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The association of hormonal contraception with increased risk of inflammatory bowel disease (IBD) observed in females suggests involvement of ovarian hormones, such as estradiol, and the estrogen receptors in the progression of intestinal inflammation. Here, we investigated the effects of prophylactic SERM2 and estradiol supplementation in dextran sulfate sodium‐induced colitis using mice with intact ovaries and ovariectomized (OVX) female mice. We found that graded colitis score was threefold reduced in the OVX mice, compared to mice with intact ovaries. Estradiol supplementation, however, aggravated the colitis in OVX mice, increasing the colitis score to a similar level than what was observed in the intact mice. Further, we observed that immune infiltration and gene expression of inflammatory interleukins Il1b, Il6, and Il17a were up to 200‐fold increased in estradiol supplemented OVX colitis mice, while a mild but consistent decrease was observed by SERM2 treatment in intact animals. Additionally, cyclo‐oxygenase 2 induction was increased in the colon of colitis mice, in correlation with increased serum estradiol levels. Measured antagonist properties of SERM2, together with the other results presented here, indicates an exaggerating role of ERα signaling in colitis. Our results contribute to the knowledge of ovarian hormone effects in colitis and encourage further research on the potential use of ER antagonists in the colon, in order to alleviate inflammation. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract affecting millions of people. Here, we investigated the expression and functions of poly(ADP‐ribose) polymerase 14 (Parp14), an important regulatory protein in immune cells, with an IBD patient cohort as well as two mouse colitis models, that is, IBD‐mimicking oral dextran sulfate sodium (DSS) exposure and oral Salmonella infection. Parp14 was expressed in the human colon by cells in the lamina propria, but, in particular, by the epithelial cells with a granular staining pattern in the cytosol. The same expression pattern was evidenced in both mouse models. Parp14‐deficiency caused increased rectal bleeding as well as stronger epithelial erosion, Goblet cell loss, and immune cell infiltration in DSS‐exposed mice. The absence of Parp14 did not affect the mouse colon bacterial microbiota. Also, the colon leukocyte populations of Parp14‐deficient mice were normal. In contrast, bulk tissue RNA‐Seq demonstrated that the colon transcriptomes of Parp14‐deficient mice were dominated by abnormalities in inflammation and infection responses both prior and after the DSS exposure. Overall, the data indicate that Parp14 has an important role in the maintenance of colon epithelial barrier integrity. The prognostic and predictive biomarker potential of Parp14 in IBD merits further investigation. [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]

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]

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]

Aim: Prevention and early intervention efforts of serious mental illnesses has yielded promising results. However, alongside benefits, several ethical concerns have been raised, including the effects of being identified as being at‐risk. In these debates, the voice of parents or carers is conspicuously absent. This is especially concerning as several at‐risk interventions are trialled in under‐age youth where parents consent on behalf of young people. Therefore, this study aimed to understand carer's experiences of their teenager being identified as at risk for psychosis. Methods: Semi‐structured interviews were conducted with seven carers who had provided consent for their teenager to participate in a stepped intervention study for youth at‐risk for psychosis. Questions explored their experiences regarding having their teenager being identified as at‐risk. Transcripts were analysed using thematic analysis. Results: We identified five main themes from seven female carers' experiences of risk identification including: (a) recall of risk information was limited, or variable, (b) goal of risk disclosure was perceived to be positive, (c) negative emotions were associated with knowledge of risk, (d) relief from uncertainty and helplessness and (e) effects of risk disclosure were mediated by individual circumstance. Conclusion: Overall, the results demonstrate that carers' experience of risk disclosure varied with factors surrounding their individual circumstances, and the process of disclosure. Whilst participants acknowledged potential adverse effects associated with risk disclosure, many still adopted a positive outlook. Tailoring safe and effective disclosure of risk to suit the needs of youth and carers could outweigh the potential risks. [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]

