Five interdisciplinary tensions and opportunities in neurodiversity research.

Improving our understanding of autism, ADHD, dyslexia and other neurodevelopmental conditions requires collaborations between genetics, psychiatry, the social sciences and other fields of research.

Evaluating the utility of procalcitonin and a clinical decision support tool to determine duration of antimicrobial therapy for respiratory tract infections.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Procalcitonin (PCT) levels may play a role in decreasing the duration of antimicrobial therapy in institutions that have long durations of therapy for management of community-acquired pneumonia. We assessed the impact of the combination of pharmacist stewardship interventions assisted by a clinical decision support (CDS) tool and PCT assessment on the antimicrobial days of therapy (DOT) prescribed for respiratory tract infections (RTIs). METHODS: We conducted a quasi-experimental study in which patients in the preintervention group were admitted between April and June 2021 and patients in the intervention group were admitted between April and June 2022. In the intervention phase, a CDS tool was utilized to alert clinical pharmacists when patients met specific criteria. This alert was programmed to activate for individual patients when a reported PCT level was less than 0.25 ng/mL and on antimicrobials prescribed for an RTI as indicated by providers in the electronic health record. Stewardship interventions were made by pharmacists via prospective audit and feedback. The primary endpoint was inpatient antimicrobial DOT for RTIs. RESULTS: There were 90 patients in the preintervention group and 104 patients in the intervention group. Although baseline characteristics were not well matched between the groups, favoring the preintervention group, the median DOT was lower in the intervention group at 3 days (interquartile range [IQR], 2-4 days), compared to 4 days (IQR, 2.8-5 days) in the preintervention group (P = 0.001). CONCLUSION: The results of our study demonstrate the utility of pharmacist interventions coupled with CDS and PCT in reducing antimicrobial DOT prescribed for RTIs. Antimicrobial stewardship programs may benefit from implementing a PCT bundle.

Unpacking the overlap between Autism and ADHD in adults: A multi-method approach.

The overlap between Autism and Attention-Deficit Hyperactivity Disorder (ADHD) is widely observed in clinical settings, with growing interest in their co-occurrence in neurodiversity research. Until relatively recently, however, concurrent diagnoses of Autism and ADHD were not possible. This has limited the scope for large-scale research on their cross-condition associations, further stymied by a dearth of open science practices in the neurodiversity field. Additionally, almost all previous research linking Autism and ADHD has focused on children and adolescents, despite them being lifelong conditions. Tackling these limitations in previous research, 5504 adults - including a nationally representative sample of the UK (Study 1; n = 504) and a large pre-registered study (Study 2; n = 5000) - completed well-established self-report measures of Autism and ADHD traits. A series of network analyses unpacked the associations between Autism and ADHD at the individual trait level. Low inter-item connectivity was consistently found between conditions, supporting the distinction between Autism and ADHD as separable constructs. Subjective social enjoyment and hyperactivity-impulsivity traits were most condition-specific to Autism and ADHD, respectively. Traits related to attention control showed the greatest Bridge Expected Influence across conditions, revealing a potential transdiagnostic process underlying the overlap between Autism and ADHD. To investigate this further at the cognitive level, participants completed a large, well-powered, and pre-registered study measuring the relative contributions of Autism and ADHD traits to attention control (Study 3; n = 500). We detected age- and sex-related effects, however, attention control did not account for the covariance between Autism and ADHD traits. We situate our findings and discuss future directions in the cognitive science of Autism, ADHD, and neurodiversity, noting how our open datasets may be used in future research.

Linearly integrating speed and accuracy to measure individual differences in theory of mind: Evidence from autistic and neurotypical adults.

