Difficulties in Emotion Regulation in Avoidant/Restrictive Food Intake Disorder.

OBJECTIVE: Despite substantial research indicating difficulties with emotion regulation across eating disorder presentations, emotion regulation has yet to be studied in adults with avoidant/restrictive food intake disorder (ARFID). We hypothesized that (1) those with ARFID would report greater overall emotion regulation difficulties than nonclinical participants, and (2) those with ARFID would not differ from those with other eating disorders on the level of emotion regulation difficulty. METHODS: One hundred and thirty-seven adults (age 18-30) from an outpatient clinic with ARFID (n = 27), with other primarily restrictive eating disorders (e.g., anorexia nervosa; n = 34), and with binge/purge eating disorders (e.g., bulimia nervosa; n = 51), as well as nonclinical participants (n = 25) recruited via Amazon Mechanical Turk (MTurk) completed the Difficulties in Emotion Regulation Scale (DERS). We compared DERS scores across groups. RESULTS: In line with expectations, patients with ARFID scored significantly higher than nonclinical participants on the DERS Total (p = 0.01) with a large effect size (d = 0.87). Also as hypothesized, those with ARFID did not differ from those with other primarily restrictive (p = 0.99) or binge/purge disorders (p = 0.29) on DERS Total. DISCUSSION: Adults with ARFID appear to exhibit emotion regulation difficulties which are greater than nonclinical participants, and commensurate with other eating disorders. These findings highlight the possibility of emotion regulation difficulties as a maintenance mechanism for ARFID.

Transitions of care for adolescents with disorders of gut-brain interaction.

OBJECTIVES: Little is known about the experience of adolescents and young adults (AYA) with disorders of gut-brain interaction (DGBI) who transition from pediatric to adult gastroenterology care. In this two-part study, we used quantitative and qualitative methods to: (1) assess incidence of optimal versus suboptimal transitions of care for AYA with DGBI, (2) characterize health and quality of life effects of the transition, and (3) identify barriers and facilitators for optimal transition of care. METHODS: In Part 1, we conducted a retrospective review of AYA referrals to our adult neurogastroenterology clinic who had transitioned from pediatric gastroenterology care (N = 109, 17-23 years, 72% female). We collected demographic, psychosocial, and healthcare utilization data to determine rate and risk factors for suboptimal transitions. In Part 2, we recruited 24 AYA and parents (n = 19 AYA, n = 5 parents) for completion of a survey and semistructured interview, which was analyzed using validated rapid qualitative analysis method. RESULTS: In Part 1, 20% (22/109) of AYA met the criteria for suboptimal transition of care, which was associated with treatment adherence concern and functional impairment. In Part 2, we identified two principal themes: (1) AYA's health and quality of life are impacted during the transition, and (2) parental involvement and collaboration with pediatric gastrointestinal (GI) are facilitators to successful transitions, whereas access to care and practice style change are barriers. CONCLUSION: AYA with DGBI have high rates of suboptimal care transitions, affecting their health and quality of life. Our study highlights the need for a comprehensive approach that incorporates parents and pediatric providers.

Low Prevalence of Reporting of Participant Race and Ethnicity in Gastroenterology Research Publications.

INTRODUCTION: Empirical information on the evolution of reporting race and ethnicity information in gastroenterology research is lacking. To facilitate understanding of where improvements are needed to increase diversity, equity, and inclusion in gastroenterology research, we aimed to evaluate reporting and representation by race and ethnicity in studies published in flagship US-based gastroenterology journals over 20 years. METHODS: We manually reviewed reporting and representation by race and ethnicity in all original research articles published in the American Journal of Gastroenterology and Gastroenterology in 2000, 2010, and 2020. RESULTS: Of 1,168 publications, 24% reported information on race/ethnicity, significantly more commonly reported in US-based study samples vs non-US-based samples. While reporting significantly increased over time, reporting rates were still low as of 2020 (37% overall; 54% with US-based samples). DISCUSSION: We recommend that gastroenterology journals create standard reporting requirements for sociodemographic information, including information on race, ethnicity, and/or cultural background.

Maladaptive weight control and eating behaviours in female adolescents/young adults are associated with increased risk of irritable bowel syndrome in adulthood: Results from the Growing Up Today Study (GUTS).

