Speech-language pathologist, physical therapist, and occupational therapist experiences of interprofessional collaborations.

Interprofessional collaboration among speech-language pathology, physical therapy, and occupational therapy is considered to promote best practice in rehabilitation as it can enhance efficiency, patient outcomes, and clinician and patient satisfaction. Although clinician experiences with interprofessional collaboration have been studied in each of the rehabilitation professions separately, limited research has been conducted on the shared attitudes or experiences across speech-language pathology, physical therapy, and occupational therapy. The purpose of this study was to understand speech-language pathologist, physical therapist, and occupational therapist experiences of interprofessional collaborations. We conducted an exploratory cross-sectional online survey study. The survey included Likert-scale questions and open-ended questions that probed clinicians' general experiences with interprofessional practice and views and beliefs regarding barriers and facilitators to interprofessional collaboration. Responses from 213 clinician respondents were analyzed using descriptive quantitative methods and a qualitative content analysis. The results revealed overlap in attitudes and experiences across speech-language pathology, physical therapy, and occupational therapy about barriers and benefits to interprofessional collaboration. Perceived respect differed among the professions, with speech-language pathologists more frequently reporting that their role is often misunderstood or undervalued by other rehabilitation professionals. These results may guide future research focused upon the predictors of successful interprofessional collaborations and interactions.

A Qualitative Analysis of Clinician Perspectives of Ultrasound Biofeedback for Speech Sound Disorders.

PURPOSE: Ultrasound biofeedback therapy (UBT) is a relatively new type of technology-assisted speech-language therapy and has shown promise in remediating speech sound disorders. However, there is a current lack of understanding of the barriers and benefits that may influence the usage behavior and clinical decision making for the implementation of UBT from a clinician perspective. In this qualitative study, we explore the perspectives of speech-language pathologists (SLPs) who have used ultrasound biofeedback in programs of speech sound therapy using the unified theory of acceptance and use of technology (UTAUT) model. METHOD: Seven SLPs who had clinical experience treating speech sound disorders with UBT participated. Semistructured in-depth interviews were conducted and video-recorded. Two coders coded and categorized the transcribed data, with consensus established with a third coder. Using thematic analysis, the data were exploratorily grouped into themes along components of the UTAUT model. RESULTS: The highest number of codes was sorted into the "effort expectancy" theme, followed by "performance expectancy," "social influence," and "facilitating conditions" themes of the UTAUT model. Clinicians identified multiple perceived barriers and benefits to the use of ultrasound technology. The top identified barrier was limited accessibility, and the top benefit was the ability to visualize a client's articulatory response to cues on a display. CONCLUSIONS: Clinicians prioritized "effort expectancy" and "performance expectancy" when reflecting on the use of ultrasound biofeedback for speech sound disorders. Clinicians spoke favorably about using UBT for speech sound disorder treatment but acknowledged institutional barriers and limitations at organizational and social levels.

Bi-allelic TTI1 variants cause an autosomal-recessive neurodevelopmental disorder with microcephaly.

Telomere maintenance 2 (TELO2), Tel2 interacting protein 2 (TTI2), and Tel2 interacting protein 1 (TTI1) are the three components of the conserved Triple T (TTT) complex that modulates activity of phosphatidylinositol 3-kinase-related protein kinases (PIKKs), including mTOR, ATM, and ATR, by regulating the assembly of mTOR complex 1 (mTORC1). The TTT complex is essential for the expression, maturation, and stability of ATM and ATR in response to DNA damage. TELO2- and TTI2-related bi-allelic autosomal-recessive (AR) encephalopathies have been described in individuals with moderate to severe intellectual disability (ID), short stature, postnatal microcephaly, and a movement disorder (in the case of variants within TELO2). We present clinical, genomic, and functional data from 11 individuals in 9 unrelated families with bi-allelic variants in TTI1. All present with ID, and most with microcephaly, short stature, and a movement disorder. Functional studies performed in HEK293T cell lines and fibroblasts and lymphoblastoid cells derived from 4 unrelated individuals showed impairment of the TTT complex and of mTOR pathway activity which is improved by treatment with Rapamycin. Our data delineate a TTI1-related neurodevelopmental disorder and expand the group of disorders related to the TTT complex.

Classification of accurate and misarticulated /ɑr/ for ultrasound biofeedback using tongue part displacement trajectories.

