". Cultivar is the main factor affecting the fatty acid profile. "Koroneiki" has the highest oleic acid content, followed by "Arbosana" and "Arbequina." Phenolic and volatile compounds are profoundly affected by cultivars and crop seasons, suggesting the relevance of these factors on the sensory and nutritional properties of virgin olive oil from super‐high‐density cultivars. Stepwise linear discriminant analysis allows selecting suitable markers among fatty acids, phenolic, and volatile compounds for cultivar, crop season, and harvest time discrimination. Practical Application: This paper constitutes the first report of a multiyear study considering quality and composition in bioactive compounds of super‐high‐density "Arbequina," "Arbosana," and "Koroneiki," planted in California, USA. This information helps processors understand the differences in oil made from the most common super‐high‐density cultivars along harvest times and for growers to make planting and harvesting decisions. [ABSTRACT FROM AUTHOR]

Muito se fala de integração sensorial na reabilitação pediátrica, no entanto, não parece haver uma conceitualização padrão entre as terapias. O objetivo deste trabalho é descrever as diferenças conceituais nas intervenções que se baseiam nos processos e estímulos sensoriais. A revisão de escopo foi baseada nas pesquisas realizadas na PubMed, Bireme e Scopus por meio de descritores "Integração Sensorial", "Integração Sensorial de Ayres", "Integração Sensório-Motora" e Estimulação Sensorial". Os artigos foram selecionados usando o software Rayyan, contemplando intervenções realizadas no Brasil. Dos 1682 artigos, 1660 foram excluídos por meio de leitura de título e/ou resumo; selecionou-se 22 artigos completos e 9 estudos atenderam a todos os critérios de inclusão para esta revisão. O termo Integração Sensorial apontase como um guarda-chuva para diversas possibilidades de intervenção. Os diferentes conceitos que embasaram as intervenções com Integração Sensorial encontrados foram Paradigma da Sala-Móvel, Estimulação Sensorial oro-gustativa, Integração Sensorial Ideal, Integração Sensório-Motora e Integração Sensorial de Ayres. Conclui-se que as diferenças percebidas entre os conceitos usados nas intervenções sugerem a Integração Sensório-Motora, para as intervenções que propõem ações motoras e o controle do corpo desejado para o sujeito no ambiente, enquanto a Integração Sensorial de Ayres propõe a realização de uma atividade e na participação desejada pelo sujeito no ambiente. [ABSTRACT FROM AUTHOR]

Objective: to compare the time Brazilian adults required to make food choices with different models of front-of-pack nutrition labeling. Methods: Interviews were conducted with 150 participants, who were instructed to select the healthiest product between two foods, with eight pairs of images presented. One of the products in each pair had warnings (high in sugars, sodium, or saturated fat), evaluated in different formats according to the group in which the individual was allocated: magnifying glass, octagon, circle, triangle, and traffic light. The number of correct answers for the healthiest product in each pair and the time to correctly select of the healthiest product were measured. Results: A lower number of correct answers for the healthier product among the pairs occurred with traffic lights than with any other model (p <0.001), which is also the format in which the longest time was necessary to correctly select the healthiest product (p < 0.001). There were no significant differences between the other formats. In the individual analysis of the products, the circle performed better, with significantly less time required to make the correct choices in seven of the eight products. Conclusion: To support healthy food choices, any of the tested formats for frontal nutrition labeling are indicated, except for the traffic light. The circle appears to be a good option to reduce consumer's time to select healthy choices. [ABSTRACT FROM AUTHOR]

Moisture and fat content, fatty acid profile, and volatile terpenes were measured for the first time for 'Kalehghouchi', 'Pete 1', and 'Lost Hills' pistachios grown at two California microclimates: Lost Hills and Parlier. 'Kalehghouchi' had the highest moisture content, followed by 'Pete 1' and 'Lost Hills', respectively. While the moisture content of 'Kalehghouchi' was not significantly affected by location, it was lower for 'Pete 1' grown at Parlier (40.8 vs. 40.8 g/100 g) and higher for 'Lost Hill' grown there (48.2 vs. 45.2 g/100 g). 'Pete 1' grown at the Parlier site had a higher fat content compared with 'Lost Hills' (47.7 vs. 43.0 g/100 g). 'Kalehghouchi' had a lower fat content at Parlier compared with Lost Hills (42.0 vs. 44.9 g/100 g), and 'Lost Hills' was unaffected by location. The main fatty acid measured in the pistachio samples was oleic acid (52% to 58%), followed by linoleic (26% to 33%) and palmitic acids (11% to 13%). While oleic acid content of 'Lost Hills' and 'Kalehghouchi' was higher for pistachios grown in Parlier, no impact of location was observed for 'Pete 1'. The fatty acid profiles of all three cultivars appeared to be more dependent on genotype and less affected by microclimate. α-pinene (95-1682 ng/kg), limonene (37-741 ng/kg), and α-terpinolene (1-368 ng/kg) were the most abundant volatiles among all the cultivars and locations. Microclimate was the primary factor in determining volatile terpenes concentration in pistachio kernels. [ABSTRACT FROM AUTHOR]

Aim: Clinical staging in psychiatry aims to classify patients according to the severity of their symptoms, from stage 0 (increased risk, asymptomatic) to stage 4 (severe illness), enabling adapted treatment at each stage of the illness. The staging model would gain specificity if one or more quantifiable biological markers could be identified. Several biomarkers reflecting possible causal mechanisms and/or consequences of the pathophysiology are candidates for integration into the clinical staging model of psychiatric illnesses. Methods: This review covers the evolution (from stage 0 to stage 4) of the most important brain functioning impairments as measured with electroencephalography (EEG), in psychosis spectrum and in severe mood disorders. Results: The present review of the literature demonstrates that it is currently not possible to draw any conclusion with regard to the state or trait character of any of the EEG impairments in both major depressive disorder and bipolar disorder. As for schizophrenia, the most promising markers of the stage of the illness are the pitch mismatch negativity as well as the p300 event‐related potentials, as these components seem to deteriorate with increasing severity of the illness. Conclusions: Given the complexity of major psychiatric disorders, and that not a single impairment can be observed in all patients, future research should most likely consider combinations of markers in the quest for a better identification of the stages of the psychiatric illnesses. [ABSTRACT FROM AUTHOR]

