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Background: Changes in cognitive impairments and their relationship with psychopathological symptoms during treatment in schizophrenia remain debatable. Especially, there is few studies specifically focusing on female patients. Further exploration of the characteristics of female schizophrenia patients can offer valuable sex-related considerations for clinicians in diagnosis and interventions. Methods: Our study involved 94 female patients with drug-naïve or drug-withdrawal schizophrenia who received antipsychotic drug for 8 weeks, along with 71 age-matched female healthy controls. The MATRICS Consensus Cognition Battery was used to assess cognition in the healthy controls at baseline and in the schizophrenia patients before and after 8 weeks of treatment. The Positive and Negative Syndrome Scale (PANSS) was employed to evaluate the psychopathological symptoms of the patients before and after 8 weeks of treatment. Results: After antipsychotic treatment, 90.43% of the patients showed a reduction rate of more than 25% in their PANSS scores. Psychopathological symptoms and overall cognitive functioning improved significantly (p < 0.05), with the exception of verbal learning and social cognition (p > 0.05). Most cognitive dimensions were negatively correlated with positive symptoms, negative symptoms, and general psychopathological symptoms (p < 0.05, Bonferroni correction), while verbal learning and social cognition were only correlated with negative symptoms (p < 0.05, Bonferroni correction). Multivariate linear regression analysis revealed that improvements in positive symptoms and negative symptoms can predict the improvement in visual learning (p < 0.05) and overall cognitive composite scores (p < 0.05), improved positive symptoms can predict the improvement in the speed of processing (p < 0.05), reasoning and problem-solving(p < 0.05), and improvement in negative symptoms can predict the improvement in attention/vigilance (p < 0.05). Conclusions: Verbal learning and social cognition may serve as core independent cognitive impairments in female schizophrenia. Improvements in the overall cognitive function, along with most cognitive dimensions, appeared to be secondary to the improvement in positive and negative symptoms during the acute stages of antipsychotic treatment. Trial registration: ClinicalTrials.gov Identifier: NCT03451734. [ABSTRACT FROM AUTHOR]

Psychosis encompasses a spectrum of mental disorders characterized by abnormalities in five key domains: delusions, hallucinations, disorganized thinking (speech), grossly disorganized or abnormal motor behavior (including catatonia), and negative symptoms. Contemporary research on developing new antipsychotic drugs addresses for improving efficacy, reducing side effects, and better management of symptoms. The physicochemical properties of drugs play a pivotal role in their efficacy, influencing factors such as absorption, distribution, metabolism, and excretion within the body. Our work describes the potential role of topological indices in quantitative structure–property relationship (QSPR) modeling of antipsychotic drugs as well as in multiple-choice decision-making. QSPR modeling is employed to assess the physiochemical properties using degree-based topological indices. Seventeen antipsychotic drugs are analyzed for various physicochemical characteristics, and a QSPR model is built using 13 topological indices. The analysis yields insights into the complexity, molar refractivity, flash point, molar volume, and other relevant factors of the drugs. The drugs are ranked on the basis of correlation of the topological indices and the properties. Furthermore, rankings obtained through both Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) and simple additive weighting (SAW) methods depict a remarkable level of agreement, enhancing the credibility of the assessment methodologies. These findings highlight the efficacy of topological indices in accurately representing the theoretical features of antipsychotic drugs and their significant correlation with physical attributes, thereby informing decision-making in drug development and clinical practice. [ABSTRACT FROM AUTHOR]

This article is an attempt to invigorate decolonisation discourse in Film and Media Studies, particularly with regard to Documentary Studies. It does so by centring a screen installation work, by a filmmaker whose formal preoccupations have returned repeatedly to the fictions and limitations of archival documents. Peripeteia (John Akomfrah, dir. 2012. Peripeteia. UK: Smoking Dogs Films.) imagines an encounter between two people, 'lost to the winds of history'. In its use of objects including sketches, photographs and written quotations, the film constructs an elliptical narrative with archival fragments. Locating its actors in a placeless landscape, wrenched from their point of origin and dependent solely on superficial images for context, Peripeteia reanimates its barely known subjects to perform a critique of the coloniality of the reenactment form, which has been used deceptively throughout the history of films defined as 'non-fiction'. Coining archival reenactment as a mode which (1) utilises a self-critical rehearsal of historical gestures to interrogate documentary film's archival function, and (2) employs archival fragments to both build and trouble the depth of its own representation, this article centres Peripeteia as a template for the decolonial critique of an over-familiar convention in the documentary mode. [ABSTRACT FROM AUTHOR]

