Felis catus as a model to study follicle biology in vitro

Purpose The current study was designed to evaluate the responseof individual intact antral follicles from adult femaledomestic cats to a luteinizing hormone (LH) stimulus in vitroby assessing cumulus-oocyte expansion (C-OE) and steroidproduction.Methods C-OE and steroid levels (estradiol [E2] and progesterone[P4]) obtained from individual antral feline follicles(n=366 follicles; n=56 cats) were analyzed after 12 or 24 hof culture in the presence or absence of LH (low [3.4 ng/ml] orhigh [100 ng/ml]).Results At the end of the culture, the highest percentage ofexpanded cumulus-oocyte complexes (COCs) was observedin the LH groups at 12 or 24 h in comparison to their controls(p<0.001). There was a significant increase in expandedCOCs when comparing LH concentrations (high vs. low) at12 or 24 h. Higher levels of both E2 and P4 were observed inthe media from antral follicles after 12 and 24 h of culture inthe presence of LH (both concentration, p<0.05). There wasno association between hormone levels and follicle diameter;high variability was observed in the steroid levels produced byantral follicles within all treatment groups.Conclusions These data indicate, for the first time, that felineantral follicles (0.5-2 mm) from different stages of the naturalestrous cycle can be cultured and will respond to an LH stimulus,based on an increase in steroid levels as well as C-OEafter 12 or 24 h in culture.Fil: Rojo, Julieta Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Linari, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Musse, Mariana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; ArgentinaFil: Peluffo, Marina Cinthia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas; Argentin

La representación indígena en las telenovelas colombianas

59 páginas.La siguiente investigación recopiló información acerca de la representación indígena en las telenovelas colombianas, por medio de la recolección de documentos y la realización de diferentes entrevistas a críticos de televisión, guionistas, productores de televisión y representantes de pueblos indígenas del país. Culminando en una serie de podcast radiales que integran las distintas perspectivas sobre la inclusión de poblaciones minoritarias, en específico los pueblos ancestrales. Este trabajo, que en un principio buscaba comprender la baja representación de las minorías en las telenovelas, pasó a tomar un enfoque indigenista a causa de la poca popularidad de dicha minoría en la televisión

Physician Perspectives on the Use of Beta Blockers in Heart Failure With Preserved Ejection Fraction.

β-blockers are commonly used in heart failure with preserved ejection fraction (HFpEF), even in the absence of a compelling indication and despite the potential to cause harm. Identifying reasons for β-blocker prescription in HFpEF could permit the development of strategies to reduce unnecessary use and potentially improve medication prescribing patterns in this vulnerable population. We administered an online survey regarding β-blocker prescribing behavior to physicians trained in internal medicine or geriatrics (noncardiology physicians) and to cardiologists at 2 large academic medical centers. The survey assessed the reasons for β-blocker initiation, agreement regarding initiation and/or continuation of β-blockers by another clinician, and deprescribing behavior. The response rate was 28.2% (n&nbsp;=&nbsp;231). Among respondents, 68.2% reported initiating β-blockers in patients with HFpEF. The most common reason for initiating a β-blocker was for treatment of an atrial arrhythmia. Notably, 23.7% of physicians reported initiating a β-blocker without an evidence-based indication. When a β-blocker was considered not necessary, 40.1% of physicians reported they were rarely or never willing to deprescribe. The most common reason for not deprescribing a β-blocker when the physician felt that a β-blocker was unnecessary was the concern about interfering with another physicians treatment plan (76.6%). In conclusion, a significant proportion of noncardiology physicians and cardiologists report prescribing β-blockers to patients with HFpEF, even when evidence-based indications are absent, and rarely deprescribe β-blockers in these scenarios

Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies

We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1. Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor. Patients were reviewed weekly for 4 weeks to monitor toxicity and immunologic responses. Toxicity was limited to grades 1 to 2. Using peptide/HLA-A*0201 tetramers and intracellular interferon-γ staining, CD8+ T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination. To monitor the kinetics of vaccine-induced CD8+ T-cell responses and disease regression after vaccination, absolute PR1 and WT1+CD8+ T-cell numbers and WT1 expression were studied weekly after vaccination. Responses occurred as early as 1 week after vaccination. After vaccination, the emergence of PR1 or WT1+CD8+ T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect. Conversely, loss of response was associated with reappearance of WT1 transcripts (P < .01). This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic. These results support further studies of combination immunization strategies in leukemia patients. This study is registered at http://clinicaltrials.gov as NCT00313638

