Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 111
Filtrar
1.
Alzheimers Dement ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934219

RESUMO

INTRODUCTION: Neighborhood socioeconomic status (SES) has been linked to dementia, but the distribution of SES within a neighborhood may also matter. METHODS: Data from 460 (47% Black, 46% White) older adults from the Michigan Cognitive Aging Project were linked to census tract-level data from the National Neighborhood Data Archive (NaNDA). Neighborhood SES included two composites reflecting disadvantage and affluence. Neighborhood racial income inequality was the ratio of median incomes for White versus Black residents. Generalized estimating equations examined associations between neighborhood factors and cognitive domains. RESULTS: Neighborhood racial income inequality was uniquely associated with worse cognitive health, and these associations did not differ by participant race. Neighborhood disadvantage was only associated with worse cognitive health among Black participants. DISCUSSION: Both the level and racial distribution of SES within a neighborhood may be relevant for dementia risk. Racial differences in the level and impact of neighborhood SES contribute to dementia inequalities. HIGHLIGHTS: Black participants lived in neighborhoods with lower socioeconomic status (SES) than White participants, on average. Neighborhood SES and racial income inequality were associated with worse cognition. Effects of neighborhood racial income inequality did not differ across racial groups. Effects of neighborhood SES were only evident among Black participants.

2.
Radiol Case Rep ; 19(8): 3376-3381, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38841601

RESUMO

Intraoperative magnetic resonance imaging (iMRI) is a powerful tool used to verify maximal safe resection of gliomas. However, unsuspected new or incidental findings can present difficult clinical scenarios. Here we present a case of a large supratentorial glioma resection where new, incidental bilateral cerebellar hemispheric enhancement was noted on iMRI. A 52-year-old male with a large intra-axial mass spanning the right temporal and parietal lobes underwent a craniotomy for tumor resection utilizing iMRI. Imaging displayed new, remote, bilateral cerebellar enhancement. Upon completion of surgery, the patient was extubated and was at his neurological baseline. An immediate CT scan showed no abnormalities in the cerebellum, and the duration of his hospital stay was unaffected by this finding. An MRI 24 hours after the procedure demonstrated complete resolution of the enhancement. New, remote contrast enhancement in the cerebellum raises concerns for the potentially emergent, well-defined pathology known as remote cerebellar hemorrhage (RCH). However, here we describe a case where these findings turned out to be clinically insignificant, CT-negative, and self-limiting. Therefore, here we call this finding remote non-hemorrhagic cerebellar contrast enhancement (RNHCCE) to differentiate it from RCE, and we discuss nuances and management considerations for differentiating the two.

3.
J Cardiovasc Dev Dis ; 11(5)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38786969

RESUMO

Collaborative multicenter research has significantly increased our understanding of fetal Ebstein anomaly, delineating risk factors for adverse outcomes as well as predictors of postnatal management. These data are incorporated into prenatal care and therapeutic strategies and inform family counseling and delivery planning to optimize care. This report details the translation of findings from multicenter studies into multidisciplinary prenatal care for a fetus with Ebstein anomaly, supraventricular tachycardia, and a circular shunt, including transplacental therapy to control arrhythmias and achieve ductal constriction, informed and coordinated delivery room management, and planned univentricular surgical palliation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38511665

RESUMO

Studies have consistently shown that psychiatric genetic counseling (pGC) helps people with psychiatric conditions by increasing empowerment and self-efficacy, and addressing emotions like guilt. Yet, it is not routinely provided. Genetic counselors and trainees express low confidence in their ability to provide meaningful pGC, especially in the absence of adequate training. Therefore, to address this gap a "Psychiatric Genetic Counseling for Genetic Counselors" (PG4GC) workshop was developed and delivered to 13 groups of participants (primarily qualified genetic counselors and trainees) between 2015 and 2023 (10 workshops were delivered in-person, and three virtually). Participants completed quantitative questionnaires both before and after completing the workshop to assess their comfort, knowledge, behavior, and feeling of being equipped to provide pGC. In total, 232 individuals completed the pre-workshop questionnaire and 154 completed the post-workshop questionnaire. Participants felt more comfortable, knowledgeable, and equipped to provide pGC, and reported being more likely to address psychiatric concerns after the workshop, regardless of whether they were trainees or practicing professionals and whether they completed the workshop in-person or virtually. This study suggests that the PG4GC workshop is an effective educational tool in pGC training that may aid in broader implementation of the service.

