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1.
Nature ; 574(7777): 264-267, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31578522

RESUMEN

Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA)1. However, the mycobiome has not been clearly implicated in tumorigenesis. Here we show that fungi migrate from the gut lumen to the pancreas, and that this is implicated in the pathogenesis of PDA. PDA tumours in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue. The composition of the mycobiome of PDA tumours was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices. Specifically, the fungal community that infiltrated PDA tumours was markedly enriched for Malassezia spp. in both mice and humans. Ablation of the mycobiome was protective against tumour growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species-but not species in the genera Candida, Saccharomyces or Aspergillus-accelerated oncogenesis. We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment-or knockdown of C3aR in tumour cells-were both protective against tumour growth. In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl- (also known as Mbl2) or C3-deficient mice. Collectively, our work shows that pathogenic fungi promote PDA by driving the complement cascade through the activation of MBL.


Asunto(s)
Adenocarcinoma/microbiología , Adenocarcinoma/patología , Carcinogénesis , Carcinoma Ductal Pancreático/microbiología , Carcinoma Ductal Pancreático/patología , Microbioma Gastrointestinal/inmunología , Lectina de Unión a Manosa/inmunología , Micobioma/inmunología , Adenocarcinoma/inmunología , Animales , Carcinoma Ductal Pancreático/inmunología , Estudios de Casos y Controles , Activación de Complemento , Complemento C3/deficiencia , Complemento C3/inmunología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL
2.
Artículo en Inglés | MEDLINE | ID: mdl-38271636

RESUMEN

Throughout time, ethnoracial groups have endured a range of traumatic experiences as historically marginalized members of the United States. The consequences of these experiences have been referred to as historical trauma (HT): a collective trauma, inflicted on a group of people who share a specific identity, that has psychological, physical, and social impacts on succeeding generations. In this review, we examine the literature on HT in relation to US ethnoracial groups by defining HT, providing a background for its development, and describing critiques of the concept. We then review the literature on HT in relation to Indigenous Americans, African Americans, and Asian Americans. For each group, we address the nature of HT, the transmission of HT and its impacts, and healing strategies. We conclude with a summary of the benefits, limitations, and complexities of HT research as well as recommendations for future work in this area. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 20 is May 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

3.
Int J Behav Med ; 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38472713

RESUMEN

BACKGROUND: Improving quality of life (QOL) in advanced and metastatic cancer is a priority with increasing survivorship. This systematic review synthesizes psychosocial and behavioral interventions incorporating culture with the goal of examining their benefit for understudied and medically underserved populations with advanced and metastatic cancer. METHOD: Reports were systematically screened for (1) a focus on advanced and metastatic cancer survivors, (2) psychosocial or behavioral intervention intended to improve QOL, (3) evidence of incorporating the culture(s) of understudied/underserved populations, and (4) availability in English. Bias was evaluated using the JBI Critical Appraisal Checklist and the Methodological index for non-randomized studies. Qualitative synthesis and quantitative meta-analyses were completed. RESULTS: Eighty-six reports containing 5981 participants' data were examined. Qualitative synthesis of 23 studies identified four overarching themes relevant for incorporating culture in interventions. Meta-analysis of 19 RCTs and 4 quasi-experimental studies containing considerable heterogeneity indicated greater improvements in QOL (g = 0.84), eudaimonic well-being (g = 0.53), distress (g = -0.49), and anxiety (g = -0.37) for main intervention conditions compared to controls. Meta-analysis of 10 single-arm trials containing minimal to moderate heterogeneity found benefit for anxiety (g = -0.54), physical symptoms (g = -0.39), and depression (g = -0.38). CONCLUSION: Psychosocial and behavioral interventions with cultural incorporation appear beneficial for improving QOL-related outcomes in advanced and metastatic cancer. Studies incorporating culture in psychosocial or behavioral interventions offer noteworthy insight and suggestions for future efforts such as attending to deep cultural structure.

