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1.
Disabil Health J ; : 101676, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39097466

RESUMO

BACKGROUND: States use Medicaid 1915(c) waiver programs to enable access to home- and community-based services for people with intellectual and/or developmental disabilities (I/DD). However, enrollment rates and potential inequities are not well documented, impeding efforts to improve care access and quality for waiver program enrollees, especially for racially minoritized beneficiaries experiencing compounded barriers to services and supports. OBJECTIVE: To characterize year-by-year 1915(c) waiver program enrollment among Medicaid-enrolled adults with I/DD from 2016 to 2019 and to analyze population-level inequities by type of I/DD and racial/ethnic group. METHODS: Our data source was 2016-2019 Medicaid Transformed Medicaid Statistical Information System Analytic Files Demographic and Eligibility files for beneficiaries with Down syndrome, autism, and intellectual disability. We used generalized estimating equation linear models to estimate the associations of type of I/DD and racial/ethnic group with the probability of 1915(c) waiver program enrollment and reported (1) unadjusted estimates and (2) estimates adjusted for demographics with state and year fixed effects. RESULTS: From 2016 to 2019, across all types of I/DD and racial/ethnic groups, unadjusted 1915(c) waiver program enrollment rates ranged from 40 to 60 % nationwide. We found modest growth in 1915(c) I/DD waiver program enrollment but persistent inequities over time. Compared to beneficiaries with intellectual disabilities, beneficiaries with autism were less likely to enroll while beneficiaries with Down syndrome were more likely. While some racial/ethnic groups had higher unadjusted mean enrollment, after adjustment, racially minoritized beneficiaries were 3.66-12.0 percentage points less likely to enroll compared to white non-Hispanic beneficiaries. CONCLUSIONS: Given extensive waiting lists for 1915(c) waiver programs, Medicaid programs should evaluate existing enrollment and authorization processes and consider alternative HCBS program authorities.

2.
MicroPubl Biol ; 20242024.
Artigo em Inglês | MEDLINE | ID: mdl-39139584

RESUMO

Aberrant endoplasmic reticulum (ER) and inner nuclear membrane (INM) proteins are destroyed through ER-associated degradation (ERAD) and INM-associated degradation (INMAD). We previously showed the Hrd1, Doa10, and Asi ERAD and INMAD ubiquitin ligases (E3s) in Saccharomyces cerevisiae confer resistance to hygromycin B, which distorts the ribosome decoding center. Here, we assessed the requirement of Ubc6 and Ubc7, the primary ERAD and INMAD ubiquitin-conjugating enzymes (E2s) for hygromycin B resistance. Loss of either E2 sensitized cells to hygromycin B, with UBC7 deletion having a greater impact, consistent with characterized roles for Ubc6 and Ubc7 in ER and INM protein quality control.

3.
J Adv Acad ; 35(3): 432-460, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39100106

RESUMO

Primarily undergraduate institutions (PUI) often struggle to provide authentic research opportunities that culminate in peer-reviewed publications due to "recipe-driven" lab courses and the comprehensive body of work necessary for traditional scientific publication. However, the advent of short-form, single-figure "micropublications" has created novel opportunities for early-career scientists to make and publish authentic scientific contributions on a scale and in a timespan compatible with their training periods. The purpose of this qualitative case study is to explore the benefits accrued by eight undergraduate and master's students who participated in authentic, small-scale research projects and disseminated their work as coauthors of peer-reviewed micropublications at a PUI. In these interviews, students reported that through the process of conducting and publishing their research, they developed specific competencies: reading scientific literature, proposing experiments, and collecting/interpreting publication-worthy data. Further, they reported this process enabled them to identify as contributing members of the greater scientific community.