BACKGROUND: Irritable bowel syndrome (IBS) is common among individuals with eating disorders. The relationship between these conditions is likely bidirectional. However, data on the risk of IBS among those with prior eating disorders is largely limited to cross-sectional studies. AIM: To prospectively evaluate the association between maladaptive weight control/eating behaviours in females during adolescence/young adulthood with subsequent IBS using the Growing Up Today Study (GUTS). METHODS: Starting in 1996 (age: 9-14) and during follow-up, participants reported frequency of maladaptive eating/weight control behaviours during the past year to lose weight: self-induced vomiting (n = 5740), laxative use (n = 5438), and fasting (n = 5522) in addition to reporting binge eating (n = 4459). Starting in 2001 and during follow-up, participants reported if they had ever been diagnosed with an eating disorder (n = 5316). Incident IBS cases were identified from four questionnaire cycles (2013, 2014, 2016, 2019), with participants specifying the year of diagnosis if occurring before the questionnaire date. Multivariable logistic regressions adjusting for age, body mass index, and depressive symptoms estimated the associations of interest. RESULTS: Maladaptive weight control/eating behaviours were associated with increased IBS risk [ORs (95% CIs) for laxatives to lose weight = 3.67 (2.52-5.35), vomiting to lose weight = 1.83 (1.29-2.60), fasting to lose weight = 2.62 (1.86-3.70), and bingeing = 2.25 (1.54-3.28)] as was history of eating disorder diagnosis [OR (95% CI) = 3.42 (2.38-4.90)]. The magnitude of IBS risk increased with the frequency of maladaptive behaviours. CONCLUSIONS: There is evidence for the potential role of early maladaptive weight control/eating behaviours in the development of adult IBS among females.

Conductivity at varying frequencies as a method for differentiating strawberry ripeness and association with colour acceptance of strawberry nectars.

BACKGROUND: Identifying the best strawberries to produce colour stable nectars is a priority for the juice industry. Although riper strawberries produce nectars with better colour stability, variability between cultivars means that surface colour cannot be used as a single quality attribute to determine stability. Conductivity and bio-impedance measurements can be used to differentiate ripeness of strawberries. The commercially available PEF Control System (ELEA) can measure cell disruption by measuring conductivity at different frequencies. Updated software measured strawberry conductivity at 121 frequencies between 100 Hz and 1 MHz to determine whether conductivity at these frequencies could differentiate ripeness, and be compared with the colour acceptance and stability of nectars produced from these strawberries. RESULTS: A high-low ratio (HLR) was calculated by dividing the conductivity at frequency 1 MHz by conductivity at 1 kHz. HLR could be used to separate five strawberry ripeness stages, with decreasing HLR associated with increasing ripeness. HLR was then compared with the colour of nectars produced from these strawberries. Although there was a good correlation between HLR and an acceptable colour to consumers on initial production (r = -0.823, P < 0.001) and after 12 weeks of storage (-0.759, P < 0.001), cultivars differed greatly in both HLR and colour stability. Additionally, HLR had a strong correlation with firmness. CONCLUSION: The PEF Control System could be used to differentiate ripeness of strawberries by HLR, and therefore was associated with colour stability. However, no additional information on colour stability was gained from conductivity beyond what could already be deduced from differentiating ripeness based on surface colour. © 2024 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Pediatric to adult transition care in neurogastroenterology and motility: A position paper from the American Neurogastroenterology and Motility Society and European Society of Neurogastroenterology and Motility.

Transition services-programs that support adolescents and young adults (AYAs) as they move from a child-centered to a more autonomous, adult-orientated healthcare system-have been associated with improved short- and long-term healthcare outcomes. Unfortunately, there is a paucity of evidence exploring transition services within the neurogastroenterology and motility (NGM) field. The overall aim of this article, endorsed by the American Neurogastroenterology and Motility Society and European Society of Neurogastroenterology and Motility, is to promote a discussion about the role of transition services for patients with NGM disorders. The AYAs addressed herein are those who have: (a) a ROME positive disorder of gut-brain interaction (DGBI), (b) a primary or secondary motility disorder (including those with motility disorders that have been surgically managed), or (c) an artificial feeding requirement (parenteral or enteral tube feeding) to manage malnutrition secondary to categories (a) or (b). The issues explored in this position paper include the specific physical and psychological healthcare needs of patients with NGM disorders; key healthcare professionals who should form part of a secondary care NGM transition service; the triadic relationship between healthcare professionals, caregivers, and patients; approaches to selecting patients who may benefit most from transition care; methods to assess transition readiness; and strategies with which to facilitate transfer of care between healthcare professionals. Key areas for future research are also addressed, including the construction of NGM-specific transition readiness questionnaires, tools to assess post-transfer healthcare outcomes, and educational programs to train healthcare professionals about transition care in NGM.