4.
Ann Behav Med ; 57(9): 733-742, 2023 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-37318273

RESUMEN

BACKGROUND: Black women have the highest mortality from breast cancer compared with other racial/ethnic groups. Black women with breast cancer also evidence compromised quality of life in some domains. Culturally relevant aspects of their experience are understudied. PURPOSE: The goal of this qualitative study was to examine the relevance of the Strong Black Woman schema in the cancer context. METHODS: Three Gatherings (i.e., culturally curated focus groups) were conducted with Black women who had been diagnosed with breast cancer and recruited from cancer-related listservs and events. A five-person team conducted reflexive thematic analysis of Gathering transcripts. RESULTS: The 37 participants ranged in age (30 to 94 years) and in diagnosis duration (2 months to 29 years). Reflexive thematic analysis yielded six themes that characterized the women's experience: historical legacy of the Strong Black Woman, navigating intersecting Strong Black Woman identities, everyday challenges encountered on the battlefield by Strong Black Women, Strong Black Woman in action during the breast cancer journey, the complexities of seeking and accepting support, and the liberated Strong Black Woman. The schema's negative consequences included the oncologic team and others expecting the participants to be strong and not to need support. Expectations to suppress emotions and continue caring for others to the neglect of the self also were evident. Positive consequences included engaging in self-advocacy in the oncologic context and redefining strength to include expressing emotions and accepting help. CONCLUSIONS: The Strong Black Woman schema is highly relevant in the breast cancer context and could be addressed in culturally centered interventions.


Compared with other racial/ethnic groups, Black American women diagnosed with breast cancer have the highest death rate and some aspects of their quality of life is lower. The authors developed Project SOAR (Speaking Our African American Realities) to shed light on the experiences of Black American women diagnosed with breast cancer. In one Project SOAR study, 37 women took part in Gatherings­small group meetings conducted in an all-Black, all-woman space­in which they talked about the relevance of the Strong Black Woman (or Black Superwoman) concept during breast cancer. Arising from a history of enslavement, the concept involves suppressing emotions, always acting strong, taking care of others while neglecting care of oneself, and declining others' support. Gathering participants ranged in age (30 to 94 years) and time elapsed since diagnosis (2 months to 29 years). Their breast cancer experiences often corresponded with the Strong Black Woman concept. For example, some medical professionals and others expected them to act strong, to keep caring for others, not to need support, and not to voice their emotions during the cancer experience. Some women redefined strength to include expressing emotions and accepting help. The authors are developing resources for Black American women breast cancer survivors.


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/psicología , Calidad de Vida/psicología , Investigación Cualitativa , Emociones , Grupos Focales
5.
Qual Health Res ; 33(8-9): 753-764, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37212719

RESUMEN

Black Americans face a multitude of problems in the healthcare system, including challenges during interactions with healthcare providers. The present study examined the quality of healthcare provider-Black patient interactions in a sample of Black American women with a breast cancer diagnosis. More specifically, the study examined potential contributors to Black Americans' current healthcare experiences and lack of trust by identifying their specific negative and positive encounters in the healthcare system. Three in-person Gatherings (i.e., culturally curated focus groups; N = 37) were conducted as part of a community-academic research partnership, Project SOAR (Speaking Our African American Realities). Four themes were identified through reflexive thematic analysis: Individual and Systemic Injustice Directed at Black Breast Cancer Survivors; Protecting Myself from an Untrustworthy Medical System; Stereotypes Interfered with My Care; and Good Care Should Include Compassion, Respect, Shared Decision Making, and Tailored Support. The present findings highlight the importance of addressing systemic and individual injustice toward Black Americans in healthcare settings generally, and Black women diagnosed with breast cancer specifically.


Asunto(s)
Negro o Afroamericano , Neoplasias de la Mama , Relaciones Profesional-Paciente , Femenino , Humanos , Atención a la Salud , Grupos Focales , Personal de Salud
6.
Curr Opin Organ Transplant ; 28(2): 65-70, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36752272