Purpose: Inflammatory bowel disease (IBD) can be imaged with positron emission tomography (PET), but existing PET radiopharmaceuticals have limited diagnostic accuracy. Vascular adhesion protein-1 (VAP-1) is an endothelial cell surface molecule that controls leukocyte extravasation into sites of inflammation. However, the role of inflammation-induced VAP-1 expression in IBD is still unclear. Therefore, this study investigated the utility of VAP-1-targeted [68Ga]Ga-DOTA-Siglec-9 positron emission tomography/computed tomography (PET/CT) for assessing inflammation in two mouse models of IBD. Procedures: Studies were performed using K8−/− mice that develop a chronic colitis-phenotype and C57Bl/6NCrl mice with acute intestinal inflammation chemically-induced using 2.5% dextran sodium sulfate (DSS) in drinking water. In both diseased and control mice, uptake of the VAP-1-targeting peptide [68Ga]Ga-DOTA-Siglec-9 was assessed in intestinal regions of interest using in vivo PET/CT, after which ex vivo gamma counting, digital autoradiography, and histopathological analyses were performed. Immunofluorescence staining was performed to determine VAP-1-expression in the intestine, including in samples from patients with ulcerative colitis. Results: Intestinal inflammation could be visualized by [68Ga]Ga-DOTA-Siglec-9 PET/CT in two murine models of IBD. In both models, the in vivo PET/CT and ex vivo studies of [68Ga]Ga-DOTA-Siglec-9 uptake were significantly higher than in control mice. The in vivo uptake was increased on average 1.4-fold in the DSS model and 2.0-fold in the K8−/− model. Immunofluorescence staining revealed strong expression of VAP-1 in the inflamed intestines of both mice and patients. Conclusions: This study suggests that the VAP-1-targeting [68Ga]Ga-DOTA-Siglec-9 PET tracer is a promising tool for non-invasive imaging of intestinal inflammation. Future studies in patients with IBD and evaluation of the potential value of [68Ga]Ga-DOTA-Siglec-9 in diagnosis and monitoring of the disease are warranted. [ABSTRACT FROM AUTHOR]

Pistachio is an economically important nut crop in California. Since temperature variations among geographical locations can influence biochemical processes during fruit development, it is of great relevance to understand the impact of growing area over the components that define the nutritional and sensory characteristics of pistachio nuts. Changes in moisture, fat content, fatty acid composition and volatile terpenes were studied during kernel development for "Kerman" and "Golden Hills" varieties in two different California Central Valley microclimates, Lost Hills and Parlier. Moisture content decreased from July to September for both cultivars at both locations. Kerman had a higher moisture content at both locations compared with Golden Hills. Harvest time affected fat content only for Kerman, where the values increased drastically from 21‐July to 4‐Aug, then remained constant. Golden Hills' fat content remained constant during the period of the study. The main fatty acid in pistachio oil is oleic acid (46% to 59%), followed by linoleic acid (26% to 36%) and palmitic acid (11% to 16%). C16:0, C16:1, C18:2, and C18:3 decreased with harvest time, while C18:1 increased. α‐Pinene was the most concentrated volatile among the cultivars and locations. It decreased with harvest time for both cultivars at both locations, ranging from 105 to 2464 mg/kg. At harvest, Golden Hills and Kerman at Parlier both had higher concentrations of α‐pinene than the two cultivars at Lost Hills. Our results demonstrate that microclimate affects biosynthesis of fatty acids and terpenes in pistachio kernels, the main compounds responsible for pistachio nutritional and sensory characteristics. [ABSTRACT FROM AUTHOR]

Aim: To examine reasons for referral to a specialist ultra‐high risk (UHR) for psychosis clinic and whether these reasons are associated with risk for subsequent transition to psychosis. Methods: Data for 127 patients referred to the Personal Assessment and Crisis Evaluation clinic were collected by medical record audit. Time to transition to psychosis was calculated from date of referral to time at which the young person was judged by their treating team to be experiencing onset of first episode psychosis. Results: Patients were primarily referred due to attenuated psychotic symptoms and depression (40.2%). There was an association with transition, with those in the attenuated psychotic‐symptom‐only category being more likely to transition. Conclusion: As well as attenuated psychotic symptoms, depression and anxiety were also important reasons for referral indicating that there is a broad clinical phenotype of young people presenting to UHR clinics. Clinical reason for referral may index level of risk for subsequent transition to psychosis. [ABSTRACT FROM AUTHOR]

Highlights • The mixture design investigated the extraction efficiency of the phenolic compounds. • Mixtures of moderately polar solvents were highly efficient in the extraction. • Addition of water to organic solvents improved the extraction efficiency. • Rosmarinic acid and myricetin are the major compounds in Brazilian chia seeds. Abstract This study investigated the efficiency of the extraction of phenolic compounds from seeds of chia, Salvia hispanica L. utilizing the statistical tool of mixture planning, simplex-lattice design. The solvents used were acetone, ethanol and water and the responses analyzed were total phenolic content (TPC), antioxidant activity by the capture of the free radical DPPH and ferric reduction ability (FRAP). Moderately polar mixtures were highly efficient to extract the antioxidant phenolic compounds. The best results were obtained for the water-acetone (1/3–2/3) binary mixture, presenting TPC, DPPP and FRAP values of 58.44 mg GAE/g, 250.20 μmol TE/g and 720.15 μmol TE/g, respectively. The best ternary mixture was water-ethanol-acetone (1/6–1/6–2/3), with 60.96 mg GAE/g, 380.53 μmol TE/g and 990.15 μmol TE/g, respectively. The phenolic profile showed that the acids rosmarinic, caffeic, salicylic and the flavonoids myricetin and quercetin are the compounds that most contribute to the elevated antioxidant activity. [ABSTRACT FROM AUTHOR]

Several analytical methods are available to evaluate virgin olive oil (VOO) minor compounds; however, multi-class methodologies are yet rarely studied. Herewith, LC-MS and GC–MS platforms were used to develop two methods capable of simultaneously determine more than 40 compounds belonging to different VOO minor chemical classes within a single run. A non-selective and highly efficient liquid-liquid extraction protocol was optimized for VOO minor components isolation. The separation and detection conditions were adjusted for determining phenolic and triterpenic compounds, free fatty acids and tocopherols by LC-MS, plus sterols and hydrocarbons by GC–MS. Chromatographic analysis times were 31 and 50 min, respectively. A comparative assessment of both methods in terms of analytical performance, easiness, cost and adequacy to the analysis of each class was carried out. The emergence of this kind of multi-class analytical methodologies greatly increases throughput and reduces cost, while avoiding the complexity and redundancy of single-chemical class determinations. [ABSTRACT FROM AUTHOR]

Signaling via estrogen receptors (ER) is recognized as an essential part of the immune regulation, and ER-mediated signaling is involved in autoimmune reactions. Especially ERα activation in immune cells has been suggested to skew cytokine production toward Th2/M2-type mediators, which can have protective effect on inflammatory diseases and reduce Th1 and Th17 responses. These effects are caused by increased alternative activation of macrophages and changes in the activation of different T cell populations. In humans, hormonal status has been shown to have a major impact on several inflammatory diseases. Selective estrogen receptor modulators (SERMs) are ER ligands that regulate ER actions in a tissue-specific manner mostly lacking the adverse effects of steroid hormones. The impact of SERMs on the immune system is less studied, but it is suggested that certain SERMs may also produce immunoprotective effects. Here, we show that two novel SERMs and raloxifene affect immune cells by promoting M2 macrophage phenotype, alleviating NFκB activity, inhibiting T cell proliferation, and stimulating the production of anti-inflammatory compounds such as IL10 and IL1 receptor antagonist. Thus, these compounds have high potency as drug candidates against autoimmune diseases. [ABSTRACT FROM AUTHOR]