Pain is a cardinal symptom cutting across Rome IV anatomical categories in disorders of gut-brain interaction: A network-based approach.

INTRODUCTION: Disorders of gut-brain interaction (DGBI) are symptom-based disorders categorized by anatomic location but have high overlap and heterogeneity. Viewing DGBI symptoms on a spectrum (i.e. dimensionally) rather than categorically may better inform interventions to accommodate complex clinical presentations. We aimed to evaluate symptom networks to identify how DGBI symptoms interact. METHODS: We used the Rome IV Diagnostic Questionnaire continuously/ordinally scored items collected from the Rome Foundation Global Epidemiology Study. We excluded participants who reported ≥1 organic/structural gastrointestinal disorder(s). We sought to (1) identify core symptoms in the DGBI symptom networks, (2) identify bridge pathways between Rome IV diagnostic categories (esophageal, bowel, gastroduodenal, anorectal), and (3) explore how symptoms group together into communities. RESULTS: Of 54,127 adults, 20,229 met criteria for at least one DGBI (age mean = 42.2 ± 15.5; 57% female). General abdominal pain and epigastric pain were the core symptoms in the DGBI symptom network (i.e., had the strongest connections to other symptoms). Pain symptoms emerged as bridge pathways across existing DGBI diagnostic anatomic location (i.e., abdominal pain connected to chest pain, epigastric pain, rectal pain). Without a priori category definitions, exploratory network community analysis showed that symptoms grouped together into "pain," "gastroduodenal," and "constipation," rather than into groups by anatomic location. CONCLUSION: Our findings suggest pain symptoms are central and serve as a key connection to other symptoms, crosscutting anatomic location. Future longitudinal research is needed to test symptom network relations longitudinally and investigate whether targeting pain symptoms (rather than anatomic- or disorder-specific symptoms) has clinical impact.

Trajectory of ghrelin and PYY around a test meal in males and females with avoidant/restrictive food intake disorder versus healthy controls.

Disruptions in appetite-regulating hormones may contribute to the development and/or maintenance of avoidant/restrictive food intake disorder (ARFID). No study has previously assessed fasting levels of orexigenic ghrelin or anorexigenic peptide YY (PYY), nor their trajectory in response to food intake among youth with ARFID across the weight spectrum. We measured fasting and postprandial (30, 60, 120 minutes post-meal) levels of ghrelin and PYY among 127 males and females with full and subthreshold ARFID (n = 95) and healthy controls (HC; n = 32). We used latent growth curve analyses to examine differences in the trajectories of ghrelin and PYY between ARFID and HC. Fasting levels of ghrelin did not differ in ARFID compared to HC. Among ARFID, ghrelin levels declined more gradually than among HC in the first hour post meal (p =.005), but continued to decline between 60 and 120 minutes post meal, whereas HC plateaued (p =.005). Fasting and PYY trajectory did not differ by group. Findings did not change after adjusting for BMI percentile (M(SD)ARFID = 37(35); M(SD)HC = 53(26); p =.006) or calories consumed during the test meal (M(SD)ARFID = 294(118); M(SD)HC = 384 (48); p <.001). These data highlight a distinct trajectory of ghrelin following a test meal in youth with ARFID. Future research should examine ghrelin dysfunction as an etiological or maintenance factor of ARFID.

Characterization of neurofibrillary tangle immunophenotype signatures to classify tangle maturity in Alzheimer's disease.

