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Antimony-doped tin oxide nanoparticles (ATO NPs) have emerged as a promising tool in biomedical applications, namely robust photothermal effects upon near-infrared (NIR) light exposure, enabling controlled thermal dynamics to induce spatial cell death. This study investigated the interplay between ATO NPs and macrophages, understanding cellular uptake and cytokine release. ATO NPs demonstrated biocompatibility with no impact on macrophage viability and cytokine secretion. These findings highlight the potential of ATO NPs for inducing targeted cell death in cancer treatments, leveraging their feasibility, unique NIR properties, and safe interactions with immune cells. ATO NPs offer a transformative platform with significant potential for future biomedical applications by combining photothermal capabilities and biocompatibility. [ABSTRACT FROM AUTHOR]

Six types of γ-polyglutamic acid (γ-PGA)/cold water-soluble starch (St) composite film models were constructed using molecular dynamics simulation, and their properties were investigated and compared with the corresponding experimental values. The compatibility between the composite film components was analyzed using the radial distribution function and mean square displacement (MSD). The hydrogen-bond number and bond energy were used to track the film-formation process. The mechanical property data of the films were extracted, and MSD was used to analyze the permeability of the film to carbon dioxide, oxygen, water vapor, and carbon-16 saturated fatty acids. Finally, the simulated values of mechanical properties and permeability were compared with the experimental values. The results demonstrated that γ-PGA is well compatible with St. The intramolecular and intermolecular hydrogen bonds of γ-PGA and St did not change considerably during the film-formation process. The simulated values of the mechanical properties exhibited a similar trend as the experimental values; however, in terms of permeability, a difference was observed between the initial values of the simulated design and actual material parameters, as well as the complexity of the experiment. [ABSTRACT FROM AUTHOR]

Background: Past research has found that family involvement in psychosis treatment leads to better patient outcomes. Thus, caregiver communication skills training can be a viable approach to reducing caregiver stress and increasing self‐efficacy and communication. Aim: The purpose of this qualitative study was to describe family caregivers' perceptions of changes in themselves and their family member with psychosis following their participation in Motivational Interviewing in Loved Ones (MILO), a brief four to five‐hour psychoeducational intervention for caregivers. Methods: Sixty‐three participants in the MILO trials provided written qualitative responses to the prompt, "Since learning the ideas and techniques in this course, what is the most significant change you noticed in yourself, your family, or your relationships?" Responses were collected immediately following MILO participation and 12 weeks later. Qualitative themes were identified through an iterative consensus process. Results: Most participants reported positive changes in multiple domains of their lives. Major themes included: (1) Changes in Self, (2) Changes in Relationships, (3) Changes in Mindset, (4) Use of MILO Skills, and (5) Challenges. Conclusion: Qualitative results support and add context to the previously reported quantitative results from this study. MILO is a promising family intervention that positively influenced family environment and communication in pilot trials. Adaptations of MILO for families outside of a highly educated North American context should be considered. [ABSTRACT FROM AUTHOR]

Background: Enlarged pituitary gland volume could be a marker of psychotic disorders. However, previous studies report conflicting results. To better understand the role of the pituitary gland in psychosis, we examined a large transdiagnostic sample of individuals with psychotic disorders. Methods: The study included 751 participants (174 with schizophrenia, 114 with schizoaffective disorder, 167 with psychotic bipolar disorder, and 296 healthy controls) across six sites in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium. Structural magnetic resonance images were obtained, and pituitary gland volumes were measured using the MAGeT brain algorithm. Linear mixed models examined between-group differences with controls and among patient subgroups based on diagnosis, as well as how pituitary volumes were associated with symptom severity, cognitive function, antipsychotic dose, and illness duration. Results: Mean pituitary gland volume did not significantly differ between patients and controls. No significant effect of diagnosis was observed. Larger pituitary gland volume was associated with greater symptom severity (F = 13.61, p = 0.0002), lower cognitive function (F = 4.76, p = 0.03), and higher antipsychotic dose (F = 5.20, p = 0.02). Illness duration was not significantly associated with pituitary gland volume. When all variables were considered, only symptom severity significantly predicted pituitary gland volume (F = 7.54, p = 0.006). Conclusions: Although pituitary volumes were not increased in psychotic disorders, larger size may be a marker associated with more severe symptoms in the progression of psychosis. This finding helps clarify previous inconsistent reports and highlights the need for further research into pituitary gland-related factors in individuals with psychosis. [ABSTRACT FROM AUTHOR]

Snow accumulation on surfaces exposed to adverse weather conditions has been studied over the years due to a variety of problems observed in different industry sectors, such as aeronautics and wind and civil engineering. With the growing interest in autonomous vehicles (AVs), this concern extends to advanced driver-assistance systems (ADAS). Weather stressors, such as snow and icing, negatively influence the sensor functionality of AVs, and their autonomy is not guaranteed by manufacturers during episodes of intense weather precipitation. As a basis for mitigating the negative effects caused by heavy snowfall, models need to be developed to predict snow accumulation over critical surfaces of AVs. The present work proposes a framework for the study of snow accumulation on road vehicles. Existing icing and snow accretion models are reviewed, and adaptations for automotive applications are discussed. Based on the new capabilities developed by the Weather on Wheels (WoW) program at Ontario Tech University, a model architecture is proposed in order to progress toward adequate snow accretion predictions for autonomous vehicle operating conditions, and preliminary results are presented. [ABSTRACT FROM AUTHOR]

Prolonged duration of untreated psychosis (DUP) predicts poor outcomes of first-episode psychosis (FEP) and is often linked to low socioeconomic status (SES). The authors sought to determine whether patients' personal income, used as a proxy for SES, predicts length of DUP and whether personal income influences the effect of an early psychosis detection campaign—called Mindmap—on DUP reduction. Data were drawn from a trial that compared the effectiveness of early detection in reducing DUP across the catchment area of an FEP service (N=147 participants) compared with an FEP service with no early detection (N=75 participants). Hierarchical regression was used to determine whether personal income predicted DUP when analyses controlled for effects of age, race, and exposure to early psychosis detection. A group × personal income interaction term was used to assess whether the DUP difference between the early detection and control groups differed by personal income. Lower personal income was significantly associated with younger age, fewer years of education, Black race, and longer DUP. Personal income predicted DUP beyond the effects of age, race, and early psychosis detection. Although Mindmap significantly reduced DUP across all income levels, this effect was smaller for participants reporting lower personal income. Patients' personal income may be an important indicator of disparity in access to specialty care clinics across a wide range of settings. Early detection efforts should measure and target personal income and other SES indicators to improve access for all individuals who may benefit from FEP services. [ABSTRACT FROM AUTHOR]