Objective: This study compares the clinical features of Treatment-Resistant Schizophrenia (TRS) and Non-Treatment-Resistant Schizophrenia (NTRS) using network analysis. Methods: We recruited 511 patients, dividing them into TRS (N = 269) and NTRS (N = 242) groups. Eight scales were used: Positive and Negative Syndrome Scale (PANSS), Positive Symptom Assessment Scale (SAPS), Scale for Assessment of Negative Symptoms (SANS), Simpson-Angus Scale (SAS), Abnormal Involuntary Movements Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Calgary Schizophrenia Depression Scale (CDSS), and Global Assessment of Functioning Scale (GAF). Demographic and clinical data were analyzed using T-tests and Chi-square tests. Network analysis was then applied to compare clinical features. Results: Significant differences were found in the overall architectures (S = 1.396, p < 0.002) and edge weights (M = 0.289, p < 0.009) of TRS and NTRS networks. Nine edges (p < 0.05) and five nodes (p < 0.01) differed, indicating a correlation between clinical symptoms of the two groups. TRS core symptoms were linked to social functions through both positive (SAPS) and negative symptoms (SANS), while NTRS core symptoms were related to general psychopathological symptoms (PANSS-G). Conclusion: For TRS, it is essential to address both negative and positive symptoms, focusing on the impact of negative symptoms on functioning. Additionally, managing medication side effects is crucial to avoid worsening negative symptoms. [ABSTRACT FROM AUTHOR]

Atypical antipsychotics are widely used for the treatment of mental and behavioral disorders such as bipolar disorder, obsessive-compulsive disorder, and schizophrenia. However, these drugs can occasionally induce neutropenia or agranulocytosis, characterized by a significant reduction in circulating neutrophils, the primary white blood cells responsible for immune responses. This drug-induced neutropenia poses a considerable risk of life-threatening infections. However, the precise mechanism by which atypical antipsychotics induce neutropenia remains unclear. This study investigates the effects of four atypical antipsychotics, namely – aripiprazole, clozapine, olanzapine, and quetiapine – on the human neutrophil model cell line HL-60. These drugs, which modulate dopamine receptor signaling alongside other mechanisms, were analyzed for their effects. Among these, aripiprazole – but not the others – uniquely induced apoptosis in a dose-dependent manner, accompanied by an increased expression of pro-apoptotic genes – BAK, BCL10, and caspase-3. Moreover, our study elucidates that while differentiated HL-60 cells express D1-like and D2-like dopamine receptors, aripiprazole's cytotoxic effects appear to operate through dopamine-independent pathways and significantly reduce phosphorylated Src family kinase levels. Our results align with previous studies suggesting that aripiprazole exhibits cytotoxic properties in neutrophils. Nevertheless, further investigations are warranted to investigate the mechanisms underlying aripiprazole-induced apoptosis in neutrophils. [ABSTRACT FROM AUTHOR]

Personalized treatment optimization considers individual clinical, genetic, and environmental factors influencing drug efficacy and tolerability. As evidence accumulates, these approaches may become increasingly integrated into standard psychiatric care, potentially transforming the treatment landscape for mental health disorders. While personalized treatment optimization shows promise in enhancing therapeutic outcomes and minimizing adverse effects, further research is needed to establish its clinical utility and cost-effectiveness across various psychiatric disorders. This review examines the potential utility of personalized treatment optimization in psychiatry, addressing the challenge of suboptimal effectiveness and variable patient responses to psychiatric medications. It explores how therapeutic drug monitoring, pharmacogenomics, and biomarker testing can be used to individualize and optimize pharmacotherapy for mental disorders such as depression, bipolar disorder, and schizophrenia. [ABSTRACT FROM AUTHOR]

Bacterial laccase exhibits substantial application potential in various fields. In this study, we constructed a mutation library of CotA laccase from Bacillus pumilus using error-prone PCR, and we performed four rounds of enrichment screening under malachite green (MG) pressure. The results demonstrated that the proportions of the four selected mutant strains were significantly increased. The enzyme activities of the four final mutants PW2, PW5, PW4G, and PW6 were 94.34, 75.74, 100.66, and 87.04 U/mg, respectively, representing a significant increase of approximately 2- to 3-fold compared to the wild-type CotA laccase. Notably, PW4 exhibited significantly improved thermal stability at 90 °C and pH tolerance at pH 12.0. Homology modeling analysis revealed that alterations in the amino acid sequence rendered the spatial structure of the enzyme's catalytic site more favorable for substrate binding. For instance, the substitution of T262A in PW2 and V426I in PW4 shortened the side chains of the amino acids, thereby enlarging the substrate-binding cavity. The G382D mutation in PW2 and PW5 may induce altered protein conformation via spatial steric hindrance or electrostatic interactions, consequently impacting enzyme activity and stability. These findings provide valuable insights for enhancing the industrial application of bacterial laccase. [ABSTRACT FROM AUTHOR]