INTRODUCTION: Tau aggregation into neurofibrillary tangles in Alzheimer's disease (AD) is a dynamic process involving changes in tau phosphorylation, isoform composition, and morphology. To facilitate studies of tangle maturity, we developed an image analysis pipeline to study antibody labeling signatures that can distinguish tangle maturity levels in AD brain tissue. METHODS: Using fluorescent immunohistochemistry, we co-labeled AD brain tissue with four antibodies that bind different tau epitopes. Mean fluorescence intensity of each antibody was measured, and spectral clustering was used to identify tangle immunophenotypes. RESULTS: Five distinct tangle populations were identified, and different tangle maturity immunophenotypes were identified with increasing Braak stage. Early tangle immunophenotypes were more prevalent in later affected regions and advanced immunophenotypes were associated with ghost morphology. DISCUSSION: Our findings indicate that tangle populations characterized by advanced tau immunophenotypes are associated with higher Braak stage and more mature morphology, providing a new framework for defining tangle maturity levels using tau antibody signatures. HIGHLIGHTS: Populations of neurofibrillary tangles exist in Alzheimer's disease. The immunophenotype of neurofibrillary tangle populations relates to their maturity. The most advanced immunophenotypes are associated with higher Braak stage. The most advanced immunophenotypes are associated with ghost morphology. The most immature immunophenotypes are associated with later affected regions.

Medical Comorbidities, Nutritional Markers, and Cardiovascular Risk Markers in Youth With ARFID.

OBJECTIVE: Avoidant/restrictive food intake disorder (ARFID) is common among populations with nutrition-related medical conditions. Less is known about the medical comorbidity/complication frequencies in youth with ARFID. We evaluated the medical comorbidities and metabolic/nutritional markers among female and male youth with full/subthreshold ARFID across the weight spectrum compared with healthy controls (HC). METHOD: In youth with full/subthreshold ARFID (n = 100; 49% female) and HC (n = 58; 78% female), we assessed self-reported medical comorbidities via clinician interview and explored abnormalities in metabolic (lipid panel and high-sensitive C-reactive protein [hs-CRP]) and nutritional (25[OH] vitamin D, vitamin B12, and folate) markers. RESULTS: Youth with ARFID, compared with HC, were over 10 times as likely to have self-reported gastrointestinal conditions (37% vs. 3%; OR = 21.2; 95% CI = 6.2-112.1) and over two times as likely to have self-reported immune-mediated conditions (42% vs. 24%; OR = 2.3; 95% CI = 1.1-4.9). ARFID, compared with HC, had a four to five times higher frequency of elevated triglycerides (28% vs. 12%; OR = 4.0; 95% CI = 1.7-10.5) and hs-CRP (17% vs. 4%; OR = 5.0; 95% CI = 1.4-27.0) levels. DISCUSSION: Self-reported gastrointestinal and certain immune comorbidities were common in ARFID, suggestive of possible bidirectional risk/maintenance factors. Elevated cardiovascular risk markers in ARFID may be a consequence of limited dietary variety marked by high carbohydrate and sugar intake.

Latent profile analysis reveals overlapping ARFID and shape/weight motivations for restriction in eating disorders.

BACKGROUND: DSM-5 differentiates avoidant/restrictive food intake disorder (ARFID) from other eating disorders (EDs) by a lack of overvaluation of body weight/shape driving restrictive eating. However, clinical observations and research demonstrate ARFID and shape/weight motivations sometimes co-occur. To inform classification, we: (1) derived profiles underlying restriction motivation and examined their validity and (2) described diagnostic characterizations of individuals in each profile to explore whether findings support current diagnostic schemes. We expected, consistent with DSM-5, that profiles would comprise individuals endorsing solely ARFID or restraint (i.e. trying to eat less to control shape/weight) motivations. METHODS: We applied latent profile analysis to 202 treatment-seeking individuals (ages 10-79 years [M = 26, s.d. = 14], 76% female) with ARFID or a non-ARFID ED, using the Nine-Item ARFID Screen (Picky, Appetite, and Fear subscales) and the Eating Disorder Examination-Questionnaire Restraint subscale as indicators. RESULTS: A 5-profile solution emerged: Restraint/ARFID-Mixed (n = 24; 8% [n = 2] with ARFID diagnosis); ARFID-2 (with Picky/Appetite; n = 56; 82% ARFID); ARFID-3 (with Picky/Appetite/Fear; n = 40; 68% ARFID); Restraint (n = 45; 11% ARFID); and Non-Endorsers (n = 37; 2% ARFID). Two profiles comprised individuals endorsing solely ARFID motivations (ARFID-2, ARFID-3) and one comprising solely restraint motivations (Restraint), consistent with DSM-5. However, Restraint/ARFID-Mixed (92% non-ARFID ED diagnoses, comprising 18% of those with non-ARFID ED diagnoses in the full sample) endorsed ARFID and restraint motivations. CONCLUSIONS: The heterogeneous profiles identified suggest ARFID and restraint motivations for dietary restriction may overlap somewhat and that individuals with non-ARFID EDs can also endorse high ARFID symptoms. Future research should clarify diagnostic boundaries between ARFID and non-ARFID EDs.

