Naive and Stem Cell Memory T Cell Subset Recovery Reveals Opposing Reconstitution Patterns in CD4 and CD8 T Cells in Chronic Graft vs. Host Disease.

The success of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of hematological malignancies remains hampered by life-threatening chronic graft vs. host disease (cGVHD). Although multifactorial in nature, cGVHD has been associated with imbalances between effector and regulatory T cells (Treg). To further elucidate this issue, we performed a prospective analysis of patients undergoing unrelated donor allo-HSCT after a reduced intensity conditioning (RIC) regimen containing anti-thymocyte globulin (ATG) and the same GVHD prophylaxis, at a single institution. We studied T cell subset homeostasis over a 24-month follow-up after HSCT in a comparative analysis of patients with and without cGVHD. We also quantified naive and memory T cell subsets, proliferation and expression of the apoptosis-related proteins Bcl-2 and CD95. Finally, we assessed thymic function by T cell receptor excision circle (TREC) quantification and T cell receptor (TCR) diversity by TCRVß spectratyping. While the total number of conventional CD4 (Tcon) and CD8 T cells was similar between patient groups, Treg were decreased in cGVHD patients. Interestingly, we also observed divergent patterns of Naive and Stem Cell Memory (SCM) subset recovery in Treg and Tcon compared to CD8. Patients with cGVHD showed impaired recovery of Naive and SCM Tcon and Treg, but significantly increased frequencies and absolute numbers of Naive and SCM were observed in the CD8 pool. Markedly increased EMRA CD8 T cells were also noted in cGVHD. Taken together, these results suggest that Naive, SCM and EMRA CD8 play a role in the emergence of cGHVD. Reduced Naive and recent thymic emigrant Tcon and Treg in cGVHD was likely due to impaired thymic output, as it was accompanied by decreased CD4 TREC and TCR diversity. On the other hand, CD8 TCR diversity was similar between patient groups. Furthermore, no correlation was observed between CD8 TREC content and Naive CD8 numbers, suggesting limited thymic production of Naive CD8 T cells in patients after transplant, especially in those developing cGVHD. The mechanisms behind the opposing patterns of CD4 and CD8 subset cell recovery in cGVHD remain elusive, but may be linked to thymic damage associated with the conditioning regimen and/or acute GVHD.

Efeito de diferentes tratamentos de superfície em fibras de resina termoplástica na resistência e módulo flexural de barras de resina acrílica / Effect of different surface treatments on the termoplasthic resin fibers in flexural strength and modulus of acrylic resin bars

Objetivo: Este trabalho avaliou a resistência flexural em barras deresina acrílica reforçada com fibras de resina termoplástica submetidas a diferentes tratamentos. Material e Método: Cinco grupos experimentais foram criados (N=10), tendo como fator em estudo o tipo do tratamento superficial das fibras (controle sem fibra (Ctrl), fibra pura (FP), silanização (Fsil), pré-impregnação com adesivo (Fimp), silanização + pré-impregnação (Fsil/imp). Barras (25x2x2mm) foram submetidas a teste de resistência à flexão de 3 pontos, obtendo-se os valores de resistência flexural (RF) e módulo flexural (MF). Os dados de RF (MPa) e MF (GPa) foram submetidos ao teste ANOVA. Resultados: A análise estatística demonstrou semelhança entre grupos (p=0,298 para RF; p=0,549 para MF). Para RF, observou-se: Ctrl (15614,68±7119,25)A, FP (14903,31±5743,65)A, Fsil (11142,47±5629,92) A, Fimp (16365,10±9284,60)A, Fsil/imp (11882,56±3544,39)A. Para MF, observou-se: Ctrl (3996,30±2025,46)A, FP (3275,14±1841,26)A, Fsil (3491,54±2812,14)A, Fimp (4544,46±3357,18)A, Fsil/imp (2842,16±1193,13)A. Conclusão: Pode-se concluir que o tipo de tratamento superficial das fibras de resina termoplástica não proporciona melhorias em RF e MF em barras de resina acrílica.

