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1.
Am J Pathol ; 194(1): 30-51, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37827216

RESUMO

Benign prostate hyperplasia (BPH) is caused by the nonmalignant enlargement of the transition zone of the prostate gland, leading to lower urinary tract symptoms. Although current medical treatments are unsatisfactory in many patients, the limited understanding of the mechanisms driving disease progression prevents the development of alternative therapeutic strategies. The probasin-prolactin (Pb-PRL) transgenic mouse recapitulates many histopathological features of human BPH. Herein, these alterations parallel urodynamic disturbance reminiscent of lower urinary tract symptoms. Single-cell RNA-sequencing analysis of Pb-PRL mouse prostates revealed that their epithelium mainly includes low-androgen signaling cell populations analogous to Club/Hillock cells enriched in the aged human prostate. These intermediate cells are predicted to result from the reprogramming of androgen-dependent luminal cells. Pb-PRL mouse prostates exhibited increased vulnerability to oxidative stress due to reduction of antioxidant enzyme expression. One-month treatment of Pb-PRL mice with anethole trithione (ATT), a specific inhibitor of mitochondrial ROS production, reduced prostate weight and voiding frequency. In human BPH-1 epithelial cells, ATT decreased mitochondrial metabolism, cell proliferation, and stemness features. ATT prevented the growth of organoids generated by sorted Pb-PRL basal and LSCmed cells, the two major BPH-associated, androgen-independent epithelial cell compartments. Taken together, these results support cell plasticity as a driver of BPH progression and therapeutic resistance to androgen signaling inhibition, and identify antioxidant therapy as a promising treatment of BPH.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Masculino , Humanos , Camundongos , Animais , Idoso , Androgênios/farmacologia , Androgênios/metabolismo , Próstata/patologia , Hiperplasia Prostática/metabolismo , Antioxidantes/farmacologia , Plasticidade Celular , Hiperplasia/patologia , Chumbo/metabolismo , Chumbo/uso terapêutico , Camundongos Transgênicos , Prolactina/metabolismo , Prolactina/uso terapêutico , Células Epiteliais/metabolismo , Sintomas do Trato Urinário Inferior/metabolismo , Sintomas do Trato Urinário Inferior/patologia
2.
Blood ; 141(15): 1812-1816, 2023 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-36626252

RESUMO

Patients with paroxysmal nocturnal hemoglobinuria (PNH) are susceptible to complement-mediated intravascular hemolysis and thrombosis. Factor H (FH) is the main regulator of the complement alternative pathway, which protects cells from unwanted complement-mediated damage. Although FH is not a glycosylphosphatidylinositol-linked molecule, it may play a role in PNH. We sought to determine if rare germline variants in complement factor H (CFH) affect the PNH course, screening 84 patients with PNH treated with eculizumab for rare variants in CFH, CFI, and C3 genes. We compared the allelic frequencies with populational data and a geographically-matched control group, looking for an association between presence of the variants and treatment response (transfusion independence by 6 months). Sixteen patients presented rare variants, 9 in CFH (10.7%). Germline CFH variants were more frequent among patients with PNH than among controls (P = .02) or public data (P < .001) and were more likely to be transfusion-dependent at 6 months after eculizumab initiation (P = .015). With a median follow-up of 5.8 years, 8 of 9 patients with the CFH variant received transfusions, and 2 developed thromboses. None of the patients with the CFH variant had severe aplastic anemia from eculizumab initiation until 6 months. We demonstrated for the first time that rare CFH variants are over-represented among patients with PNH and that germline genetic background may affect the response to eculizumab.


