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1.
J Infect Dis ; 228(11): 1571-1582, 2023 11 28.
Article in English | MEDLINE | ID: mdl-37534822

ABSTRACT

BACKGROUND: Literature on the impact of human immunodeficiency virus (HIV) on coronavirus disease 2019 (COVID-19)-related outcomes remains mixed. Few studies have evaluated COVID-19 outcomes by HIV status using population-based data. METHODS: Using data from New York City COVID-19 surveillance and HIV surveillance systems prior to the widespread availability of COVID-19 vaccines, we conducted a retrospective cohort study comparing the risk of COVID-19 hospitalization and mortality by HIV status among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnoses from 29 February to 17 October 2020. RESULTS: Risk of hospitalization and death among people with HIV (PWH) withCOVID-19 were both nearly 30% higher compared with people without HIV. In crude models, incidence of adverse COVID-19 outcomes among PWH compared to people without HIV was elevated in certain groups, including women, and black, Hispanic/Latino, Native American, and multiracial people. CD4 cell count at SARS-CoV-2 diagnosis and presence of an underlying, non-HIV-related condition were independently and strongly associated with risk for COVID-19 hospitalization and death among PWH. CONCLUSIONS: New Yorkers with HIV experienced elevated risk for poor COVID-19 outcomes compared to those without HIV during 2020. PWH, particularly those with low CD4 counts or underlying conditions, should be an ongoing focus for COVID-19 vaccination and rigorous identification and treatment of SARS-CoV-2 infections to prevent adverse outcomes.


Subject(s)
COVID-19 , HIV Infections , Humans , Female , COVID-19/epidemiology , COVID-19 Vaccines , SARS-CoV-2 , COVID-19 Testing , New York City/epidemiology , Retrospective Studies , HIV Infections/complications , HIV Infections/epidemiology
2.
AIDS Behav ; 26(4): 1017-1025, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34599419

ABSTRACT

We examined recent pre-exposure prophylaxis (PrEP) use (past 6 months) and its correlates among a large sample of men who have sex with men and transgender and gender non-conforming persons participating in a home HIV self-testing program conducted by the New York City Health Department between 11/2016 and 1/2017. Correlates examined included demographic characteristics and HIV-related behaviors in the past 6 months. Associations with recent PrEP use were assessed using log-binomial regression. 400 (22.5%) of 1776 participants reported recent PrEP use. In adjusted models, recent PrEP use was associated with Manhattan residence [adjusted prevalence ratio (aPR) 1.26; 95% confidence interval (CI) (1.04, 1.53)], higher income [aPR 1.29; 95% CI (1.03, 1.62)], and having insurance [aPR 1.89; 95% CI (1.33, 2.69)]. All HIV-related behaviors, except for injection drug use, were individually associated with PrEP use. More research is needed to better understand barriers to PrEP use among patients who are low income and/or uninsured as this may help improve current public health efforts to increase PrEP uptake among disproportionately impacted populations.


Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Transgender Persons , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/prevention & control , Homosexuality, Male , Humans , Male
3.
Am J Prev Med ; 61(5 Suppl 1): S87-S97, 2021 11.
Article in English | MEDLINE | ID: mdl-34686295