4.
J Autism Dev Disord ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046684

RESUMO

Our objective was to examine occurrence of both conditions in Medicaid; and compare Medicaid service use and cost, and chronic conditions among adults with Down syndrome and autism to those with Down syndrome alone and those with autism alone. We used ICD9 and ICD10 codes in Medicaid claims and encounters from 2011 to 2019 to identify autism and Down syndrome in adults > 18 years. We then calculated costs, claims, hospitalizations, long term care days, and chronic conditions, and compared by group- autism alone, Down syndrome alone, Down syndrome + autism. Between 2011 and 2019, there were 519,450 adult Medicaid enrollees who met our criteria for autism (N = 396,426), Down syndrome (N = 116,422), or both Down syndrome and autism (N = 6,602). In 2011, 4.1% of enrollees with Down syndrome had co-occurring autism; by 2011 it was 6.6%. The autism group had the fewest claims and inpatient hospitalizations, followed by the Down syndrome group, then the Down syndrome + autism group. After age adjustment, those with Down syndrome alone and Down syndrome + autism had elevated prevalence of atrial fibrillation, dementia, heart failure, kidney disease, and obesity compared to the autism alone group. Both groups also had decreased occurrence of depression and hypertension compared to the autism alone group. Prevalence of autism is higher among people with Down syndrome than in peers. The increased costs and service use for those with both conditions highlight the extent to which this population need health care and signal the need for more effective preventative care and therapies.

5.
MicroPubl Biol ; 20242024.
Artigo em Inglês | MEDLINE | ID: mdl-39071171

RESUMO

We recently discovered that disrupting phospholipid biosynthesis by eliminating the Ino2/4 transcriptional regulator impairs endoplasmic reticulum (ER)-associated degradation (ERAD) in Saccharomyces cerevisiae , but the mechanism is unclear. Phosphatidylcholine deficiency has been reported to accelerate degradation of Sec61 translocon beta subunit Sbh1 and ERAD cofactor Cue1. Here, we found that, unlike targeted phosphatidylcholine depletion, INO4 deletion does not destabilize Sbh1 or Cue1. However, we observed altered electrophoretic mobility of Sbh1 in ino4 Δ yeast, consistent with phospholipid-responsive post-translational modification. A better understanding of the molecular consequences of disrupted lipid homeostasis could lead to enhanced treatments for conditions associated with perturbed lipid biosynthesis.

6.
J Dev Behav Pediatr ; 45(4): e293-e301, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38896561

RESUMO

OBJECTIVE: Early treatment of autism spectrum disorder (ASD) can improve developmental outcomes. Children with ASD from minority families often receive services later. We explored factors related to child's age at time of mother's first concerns about child's development and subsequent time to service initiation among children with ASD. METHODS: Analysis included 759 preschool-age children classified with ASD based on comprehensive evaluations. Factors associated with retrospectively reported child age at time of first maternal concern and subsequent time to service initiation were investigated using multiple linear regression and Cox proportional hazards. RESULTS: Earlier maternal concern was associated with multiparity, ≥1 child chronic condition, externalizing behaviors, and younger gestational age, but not race/ethnicity. Time to service initiation was longer for children of non-Latino Black or other than Black or White race and higher developmental level and shorter for children with ≥1 chronic condition and older child age at first maternal concern. CONCLUSION: Parity, gestational age, and child health and behavior were associated with child age at first maternal concern. Knowledge of child development in multiparous mothers may allow them to recognize potential concerns earlier, suggesting that first time parents may benefit from enhanced education about normal development. Race/ethnicity was not associated with child's age when mothers recognized potential developmental problems; hence, it is unlikely that awareness of ASD symptoms causes racial/ethnic disparities in initiation of services. Delays in time to service initiation among children from racial/ethnic minority groups highlight the need to improve their access to services as soon as developmental concerns are recognized.


Assuntos
Transtorno do Espectro Autista , Mães , Humanos , Transtorno do Espectro Autista/terapia , Transtorno do Espectro Autista/etnologia , Pré-Escolar , Feminino , Masculino , Mães/estatística & dados numéricos , Fatores Etários , Tempo para o Tratamento/estatística & dados numéricos , Adulto , Estudos Retrospectivos , Paridade , Idade Gestacional
7.
Am J Med Genet C Semin Med Genet ; : e32097, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38925597