It has long been theorised that there is a direct link between individual differences in social cognition and behaviour. One of the most popular tests of this theory has involved examination of Theory of Mind (ToM) difficulties in Autism Spectrum Disorder (ASD). However, evidence for associations between ToM and social behaviour is mixed, both when testing the ToM explanation of ASD and when investigating individual differences in ToM in the general population. We argue that this is due to methodological limitations of many ToM measures, such as a lack of variability in task performance, inappropriate non-ToM control tasks, and a failure to account for general mental ability. To overcome these issues, we designed a novel task, which probed individual differences in ToM fluency through mental state attribution in response to cartoons (Cartoons Theory of Mind [CarToM] task). This task, enabling the linear combination of speed and accuracy, was used to quantify ToM ability and its association with self-reported (a)typical social behaviour in adults with and without ASD. In a large sample (N = 237), we found that having an ASD diagnosis and higher autistic traits predicted lower ToM ability, even after accounting for performance on a well-matched non-ToM condition and general mental ability. Overall, our findings provide fresh support for the existence of a link between individual differences in social cognition (specifically, ToM) and behaviour (specifically, autism). This has implications for social-cognitive theory and research, allowing large-scale, online assessment of individual differences in ToM in clinical groups and the general population.

Re-examining the association between the age of learning one is autistic and adult outcomes.

LAY ABSTRACT: An interesting recent study found that people who learned they were autistic at a younger age felt more positive about their lives (i.e., had better quality of life) than those who learned at an older age. However, this study has some limitations: (a) the study only involved a fairly small group of university students, (b) whether 'learning one is autistic' referred to learning about one's diagnosis or receiving one's diagnosis was unclear, (c) the influence of other factors on the link between age of learning one is autistic and quality of life was not considered, and (d) the assessment of different areas of quality of life was limited. Addressing these limitations, we re-examined whether the age at which one learns they are autistic relates to quality of life in adulthood. Contrary to the previous study, we found the age at which one learns about their autism does not have a significantly independent impact on their quality of life as an adult. Rather, other factors (e.g., autistic traits, sex, and additional mental health conditions) may have a greater impact. Given our participant sample was larger and more diverse in age and education level compared to previous research, this finding is likely to be more applicable to autistic adults from different backgrounds. Importantly, however, we are not suggesting that individuals should be made aware of their diagnosis later than sooner. Getting a timely diagnosis remains crucial for autistic people and their families to access appropriate support.

Evaluation of computerized clinical decision support system to reduce unnecessary nasal methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) testing.

Our health system implemented a novel clinical decision-support system to reduce unnecessary duplicate nasal methicillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction (PCR) orders. In an 8-month period, the rate of duplicate MRSA PCR orders within 7 days declined from 4.7% (370 of 7,861) to 1.2% (120 of 9,833).

The 19-Item Environmental Knowledge Test (EKT-19): A short, psychometrically robust measure of environmental knowledge.

Environmental knowledge is considered an important pre-cursor to pro-environmental behaviour. Though several tools have been designed to measure environmental knowledge, there remains no concise, psychometrically grounded measure. We validated an existing measure in a British sample, confirming that it had good one- and three-factor structures in line with previous literature. For the first time in this field, we built upon previous Classical Test Theory approaches and used discrimination values derived from Item Response Theory to select the best items, resulting in the 19-Item Environmental Knowledge Test (EKT-19). This measure retained a clear factor structure and had moderate-to-good internal reliability, indicating that it is a parsimonious and psychometrically robust measure for the assessment of overall and specific types of environmental knowledge. The theoretical implications and real-world applications of this measure are discussed.

Delayed Hemolysis With Parenteral Artesunate.

Artesunate is an effective and first-line therapy option in patients with severe malaria caused by Plasmodium species. Among adverse effects of the drug is a phenomenon of delayed hemolysis. This usually occurs at least 7 days after initiation of therapy, and is characterized by reductions in hemoglobin and haptoglobin and an increase in lactate dehydrogenase. Here, we report an instance of delayed hemolysis in a patient probably attributed to parenteral artesunate therapy.

Socio-demographic and political predictors of Theory of Mind in adulthood.

Individual differences in Theory of Mind (ToM)-the ability to understand the mental states of others-are theorised to be predicted by socio-demographic and political factors. However, inconsistent findings on the relationships between various socio-demographic predictors and ToM, as well as a paucity of research on political predictors of ToM, have left a gap in the literature. Using a recently validated self-report measure of ToM in a large sample (N = 4202) we investigated the unique contributions of age, sex, socio-economic status, and political beliefs to ToM in adults. Except for age, all variables were correlated with ToM, but when accounting for the variance of other predictors in statistical analyses, political beliefs was no longer associated with ToM. Dominance analysis revealed that participant sex was the most important predictor of ToM. These findings help to address theoretical discrepancies in the existing literature and inform future methods and directions in social cognition research.

