Development of core sets for deafblindness: an international expert survey on functioning and disability of individuals living with deafblindness using the International Classification of Functioning, Disability, and Health.

BACKGROUND: The development of International Classification of Functioning, Disability, and Health (ICF) Core Sets greatly enhances the global recognition of health conditions, thereby advancing research, education, and care provision. Aside from the work of researchers, and the viewpoint of persons with lived experience, the development of Core Sets for deafblindness needs to include the viewpoints of professionals with expertise unique to this condition. AIM: To represent the perspective of health and social service expert professionals in the development of ICF Core Sets for deafblindness. DESIGN: Cross-sectional cohort study. SETTING: Global online survey representing all six regions of the World Health Organization. POPULATION: One hundred and five professionals providing and health or social service to individuals living with deafblindness with a minimum of 2 years of work experience with this population. METHODS: An online survey was distributed through professional networks and social media for individuals working with persons living with deafblindness. Demographic items were summarized using descriptive statistics. Six open-ended questions explored the perceptions of body functions and structures that influence activities and participation, as well as environmental and personal factors that facilitate functioning. Data were linked to the ICF codes using established linking rules and procedures. RESULTS: The 2934 survey response units were linked using IFC categories. Of the 421 unique categories, 133 were used by 5% or more of respondents. Most categories within the Activities and Participation component were equally emphasized. The most frequent Environmental factors were support and relationships, services, systems, and policies, as well as and the physical environment (e.g., hearing aids or noise). Mental functions, including higher level cognitive functions, temperament and personality were frequently emphasized. CONCLUSIONS: Almost three quarters (73.3%) of the entire ICF classification categories were included in the expert survey results. This proportion emphasizes the importance of a multidimensional tool, such as the ICF, for assessing functioning and health for persons with deafblindness. CLINICAL REHABILITATION IMPACT: The representation of this professional perspective in Core Set development will improve standardized assessment and documentation, intervention planning, and facilitate interprofessional communication with the goal of improving person-centered care for persons living with deafblindness.

The development of the International Classification of Functioning, Disability and Health Core Sets for deafblindness: A study protocol.

BACKGROUND: Individuals with deafblindness experience a combination of hearing and vision impairments. The World Health Organization has developed a global framework referred to as the International Classification of Functioning, Disability and Health (ICF) to describe health and functioning. From the full ICF classification, a selection of categories, referred to as ICF Core Sets, provide users with a tool to describe functioning and disability in specific health conditions. There has been no ICF Core Set created for deafblindness. Given that core sets are instrumental in improving clinical practice, research, and service delivery, the aim of this study is to develop an ICF Core Set for deafblindness. METHODS: As part of the preparatory phase in the ICF Core Set development, there are four studies that will be conducted. This includes the [1] systematic literature review that examines the researcher's perspective, [2] qualitative study focusing on the individuals with deafblindness experience, [3] experts survey that looks at health professional's perspective, and [4] empirical study that examines the clinical perspective. The studies will be conducted using the principles outlined by the ICF Research Branch for the development of ICF Core Sets. The systematic literature review protocol was submitted for registration on PROSPERO CRD42021247952. DISCUSSION: An ICF Core Set created for deafblindness will benefit individuals living with deafblindness who are often excluded from social participation, policies, and services. An ICF Core Set for deafblindness will have a significant impact on healthcare professionals, policymakers, researchers, service providers and individuals with deafblindness by facilitating communication among all stakeholder to support the functioning of those with deafblindness.

Decrease in sleep depth is associated with higher cerebrospinal fluid neurofilament light levels in patients with Alzheimer's disease.

STUDY OBJECTIVES: The majority of studies investigating the association between sleep and Alzheimer's disease (AD) biomarkers have been performed in healthy participants. Our objective was to investigate the association between sleep and several biomarkers that reflect distinct aspects of AD physiopathology. METHODS: The cohort included 104 individuals with mild-moderate AD. The participants were submitted to one-night polysomnography, and cerebrospinal fluid was collected in the following morning to measure the selected biomarkers associated with amyloid deposition, tau pathology, neurodegeneration, axonal damage, synaptic integrity, neuroinflammation, and oxidative damage. RESULTS: There was a positive correlation between neurofilament light (NF-L) and the time spent in stage 1 of non-rapid eyes movement (NREM) (N1) sleep and a negative correlation between this marker and the time spent in stage 3 of NREM (N3) sleep. Accordingly, we observed that deep sleep was associated with lower levels of NF-L, whereas light sleep increased the probability of having higher levels of this marker. Furthermore, chitinase-3-like-1 (YKL-40) was negatively correlated with sleep efficiency, the time spent in stage 2 of NREM (N2) sleep, and the time spent in N3 sleep. Conversely, there was a positive correlation between N3 sleep and the oxidative protein damage markers N-ε-(carboxyethyl)lysine and N-ε-(malondialdehyde)lysine. CONCLUSIONS: There were significant correlations between sleep parameters and AD biomarkers related to axonal damage and neuroinflammation, such as NF-L and YKL-40. A lack of deep sleep was associated with higher levels of NF-L. This highlights a potential role for NF-L as a biomarker of sleep disruption in patients with mild-moderate AD in addition to its role in predicting neurodegeneration and cognitive decline.

Obstructive sleep apnoea and cognitive decline in mild-to-moderate Alzheimer's disease.