Objective: This study evaluated the flexural strenght and flexuralmodulus of reinforced acrylic resin bars with thermoplastic fiber ssubjected to different treatments. Material and methods: Five experimental groups were created (N = 10), with the factor under study the type of treatment surface of fibers (control without fiber (Ctrl), pure fiber (PF), silanization (Fsil), pre-impregnated with adhesive (Fimp) , silanization + pre-impregnation (Fsil/imp)). Bars (25x2x2mm) were tested for flexural strength with 3-point bending test, obtaining the values of flexural strength (FS) and flexural modulus (FM). The RF data (MPa) and MF (GPa) were submitted to ANOVA test. Results: The statistical analysis showed similarity between groups (p = 0.298 for FS, p = 0.549 for FM). For FS, it was observed: Ctrl (15614.68 ± 7119.25) A, PF (14903.31 ± 5743.65) A,Fsil (11142.47 ± 5629.92) A, Fimp (9284 ± 16365.10 60) A, Fsil/imp(11882.56 ± 3544.39) A. For FM, observed: Ctrl (3996.30 ± 2025.46) A,FP (3275.14 ± 1841.26) A, Fsil (3491.54 ± 2812.14) A, Fimp (4544.46 ±3357 18) A, Fsil/imp (2842.16 ± 1193.13) A. Conclusion: It can be concluded that the type of surface treatment of fibers of thermoplasticresin does not provide improvements in RF and MF acrylic resin bars.

Visceral fat and coronary artery calcification in patients with chronic kidney disease.

BACKGROUND: Abdominal fat is a metabolically active tissue which has been associated with cardiovascular events and death in chronic kidney disease (CKD) patients. We explore here the association between surrogates of abdominal fat and coronary artery calcium score (CACs). METHODS: Cross-sectional analysis of 232 non-dialysis-dependent CKD patients Stages 3-5 (median age 60 [25th-75th percentile 52-67] years; 60% men). Visceral adipose tissue (VAT) and CACs were assessed by computed tomography. Surrogates of abdominal fat included VAT and waist circumference (WC). RESULTS: VAT was positively associated with CACs in univariate analysis (ρ = 0.23). Across increasing VAT quartiles, patients were older, more often men and smokers. Although increasing VAT quartiles associated with higher glomerular filtration rate and leptin, better nutritional status (subjective global assessment) as well as larger muscle stores and strength, they were also more insulin resistant (HOMA-IR), dyslipidemic and inflamed (C-reactive protein and white blood cells). In addition, CACs were incrementally higher. Clinically evident coronary artery calcification (CACs ≥ 10 Agatston) was present in 63% of the patients. Both increased visceral fat (odd ratio 1.60 [95% CI 1.23-2.09] per standard deviation increase) and increased WC (1.05 [1.01-1.12] per cm increase), augmented the odds to present calcification. Such associations remained statistically significant after extensive multivariate adjustment for confounders. CONCLUSIONS: Abdominal fat is associated with coronary artery calcification in non-dialysis dependent CKD patients, supporting its potential role as a cardiovascular risk factor in uremia.

Visceral fat and coronary artery calcification in patientswith chronic kidney disease

Background. Abdominal fat is a metabolically active tissuewhich has been associated with cardiovascular events anddeath in chronic kidney disease (CKD) patients. We explorehere the association between surrogates of abdominal fat andcoronary artery calcium score (CACs).Methods. Cross-sectional analysis of 232 non-dialysisdependentCKD patients Stages 3–5 (median age 60 [25th–75thpercentile 52–67] years; 60% men). Visceral adipose tissue(VAT) and CACs were assessed by computed tomography. Surrogatesof abdominal fat included VAT and waist circumference(WC).Results. VAT was positively associated with CACs in univariateanalysis (ρ = 0.23). Across increasing VAT quartiles,patients were older, more often men and smokers. Althoughincreasing VAT quartiles associated with higher glomerular filtrationrate and leptin, better nutritional status (subjectiveglobal assessment) as well as larger muscle stores and strength,they were also more insulin resistant (HOMA-IR), dyslipidemicand inflamed (C-reactive protein and white blood cells).In addition, CACs were incrementally higher. Clinicallyevident coronary artery calcification (CACs ≥ 10 Agatston) was present in 63% of the patients. Both increased visceral fat(odd ratio 1.60 [95% CI 1.23–2.09] per standard deviation increase)and increased WC (1.05 [1.01–1.12] per cm increase),augmented the odds to present calcification. Such associationsremained statistically significant after extensive multivariateadjustment for confounders.Conclusions. Abdominal fat is associated with coronary arterycalcification in non-dialysis dependent CKD patients, supportingits potential role as a cardiovascular risk factor in uremia.

