RESUMO
Systemic iron homeostasis is regulated by the hepatic hormone hepcidin to balance meeting iron requirements while limiting toxicity from iron excess. Iron-mediated induction of bone morphogenetic protein (BMP) 6 is a central mechanism for regulating hepcidin production. Liver endothelial cells (LECs) are the main source of endogenous BMP6, but how they sense iron to modulate BMP6 transcription and thereby hepcidin is uncertain. Here, we investigate the role of endothelial cell transferrin receptor 1 (TFR1) in iron uptake, BMP6 regulation, and systemic iron homeostasis using primary LEC cultures and endothelial Tfrc (encoding TFR1) knockout mice. We show that intracellular iron regulates Bmp6 expression in a cell-autonomous manner, and TFR1 mediates iron uptake and Bmp6 expression by holo-transferrin in primary LEC cultures. In addition, endothelial Tfrc knockout mice exhibit altered iron homeostasis compared with littermate controls when fed a limited iron diet, as evidenced by increased liver iron and inappropriately low Bmp6 and hepcidin expression relative to liver iron. However, endothelial Tfrc knockout mice have a similar iron phenotype compared to littermate controls when fed an iron-rich standard diet. Finally, ferritin and non-transferrin bound iron (NTBI) are additional sources of iron that mediate Bmp6 induction in primary LEC cultures via TFR1-independent mechanisms. Together, our data demonstrate a minor functional role for endothelial cell TFR1 in iron uptake, BMP6 regulation, and hepatocyte hepcidin regulation under iron limiting conditions, and suggest that ferritin and/or NTBI uptake by other transporters have a dominant role when iron availability is high.
Assuntos
Hepcidinas , Ferro , Camundongos , Animais , Hepcidinas/genética , Hepcidinas/metabolismo , Ferro/metabolismo , Células Endoteliais/metabolismo , Proteína Morfogenética Óssea 6/genética , Proteína Morfogenética Óssea 6/metabolismo , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo , Homeostase , Hepatócitos/metabolismo , Ferritinas , Transferrina/metabolismo , Camundongos KnockoutRESUMO
Organic compounds with electronic properties, such as a small band gap, are useful in areas ranging from organic field effect transistors to solar cells. Such organic compounds can possess conjugation and/or aromatic systems, with one example being tetraphenylcyclopentadienone and its derivatives. A trio of dramatically coloured tetraphenylcyclopentadienone derivatives with varied substituents on the aromatic rings in the 3- and 4-positions were prepared. Their identities were confirmed using the usual methods, for example 1 H nuclear magnetic resonance (NMR) spectroscopy, and their purity quantified using elemental analysis. The X-ray crystal structure of compound 2 was determined. Its notable structural features involved the cyclopentadienone core with its distinct C-C and C=C bond lengths and its overall nonplanarity, both of which served to mitigate its antiaromatic nature. Chloroform solutions of compounds 2-4 exhibited absorption spectra with three absorption bands at approximately 250, 350, and 500 nm that were assigned to (π)â(π*) transitions. Computational chemistry methods assisted in assigning the observed transitions to a specific molecular orbital combination in the structures of 2-4. Emission in the red end of the visible spectrum (550-625 nm) was observed from chloroform solutions of all three of the prepared compounds.
Assuntos
Ciclopentanos , Espectroscopia de Ressonância MagnéticaRESUMO
BACKGROUND: Ileostomy is the mainstay treatment option for various gastrointestinal conditions. Given the increased risk of post-discharge complications and high readmission rates that can be further aggravated by receiving care at different facilities (care fragmentation), further examination is necessary. We thus used a national cohort to explore the associations of care fragmentation among ileostomy patients experiencing adverse outcomes and increased hospitalization expenditures. METHODS: All adult hospitalizations for ileostomy were tabulated from the 2016 to 2020 Nationwide Readmissions Database. Those readmitted within 90 days after discharge were included for analysis. Patients treated at a different facility than the original location where the index ileostomy was performed were categorized into the care-fragmented cohort. Multivariable regressions were developed to characterize the association of the care-fragmented cohort with postoperative outcomes, readmissions, and expenditures. RESULTS: Of 52,254 patients with ileostomy creation hospitalizations with 90-day nonelective readmission, 9,045 (17.3%) experienced care fragmentation. Following risk adjustment, those experiencing care fragmentation faced increased odds of mortality (adjusted odds ratio 1.81, 95% confidence interval 1.54-2.12), cardiac (adjusted odds ratio 1.63, 95% confidence interval 1.42-1.85), respiratory (adjusted odds ratio 1.71, 95% confidence interval 1.53-1.91), infectious (adjusted odds ratio 1.33, 95% confidence interval 1.23-1.43), and thromboembolic (adjusted odds ratio 1.28, 95% confidence interval 1.13-1.45) complications. Furthermore, patients experiencing care fragmentation were more likely to have increased hospitalization costs ($1,700, 95% confidence interval 0.8-2.5). CONCLUSION: Care fragmentation in ileostomy patients demonstrated an increased risk for mortality, postoperative complications, and increased hospitalization expenses. To mitigate risks for adverse outcomes, future studies should evaluate the impacts of inter-hospital communication with the goal of improving care continuity and optimizing healthcare delivery for care-fragmented populations.