The most important ligninolytic enzymes in lignin degradation include laccases and peroxidases (lignin peroxidase, manganese peroxidase, versatile peroxidase). White-rot fungi (e.g., Cerrena sp., Phlebia sp. or Trametes sp.) are their main source in nature. The ability of ligninolytic enzymes to degrade both phenolic and non-phenolic compounds has found its application in sustainable agriculture. In recent years, ligninolytic enzymes' important role has been demonstrated in the biodegradation of lignin, a poorly degradable component of plant biomass, and in removing hazardous environmental pollutants that threaten human health. These enzymes can be successfully used in waste management, composting, improving soil health and fertility, or bioremediation. The challenges of applying lignin-degrading enzymes such as laccases and peroxidases include their stability and resistance to harsh conditions. Still, the rapid development of biotechnological technologies offers the tools to overcome them. Applying biological solutions in agricultural systems involving microorganisms and their metabolic products will significantly reduce the environmental impact and develop a circular economy. [ABSTRACT FROM AUTHOR]

Neutrophils are a critical component of immunity, particularly against bacteria and other pathogens, but also in inflammation and tissue repair. As a consequence, individuals with neutropenia, defined by a reduction in absolute neutrophil counts, exhibit a strong propensity to severe infections that typically present with muted symptoms. Neutropenias encompass a heterogeneous set of disorders, comprising primary neutropenias, in which specific genes are mutated, and the more common secondary neutropenias, which have diverse non-genetic causes. These include hematological and other cancers, involving both direct effects of the cancer itself and indirect impacts via the chemotherapeutic, biological agents and cell-based approaches used for treatment. Other significant causes of secondary neutropenias are non-chemotherapeutic drugs, autoimmune and other immune diseases, infections and nutrient deficiencies. These collectively act by impacting neutrophil production in the bone marrow and/or destruction throughout the body. This review describes the biological and clinical manifestations of secondary neutropenias, detailing their underlying causes and management, with a discussion of alternative and emerging therapeutic approaches. [ABSTRACT FROM AUTHOR]

Many psychiatric disorders are associated with major cognitive deficits. However, it is uncertain whether these deficits develop as a result of psychiatric disorders and what shared risk factors might mediate this relationship. Here, we utilized the Mendelian randomization (MR) analysis to investigate the complex causal relationship between nine major psychiatric disorders and three cognitive phenotypes, while also examining the potential mediating role of oxidative stress as a shared biological underpinning. Schizophrenia (SZ), major depressive disorder (MDD), and attention deficit hyperactivity disorder (ADHD) showed a decreasing effect on cognitive performance, intelligence, and education, while bipolar disorder (BPD) increased educational attainment. MR-Clust results exhibit the shared genetic basis between SZ and other psychiatric disorders in relation to cognitive function. Furthermore, when oxidative stress was considered as a potential mediating factor, the associations between SZ and the three dimensions of cognition, as well as between MDD and intelligence and ADHD and intelligence, exhibited larger effect sizes than the overall. Mediation MR analysis also supported the causal effects between psychiatric disorders and cognition via oxidative stress traits, including carotene, vitamin E, bilirubin, and uric acid. Finally, summary-based MR identified 29 potential causal associations of oxidative stress genes with both cognitive performance and psychiatric disorders. Our findings highlight the importance of considering oxidative stress in understanding and potentially treating cognitive impairments associated with psychiatric conditions. [ABSTRACT FROM AUTHOR]

In the context of COVID-19 concerns related to the potential interactions between clozapine and vaccination arose. With the ultimate goal of deriving recommendations for clinical practice, we systematically reviewed the current evidence regarding altered vaccine effectiveness in clozapine-treated patients and safety aspects of vaccination, such as haematological changes and the impact of vaccines on clozapine blood levels, in clozapine-treated patients. A systematic PRISMA-conform literature search of four databases (PubMed, PsycINFO, EMBASE and Cochrane Library) complemented by a case-by-case analysis of the Vaccine Adverse Event Reporting System (VAERS) database was performed. We then systematically appraised the joint evidence and tried to derive recommendations for clinical practice. 14 records were included in this analysis. These records consisted of 5 original articles and 9 case reports. Among the original articles, two studies provided data on the association between clozapine use and antibody responses to vaccination, both indicating that clozapine use in schizophrenia may be associated with reduced levels of immunoglobulins. Additionally, three studies examined vaccine safety in clozapine-treated patients, with no clinically significant adverse effects directly attributable to the interplay between vaccinations and clozapine. VAERS Analysis encompassed 137 reports and showed no consistent evidence of an increased risk for clozapine blood level increases or adverse events. We found no evidence indicating that clozapine impairs the effectiveness of vaccines. Moreover, no serious safety concerns seem to apply when patients on clozapine are receiving vaccines. However, it is crucial to acknowledge that data on the interaction between clozapine and vaccines remain limited. [ABSTRACT FROM AUTHOR]