Hippocampal aggregation signatures of pathogenic UBQLN2 in amyotrophic lateral sclerosis and frontotemporal dementia.

Pathogenic variants in the UBQLN2 gene cause X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia characterised by ubiquilin 2 aggregates in neurons of the motor cortex, hippocampus, and spinal cord. However, ubiquilin 2 neuropathology is also seen in sporadic and familial amyotrophic lateral sclerosis and/or frontotemporal dementia cases not caused by UBQLN2 pathogenic variants, particularly C9orf72-linked cases. This makes the mechanistic role of mutant ubiquilin 2 protein and the value of ubiquilin 2 pathology for predicting genotype unclear. Here we examine a cohort of 44 genotypically diverse amyotrophic lateral sclerosis cases with or without frontotemporal dementia, including eight cases with UBQLN2 variants (resulting in p.S222G, p.P497H, p.P506S, p.T487I (two cases), and p.P497L (three cases)). Using multiplexed (5-label) fluorescent immunohistochemistry, we mapped the co-localisation of ubiquilin 2 with phosphorylated TDP-43, dipeptide repeat aggregates, and p62, in the hippocampus of controls (n = 6), or amyotrophic lateral sclerosis with or without frontotemporal dementia in sporadic (n = 20), unknown familial (n = 3), SOD1-linked (n = 1), FUS-linked (n = 1), C9orf72-linked (n = 5), and UBQLN2-linked (n = 8) cases. We differentiate between i) ubiquilin 2 aggregation together with phosphorylated TDP-43 or dipeptide repeat proteins, and ii) ubiquilin 2 self-aggregation promoted by UBQLN2 pathogenic variants that cause amyotrophic lateral sclerosis/and frontotemporal dementia. Overall, we describe a hippocampal protein aggregation signature that fully distinguishes mutant from wildtype ubiquilin 2 in amyotrophic lateral sclerosis with or without frontotemporal dementia, whereby mutant ubiquilin 2 is more prone than wildtype to aggregate independently of driving factors. This neuropathological signature can be used to assess the pathogenicity of UBQLN2 gene variants and to understand the mechanisms of UBQLN2-linked disease.

Avoidant/Restrictive Food Intake Disorder Symptoms Are Not as Frequent as Other Eating Disorder Symptoms When Ulcerative Colitis Is in Remission.

BACKGROUND AND AIM: Recent studies have shown that up to 53% of patients with inflammatory bowel disease [IBD] screen positive for avoidant/restrictive food intake disorder [ARFID]. There is however concern that ARFID screening rates are over-inflated in patients with active disease. We aimed to evaluate the frequency and characteristics of ARFID symptoms using the Nine Item ARFID Screen [NIAS], and to use another eating disorder measure, the Eating Disorder Examination-Questionnaire 8 [EDE-Q8], to rule-out/characterise other eating disorder cognitive and behavioural symptoms. METHODS: Participants included adults with UC who are enrolled in an ongoing cohort study with quiescent UC (Simple Clinical Colitis Activity Index [SCCAI] ≤2 or faecal calprotectin <150 µg/g with corticosteroid-free clinical remission for ≥3 months) at baseline. We used self-reported data on demographics, gastrointestinal medications, medical comorbidities, NIAS scores, and EDE-Q-8 scores. RESULTS: We included 101 participants who completed the NIAS at their baseline cohort assessment [age 49.9 ±â€…16.5 years; 55% female]. Eleven participants [11%] screened positively for ARFID on at least one NIAS subscale [n = 8 male]. Up to 30 participants [30%] screened positive for other eating disorder symptoms [EDE-Q-8 Global ≥2.3]. Overall score distributions on the EDE-Q-8 showed that participants scored highest on the Weight Concern and Shape Concern subscales. CONCLUSIONS: Among adults with UC in remission, we found a low rate of ARFID symptoms by the NIAS but a high rate of positive screens for other eating disorder symptoms.

