Pubmed du 08/09/23

Pubmed du jour

1. Bahry S, Gerhardt PF, Weiss MJ, Leaf JB, Putnam RF, Bondy A. The Ethics of Actually Helping People: Targeting Skill Acquisition Goals That Promote Meaningful Outcomes for Individuals with Autism Spectrum Disorder. Behavior analysis in practice. 2023; 16(3): 672-95.

As a field that predominately supports individuals with autism spectrum disorder (ASD), we have an ethical duty as behavior analysts to ensure that the goals we write and interventions we prescribe promote best outcomes across the lifespan. This is critical, given that as it stands now, outcomes in adulthood for individuals with ASD are poor in every area assessed. The Ethics Code for Behavior Analysts can be interpreted to provide support for teaching the right goals, the right way, with respect to inherent rights of those we serve, in order to help affect positive changes in these outcomes. The present article highlights ethical themes that are relevant in order to affect these changes that are supported by the Code, as well as actionable steps to take next. The aim is to provide a resource for practitioners to use in clinical practice and in making ethical decisions that will help to improve outcomes for individuals with autism in adulthood. In addition, recommendations are made about integrating these values and approaches in terms of training, supervision, advocacy, and research.

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2. Chan DV, Doran JD. Mental health counseling is rated as most helpful by autistic adults: Service perspectives in adulthood. Autism : the international journal of research and practice. 2023: 13623613231197446.

The number of autistic adults is growing, but there are fewer services to support them in adulthood. Many autistic adults need some support services to lead successful adult lives. We know a lot about the services autistic adults use and some of the problems with using these services, but we do not know which services are most helpful to them and how the services they use relate to how they interact with their communities. Forty autistic adults took part in a study about service use and community participation. They completed surveys, interviews, and carried a global positioning system tracker. They answered questions about which services are most helpful in adulthood, things that make it hard to use services, and what services they needed. Most participants used two services in the past 2 years, most frequently mental health and employment services. Adults who were currently seeing a mental health counselor were more likely to be working full-time and visit more locations in the community compared to those who were not seeing a counselor. Mental health services were reported as the most helpful service they received as adults, followed by employment services. We often focus on the importance of employment services after high school, but our findings show a need for both mental health and employment services for autistic adults.

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3. Delgado C, Ullery MA, Zeng G, Simpson EA, Tanner JP, Kirby RS, Duclos C, Lowry J, Salemi JL. Elevated risk for developmental disabilities in children with congenital heart defects. Birth defects research. 2023.

BACKGROUND: This study examined risk for developmental disabilities in preschool-aged children with a congenital heart defect (CHD) at the population level. METHODS: Statewide birth, birth defects, and preschool developmental disability records were integrated. The final sample included 1,966,585 children (51.0% male). Children were grouped by type(s) of CHD: critical CHD, noncritical CHD, atrial septal defect, or no major birth defects (groups were mutually exclusive). RESULTS: Children with a CHD (any type) were at increased risk for developmental disability (any type) (RR 2.08, 95% CI 2.03-2.14, P < .001). Children in the critical CHD, noncritical CHD, and atrial septal defect groups were at increased risk for developmental delay, intellectual disability, language impairment, other health impairment, and any disability. Children in the atrial septal defect group were at increased risk for autism spectrum disorder and speech impairment. For all CHD groups, risk was greatest for other health impairment and intellectual disability. CONCLUSIONS: Increased risk for developmental disabilities was identified for children with less severe CHDs as well as for children with more severe (critical) CHDs. All children with CHDs should be closely monitored so that appropriate interventions can be initiated as early as possible to maximize learning outcomes.

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4. Ellis R, Williams K, Brown A, Healer E, Grant A. A realist review of health passports for Autistic adults. PloS one. 2023; 18(9): e0279214.