The Danish Version of the 20-Item Prosopagnosia Index (PI20): Translation, Validation and a Link to Face Perception.

Developmental prosopagnosia (DP) is a neurodevelopmental condition characterized by face recognition problems. Psychometrically sound self-report measures of face recognition problems are important tools in classification of DP. A widely used measure of such problems is the 20-item prosopagnosia index (PI20). Here, we present a Danish translation of the PI20 (PI20DK). We administered the PI20DK alongside three objective measures of face and object processing performance to 119 participants to validate the PI20DK. Further, we assess the underlying factor structure of the PI20DK. Finally, as the first study in the field, we investigate the association between self-reported face recognition ability and face perception performance. The project was preregistered prior to data collection. The results suggest excellent convergent validity, discriminant validity and internal consistency for the PI20DK. A confirmatory factor analysis, however, indicates a suboptimal fit of the PI20DK to a one factor solution. An investigation of the association between the PI20DK and face perception suggests that the poor fit may reflect that the PI20DK measures problems with face recognition in general and not specifically face memory problems.

A Single-Center, Retrospective Cohort Study Evaluating the Use of Probiotics for the Prevention of Hospital-Onset Clostridioides difficile Infection in Hospitalized Patients Receiving Intravenous Antibiotics.

Background: Exposure to antimicrobials is a known risk factor for Clostridioides difficile infection (CDI). Antimicrobials cause collateral damage by disrupting the natural intestinal microbiota allowing for C. difficile to thrive and production of C. difficile toxins. Probiotics could modulate the onset and course of CDI. However, the data on probiotics for the prevention of CDI is conflicting. Objective: To evaluate the rates of hospital-onset Clostridioides difficile infection (HO-CDI) among patients who received intravenous (IV) antibiotics plus probiotics versus IV antibiotics alone. Design: Retrospective, single-center cohort study. Methods: We included adult patients that received at least 1 dose of IV antibiotics and had a hospital length of stay of at least 3 days between August 2017 and July 2020. Patients were separated into 2 cohorts, either receipt of probiotics or non-receipt of probiotics. Patients with positive C. difficile toxin test prior to antibiotic therapy, or receipt of only C. difficile active treatment were excluded. The primary outcome was incidence of HO-CDI in patients who received IV antibiotics plus probiotics compared to those that received IV antibiotics alone. Logistic regression was performed to account for confounding variables. Results: We identified 17 598 patients that received IV antibiotics alone and 2659 patients received IV antibiotics plus probiotics. HO-CDI occurred in 46 (0.26%) of those that received antibiotics alone compared to 5 (0.19%) of those that received probiotics with IV antibiotics (OR 0.72, 95% CI 0.28-1.81). ICU admission (OR 1.81, 95% CI 1.02-3.19) and history of CDI (OR 3.37, 95% CI 1.07-10.97) in the past 12 months were associated with a higher incidence of HO-CDI. Conclusion: The addition of probiotics did not reduce the incidence of HO-CDI among inpatients receiving IV antibiotics.

Psychological strengths and well-being: Strengths use predicts quality of life, well-being and mental health in autism.

LAY ABSTRACT: It is often suggested that supporting autistic people to identify and use their strengths will lead to positive outcomes. However, little research has explored if this is true. To date, no research has explored whether autistic people already have knowledge of and use their strengths, nor whether increased strengths knowledge and use is linked to good outcomes, such as a better quality of life, well-being and improved mental health. Comparing large samples of autistic and non-autistic people, this study tested these unanswered questions. We found that autistic and non-autistic people reported similar strengths, but autistic people reported less knowledge and use of their strengths compared to non-autistic people. Importantly however, autistic people who reported using their strengths often had better quality of life, well-being and mental health than autistic people who reported using their strengths less frequently. We, therefore, propose that supporting autistic people to use their strengths more often may be a valuable way to boost well-being in this population.

