Profound Disabilities Research Articles

Patients with ventricular assist device and cerebral entrapment-Supporting skullcap reimplantation.

Effects of cranioplasty (CP) and skullcap reimplantation after decompressive craniectomy (DC) for cerebral hemorrhage or malignant brain infarction in patients with left ventricular assist device (LVAD) support as bridge to transplantation has not been surveyed yet. The aim of this study was to evaluate outcome and management after CP when aiming for transplantation. Data were collected from our prospective institutional database including all patients undergoing LVAD implantation between 2010 and 2019. Six patients needed CP procedures and were included. Our analysis focused on postoperative outcome, survival, and facilitation of heart transplantation. Study endpoints included also all-cause mortality. From a total of 1010 LVAD implantations during analysis period in our center, six bridge-to-transplantation LVAD patients [median age at LVAD implantation: 32.5years (IQR: 24.8-39.5years); four male, HVAD, n=3; HM II, n=1; HM 3, n=2] underwent CP with imminent entrapment secondary to cerebral hemorrhage or malignant infarction. Primary heart failure etiology was myocarditis (n=2), dilated (n=2), or ischemic (n=2). Median INTERMACS class was 1.5 (IQR; 1.0-2.8). Median time on LVAD support to DC procedure was 33months (IQR: 16-48months). The indication for DC was intraparenchymal hemorrhage (n=4), subdural hematoma (n=1), and malignant middle cerebral artery infarction (n=1). After a median time of 4months (IQR: 3.3-4.0months, range; 2.0-10months) post DC procedure, CP was subsequently performed without profound neurologic disabilities in all patients. After median time of 26months (IQR: 21-42months) follow-up, three patients successfully received heart transplantation, one patient could undergo LVAD explantation for myocardial recovery, and the remaining two patients are still on the list awaiting heart transplantation. CP procedure with skullcap reimplantation is feasible and can be safely performed in LVAD patients, which subsequently may even be eligible for heart transplantation with beneficial prognosis.

Results of a comparative valuation of the efficiency of using the plasmid construct pBud-VEGF165-FGF2 in models of autograft of the sciatic nerve defect and tubulation with the NeuraGen® collagen tube

Traumatic injuries of peripheral nerves lead to profound disability in patients with partial or total loss of limb function. There remains the question about the use of technologies for detecting defects of the peripheral nerve with concurrent of its regeneration. In the study it has been investigated the effect of the gene-therapeutic plasmid construct pBud-VEGF165-FGF2 with various methods of overcoming 5 mm diastasis of the sciatic nerve: nerve autograft and tubulation with the NeuraGen® tube. In the study groups, assessment of sciatic nerve regeneration was based on functional and morphometric parameters. Direct injection of plasmid pBud-VEGF165-FGF2 stimulates regeneration and restoration of motor function in both groups, but with different efficacy. Comparative analysis of nerve defect replacement in combination with direct gene therapy showed the most effective approach with autologous insertion replacement by comparison to the NeuraGen. Thus, on the basis of the obtained data, we can assert that nerve autograft of the peripheral nerve remains the "gold standard” and provides the best hope of research in combination with the use of various regeneration stimulants.

Physical violence and violent threats reported by Aboriginal and Torres Strait Islander people with a disability: cross sectional evidence from a nationally representative survey