BACKGROUND: Autism is a normal part of cognitive diversity, resulting in communication and sensory processing differences, which can become disabling in a neurotypical world. Autistic people have an increased likelihood of physical and mental co-occurring conditions and die earlier than neurotypical peers. Inaccessible healthcare may contribute to this. Autism Health Passports (AHPs) are paper-based or digital tools which can be used to describe healthcare accessibility needs; they are recommended in UK clinical guidance. However, questions remained as to the theoretical underpinnings and effectiveness of AHPs. METHODS: We undertook a systematic literature search identifying studies focused on AHPs for adults (aged over 16 years) from five databases. Included literature was subjected to realist evaluation. Data were extracted using a standardised form, developed by the research team, which considered research design, study quality for realist review and the Context, Mechanisms and Outcomes (CMOs) associated with each AHP tool. FINDINGS: 162 unique records were identified, and 13 items were included in the review. Only one item was considered high quality. Contextual factors focused on the inaccessibility of healthcare to Autistic patients and staff lack of confidence and training in supporting Autistic needs. Interventions were heterogeneous, with most sources reporting few details as to how they had been developed. The most frequently included contents were communication preferences. Mechanisms were often not stated or were inferred by the reviewers and lacked specificity. Outcomes were included in four studies and were primarily focused on AHP uptake, rather than Outcomes which measured impact. CONCLUSION: There is insufficient evidence to conclude that AHPs reduce the health inequalities experienced by Autistic people. Using an AHP tool alone in a healthcare Context that does not meet Autistic needs, without the inclusion of the local Autistic community developing the tool, and a wider intervention to reduce known barriers to health inequality, may mean that AHPs do not trigger any Mechanisms, and thus cannot affect Outcomes.

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5. George FSA, Sam LE, Tanwar M, Wall L. Association of autism spectrum disorder with Waardenburg syndrome in a toddler. BMJ case reports. 2023; 16(9).

Waardenburg syndrome is a rare genetic condition with an incidence of 1 in 212 000. The condition is classically associated with distinctive facial features, congenital hearing loss and pigmentary changes of the hair, iris and skin. There is a paucity of literature about the association of neurodevelopmental conditions with this syndrome. We present a toddler with Waardenburg syndrome type 1 who was referred to our service for developmental delay concerns. The child was diagnosed with the condition at birth, had distinctive facial features, but the hearing was normal. The child’s father also shares a similar mutation. Following a multidisciplinary assessment, the child was diagnosed to have autism spectrum disorder with possible regression. We acknowledge that there may not be a causal relationship between autism spectrum and Waardenburg syndrome. However, this highlights the need for developmental surveillance among children diagnosed with Waardenburg syndrome and to consider its association with neurodevelopmental conditions.

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6. Nemati S, Shojaeian N, Bardel M, Deetjen-Ruiz R, Khani Z, McHugh L. Exploring the Variables of the Psychological Well-Being of Mothers of Children with Autism Spectrum Disorder Through Self-Compassion and Psychological Hardiness. Journal of autism and developmental disorders. 2023.

Present study aimed to evaluate the relationship between self-compassion and psychological hardiness, and psychological well-being among mothers of children with autism. The research design was correlational, and its statistical population sample consisted of 101 mothers of children with an autism spectrum disorder. The results of a correlational analysis showed a significant positive relationship between self-compassion and psychological hardiness, and psychological well-being. Multiple regression analysis showed that among the variables of self-compassion and psychological hardiness, the variable of self-compassion had the largest share in predicting the psychological well-being of mothers. Concerning self-compassion, conscious awareness of self-kindness along with psychological hardship could predict the psychological well-being in these groups of mothers, such as raising a child with ASD.

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7. Oshima F, Mandy W, Seto M, Hongo M, Tsuchiyagaito A, Hirano Y, Sutoh C, Guan S, Nitta Y, Ozawa Y, Kawasaki Y, Ohtani T, Masuya J, Takahashi N, Sato N, Nakamura S, Nakagawa A, Shimizu E. Cognitive behavior therapy for autistic adolescents, awareness and care for my autistic traits program: a multicenter randomized controlled trial. BMC psychiatry. 2023; 23(1): 661.

