Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Endocr Pract ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39233010

RESUMO

OBJECTIVE: The risk of venous thromboembolism (VTE) with feminizing gender-affirming hormone therapy is an area of concern. This analysis aimed to assess whether gender-affirming hormone therapy and other potential risk factors are associated with VTE in transfeminine and gender diverse individuals. METHODS: We conducted a chart review of 2126 transfeminine and gender diverse adults receiving care within a large urban health system. The primary outcomes were the prevalence of VTE and odds ratios for the association of VTE with insurer, use of estrogen, and select comorbidities. RESULTS: A history of VTE was documented in 0.8% of the cohort. Those with a history of VTE were older (P < .001), more often self-identified as Hispanic or Black compared to White or Asian (P < .05) and were more likely to have Medicaid or Medicare (P < .01) when compared to those without a history of VTE. The prevalence of hyperlipidemia (P < .001), diabetes mellitus (P < .05), and hypercoagulable conditions (P < .001) were all greater in the positive VTE group. Hyperlipidemia (P < .001), diabetes mellitus (P < .05), and insurer (P < .05) were associated with increased odds of VTE in univariate analyses. None of the exposure variables analyzed were associated with VTE when controlling for age, race, and the number of comorbidities. CONCLUSIONS: The prevalence of VTE in our cohort was lower than previously observed. VTE was not associated with any one risk factor, including estrogen use, when controlling for age, race, and the number of comorbidities. Those of advanced age and those with multiple cardiometabolic comorbidities may benefit from increased surveillance and mitigation of modifiable risk factors.

2.
Cell ; 187(3): 733-749.e16, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306984

RESUMO

Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long non-coding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes to achieve gene dosage compensation. Here, we show that the Xist ribonucleoprotein (RNP) complex comprising numerous autoantigenic components is an important driver of sex-biased autoimmunity. Inducible transgenic expression of a non-silencing form of Xist in male mice introduced Xist RNP complexes and sufficed to produce autoantibodies. Male SJL/J mice expressing transgenic Xist developed more severe multi-organ pathology in a pristane-induced lupus model than wild-type males. Xist expression in males reprogrammed T and B cell populations and chromatin states to more resemble wild-type females. Human patients with autoimmune diseases displayed significant autoantibodies to multiple components of XIST RNP. Thus, a sex-specific lncRNA scaffolds ubiquitous RNP components to drive sex-biased immunity.


Assuntos
Autoanticorpos , Doenças Autoimunes , RNA Longo não Codificante , Animais , Feminino , Humanos , Masculino , Camundongos , Autoanticorpos/genética , Doenças Autoimunes/genética , Autoimunidade/genética , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Cromossomo X/genética , Cromossomo X/metabolismo , Inativação do Cromossomo X , Caracteres Sexuais
4.
Nature ; 619(7970): 572-584, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37468586

RESUMO

The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health1. The intesting has a length of over nine metres, along which there are differences in structure and function2. The localization of individual cell types, cell type development trajectories and detailed cell transcriptional programs probably drive these differences in function. Here, to better understand these differences, we evaluated the organization of single cells using multiplexed imaging and single-nucleus RNA and open chromatin assays across eight different intestinal sites from nine donors. Through systematic analyses, we find cell compositions that differ substantially across regions of the intestine and demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighbourhoods and communities, highlighting distinct immunological niches that are present in the intestine. We also map gene regulatory differences in these cells that are suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation and organization for this organ, and serve as an important reference map for understanding human biology and disease.


Assuntos
Intestinos , Análise de Célula Única , Humanos , Diferenciação Celular/genética , Cromatina/genética , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Mucosa Intestinal/citologia , Intestinos/citologia , Intestinos/imunologia , Análise da Expressão Gênica de Célula Única
5.
Adv Exp Med Biol ; 1401: 227-241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35882775

RESUMO

Understanding cellular processes involved in wound healing is very important given that there are diseases, such as diabetes, in which wounds do not heal. To model tissue regeneration, we focus on two cellular processes: cellular proliferation, to replace cells lost to the wound, and cell motility, activated at the wound edges. We address these two processes in separate, drug responsive, in vitro models. The first model is a scaffold-free three-dimensional (3D) spheroid model, in which spheroids grow larger - to a certain extent - with increased time in culture. The second model, the scratch wound assay, is focused on cell motility. In conjunction with collagen staining, it analyzes changes to the coverage of the wound edge and wound bed. Our workflow gives insights into candidate compounds for wound healing as we show using manuka honey (MH) as an example. Spheroids are responsive to oxidative damage by hydrogen peroxide (H2O2) which affects viability but mostly produces disaggregation. Conversely, MH supports spheroid health, shown by size measurements and viability. In two-dimensional scratch wound assays, MH helps close wounds with relative less collagen production and increases the loose cellular coverage adjacent to and within the wound. We use these methods in the undergraduate research laboratory as teaching and standardization tools, and we hope these will be useful in similar settings.