Maternal cytokine profiles during pregnancy are characterized by significant deviations, varying substantially between gestational time points and tissues. Obesity, in turn, is linked with low-grade inflammation in adipose tissue and increased concentrations of systemic inflammatory mediators. However, the balance of pro- and anti-inflammatory cytokines in obese pregnancy has remained elusive. In view of the demonstrations that the obesity is a global epidemic in the population at reproductive age with a strong intergenerational impact, we investigated the relation of gestational immune adaptations and obesity-induced inflammation. We found a significant decrease in systemic IL-1β and MCP-1 concentration from 1st to 3rd trimester of pregnancy while IL-10 concentration increased, respectively. However, in obese pregnancies this reduction of pro-inflammatory mediators was not detected. This may constitute an additional risk factor in obese pregnancies in which the concentration of MCP-1 is already upregulated compared to normal weight mothers. [ABSTRACT FROM AUTHOR]

Hammer mill crushing variables and malaxation time are studied through a two‐level factor factorial experimental design in order to assess the impact of these parameters and their interactions on olive oil extraction efficiency, overall quality, and minor components composition. Extraction efficiency is mainly affected by the interaction between hammer mill grid size and malaxation time; higher yields are obtained when smaller grid sizes are combined with longer malaxation times. Regarding quality parameters and volatile compounds, the main effect is caused by malaxation time. Phenolic compounds are affected by all the studied parameters, hammer mill grid size has the highest impact on their final concentration in the oil. The results show that the effect of malaxation time on the studied variables is conditioned by the crushing parameters used during paste preparation. Practical Applications: Traditionally, the impact of processing variables on olive oil composition has been studied following a one‐variable‐at‐a‐time approach. A factor factorial experimental design allows the interactions among crushing conditions and malaxation time to be determined, as well as the individual contributions to extraction efficiency and minor components composition of these variables. Considering a more holistic approach to the study of olive oil extraction might provide processors with a wider spectrum of tools to maximize both yield and quality during olive oil processing. Interaction of grid size, rotor speed, and malaxation time during olive oil extraction affects extraction efficiency, volatiles, and phenolics. [ABSTRACT FROM AUTHOR]

Background: Traditionally, research in the ultra-high risk (UHR) for psychosis population has focused on the treatment of existing symptomatology and prevention of transition to psychosis. Recently, there has been an increase in focus on outcomes in individuals who do not transition to psychosis. However, there is a lack of standardised definitions of remission, recovery, recurrence and relapse in UHR, resulting in the inability to generalise and replicate outcomes.Method: The aims of the current study were to develop definitions for remission, recovery, recurrence and relapse, and apply them to a UHR cohort allowing the identification of longitudinal clinical trajectories. Further stratification in broader categories of favourable and unfavourable outcomes was applied. The predictive value of various baseline factors on specific clinical trajectories was also assessed.Results: 17 different trajectories were identified in a cohort of 202 individuals within a 12-month period and classified according to the suggested definitions for recovery (35.7%), remission (7.5%), any recurrence (20%), no remission (17.3%), relapse (4.0%) and transition to psychosis (15.8%). Favourable and unfavourable trajectories represented 43.2% and 57.1% respectively. Long duration of untreated symptoms and high depression scores were associated with unfavourable outcomes.Discussion: It is possible to apply clear definitions of remission, recovery, recurrence, relapse and transition to psychosis to a UHR cohort to evaluate longitudinal clinical trajectories. Acceptance and use of these definitions will help to facilitate comparisons between trials and to improve clinical clarity across the range of available therapeutic options in UHR individuals. [ABSTRACT FROM AUTHOR]

Crushing is a key step during olive oil extraction. Among commercial crushers, the hammer mill is the most widely used due to its robustness and high throughput. In the present work, the impact of hammer mill rotor speed on extraction yield and overall quality of super-high-density Arbosana olive oils were assessed in an industrial facility. Our results show that increasing the rotor speed from 2400 rpm to 3600 rpm led to a rise in oil yield of 1.2%, while conserving quality parameters. Sensory analysis showed more pungency with increased rotation speed, while others attributes were unaffected. Volatile compounds showed little variation with the differences in crusher speed; however, total phenols content, two relevant secoiridoids, and triterpenoids levels increased with rotor speed. Hammer mill rotor speed is a processing variable that can be tuned to increase the extraction efficiency and modulate the chemical composition of extra virgin olive oil. [ABSTRACT FROM AUTHOR]

Aim The 'ultra-high-risk' criteria identify a clinical population at substantially increased risk for progressing to schizophrenia and other psychotic disorders. Although a number of clinical variables predictive of transition to psychotic disorder have been identified within this population, the predictive value of the level of distress associated with attenuated psychotic symptoms has not yet been examined. This was the aim of the present study. Method The level of distress (0-100) associated with attenuated psychotic symptoms was recorded for 70 ultra-high-risk ( UHR) patients using the Comprehensive Assessment of At-Risk Mental State ( CAARMS). Transition to psychosis was assessed over a 16-month follow-up period. Results Of the 70 UHR patients, 15 transitioned to psychosis (21.4%). Of the four CAARMS subscales measuring attenuated positive symptoms, Perceptual Abnormalities was rated as the most distressing. There were no differences in CAARMS scales rated as the most distressing between those who transitioned to psychosis and those who did not. There was also no association between higher levels of distress associated with attenuated psychotic symptoms and transition to psychosis. Conclusion Although the findings require replication, they indicate that the degree of distress associated with attenuated psychotic symptoms should not be used as a criterion for enriching UHR samples for risk of frank psychotic disorder. [ABSTRACT FROM AUTHOR]

The pleasant taste and flavor of coffee are responsible for making it one of the most preferred and consumed beverages around the world. Industrial coffee plants usually roast both coffee and adulterants together, which affects directly the quality of the product, specially the sensorial characteristics of the drink. Therefore, this work aims the identification of adulterations in ground roasted coffees (due to the presence of husks and sticks) using ultraviolet–visible spectroscopy and the Successive Projections Algorithm for variable selection in association with Linear Discriminant Analysis (SPA-LDA). For this purpose, extracts of ground roasted coffees prepared in hot water alone (representing the final product as ingested by the consumers) were then analyzed. The proposed methodology obtained a 100% classification in both training and test sets, providing a simple and fast analysis of the aqueous extracts of ground roasted coffees. Moreover, it can also afford security to coffee consumers and regulatory agencies, preventing the fraudulent labeling. [ABSTRACT FROM AUTHOR]