Cost-effectiveness analysis of Oncotype DX from a Brazilian private medicine perspective: a GBECAM multicenter retrospective study

Background: Oncotype DX (ODX) is a validated assay for the prediction of risk of recurrence and benefit of chemotherapy (CT) in both node negative (N0) and 1–3 positive nodes (N1), hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer (eBC). Due to limited access to genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective in different health system, but limited data are available considering the reality of middle-income countries such as Brazil. We aim to evaluate the cost-effectiveness of ODX across strata of clinical risk groups using data from a dataset of patients from Brazilian institutions. Methods: Clinicopathologic and ODX information were analyzed for patients with T1–T3, N0–N1, HR+/HER2− eBC who had an ODX performed between 2005 and 2020. Projections of CT indication by clinicopathologic criteria were based on binary clinical risk categorization based on the Adjuvant! Algorithm. The ODX score was correlated with the indication of CT according to TAILORx and RxPONDER data. Two decision-tree models were developed. In the first model, low and high clinical risk patients were included while in the second, only high clinical risk patients were included. The cost for ODX and CT was based on the Brazilian private medicine perspective. Results: In all, 645 patients were analyzed; 411 patients (63.7%) had low clinical risk and 234 patients (36.3%) had high clinical risk disease. The ODX indicated low (25) risk in 119 (18.4%), 415 (64.3%), and 111 (17.2%) patients, respectively. Among 645 patients analyzed in the first model, ODX was effective (5.6% reduction in CT indication) though with an incremental cost of United States Dollar (US$) 2288.87 per patient. Among 234 patients analyzed in the second model (high clinical risk only), ODX led to a 57.7$ 4350.66 per patient. Conclusions: Our study suggests that ODX is cost-saving for patients with high clinical risk HR+/HER2− eBC and cost-attractive for the overall population in the Brazilian private medicine perspective. Its incorporation into routine practice should be strongly considered by healthcare providers

Lymphodepletion is permissive to the development of spontaneous T-cell responses to the self-antigen PR1 early after allogeneic stem cell transplantation and in patients with acute myeloid leukemia undergoing WT1 peptide vaccination following chemotherapy

PR1, an HLA-A*0201 epitope shared by proteinase-3 (PR3) and elastase (ELA2) proteins, is expressed in normal neutrophils and overexpressed in myeloid leukemias. PR1-specific T cells have been linked to graft-versus-leukemia (GVL) effect. We hypothesized that lymphopenia induced by chemo-radiotherapy can enhance weak autoimmune responses to self-antigens such as PR1. We measured PR1-specific responses in 27 patients 30–120 days following allogeneic stem cell transplant (SCT) and correlated these with ELA2 and PR3 expression and minimal residual disease (MRD). Post-SCT 10/13 CML, 6/9 ALL, and 4/5 solid tumor patients had PR1 responses correlating with PR3 and ELA2 expression. At day 180 post-SCT, 8/8 CML patients with PR1 responses were BCR-ABL-negative compared with 2/5 BCR-ABL-positive patients (P = 0.025). In contrast, PR1 responses were detected in 2/4 MRD-negative compared with 4/5 MRD-positive ALL patients (P = 0.76). To assess whether the lymphopenic milieu also exaggerates weak T-cell responses in the autologous setting, we measured spontaneous induction of PR1 responses in 3 AML patients vaccinated with WT1-126 peptide following lymphodepletion. In addition to WT1-specific T cells, we detected PR1-specific T cells in 2 patients during hematopoietic recovery. Our findings suggest that lymphopenia induced by chemo-radiotherapy enhances weak autoimmune responses to self-antigens, which may result in GVL if the leukemia expresses the relevant self-antigen.Katayoun Rezvani, Agnes S. M. Yong, Stephan Mielke, Bipin N. Savani, Behnam Jafarpour, Rhoda Eniafe, Robert Quan Le, Laura Musse, Carole Boss, Richard Childs, A. John Barret