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1.
Annu Rev Immunol ; 31: 563-604, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23516985

RESUMEN

Dendritic cells (DCs) form a remarkable cellular network that shapes adaptive immune responses according to peripheral cues. After four decades of research, we now know that DCs arise from a hematopoietic lineage distinct from other leukocytes, establishing the DC system as a unique hematopoietic branch. Recent work has also established that tissue DCs consist of developmentally and functionally distinct subsets that differentially regulate T lymphocyte function. This review discusses major advances in our understanding of the regulation of DC lineage commitment, differentiation, diversification, and function in situ.


Asunto(s)
Diferenciación Celular/inmunología , Linaje de la Célula/inmunología , Células Dendríticas/inmunología , Células Dendríticas/patología , Animales , Movimiento Celular/inmunología , Células Dendríticas/citología , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Mediadores de Inflamación/fisiología , Tejido Linfoide/citología , Tejido Linfoide/inmunología , Tejido Linfoide/patología
2.
Nature ; 601(7892): 234-239, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34931044

RESUMEN

Humans evolved in a patchwork of semi-connected populations across Africa1,2; understanding when and how these groups connected is critical to interpreting our present-day biological and cultural diversity. Genetic analyses reveal that eastern and southern African lineages diverged sometime in the Pleistocene epoch, approximately 350-70 thousand years ago (ka)3,4; however, little is known about the exact timing of these interactions, the cultural context of these exchanges or the mechanisms that drove their separation. Here we compare ostrich eggshell bead variations between eastern and southern Africa to explore population dynamics over the past 50,000 years. We found that ostrich eggshell bead technology probably originated in eastern Africa and spread southward approximately 50-33 ka via a regional network. This connection breaks down approximately 33 ka, with populations remaining isolated until herders entered southern Africa after 2 ka. The timing of this disconnection broadly corresponds with the southward shift of the Intertropical Convergence Zone, which caused periodic flooding of the Zambezi River catchment (an area that connects eastern and southern Africa). This suggests that climate exerted some influence in shaping human social contact. Our study implies a later regional divergence than predicted by genetic analyses, identifies an approximately 3,000-kilometre stylistic connection and offers important new insights into the social dimension of ancient interactions.


Asunto(s)
Cáscara de Huevo , Migración Humana/historia , Struthioniformes , África Oriental , África Austral , Animales , Historia Antigua , Humanos , Red Social
3.
Nature ; 593(7857): 95-100, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33953416

RESUMEN

The origin and evolution of hominin mortuary practices are topics of intense interest and debate1-3. Human burials dated to the Middle Stone Age (MSA) are exceedingly rare in Africa and unknown in East Africa1-6. Here we describe the partial skeleton of a roughly 2.5- to 3.0-year-old child dating to 78.3 ± 4.1 thousand years ago, which was recovered in the MSA layers of Panga ya Saidi (PYS), a cave site in the tropical upland coast of Kenya7,8. Recent excavations have revealed a pit feature containing a child in a flexed position. Geochemical, granulometric and micromorphological analyses of the burial pit content and encasing archaeological layers indicate that the pit was deliberately excavated. Taphonomical evidence, such as the strict articulation or good anatomical association of the skeletal elements and histological evidence of putrefaction, support the in-place decomposition of the fresh body. The presence of little or no displacement of the unstable joints during decomposition points to an interment in a filled space (grave earth), making the PYS finding the oldest known human burial in Africa. The morphological assessment of the partial skeleton is consistent with its assignment to Homo sapiens, although the preservation of some primitive features in the dentition supports increasing evidence for non-gradual assembly of modern traits during the emergence of our species. The PYS burial sheds light on how MSA populations interacted with the dead.