Obesity and white adipose tissue (WAT) inflammation are associated with enhanced aromatization in women, but little is known about the regulation of aromatase ( CYP19A1 ) gene expression in male WAT. We investigated the impact of weight gain and WAT inflammation on the regulation of CYP19A1 in males, by utilizing the hARO-Luc aromatase reporter mouse model containing a >100-kb 5′-region of the human CYP19A1 gene. We show that hARO-Luc reporter activity is enhanced in WAT of mice with increased adiposity and inflammation. Dexamethasone and TNFα, as well as forskolin and phorbol 12-myristate 13-acetate, upregulate hARO-Luc activity, suggesting the involvement of promoters I.4 and I.3/II. Furthermore, we show that diet enriched with antioxidative plant polyphenols attenuates WAT inflammation and hARO-Luc activity in obese males. In conclusion, our data suggest that obesity-associated WAT inflammation leads to increased peripheral CYP19A1 expression in males, and that polyphenol-enriched diet may have the potential to attenuate excessive aromatization in WAT of obese men. [ABSTRACT FROM AUTHOR]

Chromatographic techniques such as GC and HPLC are traditionally used for the analysis and classification of olive oil, while NMR is another powerful technique. In this paper we used NMR for the first time to classify olive oil produced by four cultivars, namely 'Arbequina', 'Arbosana', 'Koroneiki', and 'Sikitita', planted in super-high-density frames in California, United States. We compared the results with the targeted analysis of fatty acids and triglycerides obtained by GC-FID and UHPLC-CAD, respectively. All three techniques were able to distinguish between cultivars, with fatty acids from GC-FID generating the best models. GC-FID require time-consuming sample preparation; both GC-FID and UHPLC-CAD require lengthy analysis time and protocols for different classes of compounds, while NMR is rapid and able to conduct a simultaneous broad-spectrum analysis of compounds, which led to the discovery of more biomarkers. In addition, NMR was in a good agreement with GC-FID for the determination of fatty acids, as found by Bland-Altman analysis, although in several cases it was not able to distinguish among individual fatty acids. [Display omitted] • NMR is a rapid and robust tool for the targeted and untargeted analysis of olive oil. • NMR was in a good agreement with GC-FID for the determination of fatty acids. • NMR, GC-FID, and UHPLC-CAD were able to distinguish between olive oil cultivars. • Fatty acids from GC-FID generated the best models. [ABSTRACT FROM AUTHOR]

Background: There is a higher incidence of psychotic disorders in neighbourhoods of greater social deprivation. However, it is not known whether this represents a causal relationship, as the stage at which social deprivation exerts its influence on the development of psychotic disorders is yet to be elucidated. We aimed to investigate the association between neighbourhood-level social deprivation and the rate of identification of individuals at Ultra-High Risk for psychosis (UHR), as well as the risk of transition to psychosis in UHR individuals. Methods: The cohort included all young people aged 15 to 24 identified as UHR attending an Early Intervention clinic in northwestern Melbourne over a 5-year period (2012–2016). Australian census data were used to obtain the at-risk population and social deprivation information according to the postcode of residence. Levels of social deprivation were arranged into quartiles. Poisson regression was used to calculate rate ratios and Cox regression analysis determined hazard ratios. Results: Of the 461 young people identified as UHR, 11.1% (n = 49) lived in the most affluent neighbourhoods (Quartile 1) compared to 36.7% (n = 162) in the most deprived neighbourhoods (Quartile 4). There was a 35% higher rate of identification of young people who were UHR from the most deprived neighbourhoods (aIRR = 1.35, 95% CI [0.98, 1.86]). Over a median follow-up of approximately 10 months (308 days (IQR: 188–557), 17.5% (n = 77) were known to have transitioned to a full-threshold psychotic disorder. Residing in a neighbourhood of above average deprivation had a hazard ratio of 2.05 (95% CI [0.88, 4.80]) for risk of transition, when controlling for age, sex and substance use. Conclusions: These findings provide more support that EI services should be funded as per the expected incidence of psychotic disorders. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common cancer of men in the Western world, and novel approaches for prostate cancer risk reduction are needed. Plant-derived phenolic compounds attenuate prostate cancer growth in preclinical models by several mechanisms, which is in line with epidemiological findings suggesting that consumption of plant-based diets is associated with low risk of prostate cancer. The objective of this study was to assess the effects of a novel lignan-stilbenoid mixture in PC-3M-luc2 human prostate cancer cells in vitro and in orthotopic xenografts. Lignan and stilbenoid –rich extract was obtained from Scots pine (Pinus sylvestris) knots. Pine knot extract as well as stilbenoids (methyl pinosylvin and pinosylvin), and lignans (matairesinol and nortrachelogenin) present in pine knot extract showed antiproliferative and proapoptotic efficacy at ≥40 μM concentration in vitro. Furthermore, pine knot extract derived stilbenoids enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced apoptosis already at ≥10 μM concentrations. In orthotopic PC-3M-luc2 xenograft bearing immunocompromized mice, three-week peroral exposure to pine knot extract (52 mg of lignans and stilbenoids per kg of body weight) was well tolerated and showed anti-tumorigenic efficacy, demonstrated by multivariate analysis combining essential markers of tumor growth (i.e. tumor volume, vascularization, and cell proliferation). Methyl pinosylvin, pinosylvin, matairesinol, nortrachelogenin, as well as resveratrol, a metabolite of pinosylvin, were detected in serum at total concentration of 7−73 μM, confirming the bioavailability of pine knot extract derived lignans and stilbenoids. In summary, our data indicates that pine knot extract is a novel and cost-effective source of resveratrol, methyl pinosylvin and other bioactive lignans and stilbenoids. Pine knot extract shows anticarcinogenic efficacy in preclinical prostate cancer model, and our in vitro data suggests that compounds derived from the extract may have potential as novel chemosensitizers to TRAIL. These findings promote further research on health-related applications of wood biochemicals. [ABSTRACT FROM AUTHOR]

Aim: Duration of untreated psychosis (DUP) refers to the time elapsing between psychosis onset and treatment initiation. Despite a certain degree of consensus regarding the definition of psychosis onset, the definition of treatment commencement varies greatly between studies and DUP may be underestimated due to lack of agreement. In the present study, three sets of criteria to define the end of the untreated period were applied in a first-episode psychosis cohort to assess the impact of the choice of definition on DUP estimation. Methods: The DUP of 117 patients admitted in the Treatment and Early Intervention in Psychosis Program Psychosis in Lausanne was measured using the following sets of criteria to define treatment onset: (i) initiation of antipsychotic medication; (ii) entry into a specialized programme; and (iii) entry into a specialized programme and adequate medication with a good compliance. Results: DUP varied greatly according to definitions, the most restrictive criteria leading to the longest DUP (median DUP1 = 2.2 months, DUP2 = 7.4 months and DUP3 = 13.6 months). A percentage of 19.7 of the patients who did not meet these restrictive criteria had poorer premorbid functioning and were more likely to use cannabis. Longer DUP3 was associated with poorer premorbid functioning and with younger age at onset of psychosis. Conclusion: These results underline the need for a unique and standardized definition of the end of DUP. We suggest that the most restrictive definition of treatment should be used when using the DUP concept in future research. [ABSTRACT FROM AUTHOR]

