Development and Psychometric Properties of the Pain and Sensitivity Reactivity Scale in a Diverse Sample of Autistic People

Abstract: Background: Recent studies indicate the need to examine how the gut microbiota–brain axis is implicated in pain, sensory reactivity and gastro-intestinal symptoms in autism spectrum disorder (ASD), but no scale exists that assesses all these constructs simultaneously. Methods: We created a pool of 100 items based on the real-world experience of autistic people, and a multidisciplinary team and stakeholders reduced this pool to 50 items assessing pain, sensory hypersensitivity, and sensory hyposensitivity. In the present study, we present this new assessment tool, the Pain and Sensitivity Reactivity Scale (PSRS), and examine its psychometric properties in a sample of 270 individuals with autism spectrum disorder (ASD; mean age = 9.44, SD = 4.97), of which almost half (45%) had intellectual disability (ID). Results: A factorial model of three factors (pain, hyporeactivity, and hyperreactivity) and five specific factors for sensory hypo- and hyperreactivity, respectively, fitted the data well. Good to excellent internal consistency and adequate test–retest reliability was found for most PSRS scales. Sound psychometric properties were found in individuals with and without ID. Correlations with other measures of sensory sensitivity and pain indicated sound convergent validity. Conclusions: PSRS shows promise as a reliable measure to analyze pain and sensory reactivity in autistic people regardless of whether they have ID or not. The measure overcomes several limitations of previous assessment tools and includes variables that are important for the understanding of the gut microbiota–brain axis in ASD

Effects of cognitive-behavioral therapy on core aspects of anxiety in anxious youth with autism

Background: Anxiety disorders (ADs) are common in youth with autism and cognitive-behavioral therapy (CBT) may be less efficacious than among anxious youth without autism. Yet, little is known about which aspects of anxiety are targeted less effectively by CBT in youth with autism. Method: We pooled youth with autism and ADs randomized to CBT or a control condition from five randomized controlled trials (RCTs; CBT, n = 197, Mage = 10.30 [2.05], age range: 7–16; control conditions, n = 83; Mage = 10.57 [2.30], age range: 7–16) and examined whether CBT outperformed control conditions across core aspects of anxiety and whether more pronounced autism traits predicted outcomes. CBT response in youth with autism was also compared to CBT response among anxious youth without autism (n = 129; Mage = 11.16 [2.80], age range: 7–17). Results: CBT for youth with autism yielded significantly better effects than control conditions for frequency of symptoms, intensity of anxiety, avoidance, family interference, and social interference but not for physical symptoms of anxiety. Youth with more pronounced autism traits had poorer outcomes for frequency of symptoms, family interference, and social interference. Compared to anxious youth without autism, youth with autism had poorer outcomes for physical symptoms and family interference. Conclusions: CBT is efficacious across core aspects of anxiety for youth with autism, but outcomes for anxiety-related interference, particularly for those with more pronounced autism traits, may be poorer than among youth without autism. More work is needed to better understand how anxiety impacts the everyday lives of anxious youth with autism and which interventions and support are needed.Temple University. College of Liberal ArtsPsychology and Neuroscienc

Double Heterozygous Mutations Involving Both HNF1A/MODY3 and HNF4A/MODY1 Genes: A case report

none9Abstract We describe the first MODY case with mutations involving both HNF4A and HNF1A genes. History and Examination. A male patient was diagnosed with diabetes at age 17; the metabolic control rapidly worsened to insulin requirement. At that time no relatives were known to be affected by diabetes, which was diagnosed years later in both parents (father at age 50, mother at age 54) and the sister (age 32 during pregnancy). Investigations. The genetic screening showed a double heterozygosity for the mutation p.E508K in HNF1A/MODY3 gene and the novel variant p.R80Q in HNF4A/MODY1 gene. The genetic testing of the family showed that the father carried the MODY3 mutation while the mother, the sister and her two children carried the MODY1 mutation. Conclusions. MODY1 and MODY3 mutations may interact by chance to give a more severe form of diabetes (younger age at presentation, early need of insulin therapy to control hyperglycemia).mixedG. Forlani; S. Zucchini; A. Di Rocco; R. Di Luzio; M. Scipione; E. Marasco; G. Romeo; G. Marchesini Reggiani; V. MantovaniG. Forlani; S. Zucchini; A. Di Rocco; R. Di Luzio; M. Scipione; E. Marasco; G. Romeo; G. Marchesini Reggiani; V. Mantovan

