Long-term prognosis for 1-year relapse-free survivors of CD34 cell-selected allogeneic hematopoietic stem cell transplantation : a landmark analysis

Altres ajuts: This research was supported in part by National Institutes of Health award number P01 CA23766 and NIH/NCI Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.CD34 selection significantly improves GVHD-free survival in allogeneic hematopoietic cell transplantation (allo-HSCT). Specific information regarding long-term prognosis and risk factors for late mortality after CD34-selected allo-HSCT is lacking, however. We conducted a single-center landmark analysis in 276 patients alive without relapse 1 year after CD34-selected allo-HSCT for AML (n=164), ALL (n=33), or MDS (n=79). At 5 years' follow-up after the 1-year landmark (range 0.03-13 years), estimated RFS was 73% and OS 76%. The 5-year cumulative incidence of relapse and NRM were 11% and 16%, respectively. In multivariate analysis, HCT-CI score ≥ 3 correlated with marginally worse RFS (HR 1.78, 95% CI 0.97-3.28, p=0.06) and significantly worse OS (HR 2.53, 95% CI 1.26-5.08, p=0.004). Despite only 24% of patients with acute GVHD within 1 year, this also significantly correlated with worse RFS and OS, with increasing grades of acute GVHD associating with increasingly poorer survival on multivariate analysis (p<0.0001). Of 63 deaths after the landmark, GVHD accounted for 27% of deaths and was the most common cause of late mortality, followed by relapse and infection. While prognosis is excellent for patients alive without relapse 1 year after CD34-selected allo-HSCT, risks of late relapse and NRM persist, particularly due to GVHD

The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

Principal Component and Cluster Analysis to study wind to support energy generation in the region of Ceará, Paraíba, Pernambuco and Rio Grande do Norte, Brazil

This study presents a methodology using multivariate analysis: Principal Component Analysis (PCA) and Cluster Analysis (CA) to analyze data of hourly averaged speed in hours from 28 stations distributed in four states of Northeastern Brazil: Ceará with 10 stations, Paraíba with 5 stations, Pernambuco with 8 stations and Rio Grande do Norte with 5 stations. All stations are well distributed spatially and period of data between 1977 to 1981. The results of the Principal Component Analysis (PCA) showed that the coastal and mountainous regions have the greatest potential for energy generation results, in particularly at the stations of Acaraú-CE and Macaú-RN, while Barbalha-CE had the lowest potential, possibly due to its location. The Cluster Analysis (CA), using the Ward method, allowed the distribution of the stations into six homogeneous groups

A design methodology for audio amplifiers with no global negative feedback: proposal and validation

This paper proposes a structured methodology for the design of high-performance audio amplifiers without the use of global negative feedback. This type of amplifier is being suggested in order to minimize supposed deleterious effects on audio quality. The proposed methodology uses a minimum number of stages with local negative feedback operating in a high voltage range in order to minimize harmonic distortion without the need to use global feedback. As an example of applying the methodology, a 50W power amplifier is designed and built. In this design example, three stages are used with field effect transistors operating with a symmetrical voltage of }90V in the voltage gain stages and }45V in the output stage. The practical results obtained satisfied the design requirements, such as: Slew Rate above 3.6V/μs (14V/μs), Upper Cutoff Frequency above 40kHz (125kHz), THD+N below 0.5% (0.2%). Also, to ensure that the designed amplifier has a good linearity, the IMD intermodulation distortion was measured. The value of −62.5dB was obtained. In this way, the effectiveness of the proposed method for the design of audio amplifiers without global negative feedback was proven

Coexistence of prostate neoplasia in patients undergoing radical cystoprostatectomy due to vesical neoplasia