Assuntos
Fator H do Complemento , Hemoglobinúria Paroxística , Trombose , Humanos , Anemia Aplástica , Fator H do Complemento/genética , Hemoglobinúria Paroxística/tratamento farmacológico , Hemoglobinúria Paroxística/genética , Hemólise
3.
Br J Haematol ; 204(1): e1-e5, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37795523

RESUMO

How important is choice of conditioning regimen in allogeneic haematopoietic stem cell transplantation (HSCT) for sickle cell disease (SCD)? We compared HSCT outcomes by conditioning regimen in paediatric patients with SCD from the EBMT registry. In 2010-2020, 251 patients aged <18 years underwent a first matched sibling donor (MSD) HSCT with conditioning based on busulfan-fludarabine (bu-flu; n = 89) or treosulfan-fludarabine (treo-flu; n = 162). In the bu-flu and treo-flu groups, 51.7% and 99.4% of patients, respectively, received thiotepa. Median follow-up was 2.7 years. Two-year overall survival (OS) was 98.7% (95% confidence interval [CI]: 90.9-99.8) with bu-flu and 99.3% (95% CI: 95.2-99.9) with treo-flu (p = 0.63). Grade III-IV acute graft-versus-host disease (GVHD) at 100 days was 2.4% (95% CI: 0.4-7.5) and 0.6% (0.1%-3.2%) for bu-flu and treo-flu respectively (p = 0.25). The 2-year incidence of extensive chronic GVHD was 1.5% (95% CI: 0.1-7.3) with bu-flu and 8.0% (95% CI: 4.1-13.3) with treo-flu (p = 0.057). These multinational data confirm the excellent curative capacity of MSD HSCT with myeloablative conditioning. Both conditioning regimens yielded excellent OS, low rates of acute and chronic GVHD, and low rates of graft failure.


Assuntos
Anemia Falciforme , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Criança , Bussulfano/uso terapêutico , Irmãos , Vidarabina/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Condicionamento Pré-Transplante , Anemia Falciforme/terapia , Estudos Retrospectivos
4.
Br J Haematol ; 204(1): 250-259, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37784256

RESUMO

We investigated whether secondary versus de novo acute myeloid leukaemia (AML) would be associated with poor outcomes in adult acute AML patients in first complete remission (CR1) receiving unrelated cord blood transplantation (CBT). This is a retrospective study from the acute leukaemia working party of the European Society for Blood and Marrow Transplantation. Inclusion criteria included adult at first allogeneic haematopoietic cell transplantation between 2000 and 2021, unrelated single or double unit CBT, AML in CR1, no ex vivo T-cell depletion and no post-transplant cyclophosphamide. The primary end-point of the study was leukaemia-free survival (LFS). A total of 879 patients with de novo (n = 696) or secondary (n = 183) AML met the inclusion criteria. In multivariable analyses, sAML patients had non-significantly different LFS (HR = 0.98, p = 0.86), overall survival (HR = 1.07, p = 0.58), relapse incidence (HR = 0.74, p = 0.09) and non-relapse mortality (HR = 1.26, p = 0.13) than those with de novo AML. Our results demonstrate non-significantly different LFS following CBT in adult patients with secondary versus de novo AML.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Segunda Neoplasia Primária , Adulto , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Leucemia Mieloide Aguda/complicações , Transplante de Células-Tronco Hematopoéticas/métodos , Segunda Neoplasia Primária/etiologia , Condicionamento Pré-Transplante/métodos , Doença Enxerto-Hospedeiro/etiologia , Receptores de Complemento 3b
5.
Haematologica ; 109(7): 2122-2130, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38186346

