Effects of an enrichment device on voluntary alcohol consumption on single-housed rats.

We evaluated the effect of an enrichment device (that is, a polyurethane bone) on the voluntary consumption of ethanol containing gel by single-housed rats. Male Sprague-Dawley rats (n = 5 per group) were exposed for 4 d to each of the following 3 treatments: access to a new synthetic bone and ethanol gel for 1 h daily (treatment 1); a new bone was left in the cage for 24 h, with access to ethanol gel for 1 h daily (treatment 2); and both the bone and ethanol gel remained in the cage for 24 h (treatment 3). Average alcohol consumption over 4 d was 0.86 +/- 0.13, 0.99 +/- 0.13, and 5.19 +/- 0.37 g/kg in the absence of the bone for treatments 1, 2, and 3, respectively, and 1.00 +/- 0.13, 0.620 +/- 0.07, and 5.55 +/- 0.38 g/kg with the bone for treatments 1, 2 and 3, respectively; none of these values differed significantly with regard to presence of the bone. During treatment 1, time spent with the synthetic bone was highest on the first 2 d, which altered the rate of ethanol consumption but not the total amount of ethanol consumed. During treatments 2 and 3, the rate and amount of ethanol consumption were comparable to basal levels. We conclude that adding an enrichment device that rats can chew and manipulate does not alter ethanol gel consumption. If used, environmental enrichment techniques should be evaluated during the research planning stages to avoid unintended alterations in the response to variables of interest.     

Preserved executive function in high‐performing elderly is driven by large‐scale recruitment of prefrontal cortical mechanisms

High‐density electrical mapping of event‐related potentials was used to investigate the neural processes that permit some elderly subjects to preserve high levels of executive functioning. Two possibilities pertain: (1) high‐performance in elderly subjects is underpinned by similar processing mechanisms to those seen in young adults; that is, these individuals display minimal functional decay across the lifespan, or (2) preserved function relies on successfully recruiting and amplifying control processes to compensate for normal sensory‐perceptual decline with age. Fifteen young and nineteen elderly participants, the latter split into groups of high and low performers, regularly alternated between a letter and a number categorization task, switching between tasks every third trial (AAA‐BBB‐AAA…). This allowed for interrogation of performance during switch, repeat, and preparatory pre‐switch trials. Robust effects of age were observed in both frontal and parietal components of the task‐switching network. Greatest differences originated over prefrontal regions, with elderly subjects generating amplified, earlier, and more differentiated patterns of activity. This prefrontal amplification was evident only in high‐performing (HP) elderly, and was strongest on pre‐switch trials when participants prepared for an upcoming task‐switch. Analysis of the early transient and late sustained activity using topographic analyses and source localization collectively supported a unique and elaborated pattern of activity across frontal and parietal scalp in HP‐elderly, wholly different to that seen in both young and low‐performing elderly. On this basis, we propose that preserved executive function in HP‐elderly is driven by large‐scale recruitment and enhancement of prefrontal cortical mechanisms. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Immunological monitoring to prevent and treat sepsis

The clinical, human and economic burden associated with sepsis is huge. Initiatives such as the Surviving Sepsis Campaign aim to effectively reduce risk of death from severe sepsis and septic shock. Nonetheless, although substantial benefits raised from the implementation of this campaign have been obtained, much work remains if we are to realise the full potential promised by this strategy. A deeper understanding of the processes leading to sepsis is necessary before we can design an effective suite of interventions. Dysregulation of the immune response to infection is acknowledged to contribute to the pathogenesis of the disease. Production of both proinflammatory and immunosuppressive cytokines is observed from the very first hours following diagnosis. In addition, hypogammaglobulinemia is often present in patients with septic shock. Moreover, levels of IgG, IgM and IgA at diagnosis correlate directly with survival. In turn, nonsurvivors have lower levels of C4 (a protein of the complement system) than the survivors. Natural killer cell counts and function also seem to have an important role in this disease. HLA-DR in the surface of monocytes and counts of CD4⁺CD25⁺ T-regulatory cells in blood could also be useful biomarkers for sepsis. At the genomic level, repression of networks corresponding to major histocompatibility complex antigen presentation is observed in septic shock. In consequence, cumulative evidence supports the potential role of immunological monitoring to guide measures to prevent or treat sepsis in a personalised and timely manner (early antibiotic administration, immunoglobulin replacement, immunomodulation). In conclusion, although diffuse and limited, current available information supports the development of large comprehensive studies aimed to urgently evaluate immunological monitoring as a tool to prevent sepsis, guide its treatment and, as a consequence, diminish the morbidity and mortality associated with this severe condition.     