Assuntos
Ileostomia , Alta do Paciente , Adulto , Humanos , Ileostomia/efeitos adversos , Readmissão do Paciente , Assistência ao Convalescente , Hospitalização , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Multi-arterial coronary bypass grafting with the left internal mammary artery as a conduit has been shown to offer superior long-term survival compared to single-arterial coronary bypass grafting. Nevertheless, the selection of a secondary conduit between the right internal mammary artery and the radial artery remains controversial. Using a national cohort, we examined the relationships between the right internal mammary artery and the radial artery with acute clinical and financial outcomes. METHODS: Adults undergoing on-pump multivessel coronary bypass grafting with left internal mammary artery as the first arterial conduit were identified in the 2016 to 2020 Nationwide Readmissions Database. Patients receiving either the right internal mammary artery or the radial artery, but not both, were included in the analysis. Multivariable regression models were fitted to examine the association between the conduits and in-hospital mortality, as well as additional secondary outcomes. RESULTS: Of an estimated 49,798 patients undergoing multi-arterial coronary bypass grafting, 29,729 (59.7%) comprised the radial artery cohort. During the study period, the proportion of multi-arterial coronary bypass grafting utilizing the radial artery increased from 51.3% to 65.2% (nptrend <0.001). Following adjustment, the radial artery was associated with reduced odds of in-hospital mortality (adjusted odds ratio 0.44), prolonged mechanical ventilation (adjusted odds ratio 0.78), infectious complications (adjusted odds ratio 0.69), and 30-day nonelective readmission (adjusted odds ratio 0.77, all P < .05). CONCLUSION: Despite no definite endorsement from surgical societies, the radial artery is increasingly utilized as a secondary conduit in multi-arterial coronary bypass grafting. Compared to the right internal mammary artery, the radial artery was associated with lower odds of in-hospital mortality, complications, and reduced healthcare expenditures. These results suggest that whenever feasible, the radial artery should be the favored conduit over the right internal mammary artery. Nevertheless, future studies examining long-term outcomes associated with these vessels remain necessary.
Assuntos
Ponte de Artéria Coronária , Mortalidade Hospitalar , Artéria Torácica Interna , Artéria Radial , Humanos , Masculino , Feminino , Idoso , Artéria Radial/transplante , Pessoa de Meia-Idade , Artéria Torácica Interna/transplante , Ponte de Artéria Coronária/economia , Ponte de Artéria Coronária/métodos , Ponte de Artéria Coronária/efeitos adversos , Estudos Retrospectivos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/economia , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estados Unidos/epidemiologiaRESUMO
Transplant care continues to advance with increasing clinical experience and improvements in immunosuppressive therapy. As the population ages and long-term survival improves, transplant patient care has become more complex due to comorbidities, frailty, and the increased prevalence of cancer posttransplantation. Immune checkpoint inhibitors (ICIs) have become a standard treatment option for many cancers in non-transplant patients, but the use of ICIs in transplant patients is challenging due to the possibility of disrupting immune tolerance. However, over the past few years, ICIs have gradually started to be used in transplant patients as well. In this study, we review the current use of ICIs after all solid organ transplantation procedures (kidney, liver, heart, and lung). Increasing data suggest that the type and number of immunosuppressants may affect the risk of rejection after immunotherapy. Immunotherapy for cancer in transplant patients may be a feasible option for selected patients; however, prospective trials in specific organ transplant recipients are needed.