265 research outputs found

    Developmental outcomes of HIV-exposed infants in a low-income South African context

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    Background: Effective HIV transmission prevention strategies have led to a growing population of vulnerable HIV- and antiretroviral-exposed infants in sub-Saharan Africa, however uncertainty exists regarding their development. Objective: To determine the developmental outcomes of HIV-exposed (HE) infants in a low-income South African context, when compared to HIV-unexposed (HU) counterparts. Methods: In this prospective cross-sectional, group comparison study, the development of 41 HE and 40 HU infants (mean age=8.4 months, SD=2.1 months) from a low-income context was assessed. Caregivers were interviewed using the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) to evaluate infants\u2019 development. Results: Most HE participants had age-appropriate overall development (90.2%;n=37). Some HE participants, however, presented with delays in domains of communication (9.8%;n=4), daily living skills (2.4%;n=1), socialisation (19.5%;n=8), and motor development (7.3%;n=3). HU participants also demonstrated some domain-specific delays, thus delays were present in both groups. No statistically significant between-group differences regarding development were found. Conclusion: Findings were reassuring and suggested that HE and HU participants had similar development. Developmental differences may, however, only emerge with age, therefore large-scale longitudinal research is recommended. It is suggested that the entire sample was vulnerable, highlighting the importance of developmental surveillance in low-income contexts, irrespective of HIV and antiretroviral exposure status

    Elephant (Loxodonta africana) Home Ranges in Sabi Sand Reserve and Kruger National Park: A Five-Year Satellite Tracking Study

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    During a five-year GPS satellite tracking study in Sabi Sand Reserve (SSR) and Kruger National Park (KNP) we monitored the daily movements of an elephant cow (Loxodonta africana) from September 2003 to August 2008. The study animal was confirmed to be part of a group of seven elephants therefore her position is representative of the matriarchal group. We found that the study animal did not use habitat randomly and confirmed strong seasonal fidelity to its summer and winter five-year home ranges. The cow's summer home range was in KNP in an area more than four times that of her SSR winter home range. She exhibited clear park habitation with up to three visits per year travelling via a well-defined northern or southern corridor. There was a positive correlation between the daily distance the elephant walked and minimum daily temperature and the elephant was significantly closer to rivers and artificial waterholes than would be expected if it were moving randomly in KNP and SSR. Transect lines established through the home ranges were surveyed to further understand the fine scale of the landscape and vegetation representative of the home ranges

    Evaluation of the brain-penetrant microtubule-stabilizing agent, dictyostatin, in the PS19 tau transgenic mouse model of tauopathy

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    Neurodegenerative disorders referred to as tauopathies, which includes Alzheimer's disease (AD), are characterized by insoluble deposits of the tau protein within neuron cell bodies and dendritic processes in the brain. Tau is normally associated with microtubules (MTs) in axons, where it provides MT stabilization and may modulate axonal transport. However, tau becomes hyperphosphorylated and dissociates from MTs in tauopathies, with evidence of reduced MT stability and defective axonal transport. This has led to the hypothesis that MT-stabilizing drugs may have potential for the treatment of tauopathies. Prior studies demonstrated that the brain-penetrant MT-stabilizing drug, epothilone D, had salutary effects in transgenic (Tg) mouse models of tauopathy, improving MT density and axonal transport, while reducing axonal dystrophy. Moreover, epothilone D enhanced cognitive performance and decreased hippocampal neuron loss, with evidence of reduced tau pathology. To date, epothilone D has been the only non-peptide small molecule MT-stabilizing agent to be evaluated in Tg tau mice. Herein, we demonstrate the efficacy of another small molecule brain-penetrant MT-stabilizing agent, dictyostatin, in the PS19 tau Tg mouse model. Although dictyostatin was poorly tolerated at once-weekly doses of 1 mg/kg or 0.3 mg/kg, likely due to gastrointestinal (GI) complications, a dictyostatin dose of 0.1 mg/kg was better tolerated, such that the majority of 6-month old PS19 mice, which harbor a moderate level of brain tau pathology, completed a 3-month dosing study without evidence of significant body weight loss. Importantly, as previously observed with epothilone D, the dictyostatin-treated PS19 mice displayed improved MT density and reduced axonal dystrophy, with a reduction of tau pathology and a trend toward increased hippocampal neuron survival relative to vehicle-treated PS19 mice. Thus, despite evidence of dose-limiting peripheral side effects, the observed positive brain outcomes in dictyostatin-treated aged PS19 mice reinforces the concept that MT-stabilizing compounds have significant potential for the treatment of tauopathies

