Immune parameters identify Italian centenarians with a longer five-year survival independent of their health and functional status.

Centenarians are rare and exceptional individuals characterized by a peculiar phenotype. They are the best example of healthy aging in humans as most of them have escaped or substantially delayed the onset of major age-related diseases. Within this scenario, the purpose of the present work was to understand if immune status is associated with survival and health status in centenarians. To this aim, 116 centenarians were concomitantly characterized for their immunological, health and functional status, and followed-up for five-year survival. On the basis of previous knowledge we focused on a core of fundamental and basic immune parameters (number of leukocytes, monocytes, total lymphocytes, CD3(+) T lymphocytes, CD4(+) helper T lymphocytes, CD8(+) cytotoxic T lymphocytes, CD19(+) B lymphocytes and plasma levels of IgM), and the most important findings can be summarized as follows: i. a hierarchical cluster analysis was able to define Cluster1 (88 centenarians) and Cluster2 (28 centenarians) characterized by low and high values of all these immune parameters, respectively; ii. centenarians of Cluster2 showed a statistically longer five-year survival and more favorable values of other important immune (naïve, activated/memory and effector/memory T cells) and metabolic (glycemia, insulin and HOMA-IR) parameters, in accord with previous observations that centenarians have a peculiar immune profile, a preserved insulin pathway and a lower incidence of type 2 diabetes; and iii. unexpectedly, parameters related to frailty, as well as functional and cognitive status, did not show any significant correlation with the immune clustering, despite being capable per se of predicting survival. In conclusion, high values of basic immunological parameters and important T cell subsets correlate with five-year survival in centenarians, independent of other phenotypic characteristics. This unexpected biological scenario is compatible with the general hypothesis that in centenarians a progressive disconnection and loss of biological coherence among the different functions of the body occur, where survival/mortality result from the failure of any of these domains which apparently follow an independent age-related trajectory.

Stochastic analysis of a miRNA-protein toggle switch.

Within systems biology there is an increasing interest in the stochastic behavior of genetic and biochemical reaction networks. An appropriate stochastic description is provided by the chemical master equation, which represents a continuous time Markov chain (CTMC). In this paper we consider the stochastic properties of a toggle switch, involving a protein compound (E2Fs and Myc) and a miRNA cluster (miR-17-92), known to control the eukaryotic cell cycle and possibly involved in oncogenesis, recently proposed in the literature within a deterministic framework. Due to the inherent stochasticity of biochemical processes and the small number of molecules involved, the stochastic approach should be more correct in describing the real system: we study the agreement between the two approaches by exploring the system parameter space. We address the problem by proposing a simplified version of the model that allows analytical treatment, and by performing numerical simulations for the full model. We observed optimal agreement between the stochastic and the deterministic description of the circuit in a large range of parameters, but some substantial differences arise in at least two cases: (1) when the deterministic system is in the proximity of a transition from a monostable to a bistable configuration, and (2) when bistability (in the deterministic system) is "masked" in the stochastic system by the distribution tails. The approach provides interesting estimates of the optimal number of molecules involved in the toggle switch. Our discussion of the points of strengths, potentiality and weakness of the chemical master equation in systems biology and the differences with respect to deterministic modeling are leveraged in order to provide useful advice for both the bioinformatician and the theoretical scientist.

[Protection and risk factors with respect to "burnout" of operatives. A comparative study of the psychosocial centers of Milan and Trieste]. / Fattori di protezione e di rischio rispetto al "burn out" degli operatori. Uno studio comparativo tra centri psicosociali di Milano e Trieste.

The Maslach Burn Out Inventory (1981) has been applied to a group of workers at three Psychosocial Centres at Milan and Trieste characterised by differing work styles. Point scores were related to a number of variables relative to the professional situation and work organisation. The same scores were related to the results of a questionnaire (Contessa 1987) on the operator's perception of his activity and on motivational factors with respect to the professional choice in actuality and at the beginning of the career. It was therefore possible to identify a set of positive correlations that indicate the presence of factors which increase or reduce B.O. Level.