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A nature-inspired approach was employed through the development of dopamine-modified epoxy coating for anti-icing applications. The strong affinity of dopamine's catechol groups for hydrogen bonding with water molecules at the ice/coating interface was utilized to induce an aqueous quasi-liquid layer (QLL) on the surface of the icephobic coatings, thereby reducing their ice adhesion strength. Epoxy resin modification was studied by attenuated total reflectance infrared spectroscopy (ATR-FTIR) and nuclear magnetic resonance spectroscopy (NMR). The surface and mechanical properties of the prepared coatings were studied by different characterization techniques. Low-temperature ATR-FTIR was employed to study the presence of QLL on the coating's surface. Moreover, the freezing delay time and temperature of water droplets on the coatings were evaluated along with push-off and centrifuge ice adhesion strength to evaluate their icephobic properties. The surface of dopamine-modified epoxy coating presented enhanced hydrophilicity and QLL formation, addressed as the main reason for its remarkable icephobicity. The results demonstrated the potential of dopamine-modified epoxy resin as an effective binder for icephobic coatings, offering notable ice nucleation delay time (1316 s) and temperature (-19.7 °C), reduced ice adhesion strength (less than 40 kPa), and an ice adhesion reduction factor of 7.2 compared to the unmodified coating.

Ursolic acid and uvaol are naturally occurring triterpenoids that exhibit a broad spectrum of pharmacological activities, including cytotoxicity. However, a primary challenge in the development of ursane-type pentacyclic triterpenoids for pharmacological use is their poor aqueous solubility, which can impede their effectiveness as therapeutics agents. In this study, we present the facile synthesis of ursolic acid monodesmosides and uvaol bidesmosides, incorporating naturally occurring and water-soluble pentoses and deoxyhexose sugar moieties of opposite d- and l-configurations at the C3 or C3/C28 positions of the ursane core. The twenty synthetic saponins were evaluated in vitro for their cytotoxicity against lung carcinoma (A549) and colorectal adenocarcinoma (DLD-1) cell lines. Notably, all the bidesmosidic uvaol saponins were shown to be cytotoxic as compared to their non-cytotoxic parent triterpenoid. For each series of ursane-type saponins, the most active compounds were 3-O-α-l-arabinopyranosyl ursolic acid (3h) and 3,28-di-O-α-l-rhamnopyranosyl uvaol (4f), showing IC 50 values in the low micromolar range against A549 and DLD-1 cancer lines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andre Pichette reports financial support was provided by Canadian Institutes of Health Research. Jean Legault reports financial support was provided by Canadian Institutes of Health Research. Charles Gauthier reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Charles Gauthier reports financial support was provided by Quebec Health Research Fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS)., Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences., Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS., Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

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., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

We present the isolation and structural characterization of a novel nonionic dirhamnolipid methyl ester produced by the bacterium Burkholderia lata. The structure and the absolute configuration of the isolated dirhamnolipid bearing a symmetrical C 14 -C 14 methyl ester chain were thoroughly investigated through chemical degradation and spectroscopic methods including 1D and 2D NMR analysis, HR-ESI-TOF-MS, chiral GC-MS, and polarimetry. Our work represents the first mention in the literature of a rhamnolipid methyl ester from Burkholderia species., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Charles Gauthier reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Eric Deziel reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Serge Lavoie reports financial support was provided by Natural Sciences and Engineering Research Council of Canada. Charles Gauthier reports financial support was provided by Quebec Health Research Fund. Stephan Thies reports financial support was provided by Ministry of Culture and Science (NRW, Germany). Sonja Kubicki reports financial support was provided by Ministry of Culture and Science (NRW, Germany). Sonja Kubicki reports financial support was provided by Mitacs Canada. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Climate change represents a serious threat to human health, including mental health, due to both the traumatizing effects of extreme climate events and the psychological effect of worry about climate change., Objectives: This scoping review aims to search the literature for original research investigating mental health and climate-related negative emotions in young people. Findings will help to understand the current landscape, gaps in the literature, and provide recommendations for future youth mental health research and practice., Methods: A scoping review of the literature examining negative emotions associated with climate change in young people was undertaken. Studies published prior to March 2022 were included if they examined mental ill-health (e.g., symptoms of depression or anxiety) or negative emotions (e.g., distress, worry, concern) associated with the threat of climate change., Results: Of 3939 articles screened, 26 met the inclusion criteria. Together, studies show that young people are worried about climate change. Negative emotions about climate change were correlated with symptoms of mental ill-health. Studies also explored coping strategies young people use to manage their distress caused by climate change., Discussion: The limited literature in this area indicates a key gap in youth mental health research. While available evidence suggests that young people are concerned about climate change, more research is needed on the relationship between climate-related negative emotions and mental ill-health. Clinicians should assess for and address climate-related negative emotions in young people. Mental health leaders are urged to advocate for actions to mitigate the mental health impact of climate change., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

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., (© 2022 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background: Nutrition optimisation is imperative in paediatric patients with heart failure. Energy needs can be assessed using indirect calorimetry., Methods: Presented are two cases of children with clinical heart failure who benefited from indirect calorimetry., Results: Using indirect calorimetry, it was determined both cases were hypermetabolic., Conclusion: These cases demonstrate the impact of heart failure on metabolic rate and growth. Energy requirements were up to two times higher than estimations from predictive equations.

Idose is unique among other aldohexoses because of its high conformational flexibility in solution. We herein show that benzylidene acetal-protected 3- O -acyl-β-d-idopyranosides undergo Lewis acid-catalyzed C7 epimerization with concomitant 4 C 1 to 1 C 4 ring inversion. The reaction conditions and structural parameters for this transformation to occur have been thoroughly investigated through an extensive glycosylation study combined with NMR analyses, X-ray diffraction, and quantum molecular modeling. In addition to reporting a direct, β-stereoselective idosylation approach, our work brings fundamental structural insights into the conformational flexibility of idose.

Aim: To explore the occupational and personal life dimensions that have been impacted by the COVID-19 pandemic for registered nurses (RN) and licensed practical nurses (LPN)., Design: Qualitative interpretive description approach., Methods: Between July and September 2020, a web-based cross-sectional study was conducted among RNs and LPNs in Quebec, Canada. Included in this survey was an open-ended question allowing nurses to describe the occupational and personal life dimensions that were impacted by the COVID-19 pandemic. Thematic analysis was used to interpret the qualitative data from this open-ended question. Reporting followed the Standards For Reporting Qualitative Research (SRQR)., Results: Of the 1860 survey respondents, 774 RNs and 43 LPNs responded to the open-ended question (total n = 819). For the occupational dimension, six themes were identified: impacts of infection control on work, change in daily work tasks, offloading and reorganization of care, deterioration of working conditions, increased stress at work and issues related to the profession. For the personal dimension, four themes were found: impacts on the family, dealing with changes about leisure and personal life, impacts on physical and psychological health., Conclusion: Knowing the dimensions affected by the COVID-19 pandemic could help to identifying appropriate interventions to support RNs and LPNs., Impact: The COVID-19 pandemic has significantly impacted the occupational and personal lives RNs and LPNs working in the Quebec healthcare system. More specifically, Quebec's nurses experienced a major reorganization of care generated by important government decisions. Knowing how the pandemic affected different life dimensions will help in the development of support adapted to nurses' realities. Even in a pandemic context, improvements in the work environment or appropriate support could lead to an improved psychological health for nurses., (© 2022 John Wiley & Sons Ltd.)

