Enhanced chondrogenic potential in GelMA-based 3D cartilage model via Wnt3a surface immobilization.

Cartilage tissue engineering aims to develop functional substitutes for treating cartilage defects and osteoarthritis. Traditional two-dimensional (2D) cell culture systems lack the complexity of native cartilage, leading to the development of 3D regenerative cartilage models. In this study, we developed a 3D model using Gelatin Methacryloyl (GelMA)-based hydrogels seeded with Y201 cells, a bone marrow mesenchymal stem cell line. The model investigated chondrogenic differentiation potential in response to Wnt3a stimulation within the GelMA scaffold and validated using known chondrogenic agonists. Y201 cells demonstrated suitability for the model, with increased proteoglycan content and upregulated chondrogenic marker expression under chondrogenic conditions. Wnt3a enhanced cell proliferation, indicating activation of the Wnt/ß-catenin pathway, which plays a role in cartilage development. GelMA hydrogels provided an optimal scaffold, supporting cell viability and proliferation. The 3D model exhibited consistent responses to chondrogenic agonists, with TGF-ß3 enhancing cartilage-specific extracellular matrix (ECM) production and chondrogenic differentiation. The combination of Wnt3a and TGF-ß3 showed synergistic effects, promoting chondrogenic differentiation and ECM production. This study presents a 3D regenerative cartilage model with potential for investigating cartilage biology, disease mechanisms, and drug screening. The model provides insights into complex cartilage regeneration mechanisms and offers a platform for developing therapeutic approaches for cartilage repair and osteoarthritis treatment.

Factors influencing uptake of protective behaviours by healthcare workers in England during the COVID-19 pandemic: A theory-based mixed-methods study.

BACKGROUND: Hospital infection control policies protect patients and healthcare workers (HCWs) and limit the spread of pathogens, but adherence to COVID-19 guidance varies. We examined hospital HCWs' enactment of social distancing and use of personal protective equipment (PPE) during the COVID-19 pandemic, factors influencing these behaviours, and acceptability and feasibility of strategies to increase social distancing. METHODS: An online, cross-sectional survey (n = 86) and semi-structured interviews (n = 22) with HCWs in two English hospitals during the first wave of the COVID-19 pandemic (May-December 2020). The Capability, Opportunity, Motivation (COM-B) model of behaviour change underpinned survey and topic guide questions. Spearman Rho correlations examined associations between COM-B domains and behaviours. Interviews were analysed using inductive and deductive thematic analysis. Potential strategies to improve social distancing were selected using the Behaviour Change Wheel and discussed in a stakeholder workshop (n = 8 participants). RESULTS: Social distancing enactment was low, with 85% of participants reporting very frequently or always being in close contact with others in communal areas. PPE use was high (88% very frequently or always using PPE in typical working day). Social distancing was associated with Physical Opportunity (e.g., size of physical space), Psychological Capability (e.g., clarity of guidance), and Social Opportunity (e.g., support from managers). Use of PPE was associated with Psychological Capability (e.g., training), Physical Opportunity (e.g., availability), Social Opportunity (e.g., impact on interactions with patients), and Reflective Motivation (e.g., beliefs that PPE is effective). Local champions and team competition were viewed as feasible strategies to improve social distancing. CONCLUSIONS: It is valuable to understand and compare the drivers of individual protective behaviours; when faced with the same level of perceived threat, PPE use was high whereas social distancing was rarely enacted. Identified influences represent targets for intervention strategies in response to future infectious disease outbreaks.

On the proportion of patients who experience a prodrome prior to psychosis onset: A systematic review and meta-analysis.