Abstract: UV–Vis spectrometry and chemometric techniques were used to classify aqueous extracts of Brazilian ground roast coffee with respect to type (caffeinated/decaffeinated) and conservation state (expired and non-expired shelf-life). Two classification methods were compared: soft independent modelling of class analogy (SIMCA) and linear discriminant analysis (LDA) with wavelength selection by the successive projections algorithm (SPA). The best results were obtained by SPA–LDA, which correctly classified all test samples. The classification accuracy of this model remained high (96%) even after the introduction of artificial spectral noise. These results suggest that UV–Vis spectrometry and SPA–LDA modelling provide a promising alternative for assessment of conservation state and decaffeination condition of coffee samples. [Copyright &y& Elsevier]

• Interplay of different flow regimes influences the Amazonian nocturnal boundary layer. • Strong stability in the Amazonia NBL allows the interaction of a gravity wave and LLJ. • During the inception of the gravity wave the turbulent fluxes are very small. • Confining the scalar below the LLJ nose at the forest-atmosphere interface. We investigated the role of turbulent coherent structures (CS), gravity waves (GW) and low-level jet (LLJ) propagation in the flow dynamics of the Nocturnal Boundary Layer (NBL) within and above a forest canopy at the Amazon Tall Tower Observatory (ATTO), in Central Amazon. Seven levels of wind velocity and temperature measurements allowed the study of the flow structure below and above the surface layer. We analyzed one dynamically rich night in 2015, which includes three distinct periods. In the first one, the NBL is characterized by CS generated at the canopy top. In the second period, the change in wind direction triggers the onset of a orographic GW above the roughness sublayer. The wave, suppressing the propagation of CS, strongly influences the boundary layer structure, both above and below the canopy. In the third period, low turbulence intensity at the canopy top enables the development of a LLJ. As the jet shear layer propagates upward, it disrupts the wave oscillations, while LLJ dominates the flow dynamics. The wavelet analyses identified i) turbulent and non-turbulent structures with different length and time-scales; ii) coupling of the flow at different levels and the vertical propagation of turbulent and wave motions; and iii) the ability of turbulent and low frequency processes associated with the orographic GW to penetrate within the canopy. Further, scalar measurements of methane, carbon monoxide and carbon dioxide identified the LLJ nose as upward limit for how far scalars can be transported. [ABSTRACT FROM AUTHOR]

Labeling terms for high-risk state for psychosis, such as 'ultra-high risk' (UHR), 'attenuated psychosis syndrome' (APS), and 'at-risk mental state' (ARMS), have been criticized for their potential to lead to stigma. Hence, mental health service users in Melbourne recently proposed new terms illustrating the at-risk concept ['pre-diagnosis stage' (PDS), 'potential of developing a mental illness' (PDMI), and 'disposition for developing a mental illness' (DDMI)]. We aimed at testing the suitability of these existing and new terms in the clinical settings of early psychiatric intervention in Japan. At two centers of early intervention (Toyama and Tokyo), a questionnaire on the understanding and opinion of high-risk terminology was administered to 62 high-risk patients, 44 caregivers, and 64 clinicians. The questionnaire contained the existing and new terms, where the term ARMS was translated into two different Japanese terms ARMS-psychosis and ARMS- kokoro. Participants' opinion on the disclosure of high-risk status was also obtained. ARMS- kokoro was most preferred, least stigmatizing, and best explaining the patients' difficulties for all groups, while UHR and other terms including the Japanese word 'psychosis' (i.e., APS and ARMS-psychosis) were not preferred. New labeling terms were generally not well received. All groups preferred full disclosure of high-risk terms by the psychiatrist with or without the presence of family members. The term ARMS- kokoro was commonly accepted as a favorable labeling term for the high-risk state for psychosis in Japan. However, another translation ARMS-psychosis was considered stigmatizing, demonstrating the importance of appropriate translation of high-risk terminology into local languages. • Existing terms for psychosis high-risk status may lead to stigma. • Patients, family members, and clinicians were surveyed about high-risk terms. • ARMS- kokoro was most preferred and least stigmatizing among high-risk terms. • Ultra-high risk and other terms including 'psychosis' were not preferred. [ABSTRACT FROM AUTHOR]

The dynamics of maturation index, water and oil concentrations, and total phenols in olive fruit, together with fatty acids and total phenols content in olive oil, was studied as a function of time after flowering for super-high-density 'Arbequina', 'Arbosana' and 'Koroneiki' using data collected in three seasons. Oil concentration increased linearly from the middle of August until reaching a plateau by the end of November for all three cultivars, with 'Koroneiki' (45.7 g/100 g) and 'Arbosana' (45.4 g/100 g) showing higher maximum oil concentration than 'Arbequina' (41.8 g/100 g). While total phenols in the fruit decreased linearly during the harvest for all three cultivars, phenolics in oil peaked at 180 days after flowering (400 mg/kg) for 'Arbequina' and at 160 days after flowering (600 mg/kg) for 'Koroneiki'. For 'Arbosana', total phenols in oil decreased linearly with a maximum of 400 mg/kg for early harvest oils. Fatty acid dynamics was largely affected by genotype, with 'Arbequina' displaying the largest variation in fatty acid concentrations along the season. 'Koroneiki' presented the highest values of oleic acid (73.0–77.1%), followed by 'Arbosana' (70.2–72.4%) and 'Arbequina' (64.4–74.0%). Results presented here are useful for growers to make planting and harvesting decisions, for producers to understand the differences in oil made from the most common super-high-density cultivars during the harvest seasons, and for regulators to consider legal standards for authentic olive oil. [ABSTRACT FROM AUTHOR]

