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1.
J Pediatr Hematol Oncol ; 44(3): e682-e688, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35319508

RESUMO

Expanding services in Ghana for people with sickle cell disease is expected to increase childhood survival and need for transition to adult care. Little is known about patient transition experiences in sub-Saharan Africa. We sought to understand those experiences of adolescents and young adults at an adult sickle cell clinic in Accra, Ghana. Individuals 13 to 22 years of age receiving sickle cell care at the Ghana Institute of Clinical Genetics were interviewed to recall their advance preparation and early experiences in adult sickle cell clinic. Mean age of the 100 participants interviewed was 17.9±2.9 years, 65% female. Most had hemoglobin SS (77%) or hemoglobin SC (20%). Twenty-nine participants recalled pretransition preparation; 93% of them (27) had received care at Korle Bu Pediatric Sickle Cell Clinic. Among the remaining 71 who did not recall advance preparation, 54% (34) had received pediatric care at that clinic (P<0.001). More in the group recalling preparation had positive feelings about needing to transition care compared with those not recollecting preparation (55% vs. 32%, P=0.04). Our results suggest that pretransition preparation may ease the peritransition experience. Conduct and evaluation of a program for transitioning into adult sickle cell care in Ghana may facilitate the transfer process.


Assuntos
Anemia Falciforme , Doença da Hemoglobina SC , Adolescente , Adulto , Anemia Falciforme/genética , Anemia Falciforme/terapia , Criança , Feminino , Gana , Hemoglobina Falciforme , Humanos , Masculino , Satisfação Pessoal , Adulto Jovem
2.
J Gen Intern Med ; 36(1): 200-202, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33083920

RESUMO

This article highlights the timely situation that resident physicians, faculty, and staff are facing after the recent highly publicized murders of Black Americans and its impact on our healthcare communities. We discuss our experiences of how the hospital can serve as a meeting place for anti-racism, as well as how anti-racist events at the hospital can raise public consciousness and be catalysts for creating a more inclusive, diverse, and welcoming environment for all members of hospital communities.


Assuntos
Racismo , Negro ou Afro-Americano , Atenção à Saúde , Hospitais , Humanos , Justiça Social
3.
J Biol Chem ; 292(29): 12153-12164, 2017 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-28584055

RESUMO

Twenty-four hours of fasting is known to blunt activation of the human NLRP3 inflammasome. This effect might be mediated by SIRT3 activation, controlling mitochondrial reactive oxygen species. To characterize the molecular underpinnings of this fasting effect, we comparatively analyzed the NLRP3 inflammasome response to nutrient deprivation in wild-type and SIRT3 knock-out mice. Consistent with previous findings for human NLRP3, prolonged fasting blunted the inflammasome in wild-type mice but not in SIRT3 knock-out mice. In SIRT3 knock-out bone marrow-derived macrophages, NLRP3 activation promoted excess cytosolic extrusion of mitochondrial DNA along with increased reactive oxygen species and reduced superoxide dismutase 2 (SOD2) activity. Interestingly, the negative regulatory effect of SIRT3 on NLRP3 was not due to transcriptional control or priming of canonical inflammasome components but, rather, occurred via SIRT3-mediated deacetylation of mitochondrial SOD2, leading to SOD2 activation. We also found that siRNA knockdown of SIRT3 or SOD2 increased NLRP3 supercomplex formation and activation. Moreover, overexpression of wild-type and constitutively active SOD2 similarly blunted inflammasome assembly and activation, effects that were abrogated by acetylation mimic-modified SOD2. Finally, in vivo administration of lipopolysaccharide increased liver injury and the levels of peritoneal macrophage cytokines, including IL-1ß, in SIRT3 KO mice. These results support the emerging concept that enhancing mitochondrial resilience against damage-associated molecular patterns may play a pivotal role in preventing inflammation and that the anti-inflammatory effect of fasting-mimetic diets may be mediated, in part, through SIRT3-directed blunting of NLRP3 inflammasome assembly and activation.


