Detached, distraught or discerning? Fathers of adolescents with chronic illness: a review of the literature.

Abstract Parenting a child with chronic disease provides a unique set of challenges for both mothers and fathers throughout all phases of the illness. However, fathers of these children are under-represented in existing research. This review focuses on the fathers of children with chronic disease included in 44 original articles. We address the challenges to the father's role as breadwinner, leader and strength-giver in the family. Three time-periods describe the obstacles fathers tackle when parenting children with chronic disease: a) diagnosis and short-term, characterized by distress, isolation and uncertainty; b) the mastery period, characterized by the struggle to establish routine and by support and spirituality; and c) the long-term, characterized by relationship and personality change, worries and bereavement. Overall, whilst current research has revealed some key themes pertaining to fathers of children with chronic disease, further studies are required to foster the development of support mechanisms for the specific needs of these fathers.

PPAR alpha structure-function relationships derived from species-specific differences in responsiveness to hypolipidemic agents.

The nuclear receptor PPAR alpha is a key regulatory transcription factor in lipid homeostasis, some liver detoxification processes and the control of inflammation. Recent findings suggest that many hypolipidemic drugs and anti-inflammatory agents can potentially act by binding to PPAR alpha and inducing its activity. Here, we identify some structure-function relationships in PPAR alpha, by using the species-specific responsiveness to the two hypolipidemic agents, Wy 14,643 and 5,8,11,14-eicosatetraynoic acid (ETYA). We first show that the species-specific differences are mediated primarily via the ligand binding domain of the receptor and that these two drugs are indeed ligands of PPAR alpha. By mutagenesis analyses we identify amino acid residues in the ligand binding domains of Xenopus, mouse and human PPAR alpha, that confer preferential responsiveness to ETYA and Wy 14,643. These findings will aid in the development of new synthetic PPAR alpha ligands as effective therapeutics for lipid-related diseases and inflammatory disorders.

Cholesterol is the major component of native lipoproteins activating the p38 mitogen-activated protein kinases.

Elevated low-density lipoprotein (LDL) levels induce activation of the p38 mitogen-activated protein kinase (MAPK), a stress-activated protein kinase potentially participating in the development of atherosclerosis. The nature of the lipoprotein components inducing p38 MAPK activation has remained unclear however. We show here that both LDLs and high-density lipoproteins (HDLs) have the ability to stimulate the p38 MAPKs with potencies that correlate with their cholesterol content. Cholesterol solubilized in methyl-beta-cyclodextrin was sufficient to activate the p38 MAPK pathway. Liposomes made of phosphatidylcholine (PC) or sphingomyelin, the two main phospholipids found in lipoproteins, were unable to stimulate the p38 MAPKs. In contrast, PC liposomes loaded with cholesterol potently activated this pathway. Reducing the cholesterol content of LDL particles lowered their ability to activate the p38 MAPKs. Cell lines representative of the three main cell types found in blood vessels (endothelial cells, smooth muscle cells and fibroblasts) all activated their p38 MAPK pathway in response to LDLs or cholesterol-loaded PC liposomes. These results indicate that elevated cholesterol content in lipoproteins, as seen in hypercholesterolemia, favors the activation of the stress-activated p38 MAPK pathway in cells from the vessel wall, an event that might contribute to the development of atherosclerosis.

The role of oxidative stress during inflammatory processes.

Abstract The production of various reactive oxidant species in excess of endogenous antioxidant defense mechanisms promotes the development of a state of oxidative stress, with significant biological consequences. In recent years, evidence has emerged that oxidative stress plays a crucial role in the development and perpetuation of inflammation, and thus contributes to the pathophysiology of a number of debilitating illnesses, such as cardiovascular diseases, diabetes, cancer, or neurodegenerative processes. Oxidants affect all stages of the inflammatory response, including the release by damaged tissues of molecules acting as endogenous danger signals, their sensing by innate immune receptors from the Toll-like (TLRs) and the NOD-like (NLRs) families, and the activation of signaling pathways initiating the adaptive cellular response to such signals. In this article, after summarizing the basic aspects of redox biology and inflammation, we review in detail the current knowledge on the fundamental connections between oxidative stress and inflammatory processes, with a special emphasis on the danger molecule high-mobility group box-1, the TLRs, the NLRP-3 receptor, and the inflammasome, as well as the transcription factor nuclear factor-κB.

Postglacial recolonization of the Valais (Switzerland) by the shrew Sorex antinorii: is dispersal sex-biased? A preliminary study

One male inherited and 8 biparentaly inherited microsatellite markers developed in the shrew Sorex antinorii were used to analyse population of this species from the Valais mountainous region of Switzerland. The analysis of the Y-chromosome microsatellite showed a nearly complete absence of male gene flow between populations from the Simplon Pass and the St-Bernard pass. These results suggest that the recolonization of the Valais from the Italian refugia after the last Pleistocene glaciations has been done through these two potential routes. To complete these results, we studied the same samples, as well as additional samples from intermediate localities, with a female inherited mtDNA marker. The highly variable D-Loop region of mtDNA was sequenced in 44 individuals. This mtDNA marker does not show a clear geographical structuration. The populations of the intermediate valleys are genetically closer to the populations of the Simplon region for the male marker, but not for the mtDNA marker. Simplon appears to have been the first route of colonisation of Valais. Female-biased dispersal could explain our results. This preliminary study exemplifies the interest of the analysis of sex-specific genetic markers in phylogeography.

Preimplantation genetic diagnosis (PGD) for HLA typing: bases for setting up an open international collaboration when PGD is not available.

In severe forms of Diamond-Blackfan anemia, preimplantation genetic diagnosis (PGD) of histocompatibility leukocyte antigen-compatible embryos for enabling the next sibling in the family to be a stem-cell transplantation donor constitutes the sole lasting cure capable of terminating the enduring need for iterative transfusions. We report here an open collaboration between two renowned institutions to provide a family desiring this treatment even though they resided where the preimplantation genetic diagnosis procedure is banned.