Background: In 2018, the Community-Based Research Centre (CBRC) invited gay, bisexual, trans, queer men and Two-Spirit and non-binary people (GBT2Q) at Pride Festivals across Canada to complete in-person Sex Now surveys and provide optional dried blood spot (DBS) samples screening for human immunodeficiency virus (HIV) and hepatitis C virus (HCV). As there is a lack of research evaluating the implementation of DBS sampling for GBT2Q in community settings, we aimed to evaluate this intervention, identifying key facilitators and ongoing challenges to implementing community-based DBS screening for HIV/HCV among GBT2Q., Methods: We conducted sixteen one-on-one interviews with individuals involved with the community-based DBS collection protocol, including research staff, site coordinators, and volunteer DBS collectors. Most individuals involved with DBS collection were "peers" (GBT2Q-identified). The Consolidated Framework for Implementation Research (CFIR) guided our data collection and analysis., Results: Interviewees felt that DBS collection was a low-barrier, cost-effective, and simple way for peers to quickly screen a large number of Sex Now respondents. Interviewees also noted that the community and peer-based aspects of the research helped drive recruitment of Sex Now respondents. Most interviewees felt that the provision of results took too long, and that some Sex Now respondents would have preferred to receive their test results immediately (e.g., rapid or point-of-care testing)., Conclusion: Peer-based DBS sampling can be an effective and relatively simple way to screen GBT2Q at Pride Festivals for more than one sexually transmitted and blood borne infection., (© 2022. The Author(s).)

Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class trajectories of cognitive performance over 12-months in UHR individuals, ii) identify baseline demographic and clinical predictors of the resulting classes, and iii) determine whether trajectory classes were associated with transition to psychosis or functional outcomes. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline, 6- and 12-months ( N = 288). Using Growth Mixture Modeling, a single unimpaired improving trajectory class was observed for motor function, speed of processing, verbal fluency, and BACS composite. A two-class solution was observed for executive function and working memory, showing one unimpaired and a second impaired class. A three-class solution was found for verbal learning and memory: unimpaired, mildly impaired, and initially extremely impaired, but improved ("caught up") to the level of the mildly impaired. IQ, omega-3 index, and premorbid adjustment were associated with class membership, whereas clinical variables (symptoms, substance use), including transition to psychosis, were not. Working memory and verbal learning and memory trajectory class membership was associated with functioning outcomes. These findings suggest there is no short-term progressive cognitive decline in help-seeking UHR individuals, including those who transition to psychosis. Screening of cognitive performance may be useful for identifying UHR individuals who may benefit from targeted cognitive interventions., Competing Interests: The authors have declared that there are no conflicts of interest in relation to the subject of this study., (© The Author(s) 2022. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Background: Reported cases of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are increasing among Canadian men. Estimates of community-based CT/NG prevalence are lacking among gay, bisexual, and other men who have sex with men (GBM)., Methods: Respondent driven sampling was used to recruit GBM in Montréal, Canada between February 2017 and June 2018. Specimens provided from urogenital, rectal, and pharyngeal sites were analyzed using nucleic acid amplification test to detect CT/NG. Prevalence estimates of CT/NG, overall and by anatomical site were calculated. All estimates are respondent-driven sampling-adjusted., Results: Among 1177 GBM, the prevalence of rectal, urogenital, pharyngeal and overall were respectively 2.4%, 0.4%, 0.4%, and 2.8% for CT infections, and 3.1%, 0.4%, 3.5%, and 5.6% for NG infections. If testing had been limited to the urogenital site, 80% and 94% of CT and NG infections, respectively, would have been missed., Conclusions: This community-based study among GBM shows that the CT prevalence was about half of that observed for NG. A large part of CT/NG infections involves only the extragenital sites, highlighting the need for systematic multisite screening regardless of symptoms. In the mist of the COVID-19 pandemic and the limited CT/NG screening capacity due to test kits shortage, it might be considered to prioritize rectal and pharyngeal CT/NG testing over urogenital testing in asymptomatic GBM., Competing Interests: Conflict of Interest: S.H.-L., A.-C.L., E.E.M.M., J.J., and C.F. have no conflict of interest to disclose. H.A., J.C., M.M.-P., A.F., G.L., D.G., T.A.H., D.M., and N.J.L. report grants from Canadian Institutes for Health Research, Canadian Foundation for AIDS Research, Ontario HIV Treatment Network and Public Health Agency of Canada, during the conduct of the study. H.A., J.C., M.M.-P., A.F., and G.L. report grants from Ministère de la Santé et des Services sociaux, as well as non-financial support from CIUSSS Centre-Sud-de-l'Ile-de-Montréal, Direction régionale de santé publique de Montréal, during the conduct of the study. J.C. received grants and personal fees from ViiV Healthcare and Gilead Canada and personal fees from Merck Canada, outside the submitted work. D.M. reports grants from Michael Smith Foundation for Health Research, during the conduct of the study. N.J.L. received grants from Canadian Institutes of Health Research, Michael Smith Foundation for Health Research, Canadian Blood Services, Vancouver Island Health Authority, Canadian Foundation of AIDS Research, Gilead Sciences Canada, Vancouver Foundation, Public Health Agency of Canada, University of Victoria, and MITACS, outside the submitted work., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Interbody fusion is a widely utilized and accepted procedure to treat advanced debilitating lumbar degenerative disc disease (DDD). Increasingly, surgeons are seeking interbody devices that are large for stability and grafting purposes but can be inserted with less invasive techniques. To achieve these contrary objectives a novel, conformable mesh interbody fusion device was designed to be placed in the disc space through a small portal and filled with bone graft in situ to a large size. This design can reduce the risk of trauma to surrounding structures while creating a large graft footprint that intimately contours to the patient's own anatomy. The purpose of this Investigational Device Exempt (IDE) trial was to evaluate the perioperative and long-term results of this novel conformable mesh interbody fusion device., Methods: This investigation is a prospective, multicenter, single-arm, Food and Drug Administration and Institutional Review Board-approved IDE, performance goal trial. A total of 102 adults presenting with DDD at a single level between L2 and S1 and unresponsive to 6 months conservative care had instrumented lumbar interbody fusion. Validated assessment tools include 100 mm visual analog scale for pain, Oswestry Disability Index (ODI) for function, single question survey for patient satisfaction, and computed tomography (CT) scan for fusion. Patients were enrolled across 10 geographically distributed sites. Pain/ODI surveys, physical evaluations, and imaging were performed serially through 24 months. Specifically, CT was performed at 12 and, if not fused, 24 months. Independent radiologists assessed CTs for fusion. An independent committee adjudicated adverse events. Patients with complete data at 24 months were included in the analysis., Results: Ninety-six (96, 94% follow-up rate) patients (57.0 ± 12.0 years, 50.0% female, Body Mass Index 30.6 ± 4.9) reported average decreased low back pain from baseline of 45.0 ± 26.6 at 6 weeks and 51.4 ± 26.2 at 24 months. Right/left leg pain reduced by 28.9 ± 36.7/37.8±32.4 at 6 weeks and 30.5±33.0/40.3 34.6 at 24 months. Mean ODI improved 17.1 ± 18.7 from baseline to 6 weeks and 32.0 ± 18.5 by 24 months. At 24 months, 91.7% of patients rated their procedure as excellent/good. Fusion rates were 97.9% (94/96) at 12 months, and 99% (95/96) at 24 months. Mean operative time, estimated blood loss, and length of stay were 2.6 ± 0.9 hours, 137 ± 217 mL, and 2.3 ± 1.2 days, respectively. No device-related serious adverse events have occurred., Conclusions: Clinically significant outcomes for pain, function, fusion, and device safety were demonstrated in this population. Substantial clinical improvements occur by 6 weeks postoperative and continue to improve to 24 months. The successful outcomes observed in this trial support use of this novel device in an instrumented lumbar interbody fusion., Level of Evidence: 3., Clinical Relevance: This reports substantiates that the preliminary 1-year findings published earlier for this investigation are confirmed and the fusion rates and that patient improvements reported are sustained through 2 years., Competing Interests: Financial Disclosures and Conflicts of Interest: John Chi discloses consulting fees from DePuy Spine and Stryker/K2M. Pierce Nunley discloses royalties or licenses from Stryker, Zimmer Biomet, and IMSE; consulting fees from Spineology, Stryker, IMSE, Integrity Implants, Kuros, NEO Spine, and Simplify Medical; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or education events from Instrinsic Therapeutics and Organogenesis; and stock or stock options from Spinelogy and Surgalign. Stephane Lavoie discloses royalties or licenses from Spineology and consulting fees from Choice Spine and Spineology. Yi Lu discloses grants from the Stepping Strong Foundation (paid to institution); consulting fees from DePuy/Synthes; and stock or stock options in AxioMed LLC. Marcus Stone discloses support for the present article (eg, funding, provision of study materials, medical writing, etc) from Spineology; grants or contracts from Wright Medical (paid to institution); consulting fees from Spineology and Organogenesis (paid to Marcus Stone) and from Simplify Medical, Zimmer Biomet, and Spineology (paid to institution). All remaining authors report no relevant disclosures., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2021 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Aim: Investigating biological processes in at-risk individuals may help elucidate the aetiological mechanisms underlying psychosis development, refine prediction models and improve intervention strategies. This study examined the associations between sleep disturbances, chronotype, depressive and psychotic symptoms in individuals at ultra-high risk for psychosis., Methods: A sample of 81 ultra-high risk patients completed clinical interviews and self-report assessments of chronotype and sleep during the Neurapro clinical trial. Mixed regression was used to investigate the cross-sectional associations between symptoms and sleep disturbances/chronotype., Results: Sleep disturbances were significantly associated with increased depressive and attenuated positive psychotic symptoms. Greater preference for eveningness was significantly associated with increased negative symptoms, but not with depressive or attenuated positive psychotic symptoms., Conclusion: Sleep disturbances and chronotype may impact the emerging psychopathology experienced by ultra-high risk individuals. Further, the preliminary relationship observed between greater preference for eveningness and negative symptoms offers a unique opportunity to treat negative symptoms through chronobiological approaches., (© 2021 John Wiley & Sons Australia, Ltd.)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Roughly 3% of adults aged 50 years or older experience significant symptoms of attention-deficit/hyperactivity disorder (ADHD). They are often diagnosed for the first time in later adulthood, because ADHD is a relatively new diagnosis with only recent awareness of later-life cases, and because many symptomatic adults have high early-life functioning due to supportive environmental and social structures. Current Diagnostic and Statistical Manual of Mental Disorders-5 criteria require evidence of symptom onset prior to age 12, which rests on self-report in older adults for whom ancillary sources are unavailable or unreliable. In this review, we summarize evidence from several bodies of literature which suggest this criterion may be invalid in older adults. The authors hypothesize that demonstrating childhood symptom onset in older adults is not feasible (i.e., no awareness of ADHD prior to 1970; no good current ancillary sources of childhood behaviors), unreliable (i.e., severely flawed retrospective self-report) and unethical (i.e., unreasonable denial of support to people who need it, with demonstrated poor outcomes associated with untreated ADHD in adults). The authors outline additional research that is needed to establish the validity of self-reported childhood symptom onset in this under-studied demographic, including the identification of contextual factors (perhaps unique to late life) that are associated with the emergence of ADHD symptoms in older adulthood; determining the impact of memory biases on recall of childhood symptoms in older adults with ADHD; quantifying self-perception deficits; and investigating the usefulness of executive functioning rating scales to complement diagnostic assessment in older adults., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: Instrument-navigation modalities including CT-guided and robot-assisted methods claim both efficacy and accuracy when applied to spine surgery, yet often increase setup and operating times which can translate to increased costs. To see the impact of different technologies on surgical efficiency, we studied the impact of a single surgeon's experience with a multitude of instrument navigational technologies., Methods: Consecutive patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) were analyzed. Consecutive cases were done with assistance of a robot (Mazor, Medtronic, Minneapolis, MN), with the assistance of fluoroscopic instrument-tracking (TrackX, North Carolina, USA), or fluoroscopy alone without adjunctive navigation in consecutive blocks of time. The cases done without assistance were used to normalize for number of interbody implants and decompressions performed as well as hardware removal if needed. Age, body mass index (BMI), sex, operative levels, laminectomy, need for hardware removal, and total operative time were recorded., Results: A total of 119 cases (74 conventional, 13 robot-assisted, 32 instrument-tracking) were included in analysis. There were no significant differences in age, sex, or BMI between modalities. Average total operative time for robot-assisted, and instrument-tracking-assisted cases was 175.46 ± 46.86 min 119.63 ± 34.33 min, respectively, for each level (p < 0.05 across each group). After normalization against operative times from similar cases performed with conventional fluoroscopy, robotic-navigation added an average of 42.25 ± 28.35 min while use of instrument-tracking saved an average of 13.88 ± 38.69 min. There was no learning curve seen using robotic navigation, as operative times remained consistently longer than similar cases using conventional fluoroscopy and showed no sign of improvement over time. Cases using instrument-tracking were initially slower but trended downwards through approximately 11 patients, at which point operative times were consistently quicker (R 2 = 0.39). None of the assisted cases were abandoned in favor of standard fluoroscopy or required hardware revision., Conclusion: Enabling technology can have a significant impact on surgical efficiency. Compared to MIS-TLIFs performed with standard fluoroscopy, those done with robotic-assistance consistently negatively impacted operative times while instrument-tracking was associated with a short learning curve and in the majority of cases studied showed improved operative times., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder., Methods: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model., Results: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51)., Conclusions: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.

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., (© 2020 John Wiley & Sons Australia, Ltd.)

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants' understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics.