BACKGROUND: Preventing or delaying the onset of psychosis requires identification of those at risk for developing psychosis. For predictive purposes, the prodrome - a constellation of symptoms which may occur before the onset of psychosis - has been increasingly recognized as having utility. However, it is unclear what proportion of patients experience a prodrome or how this varies based on the multiple definitions used. METHODS: We conducted a systematic review and meta-analysis of studies of patients with psychosis with the objective of determining the proportion of patients who experienced a prodrome prior to psychosis onset. Inclusion criteria included a consistent prodrome definition and reporting the proportion of patients who experienced a prodrome. We excluded studies of only patients with a prodrome or solely substance-induced psychosis, qualitative studies without prevalence data, conference abstracts, and case reports/case series. We searched Ovid MEDLINE, Embase (Ovid), APA PsycInfo (Ovid), Web of Science Core Collection (Clarivate), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, APA PsycBooks (Ovid), ProQuest Dissertation & Thesis, on March 3, 2021. Studies were assessed for quality using the Critical Appraisal Checklist for Prevalence Studies. Narrative synthesis and proportion meta-analysis were used to estimate prodrome prevalence. I2 and predictive interval were used to assess heterogeneity. Subgroup analyses were used to probe sources of heterogeneity. (PROSPERO ID: CRD42021239797). RESULTS: Seventy-one articles were included, representing 13,774 patients. Studies varied significantly in terms of methodology and prodrome definition used. The random effects proportion meta-analysis estimate for prodrome prevalence was 78.3% (95% CI = 72.8-83.2); heterogeneity was high (I2 97.98% [95% CI = 97.71-98.22]); and the prediction interval was wide (95% PI = 0.411-0.936). There were no meaningful differences in prevalence between grouped prodrome definitions, and subgroup analyses failed to reveal a consistent source of heterogeneity. CONCLUSIONS: This is the first meta-analysis on the prevalence of a prodrome prior to the onset of first episode psychosis. The majority of patients (78.3%) were found to have experienced a prodrome prior to psychosis onset. However, findings are highly heterogenous across study and no definitive source of heterogeneity was found despite extensive subgroup analyses. As most studies were retrospective in nature, recall bias likely affects these results. While the large majority of patients with psychosis experience a prodrome in some form, it is unclear if the remainder of patients experience no prodrome, or if ascertainment methods employed in the studies were not sensitive to their experiences. Given widespread investment in indicated prevention of psychosis through prospective identification and intervention during the prodrome, a resolution of this question as well as a consensus definition of the prodrome is much needed in order to effectively direct and organize services, and may be accomplished through novel, densely sampled and phenotyped prospective cohort studies that aim for representative sampling across multiple settings.

A framework for evaluating the diversity of clinical trials.

OBJECTIVES: The topic of diversity in clinical trials is rising to the forefront of many conversations in evidence-based medicine, and efforts are being made to improve the diversity of clinical trials. However, there is little uniformity in the methods used to evaluate these efforts. In this article, we describe our Clinical trial Diversity Rating (CDR) framework and the development process, including the broader considerations for evaluating the demographic diversity of clinical trials and their implications, and demonstrate its use through an illustrative example. STUDY DESIGN AND SETTING: The development of the framework was a four-step process, including a scoping review, a cross-sectional study, creation of the tool, and integration of feedback from an advisory group. RESULTS: Our scoping review identified 110 publications that examined clinical trial diversity. Race/ethnicity, sex, and age were the most common characteristics evaluated. About 85% clearly defined the benchmark used for evaluation, but less than half (48%) used disease prevalence as the benchmark. Only 64% of studies defined what would be considered adequate representation. The cross-sectional study, which applied some of the approaches identified in the literature, helped to identify the complexities of evaluating multinational trials and certain demographic characteristics. Key decisions for the CDR framework, such as the demographic characteristics to be evaluated, the benchmark and thresholds for evaluation, and how these factors contribute to the overall rating of clinical trial diversity, were informed by the two earlier phases and feedback from an advisory group. CONCLUSION: The CDR framework provides an objective and transparent approach to evaluating clinical trial diversity. Groups such as Health Technology Assessment bodies, clinical trial regulators, policymakers, journal editors, and individual researchers can use this tool to examine, monitor, and improve diversity in clinical trials.

Experiencing hallucinations in daily life: The role of metacognition.