RESUMO

BACKGROUND: Mosaic Down syndrome is a triplication of chromosome 21 in some but not all cells. Little is known about the epidemiology of mosaic Down syndrome. We described prevalence of mosaic Down syndrome and the co-occurrence of common chronic conditions in 94,533 Medicaid enrolled adults with any Down syndrome enrolled from 2016 to 2019. METHODS: We identified mosaic Down syndrome using the International Classification of Diseases and Related Health Problems, tenth edition code for mosaic Down syndrome and compared to those with nonmosaic Down syndrome codes. We identified chronic conditions using established algorithms and compared prevalence by mosaicism. RESULTS: In total, 1966 (2.08%) had claims for mosaic Down syndrome. Mosaicism did not differ by sex or race/ethnicity with similar age distributions. Individuals with mosaicism were more likely to present with autism (13.9% vs. 9.6%) and attention deficit hyperactivity disorder (17.7% vs. 14.0%) compared to individuals without mosaicism. In total, 22.3% of those with mosaic Down syndrome and 21.5% of those without mosaicism had claims for Alzheimer's dementia (Prevalence difference: 0.8; 95% Confidence interval: -1.0, 2.8). The mosaic group had 1.19 times the hazard of Alzheimer's dementia compared to the nonmosaic group (95% CI: 1.0, 1.3). DISCUSSION: Mosaicism may be associated with a higher susceptibility to certain neurodevelopmental and neurodegenerative conditions, including Alzheimer's dementia. Our findings challenge previous assumptions about its protective effects in Down syndrome. Further research is necessary to explore these associations in greater depth.

8.
Autism Res ; 17(3): 650-667, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38415400

RESUMO

Intellectual disability (ID) commonly co-occurs in children with autism. Although diagnostic criteria for ID require impairments in both cognitive and adaptive functioning, most population-based estimates of the frequency of co-occurring ID in children with autism-including studies of racial and ethnic disparities in co-occurring autism and ID-base the definition of ID solely on cognitive scores. The goal of this analysis was to examine the effect of including both cognitive and adaptive behavior criteria on estimates of co-occurring ID in a well-characterized sample of 2- to 5-year-old children with autism. Participants included 3264 children with research or community diagnoses of autism enrolled in the population-based Study to Explore Early Development (SEED) phases 1-3. Based only on Mullen Scales of Early Learning (MSEL) composite cognitive scores, 62.9% (95% confidence interval [CI]: 61.1, 64.7%) of children with autism were estimated to have co-occurring ID. After incorporating Vineland Adaptive Behavior Scales, Second Edition (VABS-II) composite or domains criteria, co-occurring ID estimates were reduced to 38.0% (95% CI: 36.2, 39.8%) and 45.0% (95% CI: 43.1, 46.9%), respectively. The increased odds of meeting ID criteria observed for non-Hispanic (NH) Black and Hispanic children relative to NH White children when only MSEL criteria were used were substantially reduced, though not eliminated, after incorporating VABS-II criteria and adjusting for selected socioeconomic variables. This study provides evidence for the importance of considering adaptive behavior as well as socioeconomic disadvantage when describing racial and ethnic disparities in co-occurring ID in epidemiologic studies of autism.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Transtornos Globais do Desenvolvimento Infantil , Deficiência Intelectual , Humanos , Criança , Pré-Escolar , Deficiência Intelectual/complicações , Deficiência Intelectual/epidemiologia , Transtorno Autístico/complicações , Transtorno Autístico/epidemiologia , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/diagnóstico , Adaptação Psicológica
9.
Health Serv Res ; 59(3): e14287, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38264862

RESUMO

OBJECTIVE: Given high rates of un- and underemployment among disabled people, adults with intellectual and developmental disabilities rely on Medicaid, Medicare, or both to pay for healthcare. Many disabled adults are Medicare eligible before the age of 65 but little is known as to why some receive Medicare services while others do not. We described the duration of Medicare enrollment for adults with intellectual and developmental disabilities in 2019 and then compared demographics by enrollment type (Medicare-only, Medicaid-only, dual-enrolled). Additionally, we examined the percent in each enrollment type by state, and differences in enrollment type for those with Down syndrome. DATA SOURCES AND STUDY SETTING: 2019 Medicare and Medicaid claims data for all adults (≥18 years) in the US with claim codes for intellectual disability, Down syndrome, or autism at any time between 2011 and 2019. STUDY DESIGN: Administrative claims cohort. DATA COLLECTION AND ABSTRACTION METHODS: Data were from the Transformed Medicaid Statistical Information System Analytic Files and Medicare Beneficiary Summary files. PRINCIPLE FINDINGS: In 2019, Medicare insured 582,868 adults with identified intellectual disability, autism, or Down syndrome. Of 582,868 Medicare beneficiaries, 149,172 were Medicare only and 433,396 were dual-enrolled. Most Medicare enrollees were enrolled as child dependents (61.5%) Medicaid-only enrollees (N = 819,256) were less likely to be white non-Hispanic (58.5% white non-Hispanic vs. 72.9% white non-Hispanic in dual-enrolled), more likely to be Hispanic (19.6% Hispanic vs. 9.2% Hispanic in dual-enrolled) and were younger (mean 34.2 years vs. 50.5 years dual-enrolled). CONCLUSION: There is heterogeneity in public insurance enrollment which is associated with state and disability type. Action is needed to ensure all are insured in the program that works for their healthcare needs.