Rhamnolipids are a specific class of microbial surfactants, which hold great biotechnological and therapeutic potential. However, their exploitation at the industrial level is hampered because they are mainly produced by the opportunistic pathogen Pseudomonas aeruginosa . The non-human pathogenic bacterium Pantoea ananatis is an alternative producer of rhamnolipid-like metabolites containing glucose instead of rhamnose residues. Herein, we present the isolation, structural characterization, and total synthesis of ananatoside A, a 15-membered macrodilactone-containing glucolipid, and ananatoside B, its open-chain congener, from organic extracts of P. ananatis . Ananatoside A was synthesized through three alternative pathways involving either an intramolecular glycosylation, a chemical macrolactonization or a direct enzymatic transformation from ananatoside B. A series of diasteroisomerically pure (1→2), (1→3), and (1→4)-macrolactonized rhamnolipids were also synthesized through intramolecular glycosylation and their anomeric configurations as well as ring conformations were solved using molecular modeling in tandem with NMR studies. We show that ananatoside B is a more potent surfactant than its macrolide counterpart. We present evidence that macrolactonization of rhamnolipids enhances their cytotoxic and hemolytic potential, pointing towards a mechanism involving the formation of pores into the lipidic cell membrane. Lastly, we demonstrate that ananatoside A and ananatoside B as well as synthetic macrolactonized rhamnolipids can be perceived by the plant immune system, and that this sensing is more pronounced for a macrolide featuring a rhamnose moiety in its native 1 C 4 conformation. Altogether our results suggest that macrolactonization of glycolipids can dramatically interfere with their surfactant properties and biological activity., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: HIV-exposed but uninfected (HEU) infants are at increased risk of impaired early linear growth and cognitive development. We examined associations between prenatal and postnatal growth and subsequent neurodevelopment in Ugandan HEU infants, hypothesizing that early insults may explain alterations in both somatic growth and brain development., Methods: We prospectively followed a cohort of HEU infants from birth to 18 months of age, and measured length/height, weight, head, and arm circumference longitudinally. The Malawi Development Assessment Tool (MDAT, 12 and 18 months) and the Color Object Association Test (18 months) were used for developmental assessments., Results: Among 170 HEU infants, the prevalence of low-birth weight and failure to thrive was 7.6% and 37%, respectively. HEU infants had MDAT scores that were similar to the reference population. The mean (SD) score on the Color Object Association Test was 5.5 (3.1) compared with 6.9 (5.3) in developmentally normal children. Developmental ability at age 18 months showed strong cross-sectional correlation with weight-for-age (ρ = 0.36, P < 0.0001), length/height-for-age (ρ = 0.41, P < 0.0001), head circumference-for-age (ρ = 0.26, P = 0.0011), and mid-upper arm circumference-for-age (ρ = 0.34, P = 0.0014). There was a statistically significant correlation between birth weight and MDAT z-score at 18 months (ρ = 0.20, P = 0.010). Failure to thrive was associated with lower MDAT z-score [median -0.13 (IQR -0.75 to +0.14) versus +0.14 (IQR -0.44 to +0.63), P = 0.042]., Conclusion: Growth faltering in HEU infants was associated with lower attainment of developmental milestones at age 18 months. Our findings point to a simple screening method for identifying HEU infants at risk for developmental intervention., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The distinction between the schizophrenia spectrum and other types of disorders may be clinically relevant in terms of its predictive validity as suggested by studies showing schizophrenia spectrum patients have more unfavourable outcomes compared to other psychotic disorders. The present study aimed to investigate whether basic self-disturbances and neurocognitive processes that have been linked to psychosis risk have discriminative power for schizophrenia spectrum disorders in patients presenting with first episode psychosis (FEP) and at ultra-high risk for psychosis (UHR)., Methods: 38 FEP patients, 48 UHR patients, and 33 healthy controls were assessed for basic self-disturbances (using the Examination of Anomalous Self-Experience, EASE, interview), source monitoring and aberrant salience (behavioural tasks to measure neurocognitive constructs). Clinical groups were divided into patients with schizophrenia spectrum disorders and those with other non-spectrum disorders and were further compared on measures controlling for symptom severity and age., Results: Basic self-disturbances distinguished schizophrenia spectrum from non-spectrum disorders in the 'FEP only' sample, F = 19.76, p < 0.001, η 2 partial  = 0.37, and also in the combined UHR/FEP sample, F = 23.56, p < 0.001, η 2 partial  = 0.22. Additionally, some processes related to source monitoring deficits were elevated in schizophrenia spectrum disorders. In contrast, the two groups (schizophrenia spectrum vs other diagnoses) performed similarly in aberrant salience tasks. Comparable results were obtained for analyses performed with an FEP/UHR combined sample and the 'FEP only' sample., Discussion: Basic self-disturbances at the phenomenological level and source monitoring deficits on the neurocognitive level may be useful in identifying risk of schizophrenia spectrum disorders at the earliest clinical presentation., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Study Design: A prospective multicenter investigational device exempt trial is underway evaluating a novel conformable mesh interbody fusion device in subjects undergoing single-level fusion for degenerative disc disease. Patients meeting inclusion and exclusion criteria were offered enrollment. There is no comparative group in this study., Objective: Establish the short and long-term safety and effectiveness of a novel conformable mesh interbody fusion device in subjects undergoing single-level fusion for degenerative disc disease unresponsive to conservative care., Summary of Background Data: Transforaminal lumbar interbody fusion remains a critical procedure for patients with degenerative lumbar disc disease. Increasingly minimally invasive techniques have been proposed to minimize muscle dissection and tissue damage with the goal of minimizing pain and length of stay., Methods: One hundred two subjects were enrolled across 10 sites. Ninety nine subjects remained available for follow-up at 12-months. Physical evaluations/imaging were performed serially through 12-months. Validated assessment tools included 100 mm visual analogue scale (VAS) for pain, Oswestry Disability Index (ODI) for function, and computerized tomography scan for fusion. Independent committees were used to identify adverse events and for assessment of radiographic fusion., Results: Reductions in low back pain (LBP)/leg pain and improvements in functional status occur early and are maintained through 12-month follow-up. Mean VAS-LBP change from baseline to 6-weeks post-op (-46 mm) continued to improve through 12 months (-51 mm). Similar trends were observed for leg pain. Mean ODI change from baseline to 6 weeks post-op (-17) was almost doubled by 12 months (-32). Fusion rates at 12-months are high (98%). No device-related serious adverse events have occurred., Conclusion: 12-month outcomes demonstrated excellent patient compliance and positive outcomes for pain, function, fusion, and device safety. Clinical improvements were observed by 6-weeks post-op and appear durable up to 1 year later. A novel mesh interbody device may provide an alternative means of interbody fusion that reduces connective tissue disruption.Level of Evidence: 3., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Individuals at ultra-high risk (UHR) for psychosis have an elevated risk of developing psychosis and other psychiatric outcomes. Risk biomarkers can assist in delineating individual risk and allow better prediction of longer-term outcomes. The aim of the present study was to examine if allostatic load (AL), a multisystem index of neuroendocrine, cardiovascular, immune and metabolic dysregulation, is associated with clinical outcomes in youth at UHR for psychosis. AL was measured in 106 participants of the NEURAPRO study (n = 70 female, n = 36 male; mean age 17.21, SD 2.37), a multicentre randomized-controlled trial of long-chain omega-3 polyunsaturated fatty acids versus placebo in people at UHR for psychosis. Psychiatric symptoms and social and occupational functioning were assessed at baseline and 6 and 12 months after study intake. Multivariate linear and logistic regression models were used to test the relationship between AL and clinical outcomes. High AL at baseline was associated with poor social and occupational functioning at 6 months (β = -0.224, p = 0.025) and with more severe manic symptoms at 6 months (β = 0.207, p = 0.026), taking into account relevant covariates including age and smoking status. No significant associations were observed at the 12-month follow-up assessment or with any other clinical outcome measures. Our data provide initial evidence for a link between AL and impaired functioning in individuals at UHR for psychosis. Further studies are needed to evaluate AL as a potential predictor of early treatment response., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To determine which narrative performance level for each general pediatrics entrustable professional activity (EPA) reflects the minimum level clinical competency committees (CCCs) felt should be associated with graduation as well as initial entrustment and compare expected narrative performance levels (ENPLs) for each EPA with actual narrative performance levels (ANPLs) assigned to residents at initial entrustment., Method: A series of 5 narratives, corresponding to the 5 milestone performance levels, were developed for each of the 17 general pediatrics EPAs. In academic year (AY) 2015-2016, the CCCs at 22 Association of Pediatric Program Directors Longitudinal Educational Assessment Research Network member sites reported ENPLs for initial entrustment and at time of graduation. From AYs 2015-2016 to 2017-2018, programs reported ANPLs for initial entrustment decisions. ENPLs and ANPLs were compared using a logistic mixed effects model., Results: ENPLs for graduation and entrustment were most often level 3 (competent) followed by level 4 (proficient). For 8 EPAs, the ENPLs for graduation and entrustment were the same. For the remaining 9, some programs would entrust residents before graduation or graduate them before entrusting them. There were 4,266 supervision level reports for initial entrustment for which an ANPL was provided. ANPLs that were lower than the ENPLs were significantly more likely to be assigned to the medical home-well child (OR = 0.39; 95% CI: 0.26-0.57), transition to adult care (OR = 0.43; 95% CI: 0.19-0.95), behavioral or mental health (OR = 0.36; 95% CI: 0.18-0.71), make referrals (OR = 0.31; 95% CI: 0.17-0.55), lead a team (OR = 0.34; 95% CI: 0.22-0.52), and handovers (OR = 0.18; 95% CI: 0.09-0.36) EPAs., Conclusions: CCCs reported lower ENPLs for graduation than for entrustment for 5 EPAs, possibly indicating curricular gaps that milestones and EPAs could help identify.