RESUMEN

PURPOSE OF REVIEW: The aim of this study was to highlight recent progress in xenotransplantation and discuss the remaining obstacles/steps before the FDA is likely to approve a clinical trial. RECENT FINDINGS: Long-term survival of life-supporting xenografts in preclinical models has led to discussion of clinical trials of xenotransplantation. The reports of clinical cardiac xenotransplant based on compassionate use FDA approval and renal xenotransplants to brain-dead humans have led to further considerations of clinical trials. Discussions between the transplant community and the FDA have established critical next steps before a clinical trial of xenotransplants is likely to be approved. These steps include testing the clinical immunosuppression protocol and the organ from a genetically modified source animal in nonhuman primates with reproducible survival of at least 6 months. In addition, appropriate viral surveillance protocols and confirmation that the xenografts support appropriate human physiology are likely to be critical elements for FDA-approval. Finally, further studies in the human decedent model are likely to provide critical information about human immune and physiologic responses to xenografts. SUMMARY: This review highlights the current progress in nonhuman primate models and recent reports of human xenotransplantation. It also describes the remaining hurdles and currently understood FDA requirements that remain to be achieved before a clinical trial of xenotransplantation can be approved.


Asunto(s)
Trasplantes , Animales , Humanos , Trasplante Heterólogo/métodos , Terapia de Inmunosupresión , Primates , Animales Modificados Genéticamente
7.
Artículo en Inglés | MEDLINE | ID: mdl-36315616

RESUMEN

OBJECTIVES: Racial/ethnic discrimination has been linked to behavioral and emotional problems in youth from marginalized groups. However, the psychological experience associated with discrimination may differ between immigrant and nonimmigrant youth. Race-based discrimination may impact an adolescent's view of their own group (private regard) and/or their sense of how others view their group (public regard). Owing to differences in racialization, immigrant adolescents may be affected differently by experiences of discrimination than their U.S.-born peers. The present study examined whether nativity moderated the paths from racial/ethnic discrimination to private and public regard to mental health problems among Vietnamese American youth. METHOD: Surveys were completed by 718 Vietnamese American 10th and 11th graders (Mage = 15.54 years, 61.4% female, 38.6% male). In this sample, 21.2% were first-generation (i.e., born outside of the United States) and 78.8% were second-generation (i.e., born in the United States with at least one parent born outside of the United States). RESULTS: Multigroup path analysis tested the direct and indirect effects of racial/ethnic discrimination on behavioral and emotional problems via private and public regard and whether associations differed for first- versus second-generation youth. Racial/ethnic discrimination was associated with lower public regard, but not private regard, for both first- and second-generation Vietnamese American youth. Public regard was negatively associated with behavioral and emotional problems only among second-generation youth. No indirect effects were significant. CONCLUSIONS: Findings suggest differences in racialized experiences, as well as opportunities to support second-generation Vietnamese American and other marginalized youth from immigrant families from the mental health impacts of discrimination. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

8.
J Behav Med ; 44(1): 1-17, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32535673

RESUMEN

The objective of this study was to determine whether: (a) cancer-related coping profiles change across time; (b) coping profile transition types predict changes in depressive and physical symptoms. Latent transition analysis was conducted with repeated measures of seven cancer-related coping processes from 460 women recently diagnosed with breast cancer. In multilevel models, coping profile transition groups were entered as predictors of symptoms across 12 months. Three coping profiles emerged at study entry, with two profiles at later assessments. Forty-eight percent of women maintained high-moderate approach-oriented coping over time. Specific factors (e.g., age, acceptance of emotions) differentiated the transition groups. Women who increased and then maintained high-moderate approach-oriented coping had relatively high initial depressive symptoms that declined steeply. When cancer-related acceptance predominated, women experienced increasing physical symptoms. Distinct cancer-related coping patterns are related to the level of and change in depressive and physical symptoms longitudinally. Early intervention to increase approach-oriented coping strategies could yield favorable outcomes.


Asunto(s)
Neoplasias de la Mama , Adaptación Psicológica , Depresión/diagnóstico , Emociones , Femenino , Humanos
9.
J Clin Child Adolesc Psychol ; 50(5): 565-578, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-31464533

RESUMEN

Objective: Recent research has documented cultural differences in the extent and manner in which various forms of emotion regulation are linked with psychological well-being. Most of these studies, however, have been cross-sectional, nor have they directly examined the values underlying the use of emotion regulation. The present study examined emotion restraint values and their interactions with life stress in predicting internalizing symptoms across time among Vietnamese American and European American adolescents. The study focused on adolescence as a critical developmental period during which life stress and internalizing symptoms increase significantly. Method: Vietnamese American (n = 372) and European American (n = 304) adolescents' levels of emotion restraint values, internalizing symptoms, and stress were assessed at two timepoints six months apart. Results: Results indicated differential associations between emotion restraint values, stress, and symptoms over time for the two groups. For Vietnamese American adolescents, emotion restraint values did not predict depressive, anxiety, or somatic symptoms. For European American adolescents, emotion restraint values predicted higher somatic symptoms but buffered against the effects of interpersonal stress on anxiety and depressive symptoms. Conclusions: These results provide increased understanding of the role of values related to emotion restraint in shaping adolescent internalizing symptoms and responses to stress across cultural groups. Implications of the findings for guiding intervention efforts are discussed.