• Keratins are key players in the integrity and homeostasis of the colonic epithelium • Keratin 8 is the single most important keratin in the colon • Keratin 8 levels modulate colonocyte ion transport and cell proliferation • Keratins are structural components but also dynamic bioactive molecules • Cancer diagnostics use keratin patterns to track down the origin of metastasis Keratin intermediate filament proteins are major cytoskeletal components of the mammalian simple layered columnar epithelium in the gastrointestinal tract. Human colon crypt epithelial cells express keratins 18, 19 and 20 as the major type I keratins, and keratin 8 as the type II keratin. Keratin expression patterns vary between species, and mouse colonocytes express keratin 7 as a second type II keratin. Colonic keratin patterns change during cell differentiation, such that K20 increases in the more differentiated crypt cells closer to the central lumen. Keratins provide a structural and mechanical scaffold to support cellular stability, integrity and stress protection in this rapidly regenerating tissue. They participate in central colonocyte processes including barrier function, ion transport, differentiation, proliferation and inflammatory signaling. The cell-specific keratin compositions in different epithelial tissues has allowed for the utilization of keratin-based diagnostic methods. Since the keratin expression pattern in tumors often resembles that in the primary tissue, it can be used to recognize metastases of colonic origin. This review focuses on recent findings on the biological functions of mammalian colon epithelial keratins obtained from pivotal in vivo models. We also discuss the diagnostic value of keratins in chronic colonic disease and known keratin alterations in colon pathologies. This review describes the biochemical properties of keratins and their molecular actions in colonic epithelial cells and highlights diagnostic data in colorectal cancer and inflammatory bowel disease patients, which may facilitate the recognition of disease subtypes and the establishment of personal therapies in the future. [ABSTRACT FROM AUTHOR]

Vegetable oils are subjected to heat treatments during processing and changes during storage. Thus, it is required, for usage as a food source, the evaluation of their thermo-oxidative stability and physicochemical characteristics. In this context, the objective of this paper was to evaluate the oil of catole coconut (Syagrus cearensis), aiming to characterize its identity and quality, as well as its antioxidant capacity and thermo-oxidative stability. The catole coconut was collected in the city of Lagoa Seca-PB, Brazil, its almonds were dried in a stove and the catole oil was obtained by cold pressing. The results of the physicochemical parameters complied with the current legislation, with average values ​​of 2.48 mg KOH g−1 oil for acid value, 0.14 meq peroxide kg−1 oil for peroxide value and 253 mg KOH g−1 oil for saponification value. Catole oil presented the profile of saturated fatty acids (84.42%), with the predominance of lauric acid (45.06%), besides major phenolic compounds such as salicylic acid [12.324 mg (100 g−1) of oil] and myricetin [1.405 mg (100 g−1) of oil]. The thermogravimetric profile remained stable to decomposition at temperatures up to around 240 °C and oxidative stability withstood at 110 °C for more than 48 h. Therefore, it was possible to identify and characterize this unexplored oilseed species of the Brazilian semiarid, diversifying its use in the food industry. [ABSTRACT FROM AUTHOR]

The article discusses the results of studies on the relationship between duration of untreated psychosis (DUP) and outcome. Imaging data indicate that if there is an active process of neuroprogression underlying active and progressive structural change in key brain areas such as the hippocampus, then the longer the DUP, the greater the time available for the potentially neurotoxic process to unfold.

For the first time, a multi-class GC–MS method was applied to perform the quantitative-profiling of the minor fraction of VOOs (considering >40 compounds) in a single run. This comprehensive methodology has demonstrated a remarkable profiling ability on five groups of compounds (phenolic and triterpenic compounds, tocopherols, sterols and free fatty acids) with wide range of polarities/volatilities and chemical entities. After the complete analytical validation of the method, 32 VOO samples from eight different cultivars (some of them very scarcely studied before) were analyzed and the quantitative results were subjected to both non-supervised and supervised multivariate statistics for testing the capability of the determined VOO minor compounds to discriminate the varietal origin of the samples. Typical compositional profiles were defined for each cultivar and promising potential varietal markers were pointed out. The models built to discriminate Cayon and Maurino samples from the rest exhibited the best quality parameters. The relative levels of tocopherols together with characteristic concentration of luteolin, β- sitosterol and tyrosol were, for instance, the most specific features of Cayon VOOs. Unlabelled Image • A GC–MS multi-class method was applied to the analysis of virgin olive oil samples. • Comprehensive quantitative characterization of samples was achieved. • >40 compounds (5 different chemical classes) were determined in a single run. • PLS–DA models were established to discriminate among the 8 studied olive cultivars. • Potential varietal markers for each cultivar were pointed out. [ABSTRACT FROM AUTHOR]

Crushing of the olive fruit is the first operation for olive oil extraction. The hammer mill is one of the most popular devices used in modern facilities due to its easy maintenance and high product output. The effect of hammer mill rotor speed and sieve design, including screen size and screen open area on extraction yield, overall quality and minor component composition, is evaluated at the laboratory scale. Quality parameters such as free fatty acids (FFA), peroxide value (PV), and UV absorbances (K232, K270, and ΔK) are unaltered by crushing parameters. Extraction efficiency, chlorophylls content, total phenol content, 3,4‐DHPEA‐EDA, and p‐HPEA‐EDA increase with faster hammer mill rotor speed and smaller screen size. Volatiles (E)‐2‐hexenal, hexanal, 1,5‐hexadiene‐(3,4)‐diethyl, 3‐ethyl‐1,5‐octadiene, and (E)‐2‐hexenol are only affected by screen size. Screen open area is found to be a relevant factor regarding extraction efficiency, chlorophylls, total, and individual phenols as well as the volatile compounds 1,5‐hexadiene (3,4)‐diethyl, 3‐ethyl‐1,5‐octadiene, hexanal, and (E)‐2‐hexenal. Practical Application: It is found that screen open area is a relevant factor regarding extraction efficiency, chlorophylls, total and individual phenols and volatile compounds, in addition to the screen size and rotor speed. This is useful information for millers who are interested in optimizing extraction efficiency as well as the minor compounds of extra virgin olive oil. Hammer mill sieve design impacts extraction efficiency, chlorophylls, total and individual phenols, and the volatile compounds during laboratory‐scale extraction of olive oil. [ABSTRACT FROM AUTHOR]

Aim: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self‐disturbance model of psychosis by examining the relationship between specific clinical, neurocognitive, and neurophysiological variables in UHR patients, and (2) develop a prediction model using these neurophenomenological disturbances for persistence or deterioration of UHR symptoms at 12‐month follow‐up. Methods: SNAP is a longitudinal observational study. Participants include 400 UHR individuals, 100 clinical controls with no attenuated psychotic symptoms, and 50 healthy controls. All participants complete baseline clinical and neurocognitive assessments and electroencephalography. The UHR sample are followed up for a total of 24 months, with clinical assessment completed every 6 months. Results: This paper presents the protocol of the SNAP study, including background rationale, aims and hypotheses, design, and assessment procedures. Conclusions: The SNAP study will test whether neurophenomenological disturbances associated with basic self‐disturbance predict persistence or intensification of UHR symptomatology over a 2‐year follow up period, and how specific these disturbances are to a clinical population with attenuated psychotic symptoms. This may ultimately inform clinical care and pathoaetiological models of psychosis. [ABSTRACT FROM AUTHOR]