Intensive use of the chlorinated pesticide chlordecone from the 1970s to 1993 to prevent crop damage in banana plantations of Guadeloupe and Martinique led to diffuse pollution of soils and surface waters, affecting both fauna and human beings in the contaminated areas. Since 2001, drinking water production plants have been equipped with filters containing activated carbon that must be treated after saturation. The objective of this work is to produce a hybrid material composed of activated carbon and vitamin B12 (VB12) for the degradation of chlordecone (CLD). The preparation of such a hybrid material is carried out by non-covalent fixation to achieve an eco-friendly solution for the serious environmental problem of contamination by chlorinated pesticides. It is thus proposed to degrade CLD by a physico-chemical treatment allowing salvage of the catalyst, which is adsorbed on the carbon surface to generate less waste that is inexpedient to treat. Activated carbon (AC) is produced locally from available sugarcane bagasse subjected to phosphoric acid activation. The main characteristics of this material are a major mesoporous structure (0.91%) and a specific (BET) surface area ranging from 1000 to 1500 m 2  g -1 . The experimental results showed that BagP1.5 has a high adsorption capacity for VB12 due to its large surface area (1403 m 2  g -1 ). The binding of VB12 to the bagasse-derived AC is favoured at high temperatures. The adsorption is optimal at a pH of approximately 6. The maximum adsorption capacity of VB12 on the AC, deduced from the Langmuir model, was 306 mg g -1 , confirming the high affinity between the two components. The hybrid material was characterised by FTIR, Raman, X-ray fluorescence spectroscopy and SEM analysis. CLD removal by this hybrid material was faster than that by VB12 or BagP1.5 alone. The CLD degradation products were characterised by mass spectrometry.

Background and Aims: The notion of basic self-disturbance has been proposed as a core feature of schizophrenia-spectrum disorders and as an indicator of future transition to psychosis in high-risk populations. However, the relation of this notion to many clinical characteristics has not been explored. The aim of this study was: (a) to investigate the distribution of self-disturbance and other symptoms dimensions in ultra-high risk (UHR), first-episode psychosis (FEP) and healthy control groups; and (b) to explore the association of self-disturbance with a history of self-harm, suicidal attempt, eating disorder symptomatology, school bullying victimization and sexual or physical abuse., Methods: Patients with UHR status (n = 38) or FEP (n = 26) and healthy controls (n = 33) were assessed with the Examination of Anomalous Self-Experience (EASE) and the Comprehensive Assessment of at Risk Mental States (CAARMS). The clinical-historical variables were assessed through medical records., Results: The FEP group scored significantly higher on the EASE than the UHR group, which scored significantly higher than the healthy control group, which had a very low score. Multivariate logistic regression analyses revealed that higher EASE score was significantly associated with a history of self-harm, disordered eating and bullying victimization (but not with suicide attempts or sexual/physical abuse) after controlling for positive, negative and depressive symptoms., Conclusion: These novel findings suggest that self-disturbance may be related to a history of school bullying victimization, self-harm and eating disorder symptomatology in patients with or at-risk of psychosis. If further confirmed, these findings are potentially relevant to clinical risk assessment and therapy., (© 2019 John Wiley & Sons Australia, Ltd.)