The landscape of psychiatric care is poised for transformation through the integration of pharmaco-multiomics, encompassing genomics, proteomics, metabolomics, transcriptomics, epigenomics, and microbiomics. This review discusses how these approaches can revolutionize personalized treatment strategies in psychiatry by providing a nuanced understanding of the molecular bases of psychiatric disorders and individual pharmacotherapy responses. With nearly one billion affected individuals globally, the shortcomings of traditional treatments, characterized by inconsistent efficacy and frequent adverse effects, are increasingly evident. Advanced computational technologies such as artificial intelligence (AI) and machine learning (ML) play crucial roles in processing and integrating complex omics data, enhancing predictive accuracy, and creating tailored therapeutic strategies. To effectively harness the potential of pharmaco-multiomics approaches in psychiatry, it is crucial to address challenges such as high costs, technological demands, and disparate healthcare systems. Additionally, navigating stringent ethical considerations, including data security, potential discrimination, and ensuring equitable access, is essential for the full realization of this approach. This process requires ongoing validation and comprehensive integration efforts. By analyzing recent advances and elucidating how different omic dimensions contribute to therapeutic customization, this review aims to highlight the promising role of pharmaco-multiomics in enhancing patient outcomes and shifting psychiatric treatments from a one-size-fits-all approach towards a more precise and patient-centered model of care. [ABSTRACT FROM AUTHOR]

Background: Although previous studies have highlighted the detrimental impact of sexism on other substance use and use-related outcomes among women, limited empirical attention has tested whether sexism is related to worse cannabis-related outcomes. It may be that women use cannabis to cope with negative affect related to experiencing sexism, and thus continue to use despite cannabis-related problems. However, no known studies have tested this hypothesis. Objectives: We tested whether experiencing sexism was related to more cannabis use-related problems via the serial effects of negative affect (anxiety, depression) and coping-motivated cannabis use among 304 women who endorsed current (past three-month) cannabis use. Results: Sexism was significantly positively related to coping-motivated-cannabis use and use-related problems. Sexism was indirectly related to cannabis problems via the serial effects of anxiety and coping motives and via the serial effects of depression and coping motives, but not via the indirect effects of anxiety, depression, or coping motives alone. Conclusions: Findings suggest that women may use cannabis to cope with sexism-related negative affect, and thus continue to use despite experiencing greater cannabis problems. These results may have important clinical implications and emphasize the need for greater gender-responsive approaches in prevention and intervention efforts for women who use cannabis. [ABSTRACT FROM AUTHOR]

Background/Objectives: Individuals diagnosed with schizophrenia are susceptible to constipation induced by antipsychotic medications. However, research investigating the prevalence of this adverse effect and its underlying mechanisms is limited. Methods: To address this knowledge gap, a narrative review was conducted on the subject of constipation in patients with schizophrenia. A comprehensive electronic search was conducted in the PubMed and J-Stage databases. Results: The prevalence of constipation in individuals with schizophrenia is high, ranging from 30% to 60%. The risk of constipation increases with high doses of antipsychotics and with the concomitant use of anticholinergics and mood stabilizers. The prevalence of constipation varies by sex, with women demonstrating a higher risk compared to men. Conclusions: Constipation is a prevalent complaint among individuals with schizophrenia, with women exhibiting a higher risk. The underlying pathophysiology of sex differences in constipation is attributed to variations in monoamines within the descending pain inhibitory pathway, which governs the neural circuitry associated with defecation. Constipation can lead to significant complications, underscoring the need for a multifaceted approach to treatment that considers the intestinal environment beyond the mere use of laxatives. [ABSTRACT FROM AUTHOR]

Background: Synthetic cathinones and cannabinoids have emerged as significant public health concerns, particularly in pediatric populations. Marketed under deceptive names such as "bath salts" and "K2/Spice", these substances pose unique challenges due to their accessibility, potency, and unpredictable effects. This narrative review synthesizes evidence on the toxicological effects of synthetic cathinones and cannabinoids in pediatric patients, emphasizing clinical presentations, management challenges, and public health implications. Methods: A structured narrative review was conducted using PubMed and Scopus databases to identify peer-reviewed studies published between January 2010 and September 2024. The selected articles focus on neuropsychiatric, systemic, and management outcomes associated with these substances in individuals aged 0–18 years. Results: Five studies demonstrate that synthetic cathinones frequently cause seizures, sympathomimetic toxidrome (tachycardia, hypertension), and neuropsychiatric effects like paranoia and catatonia. Seven studies show synthetic cannabinoids induce psychosis, respiratory depression requiring ventilation in 12% of cases, and cardiovascular complications like myocardial ischemia. One study highlighted severe outcomes in pediatric accidental exposures, emphasizing the unpredictable and life-threatening effects of these substances, often exacerbated by co-ingestion with alcohol or THC. Conclusions: Pediatric exposure to synthetic cathinones and cannabinoids results in severe and unpredictable toxicological effects, necessitating tailored clinical management strategies and enhanced diagnostic capabilities. Public health measures, including stringent regulatory controls, targeted education initiatives, and robust surveillance systems, are critical to mitigating these risks. A multidisciplinary approach is essential to safeguard vulnerable pediatric populations from the escalating dangers posed by synthetic drugs, and future research must address the long-term impacts and mechanisms of toxicity. [ABSTRACT FROM AUTHOR]