Aim: Early interventions are well understood to improve psychosis outcomes, but their successful implementation remains limited. This article introduces a three‐step roadmap for advancing the implementation of evidence‐based practices to operate as a learning health system, which can be applied to early interventions for psychosis and is intended for an audience that is relatively new to systematic approaches to implementation. Methods: The roadmap is grounded in implementation science, which specializes in methods to promote routine use of evidence‐based innovations. The roadmap draws on learning health system principles that call for commitment of leadership, application of evidence, examination of care experiences, and study of health outcomes. Examples are discussed for each roadmap step, emphasizing both data‐ and stakeholder‐related considerations applicable throughout the roadmap. Conclusions: Early psychosis care is a promising topic through which to discuss the critical need to move evidence into practice. Despite remarkable advances in early psychosis interventions, population‐level impact of those interventions is yet to be realized. By providing an introduction to how implementation science principles can be operationalized in a learning health system and sharing examples from early psychosis care, this article prompts inclusion of a wider audience in essential discourse on the role that implementation science can play for moving evidence into practice for other realms of psychiatric care as well. To this end, the proposed roadmap can serve as a conceptual guiding template and framework through which various psychiatric services can methodically pursue timely implementation of evidence‐based interventions for higher quality care and improved outcomes. [ABSTRACT FROM AUTHOR]

Honey quality is conventionally controlled by checking its compliance with the regulatory standards mainly through physical properties. A new index of honey quality known as the Honey Health Impact Metric (HHIM) which considers two main parameters related to health was developed for use as a more market-relatable criteria in the honey industry. The HHIM incorporates the balancing of the positive health-beneficial 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with the negative health-detrimental hydroxymethylfurfural (HMF) concentration present in honey. It is defined as the average score between fractional DPPH and the normalised HMF. The HHIM was tested using 30 randomly selected honey samples from different origins which were then graded by the different categories of quality. As both parameters are also affected by honey storage period, the HHIM was also used to monitor changes in two specific honey samples, the Kelulut Itama and Tualang Dorsata. With quality of honey deteriorating over storage time following a zero-order kinetic model, the indications by HHIM gave a storage recommendations of 10 to 12 months for both these honey samples. This idea of HHIM as an alternative honey quality indicator to gauge health potential of honey will support the genuine and real products in the honey industry. [ABSTRACT FROM AUTHOR]

The reading the mind in the eyes test (RMET) – which assesses the theory of mind component of social cognition – is often used to compare social cognition between patients with schizophrenia and healthy controls. There is, however, no systematic review integrating the results of these studies. We identified 198 studies published before July 2020 that administered RMET to patients with schizophrenia or healthy controls from three English-language and two Chinese-language databases. These studies included 41 separate samples of patients with schizophrenia (total n = 1836) and 197 separate samples of healthy controls (total n = 23 675). The pooled RMET score was 19.76 (95% CI 18.91–20.60) in patients and 25.53 (95% CI 25.19–25.87) in controls (z = 12.41, p < 0.001). After excluding small-sample outlier studies, this difference in RMET performance was greater in studies using non-English v. English versions of RMET (Chi [Q] = 8.54, p < 0.001). Meta-regression analyses found a negative association of age with RMET score and a positive association of years of schooling with RMET score in both patients and controls. A secondary meta-analysis using a spline construction of 180 healthy control samples identified a non-monotonic relationship between age and RMET score – RMET scores increased with age before 31 and decreased with age after 31. These results indicate that patients with schizophrenia have substantial deficits in theory of mind compared with healthy controls, supporting the construct validity of RMET as a measure of social cognition. The different results for English versus non-English versions of RMET and the non-monotonic relationship between age and RMET score highlight the importance of the language of administration of RMET and the possibility that the relationship of aging with theory of mind is different from the relationship of aging with other types of cognitive functioning. [ABSTRACT FROM AUTHOR]

Background: A quantitative measurement of serum proteome biomarkers that would associate with disease progression endpoints can provide risk stratification for persons with multiple sclerosis (PwMS) and supplement the clinical decision‐making process. Materials and Methods: In total, 202 PwMS were enrolled in a longitudinal study with measurements at two time points with an average follow‐up time of 5.4 years. Clinical measures included the Expanded Disability Status Scale, Timed 25‐foot Walk, 9‐Hole Peg, and Symbol Digit Modalities Tests. Subjects underwent magnetic resonance imaging to determine the volumetric measures of the whole brain, gray matter, deep gray matter, and lateral ventricles. Serum samples were analyzed using a custom immunoassay panel on the Olink™ platform, and concentrations of 18 protein biomarkers were measured. Linear mixed‐effects models and adjustment for multiple comparisons were performed. Results: Subjects had a significant 55.6% increase in chemokine ligand 20 (9.7 pg/mL vs. 15.1 pg/mL, p < 0.001) and neurofilament light polypeptide (10.5 pg/mL vs. 11.5 pg/mL, p = 0.003) at the follow‐up time point. Additional changes in CUB domain‐containing protein 1, Contactin 2, Glial fibrillary acidic protein, Myelin oligodendrocyte glycoprotein, and Osteopontin were noted but did not survive multiple comparison correction. Worse clinical performance in the 9‐HPT was associated with neurofilament light polypeptide (p = 0.001). Increases in several biomarker candidates were correlated with greater neurodegenerative changes as measured by different brain volumes. Conclusion: Multiple proteins, selected from a disease activity test that represent diverse biological pathways, are associated with physical, cognitive, and radiographic outcomes. Future studies should determine the utility of multiple protein assays in routine clinical care. [ABSTRACT FROM AUTHOR]

Summary: Post‐harvest maturation of two Malaysian honeys, the Tualang and Kelulut was studied by measuring changes in physicochemical and antioxidant properties, hydroxymethylfurfural (HMF) contents and bacterial profiles at room temperature of 23–26 °C. After maturation at the recommended period of 26 weeks, water activity of both honeys increased between 0.89% and 2.34% while free acidity increased between 2.05% and 2.24%. Results suggested the prominence of fermentation reactions in honey during post‐harvest maturation as fructose concentration reduced by 10.6% and 1.05% for the Tualang and Kelulut honey, respectively, while HMF concentrations were kept at a safe limit of 48.00 and 61.23 mg/kg honey. The total phenolic content of Tualang and Kelulut honey increased significantly by 12.61% and 54.66% respectively. The highlight of this post‐harvest maturation process for Kelulut honey was the improvement found in antioxidant properties of DPPH radical scavenging activity by 10.01%–54.74% and also the probiotic‐like potential in terms significant increase in relative abundance of the Bacillus genera to 2.6% and Lactobacillus to 6.25% at 26 weeks. The prolonged maturation process up to 1 year however revealed continuous accumulation of HMF to values above 80 mg/kg honey, surpassing the limits by the Codex Alimentarius Commission despite improvements of antioxidant properties and bacterial profiles. [ABSTRACT FROM AUTHOR]