Asunto(s)
Entierro/historia , Fósiles , Esqueleto/anatomía & histología , Animales , Huesos/anatomía & histología , Preescolar , Evolución Cultural/historia , Dentición , Historia Antigua , Hominidae/anatomía & histología , Hominidae/clasificación , Humanos , Kenia
4.
Nat Immunol ; 14(6): 619-32, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23644507

RESUMEN

The differentiation of αßT cells from thymic precursors is a complex process essential for adaptive immunity. Here we exploited the breadth of expression data sets from the Immunological Genome Project to analyze how the differentiation of thymic precursors gives rise to mature T cell transcriptomes. We found that early T cell commitment was driven by unexpectedly gradual changes. In contrast, transit through the CD4(+)CD8(+) stage involved a global shutdown of housekeeping genes that is rare among cells of the immune system and correlated tightly with expression of the transcription factor c-Myc. Selection driven by major histocompatibility complex (MHC) molecules promoted a large-scale transcriptional reactivation. We identified distinct signatures that marked cells destined for positive selection versus apoptotic deletion. Differences in the expression of unexpectedly few genes accompanied commitment to the CD4(+) or CD8(+) lineage, a similarity that carried through to peripheral T cells and their activation, demonstrated by mass cytometry phosphoproteomics. The transcripts newly identified as encoding candidate mediators of key transitions help define the 'known unknowns' of thymocyte differentiation.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Diferenciación Celular/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/inmunología , Animales , Antígenos CD/inmunología , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/inmunología , Antígenos de Diferenciación de Linfocitos T/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/metabolismo , Diferenciación Celular/genética , Linaje de la Célula/genética , Linaje de la Célula/inmunología , Proliferación Celular , Células Cultivadas , Análisis por Conglomerados , Citometría de Flujo , Antígenos de Histocompatibilidad/genética , Antígenos de Histocompatibilidad/inmunología , Antígenos de Histocompatibilidad/metabolismo , Lectinas Tipo C/inmunología , Lectinas Tipo C/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosforilación/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Timocitos/citología , Timocitos/inmunología , Timocitos/metabolismo , Transcriptoma/genética , Transcriptoma/inmunología
5.
Nat Immunol ; 14(6): 633-43, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23624555

RESUMEN

The differentiation of hematopoietic stem cells into cells of the immune system has been studied extensively in mammals, but the transcriptional circuitry that controls it is still only partially understood. Here, the Immunological Genome Project gene-expression profiles across mouse immune lineages allowed us to systematically analyze these circuits. To analyze this data set we developed Ontogenet, an algorithm for reconstructing lineage-specific regulation from gene-expression profiles across lineages. Using Ontogenet, we found differentiation stage-specific regulators of mouse hematopoiesis and identified many known hematopoietic regulators and 175 previously unknown candidate regulators, as well as their target genes and the cell types in which they act. Among the previously unknown regulators, we emphasize the role of ETV5 in the differentiation of γδ T cells. As the transcriptional programs of human and mouse cells are highly conserved, it is likely that many lessons learned from the mouse model apply to humans.


Asunto(s)
Algoritmos , Regulación de la Expresión Génica/inmunología , Sistema Inmunológico/metabolismo , Transcripción Genética/inmunología , Animales , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Linaje de la Célula/genética , Linaje de la Célula/inmunología , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/inmunología , Perfilación de la Expresión Génica , Redes Reguladoras de Genes/inmunología , Humanos , Sistema Inmunológico/citología , Ratones , Análisis de Secuencia por Matrices de Oligonucleótidos , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Transactivadores/genética , Transactivadores/inmunología , Factores de Transcripción/genética , Factores de Transcripción/inmunología , Transcriptoma/genética , Transcriptoma/inmunología
6.
Nat Immunol ; 13(11): 1118-28, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23023392

RESUMEN

We assessed gene expression in tissue macrophages from various mouse organs. The diversity in gene expression among different populations of macrophages was considerable. Only a few hundred mRNA transcripts were selectively expressed by macrophages rather than dendritic cells, and many of these were not present in all macrophages. Nonetheless, well-characterized surface markers, including MerTK and FcγR1 (CD64), along with a cluster of previously unidentified transcripts, were distinctly and universally associated with mature tissue macrophages. TCEF3, C/EBP-α, Bach1 and CREG-1 were among the transcriptional regulators predicted to regulate these core macrophage-associated genes. The mRNA encoding other transcription factors, such as Gata6, was associated with single macrophage populations. We further identified how these transcripts and the proteins they encode facilitated distinguishing macrophages from dendritic cells.


