A randomized controlled trial of alanyl-glutamine supplementation in peritoneal dialysis fluid to assess impact on biomarkers of peritoneal health.

In early clinical testing, acute addition of alanyl-glutamine (AlaGln) to glucose-based peritoneal dialysis (PD) fluids restored peritoneal cellular stress responses and leukocyte function. This study was designed to test the effect of extended treatment with AlaGln-supplemented PD fluid on biomarkers of peritoneal health. In a double-blinded, randomized crossover design, stable PD patients were treated with AlaGln (8 mM) or placebo added to PD fluid for eight weeks. As primary outcome measures, dialysate cancer-antigen 125 (CA-125) appearance rate and ex vivo stimulated interleukin-6 (IL-6) release were assessed in peritoneal equilibration tests. In 8 Austrian centers, 54 patients were screened, 50 randomized, and 41 included in the full analysis set. AlaGln supplementation significantly increased CA-125 appearance rate and ex vivo stimulated IL-6 release. AlaGln supplementation also reduced peritoneal protein loss, increased ex vivo stimulated tumor necrosis factor (TNF)-α release, and reduced systemic IL-8 levels. No adverse safety signals were observed. All 4 peritonitis episodes occurred during standard PD fluid treatment. A novel AlaGln-supplemented PD fluid improves biomarkers of peritoneal membrane integrity, immune competence, and systemic inflammation compared to unsupplemented PD fluid with neutral pH and low-glucose degradation. A phase 3 trial is needed to determine the impact of AlaGln supplementation on hard clinical outcomes.

Education, Employment, and Financial Outcomes in Adolescent and Young Adult Cancer Survivors-A Systematic Review.

Adolescents and young adults (AYAs) with cancer face unique challenges. We aimed to describe (i) education, employment, and financial outcomes and (ii) determinants for adverse outcomes in AYA cancer survivors. We performed a systematic literature search. We included original research articles on AYA (15-39 years of age) cancer survivors (≥2 years after diagnosis) and our outcomes of interest. We narratively synthesized the results of the included articles. We included 35 articles (24 quantitative and 11 qualitative studies). Patients in education had to interrupt their education during cancer treatment, and re-entry after treatment was challenging. After treatment, most survivors were employed but started their employment at an older age than the general population. Overall, no disadvantages in income were found. Survivors reported more absent workdays than comparisons. We identified chemotherapy, radiotherapy, late effects or health problems, female sex, migration background, and lower education associated with adverse outcomes. Although most AYA cancer survivors were able to re-enter education and employment, they reported difficulties with re-entry and delays in their employment pathway. To facilitate successful re-entry, age-tailored support services should be developed and implemented.

An In Vitro HSV-1 Reactivation Model Containing Quiescently Infected PC12 Cells.

Advances in the understanding of the infection and reactivation process of herpes simplex type 1 (HSV-1) are generally gained by monolayer cultures or extensive and cost-intensive animal models. So far, no reliable in vitro skin model exists either to investigate the molecular mechanisms involved in controlling latency and virus reactivation or to test pharmaceuticals. Here we demonstrate the first in vitro HSV-1 reactivation model generated by using the human keratinocyte cell line HaCaT grown on a collagen substrate containing primary human fibroblasts. We integrated the unique feature of a quiescently infected neuronal cell line, the rat pheochromocytoma line PC12, within the dermal layer of the three-dimensional skin equivalent. Transmission electron microscopy, a cell-based TCID50 assay, and polymerase chain reaction analysis were used to verify cell latency. Thereby viral DNA could be detected, whereas extracellular as well as intracellular virus activity could not be found. Further, the infected PC12 cells show no spontaneous reactivation within the in vitro skin equivalent. In order to simulate a physiologically comparable HSV-1 infection, we achieved a specific and pointed reactivation of quiescently HSV-1 infected PC12 cells by UVB irradiation at 1000 mJ/cm(2).