Background Individuals with psychotic symptoms experience substantial morbidity and have shortened life expectancies; early treatment may mitigate the worst effects. Understanding care preceding a first psychotic disorder diagnosis is critical to inform early detection and intervention. Study Design In this observational cohort study using comprehensive information from the Massachusetts All-Payer Claims Database, we identified the first psychotic disorder diagnosis in 2016, excluding those with historical psychotic disorder diagnoses in the prior 48 months among those continuous enrollment data. We reviewed visits, medications, and hospitalizations 2012–2016. We used logistic regression to examine characteristics associated with pre-diagnosis antipsychotic use. Study Results There were 2505 individuals aged 15–35 years (146 per 100 000 similarly aged individuals in the database) with a new psychotic disorder diagnosis in 2016. Most (97%) had at least one outpatient visit in the preceding 48 months; 89% had a prior mental health diagnosis unrelated to psychosis (eg, anxiety [60%], depression [60%]). Many received psychotropic medications (77%), including antipsychotic medications (46%), and 68% had a visit for injury or trauma during the preceding 48 months. Characteristics associated with filling an antipsychotic medication before the psychotic disorder diagnosis included male sex and Medicaid insurance at psychosis diagnosis. Conclusions In this insured population of Massachusetts residents with a new psychotic disorder diagnosis, nearly all had some healthcare utilization, visits for injury or trauma were common, and nearly half filled an antipsychotic medication in the preceding 48 months. These patterns of care could represent either pre-disease signals, delays, or both in receiving a formal diagnosis. [ABSTRACT FROM AUTHOR]

β‐Carotene, a precursor of vitamin A, can alleviate the deficiency of this vitamin prevalent worldwide. Earlier research studies have addressed the extraction of β‐carotene at relatively low temperatures (up to 70°C) due to its perceived instability at higher temperatures, as a result of which extraction rates recorded are relatively low. This study models the net rate of β‐carotene extraction by considering both extraction and degradation kinetics. The model developed, which accounts for degradation occurring in solid and extract phases, has been experimentally validated for the extraction of β‐carotene from freeze‐dried carrot powder into sunflower oil over a range of temperatures 90–150°C. This study also gives insights into the application of sunflower oil as a carrier for β‐carotene during cooking and food processing, by monitoring and modeling the thermal degradation and isomerization of β‐carotene at temperatures up to 220°C. The modeling of extraction kinetics shows that it is possible to achieve viable extraction rates by employing temperatures in the range (90–150°C) for relatively short times (<5 min). The degradation kinetics shows that almost 75% of the β‐carotene can survive heating at 180°C for 10 min—indicating the possibility of using β‐carotene enriched edible oils for frying. This study also reports on the formation of three isomers of β‐carotene identified using HPLC: trans‐, 9‐cis, and 13‐cis. The reaction network model developed in this study was able to account for the transient variation of the concentration of all three isomers. Practical Application: β‐Carotene is a precursor of vitamin A and its consumption can potentially alleviate the deficiency of this vitamin prevalent worldwide. This study validates a model for the extraction of β‐carotene in sunflower oil, which takes into account extraction as well as degradation occurring during extraction, so that a rational method is available for the design of efficient extractors for this purpose. This paper also establishes the thermal stability of β‐carotene under frying conditions by quantifying its thermal degradation as well as isomerization. [ABSTRACT FROM AUTHOR]

Background: Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models. Methods: Participants from both the NAPLS2 and NAPLS3 samples were classified as either 'long' or 'short' symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis. Results: The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78). Conclusions: These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Although age is the biggest known risk factor for dementia, there remains uncertainty about other factors over the life course that contribute to a person's risk for cognitive decline later in life. Furthermore, the pathological processes leading to dementia are not fully understood. The main goals of Insight 46—a multi-phase longitudinal observational study—are to collect detailed cognitive, neurological, physical, cardiovascular, and sensory data; to combine those data with genetic and life-course information collected from the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort); and thereby contribute to a better understanding of healthy ageing and dementia. Methods/Design: Phase 1 of Insight 46 (2015–2018) involved the recruitment of 502 members of the NSHD (median age = 70.7 years; 49% female) and has been described in detail by Lane and Parker et al. 2017. The present paper describes phase 2 (2018–2021) and phase 3 (2021–ongoing). Of the 502 phase 1 study members who were invited to a phase 2 research visit, 413 were willing to return for a clinic visit in London and 29 participated in a remote research assessment due to COVID-19 restrictions. Phase 3 aims to recruit 250 study members who previously participated in both phases 1 and 2 of Insight 46 (providing a third data time point) and 500 additional members of the NSHD who have not previously participated in Insight 46. Discussion: The NSHD is the oldest and longest continuously running British birth cohort. Members of the NSHD are now at a critical point in their lives for us to investigate successful ageing and key age-related brain morbidities. Data collected from Insight 46 have the potential to greatly contribute to and impact the field of healthy ageing and dementia by combining unique life course data with longitudinal multiparametric clinical, imaging, and biomarker measurements. Further protocol enhancements are planned, including in-home sleep measurements and the engagement of participants through remote online cognitive testing. Data collected are and will continue to be made available to the scientific community. [ABSTRACT FROM AUTHOR]

In this review, we detail the current state of application of gene therapy to primary mitochondrial disorders (PMDs). Recombinant adeno‐associated virus‐based (rAAV) gene replacement approaches for nuclear gene disorders have been undertaken successfully in more than ten preclinical mouse models of PMDs which has been made possible by the development of novel rAAV technologies that achieve more efficient organ targeting. So far, however, the greatest progress has been made for Leber Hereditary Optic Neuropathy, for which phase 3 clinical trials of lenadogene nolparvovec demonstrated efficacy and good tolerability. Other methods of treating mitochondrial DNA (mtDNA) disorders have also had traction, including refinements to nucleases that degrade mtDNA molecules with pathogenic variants, including transcription activator‐like effector nucleases, zinc‐finger nucleases, and meganucleases (mitoARCUS). rAAV‐based approaches have been used successfully to deliver these nucleases in vivo in mice. Exciting developments in CRISPR‐Cas9 gene editing technology have achieved in vivo gene editing in mouse models of PMDs due to nuclear gene defects and new CRISPR‐free gene editing approaches have shown great potential for therapeutic application in mtDNA disorders. We conclude the review by discussing the challenges of translating gene therapy in patients both from the point of view of achieving adequate organ transduction as well as clinical trial design. [ABSTRACT FROM AUTHOR]