Cubic silicon-carbide crystals (3C-SiC), known for their high thermal conductivity and in-plane stress, hold significant promise for the development of high-quality (Q) mechanical oscillators. We reveal degeneracy-breaking phenomena in 3C-phase crystalline silicon-carbide membrane and present high-Q mechanical modes in pairs or clusters. The 3C-SiC material demonstrates excellent microwave compatibility with superconducting circuits. Thus, we can establish a coherent electromechanical interface, enabling precise control over 21 high-Q mechanical modes from a single 3C-SiC square membrane. Benefiting from extremely high mechanical frequency stability, this interface enables tunable light slowing with group delays extending up to an impressive duration of an hour. Coherent energy transfer between distinct mechanical modes are also presented. In this work, the studied 3C-SiC membrane crystal with their significant properties of multiple acoustic modes and high-quality factors, provide unique opportunities for the encoding, storage, and transmission of quantum information via bosonic phonon channels. Coherent electrical manipulation of long-lived, multimode mechanical resonators is crucial for several applications. Here the authors report the integration of a high quality cubic SiC-membrane mechanical resonator with a 3D microwave cavity, enabling long-lived phononic memory and tunable light slowing. [ABSTRACT FROM AUTHOR]

DIII-D research is being accelerated by leveraging high performance computing (HPC) and data resources available through the National Energy Research Scientific Computing Center (NERSC) Superfacility initiative. As part of this initiative, a high-resolution, fully automated, whole discharge kinetic equilibrium reconstruction workflow was developed that runs at the NERSC for most DIII-D shots in under 20 min. This has eliminated a long-standing research barrier and opened the door to more sophisticated analyses, including plasma transport and stability. These capabilities would benefit from being automated and executed within the larger Department of Energy Advanced Scientific Computing Research program's Integrated Research Infrastructure (IRI) framework. The goal of IRI is to empower researchers to meld DOE's world-class research tools, infrastructure, and user facilities seamlessly and securely in novel ways to radically accelerate discovery and innovation. For transport, we are looking at producing flux matched profiles and also using particle tracing to predict fast ion heat deposition from neutral beam injection before a shot takes place. Our starting point for evaluating plasma stability focuses on the pedestal limits that must be navigated to achieve better confinement. This information is meant to help operators run more effective experiments, so it needs to be available rapidly inside the DIII-D control room. So far this has been achieved by ensuring the data is available with existing tools, but as more novel results are produced new visualization tools must be developed. In addition, all of the high-quality data we have generated has been collected into databases that can unlock even deeper insights. This has already been leveraged for model and code validation studies as well as for developing AI/ML surrogates. The workflows developed for this project are intended to serve as prototypes that can be replicated on other experiments and can be run to provide timely and essential information for ITER, as well as next stage fusion power plants. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a complex psychiatric disorder, and in patients treated with clozapine, it may induce or exacerbate obsessive-compulsive symptoms (OCS), which negatively affect patients' quality of life, functionality and treatment adherence. Despite its clinical relevance, the reported prevalence and characteristics of clozapine associated OCS vary widely, limiting effective management. Objective: This scoping review synthesizes evidence on the prevalence of OCS in patients with schizophrenia treated with clozapine and explores treatment characteristics (types, severity, dose, and time to onset/exacerbation). Methods: The PRISMA-ScR methodology guided the search in PubMed, LILACS, Embase, and Scielo. Observational studies in Spanish, English, Portuguese, and French reporting prevalence, incidence, or frequency of OCS in patients over 18 years with schizophrenia treated with clozapine were included. Clinical, qualitative studies, and those with access restrictions were excluded. Risk of bias was assessed using JBI tools. Results: Fourteen studies were included, reporting OCS prevalence between 20% and 76%, and de novo OCS between 4.8% and 46.4%. Clozapine dose ranged from 196 to 525 mg/day, and treatment duration from 5 to 210 months. The most common obsessions were aggression and checking, with severity ranging from mild to moderate. Conclusions: The prevalence of OCS in patients treated with clozapine varies widely. Further research is needed to clarify the relationship between dose, treatment duration, and the onset/exacerbation of OCS. [ABSTRACT FROM AUTHOR]