Obesity is a risk factor for postmenopausal breast cancer. Obesity‐related inflammation upregulates aromatase expression, the rate‐limiting enzyme for estrogen synthesis, in breast adipose tissue (BAT), increasing estrogen production and cancer risk. The regulation of aromatase gene (CYP19A1) in BAT is complex, and the mechanisms linking obesity and aromatase dysregulation are not fully understood. An obesity‐associated factor that could regulate aromatase is the CC chemokine ligand (CCL) 2, a pro‐inflammatory factor that also activates signaling pathways implicated in CYP19A1 transcription. By using human primary breast adipose stromal cells (ASCs) and aromatase reporter (hARO‐Luc) mouse mammary adipose explants, we demonstrated that CCL2 enhances the glucocorticoid‐mediated CYP19A1 transcription. The potential mechanism involves the activation of PI.4 via ERK1/2 pathway. We also showed that CCL2 contributes to the pro‐inflammatory milieu and aromatase expression in obesity, evidenced by increased expression of CCL2 and CYP19A1 in mammary tissues from obese hARO‐Luc mice, and subcutaneous adipose tissue from obese women. In summary, our results indicate that postmenopausal obesity may promote CCL2 production in BAT, leading to exacerbation of the menopause‐related inflammatory state and further stimulation of local aromatase and estrogens. These results provide new insights into the regulation of aromatase and may aid in finding approaches to prevent breast cancer. [ABSTRACT FROM AUTHOR]

Estrogen-receptor-mediated signaling has been suggested to decrease the inflammatory response in monocyte macrophages. Previously, we showed that a novel selective estrogen receptor modulator (SERM2) promotes anti-inflammatory phenotype of monocytes in vitro. In this study, we demonstrate the potential of SERM2 in amelioration of colitis. We utilized a dextran sodium sulfate (DSS)-induced colitis model in FVB/n mice to demonstrate the effects of orally administered SERM2 on the clinical status of the mice and the histopathological changes in the colon, as well as proportion of Mrc-1 positive macrophages. SERM2 nuclear receptor affinities were measured by radioligand binding assays. Orally administered, this compound significantly alleviated DSS-induced colitis in male mice and induced local estrogen receptor activation in the inflamed colon, as well as promoting anti-inflammatory cytokine expression and infiltration of anti-inflammatory monocytes. We show that this novel drug candidate has an affinity to estrogen receptors α and β and progesterone receptors, but not to glucocorticoid receptor, thus expressing unique binding properties compared to other sex steroid receptor ligands. These results indicate that novel drug candidates to alleviate inflammatory conditions of the colon could be found among sex steroid receptor activating compounds. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are known to stimulate the survival and growth of endothelial cells (ECs) by producing paracrine signals, as well as to differentiate into pericytes and thereby support blood vessel formation and stability. On the other hand, cells with an EC-like phenotype have been found within the CD14+ and CD34+ cell populations of peripheral blood (PB) mononuclear cells (MNCs). The aim of this study was to investigate the proangiogenic differentiation potential of human MSC-MNC co-cultures. Bone marrow-derived MSCs (2,500 cells/cm2) were co-cultured with MNCs (50,000 cells/cm2), which were isolated from the PB of healthy donors. MSCs and MNCs cultured alone at same cell densities were used as controls. Cells in MNC fraction and in co-cultures were isolated for CD14, CD34, and CD31 surface markers with magnetic-activated cell sorting. Co-cultures were analyzed for cell proliferation and morphology, as well as for the expression of various hematopoietic, endothelial, and pericyte markers by immunocytochemistry, quantitative PCR (qPCR), and flow cytometry. Vascular endothelial growth factor (VEGF) expression and secretion was measured with qPCR and enzyme-linked immunosorbent assay, respectively. Our results show that in co-cultures with MSCs, CD14+CD45+ MNCs differentiated into spindle-shaped, nonproliferative, EC-like, myeloid angiogenic cells (MACs) expressing CD31, but also into pericyte-like cells expressing neural/glial antigen 2 (NG2) and CD146. Functionality of the isolated MACs was demonstrated in co-cultures with human umbilical vein endothelial cells, where they supported the formation of tube-like structures. NG2+ cells of MNC-origin were found among both CD34−CD14+ and CD34−CD14− cell populations, indicating the existence of different subtypes of pericyte-like cells. In addition, VEGF was shown to be secreted in MSC-MNC co-cultures, mainly by MSCs. In conclusion, MSCs were shown to possess proangiogenic capacity in MSC-MNC co-cultures as they supported the differentiation of functional MACs, as well as the differentiation of pericyte-like cells of MNC origin. This phenomenon was mediated at least partially via secreted VEGF. [ABSTRACT FROM AUTHOR]

Psychotic symptoms are typically measured using clinical ratings, but more objective and sensitive metrics are needed. Hence, we will assess thought disorder using the Research Domain Criteria (RDoC) heuristic for language production, and its recommended paradigm of "linguistic corpus-based analyses of language output". Positive thought disorder (e.g., tangentiality and derailment) can be assessed using word-embedding approaches that assess semantic coherence, whereas negative thought disorder (e.g., concreteness, poverty of speech) can be assessed using part-of-speech (POS) tagging to assess syntactic complexity. We aim to establish convergent validity of automated linguistic metrics with clinical ratings, assess normative demographic variance, determine cognitive and functional correlates, and replicate their predictive power for psychosis transition among at-risk youths. This study will assess language production in 450 English-speaking individuals in Australia and Canada, who have recent onset psychosis, are at clinical high risk (CHR) for psychosis, or who are healthy volunteers, all well-characterized for cognition, function and symptoms. Speech will be elicited using open-ended interviews. Audio files will be transcribed and preprocessed for automated natural language processing (NLP) analyses of coherence and complexity. Data analyses include canonical correlation, multivariate linear regression with regularization, and machine-learning classification of group status and psychosis outcome. This prospective study aims to characterize language disturbance across stages of psychosis using computational approaches, including psychometric properties, normative variance and clinical correlates, important for biomarker development. SPEAK will create a large archive of language data available to other investigators, a rich resource for the field. [ABSTRACT FROM AUTHOR]

Decreased brain activity in the frontal region, as indicated by increased slow wave EEG power measured by electrodes place on the skull over this area, in association with negative symptoms has previously been shown to distinguish ultra-high risk (UHR) individuals who later transitioned to psychosis (UHR-P) from those who did not transition (UHR-NP). The aims of the current study were to: 1) replicate these results and 2) investigate whether similar association between increased frontal slow wave activity and functioning shows any value in the prediction of transition to psychosis in UHR individuals. The brain activity, recorded using EEG, of 44 UHR individuals and 38 healthy controls was included in the analyses. Symptom severity was assessed in UHR participants and functioning was measured in both groups. The power in the theta frequency band in the frontal region of UHR individuals was higher than in controls. However, there was no difference between the UHR-P and the UHR-NP groups, and no change in slow frequency power following transition to psychosis. The correlation between delta frequency power and negative symptoms previously observed was not present in our UHR cohort, and there was no association between frontal delta or theta and functioning in either group. Increased delta power was rather correlated with depressive symptoms in the UHR group. Future research will be needed to better understand when, in the course of the illness, does the slow wave activity in the frontal area becomes impaired. [ABSTRACT FROM AUTHOR]