This cohort study examines the association between area-level ethnic density during childhood, perceived discrimination, and psychosis risk outcomes among ethnoracial minoritized individuals at clinical high risk for psychosis. Key Points: Question: Is area-level ethnic density during childhood associated with clinical outcomes among ethnoracial minoritized individuals with clinical high risk for psychosis (CHR-P) syndrome in the US? Findings: In this cohort study of 193 ethnoracial minoritized individuals with CHR-P syndrome, greater area-level minoritized ethnic density during childhood was associated with a higher likelihood of remission at 2-year follow-up compared with staying symptomatic and getting progressively worse. This association between ethnic density and the probability of remission was partly explained by lower lifetime exposure to discrimination in high minoritized ethnic density areas. Meaning: The sociocultural environment during childhood may play a pivotal role in the development of clinical outcomes among minoritized youth at risk for psychosis. Importance: The protective ethnic density effect hypothesis, which suggests that minoritized individuals who grow up in neighborhoods with a high proportion of ethnoracial minoritized groups are protected from the effects of perceived discrimination, has not been examined among individuals at clinical high risk of psychosis (CHR-P). This level of examination may help identify intervention targets for preventing psychosis among high-risk individuals. Objective: To examine the association between area-level ethnic density during childhood, perceived discrimination, and psychosis risk outcomes among ethnoracial minoritized individuals with CHR-P. Design, Setting, and Participants: Data were collected as part of the North American Prodrome Longitudinal Study-2 (NAPLS 2) between November 2008 and March 2013. Participants included ethnoracial minoritized youth with CHR-P. Area-level ethnoracial minoritized density pertained to the percent of ethnoracial minoritized individuals within the participant's county during childhood. Generalized mixed-effects models with random intercepts for participants, NAPLS 2 site, and county estimated the associations between area-level ethnic density and the risk of psychosis risk outcomes. Self-reported experience of discrimination was assessed. Mediation analyses computed the indirect association of perceived discrimination in the prospective correlation between ethnic density and psychosis risk outcomes. Analyses took place between December 2021 and June 2023. Main Outcomes and Measures: Psychosis risk outcomes included remission, symptomatic, progression, and conversion to psychosis and were assessed throughout 24-month follow-up. Results: Of 193 individuals, the mean (SD) age was 17.5 (3.4) years and 113 males (58.5%) were included. Participants self-identified as Asian (29 [15.0%]), Black (57 [29.0%]), Hispanic (any race; 87 [45.0%]), or other (First Nations, Middle Eastern, and interracial individuals; 20 [10.4%]). Greater area-level minoritized density was associated with a lower likelihood of remaining symptomatic (relative risk [RR], 0.54 [95% CI, 0.33-0.89]) and having progressively worsening symptoms (RR, 0.52 [95% CI, 0.32-0.86]) compared with being in remission. More perceived discrimination was associated with a higher risk of staying symptomatic (RR, 1.43 [95% CI, 1.09-1.88]) and progressively worsening (RR, 1.34 [95% CI, 1.02-1.78]) compared with being in remission. Perceived discrimination significantly mediated 21.7% (95% CI, 4.1%-67.0%; P =.02) of the association between area-level minoritized density and the likelihood of being in remission. Conclusions and Relevance: This study found that among ethnoracial minority youth with CHR-P, growing up in communities with a greater proportion of ethnically minoritized individuals was associated with remission of psychosis risk symptoms partly through lower levels of perceived discrimination. Understanding how the social environment impacts early psychosis risk may help develop effective interventions to prevent psychosis, especially for vulnerable minoritized youth. [ABSTRACT FROM AUTHOR]

The spirochete bacterial pathogen Borrelia (Borreliella) burgdorferi (Bbu) affects more than 10% of the world population and causes Lyme disease in about half a million people in the US annually. Therapy for Lyme disease includes antibiotics that target the Bbu ribosome. Here we present the structure of the Bbu 70S ribosome obtained by single particle cryo-electron microscopy at 2.9 Å resolution, revealing a bound hibernation promotion factor protein and two genetically non-annotated ribosomal proteins bS22 and bL38. The ribosomal protein uL30 in Bbu has an N-terminal α-helical extension, partly resembling the mycobacterial bL37 protein, suggesting evolution of bL37 and a shorter uL30 from a longer uL30 protein. Its analogy to proteins uL30m and mL63 in mammalian mitochondrial ribosomes also suggests a plausible evolutionary pathway for expansion of protein content in mammalian mitochondrial ribosomes. Computational binding free energy predictions for antibiotics reflect subtle distinctions in antibiotic-binding sites in the Bbu ribosome. Discovery of these features in the Bbu ribosome may enable better ribosome-targeted antibiotic design for Lyme disease treatment. Ribosomes are prime targets for antibiotics in pathogenic bacteria. Here, cryo-electron microscopy reveals features in the Borrelia burgdorferi ribosome that provide insights into ribosome evolution, dormancy, and antibiotic binding. [ABSTRACT FROM AUTHOR]

The problem of finite‐time state recovery for multivariable second‐order systems with a time‐varying coefficient is considered in this study. The key challenge lies in the time‐varying nature of the regressor coefficient, which possibly results in the lack of a well‐defined relative degree, and renders the synthesis of a finite‐time state observer difficult for such systems. In order to overcome this challenge, a novel multivariable sliding‐mode observer is developed that relies on an information‐rich term based on concurrent learning to ensure observer convergence. In particular, the concurrent learning‐based augmentation term leverages information contained in prior data, which is recorded over a sliding time window in the recent past, so that the resulting observer structure need only satisfy a relaxed observability condition for ensuring finite‐time convergence. A Lyapunov‐based stability analysis is undertaken to demonstrate finite‐time convergence of the observer estimates to a small uniform ultimate bound around the ground truth for a sufficiently large choice of observer gains. The observer is then applied to accomplish the task of structure and motion recovery from machine vision that involves tracking of a single stationary object feature by a moving camera across the image sequence. Numerical results are used to validate accurate observer performance in the presence of model uncertainty and measurement noise for weakly persistently exciting systems. Furthermore, a detailed comparison study with leading alternative designs is also included that demonstrates the superior performance of the proposed scheme. As the current approach precludes any reliance on a restrictive persistency of excitation condition that is difficult to satisfy apriori, an important advantage of the proposed scheme is its suitability to practical applications such as visual servo control. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does accounting for short-term longitudinal change in clinical variables improve outcome prediction in the clinical high risk for psychosis (CHR-P) population? Findings: In this prognostic study, using a joint modeling approach, which combines linear mixed-effects modeling with Cox proportional hazard regression, a high level of prognostic accuracy in predicting both conversion to psychosis and symptom remission was demonstrated compared with baseline models. Meaning: In this study, dynamic prediction models helped to elucidate heterogeneous clinical profiles and trajectories, provided more accurate estimates of eventual clinical outcomes compared with baseline prediction models, and enabled more targeted interventions for this high-risk population. This prognostic study evaluates the improvement in performance of prediction models and elucidates dynamic clinical profiles using joint modeling to predict conversion to psychosis and symptom remission. Importance: Leveraging the dynamic nature of clinical variables in the clinical high risk for psychosis (CHR-P) population has the potential to significantly improve the performance of outcome prediction models. Objective: To improve performance of prediction models and elucidate dynamic clinical profiles using joint modeling to predict conversion to psychosis and symptom remission. Design, Setting, and Participants: Data were collected as part of the third wave of the North American Prodrome Longitudinal Study (NAPLS 3), which is a 9-site prospective longitudinal study. Participants were individuals aged 12 to 30 years who met criteria for a psychosis-risk syndrome. Clinical, neurocognitive, and demographic variables were collected at baseline and at multiple follow-up visits, beginning at 2 months and up to 24 months. An initial feature selection process identified longitudinal clinical variables that showed differential change for each outcome group across 2 months. With these variables, a joint modeling framework was used to estimate the likelihood of eventual outcomes. Models were developed and tested in a 10-fold cross-validation framework. Clinical data were collected between February 2015 and November 2018, and data were analyzed from February 2022 to December 2023. Main Outcomes and Measures: Prediction models were built to predict conversion to psychosis and symptom remission. Participants met criteria for conversion if their positive symptoms reached the fully psychotic range and for symptom remission if they were subprodromal on the Scale of Psychosis-Risk Symptoms for a duration of 6 months or more. Results: Of 488 included NAPLS 3 participants, 232 (47.5%) were female, and the mean (SD) age was 18.2 (3.4) years. Joint models achieved a high level of accuracy in predicting conversion (balanced accuracy [BAC], 0.91) and remission (BAC, 0.99) compared with baseline models (conversion: BAC, 0.65; remission: BAC, 0.60). Clinical variables that showed differential change between outcome groups across a 2-month span, including measures of symptom severity and aspects of functioning, were also identified. Further, intra-individual risks for each outcome were more negatively correlated when using joint models (r = −0.92; P <.001) compared with baseline models (r = −0.50; P <.001). Conclusions and Relevance: In this study, joint models significantly outperformed baseline models in predicting both conversion and remission, demonstrating that monitoring short-term clinical change may help to parse heterogeneous dynamic clinical trajectories in a CHR-P population. These findings could inform additional study of targeted treatment selection and could move the field closer to clinical implementation of prediction models. [ABSTRACT FROM AUTHOR]