Attention-deficit hyperactivity disorder traits are a more important predictor of internalising problems than autistic traits.

Autism Spectrum Disorder (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) are both linked to internalising problems like anxiety and depression. ASD and ADHD also often co-occur, making their individual statistical contributions to internalising disorders difficult to investigate. To address this issue, we explored the unique associations of self-reported ASD traits and ADHD traits with internalising problems using a large general population sample of adults from the United Kingdom (N = 504, 49% male). Classical regression analyses indicated that both ASD traits and ADHD traits were uniquely associated with internalising problems. Dominance and Bayesian analyses confirmed that ADHD traits were a stronger, more important predictor of internalising problems. However, brief depression and anxiety measures may not provide a comprehensive index of internalising problems. Additionally, we focused on recruiting a sample that was representative of the UK population according to age and sex, but not ethnicity, a variable that may be linked to internalising disorders. Nevertheless, our findings indicate that while ASD and ADHD uniquely predict internalising problems, ADHD traits are a more important statistical predictor than ASD traits. We discuss potential mechanisms underlying this pattern of results and the implications for research and clinical practice concerning neurodevelopmental conditions.

Understanding the Contributions of Trait Autism and Anxiety to Extreme Demand Avoidance in the Adult General Population.

Autism and anxiety are thought to be related to extreme demand avoidance (EDA), which is characterised by intense avoidance of everyday demands. However, the relative importance of autism and anxiety to EDA has yet to be investigated, and little is known about EDA in adulthood. We conducted two online survey studies (Ns = 267 and 549) with adults in the general population to establish the relative importance of autistic traits and anxiety as predictors of demand avoidance, using dominance analysis. Both autistic traits and anxiety were unique and equally important predictors of demand avoidance. These findings suggest EDA is linked to autism and are consistent with the theory that demand avoidance behaviours are potentially anxiety-driven in adults.

Comparison of antimicrobial utilization metrics: Food for thought for an antimicrobial stewardship programme.

Given the overuse of antimicrobials and increasing antimicrobial resistance, the World Health Organization and Centers for Disease Control and Prevention recommend antimicrobial stewardship programmes to measure and assess the use of antimicrobials. Several antimicrobial use metrics have been described, including days of therapy, defined daily doses and standardized antimicrobial administration ratio. Understanding these metrics, including the advantages and disadvantages, can help antimicrobial stewardship programmes to monitor antimicrobial use at their institution, and assess the impact of antimicrobial stewardship efforts. This review discusses the three commonly used antimicrobial use metrics, their pros and cons, and how antimicrobial stewardship programmes can use these metrics to help assess the use of antimicrobials.

Desmoplastic ameloblastoma with mucous cell differentiation: A Rare case report.

Ameloblastomas are tumors arising from the odontogenic epithelium. Ninety cases of desmoplastic ameloblastoma have been reported so far in the literature, out of which only five cases with mucous cell differentiation have been reported. We are presenting a case of 24-year-old female having a chief complaint of a painless swelling on the left side of the face for 7 months. After radiological, histopathological findings lesion was diagnosed with unicystic ameloblastoma which was treated by segmental resection. The purpose of this article is to present a case of desmoplastic ameloblastoma that has occurred in an unusual site and has unique histopathological features.

The Next Frontier: Translational Development of Ubiquitination, SUMOylation, and NEDDylation in Cancer.