Asunto(s)
Asiático , Emociones , Adolescente , Ansiedad , Estudios Transversales , Humanos , Estrés Psicológico , Estados Unidos
11.
J Fam Issues ; 39(13): 3641-3663, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30906094

RESUMEN

Drawing from an ecological systems framework, we qualitatively explored how Confucian-heritage Asian American emerging adults compared with non-Hispanic European American emerging adults on views of sibling relationships and birth order. Thematic analysis of 48 semi-structured interviews revealed positive sibling relationship themes for both ethnocultural groups: mutual support, companionship, and appreciation; comfort from shared burden of negative parental interactions; and pride in one another. Birth-order themes were also similar across the groups. First-borns overall reported a strong pressure to be a role model to later-borns, provide sibling care, assume family responsibilities, and not expect to rely on younger siblings. Despite these similarities, Asian American first-borns were unique in taking comfort in having siblings who shared a less traditional Asian cultural perspective than their parents. They also described additional pressure from being the oldest within an immigrant family.

13.
Int Orthop ; 39(10): 2011-6, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26156715

RESUMEN

PURPOSE: Because the occurrence of postoperative myocardial ischaemia (MI) predicts subsequent cardiac morbidity and mortality, we determined the prevalence of and risk factors for MI in hip and knee arthroplasty patients. METHODS: High-sensitivity cardiac troponin T (hs-cTnT) was measured on stored samples from postoperative day two in 394 hip and knee arthroplasty patients ≥ 65 years of age enrolled in the Genetics-InFormatics Trial (GIFT). RESULTS: Fifty-three (13.5 %) participants had MI, of whom only three were diagnosed clinically during their hospitalisation. The risk of MI increased with age [odds ratio (OR) 3.52 per decade, 95 % confidence interval (CI) 2.00-6.19] and diabetes (OR 2.23, 95 % CI 1.04-4.77). MI was rarer with statins (OR 0.74, 95 % CI 0.40-1.35) and more common with hypertension, coronary artery disease and tobacco use, although these were not statistically significant. CONCLUSIONS: Subclinical MI occurs frequently after arthroplasty. Diabetic and elderly patients are at highest risk.


Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Isquemia Miocárdica/epidemiología , Factores de Edad , Anciano , Complicaciones de la Diabetes/complicaciones , Femenino , Humanos , Incidencia , Masculino , Isquemia Miocárdica/etiología , Prevalencia , Factores de Riesgo
14.
Cleft Palate Craniofac J ; 52(2): 240-5, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24605928

RESUMEN

Objective : To present the case report of a patient with expanded hemifacial microsomia (HFM) that illustrates the complex interactions of these embryogenic factors and to review current theories and mechanism regarding the etiopathogenesis of HFM. Design and Method : We present the case of an African American girl who was born at full term by cesarean section and transferred to our institution for systemic malformations. Her craniofacial findings include holoprosencephaly, cleft lip and palate, low set and posteriorly rotated ears, flat midfacial features, micrognathia, left HFM with grade 1 microtia, hypoplastic mandible, and a small preauricular pharyngeal arch remnant. Systemic anomalies included ectopic kidney, atrial-septal defect, bilateral hip dysplasia, bilateral humeroradial fusion, bilateral club feet, and bilateral low-set thumbs with the right side also being triphalangeal. Genetic evaluation did not identify a molecular diagnosis or other known syndrome. Conclusions : Although vasculogenic disruption of the stapedial artery during early fetal gestation has been implicated in the etiology of HFM, the grouping and bilateral findings seen in our patient argue against this relatively simple and localized phenomenon. Instead, such diverse and widespread anomalies in the setting of expanded spectrum HFM seem to support the theory of a disorder in blastogenesis as the cause of HFM.