BackgroundA recent Royal Commission into the treatment of Australians living with disabilities has underscored the considerable exposure to violence and harm in this population. Yet, little is known about exposure to violence among Aboriginal and Torres Strait Islander people living with disabilities. The objective of this paper was to examine the prevalence, disability correlates and aspects of violence and threats reported by Aboriginal and Torres Strait Islander people living with disabilities.MethodsData from the 2014–15 National Aboriginal and Torres Strait Islander Social Survey were used to measure physical violence, violent threats and disability. Multivariable logistic and ordinal logistic regression models adjusted for complex survey design were used to examine the association between measures of disability and exposure to violence and violent threats.ResultsIn 2014–15, 17% of Aboriginal and Torres Strait Islander people aged 15–64 with disability experienced an instance of physical violence compared with 13% of those with no disability. Approximately 22% of those with a profound or severe disability reported experiencing the threat of physical violence. After adjusting for a comprehensive set of confounding factors and accounting for complex survey design, presence of a disability was associated with a 1.5 odds increase in exposure to physical violence (OR = 1.54 p < 0.001), violence with harm (OR = 1.55 p < 0.001), more frequent experience of violence (OR = 1.55 p < 0.001) and a 2.1 odds increase (OR = 2.13 p < 0.001) in exposure to violent threats. Severity of disability, higher numbers of disabling conditions as well as specific disability types (e.g., psychological or intellectual) were associated with increased odds of both physical violence and threats beyond this level. Independent of these effects, removal from one’s natural family was strongly associated with experiences of physical violence and violent threats. Aboriginal and Torres Strait Islander women, regardless of disability status, were more likely to report partner or family violence, whereas men were more likely to report violence from other known individuals.ConclusionAboriginal and Torres Strait Islander people with disability are at heightened risk of physical violence and threats compared to Aboriginal and Torres Strait Islander people without disability, with increased exposure for people with multiple, severe or specific disabilities.

Communication-related assessments in an Angelman syndrome mouse model.

IntroductionAngelman syndrome (AS) is a neurodevelopmental disorder characterized by motor deficits, seizures, some autistic‐like behaviors, and severe impairment of speech. A dysfunction of the maternally imprinted UBE3A gene, coupled with a functional yet silenced paternal copy, results in AS. Although studies of transgenic mouse models have revealed a great deal about neural populations and rescue timeframes for specific features of AS, these studies have largely failed to examine intermediate phenotypes that contribute to the profound communicative disabilities associated with AS.MethodsHere, we use a variety of tasks, including assessments of rapid auditory processing and social communication. Expressive vocalizations were directly assessed and correlated against other core behavioral measures (motor, social, acoustic perception) to model putative influences on communication.ResultsAS mice displayed the characteristic phenotypes associated with Angelman syndrome (i.e., social and motor deficits), as well as marginal enhancements in rapid auditory processing ability. Our characterization of adult ultrasonic vocalizations further showed that AS mice produce fewer vocalizations and vocalized for a shorter amount of time when compared to controls. Additionally, a strong correlation between motor indices and ultrasonic vocalization output was shown, suggesting that the motor impairments in AS may contribute heavily to communication impairments.ConclusionIn summary, the combination of motor deficits, social impairment, marginal rapid auditory enhancements, and altered ultrasonic vocalizations reported in a mouse model of AS clearly parallel the human symptoms of the disorder. This mouse model offers a novel route to interrogate the underlying genetic, physiologic, and behavioral influences on the under‐studied topic of impaired communication in AS.

Inter-rater reliability of the assessment of learning powered mobility use, version 2.0, when applied with children and adults engaged in Driving to Learn in a powered wheelchair.

The Assessment of Learning Powered mobility use (ALP) tool including the ALP instrument and facilitating strategies, was developed for Driving to Learn. This therapeutic intervention aims to provide children and adults who have profound cognitive disabilities with opportunities to learn tool use through powered mobility practise. To allow for longer intervention periods, a partnership was developed between professionals supervising Driving to Learn and persons accompanying children or adults to their practice sessions. Accompanying persons (relatives or assistants) gradually took on shared responsibility for applying the intervention and conducting assessments with the ALP-instrument. The aim of this study was to test the inter-rater reliability of the ALP-instrument version 2.0 as applied in this novel partnership in assessment and intervention. A psychometric analysis compared pair-wise assessments with the ALP-instrument version 2.0, made independently by professional supervisors and accompanying persons following each Driving to Learn session. Weighted kappa statistic was used to compare the matched pair ordinal data. Eight professional supervisors and 22 accompanying persons independently completed assessments with the ALP-instrument after 55 sessions with six children and five adults, who each participated in five Driving to Learn sessions. When the scores from the 55 pairs of assessments were compared, a weighted kappa value of 0.85 was obtained, indicating very good inter-rater reliability between the two rater groups. The resulting inter-rater reliability suggests that it is reliable to implement the ALP-instrument as part of partnership in intervention between supervisors and accompanying persons. Provision of longer periods of Driving to Learn is possible when those who accompany the child or adult are able to gradually assume responsibility for practice and assessment under the supervision of a professional. This partnership approach enables children and adults with multiple and complex disabilities to practise and learn in accordance with their conditions and needs.