RESUMO

In children with acute myeloid leukemia (AML) who lack a human leukocyte antigen (HLA) identical sibling, the donor can be replaced with an HLA-matched unrelated donor (MUD) or a haploidentical donor (haplo). We compared outcomes of patients <18 years with AML in first and second complete remission (CR1 and CR2) undergoing a hematopoietic stem cell transplantation (HCT) either with a MUD with anti-thymocyte globulin (ATG) (N=420) or a haplo HCT with post-transplant cyclophosphamide (PT-CY) (N=96) after a myeloablative conditioning regimen (MAC) between 2011 and 2021, reported to the European Society for Blood and Marrow Transplantation. A matched pair analysis was performed to adjust for differences among groups. The final analysis was performed on 253 MUD and 95 haplo-HCT. In the matched cohort, median age at HCT was 11.2 and 10 years and median year of HCT was 2017 and 2018, in MUD and haplo-HCT recipients, respectively. The risk of grade III-IV acute graft-versus-host disease (aGVHD) was significantly higher in the haplo group (hazard ratio [HR]=2.33, 95% confidence interval [CI]: 1.18-4.58; P=0.01). No significant differences were found in 2 years overall survival (OS; 78.4% vs. 71.5%; HR=1.39, 95% CI: 0.84-2.31; P=0.19), leukemia-free survival (LFS; 72.7% vs. 69.5%; HR=1.22, 95% CI: 0.76-1.95; P=0.41), CI of relapse (RI; 19.3% vs. 19.5%; HR=1.14, 95% CI: 0.62-2.08; P=0.68) non-relapse-mortality (NRM; 8% vs. 11%; HR=1.39, 95% CI: 0.66-2.93; P=0.39) and graft-versus-host free relapse-free survival (GRFS; 60.7% vs. 54.5%, HR=1.38, 95% CI: 0.95-2.02; P=0.09) after MUD and haplo-HCT respectively. Our study suggests that haplo-HCT with PT-CY is a suitable option to transplant children with AML lacking a matched related donor.


Assuntos
Ciclofosfamida , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Condicionamento Pré-Transplante , Transplante Haploidêntico , Doadores não Relacionados , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidade , Criança , Feminino , Masculino , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Haploidêntico/métodos , Adolescente , Pré-Escolar , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Condicionamento Pré-Transplante/métodos , Lactente , Resultado do Tratamento , Teste de Histocompatibilidade
6.
Am J Hematol ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856236

RESUMO

We compared relapse incidence (RI) post-unrelated transplantation with post-transplant cyclophosphamide (PTCy) versus no PTCy graft-versus-host disease (GVHD) prophylaxis, in 7049 acute myeloid leukemia (AML) patients in remission, 707 with PTCy, and 6342 without (No PTCy). The patients in the PTCy group were younger, 52.7 versus 56.6 years (p < .001). There were more 9/10 donors in the PTCy group, 33.8% versus 16.4% (p < .001), and more received myeloablative conditioning, 61.7% versus 50.2% (p < .001). In the No PTCy group, 87.7% of patients received in vivo T-cell depletion. Neutrophil and platelet engraftment were lower in the PTCy versus No PTCy group, 93.8% and 80.9% versus 97.6% and 92.6% (p < .001). RI was not significantly different in the PTCy versus the No PTCy group, hazard ratio (HR) of 1.11 (95% confidence interval [CI] 0.9-1.37) (p = .31). Acute GVHD grades II-IV and III-IV, were significantly lower in the PTCy versus the No PTCy group, HR of 0.74 (95% CI 0.59-0.92, p = .007) and HR = 0.56 (95% CI 0.38-0.83, p = .004), as were total and extensive chronic GVHD, HRs of 0.5 (95% CI 0.41-0.62, p < .001) and HR = 0.31 (95% CI 0.22-0.42, p < .001). Non-relapse mortality (NRM) was significantly lower with PTCy versus the No PTCy group, HR of 0.67 (95% CI 0.5-0.91, p = .007). GVHD-free, relapse-free survival (GRFS) was higher in the PTCy versus the No PTCy group, HR of 0.69 (95% CI 0.59-0.81, p = .001). Leukemia-free survival (LFS) and overall survival (OS) did not differ between the groups. In summary, we observed comparable RI, OS, and LFS, significantly lower incidences of GVHD and NRM, and significantly higher GRFS in AML patients undergoing unrelated donor-hematopoietic stem cell transplantation with PTCy versus No PTCy GVHD prophylaxis.