ABSTRACT

Although HIV pre-exposure prophylaxis can decrease new cases of HIV by up to 99%, many patients who could benefit from pre-exposure prophylaxis never receive prescriptions for it. Because pre-exposure prophylaxis is indicated for patients who do not have an infectious disease, increasing pre-exposure prophylaxis prescribing by primary care and generalist clinicians represents a key element of the Ending the HIV Epidemic in the U.S. initiative. This review provides an overview of academic detailing and how it is currently being used to increase pre-exposure prophylaxis prescribing. Academic detailing is outreach education that engages with clinicians in 1-to-1 or small group interactions focused on identifying and addressing an individual clinician's needs to increase their use of evidence-based practices. Academic detailing has been proven in multiple previous research studies, and the principles required for successful implementation include interactivity, clinical relevance of content, and focus on defined behavior change objectives. Clinician barriers to pre-exposure prophylaxis prescribing may occur in the domains of knowledge, attitudes, or behavior, and academic detailing has the potential to address all of these areas. State and local health departments have developed academic detailing programs focused on pre-exposure prophylaxis prescribing and other elements of HIV prevention-sometimes describing the approach as public health detailing. Few studies of academic detailing for pre-exposure prophylaxis have been published to date; rigorous evaluation of HIV-specific adaptations and innovations of the approach would represent an important contribution. In the setting of the COVID-19 pandemic, interest in virtual delivery of academic detailing has grown, which could inform efforts to implement academic detailing in rural communities and other underserved areas. Increasing this capacity could make an important contribution to Ending the HIV Epidemic in the U.S. and other HIV prevention efforts.


Subject(s)
COVID-19 , HIV Infections , Pre-Exposure Prophylaxis , HIV Infections/prevention & control , Humans , Pandemics , Practice Patterns, Physicians' , SARS-CoV-2
4.
Am J Prev Med ; 61(5 Suppl 1): S98-S107, 2021 11.
Article in English | MEDLINE | ID: mdl-34686296

ABSTRACT

INTRODUCTION: Equitable access to HIV pre- and postexposure prophylaxis for women is essential to ending the HIV epidemic. Providers' lack of knowledge and comfort in discussing and prescribing pre-exposure prophylaxis to women persist as barriers. METHODS: From May to November 2019, the New York City Health Department conducted its first public health detailing campaigns among women's healthcare providers to promote pre- and postexposure prophylaxis and the associated best practices. Over 2 campaigns (10 weeks each), trained Health Department representatives visited providers for 1-on-1 visits at select practices to promote key messages. Representatives distributed an Action Kit that addressed knowledge gaps and practice needs on providing pre-exposure prophylaxis and postexposure prophylaxis to cisgender and transgender women. Providers completed an assessment at the beginning of initial and follow-up visits, used to compare responses across visits. Statistically significant changes were evaluated by generalized linear models of bivariate outcomes, adjusted for nonindependence of providers at the same practice. RESULTS: Representatives visited 1,348 providers specializing in primary care (47%), women's health (30%), adolescent health (7%), infectious disease (4%), and other (12%) at 860 sites; 1,097 providers received initial and follow-up visits. Provider report of ever prescribing pre-exposure prophylaxis increased by 12% (n=119 providers); increases were reported in measures of taking sexual history, asking about partners' HIV status, providing postexposure prophylaxis, recognizing pre-exposure prophylaxis's effectiveness, and discussing and referring for pre-exposure prophylaxis. CONCLUSIONS: After public health detailing, women's healthcare providers report increased adoption of recommended practices that promote pre- and postexposure prophylaxis uptake and sexual wellness among women. Detailing may be adaptable to other regions and contexts to reach providers.


Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Adolescent , Anti-HIV Agents/therapeutic use , Female , HIV Infections/drug therapy , HIV Infections/prevention & control , Health Personnel , Humans , New York City , Public Health
5.
Clin Infect Dis ; 72(12): e1021-e1029, 2021 06 15.
Article in English | MEDLINE | ID: mdl-33252620