Assuntos
Deficiências do Desenvolvimento , Deficiência Intelectual , Medicaid , Medicare , Humanos , Estados Unidos , Medicare/estatística & dados numéricos , Medicaid/estatística & dados numéricos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Síndrome de Down , Pessoas com Deficiência/estatística & dados numéricos , Definição da Elegibilidade , Adulto Jovem , Revisão da Utilização de Seguros
10.
Am J Med Genet C Semin Med Genet ; 196(1): e32041, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37072379

RESUMO

Research regarding caregivers for individuals with Down syndrome mainly focuses on outcomes for the pediatric population and not on the experience of caregivers themselves. Our objective was to understand caregiver-reported experiences and concerns for themselves and the individual they care for through a survey of caregivers of adults with Down syndrome. We conducted a survey of N = 438 caregivers of adults with Down syndrome and asked about the perspectives of the respondents surrounding caregiving and demographics. The most common concerns among caregivers were planning for future needs (72.1%) and what happens when they (the caregiver) are gone (68.3%). Concerns they had for the individual they cared for were employment (63.2%) and friendships/relationships (63.2%). We found no significant difference in responses based on caregiver education level. Our survey identified six themes for the feedback about what clinical and research professionals should know to better serve individuals with Down syndrome, their families, and those who support them. Many caregivers discussed topics including healthcare, coordination, competence, and ability. More efforts for research into the caregiver experience for adults with Down syndrome are needed.


Assuntos
Cuidadores , Síndrome de Down , Adulto , Humanos , Criança , Inquéritos e Questionários
11.
MicroPubl Biol ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-38021175

RESUMO

Proteins that persistently engage endoplasmic reticulum (ER) translocons are degraded by multiple translocon quality control (TQC) mechanisms. In Saccharomyces cerevisiae , the model translocon-associated protein Deg1 -Sec62 is subject to ER-associated degradation (ERAD) by the Hrd1 ubiquitin ligase and, to a lesser extent, proteolysis mediated by the Ste24 protease. In a recent screen, we identified nine methionine-biosynthetic genes as candidate TQC regulators. Here, we found methionine restriction impairs Hrd1-independent Deg1 -Sec62 degradation. Beyond revealing methionine as a novel regulator of TQC, our results urge caution when working with laboratory yeast strains with auxotrophic mutations, often presumed not to influence cellular processes under investigation.

12.
JAMA Psychiatry ; 80(12): 1284-1287, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37792361

RESUMO

Importance: The reported prevalence of autism in children has consistently risen over the past 20 years. The concurrent implications for the adult Medicaid system, which insures autistic adults due to low income or disability, have not been studied. Objective: To estimate the prevalence of adults identified as autistic in Medicaid claims data and to examine the prevalence by year, age, and race and ethnicity to understand enrollment patterns. Design, Setting, and Participants: This cohort study used data from a longitudinal Medicaid claims cohort of enrollees aged 18 years or older with a claim for autism at any point from January 1, 2011, to December 31, 2019, and an approximately 1% random sample of all adult Medicaid enrollees. The data were analyzed between February 22 and June 22, 2023. Exposure: Adults enrolled in Medicaid with a claim for autism. Main Outcome and Measures: Prevalence of autism per 1000 Medicaid enrollees for each year was calculated using denominator data from the Centers for Medicare & Medicaid Services weighted to nondisabled population demographic characteristics. Prevalence by race and ethnicity were calculated for study year 2019. Results: Across 9 years, 403 028 unique adults had autism claims in their Medicaid records (25.7% female, 74.2% male, 3.3% Asian, 16.8% Black, 12.2% Hispanic, 0.8% Native American, 0.8% Pacific Islander, 74.3% White, and 4.2% of multiple races). Across all ages, autism prevalence increased from 4.2 per 1000 enrollees in 2011 to 9.5 per 1000 enrollees in 2019. The largest increase over the 9 years was in the 25- to 34-year age group (195%), and the smallest increase was in the 55- to 64-year age group (45%). The prevalence of White enrollees was at least 2 times that of the prevalence of every other racial group in all age categories. Conclusions and Relevance: The study findings suggest that despite difficulties in identifying autism in adults, there is a considerable and growing population of autistic adults enrolled in Medicaid. As children on the autism spectrum become autistic adults, Medicaid is an important insurance provider for an increasing number of autistic adults and can be a valuable resource for understanding the health of the autistic population.