OBJECTIVE: To assess the incidence of bladder carcinoma infiltrating the prostate and prostate adenocarcinoma in patients undergoing radical cystoprostatectomy due to bladder cancer, as well as to assess if the characteristics of the bladder neoplasia influence the prostatic involvement by this neoplasia. MATERIALS AND METHODS: We retrospectively assessed 60 male patients, who underwent radical cystoprostatectomy between July 1997 and December 2003. Mean age was 66.7 years (40 and 93 years). The product of radical cystoprostatectomies was checked for involvement of urethra and prostate parenchyma by the primary neoplasia, and for the presence of associated prostate adenocarcinoma. Bladder neoplasia characteristics, such as localization, size, multifocality, association with in situ carcinoma and histological grade, were studied in order to assess the possibility of using such characteristics as predictive factors of prostate infiltration by bladder urothelial carcinoma. RESULTS: We observed the presence of 20% of patients with bladder carcinoma infiltrating the prostatic urethra, 23.3% of patients with infiltration of the prostate parenchyma and 28.3% of patients with associate prostate adenocarcinoma, resulting in a total of 55% of patients with prostatic involvement (infiltrative bladder carcinoma and/or adenocarcinoma). We also observed a statistically significant correlation between tumor location in the trigone, the presence of in situ carcinoma and the histological grade of the bladder tumor with prostatic infiltration by the vesical neoplasia. CONCLUSION: The coexistence of prostatic neoplasia in patients operated for bladder neoplasia was frequent in our sample (55%). We observed that the prostatic infiltration by bladder tumors occurs more frequently with tumors located in the trigone, with associated in situ carcinoma and with high histological grade. There was no correlation between neoplastic infiltration of prostate and multifocality or size of the bladder tumor in the studied sample

Adoptive Transfer of Bone Marrow-Derived Monocytes Ameliorates Schistosoma mansoni -Induced Liver Fibrosis in Mice

Submitted by Sandra Infurna ([email protected]) on 2019-08-27T16:02:21Z No. of bitstreams: 1 LigiaPaiva_PatriciaBozza_etal_IOC_2019.pdf: 2005612 bytes, checksum: 2e2972526ba6a74ba6c014cbe3ab3614 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-08-27T16:12:39Z (GMT) No. of bitstreams: 1 LigiaPaiva_PatriciaBozza_etal_IOC_2019.pdf: 2005612 bytes, checksum: 2e2972526ba6a74ba6c014cbe3ab3614 (MD5)Made available in DSpace on 2019-08-27T16:12:39Z (GMT). No. of bitstreams: 1 LigiaPaiva_PatriciaBozza_etal_IOC_2019.pdf: 2005612 bytes, checksum: 2e2972526ba6a74ba6c014cbe3ab3614 (MD5) Previous issue date: 2019Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Universidade Federal de Pernambuco. Centro Acadêmico de Vitória. Vitória de Santo Antão, PE, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Liver diseases are a major health problem worldwide leading to high mortality rates and causing a considerable economic burden in many countries. Cellular therapies as potential treatments for liver diseases have proven beneficial in most of the conditions. In recent years, studies involving therapy with bone marrow cells have been implemented to promote liver regeneration and to reduce hepatic fibrosis, however identifying the cell population present in the bone marrow that is responsible for hepatic improvement after therapy is still necessary. The aim of the present study was the evaluation of the therapeutic efficacy of monocytes obtained from bone marrow in fibrosis resulting from S. mansoni infection in C57BL/6 mice. Monocytes were isolated by immunomagnetic separation and administered to the infected animals. The effects of treatment were evaluated through morphometric, biochemical, immunological and molecular analyzes. Monocyte therapy promoted reduction of liver fibrosis induced by S. mansoni infection, associated with a decrease in production of inflammatory and pro-fibrogenic mediators. In addition, monocyte infusion caused downregulation of factors associated with the M1 activation profile, as well as upregulation of M2reg markers. The findings altogether reinforce the hypothesis that the predominance of M2reg macrophages, producers of immunosuppressive cytokines, may favor the improvement of hepatic fibrosis in a preclinical model, through fibrous tissue remodeling, modulation of the inflammatory response and fibrogenesis

Nutrient Sensor mTORC1 Regulates Insulin Secretion by Modulating β-Cell Autophagy

The dynamic regulation of autophagy in β-cells by cycles of fasting-feeding and its effects on insulin secretion are unknown. In β-cells, mechanistic target of rapamycin complex 1 (mTORC1) is inhibited while fasting and is rapidly stimulated during refeeding by a single amino acid, leucine, and glucose. Stimulation of mTORC1 by nutrients inhibited the autophagy initiator ULK1 and the transcription factor TFEB, thereby preventing autophagy when β-cells were continuously exposed to nutrients. Inhibition of mTORC1 by Raptor knockout mimicked the effects of fasting and stimulated autophagy while inhibiting insulin secretion, whereas moderate inhibition of autophagy under these conditions rescued insulin secretion. These results show that mTORC1 regulates insulin secretion through modulation of autophagy under different nutritional situations. In the fasting state, autophagy is regulated in an mTORC1-dependent manner, and its stimulation is required to keep insulin levels low, thereby preventing hypoglycemia. Reciprocally, stimulation of mTORC1 by elevated leucine and glucose, which is common in obesity, may promote hyperinsulinemia by inhibiting autophagy