Reconceptualising teacher education for teachers of learners with severe to profound disabilities

ABSTRACT This paper considers teacher education for teachers of learners with severe to profound disabilities (SPD) in South Africa, in both formal and non-formal learning programmes within a disability studies in education framework. Qualitative data were collected from a range of education stakeholders including non-governmental (NGOs) and disabled people organisations (DPOs). Based on a thematic analysis, findings show limited pre-service teacher education programmes focused on teaching learners with SPD. In-service teacher training through education departments and NGOs and DPOs, is usually through basic short courses or workshops and are not complemented by on-going support. We argue for a reconceptualization of teacher education in South Africa to prepare teachers to meet the diverse needs of learners, including those with SPDs within an inclusive education context. Skills in addressing barriers to learning should be infused throughout initial teacher education, in line with the principles of universal design for learning while impairment-specific knowledge can be offered in related modules that focus on reasonable accommodation for children with disabilities. In-service education can occur in formal and informal programmes and should empowers teachers to become lifelong learners.

Promoting Object Manipulation and Reducing Tongue Protrusion in Seven Children with Angelman Syndrome and Developmental Disabilities through Microswitch-Cluster Technology: a Research Extension

We further extended the use of a microswitch-cluster technology to promote object manipulation and to reduce tongue protrusion in seven children with Angelman syndrome. Study I included seven participants with severe to profound developmental disabilities. An ABB1AB1 experimental sequence was implemented. During the baselines (i.e., A phases) the technology was available but inactive. During the intervention (i.e., B phase) the adaptive responding was positively reinforced irrespective of the challenging behavior. During the cluster (i.e., B1 phases) the adaptive responding was contingently reinforced only if it occurred free of the challenging behavior. A long-term follow-up (i.e., 24 months) was conducted. Intervals with indices of positive participation as an outcome measure of the participants’ constructive engagement and favorable occupation were additionally recorded. Study II recruited 56 external raters (i.e., equally divided in 4 groups among caregivers, physiotherapists, psychologists, and teachers) in a social validation procedure. Results evidenced the effectiveness and the suitability of the technology to pursue the dual goal (i.e., increasing the adaptive responding and simultaneously decreasing the challenging behavior). All the participants consolidated their learning process and positively participated along the intervention phases. Social raters favorably scored the use of the technology. Educational, clinical, psychological, and rehabilitative implications of the findings were critically discussed. Some useful insights for future research and practice were emphasized.

Health problems and access to health care services for the persons with disabilities in Lahore.

Objectives: This study aims to explore the major health problems of persons with disabilities, to see the difference between the health problems of persons with mild to moderate and severe to profound disabilities, and highlight the problems. Study Design: Quantitative Study. Setting: University of the Punjab, Lahore. Period: 15 March 2018 to 14 Dec 2020. Material &amp; Methods: The study included a quantitative survey conducted with interviews of 100 persons with different disabilities (50 mild to moderate disabilities, 50 severe to profound disabilities) selected by applying convenient sampling method. A questionnaire was used for the data collection. The questionnainaire comprised of three parts: first part was about demographics,the second part consisted of items related to the health problems and third part consisted of items related to the access to health care services. Non-parametric statistical analysis was used for the data analysis. Comparison between persons with mild to moderate and severe to profound disabilities was made. Results: Results showed that persons with severe to profound disabilities generally experienced more health problems and problems in accessing health care services as compared to persons with mild to moderate disabilities. Conclusion: The study concluded that persons with disabilities experience physical, attitudinal and communication problems while accessing health services.

Using Musical Play with children with profound and multiple learning disabilities at school

We all ‘play’ music! Play experiences for children with profound and multiple learning disabilities (PMLD) are often compromised, lost in complex care routines, increasingly stretched timetables and a lack of suitable play interventions. This study investigates combining music with play, using a set of guidelines and principles developed by the researcher and staff participants: Musical Play. It evaluates the impact of Musical Play on the play experiences of both the learners and staff. This study included five primary‐aged children and four teaching staff, during a five‐week implementation period in a UK special school. The study collected multiple data sources to evaluate the impact of the intervention. Results reveal that Musical Play elicited engaged, playful and creative responses, encouraging peer‐awareness and interactions. The intervention allowed staff a sense of freedom from target‐driven work, providing a unique opportunity to immerse themselves fully in the play experience.