Asunto(s)
Antígenos CD/genética , Macrófagos/metabolismo , ARN Mensajero/genética , Factores de Transcripción/genética , Transcripción Genética , Animales , Antígenos CD/inmunología , Diferenciación Celular , Células Dendríticas/citología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Variación Genética , Hígado/citología , Hígado/inmunología , Hígado/metabolismo , Pulmón/citología , Pulmón/inmunología , Pulmón/metabolismo , Macrófagos/citología , Macrófagos/inmunología , Ratones , Microglía/citología , Microglía/inmunología , Microglía/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Especificidad de Órganos , ARN Mensajero/inmunología , Bazo/citología , Bazo/inmunología , Bazo/metabolismo , Factores de Transcripción/inmunología
7.
Nat Immunol ; 13(9): 888-99, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22797772

RESUMEN

Although much progress has been made in the understanding of the ontogeny and function of dendritic cells (DCs), the transcriptional regulation of the lineage commitment and functional specialization of DCs in vivo remains poorly understood. We made a comprehensive comparative analysis of CD8(+), CD103(+), CD11b(+) and plasmacytoid DC subsets, as well as macrophage DC precursors and common DC precursors, across the entire immune system. Here we characterized candidate transcriptional activators involved in the commitment of myeloid progenitor cells to the DC lineage and predicted regulators of DC functional diversity in tissues. We identified a molecular signature that distinguished tissue DCs from macrophages. We also identified a transcriptional program expressed specifically during the steady-state migration of tissue DCs to the draining lymph nodes that may control tolerance to self tissue antigens.


Asunto(s)
Diferenciación Celular/inmunología , Linaje de la Célula/inmunología , Células Dendríticas/inmunología , Transcripción Genética , Diferenciación Celular/genética , Células Dendríticas/citología , Perfilación de la Expresión Génica , Humanos
8.
Immunity ; 42(6): 1143-58, 2015 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-26070485

RESUMEN

Tissue effector cells of the monocyte lineage can differentiate into different cell types with specific cell function depending on their environment. The phenotype, developmental requirements, and functional mechanisms of immune protective macrophages that mediate the induction of transplantation tolerance remain elusive. Here, we demonstrate that costimulatory blockade favored accumulation of DC-SIGN-expressing macrophages that inhibited CD8(+) T cell immunity and promoted CD4(+)Foxp3(+) Treg cell expansion in numbers. Mechanistically, that simultaneous DC-SIGN engagement by fucosylated ligands and TLR4 signaling was required for production of immunoregulatory IL-10 associated with prolonged allograft survival. Deletion of DC-SIGN-expressing macrophages in vivo, interfering with their CSF1-dependent development, or preventing the DC-SIGN signaling pathway abrogated tolerance. Together, the results provide new insights into the tolerogenic effects of costimulatory blockade and identify DC-SIGN(+) suppressive macrophages as crucial mediators of immunological tolerance with the concomitant therapeutic implications in the clinic.


Asunto(s)
Moléculas de Adhesión Celular/metabolismo , Rechazo de Injerto/prevención & control , Trasplante de Corazón , Lectinas Tipo C/metabolismo , Macrófagos/inmunología , Receptores de Superficie Celular/metabolismo , Linfocitos T Reguladores/inmunología , Animales , Linfocitos T CD8-positivos/inmunología , Moléculas de Adhesión Celular/genética , Células Cultivadas , Factores de Transcripción Forkhead/metabolismo , Rechazo de Injerto/etiología , Tolerancia Inmunológica , Interleucina-10/metabolismo , Lectinas Tipo C/genética , Factor Estimulante de Colonias de Macrófagos/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Terapia Molecular Dirigida , Receptores de Superficie Celular/genética , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Tolerancia al Trasplante , Regulación hacia Arriba
9.
Artículo en Inglés | MEDLINE | ID: mdl-39251020