BACKGROUND: Hallucinations have been linked to failures in metacognitive reflection suggesting an association between hallucinations and overestimation of performance, although the cross-sectional findings are inconsistent. This inconsistency may relate to the fluctuating hallucinatory experiences that are not captured in cross-sectional studies. Ecological Momentary Assessment (EMA) captures in-the-moment experiences over time so can identify causal relationships between variables such as the associations between metacognition and hallucinatory experience in daily life and overcome problems in cross-sectional designs. METHODS: Participants (N = 41) experiencing daily hallucinations completed baseline questionnaires and smartphone surveys 7 times per day for 14 days. They were prompted to identify a task they would complete in the next 4 h and to make metacognitive predictions around the likelihood of completing the task, the difficulty of the task, and how well they would complete it (standard of completion). RESULTS: 76 % finished the 14-days of assessment with an average of 42.2 % survey completion. Less accurate metacognition was associated with more hallucinations, but less accurate likelihood and standard of completion was associated with fewer hallucinations. Using a cross-lagged analysis, metacognitive predictions around the likelihood of completion (p < .001) and standard of completion (p = .01) predicted hallucination intensity at the following timepoint, and metacognitive predictions regarding likelihood of completion (p = .02) predicted hallucination control at the following timepoint. DISCUSSION: Interventions that aim to improve metacognitive ability in-the-moment may serve to reduce the intensity and increase the control of hallucinations.

Evaluation of Diversity of Clinical Trials Informing Health Technology Assessments in the United States: A 5-Year Analysis of Institute for Clinical and Economic Review Assessments.

OBJECTIVES: This study aimed to evaluate the diversity of clinical trials informing assessments conducted by the Institute for Clinical and Economic Review. METHODS: This was a cross-sectional study of pivotal trials included in completed Institute for Clinical and Economic Review assessments over 5 years (2017-2021). Representation of racial/ethnic minority groups, females, and older adults was compared with the disease-specific and US population, using a relative representation cutoff of 0.8 for adequate representation. RESULTS: A total of 208 trials, evaluating 112 interventions for 31 unique conditions, were examined. Race/ethnicity data were inconsistently reported. The median participant-to-disease representative ratio (PDRR) for Blacks/African Americans (0.43 [interquartile range (IQR) 0.24-0.75]), American Indians/Alaska Natives (0.37 [IQR 0.09-0.77]), and Hispanics/Latinos (0.79 [IQR 0.30-1.22]) were below the adequate representation cutoff. In contrast, Whites (1.06 [IQR 0.92-1.2]), Asians (1.71 [IQR 0.50-3.75]), and Native Hawaiian/Other Pacific Islanders (1.61 [IQR 0.77-2.81]) were adequately represented. Findings were similar when compared with the US Census, except for Native Hawaiian/Pacific Islanders, which was substantially worse. Relative to all trials, a higher proportion of US-based trials adequately represented Blacks/African Americans (61% vs 23%, P < .0001) and Hispanics/Latinos (68% vs 50%; P = .047), but a lower proportion adequately represented Asians (15% vs 67%, P < .0001). Females were adequately represented in 74% of trials (PDRR: 1.02 [IQR 0.79-1.14]). Nevertheless, older adults were adequately represented in only 20% of trials (PDRR: 0.30 [IQR 0.13-0.64]). CONCLUSIONS: The representation of racial/ethnic minorities and older adults was inadequate. Efforts are needed to enhance the diversity of clinical trials. Standardized and transparent evaluation of trial diversity should be part of the health technology assessment process.

Metacognition and psychosis-spectrum experiences: A study of objective and subjective measures.