Assuntos
Transtorno Autístico , Medicaid , Criança , Adulto , Humanos , Masculino , Idoso , Estados Unidos/epidemiologia , Feminino , Transtorno Autístico/diagnóstico , Transtorno Autístico/epidemiologia , Estudos de Coortes , Prevalência , Medicare
13.
bioRxiv ; 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37662264

RESUMO

Primarily undergraduate institutions (PUIs) often struggle to provide authentic research opportunities that culminate in peer-reviewed publications due to "recipe-driven" lab courses and the comprehensive body of work necessary for traditional scientific publication. However, the advent of short-form, single-figure "micropublications" has created novel opportunities for early-career scientists to make and publish authentic scientific contributions on a scale and in a timespan compatible with their training periods. The purpose of this qualitative case study is to explore the benefits accrued by eight undergraduate and master's students who participated in authentic, small-scale research projects and disseminated their work as coauthors of peer-reviewed micropublications at a PUI. In these interviews, students reported that through the process of conducting and publishing their research, they developed specific competencies: reading scientific literature, proposing experiments, and collecting/interpreting publication-worthy data. Further, they reported this process enabled them to identify as contributing members of the greater scientific community.

14.
Autism ; : 13623613231193194, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37609907

RESUMO

LAY ABSTRACT: Autistic people are often described as "low-" or "high-functioning" based on their scores on cognitive tests. These terms are common in publications and in everyday communication. However, recent research and feedback from the autistic community suggests that relying on cognitive ability alone to describe functioning may miss meaningful differences in the abilities of autistic children and adults and in the kinds of support they may need. Additional methods are needed to describe "functioning" in autistic children. We examined whether scores from a test measuring adaptive behaviors would provide information on the functional abilities of children with autism that is different from cognitive ability and autism symptom severity. Adaptive behaviors include age-appropriate skills that allow people to function in their everyday lives and social interactions. We found that a large amount of the variation in adaptive behavior scores was not explained by cognitive development, autism symptom severity, and behavioral and emotional problems. In addition, there was a wide range of adaptive ability levels in children with autism in our study, including in those with low, average, or high cognitive scores. Our results suggest that adaptive behavior scores could provide useful information about the strengths and support needs of autistic children above and beyond measures of cognitive ability and autism symptom severity. Adaptive behavior scores provide important information on the needs of autistic people.

15.
JBJS Case Connect ; 13(3)2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37590426

RESUMO

CASE: Primary spinal epidural lymphoma (PSEL) presenting as myelopathy is extremely rare, particularly within young, healthy adults. This case report describes a 26-year-old man presenting with progressive thoracic myelopathy. Magnetic resonance imaging revealed spinal epidural masses spanning T5-T10 and T12-L2 with multilevel cord compression and edema. After evaluation, the patient underwent emergent posterior decompression to prevent progressive neurological decline. Histology was consistent with diffuse large B-cell lymphoma, germinal center type. At 3 months postoperatively, the patient regained full neurologic function. CONCLUSION: Although rare, PSELs should be considered in patients presenting with myelopathy to facilitate timely diagnosis and treatment.


Assuntos
Doenças da Medula Óssea , Linfoma Difuso de Grandes Células B , Doenças Musculoesqueléticas , Compressão da Medula Espinal , Doenças da Medula Espinal , Masculino , Humanos , Adulto Jovem , Adulto , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico por imagem
16.
JAMA Health Forum ; 4(8): e232320, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37566429

