Systems healthcare: a holistic paradigm for tomorrow

Systems healthcare is a holistic approach to health premised on systems biology and medicine. The approach integrates data from molecules, cells, organs, the individual, families, communities, and the natural and man-made environment. Both extrinsic and intrinsic influences constantly challenge the biological networks associated with wellness. Such influences may dysregulate networks and allow pathobiology to evolve, resulting in early clinical presentation that requires astute assessment and timely intervention for successful mitigation. Herein, we describe the components of relevant biological systems and the nature of progression from at-risk to manifest disease. We illustrate the systems approach by examining two relevant clinical examples: Alzheimer’s and cardiovascular diseases. The implications of systems healthcare management are examined through the lens of economics, ethics, policy and the law. Finally, we propose the need to develop new educational paradigms to enhance the training of the health professional in an era of systems medicine.     

Loss of Allograft Inflammatory Factor-1 Ameliorates Experimental Autoimmune Encephalomyelitis by Limiting Encephalitogenic CD4 T-Cell Expansion

Experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS), is mediated by myelin-specific autoreactive T cells that cause inflammation and demyelination in the central nervous system (CNS), with significant contributions from activated microglia and macrophages. The molecular bases for expansion and activation of these cells, plus trafficking to the CNS for peripheral cells, are not fully understood. Allograft inflammatory factor-1 (Aif-1) (also known as ionized Ca²⁺ binding adapter-1 [Iba-1]) is induced in leukocytes in MS and EAE; here we provide the first assessment of Aif-1 function in this setting. After myelin oligodendrocyte glycoprotein peptide (MOG_35–55) immunization, Aif-1–deficient mice were less likely than controls to develop EAE and had less CNS leukocyte infiltration and demyelination; their spinal cords contained fewer CD4 T cells and microglia and more CD8 T cells. These mice also showed significantly less splenic CD4 T-cell expansion and activation, plus decreased proinflammatory cytokine expression. These findings identify Aif-1 as a potent molecule that promotes expansion and activation of CD4 T cells, plus elaboration of a proinflammatory cytokine milieu, in MOG_35–55-induced EAE and as a potential therapeutic target in MS.     

Terrestrial Activity in Pitheciins (Cacajao,Chiropotes, and Pithecia)

Neotropical monkeys of the genera Cacajao, Chiropotes, and Pithecia (Pitheciidae) are considered to be highly arboreal, spending most of their time feeding and traveling in the upper canopy. Until now, the use of terrestrial substrates has not been analyzed in detail in this group. Here, we review the frequency of terrestrial use among pitheciin taxa to determine the ecological and social conditions that might lead to such behavior. We collated published and unpublished data from 14 taxa in the three genera. Data were gleaned from 53 published studies (including five on multiple pitheciin genera) and personal communications of unpublished data distributed across 31 localities. Terrestrial activity was reported in 61% of Pithecia field studies (11 of 18), in 34% of Chiropotes studies (10 of 29), and 36% of Cacajao studies (4 of 11). Within Pithecia, terrestrial behavior was more frequently reported in smaller species (e.g. P. pithecia) that are vertical clingers and leapers and make extensive use of the understory than in in the larger bodied canopy dwellers of the western Amazon (e.g. P. irrorata). Terrestrial behavior in Pithecia also occurred more frequently and lasted longer than in Cacajao or Chiropotes. An apparent association was found between flooded habitats and terrestrial activity and there is evidence of the development of a “local pattern” of terrestrial use in some populations. Seasonal fruit availability also may stimulate terrestrial behavior. Individuals also descended to the ground when visiting mineral licks, escaping predators, and responding to accidents such as a dropped infant. Overall, the results of this review emphasize that terrestrial use is rare among the pitheciins in general and is usually associated with the exploitation of specific resources or habitat types. Am. J. Primatol. 74:1106‐1127, 2012. © 2012 Wiley Periodicals, Inc.     

Isolation of the fourth component (C4) of rat complement.

The fourth component of rat complement was purified to homogeneity by sequential chromatography of rat plasma in benzamidine on QAE-A50, SP-C50, hydroxyapatite, and gel filtration on Bio-Gel A 1.5. The final material was homogeneous on SDS-PAGE analysis and had a calculated m.w. of 198,000. A monospecific antibody against rat C4 was obtained from immunized rabbits. The concentration of rat C4 in the plasma of normal 4-month-old Wistar rats was 190 +/- 34 microgram/ml (mean +/- 1 S.D.).     

Mitochondrial DNA analysis of Rhipicephalus sanguineus s.l. from the western Iberian peninsula

Rhipicephalus sanguineus Latreille (1806) (Ixodida: Ixodidae) is considered to be the most widely distributed tick and to have a vast range of habitats and hosts, including livestock, pets and wildlife. In addition to morphological differences, recent investigations using approaches based on molecular genetic markers have revealed the existence of different R. sanguineus lineages in different geographic regions. In this study, 475 ticks collected from dogs in the western Iberian peninsula were studied both morphologically and genetically, using 12S and 16S rDNA and COI gene markers in order to clarify the controversy over the systematic status of R. sanguineus sensu lato in Western Europe, and to compare the present data with those sourced from studies conducted in other regions of the world. Despite the high morphometric variability, particularly on spiracles in both genders and in female genitalia, data obtained with different genetic molecular markers show very low variability, suggesting the existence of a unique species. In addition, the phylogenetic analysis showed genetic uniformity, supporting the existence of a well‐defined clade consisting of R. sanguineus s.l. specimens from Western Europe that are distinct from R. sanguineus s.l. from Africa. Furthermore, these data corroborate the existence of a polymorphic species in Western Europe, which requires to be consensually redescribed in view of its medical and veterinary importance in pathogen transmission.