BACKGROUND: Metacognition refers to appraising one's thoughts and behaviours. Deficits in metacognition are associated with psychosis-spectrum experiences, such as hallucinations and delusions, in both clinical and non-clinical populations. Assessments of metacognitive function and abilities in clinical populations often vary in administration duration, and subjectivity of scores. This study investigates associations between different measures of metacognition and their prediction of psychosis spectrum experiences using objective and self-report measures in a cross-sectional study of psychosis-spectrum disorder (PSD) participants and controls. METHOD: Twenty-three individuals with PSD and forty-four controls were recruited online and completed in-the-moment objective ratings of metacognitive accuracy (meta-Dots Task), and retrospective self-report of metacognitive self-reflection (Beck Cognitive Insight Scale) and abilities (Metacognition Self-Assessment Scale). RESULTS: There were group differences in self-reported metacognition, with PSD participants having lower scores of metacognitive ability, but no differences in self-reflectiveness or objective metacognitive accuracy. In the PSD group, only self-reported metacognitive ability was associated with and predicted distress about, and conviction in, delusional thoughts. CONCLUSIONS: The findings demonstrate group differences in some self-reported, but not objective, measures of metacognition, and highlight that prediction of PSD experiences depends on the metacognitive construct being measured, and the type of measurement used.

Clinical insight in first episode psychosis: the role of metacognition.

BACKGROUND: Poor clinical insight has been commonly reported in those with First Episode Psychosis (FEP) and thought to be influenced by a range of factors, including neurocognition and symptoms. Clinical insight may be compromised as a result of alterations in higher-level reflective processes, such as metacognitive ability and cognitive insight. AIMS: To explore whether metacognitive ability and cognitive insight are associated with clinical insight while controlling for IQ, depression, and symptoms in FEP. METHODS: 60 individuals with FEP completed measures for clinical insight, metacognitive ability, cognitive insight, positive and negative symptoms, depression, and IQ. RESULTS: Higher levels of metacognitive ability were associated with better clinical insight, even when controlling for IQ, depression, positive and negative symptoms, and medication. Integration subscale of metacognitive ability was most strongly associated with clinical insight. Cognitive insight was associated with clinical insight when controlling for covariates. However, when including metacognitive ability and cognitive insight in the predictive model, only metacognitive ability was significantly related to clinical insight. DISCUSSION: Metacognitive ability, specifically the ability to describe one's evolving mental state to provide a coherent narrative, was significantly related to clinical insight, independent of covariates, and may be a potentially important target for intervention in FEP.

Relationship between patterns of cannabis use and functional and symptomatic trajectories in first-episode psychosis.

Cannabis use is common in first-episode psychosis (FEP) but evidence is mixed about the extent to which cannabis use predicts symptoms and functional outcomes among those who seek treatment. This study sought to characterize cannabis use patterns and examine the relationship with clinical outcomes, including interactions with early intervention services (EIS). Data were drawn from the Recovery After an Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study including FEP individuals receiving treatment at sites randomized to provide either EIS (NAVIGATE) or community care (CC). Cannabis use was assessed monthly and symptom and functioning data were collected at baseline, 6, 12, 18, and 24 months. Among the 404 participants enrolled, 334 were classified into four cannabis use groups (consistent, sporadic, stopped, and never users) based on their use during the first year. Consistent and sporadic cannabis users were younger, whereas those who had stopped using were older. Sporadic users had the highest depression and the lowest functioning at baseline and improved less during treatment in negative emotions and intrapsychic foundations (e.g., motivation and sense of purpose) than non-users. However, sporadic users who received NAVIGATE improved more in overall symptoms and functioning than those who received CC. Consistent users did not tend to differ in their trajectories from non-users. Individuals with FEP who use cannabis sporadically showed less clinical improvement than non-users. However, EIS treatment reduced the negative effects of sporadic cannabis use on clinical outcomes. Those who use cannabis sporadically may have unique needs that require attention in EIS.

'Feeling' or 'sensing' the future? Testing for anomalous cognitions in clinical versus healthy populations.

In the study and treatment of psychosis, emotional intelligence (EI) and thinking styles are important patient characteristics for successful outcomes in clinical intervention. Anticipation of unpredictable stimuli (AUS) may be understood as an anomalous perception and anomalous cognition in which an individual supposedly senses and recognizes future stimuli in an unexpected way, also referred to as "hunches or premonitions." This examined the roles of EI and thinking styles in AUSs in convenience samples of healthy participants (n = 237) versus patients diagnosed with psychosis (n = 118). We adjusted several quadratic and exponential regression models according to the obtained functions. Group means were also compared to examine differences in EI scores for participants with psychosis compared to healthy participants. In the healthy group, EI predicted AUSs with a weight between 42% and 58%. Thinking styles were not correlated with AUSs. However, EI was not correlated with AUSs in the clinical group. Patients with psychosis tended to score higher on AUSs and lower on EI and thinking styles compared to participants in the healthy group. We discuss EI as a variable that can contextualize some anomalous perceptions which are otherwise difficult to classify or measure within the classic psychosis continuum model.