Asunto(s)
Anomalías Múltiples/patología , Síndrome de Goldenhar/patología , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/cirugía , Femenino , Síndrome de Goldenhar/diagnóstico por imagen , Síndrome de Goldenhar/cirugía , Humanos , Recién Nacido
15.
Cleft Palate Craniofac J ; 52(4): 447-51, 2015 07.
Artículo en Inglés | MEDLINE | ID: mdl-25137604

RESUMEN

OBJECTIVE: To analyze the hospital course of 100 consecutive infants after primary cleft lip repair (PCLR) and identify factors related to length of stay (LOS). DESIGN: Retrospective analysis of 100 consecutive infants who were routinely admitted after PCLR. SETTING: Tertiary care center. PATIENTS: One hundred consecutive infants undergoing PCLR. Demographic and perioperative data were collected and analyzed. MAIN OUTCOME MEASURE: LOS, planned before data collection. RESULTS: Male:female ratio was 65:35. Seventy-two infants had unilateral cleft lip; syndromic association was documented in 15 patients. Mean age and weight at PCLR were 5.6 ± 4.0 months and 6.7 ± 1.3 kg, respectively. Mean duration of surgery was 2.5 ± 0.9 hours, and mean duration of general anesthesia was 3.4 ± 0.9 hours. A total of 3.3 ± 1.5 mL of intraoperative local anesthetic was used per patient. Intravenous fluids were necessary after transfer from the post-anesthesia care unit to the general ward in 98% of patients. Almost half (44%) of all patients received intravenous morphine 23 hours or more after hospital admission. Mean LOS was 35.8 ± 13.9 hours. No association was identified between patient demographic factors and LOS. Multivariate linear regression models identified significant positive correlation between LOS and duration of general anesthesia (P = .002). Greater volume of postoperative oral intake (P = .000) and higher acetaminophen dosage on the floor (P = .000) correlated with decreased LOS. CONCLUSIONS: This study identifies perioperative factors associated with LOS. Our findings question the safety of routine outpatient or short-stay observation after PCLR.


Asunto(s)
Labio Leporino/cirugía , Tiempo de Internación/estadística & datos numéricos , Femenino , Humanos , Lactante , Masculino , Tempo Operativo , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
16.
Transplantation ; 108(6): 1440-1447, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38361232

RESUMEN

BACKGROUND: Organs from Public Health Service criteria (PHSC) donors, previously referred to as PHS infectious-risk donors, have historically been recovered but not used, traditionally referred to as "discard," at higher rates despite negligible risk to recipients. On March 1, 2021, the definition of PHSC donors narrowed to include only the subset of donors deemed to have meaningfully elevated risk in the current era of improved infectious disease testing. METHODS: Using Scientific Registry of Transplant Recipients data from May 1, 2019, to December 31, 2022, we compared rates of PHSC classification and nonutilization of PHSC organs before versus after the March 1, 2021, policy change among recovered decedents using the χ 2 tests. We performed an adjusted interrupted time series analysis to examine kidney and liver recovery/nonuse (traditionally termed "discard") and kidney, liver, lung, and heart nonutilization (nonrecovery or recovery/nonuse) prepolicy versus postpolicy. RESULTS: PHSC classification dropped sharply from 24.5% prepolicy to 15.4% postpolicy ( P  < 0.001). Before the policy change, PHSC kidney recovery/nonuse, liver nonuse, lung nonuse, and heart nonuse were comparable to non-PHSC estimates (adjusted odds ratio: kidney =  0.98 1.06 1.14 , P  = 0.14; liver =  0.85 0.92 1.01 , P  = 0.07; lung =  0.91 0.99 1.08 , P  = 0.83; heart =  0.89 0.97 1.05 , P  = 0.47); following the policy change, PHSC kidney recovery/nonuse, liver nonuse, lung nonuse, and heart nonuse were lower than non-PHSC estimates (adjusted odds ratio: kidney =  0.77 0.84 0.91 , P  < 0.001; liver =  0.77 0.84 0.92 , P  < 0.001; lung =  0.74 0.81 0.90 , P  < 0.001; heart =  0.61 0.67 0.73 , P  < 0.001). CONCLUSIONS: Even though PHSC donors under the new definition are a narrower and theoretically riskier subpopulation than under the previous classification, PHSC status appears to be associated with a reduced risk of kidney and liver recovery/nonuse and nonutilization of all organs. Although historically PHSC organs have been underused, our findings demonstrate a notable shift toward increased PHSC organ utilization.


