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Previous research has found that rural children are more likely to be disabled but are less likely to receive care. Both rural and disabled children were significantly impacted by the pandemic, particularly in terms of service utilization. Therefore, this study seeks to identify rural-urban differences in the prevalence of various disability indicators and in the receipt of educational and healthcare services. Data from 12,828 children aged 2-17 who participated in the 2021-2022 National Health Interview Survey (NHIS) was used to examine rural-urban differences in three different disability indicators and in education and health services utilization. Disability indicators included the Washington Group Short Set Composite Disability Indicator, a developmental disability indicator, and a neurodivergence indicator. Bivariate analysis, via Rao-Scott chi-square tests, was used to examine rural-urban disparities. Compared to their urban counterparts, rural children were more likely to have a positive Washington Group Short Set Composite Disability Indicator (14.3% vs. 10.6%) and neurodivergence indicator (17Ð.3% vs. 14.1%). Rural children with disabilities were more likely to have received prescription medication for behavioral, mental, or emotional health or concentration in the past year than urban children (34.2% vs. 25.9%). There was no rural-urban difference in the prevalence of developmental disabilities or other forms of health care use and special education participation. This report highlights the need for further investigation into underlying causes of rural-urban disparities in the prevalence of disabilities, as well as the need for continued support for programs and policies designed to support rural children with disabilities.
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PLAIN ENGLISH SUMMARY: Usher syndrome is the most common cause of deafblindness worldwide and is estimated to affect between 3 and 6 people in every 100,000. Children are born with hearing loss and develop sight loss in their early years of life. A barrier to the involvement and participation of deafblind people in research is access to information in appropriate formats. The degree of sight and hearing impairment experienced by individuals is variable, so there is not a one size fits all solution. We held a research discussion group, that included five people with Usher syndrome, to consider people's accessibility needs for an upcoming research project involving this condition.We have identified a number of considerations for including deafblind people in conversations about research: i) using appropriately sized meeting rooms which offer control over lighting, layout and sound; ii) where appropriate, ensuring written/printed materials are high contrast (e.g. black text with a yellow background) and in large (18 point and above), sans-serif fonts (e.g. Arial); iii) identifying the relevant communication support for the individual whether that be sign language interpretation, lip reading, hearing loop, speech to text reporting or a combination; iv) ensuring that there is access to emotional support for both people who are deafblind and their families before, during and after the research.The outcome of this work is a checklist of considerations when planning to hold a research conversation with someone who is deafblind and hinges on earlier interactions to identify the appropriate support needs for the individual. ABSTRACT: Background Usher syndrome is the most common cause of deafblindness worldwide. Children are born with hearing loss and develop sight loss in their early years of life. It is estimated to affect between 3 and 6 people in every 100,000. A barrier to the involvement and participation of deafblind people in research is access to information in appropriate formats. Individuals have varying degrees of sight and hearing impairment meaning there is not a singular solution to supporting all people's communication needs. There is evidence that severe sight and hearing impairments are used as exclusion criteria in some research studies. This exclusion may extend into involvement activities. Methods Eight people, including five people with Usher syndrome, attended a research discussion group. Through this activity, we identified what to consider when looking to improve the experience of taking part in a discussion about research for deafblind individuals. Results Among contributors two people made use of standard British Sign Language interpretation and one communicated using hands-on signing. Contributors highlighted the limitations associated with signing and lip reading such as exhaustion and clear lines of sight as well as the need for additional formats such as speech to text reporting, and high contrast (e.g. black text with a yellow background) printouts with large (18 point and above), sans-serif fonts (e.g. Arial). A large proportion of discussions were on the importance of wrap around emotional support for people who are deafblind and their family throughout the research pathway. This includes counselling, peer support and sensitive and mindful facilitators of involvement activities. Conclusions The range and specific nature of the communication methods and support offerings that deafblind people depend on are broad and require researchers and involvement practitioners to reach out to deafblind contributors earlier on, in order to appropriately tailor approaches and put the most suitable support in place. Informed by this discussion group, we have developed a checklist of key considerations to support the inclusion of deafblind individuals in research conversations, supplemented with input from the sensory disability charity Sense.
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Ionizing radiation, oxidative stress and endogenous DNA-damage processing can result in a variety of single-strand breaks with modified 5' and/or 3' ends. These are thought to be one of the most persistent forms of DNA damage and may threaten cell survival. This study addresses the mechanism involved in recognition and processing of DNA strand breaks containing modified 3' ends. Using a DNA-protein cross-linking assay, we followed the proteins involved in the repair of oligonucleotide duplexes containing strand breaks with a phosphate or phosphoglycolate group at the 3' end. We found that, in human whole cell extracts, end-damage-specific proteins (apurinic/apyrimidinic endonuclease 1 and polynucleotide kinase in the case of 3' ends containing phosphoglycolate and phosphate, respectively) which recognize and process 3'-end-modified DNA strand breaks are required for efficient recruitment of X-ray cross-complementing protein 1-DNA ligase IIIalpha heterodimer to the sites of DNA repair.
Assuntos
Complemento C1/metabolismo , Dano ao DNA , Reparo do DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Polinucleotídeo 5'-Hidroxiquinase/metabolismo , Aminopeptidases/genética , Aminopeptidases/isolamento & purificação , Aminopeptidases/metabolismo , Sequência de Bases , Biotinilação , Extratos Celulares , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/farmacologia , DNA Ligases/metabolismo , DNA Polimerase beta/metabolismo , DNA de Cadeia Simples/efeitos dos fármacos , DNA de Cadeia Simples/efeitos da radiação , Desoxirribonuclease IV (Fago T4-Induzido)/genética , Desoxirribonuclease IV (Fago T4-Induzido)/metabolismo , Formaldeído/química , Formaldeído/farmacologia , Células HeLa , Humanos , Cinética , Magnetismo , Microesferas , Modelos Biológicos , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Oligonucleotídeos/química , Oligonucleotídeos/metabolismo , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/isolamento & purificação , Proteínas de Saccharomyces cerevisiae/metabolismo , Estreptavidina/metabolismo , Especificidade por Substrato , Raios XRESUMO
The low density lipoprotein (LDL) receptor is a modular protein involved in the endocytosis of cholesterol-rich lipoproteins from the circulation. Mutations to the receptor result in familial hypercholesterolemia, and over 60 of these occur in the calcium-binding epidermal growth factor-like domain pair. Two selected mutations in this region (G322S and R329P) were introduced into the domain pair and analyzed by in vitro refolding. Both exhibited differing levels of protein misfolding with R329P being the most pronounced. Solution NMR studies of the mutant domain pairs after purification established that a fraction of protein maintains a native-like fold and that this fraction contains two intact calcium-binding sites. An in vivo analysis of intact receptors containing these binding sites showed significantly reduced cell-surface expression compared with the native LDL receptor levels, again with R329P showing the most severe decrease. The sum of these results suggests that either local changes in structure or domain misfolding may be associated with the mutations. There is also the possibility that the misfolding of the calcium-binding epidermal growth factor-like pair region is propagated to other regions of the intact receptor, resulting in more global defects. Surprisingly, for both mutants, those full-length receptors that fold and reach the cell surface retain the ability to bind LDL and release the ligand upon exposure to low pH. This analysis provides significant insight into the protein defect resulting from each of the two mutations and allows their classification to be 2B (partially transport-defective). The results also highlight a range of misfolding defects that may be associated with familial hypercholesterolemia and may enable the prediction of the consequences of homologous disease-causing mutations to other proteins.