RESUMEN

BACKGROUND: Penicillin (PCN) allergy labels are the most common drug allergy label and limit use of first-line antibiotics for many pediatric bacterial infections. Improving access to PCN allergy evaluations is a priority for allergy and immunology (A&I) and infectious diseases (ID) programs. OBJECTIVE: To increase the number of completed PCN allergy evaluations from 6 to 24 per month from January 2022 to December 2023. METHODS: A collaborative PCN allergy stewardship team was established in the A&I and ID divisions at Texas Children's Hospital. Telemedicine evaluations and, when clinically indicated, in-person PCN allergy evaluations were conducted from January 2022 to December 2023. Plan-do-study-act cycles were conducted to increase awareness about the clinics. The primary outcome measure was the average number of monthly completed PCN allergy evaluations. RESULTS: The average number of completed PCN allergy evaluations increased from 6 to 19 per month. Children were seen rapidly in the ID telemedicine clinic (20 vs 62 days, P < .001), and 428 of 627 (68%) children who required in-person challenge were scheduled for their in-person evaluation. Among the 211 children delabeled, 71 (33.6%) were subsequently diagnosed with a bacterial infection requiring PCN during the study period. CONCLUSION: A collaborative PCN allergy stewardship team consisting of ID and A&I specialists increased the number of completed PCN allergy evaluations 3-fold. ID telemedicine services allowed prompt access to care, and most children were delabeled and subsequently able to receive PCN antibiotics for bacterial respiratory tract infections. Future work should explore ways to minimize barriers to PCN allergy evaluations and further expand testing services in other settings.

10.
J Pediatr Psychol ; 49(6): 394-404, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38216126

RESUMEN

OBJECTIVES: Adolescents with type 1 diabetes (T1D) and their caregivers endorse high diabetes distress (DD). Limited studies have documented the impact of DD on Black youth. The aims of the present study were to (1) describe DD among a sample of Black adolescents with T1D and their caregivers, (2) compare their DD levels with published normative samples, and (3) determine how DD relates to glycemic outcomes, diabetes self-management, parental monitoring of diabetes, and youth depressive symptoms. METHODS: Baseline data from a multicenter clinical trial were used. Participants (N = 155) were recruited from 7 Midwestern pediatric diabetes clinics. Hemoglobin A1c (HbA1c) and measures of DD, parental monitoring of diabetes care, youth depression and diabetes management behaviors were obtained. The sample was split into (1) adolescents (ages 13-14; N = 95) and (2) preadolescents (ages 10-12; N = 60). Analyses utilized Cohen's d effect sizes, Pearson correlations, t-tests, and multiple regression. RESULTS: DD levels in youth and caregivers were high, with 45%-58% exceeding either clinical cutoff scores or validation study sample means. Higher DD in youth and caregivers was associated with higher HbA1c, lower diabetes self-management, and elevated depressive symptoms, but not with parental monitoring of diabetes management. CONCLUSIONS: Screening for DD in Black youth with T1D and caregivers is recommended, as are culturally informed interventions that can reduce distress levels and lead to improved health outcomes. More research is needed on how systemic inequities contribute to higher DD in Black youth and the strategies/policy changes needed to reduce these inequities.


Asunto(s)
Negro o Afroamericano , Cuidadores , Depresión , Diabetes Mellitus Tipo 1 , Control Glucémico , Conductas Relacionadas con la Salud , Humanos , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/terapia , Adolescente , Femenino , Cuidadores/psicología , Masculino , Negro o Afroamericano/psicología , Niño , Depresión/psicología , Depresión/etnología , Control Glucémico/psicología , Hemoglobina Glucada , Población Urbana , Automanejo/psicología , Distrés Psicológico , Estrés Psicológico/psicología
11.
J Pediatr Psychol ; 49(8): 538-546, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38775162

RESUMEN

OBJECTIVE: Due to systemic inequities, Black adolescents with type 1 diabetes are more likely to have suboptimal glycemic control and high rates of diabetes distress, but tailored interventions for this population are lacking. In primary outcomes of a randomized clinical trial, a family-based eHealth intervention improved glycemic control in Black adolescents with type 1 diabetes and elevated depressive symptoms. The present study is a secondary analysis of these clinical trial data examining the moderating effect of diabetes distress on the efficacy of the intervention. METHODS: Using secondary data from a multicenter randomized clinical trial (Clinicaltrials.gov [NCT03168867]), caregiver-adolescent dyads were randomly assigned to either up to three sessions of an eHealth parenting intervention (n = 75) or a standard medical care control group (n = 74). Black adolescents (10 years, 0 months to 14 years, 11 months old) with type 1 diabetes and a caregiver willing to participate were eligible. Adolescents reported their diabetes distress at baseline, and hemoglobin A1c (HbA1c) data were collected at baseline, 6-, 13-, and 18-month follow-up. RESULTS: No between-group contrasts emerged in a linear mixed-effects regression (p's > .09). Within-group contrasts emerged such that adolescents assigned to the intervention who reported high diabetes distress had lower HbA1c at the 18-month follow-up relative to baseline (p = .004); the 18-month decrease in HbA1c was -1.03%. CONCLUSIONS: Black adolescents with type 1 diabetes and high levels of diabetes distress showed significant decreases in HbA1c following a family-based eHealth intervention, suggesting diabetes distress may be a key moderator of intervention efficacy within this population.