Since the late 1960s, NSS have been a focus of study across psychiatric illnesses, including depression, bipolar disorder, and schizophrenia in particular. Utilizing these subtle neurological impairments as biomarkers of illness has numerous benefits; NSS offer a direct connection between clinical presentation and neurological functioning, and assessments are cost-effective. However, incongruent measurement scales, confounding variables, and rating system subjectivity have hindered the advancement and scalability of NSS research and clinical implementation. This article provides a brief overview of the literature on NSS as related to schizophrenia, and proposes utilizing smartphone sensing technology to create standardized NSS assessments with objective scoring. Incorporating digital phenotyping into NSS assessment offers the potential to make measurement more scalable, accessible, and directly comparable across locations, cultures, and demographics. We conducted a narrative search in PubMed and APA PsycInfo using the following keywords: neurological soft signs, schizophrenia spectrum disorders, and psychotic illnesses. No date limitations were used. There is no other direct work on NSS and new smartphone methods like digital phenotyping; though, there is related work in neurology. Harnessing advances in smartphone technology could provide greater insight into and further our understanding of specific aspects of the NSS field. For instance, it could help us distinguish trait vs. state markers and better understand how distinct groups of signs may reflect different aspects of psychiatric illness and neurological impairment. In addition, such technology can help advance research on the capabilities of NSS as an effective diagnostic tool. [ABSTRACT FROM AUTHOR]

Traditional diagnostic formulations of psychotic disorders have low correspondence with underlying disease neurobiology. This has led to a growing interest in using brain-based biomarkers to capture biologically-informed psychosis constructs. Building upon our prior work on the B-SNIP Psychosis Biotypes, we aimed to examine whether structural MRI (an independent biomarker not used in the Biotype development) can effectively classify the Biotypes. Whole brain voxel-wise grey matter density (GMD) maps from T1-weighted images were used to train and test (using repeated randomized train/test splits) binary L2-penalized logistic regression models to discriminate psychosis cases (n = 557) from healthy controls (CON, n = 251). A total of six models were evaluated across two psychosis categorization schemes: (i) three Biotypes (B1, B2, B3) and (ii) three DSM diagnoses (schizophrenia (SZ), schizoaffective (SAD) and bipolar (BD) disorders). Above-chance classification accuracies were observed in all Biotype (B1 = 0.70, B2 = 0.65, and B3 = 0.56) and diagnosis (SZ = 0.64, SAD = 0.64, and BD = 0.59) models. However, the only model that showed evidence of specificity was B1, i.e., the model was able to discriminate B1 vs. CON and did not misclassify other psychosis cases (B2 or B3) as B1 at rates above nominal chance. The GMD-based classifier evidence for B1 showed a negative association with an estimate of premorbid general intellectual ability, regardless of group membership, i.e. psychosis or CON. Our findings indicate that, complimentary to clinical diagnoses, the B-SNIP Psychosis Biotypes may offer a promising approach to capture specific aspects of psychosis neurobiology. [ABSTRACT FROM AUTHOR]

Aim: Expressed emotion of family members is a key target for intervention for bettering psychosocial outcomes for transitional‐age youth experiencing mental health crises. Motivational Interviewing for Loved Ones (MILO) seeks to reduce expressed emotion by teaching parents motivational interviewing skills such as taking a non‐judgmental stance, exploring their loved one's thoughts and feelings, expressing optimism and confidence, and avoiding taking an expert role. This report details the creation of the Motivational Interviewing for Loved Ones‐ Skills Assessment (MILO‐SA), its psychometric properties, and convergent validity with other measures of motivational interviewing adeptness. Methods: Our sample (n = 54) consisted of baseline assessments from parents participating in a pilot study of MILO. Parents were assessed for baseline knowledge of motivational interviewing as well as MILO skills with the MILO‐SA and a traditional assessment clinician application of motivational interviewing skills. Results: We found that the MILO‐SA displayed high interrater reliability (k = 0.81), and convergent validity with motivational interviewing knowledge (r = 0.32) as well as traditional assessments of clinician adeptness applying motivational interviewing skills (r = 0.67). Conclusions: Our findings suggest that the MILO‐SA has strong psychometric properties and is a useful tool for assessing parent acquisition of motivational interviewing skills. Specifically, the MILO‐SA can be used in future studies focused on teaching non‐clinicians motivational interviewing skills. [ABSTRACT FROM AUTHOR]

Aim: Although violent behaviour has been studied in schizophrenia, violence risk has received little attention in individuals at clinical high risk for psychosis (CHR). This manuscript aims to report and discuss the overall results of the Structured Assessment for Violence Risk in Youth (SAVRY) from the NAPLS‐3 project to explore the risk of violence in CHR youth and to determine the relationship between SAVRY violence risk scores, psychosis risk symptoms, and global functioning. We hypothesized that CHR young people are at higher risk of violence as compared to healthy comparison participants due to a similarity between risk factors for psychosis and risk factors for violence, and that this risk is associated with greater severity of symptoms, poor functioning, and risk for conversion to psychosis. Methods: Participants from the North American Prodrome Longitudinal Study consortium phase 3 (NAPLS‐3) included 684 CHR and 96 HC. Assessments included the Structural Assessment of Violence Risk in Youth (SAVRY), clinical and functional measures. Results: The majority of participants across groups were deemed to be at low risk for violence. There were significantly more CHR participants (29.8%) who had moderate or high scores on the SAVRY Summary Risk Rating compared to HC participants (3.1%). Low versus moderate‐high SAVRY scores were associated with better social (p <.005) and role (p <.002) functioning and fewer positive (p <.002), negative (p <.002), disorganized (p <.01) and general symptoms (p <.002). CHR participants with higher SAVRY scores were more likely to be diagnosed with borderline personality disorder, ADHD and substance misuse. Among CHR, overall violence risk was not associated with conversion to psychosis. However, those who converted to psychosis scored lower on the protective factors index, primarily driven by less prosocial involvement and fewer resilient personality traits. Conclusions: This is the first study to assess violence risk in CHR adolescents. Violence risk factors overlap with risk factors for psychosis in general, perhaps accounting for the association. These findings have implications for intervention efforts to reduce violence risk and bolster resiliency in CHR youth. [ABSTRACT FROM AUTHOR]