Presence and characteristics of disordered eating and orthorexia in irritable bowel syndrome.

INTRODUCTION: Orthorexia, a harmful obsession with eating healthily, may develop from illnesses characterized by dietary restriction, including irritable bowel syndrome (IBS) and eating disorders (ED). Evidence of disordered eating in IBS exists, but orthorexia has not been assessed. This cross-sectional study in adults (≥18 years) assessed presence and characteristics of disordered eating and orthorexia in IBS, compared to control subjects (CS) and ED. METHODS: IBS participants met Rome IV, and ED participants met DSM-5 criteria. Disordered eating was assessed using "sick, control, one-stone, fat, food" (SCOFF, ≥2 indicating disordered eating), and orthorexia by the eating habits questionnaire (EHQ). Secondary measures included stress (PSS); anxiety (HADS-A); food-related quality of life (Fr-QoL), and dietary intake (CNAQ). KEY RESULTS: In 202 IBS (192 female), 34 ED (34 female), and 109 CS (90 female), more IBS (33%) and ED (47%) scored SCOFF≥2 compared to CS (16%, p < 0.001, chi-square). IBS and ED had higher orthorexia symptom severity compared to CS (EHQ IBS 82.9 ± 18.1, ED 90.1 ± 19.6, and CS 73.5 ± 16.9, p < 0.001, one-way ANOVA). IBS and ED did not differ for SCOFF or EHQ (p > 0.05). Those with IBS and disordered eating had higher orthorexia symptom severity (EHQ 78.2 ± 16.6 vs. 92.4 ± 17.5, p < 0.001, independent t-test), worse symptoms (IBS-SSS 211.0 ± 78.4 vs. 244.4 ± 62.5, p = 0.008, Mann-Whitney U test), higher stress (p < 0.001, independent t-test), higher anxiety (p = 0.002, independent t-test), and worse FR-QoL (p < 0.001, independent t-test). CONCLUSIONS AND INFERENCES: Disordered eating and orthorexia symptoms occur frequently in IBS, particularly in those with worse gastrointestinal symptoms, higher stress, and anxiety. Clinicians could consider these characteristics when prescribing dietary therapies.

Age, Race, Ethnicity, and Sex of Participants in Clinical Trials Focused on Chronic Pain.

There is limited data on equitable inclusion in chronic pain trials. We aimed to 1) identify the frequency of reporting age, race, ethnicity, and sex in clinical trials targeting chronic pain, and 2) compare sociodemographic representation to the United States (US) population. We examined US-based intervention trials for chronic pain initiated between 2007 and 2021 and registered on ClinicalTrials.gov. We 1) assessed the frequency of reporting each demographic variable, 2) compared representation with US population estimates, and 3) explored change in reporting over time. Of 501 clinical trials, the frequency of reporting was as follows: 36.9% reported older adults, 54.3% reported race, 37.4% reported ethnicity, and 100% reported sex. Rates of race and ethnicity reporting increased, but older adult age reporting decreased over time (ps < .00001). Compared to 2020 US population estimates, there was an equitable representation of older adults, under-representation of individuals identifying as American Indian or Alaska Native (.8% vs .6%), Asian (5.6% vs 2.9%), Black or African American (12.6% vs 12.2%), with more than one race (2.9% vs 1.2%), and Hispanic/Latino (16.9% vs 14.1%). There was an over-representation of individuals identifying as Native Hawaiian or Pacific Islander (.2% vs .5%) or White (70.4% vs 72.9%), and of females (50.8% vs 68.4%). Some representation rates varied by chronic pain condition. Reporting of older adult age, race, and ethnicity was low in chronic pain trials in ClinicalTrials.gov, reinforcing the need for adhering to reporting guidelines. Representation varied across trials compared with US population data, particularly among those identifying as Hispanic/Latino and certain minority racial groups. PERSPECTIVE: Despite initiatives to increase the reporting of demographic information, doing so in clinical pain trials is far from ubiquitous. Moreover, efforts to improve diversity in these trials continue to be insufficient. Indeed, Black, Indigenous, and People of Color (BIPOC) remain under-represented in clinical pain trials.