Second-generation (2G) bioethanol production, derived from lignocellulosic biomass, has emerged as a sustainable alternative to fossil fuels by addressing growing energy demands and environmental concerns. Fungal sugar transporters (STs) play a critical role in this process, enabling the uptake of monosaccharides such as glucose and xylose, which are released during the enzymatic hydrolysis of biomass. This mini-review explores recent advances in the structural and functional characterization of STs in filamentous fungi and yeasts, highlighting their roles in processes such as cellulase induction, carbon catabolite repression, and sugar signaling pathways. The review also emphasizes the potential of genetic engineering to enhance the specificity and efficiency of these transporters, overcoming challenges such as substrate competition and limited pentose metabolism in industrial strains. By integrating the latest research findings, this work underscores the pivotal role of fungal STs in optimizing lignocellulosic bioethanol production and advancing the bioeconomy. Future prospects for engineering transport systems and their implications for industrial biotechnology are also discussed. Key points: STs present a conserved structure with different sugar affinities STs are involved in the signaling and transport of sugars derived from plant biomass Genetic engineering of STs can improve 2G bioethanol production [ABSTRACT FROM AUTHOR]

Background: Due to its exceptional effectiveness, clozapine (CLO), whose metabolite is norclozapine (NCLO), is a drug of choice in the management of treatment-resistant schizophrenia. The purpose of this study was to assess the factors modifying the CLO/NCLO ratio (CNR). Methods: A total of 446 blood samples (233 of which were drawn from females and 213 from males, aged from 18 to 77 years) were analyzed in this study. The patients were treated at a psychiatric hospital in the period 2016–2021. Serum CLO and NCLO levels were determined with high-performance liquid chromatography coupled with a UV detector. Results: The median CNR was 2.38 (minimum 0.30, maximum 14.36). Our analysis showed that neither sex (p= 0.135) nor smoking (p = 0.774) had any significant effect on the CNR. However, increased doses of CLO resulted in lower CNR values (p = 0.005). Concomitant use of other psychotropic drugs increased the CNR (p = 0.001). Discussion: The results of our study indicate a need for personalized CLO treatment. Assessing the CNR may be useful in identifying CLO interaction with other psychotropic drugs. [ABSTRACT FROM AUTHOR]

Objective: Paliperidone palmitate is a second-generation antipsychotic that has undergone extensive investigation in clinical trials. However, real-world studies assessing its safety in large populations are lacking. As such, this study aimed to comprehensively evaluate real-world adverse drug events (ADEs) linked to paliperidone palmitate by employing data mining techniques on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database and the Japanese Adverse Drug Event Report (JADER) database. Methods: The study retrieved ADE reports from the FAERS database covering the period from 2009 through the third quarter of 2024, and from the JADER database covering the period from 2013 through the second quarter of 2024. Utilizing disproportionality analyses such as the reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item Poisson shrinkage (MGPS), significant associations between ADEs and paliperidone palmitate were evaluated. Results: A total of 27,672 ADE reports related to paliperidone palmitate were identified in FAERS, with 285 significantly disproportionate preferred terms (PTs) identified by all four algorithms. Paliperidone palmitate-associated ADEs encompassed 27 System Organ Classes (SOCs). The top three PTs with the highest reported cases were off-label use, drug ineffective, and hospitalization. Common ADEs included increased blood prolactin, galactorrhea, and schizophrenia, which was consistent with drug label. Noteworthy, unexpected signals not listed in the drug label were also identified, such as psychosexual disorders, prolactin-producing pituitary tumors, suicide attempt, and sudden death. The median onset time for all ADEs was 40 days. Furthermore, gender-based difference in risk signals was detected. Females are more likely to experience elevated blood prolactin and weight increase, whereas males are more prone to sexual dysfunction. Among the 1,065 ADE reports from the JADER database, we identified 51 positive signals, 35 of which overlapped with those found in FAERS, including schizophrenia, hyperprolactinemia, and erectile dysfunction. Conclusion: The study findings from two independent databases serve as crucial references for ensuring the safe of paliperidone palmitate. Additionally, the gender-specific monitoring references provided can enhance clinical surveillance efforts and facilitate more effective risk identification. [ABSTRACT FROM AUTHOR]