Background Social determinants of health (SDoHs) are receiving growing attention and are particularly relevant to persons with schizophrenia-spectrum psychotic disorders (SSPDs), considering their heightened risk of comorbidities, cognitive and functional decline, and early mortality. Yet, we did not find any comprehensive review of multiple SDoHs in SSPD. Study Design We conducted a scoping review of meta-analyses and systematic reviews of nine major SDoHs in SSPD. Study Results Childhood abuse, parental psychopathology, parental communication problems, bullying, and urban settings with lower socioeconomic status were major risk factors for the greater incidence of SSPD and/or worse health. Social network size was inversely associated with overall psychopathology and negative symptoms. Experiences of racial/ethnic discrimination correlated with the prevalence of psychotic symptoms and experiences. Compared to native populations, the risk of psychosis was higher in immigrants, refugees, and asylees. Social fragmentation was associated with an increased prevalence of schizophrenia. Homeless populations had a 30-fold higher prevalence of schizophrenia than the general population. Seriously mentally ill people were 2.7 times more likely to report food insecurity than controls. The prevalence of non-affective psychosis in prisoners was 2.0%–6.5%, compared to 0.3% in the general population. Certain potentially positive factors like family and community resilience remain poorly studied. Conclusions SDoHs are associated with higher rates of and worse outcomes in SSPD. Well-designed longitudinal studies are needed to understand SDoHs' contribution to health in persons with SSPD, to develop interventions, and to implement changes in clinical care and public health policies that would reduce adverse health impacts of SDoHs. Positive SDoHs deserve greater attention. [ABSTRACT FROM AUTHOR]

Parboiled rice is recognized for its greater milling yield and reduced rice breakage compared to raw rice during processing. Additionally, parboiled rice has better glycemic control and numerous health benefits. However, the production of parboiled rice requires energy-intensive processing as well as wastewater production. This study reviews parboiled rice, including its processing condition, nutritional properties, potential use, emerging green technologies, and health benefits. It also discussed the outlook and challenges regarding parboiled rice. In addition, a novel overview of emerging green solutions applied to the process to minimize wastewater creation during parboiling and reduce excessive energy usage is provided. The limitation of parboiled rice for a new market preference is the color. An intense process would cause an unwanted physical appearance. A thorough study should balance the multiple advantages of parboiled rice with the reasonable intensity of the process. Due to its multiple advantages, parboiled rice is demonstrated to be a possible breakthrough in the agriculture and food industries. This review aims to provide a thorough understanding that can be used for academic and industrial purposes. [ABSTRACT FROM AUTHOR]

N,N′-diacetylchitobiose, also known as GlcNAc2, is a chitin oligosaccharide and is reported to possess antimicrobial activity against pathogenic bacteria. In this study, 1% (w/v) GlcNAc2 solution was applied on ready-to-eat (RTE) shrimp and evaluated as an antimicrobial coating against Listeria monocytogenes during storage at 4 °C for 16 days. Texture properties, colour, TBARS values, moisture content and bacterial counts were monitored and analysed every four days. The results indicated that the GlcNAc2 coating retarded the changes in texture properties, TBARS values and moisture content of the RTE shrimp during storage. The presence of GlcNAc2 showed no significant changes in RTE shrimp colour in contrast to the control. However, the growth of L. monocytogenes inoculated on the GlcNAc2-coated RTE shrimp was slower than that of the control sample with the highest log reduction of 0.5 log CFU/mL being observed. This study showed that the GlcNAc2 used as an antimicrobial coating was able to inhibit the growth of L. monocytogenes, while maintaining the quality of the RTE shrimp during refrigerated storage. [ABSTRACT FROM AUTHOR]

Introduction: Persistent negative symptoms (PNS) are described as continuing moderate negative symptoms. More severe negative symptoms have been associated with poor premorbid functioning in both chronic schizophrenia and first episode psychosis patients. Furthermore, youth at clinical high risk (CHR) for developing psychosis may also present with negative symptoms and poor premorbid functioning. The aim of this current study was to: (1) define the relationship between PNS and premorbid functioning, life events, trauma and bullying, previous cannabis use, and resource utilization, and (2) to examine what explanatory variables best predicted PNS. Method: CHR participants (N = 709) were recruited from the North American Prodrome Longitudinal Study (NAPLS 2). Participants were divided into two groups: those with PNS (n = 67) versus those without PNS (n = 673). A K-means cluster analysis was conducted to distinguish patterns of premorbid functioning across the different developmental stages. The relationships between premorbid adjustment and other variables were examined using independent samples t-tests or chi square for categorical variables. Results: There was significantly more males in the PNS group. Participants with PNS had significantly lower levels of premorbid adjustment in childhood, early adolescence, and late adolescence, compared to CHR participants without PNS. There were no differences between the groups in terms of trauma, bullying, and resource utilization. The non-PNS group had more cannabis use and more desirable and non-desirable life events. Conclusion: In terms of better understanding relationships between early factors and PNS, a prominent factor associated with PNS was premorbid functioning, in particular poor premorbid functioning in later adolescence. [ABSTRACT FROM AUTHOR]

Human prion diseases are remarkable for long incubation times followed typically by rapid clinical decline. Seed amplification assays and neurodegeneration biofluid biomarkers are remarkably useful in the clinical phase, but their potential to predict clinical onset in healthy people remains unclear. This is relevant not only to the design of preventive strategies in those at-risk of prion diseases, but more broadly, because prion-like mechanisms are thought to underpin many neurodegenerative disorders. Here, we report the accrual of a longitudinal biofluid resource in patients, controls and healthy people at risk of prion diseases, to which ultrasensitive techniques such as real-time quaking-induced conversion (RT-QuIC) and single molecule array (Simoa) digital immunoassays were applied for preclinical biomarker discovery. We studied 648 CSF and plasma samples, including 16 people who had samples taken when healthy but later developed inherited prion disease (IPD) ('converters'; range from 9.9 prior to, and 7.4 years after onset). Symptomatic IPD CSF samples were screened by RT-QuIC assay variations, before testing the entire collection of at-risk samples using the most sensitive assay. Glial fibrillary acidic protein (GFAP), neurofilament light (NfL), tau and UCH-L1 levels were measured in plasma and CSF. Second generation (IQ-CSF) RT-QuIC proved 100% sensitive and specific for sporadic Creutzfeldt-Jakob disease (CJD), iatrogenic and familial CJD phenotypes, and subsequently detected seeding activity in four presymptomatic CSF samples from three E200K carriers; one converted in under 2 months while two remain asymptomatic after at least 3 years' follow-up. A bespoke HuPrP P102L RT-QuIC showed partial sensitivity for P102L disease. No compatible RT-QuIC assay was discovered for classical 6-OPRI, A117V and D178N, and these at-risk samples tested negative with bank vole RT-QuIC. Plasma GFAP and NfL, and CSF NfL levels emerged as proximity markers of neurodegeneration in the typically slow IPDs (e.g. P102L), with significant differences in mean values segregating healthy control from IPD carriers (within 2 years to onset) and symptomatic IPD cohorts; plasma GFAP appears to change before NfL, and before clinical conversion. In conclusion, we show distinct biomarker trajectories in fast and slow IPDs. Specifically, we identify several years of presymptomatic seeding positivity in E200K, a new proximity marker (plasma GFAP) and sequential neurodegenerative marker evolution (plasma GFAP followed by NfL) in slow IPDs. We suggest a new preclinical staging system featuring clinical, seeding and neurodegeneration aspects, for validation with larger prion at-risk cohorts, and with potential application to other neurodegenerative proteopathies. [ABSTRACT FROM AUTHOR]