Asunto(s)
Negro o Afroamericano , Diabetes Mellitus Tipo 1 , Hemoglobina Glucada , Control Glucémico , Distrés Psicológico , Telemedicina , Humanos , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 1/sangre , Adolescente , Femenino , Masculino , Negro o Afroamericano/psicología , Control Glucémico/psicología , Hemoglobina Glucada/análisis , Niño , Estrés Psicológico/terapia , Cuidadores/psicología , Depresión/terapia , Depresión/psicología , Responsabilidad Parental/psicología
12.
BMC Med Inform Decis Mak ; 24(1): 247, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232725

RESUMEN

BACKGROUND: Artificial intelligence (AI) is increasingly used for prevention, diagnosis, monitoring, and treatment of cardiovascular diseases. Despite the potential for AI to improve care, ethical concerns and mistrust in AI-enabled healthcare exist among the public and medical community. Given the rapid and transformative recent growth of AI in cardiovascular care, to inform practice guidelines and regulatory policies that facilitate ethical and trustworthy use of AI in medicine, we conducted a literature review to identify key ethical and trust barriers and facilitators from patients' and healthcare providers' perspectives when using AI in cardiovascular care. METHODS: In this rapid literature review, we searched six bibliographic databases to identify publications discussing transparency, trust, or ethical concerns (outcomes of interest) associated with AI-based medical devices (interventions of interest) in the context of cardiovascular care from patients', caregivers', or healthcare providers' perspectives. The search was completed on May 24, 2022 and was not limited by date or study design. RESULTS: After reviewing 7,925 papers from six databases and 3,603 papers identified through citation chasing, 145 articles were included. Key ethical concerns included privacy, security, or confidentiality issues (n = 59, 40.7%); risk of healthcare inequity or disparity (n = 36, 24.8%); risk of patient harm (n = 24, 16.6%); accountability and responsibility concerns (n = 19, 13.1%); problematic informed consent and potential loss of patient autonomy (n = 17, 11.7%); and issues related to data ownership (n = 11, 7.6%). Major trust barriers included data privacy and security concerns, potential risk of patient harm, perceived lack of transparency about AI-enabled medical devices, concerns about AI replacing human aspects of care, concerns about prioritizing profits over patients' interests, and lack of robust evidence related to the accuracy and limitations of AI-based medical devices. Ethical and trust facilitators included ensuring data privacy and data validation, conducting clinical trials in diverse cohorts, providing appropriate training and resources to patients and healthcare providers and improving their engagement in different phases of AI implementation, and establishing further regulatory oversights. CONCLUSION: This review revealed key ethical concerns and barriers and facilitators of trust in AI-enabled medical devices from patients' and healthcare providers' perspectives. Successful integration of AI into cardiovascular care necessitates implementation of mitigation strategies. These strategies should focus on enhanced regulatory oversight on the use of patient data and promoting transparency around the use of AI in patient care.


Asunto(s)
Inteligencia Artificial , Enfermedades Cardiovasculares , Confianza , Humanos , Inteligencia Artificial/ética , Enfermedades Cardiovasculares/terapia
13.
Nurs Health Sci ; 26(2): e13114, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38566419