Key Points: Question: What is the association of severe maternal morbidity (SMM) during a first birth with the probability of having a subsequent birth? Findings: In this nationwide population cohort study in Sweden, women with any SMM had a significantly lower incidence rate of subsequent birth compared with those without SMM in their first delivery (136.6 vs 182.4 per 1000 person-years). The associations were not influenced by familial confounding as indicated by sibling analyses. Meaning: Women who experience SMM in their first birth are less likely to have a subsequent birth. Adequate reproductive counseling and enhancing antenatal care are crucial for these women. Importance: Women who experience severe maternal morbidity (SMM) might have lasting health issues, and the association of SMM with the probability of future reproductive intentions is unknown. Objective: To examine the association between SMM in a first birth and the probability of a subsequent birth. Design, Setting, and Participants: Retrospective, population-based cohort study conducted among 1 046 974 women in Sweden who had their first birth between 1999 and 2021. Exposure: Overall SMM and SMM subtypes were identified among all deliveries at 22 weeks of gestation or later (including complications within 42 days of delivery) from the Swedish Medical Birth Register and National Patient Register. Main Outcomes and Measures: All women with a recorded first delivery were followed up from 43 days postpartum until the first day of the last menstrual period of the second pregnancy that resulted in a birth (stillbirth or live birth) or until death, emigration, or end of follow-up on December 31, 2021. Multivariable Cox proportional hazards regression was used to estimate associations between SMM and time to subsequent birth with adjusted hazard ratios (aHRs). Sibling analysis was performed to evaluate potential genetic and familial confounding. Results: A total of 36 790 women (3.5%) experienced an SMM condition in their first birth. Women with any SMM had a lower incidence rate of subsequent birth compared with those without SMM in their first delivery (136.6 vs 182.4 per 1000 person-years), with an aHR of 0.88 (95% CI, 0.87-0.89). The probability of subsequent birth was substantially lower among women with severe uterine rupture (aHR, 0.48; 95% CI, 0.27-0.85), cardiac complications (aHR, 0.49; 95% CI, 0.41-0.58), cerebrovascular accident (aHR, 0.60; 95% CI, 0.50-0.73), and severe mental health conditions (aHR, 0.48; 95% CI, 0.44-0.53) in their first birth. The associations were not influenced by familial confounding as indicated by sibling analyses. Conclusions and Relevance: Our findings suggest that women who experience SMM in their first birth are less likely to have a subsequent birth. Adequate reproductive counseling and enhancing antenatal care are crucial for women with a history of SMM. This cohort study analyzed the association between severe maternal morbidity occurring in a first childbirth and the probability of a subsequent birth among women in Sweden. [ABSTRACT FROM AUTHOR]

Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability. Using functional MRI connectivity, we further confirmed the significance of the central and lateral amygdala, hippocampal body, and prefrontal cortex in distinguishing schizophrenia cases from controls. Our findings underscore the value of single-cell transcriptomics in understanding the polygenicity of psychiatric disorders and suggest a promising alignment of genomic, transcriptomic, and brain imaging modalities for identifying common biological targets. Circuit and cell type prioritization for complex disorders is crucial to direct future efforts. Here the authors integrate GWAS, human single-cell RNA-seq and fMRI analysis suggesting multi-modality convergence on amygdalar and hippocampal circuits. [ABSTRACT FROM AUTHOR]

Data from the National Survey on Drug Use and Health (2012–2018) were used to characterize the association between menthol cigarette use and indicators of Any (AMI) and Serious (SMI) Mental Illness among adults who smoke in the United States. In general, people who smoke menthol cigarettes were more likely to have AMI (aOR = 1.123 [1.063–1.194]) than people who smoke non-menthol cigarettes, but not SMI (aOR = 1.065 [0.966–1.175]). However, among non-Hispanic African American/Black people who smoke, those that used menthol cigarettes had lower adjusted odds of both AMI (aOR = 0.740 [0.572–0.958]) and SMI (aOR = 0.592 [0.390–0.899]) than their counterparts who used non-menthol cigarettes. Results suggest there may be race/ethnicity-specific drivers of the association between menthol cigarette use and mental illness. [ABSTRACT FROM AUTHOR]

Borderline Personality Disorder (BPD) is under-recognized in First Episode Psychosis (FEP). The aims of this investigation were: (a) to examine the prevalence of BPD in FEP patients enrolled within an Italian "Early Intervention in Psychosis" (EIP) service; (2) to compare sociodemographic, clinical and treatment characteristics at entry between FEP individuals with and without BPD; and (3) to compare their drop-out rates along a 2-year follow-up period. BPD was assessed using the Structured Clinical Interview for DSM-IV axis II personality disorders. All participants also completed the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Forty-nine (9.6%) FEP participants showed a BPD diagnosis. FEP individuals with BPD had a higher baseline prevalence of substance misuse, a lower baseline equivalent dose of antipsychotic medication, lower baseline levels of negative symptoms, and higher baseline levels of anxious-depressive features. They also had a higher 2-year drop-out rate. In conclusion, BPD is present in 10% of FEP patients. This FEP subgroup has peculiar clinical challenges (e.g. high substance misuse at entry, high drop-out rate) and additional comorbidities (e.g. high levels of depressive symptoms at entry), which would require appropriate treatment guidelines. [ABSTRACT FROM AUTHOR]

The last few years have seen exponential growth in interest, investment, advocacy, and research into psychedelics as therapeutics. This reflects an optimism about the potential promise of psychedelics as therapeutics. As with all therapeutic interventions, research is needed not only into their benefits but also potential risks. Indeed, when substances with therapeutic potential are scrutinized over time, especially in broad populations with psychiatric and medical comorbidities typically excluded from clinical trials, and applied in less well-regulated or controlled settings, a greater understanding of the cautions emerges. Here, we review the literature on the known and potential harms, including enduring perceptual disturbances; triggering or enhancing the risk for onset of mania or psychosis; overuse, misuse, and dependence; challenging experiences or "bad trips"; risks associated with increased neuroplastic potential; and acute and cumulative cardiovascular effects. Each of these issues is addressed in this review, along with the call for continued research, including recommendations for further research and monitoring. [ABSTRACT FROM AUTHOR]