RESUMO

Importance: Down syndrome is the leading genetic cause of intellectual disability and automatically qualifies individuals for Social Security Insurance. Therefore, Medicaid is the major health insurance provider for a population at high risk for dementia, obesity, and premature mortality. Despite the importance of Medicaid for adults with Down syndrome, little is known about how this population uses Medicaid. Objective: To describe enrollment in, health care use in, and cost to Medicaid for adults with Down syndrome compared with adults with intellectual disability and a random sample of adults enrolled in Medicaid. Design, Setting, and Participants: In this cohort study, the data are from a claims cohort of adults aged 18 years or older enrolled in Medicaid at any point between January 1, 2011, and December 31, 2019. Participants were enrollees with 1 or more inpatient claim or 2 or more other claims with an International Classification of Diseases, Ninth Revision code or an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code for Down syndrome or intellectual disability as well as a random sample of those without developmental disability. Analyses were conducted from June 2022 to February 2023. Main Outcomes and Measures: Data were linked across 2 data reporting systems. Main outcomes were enrollee demographic characteristics, enrollment characteristics, cost, and service use. Results: This cohort study included 123 024 individuals with Down syndrome (820 273 person-years of coverage; mean [SD] age, 35 [14.7] years; median age, 33 years [IQR, 21-48 years]; 51.6% men; 14.1% Black individuals; 16.7% Hispanic individuals; and 74.6% White individuals), 1 182 246 individuals with intellectual disability (mean [SD] age, 37.1 [16.8] years; median age, 33 years [IQR, 22-50 years]; 56.5% men; 22.0% Black individuals; 11.7% Hispanic individuals; and 69.5% White individuals), and 3 176 371 individuals with no developmental disabilities (mean [SD] age, 38 [18.6] years; median age, 33 years [IQR, 21-52 years]; 43.8% men; 23.7% Black individuals; 20.7% Hispanic individuals; and 61.3% White individuals). Median enrollment in Medicaid for a person with Down syndrome was 8.0 years (IQR, 5.0-9.0 years; mean [SD], 6.6 [2.6] years). Costs were higher for the Down syndrome group (median, $26 278 per person-year [IQR, $11 145-$55 928 per person-year]) relative to the group with no developmental disabilities (median, $6173 per person-year [IQR, $868-$58 390 per person-year]). Asian, Black, Hispanic, Native American, and Pacific Islander adults with Down syndrome had fewer costs and claims per person-year compared with White adults with Down syndrome. Conclusion and Relevance: This cohort study of individuals with Down syndrome enrolled in Medicaid found consistent enrollment and high use of health care in a population with high health care needs. Results were similar comparing individuals with Down syndrome and those with intellectual disability, with both groups differing from a sample of Medicaid enrollees with no developmental disabilities. Medicaid data are a useful tool for understanding the health and well-being of individuals with Down syndrome.


Assuntos
Síndrome de Down , Deficiência Intelectual , Masculino , Estados Unidos/epidemiologia , Humanos , Adulto , Feminino , Medicaid , Estudos de Coortes , Síndrome de Down/epidemiologia , Síndrome de Down/terapia , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/terapia , Seguro Saúde
17.
PeerJ ; 11: e15897, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37645016

RESUMO

Background: Candida albicans is the most prevalent human fungal pathogen. In immunocompromised individuals, C. albicans can cause serious systemic disease, and patients infected with drug-resistant isolates have few treatment options. The ubiquitin-proteasome system has not been thoroughly characterized in C. albicans. Research from other organisms has shown ubiquitination is important for protein quality control and regulated protein degradation at the endoplasmic reticulum (ER) via ER-associated protein degradation (ERAD). Methods: Here we perform the first characterization, to our knowledge, of ERAD in a human fungal pathogen. We generated functional knockouts of C. albicans genes encoding three proteins predicted to play roles in ERAD, the ubiquitin ligases Hrd1 and Doa10 and the ubiquitin-conjugating enzyme Ubc7. We assessed the fitness of each mutant in the presence of proteotoxic stress, and we used quantitative tandem mass tag mass spectrometry to characterize proteomic alterations in yeast lacking each gene. Results: Consistent with a role in protein quality control, yeast lacking proteins thought to contribute to ERAD displayed hypersensitivity to proteotoxic stress. Furthermore, each mutant displayed distinct proteomic profiles, revealing potential physiological ERAD substrates, co-factors, and compensatory stress response factors. Among candidate ERAD substrates are enzymes contributing to ergosterol synthesis, a known therapeutic vulnerability of C. albicans. Together, our results provide the first description of ERAD function in C. albicans, and, to our knowledge, any pathogenic fungus.