7.
Am J Hematol ; 99(7): 1250-1256, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38778766

RESUMO

In the context of T-cell replete haploidentical stem cell transplantation (Haplo-SCT) using post-transplantation cyclophosphamide (PT-Cy), it is still unknown whether peripheral blood (PB) or bone marrow (BM) is the best graft source. While PB is associated with a higher incidence of graft-versus-host disease (GVHD), it may induce a stronger graft-versus-leukemia effect compared to BM, notably in acute myeloid leukemia (AML). From the EBMT registry database, we compared T-cell replete PB (n = 595) versus BM (n = 209) grafts in a large cohort of 804 patients over the age of 60 years who underwent Haplo-SCT with PT-Cy for an AML in first or second complete remission. The risk of acute GVHD was significantly higher in the PB group (Grade II-IV: HR = 1.67, 95% CI [1.10-2.54], p = 0.01; Grade III-IV: HR = 2.29, 95% CI [1.16-4.54], p = 0.02). No significant difference was observed in chronic GVHD or non-relapse mortality. In the PB group, the risk of relapse was significantly lower in the PB group (HR = 0.65, 95% CI [0.45-0.94], p = 0.02) and leukemia-free survival was significantly better (HR = 0.76, 95% CI [0.59-0.99], p = 0.04), with a trend toward better overall survival (HR = 0.78, 95% CI [0.60-1.01], p = 0.06). We conclude that in the specific context of Haplo-SCT with PT-Cy, PB grafts represent a valid option to decrease the risk of relapse and improve outcome of older AML patients who usually do not benefit from conditioning intensification.


Assuntos
Transplante de Medula Óssea , Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda , Transplante de Células-Tronco de Sangue Periférico , Indução de Remissão , Condicionamento Pré-Transplante , Humanos , Pessoa de Meia-Idade , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidade , Masculino , Feminino , Idoso , Condicionamento Pré-Transplante/métodos , Transplante de Medula Óssea/métodos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante Haploidêntico/métodos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Europa (Continente) , Sistema de Registros , Resposta Patológica Completa
8.
Angew Chem Int Ed Engl ; : e202402608, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744668

RESUMO

Nanohoops, cyclic association of π-conjugated systems to form a hoop-shaped molecule, have been widely developed in the last 15 years. Beyond the synthetic challenge, the strong interest towards these molecules arises from their radially oriented π-orbitals, which provide singular properties to these fascinating structures. Thanks to their particular cylindrical arrangement, this new generation of curved molecules have been already used in many applications such as host-guest complexation, biosensing, bioimaging, solid-state emission and catalysis. However, their potential in organic electronics has only started to be explored. From the first incorporation as an emitter in a fluorescent organic light emitting diode (OLED), to the recent first incorporation as a host in phosphorescent OLEDs or as charge transporter in organic field-effect transistors and in organic photovoltaics, this field has shown important breakthroughs in recent years. These findings have revealed that curved materials can play a key role in the future and can even be more efficient than their linear counterparts. This can have important repercussions for the future of electronics. Time has now come to overview the different nanohoops used to date in electronic devices in order to stimulate the future molecular designs of functional materials based on these macrocycles.