As artificial intelligence (AI) becomes more deeply integrated in our personal and professional lives, there is a growing need for youth to develop skills to engage critically and productively with AI as early as elementary school. In this article, we present a promising instructional strategy, metacognitive embodiment (McE), which can be readily leveraged by teachers of K–5 students to support sensemaking in early encounters with AI. In short, McE involves creating opportunities for youth to think systematically about how they perform a cognitive task, in coordination with guided inquiry into how an AI might perform an analogous task. We propose this as a learning strategy that aims to engage K–5 students in thinking about how AI can learn to perform human-like thinking tasks through an interactive and accessible experience. In doing so, the strategy also engages youth in the core computational thinking practices of abstraction and decomposition. This strategy would also serve broader learning goals to nurture youth capacity for metacognition as a powerful strategy to support learning and a growth mindset. In this paper, we present two sets of digital and non-digital activities that employ a strategy of metacognitive embodiment and can be carried out in sequence to support the development of AI literacy for K–5 students. [ABSTRACT FROM AUTHOR]

The article offers information on clinical practice guidelines for assessing and managing cognitive impairment in schizophrenia. Topics include the cognitive domains affected by schizophrenia; the role of pharmacological and psychosocial interventions such as cognitive remediation and physical exercise; and the use of brain stimulation treatments like electroconvulsive treatment (ECT) and repetitive transcranial brain stimulation (rTMS).

Quantum transduction between microwave and optical photons offers the potential to merge the long-range connectivity of optical photons with the deterministic quantum operations of superconducting microwave qubits. A promising approach to achieving this uses an intermediary mechanical mode along with piezo-optomechanical interactions. Traditionally, these transducers are suspended to confine mechanical fields, but this complicates manufacturing and comes with the major challenge of poor thermal anchoring and a trade-off between noise and efficiency. To overcome these issues, we introduce the—to our knowledge—first design of a release-free electro-optomechanical quantum transducer. Our release-free, i.e., non-suspended, design leverages a silicon-on-sapphire platform. It combines release-free lithium niobate electromechanical crystals with silicon optomechanical crystals on a sapphire substrate, optimizing thermal anchoring and microwave and mechanical coherence. Despite departing from the traditional suspended transducer paradigm, our release-free design achieves coupling rates sufficient for quantum-level interactions between microwave photons, phonons, and optical photons. Unconventionally, it utilizes high-wavevector mechanical modes tightly confined to the chip surface. Beyond quantum science and engineering, this platform and its design principles could also propel low-power acousto-optic systems in integrated photonics. [ABSTRACT FROM AUTHOR]

The association of enteral micronutrient supplementation and the neurodevelopmental outcomes of preterm or low birth weight (LBW) infants is controversial. This research was prospectively registered (CRD42023454034). We searched MEDLINE, Embase, PsycInfo, ClinicalTrials. gov, and the Cochrane Library for randomised clinical trials (RCTs) or quasi‐RCTs comparing any enteral micronutrients supplementation with placebo or no supplementation in preterm or LBW infants. The primary outcome was neurodevelopmental impairment (NDI), with secondary outcomes involving various neurodevelopmental tests and disabilities. There was no evidence of an association between enteral micronutrients supplementation and the risk of NDI (RR, 1.03; 95% CI, 0.93–1.14; moderate certainty evidence). There was no evidence that the supplemented groups enhanced cognitive (MD, 0.65; 95% CI, −0.37 to 1.67; low certainty evidence), language (SMD, −0.01; 95% CI, −0.11 to 0.09; moderate certainty evidence), or motor scores (SMD, 0.04; 95% CI, −0.06 to 0.15; very low certainty evidence) or IQ (SMD, −0.20; 95% CI, −0.53 to 0.13; very low certainty evidence). Subgroup analysis showed that multiple micronutrients supplementation improved expressive language score (MD, 1.42; 95% CI, 0.39–2.45), and zinc supplementation enhanced fine motor score (SMD, 1.70; 95% CI, 0.98–2.43). The overall heterogeneity was low. This study demonstrates that enteral micronutrient supplementation is associated with little or no benefits in neurodevelopmental outcomes for preterm or LBW infants. Well‐designed RCTs are needed to further ascertain these associations. Key messages: There is little or no evidence that enteral micronutrient supplementation during infancy is associated with a decreased risk of neurodevelopmental impairment in preterm or low birth weight infants.Multiple micronutrient supplementation may improve expressive language score, and zinc supplementation may enhance gross motor and fine motor scores.Future well‐designed randomised clinical trials with more participants and longer follow‐up are needed to further ascertain these associations. [ABSTRACT FROM AUTHOR]