Uso de cal virgem para o controle de Salmonella spp. e Clostridium spp. em camas de aviário / Quicklime for controlling Salmonella spp. and Clostridium spp in litter from floor pens of broilers

O objetivo deste trabalho foi avaliar a eficácia do uso de cal virgem (CaO) para a redução de Salmonella spp. e Clostridium spp. em cama de aviário. Foram aplicados quatro tratamentos: T1- sem adição de cal virgem (controle), T2- aplicação de cal virgem na dose de 300g m-2, T3- aplicação de cal virgem na dose de 600g m-2 e T4- aplicação de cal virgem na dose de 900g m-2. Os valores médios observados para o pHda cama após o 12o dia de aplicação de cal virgem foram 8,95 e 9,91, 10,75 e 11,11 para os tratamentos 1, 2, 3 e 4,respectivamente. O número mais provável Log10 (UFC) de Salmonella spp. e Clostridium spp foi reduzido em 82 e 97% com a aplicação de cal na dosagem de 300g m-2 e 100% na dosagem de 600 e 900g m-2, ambos diferindo significativamente em relação ao controle (antes da aplicação da cal). A atividade de água da cama reduziu progressivamente (de 0,2 a 3,82%)com a utilização de níveis crescentes de cal. Conclui-se que o uso da cal na cama de aviário, mesmo nas doses mais baixas, reduz o número mais provável de Salmonella e Clostridium ssp.

This study aimed to evaluate the efficacy of quicklime (CaO) for reducing Salmonella and Clostridium spp. population in used litter from floor pens of broilers. Four treatments were tested: (T1) control (without quicklime); (T2) 300g quicklime m-2; (T3) 600g quicklime m-2; and (T4) 900g quicklime m-2. The following average pH values were observed 12 days after adding quicklime: 8.95, 9.91, 10.75 and 11.11 for treatments 1, 2, 3 and 4, respectively. An 82 and 97%reduction in the most probable number Log10 (CFU) of Salmonella and Clostridium spp, respectively, was observed when 300g m-2 of quicklime was added to the used litter from floor pens of broilers. Additionally, a 100% reduction was obtained when both 600 and 900g m-2 of quicklime were added,differing significantly from control (before adding quicklime). A progressive reduction in water activity (from 0.2 to 3.82%) was observed when growing levels of quicklime were used. In conclusion, even the lowest level of quicklime added to litter from floor pens of broilers reduces the most probable number of Salmonella and Clostridium spp.

Autologous stem cell transplantation in acute myeloid leukemia. Factors influencing outcome. A 13 year single institution experience.

We report our results of autologous stem cell transplantation (SCT) in patients with AML during the last 13 years. Between August 1990 and December 2003, 42 patients with acute myeloid leukemia (AML) received an autologous SCT. Patients were classified as standard risk if first complete remission (CR) was induced after one or two chemotherapy regimens and the white blood cell count at presentation was below 50,000/mL (n=12), while patients requiring more than two induction regimens to attain first CR and with CR2 ou more advanced disease and/or had a higher white blood cell count at presentation were defined as high risk (n=30). Twenty one patients were transplanted in first CR. The median patient age was 24 years (range, 2-56 years), and the median time interval from diagnosis to autologous SCT was 9 months (range 3-87 months). The conditioning regimen for SCT consisted of busulfan (BU) 16 mg/kg and melfalan (MEL) 180 mg/m2 (BUMEL) in 17 (40%) patients and busulfan 16 mg/kg and VP-16 60 mg/kg (BUVP16) in 22 (52%) patients. Three patients received a different conditioning regimen with BCNU 300 mg/m2, VP16 2 g/m2 and melphalan 160 mg/m2 (BEM). Twenty five (60%) patients received bone marrow (BM), 11 (26%) patients received peripheral blood stem cells (PBSC) and 6 patients (14%) received BM plus PBSC. With a median follow-up of 7 years, the 13 year overall survival (OS) and diseasefree survival (DFS) of all patients is 52% and 40%, respectively. In univariate analysis, males had a significantly superior DFS than females (55% vs 22%, p=0.003), and patients younger than 15 years of age had significantly superior OS and DFS than older patients (50% vs 35%, p=0.05; and 50% vs 28%, p=0.03, respectively). Patients with FAB M3 subtype also had a superior OS than the other FAB subtypes (100% vs 44%, p=0.05). There was a strong statistical correlation between risk group and survival. In fact, the patients with standard risk had a superior OS and DFS than those with high risk disease (67% vs 23%, p=0.0004; and 50% vs 27%, p=0.01, respectively). When patients with FAB M3 disease were excluded from the analysis, the group with standard risk continue to have a superior OS and DFS (67% vs 13%, p=0.008; and 50% vs 14%, p=0.02, respectively). We conclude that autologous SCT is an effective treatment in AML with the possibility of long survivorship, particularly in patients with standard risk disease.