    Towards a Rosetta Stone for translating data between information systems

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    This article was accepted for publication in the journal, Business Information Review [Sage Publications / ยฉ The Authors]. The definitive version is available at: http://dx.doi.org/10.1177/0266382115616235Information systems are an important organizational asset and offer numerous benefits. However, organizations face continued challenges when upgrading ageing information systems, and the data contained within, to newer platforms. This article explores, through conversations with information systems professionals in four organizations, the potential development of a โ€˜Rosetta Stoneโ€™, which can translate data between systems and be used to help overcome various challenges associated with their modernization. Despitemixed feedback regarding theRosetta Stone concept from interviewees, solutions highlighted in literature combinedwith participant feedback presented theories for its development, primarily as a tool to enable meaningful interpretation of data, rather than direct translation. The conclusion reflects on data collected to recommend a framework for how the tool might be developed and has the potential to be of significant interest to practitioners, open-source communities and organizations

    Molecular signatures of in vitro drug response in lung cancer

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    Poster Presentations - Molecular Classification of Tumors and Novel Biomarkers: abstract no. 5589This journal suppl. entitled : Proceedings: AACR 104th Annual Meeting 2013 ...We are developing in vitro drug response signatures based on profiling of mRNA (Illumina WG6-V3 arrays), DNA mutation (COSMIC and deep sequencing), DNA copy number (Illumina Human1M-Duov3 SNP array) and DNA methylation (Illumina HumanMethylation450) from lung cancer cell lines to predict which drugs a patient's tumor is most likely to respond to. We have generated drug response phenotypes (MTS colorimetric assays) for 25 standard, targeted, and new chemotherapy agents and combinations for 100 ...postprin

    Expression profiling of laser-microdissected intrapulmonary arteries in hypoxia-induced pulmonary hypertension

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    BACKGROUND: Chronic hypoxia influences gene expression in the lung resulting in pulmonary hypertension and vascular remodelling. For specific investigation of the vascular compartment, laser-microdissection of intrapulmonary arteries was combined with array profiling. METHODS AND RESULTS: Analysis was performed on mice subjected to 1, 7 and 21 days of hypoxia (FiO(2 )= 0.1) using nylon filters (1176 spots). Changes in the expression of 29, 38, and 42 genes were observed at day 1, 7, and 21, respectively. Genes were grouped into 5 different classes based on their time course of response. Gene regulation obtained by array analysis was confirmed by real-time PCR. Additionally, the expression of the growth mediators PDGF-B, TGF-ฮฒ, TSP-1, SRF, FGF-2, TIE-2 receptor, and VEGF-R1 were determined by real-time PCR. At day 1, transcription modulators and ion-related proteins were predominantly regulated. However, at day 7 and 21 differential expression of matrix producing and degrading genes was observed, indicating ongoing structural alterations. Among the 21 genes upregulated at day 1, 15 genes were identified carrying potential hypoxia response elements (HREs) for hypoxia-induced transcription factors. Three differentially expressed genes (S100A4, CD36 and FKBP1a) were examined by immunohistochemistry confirming the regulation on protein level. While FKBP1a was restricted to the vessel adventitia, S100A4 and CD36 were localised in the vascular tunica media. CONCLUSION: Laser-microdissection and array profiling has revealed several new genes involved in lung vascular remodelling in response to hypoxia. Immunohistochemistry confirmed regulation of three proteins and specified their localisation in vascular smooth muscle cells and fibroblasts indicating involvement of different cells types in the remodelling process. The approach allows deeper insight into hypoxic regulatory pathways specifically in the vascular compartment of this complex organ

    Challenge of Pigs with Classical Swine Fever Viruses after C-Strain Vaccination Reveals Remarkably Rapid Protection and Insights into Early Immunity

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    Pre-emptive culling is becoming increasingly questioned as a means of controlling animal diseases, including classical swine fever (CSF). This has prompted discussions on the use of emergency vaccination to control future CSF outbreaks in domestic pigs. Despite a long history of safe use in endemic areas, there is a paucity of data on aspects important to emergency strategies, such as how rapidly CSFV vaccines would protect against transmission, and if this protection is equivalent for all viral genotypes, including highly divergent genotype 3 strains. To evaluate these questions, pigs were vaccinated with the Riemserยฎ C-strain vaccine at 1, 3 and 5 days prior to challenge with genotype 2.1 and 3.3 challenge strains. The vaccine provided equivalent protection against clinical disease caused by for the two challenge strains and, as expected, protection was complete at 5 days post-vaccination. Substantial protection was achieved after 3 days, which was sufficient to prevent transmission of the 3.3 strain to animals in direct contact. Even by one day post-vaccination approximately half the animals were partially protected, and were able to control the infection, indicating that a reduction of the infectious potential is achieved very rapidly after vaccination. There was a close temporal correlation between T cell IFN-ฮณ responses and protection. Interestingly, compared to responses of animals challenged 5 days after vaccination, challenge of animals 3 or 1 days post-vaccination resulted in impaired vaccine-induced T cell responses. This, together with the failure to detect a T cell IFN-ฮณ response in unprotected and unvaccinated animals, indicates that virulent CSFV can inhibit the potent antiviral host defences primed by C-strain in the early period post vaccination
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