Feasibility, Acceptability, and Potential Utility of Peer-supported Ecological Momentary Assessment Among People with Serious Mental Illness: a Pilot Study.

To examine the feasibility, acceptability, and initial validity of using smartphone-based peer-supported ecological momentary assessment (EMA) as a tool to assess loneliness and functioning among adults with a serious mental illness diagnosis. Twenty-one adults with a diagnosis of a serious mental illness (i.e., schizophrenia, schizoaffective disorder, bipolar disorder, or treatment-refractory major depressive disorder) and at least one medical comorbidity (i.e., cardiovascular disease, obesity, diabetes, chronic obstructive pulmonary disease, hypertension, and/or high cholesterol) aged 18 years and older completed EMA surveys via smartphones once per day for 12-weeks. Nine peer support specialists prompted patients with SMI to complete the EMA surveys. Data were collected at baseline and 12-weeks. EMA acceptability (15.9%) was reported, and participants rated their experience with EMA methods positively. EMA responses were correlated with higher social support at 3 months. Higher levels of EMA-measured loneliness were significantly correlated with levels of social support, less hope, and less empowerment at 3 months. Lastly, those who contacted their peer specialist reported higher levels of loneliness and lower levels of functioning on that day suggesting that participants were able to use their peers for social support. Peer-supported EMA via smartphones is a feasible and acceptable data collection method among adults with SMI and appears to be a promising mobile tool to assess loneliness and functioning. These preliminary findings indicate EMA-measured loneliness and functioning are significantly predicted by baseline variables and such variables may impact engagement in EMA. EMA may contribute to future research examining the clinical utility of peer support specialists to alleviate feelings of loneliness and improve functioning.

Relationships among subclinical psychotic symptoms in young adults over time.

BACKGROUND: Subclinical psychotic symptoms are common in the general population and are often benign. However, those that become distressing or persistent may increase risk for the development of a psychotic disorder. Cognitive models have proposed that certain appraisals of hallucinatory experiences can lead to delusional beliefs, particularly if an individual is experiencing negative mood. However, the dynamic relationships among these symptoms are poorly understood. This study examined the longitudinal relationships among subclincal hallucinations, delusional ideation, and depression in a sample of young adults. METHODS: 677 college students completed baseline questionnaires to assess: delusional ideation (Peters Delusions Inventory), hallucinations (Launay-Slade Hallucinations Scale-Extended), and depression (Beck Depression Inventory). These measures were repeated 7, 13, 19, and 25 months later. RESULTS: Higher baseline severity of hallucinations was strongly predictive of severity of delusions across all future follow-up timepoints, specifically when baseline depression was high. However, the severity of hallucinations did not change over time, nor were they predicted by baseline delusional ideation. CONCLUSIONS: These findings support the proposal that hallucinations frequently precede more severe delusional ideation, rather than the reverse sequence, particularly when depressive symptoms are present. Such longitudinal relationships provide clues to the underlying mechanisms of psychosis, highlighting one pathway for intervention.

The impact of the COVID-19 pandemic on peer specialists.