RESUMEN

The purpose of this study was to evaluate the handoff guidance (HG) self-management intervention for multimorbid chronic obstructive pulmonary disease (COPD) patients following hospitalization for acute exacerbation of COPD (AECOPD) using HG self-management intervention compared to a control group on COPD self-management outcomes (self-care, self-efficacy, health engagement) and assess feasibility, acceptability, and healthcare utilization. A randomized pilot study used a 2-group with repeated measures design. Adults with COPD who had been hospitalized for AECOPD were recruited. After discharge, the HG self-management intervention employed health coaching delivered at: 1-3, 10-12, and 20-22 days after hospital discharge. Follow-up data collected was collected at 1-3, 10-12, 20-22, 30, 60, and 90 days after hospital discharge. A total of 29 subjects participated, with a mean age of 66 (+8.7) years old, the majority were females (n = 18). Intervention participants reported the acceptability of the HG self-management intervention. Participants in both groups continued to report COPD symptoms after discharge, which decreased over time, although not significantly different by group. The use of COPD maintenance, monitoring, and management behaviors was higher in the treatment group, although not significantly different.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Automanejo , Anciano , Femenino , Humanos , Masculino , Progresión de la Enfermedad , Hospitalización , Alta del Paciente , Proyectos Piloto , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/terapia , Persona de Mediana Edad
14.
J Med Ethics ; 49(3): 200-203, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35428737

RESUMEN

It is well established that demographic representation in clinical research is important for understanding the safety and effectiveness of novel therapeutics and vaccines in diverse patient populations. In recent years, the National Institutes of Health and Food and Drug Administration have issued guidelines and recommendations for the inclusion of women, older adults, and racial and ethnic minorities in research. However, these guidelines fail to provide an adequate explanation of why racial and ethnic representation in clinical research is important. This article aims to both provide the missing arguments for why adequate representation of racial and ethnic minorities in clinical research is essential and to articulate a number of recommendations for improving diversity going forward.Appropriate racial and ethnic representation and fair inclusion help (1) increase the generalisability of clinical trial results, (2) equitably distribute any benefits of clinical research and (3) enable trust in the research enterprise.


Asunto(s)
Grupos Minoritarios , Salud Pública , Humanos , Femenino , Anciano , Grupos Raciales
15.
Nucleic Acids Res ; 49(22): 13179-13193, 2021 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-34871450

RESUMEN

Cellular and virus-coded long non-coding (lnc) RNAs support multiple roles related to biological and pathological processes. Several lncRNAs sequester their 3' termini to evade cellular degradation machinery, thereby supporting disease progression. An intramolecular triplex involving the lncRNA 3' terminus, the element for nuclear expression (ENE), stabilizes RNA transcripts and promotes persistent function. Therefore, such ENE triplexes, as presented here in Kaposi's sarcoma-associated herpesvirus (KSHV) polyadenylated nuclear (PAN) lncRNA, represent targets for therapeutic development. Towards identifying novel ligands targeting the PAN ENE triplex, we screened a library of immobilized small molecules and identified several triplex-binding chemotypes, the tightest of which exhibits micromolar binding affinity. Combined biophysical, biochemical, and computational strategies localized ligand binding to a platform created near a dinucleotide bulge at the base of the triplex. Crystal structures of apo (3.3 Å) and ligand-soaked (2.5 Å) ENE triplexes, which include a stabilizing basal duplex, indicate significant local structural rearrangements within this dinucleotide bulge. MD simulations and a modified nucleoside analog interference technique corroborate the role of the bulge and the base of the triplex in ligand binding. Together with recently discovered small molecules that reduce nuclear MALAT1 lncRNA levels by engaging its ENE triplex, our data supports the potential of targeting RNA triplexes with small molecules.


Asunto(s)
Herpesvirus Humano 8/metabolismo , Nucleótidos/metabolismo , Poli A/metabolismo , ARN Largo no Codificante/metabolismo , ARN Viral/metabolismo , Bibliotecas de Moléculas Pequeñas/metabolismo , Secuencia de Bases , Cristalografía por Rayos X , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/fisiología , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Conformación de Ácido Nucleico , Nucleótidos/genética , Poli A/química , Poli A/genética , Estabilidad del ARN/genética , ARN Largo no Codificante/química , ARN Largo no Codificante/genética , ARN Viral/química , ARN Viral/genética , Sarcoma de Kaposi/virología , Bibliotecas de Moléculas Pequeñas/química
16.
Nurs Res ; 72(4): 292-300, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37011339