Magnetically driven three-dimensional manipulation and inductive heating of magnetic-dispersion containing metal alloys

Fundamental to the development of three-dimensional microelectronic fabrication is a material that enables vertical geometries. Here we show low-melting-point metal alloys containing iron dispersions that can be remotely manipulated by magnetic fields to create vertical geometries and thus enable novel three-dimensional assemblies. These iron dispersions enhance the mechanical properties needed for strong, reliable interconnects without significantly altering the electrical properties of the alloys. Additionally, these iron dispersions act as susceptors for magnetic induction heating, allowing the rapid melting of these novel alloys at temperatures lower than those usually reported for conventional metal alloys. By localizing high temperatures and by reducing temperature excursions, the materials and methods described have potential in a variety of device fabrication applications.     

Rural Roadway Safety Perceptions Among Rural Teen Drivers Living in and Outside of Towns

Purpose : To compare perceptions about rural road and general driving behaviors between teens who live in‐ and out‐of‐town from rural communities in Iowa. Methods : A cross‐sectional survey was conducted with 160 teens anticipating their Intermediate License within 3 months upon enrollment into this study. Self‐administered surveys were used to collect demographics and driving exposures (eg, frequency of driving, age when first drove unsupervised). Two Likert scales were included to measure agreement with safe driving behaviors on rural roads and general safe driving behaviors (eg, speeding, seat belt use). T‐tests were calculated comparing mean composite scores between in‐ and out‐of‐town teens, and between mean rural road and general driving safety attitude scores. A linear regression multivariable model was constructed to identify predictors of the rural road score. Results : While the majority of teens endorsed rural road and general safe driving behaviors, up to 40% did not. Thirty‐two percent did not believe the dangers of animals on rural roads, and 40% disagreed that exceeding the speed limit is dangerous. In‐town teens were less safety conscious about rural road hazards with a significantly lower mean composite score (4.4) than out‐of‐town teens (4.6); mean scores for general driving behaviors were similar. Living out‐of‐town and owning one's own car were significant predictors of increased rural road safety scores. Conclusion : Rural, in‐town teens have poorer safety attitudes about rural roadway hazards compared with out‐of‐town teens. Interventions that involve education, parental supervision, and practice on rural roads are critical for preventing teen crashes on rural roads.     

Possible association between Taenia solium cysticercosis and cancer: increased frequency of DNA damage in peripheral lymphocytes from neurocysticercosis patients

Helminths, particularly some Schistosoma species, have been associated with cancer in humans. Neurocysticercosis, produced by cysticerci of the helminth Taenia solium, has been associated with the emergence of brain tumours and haematological malignancies. Local tumours, such as glioblastoma, could be explained by the induction of DNA damage in cells surrounding the cysticercus and chronically exposed to an inflammatory host response. However, systemic effects such as haematological malignancies are not easy to understand. The present work was conducted in Mexico to find out whether DNA damage arises in peripheral lymphocytes in patients with neurocysticercosis. We utilized a highly sensitive technique to analyse chromosomal aberrations, in-situ hybridization with probes against chromosomes 1, 2 and 4, and in addition the blocked-cytokinesis technique was used to determine the formation of micronuclei, a peculiar form of DNA damage. The study was made in lymphocytes from 8 patients before and after the administration of praziquantel, 1 of the 2 drugs used for neurocysticercosis treatment. The frequencies of chromosome aberrations and micronuclei in peripheral blood lymphocytes were higher in the infected patients as compared to those observed both in healthy donors and in the group of patients after praziquantel therapy. Our results suggest that chromosome aberrations induced in peripheral cells during neurocysticercosis could be associated with the development of haematological neoplasias.     