ABSTRACT

BACKGROUND: New York City (NYC) was hard-hit by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and is also home to a large population of people with human immunodeficiency virus (PWH). METHODS: We matched laboratory-confirmed coronavirus disease 2019 (COVID-19) case and death data reported to the NYC Health Department as of 2 June 2020 against the NYC HIV surveillance registry. We describe and compare the characteristics and COVID-19-related outcomes of PWH diagnosed with COVID-19 with all NYC PWH and with all New Yorkers diagnosed with COVID-19. RESULTS: Through 2 June, 204 583 NYC COVID-19 cases were reported. The registry match identified 2410 PWH with diagnosed COVID-19 eligible for analysis (1.06% of all COVID-19 cases). Compared with all NYC PWH and all New Yorkers diagnosed with COVID-19, a higher proportion of PWH with COVID-19 were older, male, Black, or Latino, and living in high-poverty neighborhoods. At least 1 underlying condition was reported for 58.9% of PWH with COVID-19. Compared with all NYC COVID-19 cases, a higher proportion of PWH with COVID-19 experienced hospitalization, intensive care unit admission, and/or death; most PWH who experienced poor COVID-19-related outcomes had CD4 <500 cells/µL. CONCLUSIONS: Given NYC HIV prevalence is 1.5%, PWH were not overrepresented among COVID-19 cases. However, compared with NYC COVID-19 cases overall, a greater proportion of PWH had adverse COVID-19-related outcomes, perhaps because of a higher prevalence of factors associated with poor COVID-19 outcomes. Given the pandemic's exacerbating effects on health inequities, HIV public health and clinical communities must strengthen services and support for people living with and affected by HIV.


Subject(s)
COVID-19 , HIV Infections , HIV , HIV Infections/complications , HIV Infections/epidemiology , Humans , Male , New York City/epidemiology , SARS-CoV-2
6.
MMWR Morb Mortal Wkly Rep ; 69(46): 1725-1729, 2020 11 20.
Article in English | MEDLINE | ID: mdl-33211680

ABSTRACT

New York City (NYC) was an epicenter of the coronavirus disease 2019 (COVID-19) outbreak in the United States during spring 2020 (1). During March-May 2020, approximately 203,000 laboratory-confirmed COVID-19 cases were reported to the NYC Department of Health and Mental Hygiene (DOHMH). To obtain more complete data, DOHMH used supplementary information sources and relied on direct data importation and matching of patient identifiers for data on hospitalization status, the occurrence of death, race/ethnicity, and presence of underlying medical conditions. The highest rates of cases, hospitalizations, and deaths were concentrated in communities of color, high-poverty areas, and among persons aged ≥75 years or with underlying conditions. The crude fatality rate was 9.2% overall and 32.1% among hospitalized patients. Using these data to prevent additional infections among NYC residents during subsequent waves of the pandemic, particularly among those at highest risk for hospitalization and death, is critical. Mitigating COVID-19 transmission among vulnerable groups at high risk for hospitalization and death is an urgent priority. Similar to NYC, other jurisdictions might find the use of supplementary information sources valuable in their efforts to prevent COVID-19 infections.


Subject(s)
Coronavirus Infections/epidemiology , Disease Outbreaks , Pneumonia, Viral/epidemiology , Adolescent , Adult , Aged , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , Child , Child, Preschool , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Female , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Male , Middle Aged , New York City/epidemiology , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , SARS-CoV-2 , Young Adult
7.
MMWR Morb Mortal Wkly Rep ; 69(28): 918-922, 2020 Jul 17.
Article in English | MEDLINE | ID: mdl-32678072

ABSTRACT

To limit introduction of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), the United States restricted travel from China on February 2, 2020, and from Europe on March 13. To determine whether local transmission of SARS-CoV-2 could be detected, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) conducted deidentified sentinel surveillance at six NYC hospital emergency departments (EDs) during March 1-20. On March 8, while testing availability for SARS-CoV-2 was still limited, DOHMH announced sustained community transmission of SARS-CoV-2 (1). At this time, twenty-six NYC residents had confirmed COVID-19, and ED visits for influenza-like illness* increased, despite decreased influenza virus circulation.† The following week, on March 15, when only seven of the 56 (13%) patients with known exposure histories had exposure outside of NYC, the level of community SARS-CoV-2 transmission status was elevated from sustained community transmission to widespread community transmission (2). Through sentinel surveillance during March 1-20, DOHMH collected 544 specimens from patients with influenza-like symptoms (ILS)§ who had negative test results for influenza and, in some instances, other respiratory pathogens.¶ All 544 specimens were tested for SARS-CoV-2 at CDC; 36 (6.6%) tested positive. Using genetic sequencing, CDC determined that the sequences of most SARS-CoV-2-positive specimens resembled those circulating in Europe, suggesting probable introductions of SARS-CoV-2 from Europe, from other U.S. locations, and local introductions from within New York. These findings demonstrate that partnering with health care facilities and developing the systems needed for rapid implementation of sentinel surveillance, coupled with capacity for genetic sequencing before an outbreak, can help inform timely containment and mitigation strategies.