RESUMEN

BACKGROUND: The Patient Activation Measure (PAM) is used clinically and in research to measure an individual's knowledge, skills, and confidence related to their health management engagement. Despite the use of "patient" in the title, the instrument can be used in nonpatient populations. A group at high risk for low activation concerning their own health is family caregivers of patients with chronic illnesses. The psychometric properties of the PAM have not been established in family caregivers. OBJECTIVES: This study aimed to examine the psychometric properties of the PAM 10-item version (PAM-10) in a sample of family caregivers of patients with chronic illnesses. Our focus was on family caregivers' health activation of their own healthcare needs. METHODS: We evaluated the internal consistency reliability of the PAM-10 in a sample of 277 family caregivers. Item-total correlations and interitem correlations were used to assess item homogeneity. Construct validity of the PAM-10 was examined using exploratory factor analysis and testing hypotheses on known relationships. RESULTS: The PAM-10 demonstrated adequate internal consistency. Item-total correlation coefficients and interitem correlation coefficients were acceptable. Construct validity of the instrument was supported. Factor analysis yielded two factors that explained 62.3% of the variance in the model. Lower levels of depressive symptoms were significantly associated with better activation, providing evidence of construct validity. Caregivers with high activation levels were significantly more likely to engage in and adhere to self-care behaviors such as regular exercise, eating a healthy diet, and engaging in stress reduction strategies. DISCUSSION: This study demonstrated that the PAM-10 is a reliable and valid measure for family caregivers of patients with chronic illnesses to measure caregivers' health activation of their own healthcare needs.


Asunto(s)
Cuidadores , Participación del Paciente , Humanos , Psicometría , Reproducibilidad de los Resultados , Enfermedad Crónica , Encuestas y Cuestionarios
17.
Pediatr Dermatol ; 40(3): 413-421, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36544364

RESUMEN

OBJECTIVE: To describe the clinical and laboratory outcomes of infants with subcutaneous fat necrosis of the newborn (SCFN) and propose a care algorithm. METHODS: This single-center, retrospective study of infants diagnosed with SCFN at Ann & Robert H. Lurie Children's Hospital of Chicago from 2009 to 2019. RESULTS: Of 32 infants who met inclusion criteria, most were born full-term (84%), born via cesarean section (58%), had normal weight for gestational age (69%), and experienced delivery complications (53%). Twenty-nine infants (91%) had calcium drawn, and all had hypercalcemia. Three infants developed clinical symptoms of hypercalcemia, two required hospital admission, two developed nephrocalcinosis, and one developed acute kidney injury. The majority of infants (62%) had a peak ionized calcium between 1.5 and 1.6 mmol/L. No infants with peak ionized calcium less than 1.5 mmol/L developed complications of hypercalcemia. Most patients were diagnosed with hypercalcemia (86%) and demonstrated peak ionized calcium levels (59%) within the first 28 days of life. No patients developed hypercalcemia after 3 months of age. CONCLUSION: Hypercalcemia occurred in 100% of infants who had laboratory monitoring. We recommend obtaining an initial ionized calcium level when SCFN is suspected, and monitoring for the first 3 months of life if hypercalcemia has not been detected. In patients with asymptomatic hypercalcemia less than 1.5 mmol/L, there appears to be low likelihood of related complications. For symptomatic, markedly elevated (>1.6 mmol/L), or persistently elevated levels (>6 months) we suggest coordinated care with endocrinology or nephrology, consider hospitalization, and urinary system ultrasound.


Asunto(s)
Necrosis Grasa , Hipercalcemia , Embarazo , Recién Nacido , Niño , Humanos , Femenino , Hipercalcemia/complicaciones , Calcio , Estudios Retrospectivos , Cesárea , Grasa Subcutánea , Necrosis Grasa/complicaciones
18.
Pain Manag Nurs ; 24(5): 558-566, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37455185

