Abstract: INTRODUCTION: While fibrin sealant (FS) and equine collagen (EC) have been used as scaffold materials in experimental spinal cord injury (SCI), questions concerning neurocompatibility still remain. In this study, we assessed potential adverse effects, as well as functional and histological impact of FS and EC in subtotal hemisection of the thoracic spinal cord (SC) in rats. METHODS: 124 male rats were randomly assigned to four main groups (n=31): Sham (SH), Lesion only (L), fibrin sealant (GFS) and equine collagen group (GEC). SH animals received laminectomy only; all other animals underwent subtotal lateral hemisection at T9. Treatment consisted of application of FS or EC into the lesion gap in GFS and GEC, which was left empty in L. GFS, GEC, L and SH were each further divided into 4 subgroups: One subgroup, consisting of 10 rats was subjected to behavioural and reflex testing before surgery and followed up on days 1,7, 14, 21, 28 post op and then sacrificed. Haemalaun or cresyl violet (CV) was used to identify neutrophils in parasagittal cord sections which were obtained on day 1 (n=7). Sections stained for quantification of microglia/macrophages using ED-1 on day 3 (n=7), day 7 (n=7) and day 28 (n=7 out of 10). Additionally, neural filament (NF) staining was chosen to detect axonal regeneration and the length of ingrowth into FS and EC, Luxol blue for myelination, Von Willebrand factor for vascularisation, and glial fibrillary acidic protein (GFAP) staining for detection of astrocytes in glial scars on day 28. RESULTS: No adverse effects were observed in the treatment groups. Compared to L, GFS and GEC performed significantly better in the Basso, Beattie, Bresnahan (BBB) score and hopping responses. Proprioceptive placing was markedly improved in FS and EC compared to L. Axonal regrowth was found in GFS and GEC--the regrowth in the GFS was accompanied by myelination and vascularisation. Glial scarring occurred in all groups. Discussion Both biomatrices improved functional recovery compared to L and no adverse effects were perceived.

Abstract: It has been hypothesized that numerous genes contribute to individual variation in human cognition. An extensive search of the scientific literature was undertaken to identify candidate genes which might contribute to this complex trait. A list of over 150 candidate genes that may influence some aspect of cognition was compiled. Some genes are particularly strong candidates based on evidence for involvement in cognitive processes in humans, mice, and Drosophila melanogaster. This survey confirms that many genes are associated with cognitive variation and highlights the potential importance of animal models in the study of human cognition.

Abstract: Leptospirosis is a zoonotic bacterial disease caused by Leptospira interrogans. There is a serologic evidence that horses are exposed to L. interrogans and, as a shedder of these organisms, can be a threat to humans. We examined risk factors associated with the risk of testing seropositive to three L. interrogans serovars (L. icterohaemorrhagiae, L. grippotyphosa, and L. canicola) in the horses of New York State, in order to understand the epidemiology of the disease and suggest strategies to control and prevent equine leptospirosis. To carry out this study, blood samples were collected from a random sample of 2551 horses and tested for the presence of antibodies to the above serovars using the microscopic agglutination test. Samples with a titer $100 were considered positive. Clinical and demographic data were collected on each horse, the farms' management practices and ecology. Logistic regression analysis was used to develop a multivariate indexing system and to identify factors significantly associated with the risk of leptospirosis. Four indices were developed based on the possible sources of exposure: rodent exposure index; wildlife exposure index; soil and water index; and management index. The soil and water index was significantly associated with the risk of exposure to all three serovars. Management was positively associated with L. icterohaemorrhagiae and L. canicola. Density of horses turned out together was positively associated with the risk of exposure to L. grippotyphosa. We concluded that indirect exposure of horses to L. interrogans through contaminated soil and water appears to be significantly associated with the risk of exposure to all three serovars. Management appears to play an important role in the exposure to L. interrogans. Modification of management practices might reduce the horses' risk of exposure and hopefully minimize the human hazards.

Abstract: Lipid-lowering fibrate drugs function as agonists for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Sustained activation of PPARalpha leads to the development of liver tumors in rats and mice. However, humans appear to be resistant to the induction of peroxisome proliferation and the development of liver cancer by fibrate drugs. The molecular basis of this species difference is not known. To examine the mechanism determining species differences in peroxisome proliferator response between mice and humans, a PPARalpha-humanized mouse line was generated in which the human PPARalpha was expressed in liver under control of the tetracycline responsive regulatory system. The PPARalpha-humanized and wild-type mice responded to treatment with the potent PPARalpha ligand Wy-14643 as revealed by induction of genes encoding peroxisomal and mitochondrial fatty acid metabolizing enzymes and resultant decrease of serum triglycerides. However, surprisingly, only the wild-type mice and not the PPARalpha-humanized mice exhibited hepatocellular proliferation as revealed by elevation of cell cycle control genes, increased incorporation of 5-bromo-2'-deoxyuridine into hepatocyte nuclei, and hepatomegaly. These studies establish that following ligand activation, the PPARalpha-mediated pathways controlling lipid metabolism are independent from those controlling the cell proliferation pathways. These findings also suggest that structural differences between human and mouse PPARalpha are responsible for the differential susceptibility to the development of hepatocarcinomas observed after treatment with fibrates. The PPARalpha-humanized mice should serve as models for use in drug development and human risk assessment and to determine the mechanism of hepatocarcinogenesis of peroxisome proliferators.

Abstract: Marten and Psarakos have presented some evidence which suggests that objective self-awareness and possibly representations of self may characterize the dolphins' experience of self. Their research demonstrates the possibility of similarities in the sense of self between primate species and dolphins, although whether dolphins have subjective self-awareness, personal memories, and theories of self--all important facets of the sense of self in humans--was not examined. Clearly, even this limited evidence was difficult to achieve; the difficulties in adapting methods and coding behavior are quite apparent in their report. Future progress, however, may depend upon clarification of what are the necessary components for a sense of self and an explication of how these might be reflected in dolphin behavior. We are mindful of the authors' point (pp. 219 and 220) that the dolphin lives more in an acoustic than a visual environment. Thus, while tasks relying upon vision may reveal the presence or absence of the sense of self in primates, it might well be the case that in dolphins self-related experiences might be better revealed in auditory tasks. But then, what is the nature of human self-awareness in terms of audition? While both conceptual and methodological hurdles remain, Marten and Psarakos have demonstrated that important questions can be asked about the minds and phenomenal worlds of nonanthropoid species.