Ultrasound biofeedback therapy (UBT), which incorporates real-time imaging of tongue articulation, has demonstrated generally positive speech remediation outcomes for individuals with residual speech sound disorder (RSSD). However, UBT requires high attentional demands and may therefore benefit from a simplified display of articulation targets that are easily interpretable and can be compared to real-time articulation. Identifying such targets requires automatic quantification and analysis of movement features relevant to accurate speech production. Our image-analysis program TonguePART automatically quantifies tongue movement as tongue part displacement trajectories from midsagittal ultrasound videos of the tongue, with real-time capability. The present study uses such displacement trajectories to compare accurate and misarticulated American-English rhotic /ɑr/ productions from 40 children, with degree of accuracy determined by auditory perceptual ratings. To identify relevant features of accurate articulation, support vector machine (SVM) classifiers were trained and evaluated on several candidate data representations. Classification accuracy was up to 85%, indicating that quantification of tongue part displacement trajectories captured tongue articulation characteristics that distinguish accurate from misarticulated production of /ɑr/. Regression models for perceptual ratings were also compared. The simplest data representation that retained high predictive ability, demonstrated by high classification accuracy and strong correlation between observed and predicted ratings, was displacements at the midpoint of /r/ relative to /ɑ/ for the tongue dorsum and blade. This indicates that movements of the dorsum and blade are especially relevant to accurate production of /r/, suggesting that a predictive parameter and biofeedback target based on this data representation may be usable for simplified UBT.

Personal factors understood through the Ecological-Enactive Model of Disability and implications for rehabilitation research.

The International Classification of Functioning, Disability and Health (ICF) recognizes that disability arises from the interaction between an individual with a medical condition and the context in which they are embedded. Context in the ICF is comprised of environmental and personal factors. Personal factors, the background life and lifestyle of an individual, are poorly understood in rehabilitation. There is limited knowledge about how personal and environmental factors interact to shape the contextual conditions critical for explaining functioning and disability. In this paper, we explore how a newly proposed model of disability, the Ecological-Enactive Model of Disability, can enhance understanding of personal factors across multiple rehabilitation disciplines. We draw from a review of evidence and phenomenological interviews of individuals with Friedreich's Ataxia. We consider the practical impact of this understanding on disability and rehabilitation research and pathways for the future focusing on representative design.

Impact of vaccination on keratoplasty.

PURPOSE OF REVIEW: Corneal graft rejection has been reported after coronavirus disease 2019 (COVID-19) vaccination. The purpose of this review is to evaluate the literature regarding corneal graft rejection after vaccination, including rejection rates and risk factors. We aim to create a framework to identify patients who are at higher risk for graft rejection and may warrant consideration of prophylactic interventions. RECENT FINDINGS: Graft rejection has been reported following administration of mRNA, viral vector, and inactivated whole-virion COVID-19 vaccines. Most cases had additional risk factors associated with rejection. Vaccination increases circulation of proinflammatory cytokines, CD4+ and CD8+ T-cell responses, and antispike neutralizing antibody, all of which may contribute to graft rejection. Two prospective studies have found no relationship between recent vaccination and rejection but 20% of cornea specialists report to have seen a vaccine-associated rejection and 22% recommend delaying vaccination in certain circumstances. Many specialists recommend prophylactic topical corticosteroids before and after vaccination to mitigate rejection risk but there is no evidence to support this practice on a wider scale. SUMMARY: Our framework identified 96.8% of penetrating keratoplasty patients with vaccine-associated rejection as higher risk. Further research is needed in order to develop evidence-based guidelines.

Bilateral exudative retinal detachments and associated choroidal detachments in a patient on dapsone: a case report.

BACKGROUND: Dapsone is a synthetic sulfonamide used to treat numerous dermatologic conditions. Ocular side effects have been rarely reported and include retinal necrosis, optic atrophy, and macular infarction. We report the first known case of bilateral choroidal effusions and exudative retinal detachments associated with dapsone use. CASE PRESENTATION: A 57-year-old male with a past medical history of testicular seminoma presented with bilateral blurry vision for 2 months. His exam revealed bilateral choroidal effusions with bilateral exudative retinal detachments without evidence of intraocular tumor. The patient had recently been prescribed dapsone for urticarial vasculitis. The patient was instructed to discontinue dapsone and follow-up closely. Interval follow-up of 8 months demonstrated almost complete resolution of the choroidal effusions and retinal detachments with residual pigment epithelium changes after cessation of dapsone. The patient recovered his pre-detachment visual function. CONCLUSIONS: Patients on dapsone who present with new visual complaints should undergo a thorough ophthalmic evaluation given the multiple mechanisms by which dapsone can affect the eye.