Histological Characterisation of a Sheep Model of Mild Traumatic Brain Injury: A Pilot Study.

Large animal models of mild traumatic brain injury (mTBI) are needed to elucidate the pathophysiology of mechanical insult to a gyrencephalic brain. Sheep (ovis aries) are an attractive model for mTBI because of their neuroanatomical similarity to humans; however, few histological studies of sheep mTBI models have been conducted. We previously developed a sheep mTBI model to pilot methods for investigating the mechanical properties of brain tissue after injury. Here, we sought to histologically characterize the cortex under the impact site in this model. Three animals received a closed skull mTBI with unconstrained head motion, delivered with an impact stunner, and 3 sham animals were anesthetized but did not receive an impact. Magnetic resonance imaging (MRI) of the brain was performed before and after the impact and revealed variable degrees of damage to the skull and brain. Fluorescent immunohistochemistry revealed regions of hemorrhage in the cortex underlying the impact site in 2 of 3 mTBI sheep, the amount of which correlated with the degree of damage observed on the post-impact MRI scans. Labeling for microtubule-associated protein 2 and neuronal nuclear protein revealed changes in cellular anatomy, but, unexpectedly, glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 labeling were relatively unchanged compared to sham animals. Our findings provide preliminary evidence of vascular and neuronal damage with limited glial reactivity and highlight the need for further in-depth histological assessment of large animal mTBI models.

Gastrointestinal diagnoses in patients with eating disorders: A retrospective cohort study 2010-2020.

BACKGROUND AND AIMS: Gastrointestinal (GI) disorders are common in patients with eating disorders. However, the temporal relationship between GI and eating disorder symptoms has not been explored. We aimed to evaluate GI disorders among patients with eating disorders, their relative timing, and the relationship between GI diagnoses and eating disorder remission. METHODS: We conducted a retrospective analysis of patients with an eating disorder diagnosis who had a GI encounter from 2010 to 2020. GI diagnoses and timing of eating disorder onset were abstracted from chart review. Coders applied DSM-5 criteria for eating disorders at the time of GI consult to determine eating disorder remission status. RESULTS: Of 344 patients with an eating disorder diagnosis and GI consult, the majority (255/344, 74.2%) were diagnosed with an eating disorder prior to GI consult (preexisting eating disorder). GI diagnoses categorized as functional/motility disorders were most common among the cohort (57.3%), particularly in those with preexisting eating disorders (62.5%). 113 (44.3%) patients with preexisting eating disorders were not in remission at GI consult, which was associated with being underweight (OR 0.13, 95% CI 0.04-0.46, p < 0.001) and increasing number of GI diagnoses (OR 0.47 per diagnosis, 95% CI 0.26-0.85, p = 0.01). CONCLUSIONS: Eating disorder symptoms precede GI consult for most patients, particularly in functional/motility disorders. As almost half of eating disorder patients are not in remission at GI consult. GI providers have an important role in screening for eating disorders. Further prospective research is needed to understand the complex relationship between eating disorders and GI symptoms.

Avoidant/restrictive food intake disorder prevalence is high in children with gastroparesis and functional dyspepsia.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) prevalence in children with gastroparesis (Gp) and/or functional dyspepsia (FD) is unknown. We aimed to identify ARFID prevalence and trajectory over 2 months in children with Gp, FD, and healthy children (HC) using two screening questionnaires. We also explored the frequency of a positive ARFID screen between those with/without delayed gastric emptying or abnormal fundic accommodation. METHODS: In this prospective longitudinal study conducted at an urban tertiary care hospital, patients ages 10-17 years with Gp or FD and age- and gender-matched HC completed two validated ARFID screening tools at baseline and 2-month follow-up: the Nine Item ARFID Screen (NIAS) and the Pica, ARFID, and Rumination Disorder Interview-ARFID Questionnaire (PARDI-AR-Q). Gastric retention and fundic accommodation (for Gp and FD) were determined from gastric emptying scintigraphy. KEY RESULTS: At baseline, the proportion of children screening positive for ARFID on the NIAS versus PARDI-AR-Q was Gp: 48.5% versus 63.6%, FD: 66.7% versus 65.2%, HC: 15.3% versus 9.7%, respectively; p < 0.0001 across groups. Of children who screened positive at baseline and participated in the follow-up, 71.9% and 53.3% were positive 2 months later (NIAS versus PARDI-AR-Q, respectively). A positive ARFID screen in Gp or FD was not related to the presence/absence of delayed gastric retention or abnormal fundic accommodation. CONCLUSIONS & INFERENCES: ARFID detected from screening questionnaires is highly prevalent among children with Gp and FD and persists for at least 2 months in a substantial proportion of children. Children with these disorders should be screened for ARFID.

