ARF1-related disorder: phenotypic and molecular spectrum.

PURPOSE: ARF1 was previously implicated in periventricular nodular heterotopia (PVNH) in only five individuals and systematic clinical characterisation was not available. The aim of this study is to provide a comprehensive description of the phenotypic and genotypic spectrum of ARF1-related neurodevelopmental disorder. METHODS: We collected detailed phenotypes of an international cohort of individuals (n=17) with ARF1 variants assembled through the GeneMatcher platform. Missense variants were structurally modelled, and the impact of several were functionally validated. RESULTS: De novo variants (10 missense, 1 frameshift, 1 splice altering resulting in 9 residues insertion) in ARF1 were identified among 17 unrelated individuals. Detailed phenotypes included intellectual disability (ID), microcephaly, seizures and PVNH. No specific facial characteristics were consistent across all cases, however microretrognathia was common. Various hearing and visual defects were recurrent, and interestingly, some inflammatory features were reported. MRI of the brain frequently showed abnormalities consistent with a neuronal migration disorder. CONCLUSION: We confirm the role of ARF1 in an autosomal dominant syndrome with a phenotypic spectrum including severe ID, microcephaly, seizures and PVNH due to impaired neuronal migration.

Newcomer perceptions of COVID-19 countermeasures in Canada.

Newcomers to Canada have been disproportionally affected by COVID-19, with higher rates of infection and severity of illness. Determinants of higher rates may relate to social and structural inequities that impact newcomers' capacity to follow countermeasures. Our aim was to describe and document factors shaping newcomers' acceptance of COVID-19 countermeasures. Semi-structured qualitative interviews were conducted with individuals living in Canada for <5 years. Participants were asked to discuss their pandemic experiences, and perceptions and acceptance of measures. Five themes were identified: (i) belief in the necessity and efficacy of countermeasures; (ii) negative impact of measures on health/wellbeing; (iii) existing barriers to newcomer settlement exacerbated by pandemic measures; (iv) countermeasure adherence related to immigration status and (v) past experiences shaping countermeasure acceptance. Government should continue to provide messaging regarding the importance of measures for individual and population heath and continue to demonstrate a commitment to the interests of citizens. Importantly, newcomer trust in government should not be taken for granted, as this trust is critical for the acceptance of government interventions now and moving forward. It will be important to ensure that newcomers are given support to overcome challenges to settlement that were intensified during the pandemic.

Associations between eating occasion characteristics and age, gender, presence of children and BMI among U.S. adults.

OBJECTIVE: To describe how frequency and characteristics of traditional meal and non-meal occasions vary by age, gender, presence of children, and body mass index (BMI). DESIGN: A cross-sectional survey was administered to a national demographically balanced sample of adults via an online market research panel. SETTING: Online survey. SUBJECTS: Survey respondents were in the 18- to 80-year-old age range and had consumed any food or beverage at home or away from home the previous day. The sample included 2702 adults reporting on 6689 eating/drinking occasions. Most (80.3%) had no children at home; 43.5% were male and about two thirds were overweight/obese. MEASURES OF OUTCOME: Eating occasion characteristics and goals by age, gender, presence of children, and BMI. RESULTS: Older respondents were more likely to report planning traditional meal occasions and report on a breakfast occasion than younger respondents. Two prominent reasons that triggered consumption occasions were habit and hunger/thirst with one dominant benefit of satisfying hunger or thirst. Habit and nutrition played a larger role as a goal for eating occasions for older compared to younger respondents. When children were present in the household, respondents had a goal of connecting with "family, friends, or colleagues" at dinner compared to those without children. Few gender differences were noted; however, women more often reported goals of satisfying hunger/thirst and taste at lunch than men. BMI levels were related to a range of triggers, goals, and behaviors but not as prominently as the relationships observed with age. Those with BMI ≥ 30 were less health conscious regarding dinner and breakfast consumption compared to those with a lower BMI. CONCLUSIONS: Among demographic variables, age differences were noted in relation to eating occasion characteristics more often than other demographic characteristics or BMI. Understanding these differences can be beneficial in tailoring promotion of healthful intake at specific eating occasions for particular subgroups.

Silent aspiration and recovery from dysphagia in a case of bickerstaff brainstem encephalitis.

Bickerstaff brainstem encephalitis (BBE) is a rare inflammatory demyelinating disease with rapid progression typically followed by complete recovery. Reports of dysphagia in this population are limited and general. The purpose of this article is to heighten awareness of the potential for silent aspiration in patients with BBE. This article details the nature of dysphagia during the recovery phase of BBE and includes findings from serial videofluoroscopic swallowing evaluations. In addition, it shows the impact of cognitive impairment on the ability to eat safely. Early instrumental swallowing evaluation, close monitoring, and conservative management are essential to ensure safety in patients recovering from BBE.

Do obesity and weight loss affect vocal function?

