The functional response of a generalist predator

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AKT1 Loss Correlates with Episomal HPV16 in Vulval Intraepithelial Neoplasia

Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV), particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma–HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma-) PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN) and vulval squamous cell carcinoma (vSCC). We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy

What is the role of imaging in acute low back pain?

In patients with non specific acute low back pain, without the red flags, a conservative approach is preferable, with assessment in 4–6 weeks. The natural history of low back pain is favorable with improvement over time, thus reassurance to such patients is very important. However, a plain radiograph or more advanced imaging techniques like MRI/CT may be ordered in back pain associated with radiculopathy or spinal stenosis and back pain associated with progressive neurologic deficits. There is limited role of imaging in non specific acute low back pain without the red flags, as the findings correlate poorly with symptoms

An investigation of intensity-modulated radiation therapy versus conventional two-dimensional and 3D-conformal radiation therapy for early stage larynx cancer

<p>Abstract</p> <p>Introduction</p> <p>Intensity modulated radiation therapy (IMRT) has been incorporated at several institutions for early stage laryngeal cancer (T1/T2N0M0), but its utility is controversial.</p> <p>Methods</p> <p>In three representative patients, multiple plans were generated: 1) Conventional 2D planning, with the posterior border placed at either the anterior aspect ("tight" plan) or the mid-vertebral body ("loose" plan), 2) 3D planning, utilizing both 1.0 and 0.5 cm margins for the planning target volume (PTV), and 3) IMRT planning, utilizing the same margins as the 3D plans. A dosimetric comparison was performed for the target volume, spinal cord, arytenoids, and carotid arteries. The prescription dose was 6300 cGy (225 cGy fractions), and the 3D and IMRT plans were normalized to this dose.</p> <p>Results</p> <p>For PTV margins of 1.0 cm and 0.5 cm, the D95 of the 2D tight/loose plans were 3781/5437 cGy and 5372/5869 cGy, respectively (IMRT/3D plans both 6300 cGy). With a PTV margin of 1.0 cm, the mean carotid artery dose was 2483/5671/5777/4049 cGy in the 2D tight, 2D loose, 3D, and IMRT plans, respectively. When the PTV was reduced to 0.5 cm, the the mean carotid artery dose was 2483/5671/6466/2577 cGy to the above four plans, respectively. The arytenoid doses were similar between the four plans, and spinal cord doses were well below tolerance.</p> <p>Conclusions</p> <p>IMRT provides a more ideal dose distribution compared to 2D treatment and 3D planning in regards to mean carotid dose. We therefore recommend IMRT in select cases when the treating physician is confident with the GTV.</p

Water dispersible microbicidal cellulose acetate phthalate film

BACKGROUND: Cellulose acetate phthalate (CAP) has been used for several decades in the pharmaceutical industry for enteric film coating of oral tablets and capsules. Micronized CAP, available commercially as "Aquateric" and containing additional ingredients required for micronization, used for tablet coating from water dispersions, was shown to adsorb and inactivate the human immunodeficiency virus (HIV-1), herpesviruses (HSV) and other sexually transmitted disease (STD) pathogens. Earlier studies indicate that a gel formulation of micronized CAP has a potential as a topical microbicide for prevention of STDs including the acquired immunodeficiency syndrome (AIDS). The objective of endeavors described here was to develop a water dispersible CAP film amenable to inexpensive industrial mass production. METHODS: CAP and hydroxypropyl cellulose (HPC) were dissolved in different organic solvent mixtures, poured into dishes, and the solvents evaporated. Graded quantities of a resulting selected film were mixed for 5 min at 37°C with HIV-1, HSV and other STD pathogens, respectively. Residual infectivity of the treated viruses and bacteria was determined. RESULTS: The prerequisites for producing CAP films which are soft, flexible and dispersible in water, resulting in smooth gels, are combining CAP with HPC (other cellulose derivatives are unsuitable), and casting from organic solvent mixtures containing ≈50 to ≈65% ethanol (EtOH). The films are ≈100 µ thick and have a textured surface with alternating protrusions and depressions revealed by scanning electron microscopy. The films, before complete conversion into a gel, rapidly inactivated HIV-1 and HSV and reduced the infectivity of non-viral STD pathogens >1,000-fold. CONCLUSIONS: Soft pliable CAP-HPC composite films can be generated by casting from organic solvent mixtures containing EtOH. The films rapidly reduce the infectivity of several STD pathogens, including HIV-1. They are converted into gels and thus do not have to be removed following application and use. In addition to their potential as topical microbicides, the films have promise for mucosal delivery of pharmaceuticals other than CAP

Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

The economic impact of alcohol consumption: a systematic review

<p>Abstract</p> <p>Background</p> <p>Information on the economic impact of alcohol consumption can provide important evidence in supporting policies to reduce its associated harm. To date, several studies on the economic costs of alcohol consumption have been conducted worldwide. This study aims to review the economic impact of alcohol worldwide, summarizing the state of knowledge with regard to two elements: (1) cost components included in the estimation; (2) the methodologies employed in works conducted to date.</p> <p>Methods</p> <p>Relevant publications concerning the societal cost of alcohol consumption published during the years 1990-2007 were identified through MEDLINE. The World Health Organization's global status report on alcohol, bibliographies and expert communications were also used to identify additional relevant studies.</p> <p>Results</p> <p>Twenty studies met the inclusion criteria for full review while an additional two studies were considered for partial review. Most studies employed the human capital approach and estimated the gross cost of alcohol consumption. Both direct and indirect costs were taken into account in all studies while intangible costs were incorporated in only a few studies. The economic burden of alcohol in the 12 selected countries was estimated to equate to 0.45 - 5.44% of Gross Domestic Product (GDP).</p> <p>Conclusion</p> <p>Discrepancies in the estimation method and cost components included in the analyses limit a direct comparison across studies. The findings, however, consistently confirmed that the economic burden of alcohol on society is substantial. Given the importance of this issue and the limitation in generalizing the findings across different settings, further well-designed research studies are warranted in specific countries to support the formulation of alcohol-related policies.</p

Evaluating the Influence of Epidemiological Parameters and Host Ecology on the Spread of Phocine Distemper Virus through Populations of Harbour Seals

Catriona Harris was supported by a grant from the UK Natural Environment Research Council. The funders had no role in study design, data collections and analysis, decision to publish, or preparation of the manuscript.Background: Outbreaks of phocine distemper virus (PDV) in Europe during 1988 and 2002 were responsible for the death of around 23,000 and 30,000 harbour seals, respectively. These epidemics, particularly the one in 2002, provided an unusual opportunity to estimate epidemic parameters for a wildlife disease. There were marked regional differences in the values of some parameters both within and between epidemics. Methodology and Principal Findings: We used an individual-based model of seal movement that allowed us to incorporate realistic representations of space, time and animal behaviour into a traditional epidemiological modelling framework. We explored the potential influence of a range of ecological (foraging trip duration, time of epidemic onset, population size) and epidemiological (length of infectious period, contact rate between infectious and susceptible individuals, case mortality) parameters on four readily-measurable epidemic characteristics (number of dead individuals, duration of epidemic, peak mortality date and prevalence) and on the probability that an epidemic would occur in a particular region. We analysed the outputs as if they were the results of a series of virtual experiments, using Generalised Linear Modelling. All six variables had a significant effect on the probability that an epidemic would be recognised as an unusual mortality event by human observers. Conclusions: Regional and temporal variation in contact rate was the most likely cause of the observed differences between the two epidemics. This variation could be a consequence of differences in the way individuals divide their time between land and sea at different times of the year.Publisher PDFPeer reviewe

ACC2 Is Expressed at High Levels Human White Adipose and Has an Isoform with a Novel N-Terminus

Acetyl-CoA carboxylases ACC1 and ACC2 catalyze the carboxylation of acetyl-CoA to malonyl-CoA, regulating fatty-acid synthesis and oxidation, and are potential targets for treatment of metabolic syndrome. Expression of ACC1 in rodent lipogenic tissues and ACC2 in rodent oxidative tissues, coupled with the predicted localization of ACC2 to the mitochondrial membrane, have suggested separate functional roles for ACC1 in lipogenesis and ACC2 in fatty acid oxidation. We find, however, that human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart. Human adipose, along with human liver, expresses more ACC2 than ACC1. Using RT-PCR, real-time PCR, and immunoprecipitation we report a novel isoform of ACC2 (ACC2.v2) that is expressed at significant levels in human adipose. The protein generated by this isoform has enzymatic activity, is endogenously expressed in adipose, and lacks the N-terminal sequence. Both ACC2 isoforms are capable of de novo lipogenesis, suggesting that ACC2, in addition to ACC1, may play a role in lipogenesis. The results demonstrate a significant difference in ACC expression between human and rodents, which may introduce difficulties for the use of rodent models for development of ACC inhibitors