Highlights • Simple and low-cost methods for the detection of coffee adulterations. • Coffee adulteration detected with LDA aided by variable selection on voltammetric data. • Amount of coffee impurities determined by MLR preceded by variable selection. • Voltammetric electronic tongue performed with a single voltammetric sensor. Abstract This work presents a simple and low-cost analytical approach to detect adulterations in ground roasted coffee by using voltammetry and chemometrics. The voltammogram of a coffee extract (prepared as simulating a home-made coffee cup) obtained with a single working electrode is submitted to pattern recognition analysis preceded by variable selection to detect the addition of coffee husks and sticks (adulterated/unadulterated), or evaluate the shelf-life condition (expired/unexpired). Two pattern recognition methods were tested: linear discriminant analysis (LDA) with variable selection by successive projections algorithm (SPA), or genetic algorithm (GA); and partial least squares discriminant analysis (PLS-DA). Both LDA models presented satisfactory results. The voltammograms were also evaluated for the quantitative determination of the percentage of impurities in ground roasted coffees. PLS and multivariate linear regression (MLR) preceded by variable selection with SPA or GA were evaluated. An excellent predictive power (RMSEP = 0.05%) was obtained with MLR aided by GA. [ABSTRACT FROM AUTHOR]

Objective: To develop targeted treatment for young people experiencing mental illness, a better understanding of the biological, psychological, and social changes is required, particularly during the early stages of illness. To do this, large datasets need to be collected using standardized methods. A harmonized data collection protocol was tested in a youth mental health research setting to determine its acceptability and feasibility. Method: Eighteen participants completed the harmonization protocol, including a clinical interview, self‐report measures, neurocognitive measures, and mock assessments of magnetic resonance imaging (MRI) and blood. The feasibility of the protocol was assessed by recording recruitment rates, study withdrawals, missing data, and protocol deviations. Subjective responses from participant surveys and focus groups were used to examine the acceptability of the protocol. Results: Twenty‐eight young people were approached, 18 consented, and four did not complete the study. Most participants reported positive subjective impressions of the protocol as a whole and showed interest in participating in the study again, if given the opportunity. Participants generally perceived the MRI and neurocognitive tasks as interesting and suggested that the assessment of clinical presentation could be shortened. Conclusion: Overall, the harmonized data collection protocol appeared to be feasible and generally well‐accepted by participants. With a majority of participants finding the assessment of clinical presentation too long and repetitive, the authors have made suggestions to shorten the self‐reports. The broader implementation of this protocol could allow researchers to create large datasets and better understand how psychopathological and neurobiological changes occur in young people with mental ill‐health. [ABSTRACT FROM AUTHOR]

It is unclear whether there is a specific association between stressful experiences and obsessive-compulsive symptoms or whether this relationship is due to stressful experiences increasing risk for psychopathology generally. The current study examined the association between stressful experiences and obsessive-compulsive symptom dimensions, while adjusting for coexisting psychiatric symptoms and psychological distress in a young adult transdiagnostic at-risk sample. Forty-three participants completed self-report measures assessing obsessive-compulsive symptoms, stressful experiences, and a range of other psychiatric symptoms. Regression models examined the relationship between stressful experiences and different obsessive-compulsive symptoms dimensions (i.e., symmetry, fear of harm, contamination, and unacceptable thoughts), adjusting for the influence of coexisting psychiatric symptoms and psychological distress. The results showed that there was an association between stressful experiences and obsessive-compulsive symptoms dimension of symmetry. Symptoms of borderline personality disorder were positively associated with the obsessive-compulsive symptom dimensions of symmetry and fear of harm symptoms. Symptoms of psychosis were found to be negatively associated with the obsessive-compulsive symptoms dimension of fear of harm. These findings have implications for understanding the psychological mechanisms that underlie symmetry symptoms and highlight the need to study OCS dimensions separately to inform more precise, mechanism-targeted interventions. [ABSTRACT FROM AUTHOR]

Inclusion of 'attenuated psychosis syndrome (APS)' in the DSM-5 has been hotly debated because of the concern about stigmatising young patients with a 'psychosis risk' label. This study aimed to investigate whether current labeling terms such as 'at risk mental state', 'ultra-high risk' (UHR) and 'APS' are suitable for people who are at risk of psychosis. This study included 105 subjects (55 patients aged 15-25years who used an early interventional service to prevent psychosis and 50 professionals who worked with them). A questionnaire regarding their opinions about the stigma associated with the above labels and the Mental Health Consumers' Experience of Stigma scale were administered. The patients were less likely than the professionals to agree that there was stigma associated with the terms 'UHR' and 'APS'. Significantly more patients with a family history of psychosis and those who had transitioned to psychosis agreed that there was stigma associated with the term 'UHR' and/or that this term should be changed. Patients who agreed with the negative attitude items for the three labeling terms and the need to change the terms 'UHR' and 'schizophrenia' showed significantly higher scores on the Stigma scale. In conclusion, patients at risk of psychosis may experience less stigma related to labels than expected by professionals, suggesting that mental health professionals may not be able to help patients unless they listen to their views on nosological and treatment issues rather than make assumptions. Previous stigmatising experiences may have strengthened the stigma attached to this label. [ABSTRACT FROM AUTHOR]

Aim: Research has shown that preventative intervention in individuals at ultra‐high risk of psychosis (UHR) improves symptomatic and functional outcomes. The staged treatment in early psychosis (STEP) trial aims to determine the most effective type, timing and sequence of interventions in the UHR population by sequentially studying the effectiveness of (1) support and problem solving, (2) cognitive‐behavioural case management and (3) antidepressant medication with an embedded fast‐fail option of (4) omega‐3 fatty acids or low‐dose antipsychotic medication. This paper presents the recruitment flow and baseline clinical characteristics of the sample. Methods: STEP is a sequential multiple assignment randomized trial. We present the baseline demographics, clinical characteristics and acceptability and feasibility of this treatment approach as indicated by the flow of participants from first contact up until enrolment into the trial. Recruitment took place between April 2016 and January 2019. Results: Of 1343, help‐seeking young people who were considered for participation, 402 participants were not eligible and 599 declined/disengaged, resulting in a total of 342 participants enrolled in the study. The most common reason for exclusion was an active prescription of antidepressant medication. Eighty‐five percent of the enrolled sample had a non‐psychotic DSM‐5 diagnosis and symptomatic/functional measures showed a moderate level of clinical severity and functional impairment. Discussion: The present study demonstrates the acceptability and participant's general positive appraisal of sequential treatment. It also shows, in line with other trials in UHR individuals, a significant level of psychiatric morbidity and impairment, demonstrating the clear need for care in this group and that treatment is appropriate. [ABSTRACT FROM AUTHOR]