BACKGROUND: Autistic people demonstrate focused interests, sensitivity to sensory stimulation, and, compared with the general population, differences in social communication and interaction. We examined whether a combination of the Awareness and Care for My Autistic Traits (ACAT) program and treatment-as-usual is more effective than only treatment-as-usual in increasing the understanding of autistic attributes, reducing treatment stigma, and improving mental health and social adaptation among autistic adolescents and their parents/guardians. METHODS: Forty-nine adolescents and their parents/guardians were randomly assigned to either a combination of ACAT and treatment-as-usual or only treatment-as-usual. The combined group received six weekly 100-minute ACAT sessions, while the treatment-as-usual group received no additional intervention. The primary outcome was the change in understanding of autistic attributes (Autism Knowledge Quiz-Child), administered from pre- to post-intervention. The secondary outcomes included the change in Autism Knowledge Quiz-Parent, reduced treatment stigma, and improved mental health and social adaptation among autistic adolescents and their parents/guardians. A primary outcome measure scale was scored by assessors who were blind to the group assignment. RESULTS: The combined group (both autistic adolescents and their parents/guardians) showed an increase in Autism Knowledge Quiz scores compared to those in the treatment-as-usual group. Autistic adolescents in the combined group also demonstrated a decrease in treatment-related stigma and an improvement in general mental health compared to those in the treatment-as-usual group, while there were no group differences in the change in social adaptation. For parents/guardians, there were no group differences in the change in treatment-related stigma, general mental health, adaptive skills, or attitudes toward their children. CONCLUSIONS: The ACAT program could be an effective treatment modality to increase the understanding of autistic attributes among both autistic adolescents and their parents/guardians. The ACAT program positively affects self-understanding, reduces treatment stigma, and stabilizes behavioral issues for autistic adolescents as a part of mental health measures, but it does not effectively reduce treatment barriers or improve mental health for parents/guardians. Further research should consider whether additional support for parents/guardians could be beneficial. TRIAL REGISTRATION: The study was registered in UMIN (UMIN000029851, 06/01/2018).

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8. Persicke A, Najdowski AC, Tarbox J, St Clair M. Teaching Children with Autism Spectrum Disorder Desire-Based Emotion Prediction and Cause. Behavior analysis in practice. 2023; 16(3): 826-36.

This study aimed to expand current research in one area of perspective taking related to teaching children with autism spectrum disorder to predict others’ emotions. The current study evaluated a behavioral teaching procedure on predicting and inferring the cause of emotions based on another’s desires. The procedure included a training package including multiple-exemplar training, rules, modeling, prompting, and reinforcement across scenarios in which children with autism were asked to predict how others may feel given a met or unmet desire or nondesire. Three children with autism, who did not already demonstrate this skill at baseline, were included in the study and learned a repertoire of emotion prediction and cause that generalized to untrained novel scenarios. Generalization to situations in which it was necessary to apply information about another’s desires during play activities was not observed until direct in-vivo training was implemented. Future directions and implications of this research are discussed.

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9. Salcedo-Arellano MJ, Johnson MD, McLennan YA, Hwang YH, Juarez P, McBride EL, Pantoja AP, Durbin-Johnson B, Tassone F, Hagerman RJ, Martínez-Cerdeño V. Brain Metabolomics in Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). Cells. 2023; 12(17).

The course of pathophysiological mechanisms involved in fragile X-associated tremor/ataxia syndrome (FXTAS) remains largely unknown. Previous proteomics and metabolomics studies conducted in blood samples collected from FMR1 premutation carriers with FXTAS reported abnormalities in energy metabolism, and precursors of gluconeogenesis showed significant changes in plasma expression levels in FMR1 premutation carriers who developed FXTAS. We conducted an analysis of postmortem human brain tissues from 44 donors, 25 brains with FXTAS, and 19 matched controls. We quantified the metabolite relative abundance in the inferior temporal gyrus and the cerebellum using untargeted mass spectrometry (MS)-based metabolomics. We investigated how the metabolite type and abundance relate to the number of cytosine-guanine-guanine (CGG) repeats, to markers of neurodegeneration, and to the symptoms of FXTAS. A metabolomic analysis identified 191 primary metabolites, the data were log-transformed and normalized prior to the analysis, and the relative abundance was compared between the groups. The changes in the relative abundance of a set of metabolites were region-specific with some overlapping results; 22 metabolites showed alterations in the inferior temporal gyrus, while 21 showed differences in the cerebellum. The relative abundance of cytidine was decreased in the inferior temporal gyrus, and a lower abundance was found in the cases with larger CGG expansions; oleamide was significantly decreased in the cerebellum. The abundance of 11 metabolites was influenced by changes in the CGG repeat number. A histological evaluation found an association between the presence of microhemorrhages in the inferior temporal gyrus and a lower abundance of 2,5-dihydroxypyrazine. Our study identified alterations in the metabolites involved in the oxidative-stress response and bioenergetics in the brains of individuals with FXTAS. Significant changes in the abundance of cytidine and oleamide suggest their potential as biomarkers and therapeutic targets for FXTAS.