Post-translational modifications of proteins ensure optimized cellular processes, including proteostasis, regulated signaling, cell survival, and stress adaptation to maintain a balanced homeostatic state. Abnormal post-translational modifications are associated with cellular dysfunction and the occurrence of life-threatening diseases, such as cancer and neurodegenerative diseases. Therefore, some of the frequently seen protein modifications have been used as disease markers, while others are targeted for developing specific therapies. The ubiquitin and ubiquitin-like post-translational modifiers, namely, small ubiquitin-like modifier (SUMO) and neuronal precursor cell-expressed developmentally down-regulated protein 8 (NEDD8), share several features, such as protein structures, enzymatic cascades mediating the conjugation process, and targeted amino acid residues. Alterations in the regulatory mechanisms lead to aberrations in biological processes during tumorigenesis, including the regulation of tumor metabolism, immunological modulation of the tumor microenvironment, and cancer stem cell stemness, besides many more. Novel insights into ubiquitin and ubiquitin-like pathways involved in cancer biology reveal a potential interplay between ubiquitination, SUMOylation, and NEDDylation. This review outlines the current understandings of the regulatory mechanisms and assay capabilities of ubiquitination, SUMOylation, and NEDDylation. It will further highlight the role of ubiquitination, SUMOylation, and NEDDylation in tumorigenesis.

The Four-Item Mentalising Index (FIMI) is a valid, reliable, and practical way to assess mentalising: Reply to Murphy et al. (2022).

Murphy et al. (2022) raised concerns regarding the validity of the Four-Item Mentalising Index (FIMI). We wholeheartedly agree with Murphy et al. that there are problems in the social cognition literature hampering research. However, we maintain the FIMI is conceptually grounded in empirical and theoretical research, and that concerns regarding its construct validity are overstated. Drawing on recent research, we also discuss issues concerning the interpretation of discriminant validity analyses and discuss approaches to improve objectivity in future research. Overall, we argue that the FIMI is a conceptually and psychometrically sound measure, which has utility in future social cognition research and clinical practice. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Rethinking fast and slow processing in autism.

Following the popularity of dual process models in social and cognitive psychology, there is major interest in the possibility that autism is associated with impaired "fast" intuitive thinking but enhanced "slow" or "rational" deliberative thinking. If correct, this has great potential to help understand various strengths and difficulties characteristic of autism. Previous empirical investigations of this phenomenon, however, are marred by concerns about the measurement of intuitive and deliberative processing, as well as broader problems in clinical psychological science (e.g., small underpowered studies, lack of replication). Making a step change, we conducted four large-scale studies to examine dual processing in autism, including a preregistered comparison of 200 autistic and nonautistic adults. Participants completed contemporary cognitive and self-report measures of intuitive and deliberative processing, as well as a psychometrically robust measure of general cognitive ability. Except for lower self-reported intuitive thinking, we found no unique contributions of autism to intuitive or deliberative thinking across all four studies, as evidenced by frequentist and Bayesian analyses. Overall, these studies indicate that intuitive and deliberative thinking is neither enhanced nor particularly impaired in relation to autism. We deliberate on the implications of these findings for theories of autism and future investigation of strengths and difficulties in autistic people. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Comparative systeomics to elucidate physiological differences between CHO and SP2/0 cell lines.

Omics-based tools were coupled with bioinformatics for a systeomics analysis of two biopharma cell types: Chinese hamster ovary (M-CHO and CHO-K1) and SP2/0. Exponential and stationary phase samples revealed more than 10,000 transcripts and 6000 proteins across these two manufacturing cell lines. A statistical comparison of transcriptomics and proteomics data identified downregulated genes involved in protein folding, protein synthesis and protein metabolism, including PPIA-cyclophilin A, HSPD1, and EIF3K, in M-CHO compared to SP2/0 while cell cycle and actin cytoskeleton genes were reduced in SP2/0. KEGG pathway comparisons revealed glycerolipids, glycosphingolipids, ABC transporters, calcium signaling, cell adhesion, and secretion pathways depleted in M-CHO while retinol metabolism was upregulated. KEGG and IPA also indicated apoptosis, RNA degradation, and proteosomes enriched in CHO stationary phase. Alternatively, gene ontology analysis revealed an underrepresentation in ion and potassium channel activities, membrane proteins, and secretory granules including Stxbpt2, Syt1, Syt9, and Cma1 proteins in M-CHO. Additional enrichment strategies involving ultracentrifugation, biotinylation, and hydrazide chemistry identified over 4000 potential CHO membrane and secretory proteins, yet many secretory and membrane proteins were still depleted. This systeomics pipeline has revealed bottlenecks and potential opportunities for cell line engineering in CHO and SP2/0 to improve their production capabilities.