5.
Alzheimers Dement ; 20(5): 3342-3351, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552138

RESUMO

INTRODUCTION: Neighborhood characteristics are increasingly implicated in cognitive health disparities, but no research has investigated how the historical context of neighborhoods shapes these disparities. METHODS: Four hundred sixty-four Black (55%) and White older adults (Mage = 63.6) were drawn from the Michigan Cognitive Aging Project, a community-based, prospective study of older adults. Participants' addresses at baseline (2017-2020) were geocoded and linked to 2000-2017 measures of neighborhood socioeconomic status (NSES): disadvantage [NDis] and affluence [NAff]. Latent class growth analysis (LCGA) characterized 18 interpolated year trajectories of NSES across 1344 census tracts. Path analysis examined whether NSES trajectory classes mediated the association between race and a global cognition composite. RESULTS: LCGA identified three NDis and two NAff trajectory classes, which were associated with participant race. Only one NDis class was associated with cognition, and it mediated the association between the Black race and cognition. DISCUSSION: Disinvestment in neighborhoods may be particularly salient in race disparities in cognitive function. HIGHLIGHTS: Race is implicated in the likelihood of living in more disadvantaged neighborhoods. Historical trends in neighborhood disadvantage are associated with cognitive function in older adulthood. Identifying patterns of neighborhood change may inform neighborhood-level interventions.


Assuntos
Cognição , Classe Social , População Branca , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Michigan/epidemiologia , Cognição/fisiologia , População Branca/estatística & dados numéricos , Características da Vizinhança , Características de Residência/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Disparidades nos Níveis de Saúde
6.
Alzheimers Dement ; 20(5): 3147-3156, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38477489

RESUMO

INTRODUCTION: Depressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear. METHODS: Asian, Black, Latino, or White participants (n = 2227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over 4 years. Multilevel models stratified by race/ethnicity were used to examine whether depressive symptoms were associated with cognition or cognitive decline and whether associations differed by race/ethnicity. RESULTS: Higher depressive symptoms were associated with lower baseline verbal episodic memory scores (-0.06, 95% CI: -0.12, -0.01; -0.15, 95% CI: -0.25, -0.04), and faster decline annually in semantic memory (-0.04, 95% CI: -0.07, -0.01; -0.10, 95% CI: -0.15, -0.05) for Black and Latino participants. Depressive symptoms were associated with lower baseline but not decline in executive function. DISCUSSION: Depressive symptoms were associated with worse cognitive outcomes, with some evidence of heterogeneity across racial/ethnic groups. HIGHLIGHTS: We examined whether baseline depressive symptoms were differentially associated with domain-specific cognition or cognitive decline by race/ethnicity. Depressive symptoms were associated with worse cognitive scores for all racial/ethnic groups across different domains examined. Higher depressive symptoms were associated with faster cognitive decline for semantic memory for Black and Latino participants. The results suggest a particularly harmful association between depressive symptoms and cognition in certain racial/ethnic groups.


Assuntos
Depressão , Humanos , Masculino , Feminino , Idoso , Depressão/etnologia , Disfunção Cognitiva/etnologia , Testes Neuropsicológicos/estatística & dados numéricos , Pessoa de Meia-Idade , Etnicidade/psicologia , Etnicidade/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Negro ou Afro-Americano/psicologia , Cognição/fisiologia , População Branca/estatística & dados numéricos , Idoso de 80 Anos ou mais , Envelhecimento/psicologia
7.
Lancet Oncol ; 25(3): 366-375, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38423050