OBJECTIVE: Individuals with mental health challenges are at particularly high risk of experiencing negative outcomes (e.g., worsening of mental health, increased risk of mortality) due to the coronavirus disease (COVID-19) pandemic. Peer specialists may have the benefit of several protective factors, including higher levels of social support and better illness self-management skills that buffer against negative effects of the pandemic. In this study, we compared the differences in the impact of COVID-19 on those trained as peer specialists (e.g., certified peer specialists, recovery coaches) to those not trained in this role. METHOD: Participants with self-reported mental health and/or substance use challenges completed an online survey to collect information on their experiences during COVID-19 (Epidemic-Pandemic Impacts Inventory [EPII]), loneliness (3-item Loneliness Scale), and access to and satisfaction with mental health support. Respondents self-identified as peer specialists or not. RESULTS: One hundred seventy-three U.S. resident participants from 23 states were included in the final analysis: 109 were peer specialists and 64 were nonpeer specialists. Those who were trained as peer specialists reported fewer negative outcomes during the pandemic, including less disruption in employment, less loneliness, and less worsening of mental health, while reporting more positive attitudes in the face of difficulties. Peer specialists were also likely to report more access to and satisfaction with mental health services. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Possibly as a function of their role, peer specialists reported better mental health outcomes during COVID-19, providing key, empirical evidence to support the benefits of helping others. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Magnetic Nanoparticle-Mediated Orientation of Collagen Hydrogels for Engineering of Tendon-Mimetic Constructs.

Despite the high incidence of tendon injuries worldwide, an optimal treatment strategy has yet to be defined. A key challenge for tendon repair is the alignment of the repaired matrix into orientations which provide maximal mechanical strength. Using oriented implants for tissue growth combined with either exogenous or endogenous stem cells may provide a solution. Previous research has shown how oriented fiber-like structures within 3D scaffolds can provide a framework for organized extracellular matrix deposition. In this article, we present our data on the remote magnetic alignment of collagen hydrogels which facilitates long-term collagen orientation. Magnetic nanoparticles (MNPs) at varying concentrations can be contained within collagen hydrogels. Our data show how, in response to the magnetic field lines, MNPs align and form string-like structures orientating at 90 degrees from the applied magnetic field from our device. This can be visualized by light and fluorescence microscopy, and it persists for 21 days post-application of the magnetic field. Confocal microscopy demonstrates the anisotropic macroscale structure of MNP-laden collagen gels subjected to a magnetic field, compared to gels without MNP dosing. Matrix fibrillation was compared between non- and biofunctionalized MNP hydrogels, and different gels dosed with varying MNP concentrations. Human adipose stem cells (hASCs) seeded within the magnetically aligned gels were observed to align in parallel to MNP and collagen orientation 7 days post-application of the magnetic field. hASCs seeded in isotropic gels were randomly organized. Tenocyte-likeness of the cells 7 days post-seeding in collagen I scaffolds was confirmed by the positive expression of tenomodulin and scleraxis proteins. To summarize, we have developed a convenient, non-invasive protocol to control the collagen I hydrogel architecture. Through the presence or absence of MNP dosing and a magnetic field, collagen can be remotely aligned or randomly organized, respectively, in situ. Tendon-like cells were observed to organize in parallel to unidirectionally aligned collagen fibers and polydirectionally in non-aligned collagen constructs. In this way, we were able to engineer the constructs emulating a physiologically and pathologically relevant tendon niche. This can be considered as an innovative approach particularly useful in tissue engineering or organ-on-a-chip applications for remotely controlling collagen matrix organization to recapitulate the native tendon.

Self-defining memories among persons with mental health, substance use, cognitive, and physical health conditions: a systematic review.

BACKGROUND: Self-defining memories (SDMs) are important for identifying one's purpose in life, achieving goals, and overcoming challenging situations. Individual studies have demonstrated differences in the characteristics of SDMs between clinical and non-clinical populations. This systematic literature review aimed to summarise and compare SDM characteristics among those with mental, substance use, cognitive, neurodevelopmental, and physical health challenges. METHODS: Peer-reviewed English-language studies were included if they evaluated SDMs in these groups. RESULTS: Thirty-five studies (N = 3123) were included. SDM content across all clinical populations tended to focus on illness themes. SDMs were generally less specific and integrated in those with mental health or substance use disorders as compared to non-clinical populations. SDM specificity and integration findings were more mixed in those with cognitive, neurodevelopmental, and physical health challenges. CONCLUSIONS: Specific differences emerged between groups of individuals which may be related to illness characteristics, recovery trajectory, and individual differences in the ability to understand and process difficult life events.