Asunto(s)
Selección de Donante , Infecciones por VIH , Hepatitis B , Hepatitis C , Donantes de Tejidos , Humanos , Donantes de Tejidos/estadística & datos numéricos , Masculino , Femenino , Infecciones por VIH/transmisión , Infecciones por VIH/epidemiología , Infecciones por VIH/diagnóstico , Hepatitis B/transmisión , Hepatitis B/epidemiología , Hepatitis B/diagnóstico , Hepatitis C/transmisión , Hepatitis C/epidemiología , Hepatitis C/diagnóstico , Medición de Riesgo , Estados Unidos/epidemiología , United States Public Health Service , Persona de Mediana Edad , Factores de Riesgo , Sistema de Registros , Trasplante de Órganos , Adulto , Obtención de Tejidos y Órganos/estadística & datos numéricos
17.
JMIR Res Protoc ; 13: e50032, 2024 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-38648633

RESUMEN

BACKGROUND: Asian Americans with metastatic cancer are an understudied population. The Describing Asian American Well-Being and Needs in Cancer (DAWN) Study was designed to understand the supportive care needs of Chinese-, Vietnamese-, and Korean-descent (CVK) patients with metastatic cancer. OBJECTIVE: This study aims to present the DAWN Study protocol involving a primarily qualitative, convergent, mixed methods study from multiple perspectives (patients or survivors, caregivers, and health care professionals). METHODS: CVK Americans diagnosed with solid-tumor metastatic cancer and their caregivers were recruited nationwide through various means (registries, community outreach newsletters, newspapers, radio advertisements, etc). Potentially eligible individuals were screened and consented on the web or through a phone interview. The study survey and interview for patients or survivors and caregivers were provided in English, traditional/simplified Chinese and Cantonese/Mandarin, Vietnamese, and Korean, and examined factors related to facing metastatic cancer, including quality of life, cultural values, coping, and cancer-related symptoms. Community-based organizations assisted in recruiting participants, developing and translating study materials, and connecting the team to individuals for conducting interviews in Asian languages. Health care professionals who have experience working with CVK patients or survivors with metastatic solid cancer were recruited through referrals from the DAWN Study community advisory board and were interviewed to understand unmet supportive care needs. RESULTS: Recruitment began in November 2020; data collection was completed in October 2022. A total of 66 patients or survivors, 13 caregivers, and 15 health care professionals completed all portions of the study. We completed data management in December 2023 and will submit results for patients or survivors and caregivers to publication outlets in 2024. CONCLUSIONS: Future findings related to this protocol will describe and understand the supportive care needs of CVK patients or survivors with metastatic cancer and will help develop culturally appropriate psychosocial interventions that target known predictors of unmet supportive care needs in Chinese, Vietnamese, and Korean Americans with metastatic cancer. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50032.


Asunto(s)
Asiático , Metástasis de la Neoplasia , Neoplasias , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Asiático/psicología , Cuidadores/psicología , China/etnología , Pueblos del Este de Asia , Evaluación de Necesidades , Neoplasias/terapia , Neoplasias/psicología , Calidad de Vida , Pueblos del Sudeste Asiático , Encuestas y Cuestionarios , Vietnam/etnología , República de Corea/etnología , Estados Unidos/epidemiología
18.
Med ; 2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38776915