Biodegradable PLGA Microspheres Loaded with Ganciclovir for Intraocular Administration. Encapsulation Technique,in Vitro Release Profiles,and Sterilization Process

Purpose. The purpose of this work was to obtain a sterilized formulation consisting of biodegradable microspheres of poly (DL-lactide-co-glycolide) (PLGA) for intraocular sustained release of ganciclovir. Methods. Microspheres were prepared using a dispersion of ganciclovir in fluorosilicone oil (FSiO) that was further dispersed in an acetone solution of PLGA [50/50 and inherent viscosity 0.41 dl/g], and emulsified in silicone oil with a surfactant. Once prepared, the formulation was exposed with an effective radiation dose of 2.5 megarads. The release rate data of ganciclovir from the sterilized and nonsterilized batches were compared using the similarity factor (f₂). Results. The dispersion of the drug in FSiO contributed to achieving a drug payload of up to 95% of the theoretical in the 300-500 m microspheres. Ten mg released ganciclovir in vitroat 1.3 g/h for the first 21 days, but decreased to 0.2 g/h from day 25 until the end of the release study (42 days). No significant differences in the amounts of encapsulated drug (=0.05) were observed between the sterilized and nonsterilized microspheres. Furthermore, dissolution profiles of formulations behaved similarly before and after gamma radiation exposure. Conclusions. The technique of microsphere preparation described resulted in high ganciclovir loading (95%) and prolonged drug release. The ganciclovir formulation behaved similarly before and after the sterilization process.     

Constitutive expression of insulin-like growth factor-1 in epidermal basal cells of transgenic mice leads to spontaneous tumor promotion

Transgenic mice overexpressing insulin-like growth factor-1 (IGF-1) in the basal layer of skin epidermis were generated using the bovine keratin 5 promoter (BK5). Neonatal transgenic mice were slightly smaller at birth and exhibited early ear unfolding, wrinkled and thickened skin, and slightly enlarged ears compared with nontransgenic littermates. Morphological evaluation of the skin revealed that persistent overexpression of IGF-1 in the basal layer of the epidermis resulted in epidermal hyperplasia, hyperkeratosis, and an increased labeling index that persisted in adult mice. Phenotypic changes observed in skin were associated with transgene expression in the basal layer of the epidermis and activation of the IGF-1 receptor. Squamous papillomas (some of which converted to carcinomas) developed in a significant proportion (approximately 50%) of older BK5.IGF-1 mice. Treatment of BK5.IGF-1 transgenic mice with multiple topical applications of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, in the absence of tumor initiation led to the development of additional skin papillomas. Furthermore, treatment of BK5.IGF-1 transgenic mice with an initiating dose of 7,12-dimethylbenz[a]anthracene only led to the formation of additional papillomas in the absence of promotion. In two-stage carcinogenesis experiments, BK5.IGF-1 transgenic mice developed 7-fold more papillomas than nontransgenic littermates. Phosphatidylinositol-3-kinase and protein kinase B (Akt) activities were elevated (3-4-fold), and mitogen-activated protein kinase activity was elevated approximately 1.7-fold in the epidermis of transgenic mice compared with nontransgenic mice. In addition, UV light-induced epidermal apoptosis was significantly suppressed in BK5.IGF-1 transgenic mice. These data suggest that persistent activation of IGF-1 receptor signaling pathways in basal epithelial cells leads to spontaneous tumor promotion and that up-regulation of both mitogenic and cell survival signaling pathways may play an important role in the action of IGF-1 in this model system.