Ferroptosis, a form of iron-dependent, lipid peroxidation-driven cell death, has been extensively investigated in recent years, and several studies have suggested that the ferroptosis-inducing properties of iron-containing nanomaterials could be harnessed for cancer treatment. Here we evaluated the potential cytotoxicity of iron oxide nanoparticles, with and without cobalt functionalization (Fe2O3 and Fe2O3@Co-PEG), using an established, ferroptosis-sensitive fibrosarcoma cell line (HT1080) and a normal fibroblast cell line (BJ). In addition, we evaluated poly (ethylene glycol) (PEG)-poly(lactic-co-glycolic acid) (PLGA)-coated iron oxide nanoparticles (Fe3O4-PEG-PLGA). Our results showed that all the nanoparticles tested were essentially non-cytotoxic at concentrations up to 100 μg/mL. However, when the cells were exposed to higher concentrations (200–400 μg/mL), cell death with features of ferroptosis was observed, and this was more pronounced for the Co-functionalized nanoparticles. Furthermore, evidence was provided that the cell death triggered by the nanoparticles was autophagy-dependent. Taken together, the exposure to high concentrations of polymer-coated iron oxide nanoparticles triggers ferroptosis in susceptible human cancer cells. [ABSTRACT FROM AUTHOR]

Brain aging, which involves a progressive loss of neuronal functions, has been reported to be premature in probands affected by schizophrenia (SCZ). Evidence shows that SCZ and accelerated aging are linked to changes in epigenetic clocks. Recent cross-sectional magnetic resonance imaging analyses have uncovered reduced brain reserves and connectivity in patients with SCZ compared to typically aging individuals. These data may indicate early abnormalities of neuronal function following cyto-architectural alterations in SCZ. The current mechanistic knowledge on brain aging, epigenetic changes, and their neuropsychiatric disease association remains incomplete. With this review, we explore and summarize evidence that the dynamics of gut-resident bacteria can modulate molecular brain function and contribute to age-related neurodegenerative disorders. It is known that environmental factors such as mode of birth, dietary habits, stress, pollution, and infections can modulate the microbiota system to regulate intrinsic neuronal activity and brain reserves through the vagus nerve and enteric nervous system. Microbiota-derived molecules can trigger continuous activation of the microglial sensome, groups of receptors and proteins that permit microglia to remodel the brain neurochemistry based on complex environmental activities. This remodeling causes aberrant brain plasticity as early as fetal developmental stages, and after the onset of first-episode psychosis. In the central nervous system, microglia, the resident immune surveillance cells, are involved in neurogenesis, phagocytosis of synapses and neurological dysfunction. Here, we review recent emerging experimental and clinical evidence regarding the gut-brain microglia axis involvement in SCZ pathology and etiology, the hypothesis of brain reserve and accelerated aging induced by dietary habits, stress, pollution, infections, and other factors. We also include in our review the possibilities and consequences of gut dysbiosis activities on microglial function and dysfunction, together with the effects of antipsychotics on the gut microbiome: therapeutic and adverse effects, role of fecal microbiota transplant and psychobiotics on microglial sensomes, brain reserves and SCZ-derived accelerated aging. We end the review with suggestions that may be applicable to the clinical setting. For example, we propose that psychobiotics might contribute to antipsychotic-induced therapeutic benefits or adverse effects, as well as reduce the aging process through the gutbrain microglia axis. Overall, we hope that this review will help increase the understanding of SCZ pathogenesis as related to chronobiology and the gut microbiome, as well as reveal new concepts that will serve as novel treatment targets for SCZ. [ABSTRACT FROM AUTHOR]

Structural covariance network (SCN) studies on first-episode antipsychotic-naïve psychosis (FEAP) have examined less granular parcellations on one morphometric feature reporting lower network resilience among other findings. We examined SCNs of volume, cortical thickness, and surface area using the Human Connectome Project atlas-based parcellation (n = 358 regions) from 79 FEAP and 68 controls to comprehensively characterize the networks using a descriptive and perturbational network neuroscience approach. Using graph theoretical methods, we examined network integration, segregation, centrality, community structure, and hub distribution across the small-worldness threshold range and correlated them with psychopathology severity. We used simulated nodal "attacks" (removal of nodes and all their edges) to investigate network resilience, calculated DeltaCon similarity scores, and contrasted the removed nodes to characterize the impact of simulated attacks. Compared to controls, FEAP SCN showed higher betweenness centrality (BC) and lower degree in all three morphometric features and disintegrated with fewer attacks with no change in global efficiency. SCNs showed higher similarity score at the first point of disintegration with ≈ 54% top-ranked BC nodes attacked. FEAP communities consisted of fewer prefrontal, auditory and visual regions. Lower BC, and higher clustering and degree, were associated with greater positive and negative symptom severity. Negative symptoms required twice the changes in these metrics. Globally sparse but locally dense network with more nodes of higher centrality in FEAP could result in higher communication cost compared to controls. FEAP network disintegration with fewer attacks suggests lower resilience without impacting efficiency. Greater network disarray underlying negative symptom severity possibly explains the therapeutic challenge. [ABSTRACT FROM AUTHOR]