A case of ciliary body cyst with extrascleral extension.

We report the case of a 3-year-old girl who presented with an elevated, darkly colored, subconjunctival lesion found to be a ciliary body cyst with extrascleral extension. The patient was treated with excision of bulbar conjunctiva, sclera, and the ciliary body cystic lesion. The defect was repaired with a scleral patch graft. The patient had a small recurrent cyst after 15 months of postsurgical follow-up, and the procedure was repeated. There was no recurrence at follow-up 1 year after the second surgery.

Urinary MyProstateScore (MPS) to Rule out Clinically-Significant Cancer in Men with Equivocal (PI-RADS 3) Multiparametric MRI: Addressing an Unmet Clinical Need.

OBJECTIVE: To evaluate the complementary value of urinary MyProstateScore (MPS) testing and multiparametric MRI (mpMRI) and assess outcomes in patients with equivocal mpMRI. MATERIALS AND METHODS: Included patients underwent mpMRI followed by urine collection and prostate biopsy at the University of Michigan between 2015 -2019. MPS values were calculated from urine specimens using the validated model based on serum PSA, urinary PCA3, and urinary TMPRSS2:ERG. In the PI-RADS 3 population, the discriminative accuracy of PSA, PSAD, and MPS for GG≥2 cancer was quantified by the AUC curve. Decision curve analysis was used to assess net benefit of MPS relative to PSAD. RESULTS: There were 540 patients that underwent mpMRI and biopsy with MPS available. The prevalence of GG≥2 cancer was 13% for PI-RADS 3, 56% for PI-RADS 4, and 87% for PI-RADS 5. MPS was significantly higher in men with GG≥2 cancer [median 44.9, IQR (29.4 -57.5)] than those with negative or GG1 biopsy [median 29.2, IQR (14.8 -44.2); P <.001] in the overall population and when stratified by PI-RADS score. In the PI-RADS 3 population (n = 121), the AUC for predicting GG≥2 cancer was 0.55 for PSA, 0.62 for PSAD, and 0.73 for MPS. MPS provided the highest net clinical benefit across all pertinent threshold probabilities. CONCLUSION: In patients that underwent mpMRI and biopsy, MPS was significantly associated with GG≥2 cancer across all PI-RADS scores. In the PI-RADS 3 population, MPS significantly outperformed PSAD in ruling out GG≥2 cancer. These findings suggest a complementary role of MPS testing in patients that have undergone mpMRI.

Reciprocal Influence of Mobility and Speech-Language: Advancing Physical Therapy and Speech Therapy Cotreatment and Collaboration for Adults With Neurological Conditions.

Mobility and speech-language impairments and limitations in adults with neurological conditions manifest not in isolated anatomical components but instead in the individual-environment system and are task-dependent. Optimization of function thus requires interprofessional care to promote participation in meaningful life areas within appropriate task and environmental contexts. Cotreatment guidelines (ie, the concurrent intervention of disciplines) were established by the physical therapy, occupational therapy, and speech-language and hearing professional organizations nearly 2 decades ago to facilitate seamless interprofessional care. Despite this, cotreatment between physical therapy and speech therapy remains limited. The purpose of this Perspective article is to encourage physical therapists and speech-language pathologists to increase interprofessional collaboration through cotreatment in the management of adults with neurological conditions. Evidence from pediatrics and basic motor control literature points toward reciprocal interactions between speech-language and mobility. We provide recommendations for clinical practice with an emphasis on the gains each discipline can provide the other. This Perspective is rooted in the International Classification of Functioning, Disability and Health model and ecological theory. IMPACT: The goals of speech therapy and physical therapy are complementary and mutually supportive. Enhanced cotreatment, and collaboration more generally, between physical therapists and speech-language pathologists in the management of adults with neurological conditions can augment task-relevant conditions to improve function.

Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome.

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical and molecular spectrum of WSS in diverse populations, to identify physical features that may be more prevalent in White versus Black Indigenous People of Color individuals, to delineate genotype-phenotype correlations, to define developmental milestones, to describe the syndrome through adulthood, and to examine clinicians' differential diagnoses. Sixty-nine of the 82 variants (84%) observed in the study were not previously reported in the literature. Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%). The median ages at walking and first words were 20 months and 18 months, respectively. Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non-LoF variants. This study identifies genotype-phenotype correlations as well as race-facial feature associations in an ethnically diverse cohort, and accurately defines developmental trajectories, medical comorbidities, and long-term outcomes in individuals with WSS.

