Pre-existing invasive fungal infection is not a contraindication for allogeneic HSCT for patients with hematologic malignancies: a CIBMTR study.

Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P<0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT

Extending Epigenesis: From Phenotypic Plasticity to the Bio-Cultural Feedback

The paper aims at proposing an extended notion of epigenesis acknowledging an actual causal import to the phenotypic dimension for the evolutionary diversification of life forms. Section 1 offers introductory remarks on the issue of epigenesis contrasting it with ancient and modern preformationist views. In Section 2 we propose to intend epigenesis as a process of phenotypic formation and diversification a) dependent on environmental influences, b) independent of changes in the genomic nucleotide sequence, and c) occurring during the whole life span. Then, Section 3 focuses on phenotypic plasticity and offers an overview of basic properties (like robustness, modularity and degeneracy) that allows biological systems to be evolvable – i.e. to have the potentiality of producing phenotypic variation. Successively (Section 4), the emphasis is put on environmentally-induced modification in the regulation of gene expression giving rise to phenotypic variation and diversification. After some brief considerations on the debated issue of epigenetic inheritance (Section 5), the issue of culture (kept in the background of the preceding sections) is considered. The key point is that, in the case of humans and of the evolutionary history of the genus Homo at least, the environment is also, importantly, the cultural environment. Thus, Section 6 argues that a bio-cultural feedback should be acknowledged in the “epigenic” processes leading to phenotypic diversification and innovation in Homo evolution. Finally, Section 7 introduces the notion of “cultural neural reuse”, which refers to phenotypic/neural modifications induced by specific features of the cultural environment that are effective in human cultural evolution without involving genetic changes. Therefore, cultural neural reuse may be regarded as a key instance of the bio-cultural feedback and ultimately of the extended notion of epigenesis proposed in this work

Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis

Background: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. Methods: We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Results: Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4+IL17+, CD11b+Ly6G+ and CD11b+Ly6C+ cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3 expression levels were detected in DMSC-treated mice. DMSCs also showed a detrimental influence on the in vitro definition of the Th17 phenotype. Conclusions: DMSCs modulated the clinical course of EAE, modified the frequency and cell composition of the central nervous system infiltrates during the disease, and mediated an impairment of Th17 phenotype establishment in favor of the Th2 subtype. These results suggest that DMSCs might provide a new cell-based therapy for the control of multiple sclerosis.This work was sponsored by grants from Acción Estratégica en Salud (PI13/00297 and PI11/00581), the Neurosciences and Aging Foundation, the Francisco Soria Melguizo Foundation, Octopharma, and Parkinson Madrid (PI2012/0032).S

Mind the Gap: Transitions Between Concepts of Information in Varied Domains

The concept of 'information' in five different realms – technological, physical, biological, social and philosophical – is briefly examined. The 'gaps' between these conceptions are dis‐ cussed, and unifying frameworks of diverse nature, including those of Shannon/Wiener, Landauer, Stonier, Bates and Floridi, are examined. The value of attempting to bridge the gaps, while avoiding shallow analogies, is explained. With information physics gaining general acceptance, and biology gaining the status of an information science, it seems rational to look for links, relationships, analogies and even helpful metaphors between them and the library/information sciences. Prospects for doing so, involving concepts of complexity and emergence, are suggested