Cellular and animal models for facioscapulohumeral muscular dystrophy.

ABSTRACTFacioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy and presents with weakness of the facial, scapular and humeral muscles, which frequently progresses to the lower limbs and truncal areas, causing profound disability. Myopathy results from epigenetic de-repression of the D4Z4 microsatellite repeat array on chromosome 4, which allows misexpression of the developmentally regulated DUX4 gene. DUX4 is toxic when misexpressed in skeletal muscle and disrupts several cellular pathways, including myogenic differentiation and fusion, which likely underpins pathology. DUX4 and the D4Z4 array are strongly conserved only in primates, making FSHD modeling in non-primate animals difficult. Additionally, its cytotoxicity and unusual mosaic expression pattern further complicate the generation of in vitro and in vivo models of FSHD. However, the pressing need to develop systems to test therapeutic approaches has led to the creation of multiple engineered FSHD models. Owing to the complex genetic, epigenetic and molecular factors underlying FSHD, it is difficult to engineer a system that accurately recapitulates every aspect of the human disease. Nevertheless, the past several years have seen the development of many new disease models, each with their own associated strengths that emphasize different aspects of the disease. Here, we review the wide range of FSHD models, including several in vitro cellular models, and an array of transgenic and xenograft in vivo models, with particular attention to newly developed systems and how they are being used to deepen our understanding of FSHD pathology and to test the efficacy of drug candidates.

Indicators of blood biochemical analysis in PKU patients being on amino acid mixtures substitute nutrition

Topicality. Phenylketonuria is a congenital pathology of amino acid metabolism, which is a rare (orphan) disease. Depending on the regions of the world and the ethnic origin of the inhabitants, its prevalence can vary from 1/2600 to 1/200000. Phenylketonuria is caused by a deficiency of liver enzyme phenylalanine hydroxylase, which catalyzes the hydroxylation of phenylalanine, resulting in the formation of tyrosine. Enzyme deficiency leads to hyperphenylalaninemia, and in the absence of adequate therapeutic measures will lead to profound and irreversible disability of the patient.Aim. To conduct a comparative analysis of amino acid mixtures “Nutri-2”, “Nutri-3”, “PAM-2” and “PAM-3”, as well as to determine the biochemical parameters of the blood of four groups of patients on these diets according to their age needs.Materials and methods. On the basis of Kharkiv interregional specialized medical-genetic center of rare (orphan) diseases, treatment of phenylketonuria with the use of amino acid mixtures was introduced and further biochemical analysis of patients’ blood was performed. The results of biochemical parameters of blood of four groups of heterosexual and different-aged patients on different amino acid mixtures were taken for the study. The study involved 16 patients of different sexes aged 4 to 29 years.Results and discussion. The determined values of most biochemical markers in patients with PKU were within the reference values. In some patients taking PAM-2, minor changes were observed, which were reflected in increased urea content and activity of aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase outside the upper limit of normal.Conclusions. New therapeutic foods have more balanced nutritional composition, developed according to modern dietary recommendations, which is confirmed by stable biochemical parameters of the blood of patients with phenylketonuria.

DISCERNING PERSONS: PROFOUND DISABILITY, THE EARLY CHURCH FATHERS, AND THE CONCEPT OF THE PERSON IN BIOETHICS. By PiaMatthews. Steubenville, OH: Franciscan University Press, 2020. Pp. 368. Hardcover, $65.00.