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10. Spellun A, Herlihy M, Taketa E, Graham A, Fasano-McCarron M, Hasenbalg S, Clark T, Linnea K, Isquith P, Landsman R. Diagnostic Utility of Parent Ratings on the Behavior Assessment System for Children-Third Edition in Children who are Deaf and Hard of Hearing and Diagnosed with Autism Spectrum Disorder. Research on child and adolescent psychopathology. 2023.

Between 1 to 2 of every 1,000 children are born deaf or hard of hearing (DHH) and, of those, 30-50% have additional disabilities, including Autism Spectrum Disorder (ASD). Most measures assessing ASD characteristics rely on some degree of behavioral response to sound (e.g., responding to name, listening response), and may not be appropriate for use with children who are DHH. Further, ASD specific measures do not provide information on a child’s functional abilities across developmental domains. We conducted a cross-sectional analysis comparing mean T-scores on a standardized multidimensional measure, the Behavior Assessment System for Children, Third Edition, Parent Rating Scale (BASC-3 PRS), across three groups matched for age and sex: children who are DHH and diagnosed with ASD (DHH + ASD; n = 16); children who are DHH without ASD (DHH-ASD; n = 16); and children who are typically hearing with ASD (H + ASD; n = 16). Analyses revealed statistically significant differences across scales of Attention Problems, Atypicality, Withdrawal, Behavioral Symptoms Index, Social Skills, Leadership, Functional Communication, Activities of Daily Living, Adaptive Skills, Autism Probability Indices, and Developmental Social Disorders. Pairwise comparisons showed DHH + ASD and H + ASD mean T-scores were statistically similar and distinct from DHH-ASD mean T-scores on all these scales except for Withdrawal, Leadership, Functional Communication, and Activities of Daily Living, where pairwise comparisons varied. The findings add to the literature on ASD and DHH children and call for further exploration of the BASC-3 as a tool for both evaluation of ASD and the development of individualized treatment plans in this unique population.

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11. St Clair M, Najdowski AC, Welsh F, Simchoni L, Milne CM, Fullen JA, Acuña B, Suarez VD. Teaching Children with Autism to Identify Known and Unknown Information across Self and Others. Behavior analysis in practice. 2023; 16(3): 837-48.

This study evaluated procedures for teaching three children diagnosed with autism spectrum disorder the perspective-taking skill of identifying known and unknown information by others based on what they were sensing across all five senses: see, taste, feel, hear, and smell. Using a multiple baseline across participants design, this study evaluated a training package consisting of rules, multiple exemplar training, error correction, and reinforcement. The treatment package successfully taught participants to identify known/unknown information based on what individuals sensed. Generalization across untrained stimuli and people was observed from baseline to posttraining for all participants.

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12. Szakats S, McAtamney A, Cross H, Wilson MJ. Sex-biased gene and microRNA expression in the developing mouse brain is associated with neurodevelopmental functions and neurological phenotypes. Biology of sex differences. 2023; 14(1): 57.