RESUMEN

BACKGROUND: Xenotransplantation of genetically engineered porcine organs has the potential to address the challenge of organ donor shortage. Two cases of porcine-to-human kidney xenotransplantation were performed, yet the physiological effects on the xenografts and the recipients' immune responses remain largely uncharacterized. METHODS: We performed single-cell RNA sequencing (scRNA-seq) and longitudinal RNA-seq analyses of the porcine kidneys to dissect xenotransplantation-associated cellular dynamics and xenograft-recipient interactions. We additionally performed longitudinal scRNA-seq of the peripheral blood mononuclear cells (PBMCs) to detect recipient immune responses across time. FINDINGS: Although no hyperacute rejection signals were detected, scRNA-seq analyses of the xenografts found evidence of endothelial cell and immune response activation, indicating early signs of antibody-mediated rejection. Tracing the cells' species origin, we found human immune cell infiltration in both xenografts. Human transcripts in the longitudinal bulk RNA-seq revealed that human immune cell infiltration and the activation of interferon-gamma-induced chemokine expression occurred by 12 and 48 h post-xenotransplantation, respectively. Concordantly, longitudinal scRNA-seq of PBMCs also revealed two phases of the recipients' immune responses at 12 and 48-53 h. Lastly, we observed global expression signatures of xenotransplantation-associated kidney tissue damage in the xenografts. Surprisingly, we detected a rapid increase of proliferative cells in both xenografts, indicating the activation of the porcine tissue repair program. CONCLUSIONS: Longitudinal and single-cell transcriptomic analyses of porcine kidneys and the recipient's PBMCs revealed time-resolved cellular dynamics of xenograft-recipient interactions during xenotransplantation. These cues can be leveraged for designing gene edits and immunosuppression regimens to optimize xenotransplantation outcomes. FUNDING: This work was supported by NIH RM1HG009491 and DP5OD033430.

19.
Nat Med ; 30(5): 1448-1460, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38760586

RESUMEN

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity. Longitudinal analyses indicated the presence of ischemia reperfusion injury, exacerbated by inadequate immunosuppression of T cells, consistent with previous findings of perioperative cardiac xenograft dysfunction in pig-to-nonhuman primate studies. Moreover, at 42 h after transplantation, substantial alterations in cellular metabolism and liver-damage pathways occurred, correlating with profound organ-wide physiological dysfunction. By contrast, relatively minor changes in RNA, protein, lipid and metabolism profiles were observed in decedent 2 (female) as compared to decedent 1. Overall, these multi-omics analyses delineate distinct responses to cardiac xenotransplantation in the two human decedents and reveal new insights into early molecular and immune responses after xenotransplantation. These findings may aid in the development of targeted therapeutic approaches to limit ischemia reperfusion injury-related phenotypes and improve outcomes.


Asunto(s)
Trasplante de Corazón , Xenoinjertos , Trasplante Heterólogo , Humanos , Animales , Porcinos , Masculino , Femenino , Rechazo de Injerto/inmunología , Rechazo de Injerto/genética , Proteómica , Metabolómica , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/inmunología , Transcriptoma , Perfilación de la Expresión Génica , Linfocitos T/inmunología , Linfocitos T/metabolismo , Lipidómica , Daño por Reperfusión/inmunología , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Multiómica
20.
Behav Res Ther ; 161: 104244, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36592575

RESUMEN

BACKGROUND: Expressive writing interventions confer mental health benefits for non-Hispanic Whites. However, research is lacking in adapting this paradigm for minoritized groups. This study evaluated the impacts of two culturally adapted expressive writing interventions on depressive and anxiety symptoms and potential mediators (perceived stress and intrusive thoughts) among Chinese American breast cancer survivors (CABCS). METHODS AND RESULTS: CABCS (N = 136) were randomly assigned to one of three conditions to write three weekly essays: enhanced self-regulation condition (ESR) to write about stress and coping (Week 1), deepest feelings (Week 2), and finding benefits (Week 3); self-regulation condition (SR) to write about deepest feelings (Week 1), stress and coping (Week 2), and finding benefits (Week 3); and control condition to write about facts relevant to their cancer experience (Weeks 1-3). Compared with the control condition, the ESR but not SR, reduced depressive and anxiety symptoms at all follow-up time points (1, 3, and 6-months) through reductions in perceived stress. CONCLUSION: A cultural adaptation altering the order of expressive writing prompts resulted in the greatest benefit for CABCS' depressive and anxiety symptoms. Research testing both the content and ordering of components may be vital to advance cultural adaptation science and optimize intervention efficacy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02946619.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Humanos , Femenino , Supervivientes de Cáncer/psicología , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/psicología , Pueblos del Este de Asia , Ansiedad/terapia , Adaptación Psicológica , Escritura
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