Obesity may be associated with increased tissue bulk in the laryngeal airway, neck, and chest wall, and as such may affect vocal function. Eight obese and eight nonobese adults participated in this study; the obese participants underwent bariatric surgical procedures. This mixed-design study included cross-sectional analysis for group differences and longitudinal analysis for multidimensional changes in vocal function from four assessments collected over 6 months. No significant differences were detected between groups from the preoperative assessment. Further, no changes were detected over time for acoustic parameters, maximum phonation time, laryngeal airway resistance, and airflow during a sustained vowel for either group. Only minor differences were detected for strain, pitch, and loudness perceptions of voice over time, but not between groups. Phonation threshold pressure (PTP), at comfortable and high pitches (30% and 80% of the F0 range) changed significantly over time, but not between groups. Examination of individual data revealed a trend for PTP at 30% F0 to decrease as body mass index decreased. PTP may be informative for assessing vocal function in clients who present with obesity and voice symptoms.

Predictors of swallowing outcomes in patients with combat-injury related dysphagia.

BACKGROUND: Traumatic injuries, such as those from combat-related activities, can lead to complicated clinical presentations that may include dysphagia. METHODS: This retrospective observational database study captured dysphagia-related information for 215 US military service members admitted to the first stateside military treatment facility after sustaining combat-related or combat-like traumatic injuries. A multidimensional relational database was developed to document the nature, course, and management for dysphagia in this unique population and to explore variables predictive of swallowing recovery using Bayesian statistical modeling and inferential statistical methods. RESULTS: Bayesian statistical modeling revealed the importance of maxillofacial fractures and soft tissue loss as primary predictors of poor swallowing outcomes. The presence of traumatic brain injury (TBI), though common, did not further complicate dysphagia outcomes. A more detailed examination and rating of videofluoroscopic swallow studies from a subset of 161 participants supported greater impairment for participants with maxillofacial trauma and no apparent relationship between having sustained a TBI and swallow functioning. CONCLUSION: These analyses revealed that maxillofacial trauma is a stronger indicator than TBI of dysphagia severity and slower or incomplete recovery following combat-related injuries. LEVEL OF EVIDENCE: Therapeutic/Care Management study, level IV.

Taste Manipulation and Swallowing Mechanics in Trauma-Related Sensory-Based Dysphagia.

Purpose This study explored the effects of high-concentration taste manipulation trials on swallow function in persons with sensory-based dysphagia. Method Dysphagia researchers partnered with clinical providers to prospectively identify traumatically injured U.S. military service members (N = 18) with sensory-based dysphagia as evidenced by delayed initiation and/or decreased awareness of residue/penetration/aspiration. Under videofluoroscopy, participants swallowed trials of 3 custom-mixed taste stimuli: unflavored (40% weight/volume [wt/vol] barium sulfate in distilled water), sour (2.7% wt/vol citric acid in 40% wt/vol barium suspension), and sweet-sour (1.11% wt/vol citric acid plus 8% wt/vol sucrose in 40% wt/vol barium suspension). Trials were analyzed and compared via clinical rating tools (the Modified Barium Swallow Impairment Profile [Martin-Harris et al., 2008] and the Penetration-Aspiration Scale [Rosenbek, Robbins, Roecker, Coyle, & Wood, 1996]). Additionally, a computational analysis of swallowing mechanics (CASM) was applied to a subset of 9 swallows representing all 3 tastants from 3 participants. Results Friedman's tests for the 3 stimuli revealed significantly (p < .05) improved functional ratings for Penetration-Aspiration Scale and pharyngoesophageal opening. CASM indicated differences in pharyngeal swallowing mechanics across all tastant comparisons (p ≤ .0001). Eigenvectors revealed increased tongue base retraction, hyoid elevation, and pharyngeal shortening for sweet-sour and, to a lesser extent, sour than for unflavored boluses. Conclusion Advantageous changes in certain parameters of oropharyngeal swallowing physiology were noted with high-intensity tastants per both clinical ratings and subsequent CASM, suggesting potential therapeutic application for taste manipulation.

Dysphagia Management and Research in an Acute-Care Military Treatment Facility: The Role of Applied Informatics.

PURPOSE: This report describes the development and preliminary analysis of a database for traumatically injured military service members with dysphagia. METHODS: A multidimensional database was developed to capture clinical variables related to swallowing. Data were derived from clinical records and instrumental swallow studies, and ranged from demographics, injury characteristics, swallowing biomechanics, medications, and standardized tools (e.g., Glasgow Coma Scale, Penetration-Aspiration Scale). Bayesian Belief Network modeling was used to analyze the data at intermediate points, guide data collection, and predict outcomes. Predictive models were validated with independent data via receiver operating characteristic curves. RESULTS: The first iteration of the model (n = 48) revealed variables that could be collapsed for the second model (n = 96). The ability to predict recovery from dysphagia improved from the second to third models (area under the curve = 0.68 to 0.86). The third model, based on 161 cases, revealed "initial diet restrictions" as first-degree, and "Glasgow Coma Scale, intubation history, and diet change" as second-degree associates for diet restrictions at discharge. CONCLUSION: This project demonstrates the potential for bioinformatics to advance understanding of dysphagia. This database in concert with Bayesian Belief Network modeling makes it possible to explore predictive relationships between injuries and swallowing function, individual variability in recovery, and appropriate treatment options.