Subject(s)
Betacoronavirus/genetics , Betacoronavirus/isolation & purification , Community-Acquired Infections/diagnosis , Community-Acquired Infections/virology , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Sentinel Surveillance , Adolescent , Adult , Aged , COVID-19 , Child , Child, Preschool , Community-Acquired Infections/epidemiology , Coronavirus Infections/epidemiology , Emergency Service, Hospital , Female , Humans , Infant , Male , Middle Aged , New York City/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Sequence Analysis , Travel-Related Illness , Young Adult
8.
Sex Transm Dis ; 47(5S Suppl 1): S41-S47, 2020 05.
Article in English | MEDLINE | ID: mdl-32149955

ABSTRACT

BACKGROUND: HIV self-tests increase HIV status awareness by providing convenience and privacy, although cost and access may limit use. Since 2015, the New York City (NYC) Health Department has conducted 5 waves of an online Home Test Giveaway. METHODS: We recruited adult cisgender men who have sex with men (MSM) and transgender and gender-nonconforming (TGNC) individuals who had sex with men, who were living in NYC, not previously HIV diagnosed, and using paid digital advertisements (4-8 weeks per wave). Eligible respondents were e-mailed a code to redeem on the manufacturer's website for a free HIV self-test and an online follow-up survey ~2 months later. For key process and outcome measures, we present means across 5 waves. RESULTS: Across the 5 waves of Home Test Giveaway, there were 28,921 responses to the eligibility questionnaire: 17,383 were eligible, 12,182 redeemed a code for a free HIV self-test, and 7935 responded to the follow-up survey (46% of eligible responses). Among eligible responses, approximately half were Latino/a (mean, 32%) or non-Latino/a, black (mean, 17%). Mean report of never testing before was 16%. Among 5903 follow-up survey responses who reported test use, 32 reported reactive results with no known previous diagnosis (0.54%), of whom 78% reported receiving confirmatory testing. Report of likelihood of recommending the Home Test Giveaway to friends was high (mean, 96%). CONCLUSIONS: We recruited diverse NYC MSM and TGNC and distributed a large number of HIV self-tests to them. Among respondents who reported newly reactive tests, the majority reported confirmatory testing. This seems to be one acceptable way to reach MSM and TGNC for HIV testing, including those who have never tested before.


Subject(s)
AIDS Serodiagnosis/methods , HIV Infections/diagnosis , Mass Screening/methods , Sexual and Gender Minorities/statistics & numerical data , Adult , HIV Infections/epidemiology , Homosexuality, Male , Humans , Male , New York City/epidemiology , Reagent Kits, Diagnostic , Transgender Persons
9.
Sex Transm Dis ; 47(5S Suppl 1): S48-S52, 2020 May.
Article in English | MEDLINE | ID: mdl-32149962