RESUMO

BACKGROUND: The increased incidence of human papillomavirus (HPV)-related cancers has motivated efforts to optimise treatment for these patients with excellent prognosis. Validation of surrogates for overall survival could expedite the investigation of new therapies. We sought to evaluate candidate intermediate clinical endpoints in trials assessing definitive treatment of p16-positive oropharyngeal cancer with chemotherapy or radiotherapy. METHODS: We did a retrospective review of five multicentre, randomised trials (NRG/RTOG 9003, 0129, 0234, 0522, and 1016) that tested radiotherapy with or without chemotherapy in patients (aged ≥18 years) with p16-positive localised head or neck squamous-cell carcinomas. Eight intermediate clinical endpoints were considered as potential surrogates for overall survival: freedom from local progression, freedom from regional progression, freedom from distant metastasis, freedom from locoregional progression, freedom from any progression, locoregional progression-free survival, progression-free survival, and distant metastasis-free survival. We used a two-stage meta-analytical framework, which requires high correlation between the intermediate clinical endpoint and overall survival at the patient level (condition 1), and high correlation between the treatment effect on the intermediate clinical endpoint and the treatment effect on overall survival (condition 2). For both, an r2 greater than 0·7 was used as criteria for clinically relevant surrogacy. FINDINGS: We analysed 1373 patients with oropharyngeal cancer from May 9, 2020, to Nov 22, 2023. 1231 (90%) of patients were men, 142 (10%) were women, and 1207 (88%) were White, with a median age of 57 years (IQR 51-62). Median follow-up was 4·2 years (3·1-5·1). For the first condition, correlating the intermediate clinical endpoints with overall survival at the individual and trial level, the three composite endpoints of locoregional progression-free survival (Kendall's τ 0·91 and r2 0·72), distant metastasis-free survival (Kendall's τ 0·93 and r2 0·83), and progression-free survival (Kendall's τ 0·88 and r2 0·70) were highly correlated with overall survival at the patient level and at the trial-group level. For the second condition, correlating treatment effects of the intermediate clinical endpoints and overall survival, the composite endpoints of locoregional progression-free survival (r2 0·88), distant metastasis-free survival (r2 0·96), and progression-free survival (r2 0·92) remained strong surrogates. Treatment effects on the remaining intermediate clinical endpoints were less strongly correlated with overall survival. INTERPRETATION: We identified locoregional progression-free survival, distant metastasis-free survival, and progression-free survival as surrogates for overall survival in p16-positive oropharyngeal cancers treated with chemotherapy or radiotherapy, which could serve as clinical trial endpoints. FUNDING: NRG Oncology Operations, NRG Oncology SDMC, the National Cancer Institute, Eli Lilly, Aventis, and the University of Michigan.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Orofaríngeas , Masculino , Humanos , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/terapia , Carcinoma de Células Escamosas/terapia , Motivação , Biomarcadores
8.
Clin Genet ; 105(6): 630-638, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38342854

RESUMO

Psychiatric genetic counseling (pGC) can improve patient empowerment and self-efficacy. We explored the relationship between pGC and psychiatric hospitalizations, for which no prior data exist. Using Population Data BC (a provincial dataset), we tested two hypotheses: (1) among patients (>18 years) with psychiatric conditions who received pGC between May 2010 and Dec 2016 (N = 387), compared with the year pre-pGC, in the year post-pGC there would be fewer (a) individuals hospitalized and (b) total hospital admissions; and (2) using a matched cohort design, compared with controls (N = 363, matched 1:4 for sex, diagnosis, time since diagnosis, region, and age, and assigned a pseudo pGC index date), the pGC cohort (N = 91) would have (a) more individuals whose number of hospitalizations decreased and (b) fewer hospitalizations post-pGC/pseudo-index. We also explored total days in hospital. Within the pGC cohort, there were fewer hospitalizations post-pGC than pre- pGC (p = 0.011, OR = 1.69), and total days in hospital decreased (1085 to 669). However, when compared to matched controls, the post-pGC/pseudo index change in hospitalizations among pGC cases was not statistically significant, even after controlling for the higher number of hospitalizations prior. pGC may lead to fewer psychiatric hospitalizations and cost savings; further studies exploring this are warranted.


Assuntos
Aconselhamento Genético , Hospitalização , Transtornos Mentais , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Transtornos Mentais/genética , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Estudos de Coortes , Adulto Jovem
9.
J Int Neuropsychol Soc ; 30(3): 253-263, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37622423

RESUMO

OBJECTIVE: Adverse childhood experiences (ACEs) may be a risk factor for later-life cognitive disorders such as dementia; however, few studies have investigated underlying mechanisms, such as cardiovascular health and depressive symptoms, in a health disparities framework. METHOD: 418 community-dwelling adults (50% nonHispanic Black, 50% nonHispanic White) aged 55+ from the Michigan Cognitive Aging Project retrospectively reported on nine ACEs. Baseline global cognition was a z-score composite of five factor scores from a comprehensive neuropsychological battery. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Cardiovascular health was operationalized through systolic blood pressure. A mediation model controlling for sociodemographics, childhood health, and childhood socioeconomic status estimated indirect effects of ACEs on global cognition via depressive symptoms and blood pressure. Racial differences were probed via t-tests and stratified models. RESULTS: A negative indirect effect of ACEs on cognition was observed through depressive symptoms [ß = -.040, 95% CI (-.067, -.017)], but not blood pressure, for the whole sample. Black participants reported more ACEs (Cohen's d = .21), reported more depressive symptoms (Cohen's d = .35), higher blood pressure (Cohen's d = .41), and lower cognitive scores (Cohen's d = 1.35) compared to White participants. In stratified models, there was a negative indirect effect through depressive symptoms for Black participants [ß = -.074, 95% CI (-.128, -.029)] but not for White participants. CONCLUSIONS: These results highlight the need to consider racially patterned contextual factors across the life course. Such factors could exacerbate the negative impact of ACEs and related mental health consequences and contribute to racial disparities in cognitive aging.


Assuntos
Experiências Adversas da Infância , Adulto , Humanos , Depressão/etiologia , Estudos Retrospectivos , Grupos Raciais , Cognição
10.
J Contin Educ Nurs ; 55(1): 26-32, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37921478

RESUMO

BACKGROUND: Human trafficking (HT) is a serious public health issue. Survivors of HT seek medical care. Health care professionals may be inadequately trained to identify and support survivors. This study evaluated improvements in nurses' knowledge after a professional development workshop on HT. METHOD: Pre- and postevaluation surveys assessed nurses' self-reported changes in perceived knowledge of HT and its vulnerability factors, the health impact of HT, strategies for identification and assessment of HT, and response to and follow-up of HT. RESULTS: After the workshop, participants showed significant improvement in perceived knowledge of all measures, regardless of hours of previous training and years of practice. CONCLUSION: Perceived knowledge of HT identification and response can be improved through training of nurses, regardless of hours of previous training and years of practice. [J Contin Educ Nurs. 2024;55(1):26-32.].


Assuntos
Tráfico de Pessoas , Enfermeiras e Enfermeiros , Recursos Humanos de Enfermagem Hospitalar , Humanos , Recursos Humanos de Enfermagem Hospitalar/educação , Competência Clínica , Tráfico de Pessoas/prevenção & controle , Educação Continuada em Enfermagem , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos e Questionários
11.
Aging Ment Health ; 28(4): 658-666, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37811722

RESUMO

OBJECTIVES: This study investigates religious involvement and depressive symptoms in Hispanic older adults in the United States. We hypothesized that private prayer, religious attendance, and religious belief would have an inverse association with depressive symptoms, and that these associations would be stronger among immigrants, compared to U.S.-born participants. METHOD: This cross-sectional, within-group study included 1,566 participants from the Health and Retirement Study. Multivariate linear regression evaluated the association between religious involvement and depressive symptoms in the whole sample and in subgroups stratified by immigrant status. RESULTS: Overall, only more frequent religious attendance was associated with fewer depressive symptoms. Stratified models revealed an additional inverse association between private prayer and depressive symptoms only in the immigrant group. CONCLUSION: These findings may help incorporate religious preferences into mental health prevention and treatment to reduce depressive symptoms among older Hispanic adults.


Assuntos
Depressão , Emigrantes e Imigrantes , Humanos , Estados Unidos , Idoso , Depressão/psicologia , Estudos Transversais , Hispânico ou Latino/psicologia , Religião
12.
J Genet Couns ; 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658574

RESUMO

Parents of children with 22q11.2 deletion syndrome (22q11DS) report concern about the psychiatric manifestations of the condition, but typically receive little information about this in clinical encounters and instead find information about it elsewhere. We developed an educational booklet about the psychiatric manifestations of 22q11DS and assessed its utility among parents of children with the condition. First, six parents of individuals with 22q11DS completed cognitive interviews to review an established generic booklet about the genetics of psychiatric conditions-and to suggest 22q11DS-specific adaptations. We used these suggestions to develop a novel booklet specific to psychiatric conditions and 22q1DS. Then, before and 1-month after reading the novel 22q11DS-specific online booklet, 73 parents of children with 22q11DS (with/without psychiatric conditions) completed validated scales (measuring empowerment, stigma, intolerance of uncertainty), an adapted version of a scale measuring worry about their child developing psychiatric illness, and purpose-designed items assessing perceptions of understanding of 22q11DS and mental illness, confidence in recognizing early signs, etc. After reading the 22q11DS online booklet, participants' feelings of empowerment increased (p = 0.002), while feelings of worry about their child developing psychiatric illness decreased (p = 0.05), and they reported better understanding 22q11DS and mental illness, and increased confidence in recognizing early warning signs. There is potential benefit in broadly distributing this educational booklet to parents of children with 22q11DS.