Assuntos
Mel , Peróxido de Hidrogênio , Cicatrização , Proliferação de Células , Movimento Celular
6.
Nat Genet ; 54(7): 985-995, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35726067

RESUMO

To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from 1,000 to 10,000 cells per sample for 48 polyps, 27 normal tissues and 6 CRCs collected from patients with or without germline APC mutations. A large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC. Advanced polyps contain increasing numbers of stem-like cells, regulatory T cells and a subtype of pre-cancer-associated fibroblasts. In the cancerous state, we observe T cell exhaustion, RUNX1-regulated cancer-associated fibroblasts and increasing accessibility associated with HNF4A motifs in epithelia. DNA methylation changes in sporadic CRC are strongly anti-correlated with accessibility changes along this continuum, further identifying regulatory markers for molecular staging of polyps.


Assuntos
Adenoma , Neoplasias Colorretais , Adenoma/genética , Adenoma/patologia , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Metilação de DNA/genética , Humanos , Análise de Célula Única
7.
Front Oncol ; 12: 858017, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359364

RESUMO

Triple negative breast cancer (TNBC) is a particularly aggressive cancer subtype that is difficult to diagnose due to its discriminating epidemiology and obscure metabolome. For the first time, 3D spatial and chemometric analyses uncover the unique lipid metabolome of TNBC under the tandem modulation of two key metabolites - insulin and methionine - using non-invasive optical techniques. By conjugating heavy water (D2O) probed Raman scattering with label-free two-photon fluorescence (TPF) microscopy, we observed altered de novo lipogenesis, 3D lipid droplet morphology, and lipid peroxidation under various methionine and insulin concentrations. Quantitative interrogation of both spatial and chemometric lipid metabolism under tandem metabolite modulation confirms significant interaction of insulin and methionine, which may prove to be critical therapeutic targets, and proposes a powerful optical imaging platform with subcellular resolution for metabolic and cancer research.

8.
Ann LGBTQ Public Popul Health ; 2(3): 174-184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34901933

RESUMO

Our objective was to characterize the proportion of U.S. mental health clinics that offered LGBT-tailored mental health services between 2014 and 2018. We used data from the National Mental Health Services Survey (NMHSS) to construct a mixed logistic model of availability of LGBT-tailored mental health services over time, by region (Northeast, South, Midwest and West), and by facility type (Veterans Administration, inpatient/residential, outpatient, community mental health centers and mixed). Our results show that the overall proportion of mental health clinics that offered LGBT-tailored services decreased from 2014 to 2018. Our results also indicate that Veteran Affairs clinics and facilities in the West and Northeast were most likely to offer LGBT-tailored mental health services. Given the temporal, regional, and facility gaps in LGBT-tailored mental health services availability, more effort should be dedicated to addressing this disparity.

9.
Front Hum Neurosci ; 15: 628818, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613216

RESUMO

Impairment of spatial memory, including an inability to recall previous locations and navigate the world, is often one of the first signs of functional disability on the road to cognitive impairment. While there are many screening and diagnostic tools which attempt to measure spatial memory ability, they are often not representative of real-life situations and can therefore lack applicability. One potential solution to this problem involves the use of virtual reality (VR), which immerses individuals in a virtually-simulated environment, allowing for scenarios more representative of real-life without any of the associated risks. Here, we review the evidence surrounding the use of VR for the screening and diagnosis of spatial memory impairments, including potential limitations and how it compares to standard neuropsychological tests. We will also discuss the evidence regarding the potential use of VR in the rehabilitation of spatial memory deficits, which has not been well studied, but which could be game-changing if proven successful.

10.
J Control Release ; 329: 894-906, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33058934

RESUMO

Exosomes are extracellular vesicles released from cells and are characterized by a lipid bilayer membrane encapsulating a variety of biological molecules such as nucleic acids or proteins within the lumen or the lipid-bilayer. Under physiological environments, exosomes mediate cell-to-cell communication and cargo transport. Therefore, exosomes have been explored as drug delivery vehicles for improving therapeutic outcomes. Although recent studies have demonstrated promising advances with exosome-based drug delivery systems, several challenges severely hinder further development of exosomes for clinical applications. This review summarizes and emphasizes some of the technical challenges related to the isolation, characterization, and stability testing of exosomes. More importantly, challenges related specifically to the application of exosomes for drug delivery such as cell-uptake, drug loading, drug release, and in vivo distribution will be examined in this article.