Background & Aims: Intestinal microbes and their metabolites affect the development of colorectal cancer (CRC). Short-chain fatty acids are metabolites generated by intestinal microbes from dietary fiber. We investigated the mechanisms by which free fatty acid receptor 2 (FFAR2), a receptor for short-chain fatty acids that can affect the composition of the intestinal microbiome, contributes to the pathogenesis of CRC., Methods: We performed studies with Apc Min/+ mice, Apc Min/+ Ffar2 -/- mice, mice with conditional disruption of Ffar2 in dendritic cells (DCs) (Ffar2 fl/fl CD11c-Cre mice), Apc Min/+ Ffar2 fl/fl CD11c-Cre mice, and Ffar2 fl/fl mice (controls); some mice were given dextran sodium sulfate to induce colitis, with or without a FFAR2 agonist or an antibody against interleukin 27 (IL27). Colon and tumor tissues were analyzed by histology, quantitative polymerase chain reaction, and 16S ribosomal RNA gene sequencing; lamina propria and mesenteric lymph node tissues were analyzed by RNA sequencing and flow cytometry. Intestinal permeability was measured after gavage with fluorescently labeled dextran. We collected data on colorectal tumors from The Cancer Genome Atlas., Results: Apc Min/+ Ffar2 -/- mice developed significantly more spontaneous colon tumors than Apc Min/+ mice and had increased gut permeability before tumor development, associated with reduced expression of E-cadherin. Colon tumors from Apc Min/+ Ffar2 -/- mice had a higher number of bacteria than tumors from Apc Min/+ mice, as well as higher frequencies of CD39 + CD8 + T cells and exhausted or dying T cells. DCs from Apc Min/+ Ffar2 -/- mice had an altered state of activation, increased death, and higher production of IL27. Administration of an antibody against IL27 reduced the numbers of colon tumors in Apc Min/+ mice with colitis. Frequencies of CD39 + CD8 + T cells and IL27 + DCs were increased in colon lamina propria from Ffar2 fl/fl CD11c-Cre mice with colitis compared with control mice or mice without colitis. Apc Min/+ Ffar2 fl/fl CD11c-Cre mice developed even more tumors than Apc Min/+ Ffar2 fl/fl mice, and their tumors had even higher numbers of IL27 + DCs. Apc Min/+ mice with colitis given the FFAR2 agonist developed fewer colon tumors, with fewer IL27 + DCs, than mice not given the agonist. DCs incubated with the FFAR2 agonist no longer had gene expression patterns associated with activation or IL27 production., Conclusions: Loss of FFAR2 promotes colon tumorigenesis in mice by reducing gut barrier integrity, increasing tumor bacterial load, promoting exhaustion of CD8 + T cells, and overactivating DCs, leading to their death. Antibodies against IL27 and an FFAR2 agonist reduce tumorigenesis in mice and might be developed for the treatment of CRC., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Learning in small groups is a frequent activity in undergraduate programs to enrich learning, as well as in nursing programs during clinical experiences. Being in a small group adds elements of group dynamics that influence learning. Research into the influence of these elements on learning in small groups is not clear in the literature. This makes it challenging for educators to promote the optimal environment for learning., Objective: To explore the literature on elements of group dynamics that influence learning in small groups among undergraduate students., Design and Data Sources: A scoping review was performed, inspired by the five-stage approach of Arksey and O'Malley and the methodology outlined by the Joanna Briggs Institute. Various databases were used including CINAHL, ERIC, psycINFO, PubMed and Science Direct., Review Method: Our research question was: What are the elements of group dynamics that influence learning in small groups among undergraduate students? At least two authors analyzed the relevant studies and data were extracted to describe the elements of group dynamics that influence learning in small groups among undergraduate students., Results: Thirty papers were included in our review. Five elements emerged: engagement, openness, support, quality of communication and style of dominant behavior., Conclusions: The results suggested the utilization of these elements in establishing a group dynamic favorable for learning in small groups. Since little research has been done into group dynamics in nursing education, it was useful to explore this concept in other disciplines. Further research is needed with a focus on clinical education for nursing students., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This study examined whether distress in relation to attenuated psychotic symptoms (DAPS) is associated with clinical outcomes in an ultra-high risk (UHR) for psychosis sample. We also investigated whether DAPS is associated with cognitive style (attributional style and cognitive biases) and whether amount of psychosocial treatment provided is associated with reduction in DAPS. The study was a secondary analysis of the "Neurapro" clinical trial of omega-3 fatty acids. Three hundred and four UHR patients were recruited across 10 early intervention services. Data from baseline assessment, regular assessments over 12 months, and medium term follow-up (mean = 3.4 years) were used for analysis. Findings indicated: a positive association between DAPS assessed over time and transition to psychosis; a significant positive association between baseline and longitudinal DAPS and transdiagnostic clinical and functional outcomes; a significant positive association between baseline and longitudinal DAPS and nonremission of UHR status. There was no relationship between severity of DAPS and cognitive style. A greater amount of psychosocial treatment (cognitive-behavioral case management) was associated with an increase in DAPS scores. The study indicates that UHR patients who are more distressed by their attenuated psychotic symptoms are more likely to have a poorer clinical trajectory transdiagnostically. Assessment of DAPS may therefore function as a useful marker of risk for a range of poor outcomes. The findings underline the value of repeated assessment of variables and incorporation of dynamic change into predictive modeling. More research is required into mechanisms driving distress associated with symptoms and the possible bidirectional relationship between symptom severity and associated distress., (© The Author(s) 2020. Published by Oxford University Press on behalf of the University of Maryland’s school of medicine, Maryland Psychiatric Research Center.)

Background: The Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) study is a prospective, multicenter, Canadian cohort study investigating human immunodeficiency virus-1 (HIV-1) reservoirs, chronic inflammation, and immune responses in children with perinatally acquired HIV-1 infection. The focus of this report is HIV-1 reservoirs and correlates in the peripheral blood of children who achieved sustained virologic suppression (SVS) for ≥5 years., Methods: HIV-1 reservoirs were determined by measuring HIV-1 DNA in peripheral blood mononuclear cells and inducible cell-free HIV-1 RNA in CD4+ T-cells by a prostratin analogue stimulation assay. HIV serology was quantified by signal-to-cutoff ratio (S/CO)., Results: Of 228 enrolled participants, 69 achieved SVS for ≥5 years. HIV-1 DNA, inducible cell-free HIV-1 RNA, and S/COs correlated directly with the age of effective combination antiretroviral therapy (cART) initiation (P < .001, P = .036, and P < .001, respectively) and age when SVS was achieved (P = .002, P = .038, and P < .001, respectively) and inversely with the proportion of life spent on effective cART (P < .001, P = .01, and P < .001, respectively) and proportion of life spent with SVS (P < .001, P = .079, and P < .001, respectively). Inducible cell-free HIV-1 RNA correlated with HIV-1 DNA, most particularly in children with SVS, without virologic blips, that was achieved with the first cART regimen initiated prior to 6 months of age (rho = 0.74; P = .037) or later (rho = 0.87; P < .001). S/COs correlated with HIV-1 DNA (P = .003), but less so with inducible cell-free HIV-1 RNA (P = .09)., Conclusions: The prostratin analogue stimulation assay, with its lower blood volume requirement, could be a valuable method for evaluating inducible HIV-1 reservoirs in children. Standard commercial HIV serology may be a practical initial indirect measure of reservoir size in the peripheral blood of children with perinatally acquired HIV-1 infection., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the 'ultra high risk' (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of transition to psychotic disorder and persistent attenuated psychotic symptoms (APS) at medium term follow-up (mean = 3.4 years) in UHR patients, as well as with general psychopathology at baseline. The sample included 304 UHR participants (mean age = 19.12 years) involved in an international multicenter trial of omega-3 fatty acids. UHR individuals who also met the COGDIS criteria (basic symptoms risk criteria) did not have a greater risk of transition than those who met the UHR criteria alone. However, meeting COGDIS risk criteria was associated with a greater likelihood of meeting the UHR attenuated psychotic symptoms risk group (i.e., having persistent attenuated psychotic symptoms) at 12-month follow-up (odds ratio = 1.85; 95% CI = 1.03, 3.32). Greater severity of cognitive basic symptoms was also independently associated with more severe general psychopathology at study entry. The findings do not support the notion that combined risk identification approaches (UHR and basic symptoms) aid in the identification of individuals at greatest risk of psychosis, although this interpretation is limited by the modest transition to psychosis rate (13%) and the time of follow up. However, the findings indicate that basic symptoms may be a clinically useful marker of more severe general psychopathology in UHR groups and risk for persistent attenuated psychotic symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: An individual is considered HIV positive when a confirmatory HIV-1/HIV-2 differentiation test returns positive following an initial reactive antigen/antibody combination screen. Falsely reactive HIV screens have been reported in patients with various concomitant infectious and autoimmune conditions. Falsely positive confirmatory HIV differentiation assays are seen less frequently, but have been observed in cases of pregnancy, pulmonary embolism, and malaria., Case Presentation: A healthy 27 year-old man was referred after a reactive ADVIA Centaur® HIV Ag/Ab screen and positive Bio-Rad Geenius™ HIV 1/2 Confirmatory assay, suggesting HIV-1 infection. The patient's HIV viral load was undetectable prior to initiation of antiretroviral therapy, and remained undetectable on subsequent testing after initiation of antiretroviral therapy. Both Centaur® and Geenius™ tests were repeated and returned reactive. As this patient was believed to be at low risk of acquiring HIV infection, samples were additionally run on Genscreen™ HIV-1 Ag assay and Fujirebio Inno-LIA™ HIV-1/2 score, with both returning non-reactive. For confirmation, the patient's proviral HIV DNA testing was negative, confirming the initial results as being falsely positive. The patient disclosed that he had been using a variety of anabolic steroids before and during the time of HIV testing., Discussion and Conclusions: The erroneous diagnosis of HIV can result in decreased quality of life and adverse effects of antiretroviral therapy if initiated, hence the importance of interpreting the results of HIV testing in the context of an individual patient. This reports suggests a potential association between the use of anabolic steroids and falsely-reactive HIV testing.