Religious Studies ReviewVolume 46, Issue 3 p. 385-385 Short Reviews of Recent Publications: Theology DISCERNING PERSONS: PROFOUND DISABILITY, THE EARLY CHURCH FATHERS, AND THE CONCEPT OF THE PERSON IN BIOETHICS. By Matthews, Pia. Steubenville, OH: Franciscan University Press, 2020. Pp. 368. Hardcover, $65.00. First published: 11 November 2020 https://doi.org/10.1111/rsr.14739Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume46, Issue3Special Issue: Religion and SexualitySeptember 2020Pages 385-385 RelatedInformation

Supporting Adaptive Responding and Reducing Challenging Behaviors of Children with Rare Genetic Syndromes and Severe to Profound Developmental Disabilities Through Assistive Technology-Based Programs

Supporting Adaptive Responding and Reducing Challenging Behaviors of Children with Rare Genetic Syndromes and Severe to Profound Developmental Disabilities Through Assistive Technology-Based Programs

Targeting Serotonin 5-HT2A Receptors to Better Treat Schizophrenia: Rationale and Current Approaches.

Schizophrenia is a major mental illness associated with profound disability. Current treatments for schizophrenia (antipsychotics) all have a similar mechanism of action and are primarily dopamine type 2 receptor (D2R) antagonists. Antipsychotics are not fully effective for the majority of schizophrenia patients, suggesting the need for alternative approaches. The primary focus of this review is to assess the evidence for the role of the serotonin type 2A receptor (5-HT2AR) in schizophrenia. Topics include an overview of 5-HT2AR physiology and pathophysiology in schizophrenia, 5-HT2AR interaction with other neurotransmitter systems, including the glutamatergic system, a review of the 5-HT2AR/d-lysergic acid diethylamide (LSD) model of schizophrenia, a contrast of the 5-HT2AR and glutamatergic models of schizophrenia, and finally, a review of Food and Drug Administration (FDA)-approved and investigational 5-HT2AR-modulating compounds. Recent studies with lumeteperone, pimavanserin, and roluperidone are highlighted.

Heteromeric Kv7.2 current changes caused by loss-of-function of KCNQ2 mutations are correlated with long-term neurodevelopmental outcomes

Pediatric epilepsy caused by KCNQ2 mutations can manifest benign familial neonatal convulsions (BFNC) to neonatal-onset epileptic encephalopathy (EE). Patients might manifest mild to profound neurodevelopmental disabilities. We analysed c.853C > A (P285T) and three mutations that cause KCNQ2 protein changes in the 247 position: c.740C > T (S247L), c.740C > A (S247X), and c.740C > G (S247W). S247L, S247W, and P285T cause neonatal-onset EE and poor neurodevelopmental outcomes; S247X cause BFNC and normal outcome. We investigated the phenotypes correlated with human embryonic kidney 293 (HEK293) cell functional current changes. More cell-current changes and a worse conductance curve were present in the homomeric transfected S247X than in S247L, S247W, and P285T. But in the heteromeric channel, S247L, S247W and P285T had more current impairments than did S247X. The protein expressions of S247X were nonfunctional. The outcomes were most severe in S247L and S247W, and severity was correlated with heteromeric current. Current changes were more significant in cells with homomeric S247X, but currents were “rescued” after heteromeric transfection of KCNQ2 and KCNQ3. This was not the case in cells with S247L, S247W. Our findings support that homomeric current changes are common in KCNQ2 neonatal-onset EE and KCNQ2 BFNC; however, heteromeric functional current changes are correlated with long-term neurodevelopmental outcomes.

Relational suffering and the moral authority of love and care.

Suffering is a ubiquitous yet elusive concept in health care. In a field devoted to the pursuit of objective data, suffering is a phenomenon with deep ties to subjective experience, moral values, and cultural norms. Suffering’s tie to subjective experience makes it challenging to discern and respond to the suffering of others. In particular, the question of whether a child with profound neurocognitive disabilities can suffer has generated a robust discourse, rooted in philosophical conceptualizations of personhood as well as the academic and experiential expertise of practiced health-care professionals. The issue remains unresolved because it is difficult, perhaps impossible, to ever truly know an infant’s lived experience. But what if this is not the best question? What if instead of asking “can this infant suffer?” the discourse is broadened to ask “is there suffering here?” This latter question demands attention to patients’ subjective experiences of suffering, but also to the web of relationships that envelop them. Without losing sight of the importance of patients’ experiences, consideration of their relationships may elucidate the presence of suffering when the patients themselves are unable to provide the same clarity. In this essay, care ethics frames an examination of how suffering manifests in the loving and caring relationships that surround an infant with profound neurocognitive disabilities, changing those relationships and affecting the individuals within them. Exploring suffering through these relationships may offer clarity on the presence and content of suffering for infants with profound cognitive disabilities, in turn offering moral guidance for responding to suffering and supporting flourishing in this context.