Latent profile analysis reveals the central role of psychological symptoms in driving disease severity in chronic constipation.

BACKGROUND: Chronic constipation (CC) is defined by symptom criteria reflecting heterogenous physiology. However, many patients with CC have significant psychological comorbidities-an alternative definition using a biopsychosocial classification model could be warranted to inform future treatments. We sought to: (1) empirically derive psychological symptom profiles of patients with CC using latent profile analysis and (2) validate these profiles by comparing them on symptom severity, GI-specific anxiety, body mass index (BMI), and anorectal manometry findings. METHODS: Participants included adults presenting for anorectal manometry for CC (N = 468, 82% female, Mage = 47). Depression/anxiety symptoms and eating disorder (ED) symptoms (EAT-26) were used as indicators (i.e., variables used to derive profiles) representing unique psychological constructs. Constipation symptoms, GI-specific anxiety, BMI, and anorectal manometry results were used as validators (i.e., variables used to examine the clinical utility of the resulting profiles). KEY RESULTS: A 5-profile solution provided the best statistical fit, comprising the following latent profiles (LPs): LP1 termed "high dieting, low bulimia;" LP2 termed "high ED symptoms;" LP3 termed "moderate ED symptoms;" LP4 termed "high anxiety and depression, low ED symptoms;" and LP5 termed "low psychological symptoms." The low psychological symptom profile (61% of the sample) had lower abdominal and overall constipation severity and lower GI-specific anxiety compared to the four profiles characterized by higher psychological symptoms (of any type). Profiles did not significantly differ on BMI or anorectal manometry results. CONCLUSIONS AND INFERENCES: Profiles with high psychological symptoms had increased constipation symptom severity and GI-specific anxiety in adults with CC. Future research should test whether these profiles predict differential treatment outcomes.

Cognitive-behavioral therapy for avoidant/restrictive food intake disorder: A proof-of-concept for mechanisms of change and target engagement.

BACKGROUND: Cognitive-behavioral therapy for avoidant/restrictive food intake disorder (ARFID; CBT-AR) theoretically targets three prototypic motivations (sensory sensitivity, lack of interest/low appetite, fear of aversive consequences), aligned with three modularized interventions. As an exploratory investigation, we: (1) evaluated change in candidate mechanisms in relationship to change in ARFID severity, and (2) tested if assignment (vs. not) to a module resulted in larger improvements in the corresponding mechanism. METHOD: Males and females (N = 42; 10-55 years) participated in an open trial of CBT-AR. RESULTS: Decreases in scaled scores for each candidate mechanism had medium to large correlations with decreases in ARFID severity-sensory sensitivity: -0.7 decrease (r = .42, p = .01); lack of interest/low appetite: -0.3 decrease (r = .60, p < .0001); and fear of aversive consequences: -1.1 decrease (r = .33, p = .05). Linear mixed models revealed significant weekly improvements for each candidate mechanism across the full sample (ps < .0001). There were significant interactions for the sensory and fear of aversive consequences modules-for each, participants who received the corresponding module had significantly larger decreases in the candidate mechanism than those who did not receive the module. DISCUSSION: Sensory sensitivity and fear of aversive consequences improved more if the CBT-AR module was received, but lack of interest/low appetite may improve regardless of receipt of the corresponding module. Future research is needed to test target engagement in CBT-AR with adaptive treatment designs, and to identify valid and sensitive measures of candidate mechanisms. PUBLIC SIGNIFICANCE: The mechanisms through which components of CBT-AR work have yet to be elucidated. We conducted an exploratory investigation to test if assignment (vs. not) to a CBT-AR module resulted in larger improvements in the corresponding prototypic ARFID motivation that the module intended to target. Measures of the sensory sensitivity and the fear of aversive consequences motivations improved more in those who received the corresponding treatment module, whereas the lack of interest/low appetite measure improved regardless of if the corresponding module was received.