BACKGROUND: Sex differences pose a challenge and an opportunity in biomedical research. Understanding how sex chromosomes and hormones affect disease-causing mechanisms will shed light on the mechanisms underlying predominantly idiopathic sex-biased neurodevelopmental disorders such as ADHD, schizophrenia, and autism. Gene expression is a crucial conduit for the influence of sex on developmental processes; therefore, this study focused on sex differences in gene expression and the regulation of gene expression. The increasing interest in microRNAs (miRNAs), small, non-coding RNAs, for their contribution to normal and pathological neurodevelopment prompted us to test how miRNA expression differs between the sexes in the developing brain. METHODS: High-throughput sequencing approaches were used to identify transcripts, including miRNAs, that showed significantly different expression between male and female brains on day 15.5 of development (E15.5). RESULTS: Robust sex differences were identified for some genes and miRNAs, confirming the influence of biological sex on RNA. Many miRNAs that exhibit the greatest differences between males and females have established roles in neurodevelopment, implying that sex-biased expression may drive sex differences in developmental processes. In addition to highlighting sex differences for individual miRNAs, gene ontology analysis suggested several broad categories in which sex-biased RNAs might act to establish sex differences in the embryonic mouse brain. Finally, mining publicly available SNP data indicated that some sex-biased miRNAs reside near the genomic regions associated with neurodevelopmental disorders. CONCLUSIONS: Together, these findings reinforce the importance of cataloguing sex differences in molecular biology research and highlight genes, miRNAs, and pathways of interest that may be important for sexual differentiation in the mouse and possibly the human brain. In biomedical research, understanding the differences between males and females is essential for understanding diseases that affect one sex more than the other. This study focused on gene expression and regulation differences between male and female mouse brains during development. We found that many microRNAs, small molecules that play a role in development were expressed differently between male and female brains. These differences could be important in understanding why males and females develop differently, particularly regarding neurodevelopmental disorders like ADHD, schizophrenia, and autism. We also found that some microRNAs that differed between males and females were located near genes associated with these disorders. Overall, the study highlights the importance of understanding sex differences in molecular biology research and provides insights into potential genes and pathways of interest for further study. eng.

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13. Utami KH, Yusof N, Garcia-Miralles M, Skotte NH, Nama S, Sampath P, Langley SR, Pouladi MA. Dysregulated COMT Expression in Fragile X Syndrome. Neuromolecular medicine. 2023.

Transcriptional and proteomics analyses in human fragile X syndrome (FXS) neurons identified markedly reduced expression of COMT, a key enzyme involved in the metabolism of catecholamines, including dopamine, epinephrine and norepinephrine. FXS is the most common genetic cause of intellectual disability and autism spectrum disorders. COMT encodes for catechol-o-methyltransferase and its association with neuropsychiatric disorders and cognitive function has been extensively studied. We observed a significantly reduced level of COMT in in FXS human neural progenitors and neurons, as well as hippocampal neurons from Fmr1 null mice. We show that deficits in COMT were associated with an altered response in an assay of dopaminergic activity in Fmr1 null mice. These findings demonstrate that loss of FMRP downregulates COMT expression and affects dopamine signaling in FXS, and supports the notion that targeting catecholamine metabolism may be useful in regulating certain neuropsychiatric aspects of FXS.

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14. Valizadeh A, Moassefi M, Nakhostin-Ansari A, Heidari Some’eh S, Hosseini-Asl H, Saghab Torbati M, Aghajani R, Maleki Ghorbani Z, Menbari-Oskouie I, Aghajani F, Mirzamohamadi A, Ghafouri M, Faghani S, Memari AH. Automated diagnosis of autism with artificial intelligence: State of the art. Reviews in the neurosciences. 2023.

Autism spectrum disorder (ASD) represents a panel of conditions that begin during the developmental period and result in impairments of personal, social, academic, or occupational functioning. Early diagnosis is directly related to a better prognosis. Unfortunately, the diagnosis of ASD requires a long and exhausting subjective process. We aimed to review the state of the art for automated autism diagnosis and recognition in this research. In February 2022, we searched multiple databases and sources of gray literature for eligible studies. We used an adapted version of the QUADAS-2 tool to assess the risk of bias in the studies. A brief report of the methods and results of each study is presented. Data were synthesized for each modality separately using the Split Component Synthesis (SCS) method. We assessed heterogeneity using the I (2) statistics and evaluated publication bias using trim and fill tests combined with ln DOR. Confidence in cumulative evidence was assessed using the GRADE approach for diagnostic studies. We included 344 studies from 186,020 participants (51,129 are estimated to be unique) for nine different modalities in this review, from which 232 reported sufficient data for meta-analysis. The area under the curve was in the range of 0.71-0.90 for all the modalities. The studies on EEG data provided the best accuracy, with the area under the curve ranging between 0.85 and 0.93. We found that the literature is rife with bias and methodological/reporting flaws. Recommendations are provided for future research to provide better studies and fill in the current knowledge gaps.