Assuntos
Exossomos , Vesículas Extracelulares , Comunicação Celular , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Exossomos/metabolismo
11.
JAMA Netw Open ; 3(7): e2010001, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32662844

RESUMO

Importance: Misinformation about cannabis and opioid use disorder (OUD) may increase morbidity and mortality if it leads individuals with OUD to forego evidence-based treatment. It has not been systematically evaluated whether officially designating OUD as a qualifying condition for medical cannabis is associated with cannabis dispensaries suggesting cannabis as a treatment for OUD. Objective: To examine whether state-level policies designating OUD a qualifying condition for medical cannabis are associated with more dispensaries claiming cannabis can treat OUD. Design, Setting, and Participants: This cross-sectional, mixed-methods study of 208 medical dispensary brands was conducted in 2019 using the brands' online content. The study included dispensaries operating in New Jersey, New York, and Pennsylvania, where OUD is a qualifying condition for medical cannabis, and in Connecticut, Delaware, Maryland, Ohio, and West Virginia, where this policy does not exist. Exposures: Presence of OUD on the list of qualifying conditions for a state's medical cannabis program. Main Outcomes and Measures: Binary indicators of whether online content from the brand said cannabis can treat OUD, can replace US Food and Drug Administration-approved medications for OUD, can be an adjunctive therapy to Food and Drug Administration-approved medications for OUD, or can be used as a substitute for opioids to treat other conditions (eg, chronic pain). Results: After excluding duplicates, listings for nonexistent dispensaries, and those without online content, 167 brands across 7 states were included in the analysis (44 [26.3%] in states where OUD was a qualifying condition and 123 [73.7%] in adjacent states). A dispensary listed in a directory for West Virginia was not operational; therefore, comparison states were Connecticut, Delaware, Maryland, and Ohio. In policy-exposed states, 39% (95% CI, 23%-55%) more dispensaries claimed cannabis could treat OUD compared with unexposed states (P < .001). For replacing medications for OUD and being an adjunctive therapy, the differences were 14% (95% CI, 2%-26%; P = .002) and 28% (95% CI, 14%-42%; P < .001), respectively. The suggestion that cannabis could substitute for opioids (eg, to treat chronic pain) was made by 25% (95% CI, 9%-41%) more brands in policy-exposed states than adjacent states (P = .002). Conclusions and Relevance: In this study, state-level policies designating OUD as a qualifying condition for medical cannabis were associated with more dispensaries claiming cannabis can treat OUD. In the current policy environment, in which medical claims by cannabis dispensaries are largely unregulated, these advertisements could harm patients. Future research linking these policies to patient outcomes is warranted.


Assuntos
Maconha Medicinal/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Estudos Transversais , Política de Saúde , Humanos , Marketing/métodos , Marketing/estatística & dados numéricos , Governo Estadual , Estados Unidos
12.
Cureus ; 12(12): e12046, 2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33447476

RESUMO

Otorhinolaryngologic foreign bodies may be encountered in-office visits, the emergency department, and speciality consultations. These include food, toys, and other small items, are present in pediatric patients. Because patients may be asymptomatic and the insertion of the foreign body not observed, obtaining medical care may be delayed. Conversely, insects as foreign bodies, especially in the external ear canal, can cause a patient significant pain and distress, directing the patient to seek immediate care. Here, we present a case of an adult Japanese beetle (Popillia japonica) as a foreign body in the ear of a 14-year-old female. A review of otorhinolaryngologic foreign bodies is also discussed, with particular attention to the ear and rural location. This case highlights the potential for agricultural insects to act as invasive foreign bodies, especially in areas where they are known to be endemic pests and the consequences of delayed treatment.

13.
CBE Life Sci Educ ; 18(4): ar52, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31622168

RESUMO

Preclass reading quizzes (RQs) have been shown to enhance student performance. Many instructors implementing evidence-based teaching assign preclass RQs to ensure their students are prepared to engage in class activities. Textbook companies now offer a gamified, adaptive-learning RQ format. In these RQs, students answer point-valued questions until they reach a threshold. If students answer incorrectly, the question decreases in point value on the next attempt. These RQs also give students who answer questions incorrectly more questions on that topic and direct students to sections of a textbook they need to review. We assessed the impact of gamified, adaptive preclass RQs compared with more traditional preclass RQs on in-class RQs and course exam performance as well as students' perceptions of RQs. Students in the gamified, adaptive treatment performed equally compared with students in the traditional, static treatment on in-class RQs and course exams. While students in the gamified, adaptive treatment did have a more positive perception of preclass RQs, this factor explained less than 3% of the variation in RQ perception. Our findings suggest that instructors should verify that gamified, adaptive technologies impact student learning in their course before integrating them into their course and asking students to pay for them.