Objective: The current international trend is to create large datasets with existing data and/or deposit newly collected data into repositories accessible to the scientific community. These practices lead to more efficient data sharing, better detection of small effects, modelling of confounders, establishment of sample generalizability and identification of differences between any given disorders. In Australia, to facilitate such data-sharing and collaborative opportunities, the Neurobiology in Youth Mental Health Partnership was created. This initiative brings together specialised researchers from around Australia to work towards a better understanding of the cross-diagnostic neurobiology of youth mental health and the translation of this knowledge into clinical practice. One of the mandates of the partnership was to develop a protocol for harmonised prospective collection of data across research centres in the field of youth mental health in order to create large datasets., Methods: Four key research modalities were identified: clinical assessments, brain imaging, neurocognitive assessment and collection of blood samples. This paper presents the consensus set of assessments/data collection that has been selected by experts in each domain., Conclusion: The use of this core set of data will facilitate the pooling of psychopathological and neurobiological data into large datasets allowing researchers to tackle important questions requiring very large numbers. The aspiration of this transdiagnostic approach is a better understanding of the mechanisms underlying mental illnesses.

Background: The integration of various domains or levels of analysis (clinical, neurobiological, genetic, etc.) has been a challenge in schizophrenia research. A promising approach is to use the core phenomenological features of the disorder as an organising principle for other levels of analysis. Minimal self-disturbance (fragility in implicit first-person perspective, presence and agency) is emerging as a strong candidate to play this role. This approach was adopted in a previously described theoretical neurophenomenological model that proposed that source monitoring deficits and aberrant salience may be neurocognitive/neurobiological processes that correlate with minimal self-disturbance on the phenomenological level, together playing an aetiological role in the onset of schizophrenia spectrum disorders. The current paper presents full cross-sectional data from the first empirical test of this model., Methods: Fifty ultra-high risk for psychosis patients, 39 first episode psychosis patients and 34 healthy controls were assessed with a variety of clinical measures, including the Examination of Anomalous Self-Experience (EASE), and neurocognitive and neurophysiological (EEG) measures of source monitoring deficits and aberrant salience., Results: Linear regression indicated that source monitoring (composite score across neurocognitive and neurophysiological measures), with study group as an interaction term, explained 39.8% of the variance in EASE scores (R 2  = 0.41, F(3,85) = 14.78, p < 0.001), whereas aberrant salience (composite score) explained only 6% of the variance in EASE scores (R 2  = 0.06, F(3,85) = 1.44, p = 0.93). Aberrant salience measures were more strongly related to general psychopathology measures, particularly to positive psychotic symptoms, than to EASE scores., Discussion: A neurophenomenological model of minimal self-disturbance in schizophrenia spectrum disorders may need to be expanded from source monitoring deficits to encompass other relevant constructs such as temporal processing, intermodal/multisensory integration, and hierarchical predictive processing. The cross-sectional data reported here will be expanded with longitudinal analysis in subsequent reports. These data and other related recent research show an emerging picture of neuro-features of core phenomenological aspects of schizophrenia spectrum disorders beyond surface-level psychotic symptoms., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The Ultra-High Risk (UHR) for psychosis group is known to be heterogeneous with diverse outcomes. This study aimed to: 1. Identify subclasses of UHR individuals based on trajectories of symptomatic and functional change over time, 2. Identify predictors of these trajectories. A sample of 304 UHR individuals participating in the Neurapro trial were followed over an average of 40 months. All participants received cognitive-behavioural case management (CBCM). Symptomatic and functional profiles were investigated using latent class growth analysis. Multinomial regression was employed to investigate predictors of classes. Identified trajectories showed mostly parallel slopes (i.e. improving symptoms/functioning over time), which were primarily distinct regarding the severity of symptomatology/level of functioning at baseline (i.e. the intercept). Higher symptomatic/lower functioning classes were predicted by higher substance use, older age, female gender, and lower cognitive functioning. No divergent trajectories were identified as all classes improved over time. This may reflect effective treatment through CBCM, natural illness course, or effective engagement with mental health services. Nonetheless, classes highest in symptoms/lowest in functioning still showed considerable impairment during follow-up, highlighting the need for targeted intervention in these subgroups. The study emphasizes the need for more clinical attention directed towards UHR patients being female or using substances., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Betulinic acid and ursolic acid are ubiquitous, naturally-occurring triterpenoids exhibiting various pharmacological activities including cytotoxic and anti-inflammatory activities. However, these triterpenoids display unfavorable pharmacokinetic properties as well as low aqueous solubility. It has been shown that the presence of α-l-rhamnose moieties positively modulates the anticancer activity of secondary metabolites. Herein we report the synthesis and in vitro evaluation of cytotoxic and anti-inflammatory activities of a series of rhamnose-containing ursolic and betulinic acid saponins. Relying on Schmidt's normal and inverse procedures, monorhamnosides, (1→4)-linked dirhamnosides as well as branched trirhamnosides and tetrarhamnosides were synthesized in high yields with full control of stereoselectivity. A betulinic acid saponin bearing a 3- O -α-l-rhamnopyranosyl-(1→4)-α-l-rhamnopyranosyl residue was found to be a potent cytotoxic agent against human colorectal adenocarcinoma cells without damaging the healthy cells (selectivity ratio > 20) whereas rhamnose-containing ursolic acid saponins potently inhibited NO overproduction induced by LPS-stimulated macrophages. Our results reveal that rhamnose-containing ursolic and betulinic acid saponins represent promising therapeutic agents., Competing Interests: The authors have no conflict of interest to declare., (This journal is © The Royal Society of Chemistry.)