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15. Walton KM, Borowy AR, Gordon RA, Wainer AL. Enhancing stakeholder roles in autism early interventions in the United States: A stakeholder-driven research agenda. Autism : the international journal of research and practice. 2023: 13623613231195743.

In this article, we outline a stakeholder-driven research agenda to guide future early intervention research for children with autism. Our research team collaborated with autism service providers, parents of individuals with autism, and autistic people to create this research agenda by (1) conducting workshops with community members and (2) distributing a survey to a larger number of community members around the country. The finalized research agenda includes (1) Guiding Principles for current and future research, (2) Research Priorities focused on early intervention for individuals with autism, and (3) Systems Implications to consider in future clinical, research, and policy efforts for early intervention. The full version of the research agenda is available in Supplemental Material. This article lists the main points of the research agenda and discusses unique themes highlighted by the community members. One main conclusion is that researchers need to include community members in decision-making and consultant positions throughout the research process to best meet the needs of the broader autism community. We have created a researcher workbook which we hope may facilitate these community consultation efforts. This workbook is available in Supplemental Material.

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16. Wang X, Zhao Z, Guo J, Mei D, Duan Y, Zhang Y, Gou L. GABA(B1) receptor knockdown in prefrontal cortex induces behavioral aberrations associated with autism spectrum disorder in mice. Brain research bulletin. 2023; 202: 110755.

Autism spectrum disorder (ASD) is a set of heterogeneous neurodevelopmental disorders, characterized by social interaction deficit, stereotyped or repetitive behaviors. Apart from these core symptoms, a great number of individuals with ASD exhibit higher levels of anxiety and memory deficits. Previous studies demonstrate pronounced decrease of γ-aminobutyric acid B1 receptor (GABA(B1)R) protein level of frontal lobe in both ASD patients and animal models. The aim of the present study was to determine the role of GABA(B1)R in ASD-related behavioral aberrations. Herein, the protein and mRNA levels of GABA(B1)R in the prefrontal cortex (PFC) of sodium valproic acid (VPA)-induced mouse ASD model were determined by Western blot and qRT-PCR analysis, respectively. Moreover, the behavioral abnormalities in naive mice with GABA(B1)R knockdown mediated by recombinant adeno-associated virus (rAAV) were assessed in a comprehensive test battery consisted of social interaction, marble burying, self-grooming, open-field, Y-maze and novel object recognition tests. Furthermore, the action potential changes induced by GABA(B1)R deficiency were examined in neurons within the PFC of mouse. The results show that the mRNA and protein levels of GABA(B1)R in the PFC of prenatal VPA-induced mouse ASD model were decreased. Concomitantly, naive mice with GABA(B1)R knockdown exhibited ASD-like behaviors, such as impaired social interaction and communication, elevated stereotypes, anxiety and memory deficits. Patch-clamp recordings also revealed that GABA(B1)R knockdown provoked enhanced neuronal excitability by increasing action potential discharge frequencies. Overall, these findings support a notion that GABA(B1)R deficiency might contribute to ASD-like phenotypes, with the pathogenesis most likely resulting from enhanced neuronal excitability. SUBHEADINGS: GABA(B1) Knockdown Induces Behavioral Aberrations with ASD.

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17. Watts R, Archibald T, Hembry P, Howard M, Kelly C, Loomes R, Markham L, Moss H, Munuve A, Oros A, Siddall A, Rhind C, Uddin M, Ahmad Z, Bryant-Waugh R, Hübel C. The clinical presentation of avoidant restrictive food intake disorder in children and adolescents is largely independent of sex, autism spectrum disorder and anxiety traits. EClinicalMedicine. 2023; 63: 102190.

