Background: The golden retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression.

Pioneer work in male mouse embryonic stem (ES) cells differentiation into germ cells (GC) showed generations of male or female gametes in separate experiments, using genetically manipulated or preselected ES cells. In an attempt to produce both types of gametes from male mouse ES cells without any genetic manipulation or preselection, we induce the differentiation by retinoic acid (RA) within nonadherent embryoid bodies (EB). It seems that gamete-like cell formation occurs in the correct manner based on the expression of early and late GC-specific genes such as Oct-4, Mvh, Stella, Dazl, Piwil 2, Pdrd 1, Rex 14, Rnf 17, Bmp8b, Acrosin, Stra-8, Haprin, LH-R, Gdf9, Zp3, Zp2, Sycp1, and Sycp3. Immunofluorescence analysis of morphologically well-formed GC and presumptive gametes showed positive labeling for SSEA1, Oct-4, EMA-1, FE-J1, Dazl, Fragilis, Mvh, Acrosin, and acetylated alpha-tubulin. Conventional cytogenetic and FISH analysis indicated a chromosome reduction in ES-derived GC. Our data suggest that ES cells with XY chromosomes can produce under the same experimental conditions both types of presumptive gametes, and this production depends on their positional and temporal information within the EB context.

A liberal erythrocyte transfusion strategy with a hemoglobin trigger of 9 g/dl was associated with fewer major postoperative complications in patients having major cancer surgery compared with a restrictive strategy.

Nota: Estas diretrizes se prestam a informar e não a substituir o julgamento clínico do médico que, em última análise, deve determinar o tratamento apropriado para seus pacientes.

F or patients with solid tumors, surgery is often the main treatment, but the issue of the potential benefits and risks of red blood cell (RBC) transfusions during surgery remains. Although previous studies have indicated that a restrictive RBC transfusion strategy is as safe and effective as a liberal one, patients with cancer are not included in most such trials. This parallel-group, doubleblind, superiority, randomized controlled trial was undertaken to determine whether a restrictive strategy of RBC transfusion was superior to a liberal one for reducing mortality and severe clinical complications in patients having major oncologic surgery.At the time of intensive care unit (ICU) admission, patients were randomized in a 1:1 ratio to either a restrictive or liberal RBC transfusion strategy. Patients in the restrictive strategy group received 1 RBC unit each time their hemoglobin (Hgb) concentration decreased to less than 7 g/dL; for those in the liberal strategy group, 1 RBC unit was administered when the Hgb concentration decreased to less than 9 g/dL. No additional units were given when the goal Hgb concentration was reached, that is, 7 and 9 g/dL for the respective strategies. The primary outcome was a composite end point of death from all causes or severe clinical complications within 30 days after randomization. Severe clinical complications included major cardiovascular complications, septic shock, acute kidney injury (AKI) requiring renal replacement therapy, acute respiratory distress syndrome, and reoperation. Secondary outcomes were the 30-day incidence of infection, development of AKI, need and duration of mechanical ventilation, duration of vasopressor therapy, ICU readmission, ICU and hospital lengths of stay, and 60-day mortality. Statistical analyses were performed using SPSS version 18.0 (SPSS Inc, Chicago, Ill); 2-sided P < 0.05 indicated statistical significance.Of 1521 patients screened for eligibility, the final cohort included 97 in the liberal group and 101 in the restrictive group. The 2 study groups were balanced in baseline characteristics. Most patients had a good performance status, localized disease, and elective surgery for gastrointestinal cancer. The primary composite end point at 30 days occurred in 19 patients (19.6%) in the liberal group and in 36 patients (35.6%) in the restrictive group (P = 0.012). This is an absolute risk reduction for the liberal strategy of 16% (95% confidence interval, 3.8%-28.2%) and a number needed to treat of 6.2 (95% confidence interval, 3.5-26.5) to avoid the composite outcome. At the 30-day follow-up, 31 patients (15.7%) died, 8 in the liberal group (8.2%) compared with 23 (22.8%) in the restrictive group (P = 0.005). At 60 days, the respective mortality rates were 11.3% and 23.8% (11 and 24 patients, respectively; P = 0.022). At 30 days, fewer patients in the liberal group had major cardiovascular events and a lower incidence of intra-abdominal infection. No difference was seen in the incidence of septic shock, and no statistically significant dif...

hIDPSC showed biological compatibility with the mouse host environment and could survive, proliferate and contribute to the inner cell mass as well as to the trophoblast cell layer after introduction into early mouse embryos (n = 28), which achieved the hatching stage following 24 and 48 h in culture. When transferred to foster mice (n = 5), these blastocysts with hIDPSC (n = 57) yielded embryos (n = 3) and foetuses (n = 6); demonstrating presence of human cells in various organs, such as brain, liver, intestine and hearts, of the human/mouse chimaeras. We verified whether hIDPSC would also be able to differentiate into specific cell types in the mouse environment. Contribution of hIDPSC in at least two types of tissues (muscles and epithelial), was confirmed. We showed that hIDPSC survived, proliferated and differentiated in mouse developing blastocysts and were capable of producing human/mouse chimaeras.