We evaluated the influence of untreated obstructive sleep apnoea (OSA) on the magnitude of cognitive decline and on several cognitive subdomains in patients with mild-to-moderate Alzheimer's disease.In this single-centre study, 144 patients were recruited prospectively from a cognitive impairment unit and underwent overnight polysomnography.The mean±sd change in the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) score at 12 months was 3.19±5.61 in the non-OSA group and 0.08±5.62 in the OSA group, with an intergroup difference of -3.36 (95% CI 0.19-0.16; p=0.002). We did not observe a significant difference in any cognitive subdomains at 12 months. Regarding Mini-Mental State Examination scores at 36 months, the mean change was 1.69 (95% CI -1.26-4.64; p=0.445). No significant differences were found among different OSA severity groups.We observed that ADAS-cog scores were better in the OSA group than in the non-OSA group by a statistically but not clinically significant margin. We did not find differences in the different cognitive subdomains after 1 year or in global cognition after 3 years of follow-up.

Mitochondrial m.13513G>A Point Mutation in ND5 in a 16-Year-Old Man with Leber Hereditary Optic Neuropathy Detected by Next-Generation Sequencing.

This article reports a Leber hereditary optic neuropathy (LHON) case associated for the first time with mitochondrial m.13513G>A mutation. We present a 16-year-old man who complained of subacute, painless, visual loss. Ocular examination showed optic nerve atrophy, papillary pseudoedema, and optic disc pallor. Extraocular manifestations included hypertrophic myocardiopathy and myopathy. Initial genetic analysis excluded the three most common LHON mutations. Sanger sequencing of the whole mitochondrial deoxyribonucleic acid showed no mutation. Next-generation sequencing (NGS) revealed m.13513G>A mutation in the NADH dehydrogenase (ND5) subunit gene ( MT-ND5 ). The m.13513G>A mutation has never been associated with LHON phenotype without Leigh/mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes features. NGS techniques should be considered when this diagnosis is strongly suspected.

High BDNF serum levels are associated to good cognitive functioning in bipolar disorder.

BACKGROUND: Neurotrophins such as brain-derived neurotrophic factor (BDNF), inflammation and oxidative damage may contribute to the pathophysiology of bipolar disorder (BD) in terms of illness activity. To date, there is a lack of studies linking the cognitive impairment observed in BD with these neurobiological mechanisms. This study aimed to investigate the role of these neurobiological factors in clinical and cognitive outcomes in a sample of bipolar individuals. METHODS: We measured serum BDNF, cytokines and oxidative stress markers in a sample of 133 individuals: 52 euthymic bipolar patients, 32 manic patients and 49 healthy controls. They were all assessed with a comprehensive cognitive battery. Sociodemographic and clinical data were collected. Multiple linear regression models were built to study associations of neurotrophins and inflammatory and oxidative measures with cognitive functioning. RESULTS: BDNF levels were decreased in euthymic (p = 0.039) and manic (p < 0.001) individuals. Conversely, inflammatory (interleukin 6 (IL-6)) (p = 0.019) and oxidative stress (p = 0.003) measures were increased in bipolar individuals compared to controls. BDNF levels were associated with executive functioning (ß = 0.01, p = 0.02) and verbal memory (ß = 0.013, p = 0.005), together with other demographic variables. In particular, verbal memory was also associated with obesity (ß=-0.04, p = 0.005). Neither inflammatory markers, oxidative stress markers nor other relevant clinical variables showed any association with cognitive outcome. CONCLUSIONS: Of all the peripheral neurobiological factors analysed, BDNF was the only one significantly associated with cognitive dysfunction in bipolar disorder individuals. This study emphasizes the role of BDNF not only across mood phases but also in cognitive functioning.

Fluorescence in situ hybridization of TP53 for the detection of chromosome 17 abnormalities in myelodysplastic syndromes.

Conventional G-banding cytogenetics (CC) detects chromosome 17 (chr17) abnormalities in 2% of patients with de novo myelodysplastic syndromes (MDS). We used CC and fluorescence in situ hybridization (FISH) (LSI p53/17p13.1) to assess deletion of 17p in 531 patients with de novo MDS from the Spanish Group of Hematological Cytogenetics. FISH detected - 17 or 17p abnormalities in 13 cases (2.6%) in whom no 17p abnormalities were revealed by CC: 0.9% of patients with a normal karyotype, 0% in non-informative cytogenetics, 50% of patients with a chr17 abnormality without loss of 17p and 4.7% of cases with an abnormal karyotype not involving chr17. Our results suggest that applying FISH of 17p13 to identify the number of copies of the TP53 gene could be beneficial in patients with a complex karyotype. We recommend using FISH of 17p13 in young patients with a normal karyotype or non-informative cytogenetics, and always in isolated del(17p).

Absence of substantial copy number differences in a pair of monozygotic twins discordant for features of autism spectrum disorder.

Autism spectrum disorder (ASD) is a highly heritable disease (~0.9) with a complex genetic etiology. It is initially characterized by altered cognitive ability which commonly includes impaired language and communication skills as well as fundamental deficits in social interaction. Despite the large amount of studies described so far, the high clinical diversity affecting the autism phenotype remains poorly explained. Recent studies suggest that rare genomic variations, in particular copy number variation (CNV), may account for a significant proportion of the genetic basis of ASD. The use of disease-discordant monozygotic twins represents a powerful strategy to identify de novo and inherited CNV in the disorder. Here we present the results of a comparative genome hybridization (CGH) analysis with a pair of monozygotic twins affected of ASD with significant differences in their clinical manifestations that specially affect speech language impairment and communication skills. Array CGH was performed in three different tissues: blood, saliva, and hair follicle, in an attempt to identify germinal and somatic CNV regions that may explain these differences. Our results argue against a role of large CNV rearrangements as a molecular etiology of the observed differences. This forwards future research to explore de novo point mutation and epigenomic alterations as potential explanations of the observed clinical differences.