Deletion at an 1q24 locus reveals a critical role of long noncoding RNA DNM3OS in skeletal development.

BACKGROUND: Skeletal development and maintenance are complex processes known to be coordinated by multiple genetic and epigenetic signaling pathways. However, the role of long non-coding RNAs (lncRNAs), a class of crucial epigenetic regulatory molecules, has been under explored in skeletal biology. RESULTS: Here we report a young patient with short stature, hypothalamic dysfunction and mild macrocephaly, who carries a maternally inherited 690 kb deletion at Chr.1q24.2 encompassing a noncoding RNA gene, DNM3OS, embedded on the opposite strand in an intron of the DYNAMIN 3 (DNM3) gene. We show that lncRNA DNM3OS sustains the proliferation of chondrocytes independent of two co-cistronic microRNAs miR-199a and miR-214. We further show that nerve growth factor (NGF), a known factor of chondrocyte growth, is a key target of DNM3OS-mediated control of chondrocyte proliferation. CONCLUSIONS: This work demonstrates that DNM3OS is essential for preventing premature differentiation of chondrocytes required for bone growth through endochondral ossification.

Auditory-perceptual acuity in rhotic misarticulation: baseline characteristics and treatment response.

The rhotic sound /r/ is one of the latest-emerging sounds in English, and many children receive treatment for residual errors affecting /r/ that persist past the age of 9. Auditory-perceptual abilities of children with residual speech errors are thought to be different from their typically developing peers. This study examined auditory-perceptual acuity in children with residual speech errors affecting /r/ and the relation of these skills to production accuracy, both before and after a period of treatment incorporating visual biofeedback. Identification of items along an /r/-/w/ continuum was assessed prior to treatment. Production accuracy for /r/ was acoustically measured from standard/r/stimulability probes elicited before and after treatment. Fifty-nine children aged 9-15 with residual speech errors (RSE) affecting /r/ completed treatment, and forty-eight age-matched controls who completed the same auditory-perceptual task served as a comparison group. It was hypothesized that children with RSE would show lower auditory-perceptual acuity than typically developing speakers and that higher auditory-perceptual acuity would be associated with more accurate production before treatment. It was also hypothesized that auditory-perceptual acuity would serve as a mediator of treatment response. Results indicated that typically developing children have more acute perception of the /r/-/w/ contrast than children with RSE. Contrary to hypothesis, baseline auditory-perceptual acuity for /r/ did not predict baseline production severity. For baseline auditory-perceptual acuity in relation to biofeedback efficacy, there was an interaction between auditory-perceptual acuity and gender, such that higher auditory-perceptual acuity was associated with greater treatment response in female, but not male, participants.

Imputing HbA1c from capillary blood glucose levels in patients with type 2 diabetes in Sri Lanka: a cross-sectional study.

OBJECTIVE: To develop a population-specific methodology for estimating glycaemic control that optimises resource allocation for patients with diabetes in rural Sri Lanka. DESIGN: Cross-sectional study. SETTING: Trincomalee, Sri Lanka. PARTICIPANTS: Patients with non-insulin-treated type 2 diabetes (n=220) from three hospitals in Trincomalee, Sri Lanka. OUTCOME MEASURE: Cross-validation was used to build and validate linear regression models to identify predictors of haemoglobin A1c (HbA1c). Validation of models that regress HbA1c on known determinants of glycaemic control was thus the major outcome. These models were then used to devise an algorithm for categorising the patients based on estimated levels of glycaemic control. RESULTS: Time since last oral intake other than water and capillary blood glucose were the statistically significant predictors of HbA1c and thus included in the final models. In order to minimise type II error (misclassifying a high-risk individual as low-risk or moderate-risk), an algorithm for interpreting estimated glycaemic control was created. With this algorithm, 97.2% of the diabetic patients with HbA1c ≥9.0% were correctly identified. CONCLUSIONS: Our calibrated algorithm represents a highly sensitive approach for detecting patients with high-risk diabetes while optimising the allocation of HbA1c testing. Implementation of these methods will optimise the usage of resources devoted to the management of diabetes in Trincomalee, Sri Lanka. Further external validation with diverse patient populations is required before applying our algorithm more widely.

Clinical and molecular cytogenetic characterization of a novel 10q interstitial deletion: a case report and review of the literature.