ABSTRACT

BACKGROUND: Access to human immnodeficiency virus (HIV) testing in New York City (NYC) has increased, but disparities in testing rates still exist among most communities impacted by HIV. HIV self-tests (HIVSTs) present an opportunity to address testing barriers, but HIV-affected communities experience difficulties accessing HIVSTs, including lack of awareness and cost. To support increased access to HIVSTs, the NYC Health Department launched a partnership with select organizations to pilot distribution of free HIVSTs in 2 phases among priority populations across NYC. METHODS: Organizations that were diverse in their missions, experiences, capacities and populations served were recruited through a formal application process. The program initially launched with 10 organization partners (phase 1); as the pilot continued, partners identified necessary revisions to the program and launched a second phase in year 2. Both phases included outreach to NYC priority populations, HIVST distribution/redemption, and a follow-up survey. RESULTS: From March 2017 to August 2019, organizations distributed 75 HIVSTs during phase 1 and 252 during phase 2. All intended priority populations were reached, notably, those who had never tested before: 35% in phase 1 and 12% in phase 2. Over half of the follow-up survey respondents reported testing sooner. Respondents reported liking the HIVST because it did not require a visit to a clinic (84%) and preferred an HIVST to testing in a clinic (92%). CONCLUSIONS: Through 2 phases of implementation, this innovative partnership was able to reach and offer HIVSTs to priority populations across NYC. This program supports the feasibility of distributing HIVSTs through close partnerships with diverse organizations.


Subject(s)
HIV Infections/diagnosis , Mass Screening/methods , Self Care/methods , Self-Testing , Adolescent , Adult , Community-Based Participatory Research , Female , HIV Infections/epidemiology , HIV Infections/prevention & control , Humans , Male , Middle Aged , New York City/epidemiology , Surveys and Questionnaires , Young Adult
10.
Emerg Infect Dis ; 24(5): 827-834, 2018 05.
Article in English | MEDLINE | ID: mdl-29664375

ABSTRACT

A large number of imported cases of Zika virus infection and the potential for transmission by Aedes albopictus mosquitoes prompted the New York City Department of Health and Mental Hygiene to conduct sentinel, enhanced passive, and syndromic surveillance for locally acquired mosquitoborne Zika virus infections in New York City, NY, USA, during June-October 2016. Suspected case-patients were those >5 years of age without a travel history or sexual exposure who had >3 compatible signs/symptoms (arthralgia, fever, conjunctivitis, or rash). We identified 15 suspected cases and tested urine samples for Zika virus by using real-time reverse transcription PCR; all results were negative. We identified 308 emergency department visits for Zika-like illness, 40,073 visits for fever, and 17 unique spatiotemporal clusters of visits for fever. We identified no evidence of local transmission. Our experience offers possible surveillance tools for jurisdictions concerned about local mosquitoborne Zika virus or other arboviral transmission.


Subject(s)
Culicidae/virology , Sentinel Surveillance , Zika Virus Infection/diagnosis , Zika Virus Infection/epidemiology , Zika Virus/isolation & purification , Adolescent , Adult , Animals , Child , Female , Humans , Male , Middle Aged , New York City/epidemiology , Pregnancy , Young Adult
11.
Headache ; 58(3): 399-406, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29094343

ABSTRACT

OBJECTIVE: Migraine causes more than 1.2 million visits to US emergency departments (EDs) annually. Many of these visits are revisits among patients who had already been treated in an ED for migraine. The goal of this analysis was to determine the frequency of headache revisits among patients who present to an ED for management of migraine and sociodemographic factors associated with the revisit. METHODS: Using the New York City Department of Health and Mental Hygiene Syndromic Surveillance database, we conducted a retrospective nested cohort study. We analyzed visits from 18 NYC EDs with discharge diagnoses in the first 6 months of 2015. We conducted descriptive analyses to determine the frequency of headache revisit within 6 months of an index ED visit for migraine and the elapsed time to revisit. Using multivariable logistic regression, we assessed associations between age, sex, poverty, and revisit. RESULTS: Of 1052 ED visits with an ED discharge diagnosis of migraine during the first 6 months of 2015, 277 (26.3%) had a headache revisit within 6 months of their initial migraine visit and 131 (12.5%) had two or more revisits at the same hospital. Of the revisits for headache, 9% occur within 72 hours and 46% occur within 90 days of the initial migraine visit. Sex, age, and poverty level were not associated with an ED revisit. CONCLUSION: More than a quarter of initial ED visits for migraine are followed by headache revisits in <6 months. Future work should target interventions to decrease the frequency of headache revisits.