GM1 ganglioside-independent intoxication by Cholera toxin

Cholera toxin (CT) enters and intoxicates host cells after binding cell surface receptors via its B subunit (CTB). We have recently shown that in addition to the previously described binding partner ganglioside GM1, CTB binds to fucosylated proteins. Using flow cytometric analysis of primary human jejunal epithelial cells and granulocytes, we now show that CTB binding correlates with expression of the fucosylated Lewis X (LeX) glycan. This binding is competitively blocked by fucosylated oligosaccharides and fucose-binding lectins. CTB binds the LeX glycan in vitro when this moiety is linked to proteins but not to ceramides, and this binding can be blocked by mAb to LeX. Inhibition of glycosphingolipid synthesis or sialylation in GM1-deficient C6 rat glioma cells results in sensitization to CT-mediated intoxication. Finally, CT gavage produces an intact diarrheal response in knockout mice lacking GM1 even after additional reduction of glycosphingolipids. Hence our results show that CT can induce toxicity in the absence of GM1 and support a role for host glycoproteins in CT intoxication. These findings open up new avenues for therapies to block CT action and for design of detoxified enterotoxin-based adjuvants

Impaired Mitochondrial Function and Insulin Resistance of Skeletal Muscle in Mitochondrial Diabetes

OBJECTIVE - Impaired muscular mitochondrial function is related to common insulin resistance in type 2 diabetes. Mitochondrial diseases frequently lead to diabetes, which is mostly attributed to defective beta-cell mitochondria and secretion. RESEARCH DESIGN AND METHODS - We assessed muscular mitochondrial function and lipid deposition in liver (hepatocellular lipids [HCLs]) and muscle (intramyocellular lipids [IMCLs]) using P-31/H-1 magnetic resonance spectroscopy and insulin sensitivity and endogenous glucose production (EGP) using hyperinsulinemic-euglycemic clamps combined with isotopic tracer dilution in one female patient suffering from MELAS(myopathy,encephalopathy, lactic acidosis, and stroke-like episodes) syndrome and in six control subjects. RESULTS - The MELAS patient showed impaired insulin sensitivity (4.3 vs. 8.6 +/- 0.5 mg . kg(-1) . min(-1)) and suppression of EGP (69 vs. 94 +/- 1%), and her baseline and insulin-stimulated ATP synthesis were reduced (7.3 and 8.9 vs. 10.6 +/- 1.0 and 12.8 +/- 1.3 mu mol . l(-1) . min(-1)) compared with those of the control subjects. HCLs and IMCLs were comparable between the MELAS patient and control subjects. CONCLUSIONS - Impairment of muscle mitochondrial fitness promotes insulin resistance and could thereby contribute to the development of diabetes in some patients with the MELAS syndrome

Network Analysis Reveals Unique Associations of Mindfulness and Distress with Immunity in Māori and Non-Māori New Zealanders

Objectives: A healthy immune system is required to protect against viral infection and ensure the efficacy of vaccines. Psychological distress can threaten immune resilience, while mindfulness practices can be protective. In New Zealand, Māori experience significantly higher levels of distress compared to non-Māori. The aim of this study was to explore the role of ethnicity in the relations among immunity, depression, anxiety, stress, and mindfulness relate to each other. Method: Network analysis was used to explore unique relations among distress (depression, anxiety, stress), mindfulness facets, and immune status in matched (age, ranging from 19 to 88 years, sex, and self-classified socio-economic status) samples of Māori (n=195) and non-Māori (n=195) participants from New Zealand. Results: The networks of distress, mindfulness, and immune status were significantly different between Māori and non-Māori participants. The mindfulness facets Describe and Act with Awareness were more strongly positively linked in Māori, and Non-judge and Depression more strongly negatively linked in Māori, while Describe and Non-judge were more strongly positively linked in non-Māori. For both Māori and non-Māori, similarities included a negative link between anxiety and immune status, strong positive links between the distress variables, and positive links between the mindfulness facets of Non-judge and Act with Awareness, Observe and Non-React, and Observe and Describe. Conclusions: These findings suggest that anxiety is strongly linked to poor immunity across both Māori and non-Māori in New Zealand while networks of mindfulness and distress also demonstrated differences unique for each of these groups. Both similarities and differences between Māori and non-Māori should be considered when developing targeted interventions to improve physical and mental health in New Zealand. Preregistration: This study is not preregistered

Urinary C-Peptide Creatinine Ratio Is a Practical Outpatient Tool for Identifying Hepatocyte Nuclear Factor 1-α/Hepatocyte Nuclear Factor 4-α Maturity-Onset Diabetes of the Young From Long-Duration Type 1 Diabetes

Hepatocyte nuclear factor 1-α (HNF1A)/hepatocyte nuclear factor 4-α (HNF4A) maturity-onset diabetes of the young (MODY) is frequently misdiagnosed as type 1 diabetes, and patients are inappropriately treated with insulin. Blood C-peptide can aid in the diagnosis of MODY, but practical reasons limit its widespread use. Urinary C-peptide creatinine ratio (UCPCR), a stable measure of endogenous insulin secretion, is a noninvasive alternative. We aimed to compare stimulated UCPCR in adults with HNF1A/4A MODY, type 1 diabetes, and type 2 diabetes.RD&E staff can access the full-text of this article via OpenAthens. Click on the 'Additional Link' above to access the full-text and log in with NHS OpenAthens if prompted.PDA/02/06/098/Department of Health/United Kingdo