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., (© 2019 John Wiley & Sons Australia, Ltd.)

Group 3 innate lymphoid cells (ILC3s) sense environmental signals that are critical for gut homeostasis and host defense. However, the metabolite-sensing G-protein-coupled receptors that regulate colonic ILC3s remain poorly understood. We found that colonic ILC3s expressed Ffar2, a microbial metabolite-sensing receptor, and that Ffar2 agonism promoted ILC3 expansion and function. Deficiency of Ffar2 in ILC3s decreased their in situ proliferation and ILC3-derived interleukin-22 (IL-22) production. This led to impaired gut epithelial function characterized by altered mucus-associated proteins and antimicrobial peptides and increased susceptibility to colonic injury and bacterial infection. Ffar2 increased IL-22 + CCR6 + ILC3s and influenced ILC3 abundance in colonic lymphoid tissues. Ffar2 agonism differentially activated AKT or ERK signaling and increased ILC3-derived IL-22 via an AKT and STAT3 axis. Our findings suggest that Ffar2 regulates colonic ILC3 proliferation and function, and they identify an ILC3-receptor signaling pathway modulating gut homeostasis and pathogen defense., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Two sulfated diterpene glycosides featuring a highly substituted and sterically encumbered cyclopropane ring have been isolated from the marine red alga Peyssonnelia sp. Combination of a wide array of 2D NMR spectroscopic experiments, in a systematic structure elucidation workflow, revealed that peyssonnosides A-B (1-2) represent a new class of diterpene glycosides with a tetracyclo [7.5.0.0 1,10 .0 5,9 ] tetradecane architecture. A salient feature of this workflow is the unique application of quantitative interproton distances obtained from the rotating frame Overhauser effect spectroscopy (ROESY) NMR experiment, wherein the β-d-glucose moiety of 1 was used as an internal probe to unequivocally determine the absolute configuration, which was also supported by optical rotatory dispersion (ORD). Peyssonnoside A (1) exhibited promising activity against liver stage Plasmodium berghei and moderate antimethicillin-resistant Staphylococcus aureus (MRSA) activity, with no cytotoxicity against human keratinocytes. Additionally, 1 showed strong growth inhibition of the marine fungus Dendryphiella salina indicating an antifungal ecological role in its natural environment. The high natural abundance and novel carbon skeleton of 1 suggests a rare terpene cyclase machinery, exemplifying the chemical diversity in this phylogenetically distinct marine red alga.

Study Design: Prospective case series., Objective: Investigate the association of testosterone and thyroid-stimulating hormone (TSH) levels with depressive symptoms in women after spinal cord injury (SCI)., Setting: Community SCI clinic., Methods: Twenty-seven participants were enrolled in this study. Total testosterone (Total T) and TSH levels as well as the Center for Epidemiological Studies Depression Scale (CES-D) survey and monthly sexual activity were obtained from only 20 participants. Pearson's correlations were used to assess the relationship between age, time from injury, Total T level, TSH level, and CES-D total score. Follow-up analyses investigating the role of monthly sexual activity was also explored., Results: Participants' average age and time from injury was 44.4 ± 12.7 years old and 11.7 ± 8.89 years, respectively. Low Total T was observed in four participants and one of those participant's presented with low TSH as well. Nine women were classified as "at risk for clinical depression" on the CES-D (total score >15). Pearson's correlations revealed a significant association between time from injury and TSH ( r  = .536, p  = .015), as well as CES-D total score ( r  = -.547, p  = .013). Total T was associated with CES-D total score ( ρ  = -.541, p  = .02)., Conclusions: This study provides preliminary results on abnormal hormone levels and depressive symptoms in women after SCI. Twenty percent of this sample presented with low Total T, which was associated with increased depressive symptoms after accounting for time from injury. Further research is needed to investigate the impact of SCI on hormone function and mental health in women post SCI., Sponsorship: Sally Rynne National Association of Women's Health Quality Award 2002., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to International Spinal Cord Society 2019.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (© 2018 John Wiley & Sons Australia, Ltd.)

A series of oligomeric phenols including the known natural product 3,4,3',4'-tetrahydroxy-1,1'-biphenyl (3), the previously synthesized 2,3,8,9-tetrahydroxybenzo[ c]chromen-6-one (4), and eight new related natural products, cladophorols B-I (5-12), were isolated from the Fijian green alga Cladophora socialis and identified by a combination of NMR spectroscopy, mass spectrometric analysis, and computational modeling using DFT calculations. J-resolved spectroscopy and line width reduction by picric acid addition aided in resolving the heavily overlapped aromatic signals. A panel of Gram-positive and Gram-negative pathogens used to evaluate pharmacological potential led to the determination that cladophorol C (6) exhibits potent antibiotic activity selective toward methicillin-resistant Staphylococcus aureus (MRSA) with an MIC of 1.4 μg/mL. Cladophorols B (5) and D-H (7-11) had more modest but also selective antibiotic potency. Activities of cladophorols A-I (4-12) were also assessed against the asexual blood stages of Plasmodium falciparum and revealed cladophorols A (4) and B (5) to have modest activity with EC 50 values of 0.7 and 1.9 μg/mL, respectively.

Background: The purpose of this study was to evaluate the measurement properties of the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary, a patient-reported outcome instrument developed to meet US FDA recommendations for a symptom-based clinical trial endpoint in gastroparesis. The ANMS GCSI-DD assesses nausea, early satiety, postprandial fullness, and upper abdominal pain on a severity score from none (0) to very severe (4) and number of vomiting episodes during the past 24 hours. The composite score includes the first four symptoms, the core symptom score includes all five symptoms., Methods: Seventy-one patients diagnosed with idiopathic or diabetic gastroparesis were recruited for a four-week observational study. Patients completed the ANMS GCSI-DD at home between Baseline and Week 4. Statistical analyses included confirmatory factor analysis, item response theory analysis, internal consistency, test-retest reliability, and construct and known-groups validity., Key Results: Unidimensionality for the composite and core symptom scores was supported, and items exhibited good fit. Internal consistency (Cronbach's alpha =0.85 and 0.83) and test-retest reliability were 0.89 and 0.88, for composite and core symptom scores, respectively. Convergent validity was supported by strong correlations with patient-reported and clinician measures. Baseline and Week 4 scores differed for three measures used to define disease severity status (P < 0.0001), supporting known-groups validity., Conclusions & Inferences: The ANMS GCSI-DD has excellent reliability and validity, supporting its use to assess symptom-based endpoints in gastroparesis clinical studies. Further analyses will be conducted using clinical trial data to ascertain treatment responsiveness and define a responder., (© 2019 John Wiley & Sons Ltd.)