Subject(s)
Emergency Medical Services , Migraine Disorders/epidemiology , Migraine Disorders/therapy , Patient Readmission , Adolescent , Adult , Child , Child, Preschool , Emergency Service, Hospital , Female , Humans , Infant , Infant, Newborn , Male , New York City/epidemiology , Retrospective Studies , Socioeconomic Factors , Young Adult
12.
Public Health Rep ; 132(1_suppl): 23S-30S, 2017.
Article in English | MEDLINE | ID: mdl-28692384

ABSTRACT

INTRODUCTION: The use of syndromic surveillance has expanded from its initial purpose of bioterrorism detection. We present 6 use cases from New York City that demonstrate the value of syndromic surveillance for public health response and decision making across a broad range of health outcomes: synthetic cannabinoid drug use, heat-related illness, suspected meningococcal disease, medical needs after severe weather, asthma exacerbation after a building collapse, and Ebola-like illness in travelers returning from West Africa. MATERIALS AND METHODS: The New York City syndromic surveillance system receives data on patient visits from all emergency departments (EDs) in the city. The data are used to assign syndrome categories based on the chief complaint and discharge diagnosis, and analytic methods are used to monitor geographic and temporal trends and detect clusters. RESULTS: For all 6 use cases, syndromic surveillance using ED data provided actionable information. Syndromic surveillance helped detect a rise in synthetic cannabinoid-related ED visits, prompting a public health investigation and action. Surveillance of heat-related illness indicated increasing health effects of severe weather and led to more urgent public health messaging. Surveillance of meningitis-related ED visits helped identify unreported cases of culture-negative meningococcal disease. Syndromic surveillance also proved useful for assessing a surge of methadone-related ED visits after Superstorm Sandy, provided reassurance of no localized increases in asthma after a building collapse, and augmented traditional disease reporting during the West African Ebola outbreak. PRACTICE IMPLICATIONS: Sharing syndromic surveillance use cases can foster new ideas and build capacity for public health preparedness and response.


Subject(s)
Disease Outbreaks/prevention & control , Emergency Service, Hospital/statistics & numerical data , Population Surveillance/methods , Public Health Informatics/methods , Asthma/epidemiology , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/prevention & control , Emergency Service, Hospital/organization & administration , Heat Stroke/epidemiology , Humans , Marijuana Abuse/epidemiology , New York City/epidemiology
13.
Hum Mol Genet ; 23(18): 4758-69, 2014 Sep 15.
Article in English | MEDLINE | ID: mdl-24760770

ABSTRACT

Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional role of senataxin in disease, we examined differential gene expression in AOA2 patient fibroblasts, identifying a core set of genes showing altered expression by microarray and RNA-sequencing. To determine whether AOA2 and ALS4 mutations differentially affect gene expression, we overexpressed disease-specific SETX mutations in senataxin-haploinsufficient fibroblasts and observed changes in distinct sets of genes. This implicates mutation-specific alterations of senataxin function in disease pathogenesis and provides a novel example of allelic neurogenetic disorders with differing gene expression profiles. Weighted gene co-expression network analysis (WGCNA) demonstrated these senataxin-associated genes to be involved in both mutation-specific and shared functional gene networks. To assess this in vivo, we performed gene expression analysis on peripheral blood from members of 12 different AOA2 families and identified an AOA2-specific transcriptional signature. WGCNA identified two gene modules highly enriched for this transcriptional signature in the peripheral blood of all AOA2 patients studied. These modules were disease-specific and preserved in patient fibroblasts and in the cerebellum of Setx knockout mice demonstrating conservation across species and cell types, including neurons. These results identify novel genes and cellular pathways related to senataxin function in normal and disease states, and implicate alterations in gene expression as underlying the phenotypic differences between AOA2 and ALS4.


Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Ataxia/pathology , Cogan Syndrome/genetics , DNA Helicases/metabolism , Gene Regulatory Networks , RNA Helicases/metabolism , Animals , Apraxias/congenital , Ataxia/blood , Ataxia/genetics , Cell Line , Cerebellum/metabolism , DNA Helicases/genetics , Fibroblasts/metabolism , Gene Expression Regulation , Humans , Mice , Multifunctional Enzymes , Mutation , Oligonucleotide Array Sequence Analysis , Phenotype , RNA Helicases/genetics , Sequence Analysis, RNA
14.
Hum Mol Genet ; 21(19): 4171-86, 2012 Oct 01.
Article in English | MEDLINE | ID: mdl-22730494

ABSTRACT

RNA splicing plays a critical role in the programming of neuronal differentiation and, consequently, normal human neurodevelopment, and its disruption may underlie neurodevelopmental and neuropsychiatric disorders. The RNA-binding protein, fox-1 homolog (RBFOX1; also termed A2BP1 or FOX1), is a neuron-specific splicing factor predicted to regulate neuronal splicing networks clinically implicated in neurodevelopmental disease, including autism spectrum disorder (ASD), but only a few targets have been experimentally identified. We used RNA sequencing to identify the RBFOX1 splicing network at a genome-wide level in primary human neural stem cells during differentiation. We observe that RBFOX1 regulates a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors and synaptic proteins. Downstream alterations in gene expression define an additional transcriptional network regulated by RBFOX1 involved in neurodevelopmental pathways remarkably parallel to those affected by splicing. Several of these differentially expressed genes are further implicated in ASD and related neurodevelopmental diseases. Weighted gene co-expression network analysis demonstrates a high degree of connectivity among these disease-related genes, highlighting RBFOX1 as a key factor coordinating the regulation of both neurodevelopmentally important alternative splicing events and clinically relevant neuronal transcriptional programs in the development of human neurons.


Subject(s)
Alternative Splicing , Brain/embryology , Gene Regulatory Networks , Neural Stem Cells/cytology , Neurogenesis , RNA-Binding Proteins/metabolism , Aborted Fetus , Brain/metabolism , Humans , Neural Stem Cells/metabolism , RNA Splicing Factors , RNA-Binding Proteins/genetics
15.
Mov Disord ; 27(3): 442-6, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22287014

ABSTRACT

BACKGROUND: Sporadic-onset ataxia is common in a tertiary care setting but a significant percentage remains unidentified despite extensive evaluation. Rare genetic ataxias, reported only in specific populations or families, may contribute to a percentage of sporadic ataxia. METHODS: Patients with adult-onset sporadic ataxia, who tested negative for common genetic ataxias (SCA1, SCA2, SCA3, SCA6, SCA7, and/or Friedreich ataxia), were evaluated using a stratified screening approach for variants in 7 rare ataxia genes. RESULTS: We screened patients for published mutations in SYNE1 (n = 80) and TGM6 (n = 118), copy number variations in LMNB1 (n = 40) and SETX (n = 11), sequence variants in SACS (n = 39) and PDYN (n = 119), and the pentanucleotide insertion of spinocerebellar ataxia type 31 (n = 101). Overall, we identified 1 patient with a LMNB1 duplication, 1 patient with a PDYN variant, and 1 compound SACS heterozygote, including a novel variant. CONCLUSIONS: The rare genetic ataxias examined here do not significantly contribute to sporadic cerebellar ataxia in our tertiary care population.


Subject(s)
Cerebellar Ataxia/genetics , Enkephalins/genetics , Genetic Predisposition to Disease/genetics , Heat-Shock Proteins/genetics , Lamin Type B/genetics , Mutation/genetics , Protein Precursors/genetics , Adult , Aged , Cytoskeletal Proteins , DNA Helicases , Databases, Bibliographic/statistics & numerical data , Female , Genetic Testing , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Multifunctional Enzymes , Nerve Tissue Proteins/genetics , Nuclear Proteins/genetics , Phenotype , RNA Helicases/genetics , Transglutaminases/genetics
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