BACKGROUND: There are only ten reported cases of interstitial deletions involving cytogenetic bands 10q21.3q22.2 in the literature. Of the ten patients with overlapping 10q21.3q22.2 interstitial deletions, only nine have been characterized by chromosomal microarray analysis. Here, we report a two-and-a-half-year-old patient with a de novo 10.2-Mb deletion that extends from 10q21.3 to 10q22.3 and contains 92 protein coding genes. CASE PRESENTATION: The patient is the product of a 37-week dizygotic twin pregnancy and presented with global developmental delay, hypotonia, feeding difficulties, short stature, poor weight gain, scaphocephaly, retrognathia, hypoplasia of the optic nerves/chiasms, a distinctive facial gestalt, as well as additional minor dysmorphic features. The deletion identified in our patient is the second largest reported interstitial deletion involving the 10q21.3q22.2 region. Our patient presents with the generalized features observed in 10q21.3q22.2 deletion patients and also presents with several novel findings including scaphocephaly, hypoplasia of the optic nerves and chiasms, and a very distinctive facial gestalt. CONCLUSIONS: Based on a literature review, we identify a commonly deleted region and suggest that KAT6B is a critical gene within the 10q21.3q22.2 region. However, a review of the reported overlapping deletions also suggests that there are additional critical genes contributing to the clinical presentation of these patients.

ZMIZ1 Variants Cause a Syndromic Neurodevelopmental Disorder.

ZMIZ1 is a coactivator of several transcription factors, including p53, the androgen receptor, and NOTCH1. Here, we report 19 subjects with intellectual disability and developmental delay carrying variants in ZMIZ1. The associated features include growth failure, feeding difficulties, microcephaly, facial dysmorphism, and various other congenital malformations. Of these 19, 14 unrelated subjects carried de novo heterozygous single-nucleotide variants (SNVs) or single-base insertions/deletions, 3 siblings harbored a heterozygous single-base insertion, and 2 subjects had a balanced translocation disrupting ZMIZ1 or involving a regulatory region of ZMIZ1. In total, we identified 13 point mutations that affect key protein regions, including a SUMO acceptor site, a central disordered alanine-rich motif, a proline-rich domain, and a transactivation domain. All identified variants were absent from all available exome and genome databases. In vitro, ZMIZ1 showed impaired coactivation of the androgen receptor. In vivo, overexpression of ZMIZ1 mutant alleles in developing mouse brains using in utero electroporation resulted in abnormal pyramidal neuron morphology, polarization, and positioning, underscoring the importance of ZMIZ1 in neural development and supporting mutations in ZMIZ1 as the cause of a rare neurodevelopmental syndrome.

Modelling category goodness judgments in children with residual sound errors.

This study investigates category goodness judgments of /r/ in adults and children with and without residual speech errors (RSEs) using natural speech stimuli. Thirty adults, 38 children with RSE (ages 7-16) and 35 age-matched typically developing (TD) children provided category goodness judgments on whole words, recorded from 27 child speakers, with /r/ in various phonetic environments. The salient acoustic property of /r/ - the lowered third formant (F3) - was normalized in two ways. A logistic mixed-effect model quantified the relationships between listeners' responses and the third formant frequency, vowel context and clinical group status. Goodness judgments from the adult group showed a statistically significant interaction with the F3 parameter when compared to both child groups (p < 0.001) using both normalization methods. The RSE group did not differ significantly from the TD group in judgments of /r/. All listeners were significantly more likely to judge /r/ as correct in a front-vowel context. Our results suggest that normalized /r/ F3 is a statistically significant predictor of category goodness judgments for both adults and children, but children do not appear to make adult-like judgments. Category goodness judgments do not have a clear relationship with /r/ production abilities in children with RSE. These findings may have implications for clinical activities that include category goodness judgments in natural speech, especially for recorded productions.

De novo loss-of-function variants of ASH1L are associated with an emergent neurodevelopmental disorder.

De novo variants of ASH1L, which encodes a histone methyltransferase, have been reported in a few patients with intellectual disability and autistic features. Here, we identified a novel de novo frame-shift variant, c.2422_2423delAAinsT which predicts p.(Lys808TyrfsTer40), in ASH1L in a patient with multiple congenital anomalies (MCA), fine motor developmental delay, learning difficulties, attention deficit hyperactivity disorder, sleep apnea, and scoliosis. This frame-shift variant is expected to result in loss-of-function. Our report provides further evidence to support loss-of-function alterations of ASH1L as causative for an emergent neurodevelopmental syndrome characterized by MCA, intellectual disability, and behavioral problems, and further delineates this genetic disorder.