13.
medRxiv ; 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37732261

RESUMO

INTRODUCTION: Depressive symptoms are associated with higher risk of dementia but how they impact cognition in diverse populations is unclear. METHODS: Asian, Black, LatinX, or White participants (n=2,227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over four years. Multilevel models stratified by race/ethnicity were used to examine whether depressive symptoms were associated with cognition or cognitive decline and whether associations differed by race/ethnicity. RESULTS: Higher depressive symptoms were associated with lower baseline verbal episodic memory scores (-0.06, 95%CI: -0.12, -0.01; -0.15, 95%CI: -0.25, -0.04), and faster decline annually in semantic memory (-0.04, 95%CI: -0.07, -0.01; -0.10, 95%CI: -0.15, -0.05) for Black and LatinX participants. Depressive symptoms were associated with lower baseline but not decline in executive function. DISCUSSION: Depressive symptoms were associated with worse cognitive domains, with some evidence of heterogeneity across racial/ethnic groups.

14.
Nat Commun ; 14(1): 5850, 2023 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730674

RESUMO

We previously reported initial clinical results of post-transcriptional gene silencing of BCL11A expression (NCT03282656) reversing the fetal to adult hemoglobin switch. A goal of this approach is to increase fetal hemoglobin (HbF) expression while coordinately reducing sickle hemoglobin (HbS) expression. The resulting combinatorial effect should prove effective in inhibiting HbS polymerization at lower physiologic oxygen values thereby mitigating disease complications. Here we report results of exploratory single-cell analysis of patients in which BCL11A is targeted molecularly and compare results with cells of patients treated with hydroxyurea (HU), the current standard of care. We use single-cell assays to assess HbF, HbS, oxygen saturation, and hemoglobin polymer content in RBCs for nine gene therapy trial subjects (BCLshmiR, median HbF% = 27.9) and compare them to 10 HU-treated subjects demonstrating high and comparable levels of HbF (HU High Responders, median HbF% = 27.0). All BCL11A patients achieved the primary endpoint for NCT03282656, which was defined by an absolute neutrophil count greater than or equal to 0.5 × 109 cells/L for three consecutive days, achieved within 7 weeks following infusion. Flow cytometric assessment of single-RBC HbF and HbS shows fewer RBCs with high HbS% that would be most susceptible to sickling in BCLshmiR vs. HU High Responders: median 42% of RBCs with HbS%>70% in BCLshmiR vs. 61% in HU High Responders (p = 0.004). BCLshmiR subjects also demonstrate more RBCs resistant to HbS polymerization at lower physiologic oxygen tension: median 32% vs. 25% in HU High Responders (p = 0.006). Gene therapy-induced BCL11A down-regulation reverses the fetal-to-adult hemoglobin switch and induces RBCs with higher HbF%, lower HbS%, and greater resistance to deoxygenation-induced polymerization in clinical trial subjects compared with a cohort of highly responsive hydroxyurea-treated subjects.


Assuntos
Hemoglobina Falciforme , Hidroxiureia , Adulto , Humanos , Hidroxiureia/farmacologia , Hidroxiureia/uso terapêutico , Eritrócitos , Feto , Hemoglobina Fetal/genética , Fatores de Transcrição
15.
J Proteome Res ; 22(9): 3040-3053, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37552804

RESUMO

Tamoxifen (TMX), a selective estrogen receptor modulator, is commonly used in the treatment of hormone-responsive cancers. However, the effects of TMX in anabolic tissues harboring estrogen receptors, such as skeletal muscle, are poorly understood. We report a tandem mass-tag approach to TMX-treated myogenesis in C2C12 cells, a well-characterized model of in vitro murine skeletal muscle differentiation. A longitudinal analysis of >10,000 proteins identified in untreated C2C12 myogenesis revealed a novel subset of 1,062 myogenically regulated proteins. These proteins clustered into five distinct longitudinal expression trends which significantly overlap those obtained in similar analyses performed in human myocytes. We document a specific functional enrichment for adiponectin-signaling unique to TMX-treated myogenesis, as well as a subset of 198 proteins that are differentially expressed in TMX-treated cells relative to controls at one or more stages of myogenesis, the majority of which were involved in steroid and lipid metabolism. Further analysis highlights metallothionein-1 as a novel target of TMX treatment at each stage of C2C12 myogenesis. Finally, we present a powerful, self-validating pipeline for analyzing the total proteomic response to in vitro treatment across every stage of muscle cell development which can be easily adapted to study the effects of other drugs on myogenesis.