9.
Cancer ; 129(17): 2645-2654, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37269074

RESUMO

BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) is the only cure for acute myeloid leukemia (AML) in second complete remission (CR2). Patients lacking a matched sibling donor (MSD) receive transplants from matched unrelated donors (MUDs), mismatched unrelated donors (MMUDs), haploidentical (haplo) donors, or cord blood. METHODS: This is a retrospective, registry-based European Society for Blood and Marrow Transplantation study that investigates changes in patient- and transplant-related characteristics and posttransplant outcomes over time. RESULTS: We identified 3955 adult patients (46.7% female; median age, 52 years [range, 18-78 years]) with AML in CR2 first transplanted between 2005 and 2019 from a MUD 10/10 (61.4%), MMUD 9/10 (21.9%), or haplo donor (16.7%) and followed for 3.7 years. A total of 725 patients were transplanted between 2005 and 2009, 1600 between 2010 and 2014, and 1630 between 2015 and 2019. Over the three time periods, there was a significant increase in patient age (from 48.7 to 53.5 years; p < .001), use of a haplo donor (from 4.6% to 26.4%; p < .001), and use of posttransplant cyclophosphamide (from 0.4% to 29%; p < .001). There was a significant decrease in total body irradiation and in vivo T-cell depletion. In multivariate analysis, transplants performed more recently had better outcomes. Leukemia-free survival (hazard ratio [HR], 0.79; p = .002) and overall survival (HR, 0.73; p < .001) increased over time. Similarly, nonrelapse mortality (HR, 0.64; p < .001) decreased over time. We also observed better graft-vs-host disease (GVHD) rates (acute GVHD II-IV: HR, 0.78; p = .03; GVHD-free, relapse-free survival: HR, 0.69; p < .001). CONCLUSIONS: Even in the absence of an MSD, outcomes of allo-HCT in CR2 for AML have significantly improved over time, with most favorable outcomes achieved with a MUD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Feminino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Masculino , Medula Óssea , Estudos Retrospectivos , Leucemia Mieloide Aguda/terapia , Doença Aguda , Ciclofosfamida , Doadores não Relacionados , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Condicionamento Pré-Transplante
10.
Ann Surg Oncol ; 30(7): 4276, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36949294

RESUMO

BACKGROUND: Liver resection is indicated for resectable liver metastases of neuroendocrine tumors.1 Minimally invasive liver resection offers decreased blood loss, reduces pain, reduces postoperative complications, and reduces time to functional recovery.2 However, access to posterior section remains difficult with conventional laparoscopic tools. The robotic approach could overcome these limitations. PATIENTS AND METHODS: A 46-year-old woman had a pancreatic neuroendocrine tumor with synchronous liver metastases (18 mm in segment 6, 29 mm in segment 7, and 31 mm in segment 8). Due to stable disease after 2 years of somatostatin analog treatment, surgical management was decided. The first step was robotic distal pancreatectomy. Two months later, we performed a posterior sectionectomy associated with a wedge resection in segment 8. RESULTS: Da Vinci X robot was used. Surgery was conducted with a second surgeon located between the patient's legs using suction/irrigation device and ultrasonic dissector through laparoscopic ports. The posterior sectorial branches of the hepatic artery and portal vein were controlled via an intra-fascial approach. Robotic parenchymal dissection was performed by a four-hands method,3 with laparoscopic ultrasonic dissector and robotic irrigated bipolar guided by indocyanine green. Transection was led on the right side of right hepatic vein without clamping. Operative duration was 330 min, and estimated blood loss was 50 ml. Postoperative course was complicated by grade B biliary fistula. The patient was discharged on postoperative day 10. CONCLUSIONS: This case illustrates the feasibility and safety of a robotic approach for right posterior liver sectionectomy, which can improve the dexterity of the surgeon and thus the possibility of difficult minimally invasive liver resection.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Robótica , Feminino , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Pâncreas/patologia , Laparoscopia/métodos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Hepatectomia/métodos
11.
Haematologica ; 108(9): 2369-2379, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36951151

RESUMO

Debates on the role and timing of allogeneic hemtopoietic stem cell transplantation (HSCT) in acute myelogenous leukemia (AML) have persisted for decades. Time to transplant introduces an immortal time and current treatment algorithm mainly relies on the European LeukemiaNet disease risk classification. Previous studies are also limited to age groups, remission status and other ill-defined parameters. We studied all patients at diagnosis irrespective of age and comorbidities to estimate the cumulative incidence and potential benefit or disadvantage of HSCT in a single center. As a time-dependent covariate, HSCT improved overall survival in intermediate- and poor-risk patients (hazard ratio =0.51; P=0.004). In goodrisk patients only eight were transplanted in first complete remission. Overall, the 4-year cumulative incidence of HSCT was only 21.9% but was higher (52.1%) for patients in the first age quartile (16-57 years old) and 26.4% in older patients (57-70 years old) (P<0.001). It was negligible in patients older than 70 years reflecting our own transplant policy but also barriers to transplantation (comorbidities and remission status). However, HSCT patients need to survive, be considered eligible both by the referring and the HSCT physicians and have a suitable donor to get transplantation. We, thus, comprehensively analyzed the complete decision-making and outcome of all our AML patients from diagnosis to last followup to decipher how patient allocation and therapy inform the value of HSCT. The role of HSCT in AML is shifting with broad access to different donors including haploidentical ones. Thus, it may (or may not) lead to increased numbers of allogeneic HSCT in AML in adults.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Idoso , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Transplante Homólogo , Leucemia Mieloide Aguda/terapia , Indução de Remissão , Modelos de Riscos Proporcionais , Estudos Retrospectivos
12.
Chemistry ; 29(41): e202300934, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-36994806