RESUMEN

BACKGROUND: Substance use disorders (SUDs) are highly prevalent among adults with persistent pain. Yet, standard competencies for integrating pain and SUD content are lacking across health science student curricula. Additionally, pharmacotherapies to treat SUDs are underutilized. AIM: To address these gaps, a team of health science faculty created an interprofessional simulation activity using a standardized patient and evaluated learner outcomes related to assessment and treatment of comorbid persistent pain and substance use. METHODS: A total of 304 health science students representing nursing, medicine, pharmacy, and social work programs attended virtual learning sessions. Interprofessional student teams developed a team-based care plan for an adult with musculoskeletal pain who takes prescribed opioids while using alcohol. Pre- and post-activity surveys assessing knowledge and confidence were matched for 198 students. Descriptive statistics summarized survey data with inferential analysis of paired data. RESULTS: The largest significant improvements between pre- and post-activity knowledge were observed in items specific to pharmacotherapy options for alcohol and opioid use disorders. Similar gains were noted in students' confidence regarding pharmacotherapies. No significant differences were noted on pre-post-activity knowledge scores between the three main profession groups (medicine, nursing, and pharmacy). CONCLUSIONS: Students attending this interprofessional simulation demonstrated improved knowledge and confidence, particularly in pharmacotherapies for alcohol and opioid use disorders. Replication of such programs can be used to provide consistent content across health science disciplines to heighten awareness and receptivity to medications available to treat SUDs in people treated for persistent pain. The curriculum is freely available from the corresponding author.


Asunto(s)
Educación Interprofesional , Trastornos Relacionados con Opioides , Humanos , Adulto , Evaluación de Programas y Proyectos de Salud , Curriculum , Dolor
19.
J Cardiovasc Nurs ; 2023 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-37787727

RESUMEN

BACKGROUND: Black race, inadequate health literacy, and poor perceived control are predictors of increased cardiovascular disease (CVD) risk. The purpose of this study was to explore the relationships among race, health literacy, perceived control, and CVD risk while controlling for known risk factors in incarcerated men. METHODS: We included data from 349 incarcerated men to examine race and CVD risk (Framingham Risk Score) using a serial mediation model with health literacy and perceived control using 95% confidence intervals (CIs) from 5000 bootstrap samples. RESULTS: Of the participants (age, 36 ± 10; education, 12 ± 2; body mass index, 28.3 ± 5.0), 64.2% were White and 35.8% were Black. Black incarcerated men were younger (P = .047) with lower levels of health literacy (P < .001). All 3 indirect effects of race on CVD were significant, whereas the direct effect of race was not. Black incarcerated men had higher levels of CVD risk through health literacy (a1b1 = 0.3571; 95% CI, 0.0948-0.7162) and lower levels of CVD risk through perceived control (a2b2 = -0.1855; 95% CI, -0.4388 to -0.0077). Black incarcerated men had higher levels of CVD risk through health literacy influenced by perceived control (a1b2d21 = 0.0627; 95% CI, 0.0028-0.1409), indicating that despite the protective effect of higher levels of perceived control in Black incarcerated men, CVD risk remained higher compared with their White counterparts. CONCLUSION: Future CVD risk reduction interventions in incarcerated men, specifically Black incarcerated men, should include goals of improving health literacy and perceived control as modifiable risk factors.

20.
Res Nurs Health ; 46(5): 502-514, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37515582

RESUMEN

Research on opioid use disorder (OUD) in pregnancy has mainly considered women in urban areas receiving treatment, with less known about women in rural areas. We sought to describe demographics and substance use characteristics of pregnant women with OUD and to compare the women based on urbanicity, in a state (Kentucky) with unfavorable economic conditions in many rural counties; we hypothesized that pregnant women in rural areas would have greater adversity, broadly defined, related to substance use. Using data collected from a larger project between 2017 and 2020, we analyzed characteristics of 93 pregnant women (59 rural and 34 urban) with OUD; we examined data in medical, employment, substance use, legal, family history, relationship, and psychiatric health domains, both overall and within rural (population <50,000) and urban (population ≥50,000) strata. Pregnant women with OUD from rural and urban areas were similar on almost all attributes. Among the few significant differences, 30% from urban areas perceived inadequate prenatal care versus 11% from rural areas (p = 0.024); 21% of urban women used amphetamines/methamphetamines in the month before delivery versus 0% of rural women (p < 0.001); and rural women had longer most recent abstinence from substance use than their urban counterparts (medians 7.0 and 2.8 months, p = 0.049). The few significant differences that were discovered favored rural women. These findings, contrary to our hypothesis, suggest that tailoring interventions may require more than focusing on geography. The participants in this study were pregnant women being treated for OUD, and as such there is patient contribution of data.


Asunto(s)
Trastornos Relacionados con Opioides , Embarazo , Femenino , Humanos , Trastornos Relacionados con Opioides/epidemiología , Mujeres Embarazadas , Kentucky , Población Rural , Población Urbana
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