"Sikitita" is a relatively new olive cultivar obtained from crossbreeding between "Picual" and "Arbequina" that can be trained into the super‐high‐density orchard system. The impact of harvest time and crop season (2017 and 2018) on fruit parameters, oil quality, and minor compounds was assessed for super‐high‐density "Sikitita" in California, USA. Maximum olive fruit oil content (~49% on a dry basis) was reached between the first and second weeks of November. Quality parameters were within limits for extra virgin classification for all harvest times during both crop seasons. While total phenols were affected by harvest time, crop year, and their interaction, total volatile content was mainly influenced by harvest time. Both phenolic and volatile compounds reached a maximum concentration by the first week of October, suggesting that harvesting at the beginning of October would lead to a richer oil in terms of minor components. However, oil yield can be maximized if the harvest takes place in November. Our results demonstrated fruit parameters, oil quality, and minor compounds of super‐high‐density "Sikitita" followed a similar pattern and reached comparable values in both years, despite an earlier maturation in 2018. "Sikitita" has potential as a viable cultivar for growers and processors who are looking to expand on the traditional super‐high‐density cultivars. [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]

Antipsychotic medication has been the mainstay of treatment for psychotic illnesses for over 60 years. This has been associated with improvements in positive psychotic symptoms and a reduction in relapse rates. However, there has been little improvement in functional outcomes for people with psychosis. At the same time there is increasing evidence that medications contribute to life shortening metabolic and cardiovascular illnesses. There is also uncertainty as to the role played by antipsychotic medication in brain volume changes. Aim: The primary aim of the study is, in a population of young people with first‐episode psychosis, to compare functional outcomes between an antipsychotic dose reduction strategy with evidence‐based intensive recovery treatment (EBIRT) group (DRS+) and an antipsychotic maintenance treatment with EBIRT group (AMTx+) at 24‐months follow‐up. Methods: Our single‐blind randomized controlled trial, within a specialist early psychosis treatment setting, will test the whether the DRS+ group leads to better vocational and social recovery than, the AMTx+ group over a 2‐year period in 180 remitted first‐episode psychosis patients. Additionally, we will examine the effect of DRS+ vs AMTx+ on physical health, brain volume and cognitive functioning. This study will also determine whether the group receiving DRS+ will be no worse off in terms of psychotic relapses over 2 years follow‐up. Results: This paper presents the protocol, rationale and hypotheses for this study which commenced recruitment in July 2017. Conclusion: This study will provide evidence as to whether an antipsychotic dose‐reduction recovery treatment leads to improved functioning and safer outcomes in first‐episode psychosis patients. In addition, it will be the first‐controlled experiment of the effect of exposure to antipsychotic maintenance treatment on brain volume changes in this population. [ABSTRACT FROM AUTHOR]

Aim: It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first‐episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery; (2) whether prolonging the duration of untreated psychosis (DUP) in a sub‐group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative; and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented. Methods: This study is a triple‐blind randomized placebo‐controlled non‐inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6 months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24 years with a DSM‐IV psychotic disorder, a DUP less than 6 months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3‐Tesla‐MRI scans. Results: Ninety participants have been recruited and baseline characteristics are presented. Conclusions: Staged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines. [ABSTRACT FROM AUTHOR]

Aim: The Inventory of Psychotic‐Like Anomalous Self‐Experiences (IPASE) is a self‐report measure of minimal self‐disturbance. The aim of the current report was to assess the construct validity of the scale by examining its convergent validity with the gold‐standard measure of minimal self‐disturbance, the Examination of Anomalous Self‐Experience (EASE), and its discriminant validity. Method: The sample consisted of 46 participants (21 ultra‐high risk for psychosis patients, 14 first episode psychosis patients, 11 healthy controls). Correlations between the clinical instruments were examined. Results: The IPASE correlated strongly with general psychopathology and positive psychotic symptoms, moderately with negative symptoms, and weakly with manic symptoms. The strongest correlation (r = 0.92) was apparent between IPASE and EASE total scores. Conclusion: These preliminary data indicate construct validity of the IPASE, demonstrating both convergent and discriminant validity. The IPASE may be suitable as a screener measure for minimal self‐disturbance, but should not be used as a replacement to measure the construct of minimal self‐disturbance, which requires considerable psychopathological sophistication. [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]

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]

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]

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]

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]