RESUMO

In the field of π-conjugated nanohoops, the size of the macrocycle has a strong impact on its structural characteristics, which in turn affect its electronic properties. In this work, we report the first experimental investigations linking the size of a nanohoop to its charge transport properties, a key property in organic electronics. We describe the synthesis and study of the first example of a cyclocarbazole possessing five constituting building units, namely [5]-cyclo-N-butyl-2,7-carbazole, [5]C-Bu-Cbz. By comparison with a shorter analogue, [4]-cyclo-N-butyl-2,7-carbazole, [4]C-Bu-Cbz, we detail the photophysical, electrochemical, morphological and charge transport properties, highlighting the key role played by the hoop size. In particular, we show that the saturated field effect mobility of [5]C-Bu-Cbz is four times higher than that of its smaller analogue [4]C-Bu-Cbz (4.22×10-5 vs 1.04×10-5  cm2 V-1 s-1 ). However, the study of the other organic field-effect transistor characteristics (threshold voltage VTH and subthreshold slope SS) suggest that a small nanohoop is beneficial for good organization of the molecules in thin films, whereas a large one increases the density of structural defects, and hence of traps for the charge carriers. The present findings are of interest for the further development of nanohoops in electronics.

13.
Chemistry ; 28(3): e202103446, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-34766393

RESUMO

Inorganic red-NIR emissive materials are particularly relevant in many fields like optoelectronic, bioimaging or solar cells. Benefiting from their emission in devices implies their integration in easy-to-handle materials like liquid crystals, whose long-range ordering and self-healing abilities could be exploited and influence emission. Herein, we present red-NIR emissive hybrid materials obtained with phosphorescent octahedral molybdenum cluster anions electrostatically associated with amphiphilic guanidinium minidendrons. Polarized optical microscopy and X-ray analysis show that while the minidendron chloride salts self-organize into columnar phases, their association with the dianionic metal cluster leads to layered phases. Steady-state and time-resolved emission investigations demonstrate the influence of the minidendron alkyl chain length on the phosphorescence of the metal cluster core.


Assuntos
Líquidos Iônicos , Cristais Líquidos , Cátions , Convênios Hospital-Médico , Molibdênio
14.
Ann Hematol ; 101(3): 655-665, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34999929

RESUMO

Significant advances in supportive care for patients with transfusion-dependent thalassemia major (TDT) have improved patients' life expectancy. However, transfusion-associated iron overload remains a significant barrier to long-term survival with good quality of life. Today, allogeneic hematopoietic stem cell transplantation (HSCT) is the current curative standard of care. Alongside selection of the best available donor, an optimized conditioning regimen is crucial to maximize outcomes for patients with TDT undergoing HSCT. The aim of this retrospective analysis was to investigate the role of busulfan-fludarabine-based and treosulfan-fludarabine-based conditioning in TDT patients undergoing HSCT. We included 772 patients registered in the European Society for Blood and Marrow Transplantation (EBMT) database who underwent first HSCT between 2010 and 2018. Four hundred ten patients received busulfan-fludarabine-based conditioning (median age 8.6 years) and 362 patients received treosulfan-fludarabine-based conditioning (median age 5.7 years). Patient outcomes were retrospectively compared by conditioning regimen. Two-year overall survival was 92.7% (95% confidence interval: 89.3-95.1%) after busulfan-fludarabine-based conditioning and 94.7% (95% confidence interval: 91.7-96.6%) after treosulfan-fludarabine-based conditioning. There was a very low incidence of second HSCT overall. The main causes of death were infections, graft-versus-host disease, and rejection. In conclusion, use of busulfan or treosulfan as the backbone of myeloablative conditioning for patients with TDT undergoing HSCT resulted in comparably high cure rates. Long-term follow-up studies are warranted to address the important issues of organ toxicities and gonadal function.


Assuntos
Bussulfano/análogos & derivados , Bussulfano/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Agonistas Mieloablativos/uso terapêutico , Vidarabina/análogos & derivados , Talassemia beta/terapia , Adolescente , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Imunossupressores/uso terapêutico , Lactente , Masculino , Estudos Retrospectivos , Condicionamento Pré-Transplante , Vidarabina/uso terapêutico
15.
J Am Chem Soc ; 143(23): 8804-8820, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34077184

RESUMO

Macrocycles possessing radially oriented π-orbitals have experienced a fantastic development. However, their incorporation in organic electronic devices remains very scarce. In this work, we aim at bridging the gap between organic electronics and nanorings by reporting the first detailed structure-properties-device performance relationship study of organic functional materials based on a nanoring system. Three [4]cyclo-N-alkyl-2,7-carbazoles bearing different alkyl chains on their nitrogen atoms have been synthesized and characterized by combined experimental and theoretical approaches. This study includes electrochemical, photophysical, thermal, and structural solid-state measurements and charge transport properties investigations. An optimized protocol of the Pt approach has been developed to synthesize the [4]cyclocarbazoles in high yield (52-64%), of great interest for further development of nanorings, especially in materials science. The charge transport properties of [4]cyclocarbazoles and model compound [8]cycloparaphenylene ([8]CPP) have been studied. Although no field effect (FE) mobility was recorded for the benchmark [8]CPP, FE mobility values of ca. 10-5 cm2·V-1·s-1 were recorded for the [4]cyclocarbazoles. The characteristics (threshold voltage VTH, subthreshold swing SS, trapping energy ΔE) recorded for the three [4]cyclocarbazoles appear to be modulated by the alkyl chain length borne by the nitrogen atoms. Remarkably, the space-charge-limited current mobilities measured for the [4]cyclocarbazoles are about 3 orders of magnitude higher than that of [8]CPP (1.37/2.78 × 10-4 cm2·V-1·s-1 for the [4]cyclocarbazoles vs 1.21 × 10-7 cm2·V-1·s-1 for [8]CPP), highlighting the strong effect of nitrogen bridges on the charge transport properties. The whole study opens the way to the use of nanorings in electronics, which is now the next step of their development.

16.
Br J Haematol ; 193(4): 814-826, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33844842

RESUMO

Pure red cell aplasia (PRCA) following allogeneic haematopoietic stem cell transplantation (aHSCT) with major ABO incompatibility is responsible for transfusion dependent anaemia, impaired quality of life and iron overload. We conducted a retrospective study, over a 10-year period, which included all consecutive patients who received a major ABO mismatched aHSCT, to assess the impact of specific treatment on PRCA. We did not observe any PRCA in the 57 aHSCT issued from cord blood. Among the remaining 631 patients, cumulative incidence of PRCA was 10·5% [range 8·2-13.0]. The median duration of resolved PRCA was 171 days [IQR 116; 261]. Pre-transplant high isohaemagglutinins titre was associated with an increased risk of PRCA (P < 10-4 ). PRCA did not affect overall survival (P = 0·95). Twenty-two patients (33·3%) received at least one specific treatment. The most commonly used treatments were rituximab (17 patients) and donor lymphocyte infusion (DLI; seven patients). Regarding PRCA resolution, we did not observe a significant difference between treated or untreated subjects (HR = 0·93, 95% confidence interval (CI) 0·48- 1·80; P = 0·82). Similar results were observed with erythropoietin treatment (22 patients, HR = 0·86 95% CI: [0·47-1·57] P = 0·62). Our data do not support the use of erythropoietin, rituximab or DLI for the treatment of PRCA.


Assuntos
Sistema ABO de Grupos Sanguíneos/sangue , Incompatibilidade de Grupos Sanguíneos , Transplante de Células-Tronco Hematopoéticas , Aplasia Pura de Série Vermelha , Adolescente , Adulto , Idoso , Aloenxertos , Incompatibilidade de Grupos Sanguíneos/sangue , Incompatibilidade de Grupos Sanguíneos/mortalidade , Criança , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Aplasia Pura de Série Vermelha/sangue , Aplasia Pura de Série Vermelha/mortalidade , Aplasia Pura de Série Vermelha/terapia , Taxa de Sobrevida
17.
Molecules ; 26(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34361583

RESUMO

The persistence of effervescence and foam collar during a Champagne or sparkling wine tasting constitute one, among others, specific consumer preference for these products. Many different factors related to the product or to the tasting conditions might influence their behavior in the glass. However, the underlying factor behind the fizziness of these wines involves a second in-bottle alcoholic fermentation, also well known as the prise de mousse. The aim of this study was to assess whether a low temperature (13 °C) or a high temperature (20 °C) during the in-bottle fermentation might have an impact on the effervescence and the foaming properties (i.e., collar height and bubble size) of three French sparkling wines (a Crémant de Loire and two Champagne wines), under standard tasting conditions. Our results showed that sparkling wines elaborated at 13 °C and served in standard tasting conditions (i.e., 100 mL, 18 °C) had better ability to keep the dissolved CO2 (between 0.09 and 0.30 g/L) in the liquid phase than those elaborated at 20 °C (with P < 0.05). Most interestingly, we also observed, for the Crémant de Loire and for one Champagne wine, that the lower the temperature of the prise de mousse, the smaller (with P < 0.05) the bubbles in the foam collar throughout the wine tasting.


Assuntos
Dióxido de Carbono/química , Temperatura Baixa , Vinho
18.
Chemistry ; 25(32): 7740-7748, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-30946486

RESUMO

Nanorings, which are macrocycles possessing radially directed π-orbitals have shown fantastic development in the last ten years. Unravelling their unusual electronic properties has been one of the driving forces of this research field. However, and despite promising properties, their incorporation in organic electronic devices remains very scarce. In this work, we aim to contribute to bridge the gap between organic electronics and nanorings by reporting the synthesis, the structural and electronic properties and the incorporation in an organic field-effect transistor (OFET) of a cyclic tetracarbazole, namely [4]cyclo-N-ethyl-2,7-carbazole ([4]C-Et-Cbz). The structural, photophysical and electrochemical properties have been compared to those of structurally related analogues [4]cyclo-9,9-diethyl-2,7-fluorene [4]C-diEt-F (with carbon bridges) and [8]-cycloparaphenylene [8]CPP (without any bridge) in order to shed light on the impact of the bridging in nanorings. This work shows that nanorings can be used as an active layer in an OFET and provides a first benchmark in term of OFET characteristics for this type of molecules.

20.
Chemistry ; 24(19): 4825-4829, 2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29470849

RESUMO

Hybrid nanomaterials made of inorganic nanocomponents dispersed in an organic host raise an increasing interest as low-cost solution-processable functional materials. However, preventing phase segregation while allowing a high inorganic doping content remains a major challenge, and usual methods require a functionalization step prior integration. Herein, we report a new approach to design such nanocomposite in which ceramic-like metallic nanocluster compounds are embedded at 10 wt % in organic copolymers, without any functionalization. Dispersion homogeneity and stability are ensured by weak interactions occurring between the copolymer lateral chains and the nanocluster compound. Hybrids could be ink-jet printed and casted on a blue LED. This proof-of-concept device emits in the red-NIR area and generates singlet oxygen, O2 (1 Δg), of particular interest for lights, display, sensors or photodynamic based therapy applications.

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