BACKGROUND: Avoidant restrictive food intake disorder (ARFID) is a new eating disorder with a heterogeneous clinical presentation. It is unclear which patient characteristics contribute to its heterogeneity. METHODS: To identify these patient characteristics, we performed symptom-level correlation and driver-level regression analyses in our cross-sectional study in up to 261 ARFID patients (51% female; median age = 12.7 years) who were assessed at the Maudsley Centre for Child and Adolescent Eating Disorders, London between November 2019 and July 2022. FINDINGS: Symptoms across the three drivers 1) avoidance based on sensory characteristics of food; 2) apparent lack of interest in eating; and 3) concern about aversive consequences positively correlated with each other. Patients’ anxiety traits showed the greatest positive correlations with symptoms of concern about aversive consequences of eating. Patient sex was not significantly associated with any of the three ARFID drivers. Patients with comorbid autism spectrum disorder (ASD; 28%) showed more food-related sensory sensitivities (RR = 1.26) and greater lack of interest in eating (RR = 1.18) than those of patients without ASD (49%). INTERPRETATION: In our clinical sample, the ARFID drivers occurred together and did not show clinically meaningful differences between the sexes. ASD may accentuate food-related sensory sensitivities and lack of interest, but may not drive a completely different symptom presentation. ARFID is multi-faceted and heterogenous, requiring a comprehensive multidisciplinary assessment to sufficiently understand the drivers of the restrictive eating behaviour. Results need replication in larger samples with more statistical power. FUNDING: None.

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18. Wolbert F, Luebbert C, Sadowski G. The shelf life of ASDs: 2. Predicting the shelf life at storage conditions. International journal of pharmaceutics: X. 2023; 6: 100207.

Amorphous solid dispersions (ASDs) are a widely used formulation technology for poorly water-soluble active pharmaceutical ingredients (API). Depending on the API-polymer combination and API load in the ASD, the amorphous API might be thermodynamically metastable and crystallize over time. The crystallization onset is one critical factor that can define the shelf life of the ASD. Thus, for ASD formulations, long-term stability against crystallization of the API is of particular interest. This work presents a method for predicting the long-term physical stability of ASDs (crystallization onset time). The new approach combines the Johnson-Mehl-Avrami-Kolmogorov (JMAK) equation with classical nucleation theory. The shelf life predicted using the new approach depends on supersaturation (determined with PC-SAFT), viscosity (determined with WLF equation or Arrhenius equation) and two specific model parameters k’ and B. The latter were fitted to a few fast crystallization-kinetics measurements above the glass transition of the ASD. An additional crystallization-kinetics measurement below the glass-transition temperature of the ASD was used to determine the Arrhenius parameters. Once all parameters are determined for a given API/polymer combination and manufacturing method, they are valid for any API load, temperature, and RH. The proposed approach allows predicting the shelf life (crystallization onset) of a potential ASD in early stage of development within a few days. It was successfully verified for ASDs stored at 25 °C and 10% RH or 60% RH.

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19. Ziliotto M, Kulmann-Leal B, Kaminski VL, Nunes GT, Riesgo RDS, Roman T, Schuch JB, Chies JAB. HLA-G*14 bp indel variant in autism spectrum disorder in a population from southern Brazil. Journal of neuroimmunology. 2023; 383: 578194.

Altered immune response during pregnancy has been associated with ASD susceptibility. HLA-G is expressed by the trophoblast at the maternal/fetal interface and induces allogenic tolerance toward the fetus. A 14-bp insertion in the HLA-G 3’UTR (rs371194629) was associated with reduced levels of HLA-G. We aimed to assess the influence of the HLA-G*14 bp indel variant in ASD susceptibility and symptomatology in a Brazilian admixed sample. The insertion genotype (14 bp+/14 bp+) was firstly associated with hetero aggression, but statistical significance was lost after correction (p = 0.035, p(corrected) = 0.35). No association between the HLA-G variant and susceptibility to ASD or differential clinical manifestations were observed.

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