Assuntos
Proteoma , Tamoxifeno , Humanos , Animais , Camundongos , Proteoma/genética , Proteoma/metabolismo , Tamoxifeno/farmacologia , Proteômica , Músculo Esquelético/metabolismo , Diferenciação Celular , Desenvolvimento Muscular/genética
16.
Blood ; 142(15): 1281-1296, 2023 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-37478401

RESUMO

Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by combined immunodeficiency, eczema, microthrombocytopenia, autoimmunity, and lymphoid malignancies. Gene therapy (GT) to modify autologous CD34+ cells is an emerging alternative treatment with advantages over standard allogeneic hematopoietic stem cell transplantation for patients who lack well-matched donors, avoiding graft-versus-host-disease. We report the outcomes of a phase 1/2 clinical trial in which 5 patients with severe WAS underwent GT using a self-inactivating lentiviral vector expressing the human WAS complementary DNA under the control of a 1.6-kB fragment of the autologous promoter after busulfan and fludarabine conditioning. All patients were alive and well with sustained multilineage vector gene marking (median follow-up: 7.6 years). Clinical improvement of eczema, infections, and bleeding diathesis was universal. Immune function was consistently improved despite subphysiologic levels of transgenic WAS protein expression. Improvements in platelet count and cytoskeletal function in myeloid cells were most prominent in patients with high vector copy number in the transduced product. Two patients with a history of autoimmunity had flares of autoimmunity after GT, despite similar percentages of WAS protein-expressing cells and gene marking to those without autoimmunity. Patients with flares of autoimmunity demonstrated poor numerical recovery of T cells and regulatory T cells (Tregs), interleukin-10-producing regulatory B cells (Bregs), and transitional B cells. Thus, recovery of the Breg compartment, along with Tregs appears to be protective against development of autoimmunity after GT. These results indicate that clinical and laboratory manifestations of WAS are improved with GT with an acceptable safety profile. This trial is registered at clinicaltrials.gov as #NCT01410825.


Assuntos
Eczema , Transplante de Células-Tronco Hematopoéticas , Síndrome de Wiskott-Aldrich , Humanos , Síndrome de Wiskott-Aldrich/genética , Síndrome de Wiskott-Aldrich/terapia , Proteína da Síndrome de Wiskott-Aldrich/genética , Células-Tronco Hematopoéticas/metabolismo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Terapia Genética/métodos , Eczema/etiologia , Eczema/metabolismo , Eczema/terapia
17.
Ear Nose Throat J ; : 1455613231189116, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37501386

RESUMO

Congenital hypothyroidism rarely causes a clinically significant neck mass in newborns. We present the case of a newborn with congenital hypothyroidism and significantly enlarged goiter and discuss imaging considerations and medical and surgical management. This infant was prenatally discovered to have a midline neck mass on 28 week ultrasound measuring 6.0 cm × 3.4 cm × 5.8 cm. Diagnostic cordocentesis demonstrated elevated thyroid-stimulating hormone (TSH, 361 µIU/mL). Maternal evaluation for thyroid disease and antithyroid antibodies was negative. A Cesarean section at 38 weeks gestation was recommended due to hyperextension of the fetal neck. The infant was intubated for respiratory distress. Postnatal magnetic resonance imaging revealed a 5.5 cm × 4.4 cm × 7.6 cm goiter and laboratory studies confirmed the diagnosis of primary hypothyroidism (TSH 16.7 µIU/mL). Treatment was initiated with intravenous levothyroxine and transitioned to oral supplementation. Serial ultrasounds showed decreased goiter volume over several weeks, with recent volume per lobe being 22% and 44% of original volume. This case demonstrates the importance of prompt diagnosis and initiation of thyroid hormone replacement, allowing for significant goiter regression without surgical intervention and ensuring normal growth and neurodevelopmental outcome. Surgical management should be considered for those with persistent compressive symptoms despite optimal medical management.