Assuntos
Jejum , Inflamassomos/metabolismo , Macrófagos/metabolismo , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sirtuína 3/metabolismo , Superóxido Dismutase/metabolismo , Acetilação/efeitos dos fármacos , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Linhagem Celular , Células Cultivadas , Ativação Enzimática , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/imunologia , Lipopolissacarídeos/toxicidade , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/agonistas , Multimerização Proteica/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Interferência de RNA , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/química
4.
Int J Hematol Res ; 3(1): 171-179, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-30035240

RESUMO

AIM: Sickle Cell Disease (SCD) is associated with high child mortality and birth incidence in sub-Saharan Africa. Improved SCD medical services in Ghana aims to enhance survival into adulthood, creating emerging need for transition from pediatric to adult care. Anticipating transition for adolescents with SCD, we sought to understand patient and caretaker perspectives on transition to adult care within Ghana. MATERIALS AND METHODS: Structured interviews were conducted with a sample of patients ages 12-15 years and accompanying adults at Ghana's Komfo Anokye Teaching Hospital Sickle Cell Clinic (KATH SCC) covering four areas: SCD medical knowledge, symptom self-management, psychosocial impact, and transition preparation. RESULTS: In total, 46 children (mean age 13 years) paired with 46 adults were interviewed. Most children and caretakers had some knowledge about SCD and disease management. At least one-third lacked knowledge about SCD as an inherited condition. Youth were significantly more concerned about family burden and social stigmatization than adults. Most were unaware that patients are expected to switch care to adult medical providers by age 15 years, but were willing to transfer if needed. CONCLUSIONS: Our clinic-based assessment at KATH SCC identified needs of adolescents and caretakers for education and counseling about disease, self-management, transition, family burden, and stigmatization. These findings provide insights into perspectives and educational gaps of families treated for SCD. Results suggest consideration of transition planning for adolescents with SCD and their caretakers in Ghana. Generalizability of our findings and practical methods to address needs for transition within Africa remain to be tested.

5.
J Clin Invest ; 125(12): 4592-600, 2015 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-26529255

RESUMO

BACKGROUND: Activation of the NLRP3 inflammasome is associated with metabolic dysfunction, and intermittent fasting has been shown to improve clinical presentation of NLRP3 inflammasome-linked diseases. As mitochondrial perturbations, which function as a damage-associated molecular pattern, exacerbate NLRP3 inflammasome activation, we investigated whether fasting blunts inflammasome activation via sirtuin-mediated augmentation of mitochondrial integrity. METHODS: We performed a clinical study of 19 healthy volunteers. Each subject underwent a 24-hour fast and then was fed a fixed-calorie meal. Blood was drawn during the fasted and fed states and analyzed for NRLP3 inflammasome activation. We enrolled an additional group of 8 healthy volunteers to assess the effects of the sirtuin activator, nicotinamide riboside, on NLRP3 inflammasome activation. RESULTS: In the fasting/refeeding study, individuals showed less NLRP3 inflammasome activation in the fasted state compared with that in refed conditions. In a human macrophage line, depletion of the mitochondrial-enriched sirtuin deacetylase SIRT3 increased NLRP3 inflammasome activation in association with excessive mitochondrial ROS production. Furthermore, genetic and pharmacologic SIRT3 activation blunted NLRP3 activity in parallel with enhanced mitochondrial function in cultured cells and in leukocytes extracted from healthy volunteers and from refed individuals but not in those collected during fasting. CONCLUSIONS: Together, our data indicate that nutrient levels regulate the NLRP3 inflammasome, in part through SIRT3-mediated mitochondrial homeostatic control. Moreover, these results suggest that deacetylase-dependent inflammasome attenuation may be amenable to targeting in human disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT02122575 and NCT00442195. FUNDING: Division of Intramural Research, NHLBI of the NIH.


Assuntos
Proteínas de Transporte/sangue , Ingestão de Alimentos , Jejum/sangue , Inflamassomos/sangue , Mitocôndrias/metabolismo , Adulto , Feminino , Humanos , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Piridínio
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