Notes

Bacterial infections throughout severe forms of alcohol-related liver organ disease * Need a better look!
he RIC Flu/TBI platform for lymphomas. Allogeneic stem cell transplantation is applied to patients suffering from hematological malignancies to replace the diseased hematopoietic system with cells derived from a donor stem cell graft. The majority of 10/10 matched unrelated donors are HLA-DP-mismatched and this may result in varying degrees of graft-versus-leukemia (GVL) effect with or without the occurrence of graft-versus-host disease (GVHD). Allo-HLA-reactive T cells are commonly present in the donor T-cell repertoire and therefore a very profound allo-reactive immune response can be provoked in the HLA-DP-mismatched setting. The magnitude and the diversity of the allo-HLA-DP-specific immune response likely dictates the balance between the occurrence of GVL and/or GVHD after transplantation. To understand the nature of the allo-HLA-DP-specific immune response provoked under different stimulatory conditions, immune responses were induced from both the naïve and memory T-cell compartment using either HLA-DP-mismatched professional (monocyte-derived dendritic cells, alloDC) or HLA-DP-mismatched non-professional APC (skin-derived fibroblasts, alloFibroblasts) as stimulator cells. In this study we observed that allo-HLA-DP-reactive T cells could be provoked from both the naïve and memory compartment by both types of APC. However, the magnitude of the allo-HLA-DP-specific immune response was greater when stimulation was performed with alloDC. Moreover, we found that the frequency of allo-HLA-DP-reactive T cells was greater in the naïve T-cell compartment compared to the memory T-cell compartment, but we observed a comparable lineage specificity of these allo-HLA-DP-specific reactivities. Overall, the data in this study illustrate that the presence of professional APC of recipient origin will mostly dictate the magnitude of the allo-HLA-DP-specific immune response derived from both the naïve and memory T-cell compartment, but does not exclusively mediate the induction of these immune responses. Ibrutinib order Anti-thymocyte globulin (ATG) is used to reduce the incidence and severity of graft-versus-host disease (GVHD) with hematopoietic cell transplantation, yet optimum dosing has yet to be determined. We have previously demonstrated that 2.5 mg/kg of ATG in conditioning can reduce the incidence of GVHD in unrelated donor transplants. Recent literature has suggested that ATG dosing based on absolute lymphocyte count (ALC) could lead to more optimum exposure of the drug. We sought to determine if ALC at the time of transplant could impact clinical outcomes. We conducted a retrospective single centre study analyzing all consecutive patients at The Ottawa Hospital who received a matched unrelated donor stem cell transplant with ATG between 2009 and 2014. Patients received rabbit ATG (Thymoglobulin®) at 0.5 mg/kg on day -2 and 2.0 mg/kg on day -1. Univariate and multivariate analysis were used to determine if any patient or transplant related factors, including weight, ALC, and total ATG dose given, impacted GVHD, relre than five times the mean dose that was actually given based on weight. With GVHD outcomes being similar to that published by Admiraal et al. and ALC not independently associated with outcomes in our study, further studies are still needed to compare standard weight-based dosing to ALC-based dosing of ATG in matched unrelated donor stem cell transplant. BACKGROUND AND OBJECTIVES Acute kidney injury (AKI) is nearly universally associated with worse outcomes, especially among children after hematopoietic stem cell transplant (HCT). Our objective was to examine urinary immune biomarkers of AKI after HCT to provide insights into novel mechanisms of kidney injury in this population. Studying patients undergoing allogeneic (HCT) provides a unique opportunity to examine immune markers of AKI because the risk of AKI is high and the immune system newly develops after transplant. DESIGN, SETTING, PARTICIPANTS Children (>2 years old) and young adults undergoing their first allogeneic HCT and enrolled in a prospective, observational cohort study at two large children's hospitals had urine collected pre-HCT and monthly for the first 4 months after HCT. Urine samples at each monthly time point were assayed for 8 immune-related biomarkers. AKI was defined as a 1.5-fold increase in the monthly serum creatinine value which was recorded ±1 day from when the research urine samtential mechanism driving the key finding. CONCLUSIONS CXCL10 and CXCL9 are associated with AKI after HCT and are therefore promising biomarkers to guide improved diagnostic and treatment strategies for AKI in this high-risk population. Exposure to a temperature increase may disrupt smoltification and delay or stop the downstream migration of smolts. Thermal regimes are often different between a river and its tributaries, but the effects of a relative temperature shift are not well described. We used expression of smoltification genes coupled with gill Na+/K+-ATPase activity (NKA) and plasma cortisol and growth hormone (GH) levels to investigate the impact of a 5 °C difference between tributary and river on salmon juveniles. Responses to a temperature challenge were examined at four time points during the smoltification period, with juveniles reared under three regimes including control, early and late temperature increase. The temperature shifts reduced gill NKA, plasma GH and cortisol levels which indicate hypo-osmoregulation impairment and may reduce the survival of smolts. Out of the 22 genes examined, the expression of six genes was influenced by the temperature treatments, while changes in further eleven genes were influenced by the date of sampling. Genes usually known to be upregulated during smoltification were downregulated after the temperature increase, notably nkaα1b, nkcc1a and igf1r. Upregulation of some genes involved in the hormonal regulation and acid-base equilibrium in early June may indicate a switch towards desmoltification. This study gives further insights about the impact of temperature increase on the molecular processes underlying smoltification and possible responses to human-related water temperature increase. The data also suggest dual roles in the smoltification and desmoltification for GH and IGF1 and points to the implication of genes in the smoltification process, that have previously been unstudied (nbc) or with little data available (igf2).
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