Background: Elevated rates of alcohol, tobacco, and cannabis use are observed in both patients with psychotic disorders and individuals at clinical high risk for psychosis (CHR-P), and strong genetic associations exist between substance use disorders and schizophrenia. While individuals with 22q11.2 deletion syndrome (22qDel) are at increased genetic risk for psychosis, initial evidence suggests that they have strikingly low rates of substance use. In the current study, we aimed to directly compare substance use patterns and their neurobehavioral correlates in genetic and clinical high-risk cohorts. Methods: Data on substance use frequency and severity, clinical symptoms, and neurobehavioral measures were collected at baseline and at 12-month follow-up visits in two prospective longitudinal cohorts: participants included 89 22qDel carriers and 65 age and sex-matched typically developing (TD) controls (40.67% male, Mage = 19.26 ± 7.84 years) and 1,288 CHR-P youth and 371 matched TD controls from the North American Prodrome Longitudinal Study-2 and 3 (55.74% male; Mage = 18.71 ± 4.27 years). Data were analyzed both cross-sectionally and longitudinally using linear mixed effects models. Results: Controlling for age, sex, and site, CHR-P individuals had significantly elevated rates of tobacco, alcohol, and cannabis use relative to TD controls, whereas 22qDel had significantly lower rates. Increased substance use in CHR-P individuals was associated with increased psychosis symptom severity, dysphoric mood, social functioning, and IQ, while higher social anhedonia was associated with lower substance use across all domains at baseline. These patterns persisted when we investigated these relationships longitudinally over one-year. CHR-P youth exhibited significantly increased positive psychosis symptoms, dysphoric mood, social functioning, social anhedonia, and IQ compared to 22qDel carriers, and lower rates of autism spectrum disorder (ASD) compared to 22qDel carriers, both at baseline and at 1 year follow-up. Conclusion: Individuals at genetic and CHR-P have strikingly different patterns of substance use. Factors such as increased neurodevelopmental symptoms (lower IQ, higher rates of ASD) and poorer social functioning in 22qDel may help explain this distinction from substance use patterns observed in CHR-P individuals. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The Centiloid scale aims to harmonize amyloid beta (Aβ) positron emission tomography (PET) measures across different analysis methods. As Centiloids were created using PET/computerized tomography (CT) data and are influenced by scanner differences, we investigated the Centiloid transformation with data from Insight 46 acquired with PET/magnetic resonanceimaging (MRI). METHODS: We transformed standardized uptake value ratios (SUVRs) from 432 florbetapir PET/MRI scans processed using whole cerebellum (WC) and white matter (WM) references, with and without partial volume correction. Gaussian‐mixture‐modelling–derived cutpoints for Aβ PET positivity were converted. RESULTS: The Centiloid cutpoint was 14.2 for WC SUVRs. The relationship between WM and WC uptake differed between the calibration and testing datasets, producing implausibly low WM‐based Centiloids. Linear adjustment produced a WM‐based cutpoint of 18.1. DISCUSSION: Transformation of PET/MRI florbetapir data to Centiloids is valid. However, further understanding of the effects of acquisition or biological factors on the transformation using a WM reference is needed. HIGHLIGHTS: Centiloid conversion of amyloid beta positron emission tomography (PET) data aims to standardize results.Centiloid values can be influenced by differences in acquisition.We converted florbetapir PET/magnetic resonance imaging data from a large birth cohort.Whole cerebellum referenced values could be reliably transformed to Centiloids.White matter referenced values may be less generalizable between datasets. [ABSTRACT FROM AUTHOR]

Purpose: Migrant status is a known risk factor for psychosis, but the underlying causes of this vulnerability are poorly understood. Recently, studies have begun to explore whether migrant status predicts transition to psychosis in individuals at clinical high risk (CHR) for psychosis. Results, however, have been inconclusive. The present study assessed the impact of migrant status on clinical symptoms and functional outcome in individuals at CHR for psychosis who took part in the NAPLS-3 study. Methods: Participants' migrant status was classified as native-born, first-generation, or second-generation migrant. Clinical symptoms were assessed using the Structured Interview for Psychosis-Risk Syndromes (SIPS); functional outcome was measured using the Global Functioning Scales:Social and Role (GF:S; GF:R). Assessments were conducted at baseline, 12-months, 18-months, and 24-months follow-up. Generalized linear mixed models for repeated measures were used to examine changes over time and differences between groups. Results: The overall sample included 710 individuals at CHR for psychosis (54.2% males; Age: M = 18.19; SD = 4.04). A mixed model analysis was conducted, and no significant differences between groups in symptoms or functioning were observed at any time point. Over time, significant improvement in symptoms and functioning was observed within each group. Transition rates did not differ across groups. Conclusion: We discuss potential factors that might explain the lack of group differences. Overall, migrants are a heterogeneous population. Discerning the impact of migration from that of neighborhood ethnic density, social disadvantage or socio-economic status of different ethnic groups could help better understand vulnerability and resilience to psychosis. [ABSTRACT FROM AUTHOR]

Background The clinical high-risk (CHR) period offers a temporal window into neurobiological deviations preceding psychosis onset, but little attention has been given to regions outside the cerebrum in large-scale studies of CHR. Recently, the North American Prodrome Longitudinal Study (NAPLS)-2 revealed altered functional connectivity of the cerebello-thalamo-cortical circuitry among individuals at CHR; however, cerebellar morphology remains underinvestigated in this at-risk population, despite growing evidence of its involvement in psychosis. Study Design In this multisite study, we analyzed T1-weighted magnetic resonance imaging scans obtained from N = 469 CHR individuals (61% male, ages = 12–36 years) and N = 212 healthy controls (52% male, ages = 12–34 years) from NAPLS-2, with a focus on cerebellar cortex and white matter volumes separately. Symptoms were rated by the Structured Interview for Psychosis-Risk Syndromes (SIPS). The outcome by two-year follow-up was categorized as in-remission, symptomatic, prodromal-progression, or psychotic. General linear models were used for case-control comparisons and tests for volumetric associations with baseline SIPS ratings and clinical outcomes. Study Results Cerebellar cortex and white matter volumes differed between the CHR and healthy control groups at baseline, with sex moderating the difference in cortical volumes, and both sex and age moderating the difference in white matter volumes. Baseline ratings for major psychosis-risk dimensions as well as a clinical outcome at follow-up had tissue-specific associations with cerebellar volumes. Conclusions These findings point to clinically relevant deviations in cerebellar cortex and white matter structures among CHR individuals and highlight the importance of considering the complex interplay between sex and age when studying the neuromaturational substrates of psychosis risk. [ABSTRACT FROM AUTHOR]

Aim: A large body of evidence demonstrates the importance of the family environment in the developmental trajectory of mental illness in young people. Caregiver communication skills training represents a potential model for influencing the outcomes of adolescents and young adults struggling with emerging mental health and behavioural difficulties. The aim of the current study is to describe the development of a telehealth group training intervention for caregivers of adolescents and young adults, and to report the results of a pilot feasibility‐effectiveness study that took place in 2020–2021. Methods: The "School of Hard Talks" intervention consisted of 8 h of training in communication skills consistent with motivational interviewing techniques. All pilot study participants were assigned to receive the intervention. Outcomes of interest were family conflict, caregiver stress, caregiver self‐efficacy and expressed emotion (EE). Participants were assessed three times: prior to the intervention, after the intervention and 12 weeks later. Results: A total of 62 participants enrolled in the study, of whom 49 completed the intervention. Large, significant improvements were observed over time in all four domains of interest. Qualitative feedback from parents was very positive and added context to quantitative observations. Conclusions: The School of Hard Talks was a feasible and effective intervention targeting both caregiver wellbeing as well as important mechanisms of risk for youth psychopathology, namely family conflict and EE. Further research involving a larger sample and a control condition are needed to confirm these findings. [ABSTRACT FROM AUTHOR]