18.
J Perinatol ; 43(9): 1131-1138, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37391509

RESUMO

OBJECTIVE: Congenital Diaphragmatic Hernia (CDH) is diagnosed prenatally in ~60% of cases. Prenatal measures typically guide management and prognostication. Simple postnatal prognosticators are needed when prenatal diagnosis is lacking. We hypothesized that preoperative orogastric tube (OGT) tip position relative to the contralateral diaphragm correlates with defect severity, resource utilization, and clinical outcomes regardless of diagnostic status. STUDY DESIGN: 150 neonates with left-posterolateral CDH were analyzed. Impact of intrathoracic and intraabdominal preoperative tip position on clinical outcomes was compared. RESULTS: Ninety-nine neonates were prenatally diagnosed. Overall, intrathoracic position significantly correlated with larger diaphragmatic defects, advanced postnatal pulmonary support requirements (HFOV, pulmonary vasodilators, and ECMO), operative complexity, longer hospitalization, and poorer survival to discharge. These observations persisted when analyzing only cases lacking prenatal diagnosis. CONCLUSIONS: Preoperative OGT tip position predicts defect severity, resource utilization, and outcomes in CDH. This observation enhances postnatal prognostication and care planning for neonates without a prenatal diagnosis.


Assuntos
Hérnias Diafragmáticas Congênitas , Gravidez , Recém-Nascido , Feminino , Humanos , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Hérnias Diafragmáticas Congênitas/cirurgia , Diagnóstico Pré-Natal , Radiografia , Hospitalização , Estudos Retrospectivos
19.
Neurobiol Aging ; 129: 149-156, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37331245

RESUMO

Socioeconomic status (SES) is associated with white matter hyperintensities (WMHs) and contributes to racial and ethnic health disparities. However, traditional measures of SES may not accurately represent individual financial circumstances among non-Latinx Black and Latinx older adults due to longstanding structural inequities. This study examined associations between multiple SES indicators (education, income, subjective financial worry) and WMHs across non-Latinx Black, Latinx, and non-Latinx White older adults in the Washington Heights-Inwood Columbia Aging Project (N = 662). Latinx participants reported the lowest SES and greatest financial worry, while Black participants evidenced the most WMHs. Greater financial worry was associated with higher WMHs volume above and beyond education and income, which were not associated with WMHs. However, this association was only evident among Latinx older adults. These results provide evidence for the minority poverty hypothesis and highlight the need for systemic socioeconomic interventions to alleviate brain health disparities in older adulthood.


Assuntos
Negro ou Afro-Americano , Estresse Financeiro , Hispânico ou Latino , Substância Branca , Brancos , Idoso , Humanos , População Negra/psicologia , Encéfalo/diagnóstico por imagem , Grupos Raciais/etnologia , Grupos Raciais/psicologia , Brancos/psicologia , Hispânico ou Latino/psicologia , Estresse Financeiro/diagnóstico por imagem , Estresse Financeiro/etnologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Disparidades nos Níveis de Saúde , Classe Social , Negro ou Afro-Americano/psicologia , Cidade de Nova Iorque
20.
Public Health Genomics ; 26(1): 35-44, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37019096

RESUMO

INTRODUCTION: Though it is well established that genetic information does not produce behavior changes, there are limited data regarding whether genetic counseling can facilitate changes in lifestyle and health behaviors that can result in improved health outcomes. METHODS: To explore this issue, we conducted semi-structured interviews with 8 patients who had lived experience of psychiatric illness and who had received psychiatric genetic counseling (PGC). Using interpretive description, we used a constant comparative approach to data analysis. RESULTS: Participants talked about how, prior to PGC, they held misconceptions and/or uncertainties about the causes of and protective behaviors associated with mental illness, which caused feelings of guilt, shame, fear, and hopelessness. Participants reported that PGC reframed things in a way that provided them a sense of agency over illness management, allowed a greater acceptance of illness, and provided release from some of the negative emotions associated with their initial framing of their illness, which seemed to be related to the self-reported increase in engagement in illness management behaviors and consequently improved mental health outcomes. CONCLUSION: This exploratory study provides evidence to support the idea that through addressing emotions associated with perceived cause of illness and facilitating understanding of etiology and risk-reducing strategies, PGC may lead to an increase in behaviors, which protect mental health.


Assuntos
Aconselhamento Genético , Transtornos Mentais , Humanos , Transtornos Mentais/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...