Assuntos
Avaliação Educacional , Leitura , Currículo , Humanos , Aprendizagem , Modelos Teóricos , Aprendizagem Baseada em Problemas , Estudantes , Tecnologia
14.
J Comput Biol ; 22(1): 37-53, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25393978

RESUMO

Directed evolution is a technique that enables the identification of mutants of a particular protein that carry a desired property by successive rounds of random mutagenesis, screening, and selection. This technique has many applications, including the development of G protein-coupled receptor-based biosensors and designer drugs for personalized medicine. Although effective, directed evolution is not without challenges and can greatly benefit from the development of computational techniques to predict the functional outcome of single-point amino acid substitutions. In this article, we describe a molecular dynamics-based approach to predict the effects of single amino acid substitutions on agonist binding (salicin) to a human bitter taste receptor (hT2R16). An experimentally determined functional map of single-point amino acid substitutions was used to validate the whole-protein molecular dynamics-based predictive functions. Molecular docking was used to construct a wild-type agonist-receptor complex, providing a starting structure for single-point substitution simulations. The effects of each single amino acid substitution in the functional response of the receptor to its agonist were estimated using three binding energy schemes with increasing inclusion of solvation effects. We show that molecular docking combined with molecular mechanics simulations of single-point mutants of the agonist-receptor complex accurately predicts the functional outcome of single amino acid substitutions in a human bitter taste receptor.


Assuntos
Álcoois Benzílicos , Sinalização do Cálcio , Inibidores de Ciclo-Oxigenase , Glucosídeos , Simulação de Dinâmica Molecular , Mutação Puntual , Receptores Acoplados a Proteínas G , Substituição de Aminoácidos , Álcoois Benzílicos/química , Álcoois Benzílicos/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/genética , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Humanos , Estrutura Terciária de Proteína , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/química , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Relação Estrutura-Atividade
15.
Microbiology (Reading) ; 154(Pt 1): 42-53, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18174124

RESUMO

Phagosomal transporters (Phts), required for intracellular growth of Legionella pneumophila, comprise a novel family of multispanning alpha-helical proteins within the major facilitator superfamily (MFS). The members of this family derive exclusively from bacteria. Multiple paralogues are present in a restricted group of Alpha- and Gammaproteobacteria, but single members were also found in Chlamydia and Cyanobacteria. Their protein sequences were aligned, yielding a phylogenetic tree showing the relations of the proteins to each other. Topological analyses revealed a probable 12 alpha-helical transmembrane segment (TMS) topology. Motif identification and statistical analyses provided convincing evidence that these proteins arose from a six TMS precursor by intragenic duplication. The phylogenetic tree revealed some potential orthologous relationships, suggestive of common function. However, several probable examples of lateral transfer of the encoding genetic material between bacteria were identified and analysed. The Pht family most closely resembles a smaller MFS family (the UMF9 family) with no functionally characterized members. However, the UMF9 family occurs in a broader range of prokaryotic organism types, including Archaea. These two families differ in that organisms bearing members of the Pht family often have numerous paralogues, whereas organisms bearing members of the UMF9 family never have more than two. This work serves to characterize two novel families within the MFS and provides compelling evidence for horizontal transfer of some of the family members.


Assuntos
Bactérias/genética , Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Fagossomos/microbiologia , Motivos de Aminoácidos , Sequência de Aminoácidos , Proteínas de Bactérias/química , Proteínas de Transporte/química , Evolução Molecular , Transferência Genética Horizontal , Dados de Sequência Molecular , Filogenia , Estrutura Secundária de Proteína , Homologia de Sequência de Aminoácidos
16.
ANZ J Surg ; 76(6): 534-5, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16768784

RESUMO

Tracheal lacerations resulting from endotracheal intubation are extremely rare. We report a case where the initial diagnosis was misled by the radiological findings. Our case uniquely emphasizes several issues pertinent to the management of tracheal lacerations. We review the published works on this topic and emphasize the role of fibre-optic bronchoscopy in the assessment of airway injuries before operative management.


Assuntos
Broncoscopia , Intubação Intratraqueal/efeitos adversos , Lacerações/diagnóstico , Lacerações/etiologia , Traqueia/lesões , Adulto , Feminino , Humanos , Lacerações/terapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA