Context:
Efforts to find a cure for type 1 diabetes have focused on the removal of the autoimmune pathophysiologic substrate, with the use of immunosuppressive regimens including autologous ...hematopoietic stem cell transplantation (AHSCT).
Objective:
The main objective of determining long-term insulin independence as well as changes in glycated hemoglobin (HbA1c). Secondary outcomes were procedure morbidity and the need for hospital management.
Design:
We enrolled patients with type 1 diabetes between 2012 and 2014. Median follow-up was 34 months (range, 25–56 mo).
Setting:
Ambulatory care.
Interventions:
We decided to carry out an AHSCT protocol using a less toxic and affordable simplified method based on fludarabine in an outpatient setting.
Patients:
Patients were of both sexes, age 8–25 years, with positive levels of anti-GAD antibodies, a C-peptide level >1.0 ng/mL, and <3 months since diagnosis.
Main Outcome Measure(s):
Insulin independence.
Results:
Sixteen patients were included. Overall response was 81% with seven patients achieving insulin independence (44%); six were partial responders (37%) whereas three were nonresponders (19%). The HbA1c level showed a mean decrease of −2.3% at 6 months in the Insulin Independence group. Median age was 12 years old (range, 8–17 years old). A mean of 11.5 × 106 CD34+ cells (SD ± 8.2) was obtained. Related mortality at 100 days was 0% as well as during follow-up. Outpatient setting was 100%.
Conclusions:
Simplified AHSCT in an outpatient setting is a feasible, safe and potentially therapeutic intervention for early-onset type 1 diabetes.
We carried out an AHSCT (autologous hematopoietic stem cell transplantation) protocol using a less toxic and affordable simplified method based on fludarabine in an outpatient setting with the main objective of determining long-term insulin independence as well as changes in glycated hemoglobin (HbA1c). Simplified AHSCT in an outpatient setting is a feasible, safe and potentially therapeutic intervention for early-onset type 1 diabetes.
The piquin chili is a wild spice widely consumed from the South United States to Central America and stands out as a source of flavonoids, essential metabolites with antioxidant properties. The ...concentrations of flavonoids, carotenoids, and capsaicinoids vary according to regions, maturity stages, and ripening processes. These compounds, which are known for their health benefits and industrial applications, highlight the importance of identifying ideal environmental conditions for collecting fruits with the highest contents. Comprehensive studies of the piquin chili are essential for understanding its properties for the benefit of consumers. This approach fortifies trade, contributes to resource conservation, and advances cultivated chili production.
Introducción. El lirio acuático (Eichhornia crassipes) es una planta hidrófita libre flotante de la familia Pontederiaceae. Es una de las plantas acuáticas con mejor reproducción y tasa de ...crecimiento, por lo cual se extiende y forma tapetes o esteras que constriñen a las plantas nativas sumergidas y flotantes, disminuye la entrada de luz en los cuerpos de agua y disminuye el oxígeno disuelto en el agua. Objetivo. Realizar una revisión bibliográfica del lirio acuático que permita a la comunidad científica una mejor comprensión de una especie invasora, así como los efectos que provoca en el ecosistema. Desarrollo. La capacidad invasiva de esta planta pone en peligro diversos ecosistemas, ya que aprovecha las aguas ricas en nutrientes. Además, las densas colonias flotadoras causan que el contenido de oxígeno descienda hasta cero debajo de su manto, lo que provoca daños a los ecosistemas. Conclusiones. El lirio acuático es una de las plantas acuáticas más invasoras del mundo, ya que causa efectos ecológicos y socioeconómicos. Esta planta se ha usado como fitorremediadora, en la remoción de organofosforados, lo que indica que se puede usar para limpiar aguas residuales. Además, puede usarse en la producción de etanol, papel, composta, biogás, alimento humano, forraje animal, fibra y en la extracción de ácidos grasos volátiles.
The impact of HLA-DPB1 compatibility and its role as a transplantation antigen in haploidentical-related hematopoietic stem cell transplant (haplo-R-HSCT) have not been established, and a negative ...effect on survival has been suggested.
The objective of the determine was to study the frequency and clinical effects of incompatibility at the HLA-DPB1 locus in the haplo-R-HSCT setting.
Clinical records and electronic files of 91 patients with a hematological disease who underwent haplo-HSCT from January 2009 to October 2017 in a university medical center were scrutinized. Overall survival (OS) was estimated by the Kaplan-Meier method; the cumulative incidence of transplant-related mortality (TRM) and relapse rates was determined. Acute graft-versus-host disease was assessed by binary logistic regression. Cox regression model with a 95% confidence interval was used to examine the association between the different variables and their effect on OS.
Of the 91 donor-recipient pairs, 24 (26.37%) shared complete DPB1 identity, 60 (65.93%) had a mismatch at one allele, and 7 (7.70%) were mismatched at two alleles. Twenty-four different HLA-DPB1 alleles were found; the most frequent were DPB1*04:01 (34.1%) and DPB1*04:02 (27.5%). Two-year OS, the cumulative incidence of TRM and relapse was 51.3 ± 6.8%, 28 ± 6% and 60 ± 7.8% for all haplo-related transplants, respectively, with no statistical difference between HLA-DPB1 matched and partially matched patients. In Cox regression analysis, no risk factors associated with OS, TRM, or relapses were identified.
HLA-DPB1 mismatching in the haplo-R-HSCT setting did not influence transplant outcomes and was clinically tolerable. A high degree of homozygosity was found.
ABSTRACT
Introduction
The use of filgrastim biosimilars for healthy adult and pediatric donor mobilization in hematopoietic stem cell transplantation has been met with increased safety and efficacy ...concerns in contrast to generic small molecule drugs. In Mexico, several filgrastim‐intended copies (FIC) have been available and marketed since 2001, while no clinical comparability studies to evaluate their use in this setting have been published and thus are not considered to be true biosimilars. In this study, we report our experience using three different FIC products currently available (Filatil, Dextrifyl, and Biofilgran).
Methods
We retrospectively evaluated 118 related donors of all ages who received any brand 5 μg/kg subcutaneously twice daily for 4 days and were harvested in a single apheresis system on day 5.
Results
Donors had a median age of 38 years (range, 1‐69). A successful harvest defined as ≥2 × 106 CD34+ cells/kg of recipient weight was achieved in 95.8% of cases, with a median CD34+ cell dose of 9.4 × 106/kg (range 1‐42.8). A single apheresis session was performed in 89.8% of cases. No significant difference in cell yield between each brand was observed. All pediatric donors had a successful harvest with similar results to adult donors. No immediate severe adverse effects were documented in any case.
Conclusions
In conclusion, three FICs available in Mexico were efficacious and without immediate severe adverse effects, resulting in significant cost savings. Evaluation of immunogenicity and establishment of a pharmacovigilance program with the use of FICs is warranted.
One of the most regulated steps of translation initiation is the recruitment of mRNA by the translation machinery. In eukaryotes, this step is mediated by the 5'end cap-binding factor eIF4E bound to ...the bridge protein eIF4G and forming the eIF4F complex. In plants, different isoforms of eIF4E and eIF4G form the antigenically distinct eIF4F and eIF(iso)4F complexes proposed to mediate selective translation. Using a microarray analysis of polyribosome- and non-polyribosome-purified mRNAs from 15 day-old Arabidopsis thaliana wild type WT and eIF(iso)4E knockout mutant (iso)4E-1 seedlings we found 79 transcripts shifted from polyribosomes toward non-polyribosomes, and 47 mRNAs with the opposite behavior in the knockout mutant. The translationally decreased mRNAs were overrepresented in root-preferentially expressed genes and proteins from the endomembrane system, including several transporters such as the phosphate transporter PHOSPHATE1 (PHO1), Sucrose transporter 3 (SUC3), ABC transporter-like with ATPase activity (MRP11) and five electron transporters, as well as signal transduction-, protein modification- and transcription-related proteins. Under normal growth conditions, eIF(iso)4E expression under the constitutive promoter 35 S enhanced the polyribosomal recruitment of PHO1 supporting its translational preference for eIF(iso)4E. Furthermore, under phosphate deficiency, the PHO1 protein increased in the eIF(iso)4E overexpressing plants and decreased in the knockout mutant as compared to wild type. In addition, the knockout mutant had larger root, whereas the 35 S directed expression of eIF(iso)4E caused shorter root under normal growth conditions, but not under phosphate deficiency. These results indicate that selective translation mediated by eIF(iso)4E is relevant for Arabidopsis root development under normal growth conditions.
Hispanic patients aged < 40 years with a diagnosis of acute myeloid leukemia (AML) during 2003 to 2016 in Northeast Mexico were evaluated. The group included 46 children and 88 adolescents and young ...adults (AYAs) aged 15 to 39 years. A greater overall response rate was found in the children (87.2% vs. 69% in AYAs). Low event-free and overall survival rates for AYA patients with AML were documented.
The outcomes for adolescents and young adults (AYAs) with acute myeloid leukemia (AML) have been poorly characterized in Hispanics in low- to middle-income countries. The results are influenced by biologic and socioeconomic factors. The clinical paths for AYA patients with AML are reported.
A retrospective analysis of AYA and pediatric AML patients aged 1 to 39 years during 2003 to 2016 from a single reference center in Northeast Mexico treated with a 7+3 standard protocol was performed. The 5-year overall survival (OS) and event-free survival (EFS) were estimated using Kaplan-Meier analysis. The hazard ratios for relapse and death were estimated using a Cox regression model. The patients with promyelocytic leukemia were analyzed separately.
The study included 110 non-PML AML patients, 39 children and 71 AYAs. No difference in complete remission was found (P = .446), although the overall response rate was greater in the children (87.2% vs. 69% in AYAs; P = .034). The 5-year EFS rate was 33% for the children versus 9.3% in the AYAs at a median follow-up of 22 and 9 months, respectively (P = .008). The 5-year OS rate was 51% in the children and 22% in the AYAs (P = .001). Of the 44 AYAs with complete remission, 29 (65%) developed a relapse. Of the 39 children and 71 AYAs, 20 children (51.3%) and 21 AYAs (29.6%) underwent transplantation (P = .024). Patients with refractory disease had a 1-year OS rate of 14.4%. Older age (hazard ratio HR, 2.55; P = .002) and white blood cell count > 50 × 109/L (HR, 1.79; P = .023) were significant for death, and transplantation was protective (HR, 0.57; P = .023).
Low EFS and OS rates were found for AML patients in the AYA group. To improve survival rates, intensified chemotherapy regimens and early hematopoietic stem cell transplantation are needed.
Polyphosphates (polyPs), chains of phosphate residues found in species across nature from bacteria to mammals, were recently reported to accelerate the amyloid fibril formation of many proteins. How ...polyPs facilitate this process, however, remains unknown. To gain insight into their mechanisms, we used various physicochemical approaches to examine the effects of polyPs of varying chain lengths on ultrasonication-dependent α-synuclein (α-syn) amyloid formation. Although orthophosphate and diphosphate exhibited a single optimal concentration of amyloid formation, triphosphate and longer-chain phosphates exhibited two optima, with the second at a concentration lower than that of orthophosphate or diphosphate. The second optimum decreased markedly as the polyP length increased. This suggested that although the optima at lower polyP concentrations were caused by interactions between negatively charged phosphate groups and the positive charges of α-syn, the optima at higher polyP concentrations were caused by the Hofmeister salting-out effects of phosphate groups, where the effects do not depend on the net charge. NMR titration experiments of α-syn with tetraphosphate combined with principal component analysis revealed that, at low tetraphosphate concentrations, negatively charged tetraphosphates interacted with positively charged “KTK” segments in four KTKEGV repeats located at the N-terminal region. At high concentrations, hydrated tetraphosphates affected the surface-exposed hydrophilic groups of compact α-syn. Taken together, our results suggest that long-chain polyPs consisting of 60 to 70 phosphates induce amyloid formation at sub-μM concentrations, which are comparable with the concentrations of polyPs in the blood or tissues. Thus, these findings may identify a role for polyPs in the pathogenesis of amyloid-related diseases.
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