Human pluripotent stem cells (hPSCs) may significantly improve drug development pipeline, serving as an in vitro system for the identification of novel leads, and for testing drug toxicity. Furthermore, these cells may be used to address the issue of differential drug response, a phenomenon greatly influenced by genetic factors. This application depends on the availability of hPSC lines from populations with diverse ancestries. So far, it has been reported that most lines of hPSCs derived worldwide are of European or East Asian ancestries. We have established 23 lines of hPSCs from Brazilian individuals, and we report the analysis of their genomic ancestry. We show that embryo-derived PSCs are mostly of European descent, while induced PSCs derived from participants of a national-wide Brazilian cohort study present high levels of admixed European, African and Native American genomic ancestry. Additionally, we use high density SNP data and estimate local ancestries, particularly those of CYP genes loci. Such information will be of key importance when interpreting variation among cell lines with respect to cellular phenotypes of interest. The availability of genetically admixed lines of hPSCs will be of relevance when setting up future in vitro studies of drug response.Human pluripotent stem cells (hPSCs) are an ideal cell source for the development of cell based assays for drug response. In addition to their extensive proliferation and genetic stability in culture, these human cells can give rise to primary cell types relevant for drug response, including cardiomyocytes, hepatocytes and neurons 1 . Individual differences in drug response can result from the effects of age, sex, disease, ancestry, or drug interactions, but genetic factors play a major role in influencing adverse drug reactions and ineffective therapy 2 . Thus, a collection of genetically diverse lines of hPSCs is required for a broader study of differential drug response in vitro 3 .To date, most lines of hPSCs available are of European or Eastern Asian ancestry 4 , although one hiPSC line from a Native American, and one from an African (Yoruba) have been reported 5 . More recently, one hiPSC line of African American and of Hispanic Latino ancestry each have been described, although the authors do not show the genetic evidence of those ethnicities 6 .The Brazilian population results from 500 years of admixture among the original Native Americans, Europeans (mostly Portuguese), and sub-Saharan Africans, most of which were brought to the country as slaves 7 . Different analyses of genomic ancestry in Brazil have shown that, on average, the urban population has 60% contribution from European, 25% from African, and 15% from Native American populations, although these proportions vary according to the Brazilian geographic region analyzed [7][8][9][10][11] . Therefore, from the genetic point of view the Brazilian population is significantly distinct from the ancestral populations, containing novel genotypes and haplotypes that may impact various phenotyp...

Background In recent years, the field of cardio-oncology has grown worldwide, bringing benefits to cancer patients in terms of survival and quality of life. This study reports the experience of a pioneer cardio-oncology programme at University Cancer Hospital in Brazil over a period of 10 years, describing the clinical profile of patients and the clinical outcomes. Methods A retrospective study was conducted on a cohort of patients treated at the cardio-oncology programme from April 2009 to February 2019. We analysed the characteristics of patients and outcomes, including mortality, according to the type of clinical indication for outpatient care (general cardiology, perioperative evaluation and follow-up and treatment cardiotoxicity). Results From a total of 26,435 medical consultations, we obtained the data of 4535 individuals among the medical care outpatients. When we analysed the clinical characteristics of patients considering the clinical indication - general cardiology, perioperative evaluation and cardiotoxicity outpatient clinics, differences were observed with respect to age (59 [48–66], 66 [58–74] and 69 [62–76], p < 0.001), diabetes (67 [15%], 635 [22.6%] and 379 [29.8%]; p < 0.001), hypertension (196 [43.8%], 1649 [58.7%] and 890 [70.1%], p < 0.001) and dyslipidaemia (87 [19.7%), 735 [26.2%] and 459 [36.2%], p < 0.001). A similar overall mortality rate was observed in the groups (47.5% vs. 45.7% vs. 44.9% [p = 0.650]). Conclusion The number of oncologic patients in the Cardio-Oncology Programme has grown in the last decade. A well-structured cardio-oncology programme is the key to achieving the true essence of this area, namely, ongoing care for cancer patients throughout the disease treatment process, optimizing their cardiovascular status to ensure they can receive the best therapy against cancer.