Osteitis Pubis, Following Normal Vaginal Delivery: A Case Report

Background: The osteitis pubis is an inflammatory-noninfectious disease of the pubic symphysis, which is rarely reported in the postpartum period after normal vaginal delivery. Misdiagnosis of this disease can leave the patient disabled with a poor quality of life Case report: The case in the present study was a 35-year-old woman, admitted two days after giving birth, due to severe pain in the hypogastric and groin regions. Movement aggravated the pain in a way that disabled the patient. The pelvic radiograph showed pubic symphysis dislocation, and osteitis pubis was clinically diagnosed. Therefore, conservative treatment was prescribed for her, including relative bed rest, nonsteroidal anti-inflammatory drugs (PRN, maximum TDS), physiotherapy, and pelvic binder, for two weeks. After this period, her pain decreased gradually and in the next follow-up, which was one month later, she had no limitation of motion. Conclusion: Though it seems to be a simple disease, osteitis pubis can cause profound motion disability. Early diagnosis and treatment can prevent complications, such as joint stiffness and chronic pain.

Anti-dementia drugs for Alzheimer disease

Alzheimer’s disease (AD) is the most common cause of dementia that leads over time to profound disability. Current pharmacological interventions for AD are limited to three cholinesterase inhibitors (donepezil, rivastigmine and galantamine) and the N-Methyl-D-Aspartate (NMDA)-receptor antagonist memantine, both of which provide modest impact on cognitive and functional outcomes. In this study we aimed to evaluate the effect of current treatment for Alzheimer’s disease in different stages of dementia. Cholinesterase inhibitors alone, or in combination with memantine may be beneficial in Alzheimer’s disease depending on stage of AD. There is evidence for stabilization of cognitive function in AD for 2–5 months after the initiation of anti-dementia drugs and the efficacy over time is not fully understand.

Factors influencing the self-esteem of children with a severe or profound learning disability: a pilot study

Factors influencing the self-esteem of children with a severe or profound learning disability: a pilot study

M102. MEASURING PHYSIOLOGICAL RESPONSES ASSOCIATED WITH SOCIAL STRESS IN A VIRTUAL ENVIRONMENT AND ITS RELATIONSHIP WITH CHILDHOOD TRAUMA IN EARLY SCHIZOPHRENIA - A PILOT STUDY

BackgroundIn lower to middle income countries (LMIC), the influences of environmental stress on neurobiological processes involved in the development of schizophrenia is of great importance. High levels of stress may contribute to an increased burden of schizophrenia, including profound functional impairment and disability, decreased productivity, and even elevated mortality. Stress in Schizophrenia has been associated with behavioral disturbances such as maladaptive coping styles as well as well-established physiological abnormalities in sensorimotor gating in the form of abnormal startle responses. In turn, childhood trauma exposure is known to affect physiological stress responses. Indeed, we have found childhood trauma to be associated with both white matter and hippocampal changes in schizophrenia. Few studies, however, have explored the relationship between Childhood trauma and stress responses in schizophrenia. In recent years Virtual Reality (VR) has undergone a resurgence as a viable method for studying fear related physiological stress responses in an ecologically valid manner. Here we aim to investigate the potential relationship between abnormal physiological stress responses in schizophrenia with early life adversity.MethodsPhysiological response data were collected while participants completed a VR paradigm based on the Trier stress test, a well-established social stressor that reliably elicits a stress response in participants in VR and HPA axis attenuation in schizophrenia. Data were also collected in a fear of heights environment, not associated with abnormalities in schizophrenia. Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ). HPA axis stress responses during the course of the task were assessed using saliva cortisol samples collected at key points during the paradigms.ResultsPreliminary data of both the social anxiety and fear of heights scenario will be presented. We will focus specifically on the viability of using VR in a LMIC context.DiscussionVR could prove to be a cost-effective tool to explore the relationship between childhood trauma, stress sensitivity and schizophrenia.