Assuntos
Candida albicans , Degradação Associada com o Retículo Endoplasmático , Humanos , Candida albicans/genética , Proteômica , Proteínas Fúngicas/genética , Ubiquitina , Retículo Endoplasmático/genética
18.
Am J Intellect Dev Disabil ; 128(4): 273-281, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37470258

RESUMO

Individuals with Down syndrome (DS) have been disproportionately harmed by the COVID-19 pandemic and may have been more likely to have sacrificed opportunity and activity to avoid potential exposures. Our objective was to describe the experience one to one and half years into the COVID-19 pandemic for adults with DS, as reported by their caregivers in an online survey conducted between April 2021 and September of 2021. In our sample of 438 adults with DS, caregivers reported that adults with DS lost activities, struggled with employment, had negative behavioral changes, lost skills, and developed more mental health conditions. For adults with DS, one in five caregivers reported less healthcare usage, one in four reported delayed routine care, and 86.5% reported lost activities. As the pandemic continues, targeted support for adults with DS is needed to prevent further skill loss and mental health conditions.


Assuntos
COVID-19 , Síndrome de Down , Humanos , Adulto , Síndrome de Down/epidemiologia , Pandemias , Cuidadores/psicologia , Atenção à Saúde
19.
J Biol Chem ; 299(8): 104939, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37331602

RESUMO

The relationship between lipid homeostasis and protein homeostasis (proteostasis) is complex and remains incompletely understood. We conducted a screen for genes required for efficient degradation of Deg1-Sec62, a model aberrant translocon-associated substrate of the endoplasmic reticulum (ER) ubiquitin ligase Hrd1, in Saccharomyces cerevisiae. This screen revealed that INO4 is required for efficient Deg1-Sec62 degradation. INO4 encodes one subunit of the Ino2/Ino4 heterodimeric transcription factor, which regulates expression of genes required for lipid biosynthesis. Deg1-Sec62 degradation was also impaired by mutation of genes encoding several enzymes mediating phospholipid and sterol biosynthesis. The degradation defect in ino4Δ yeast was rescued by supplementation with metabolites whose synthesis and uptake are mediated by Ino2/Ino4 targets. Stabilization of a panel of substrates of the Hrd1 and Doa10 ER ubiquitin ligases by INO4 deletion indicates ER protein quality control is generally sensitive to perturbed lipid homeostasis. Loss of INO4 sensitized yeast to proteotoxic stress, suggesting a broad requirement for lipid homeostasis in maintaining proteostasis. A better understanding of the dynamic relationship between lipid homeostasis and proteostasis may lead to improved understanding and treatment of several human diseases associated with altered lipid biosynthesis.


Assuntos
Degradação Associada com o Retículo Endoplasmático , Lipídeos , Proteínas de Saccharomyces cerevisiae , Anti-Infecciosos/farmacologia , Farmacorresistência Fúngica/genética , Degradação Associada com o Retículo Endoplasmático/genética , Higromicina B/farmacologia , Lipídeos/biossíntese , Mutação , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
20.
Res Involv Engagem ; 9(1): 44, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37337242

RESUMO

Individuals with intellectual and developmental disabilities are often the subject of research while rarely being included in formulating research questions, planning studies, and making decisions related to protocols and analyses. In turn, most research regarding people with intellectual and developmental disabilities is not carried out by researchers with disabilities themselves. We developed a co-research training program where individuals with intellectual and developmental disabilities were taught about research. The program was designed using best practices and existing materials resources. We recruited four participants from Special Olympics Massachusetts and conducted the training in the Fall of 2021. We evaluated the program with surveys, qualitative interviews, and tracking continued involvement of co-researchers in research projects. Participants were partners in the evaluation process. The training program was six sessions and included lessons about why research is important, how to conduct research, and an experiential learning project where co-researchers conducted a study of their coaches. The program was well received by participants, and one year later they were still involved with research projects. A co-researcher training focused on public health for Special Olympics athletes is feasible and beneficial for athletes, researchers, and Special Olympics programs. However, there are still barriers like a lack of funding and time, that need to be addressed to ensure wide program success.


Co-research offers people with intellectual and developmental disabilities an opportunity to conduct research, rather than be the subjects. We developed a six-session co-researcher training in 2021 focused on public health for Special Olympics athletes. We found that co-research is feasible and rewarding for people with intellectual and developmental disabilities. Additional co-research activities and evaluation are needed. Special Olympics already conducts public health research activities and co-research training could be incorporated.

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