High-Risk Cervical Human Papillomavirus Infections among Human Immunodeficiency Virus-Positive Women in the Bahamas

Background\ud \ud High-risk (HR) HPV genotypes other than 16 and 18 have been detected in a significant proportion of immunocompromised females. We aim to evaluate the frequency of HR HPV genotypes in a population of HIV-positive Caribbean women.\ud Methods\ud \ud One hundred sixty-seven consecutive, non-pregnant, HIV-positive females ≥18 years were recruited in this study. Each participant received a vaginal examination, PAP smear, and completed a questionnaire. DNA was extracted for HPV testing in 86 patients.\ud Results\ud \ud Mean age was 39.1 years for women positive for HR HPV and 43.1 years for women negative for HR HPV (P value = 0.040). 78% (130/167) of the women had HR HPV infections; the prevalence of abnormal cervical cytology was 38% among women who were HR HPV-positive compared to women who were HR HPV-negative (22%). Fifty-one percent of the 86 women with available genotype carried infections with HPV 16 and/or HPV 18; genotypes of unknown risk were also frequently observed. Women who had a CD4+ count of ≤200 had 7 times increased odds of carrying HR HPV infection in comparison to women with CD4+>200.\ud Conclusions\ud \ud HR HPV infections in HIV infected females may consist of more than just HPV 16 and 18, but also HPV 52 and 58. Further studies are needed to determine whether HPV 52 and 58 play a significant role in the development of cervical cytological abnormalities in HIV+ women

Efficacy and safety of a multifactor intervention to improve therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): protocol for the ICEPOC study

<p>Abstract</p> <p>Background</p> <p>Low therapeutic adherence to medication is very common. Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment. The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is extremely poor according to most studies. The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence. Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients.</p> <p>Methods/Design</p> <p>A randomized controlled clinical trial with 140 COPD diagnosed patients selected by a non-probabilistic method of sampling. Subjects will be randomly allocated into two groups, using the block randomization technique. Every patient in each group will be visited four times during the year of the study. Intervention: Motivational aspects related to adherence (beliefs and behaviour): group and individual interviews; cognitive aspects: information about illness; skills: inhaled technique training. Reinforcement of the cognitive-emotional aspects and inhaled technique training will be carried out in all visits of the intervention group.</p> <p>Discussion</p> <p>Adherence to a prescribed treatment involves a behavioural change. Cognitive, emotional and motivational aspects influence this change and so we consider the best intervention procedure to improve adherence would be a cognitive and emotional strategy which could be applied in daily clinical practice. Our hypothesis is that the application of a multifactor intervention (COPD information, dose reminders and reinforcing audiovisual material, motivational aspects and inhalation technique training) to COPD patients taking inhaled treatment will give a 25% increase in the number of patients showing therapeutic adherence in this group compared to the control group.</p> <p>We will evaluate the effectiveness of this multifactor intervention on patient adherence to inhaled drugs considering that it will be right and feasible to the clinical practice context.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISCTN18841601">ISCTN18841601</a></p

Cognitive Performance and Heart Rate Variability: The Influence of Fitness Level

In the present study, we investigated the relation between cognitive performance and heart rate variability as a function of fitness level. We measured the effect of three cognitive tasks (the psychomotor vigilance task, a temporal orienting task, and a duration discrimination task) on the heart rate variability of two groups of participants: a high-fit group and a low-fit group. Two major novel findings emerged from this study. First, the lowest values of heart rate variability were found during performance of the duration discrimination task, compared to the other two tasks. Second, the results showed a decrement in heart rate variability as a function of the time on task, although only in the low-fit group. Moreover, the high-fit group showed overall faster reaction times than the low-fit group in the psychomotor vigilance task, while there were not significant differences in performance between the two groups of participants in the other two cognitive tasks. In sum, our results highlighted the influence of cognitive processing on heart rate variability. Importantly, both behavioral and physiological results suggested that the main benefit obtained as a result of fitness level appeared to be associated with processes involving sustained attention.This research was supported by the Spanish Ministerio de Educación y Cultura with a predoctoral grant (FPU-AP2010-3630) to the first author, Spanish grants SEJ2007-63645 from the Junta de Andalucía to Daniel Sanabria, Mikel Zabala and Esther Morales, and the CSD2008-00048 CONSOLIDER INGENIO (Dirección General de Investigación) to Daniel Sanabria

Mechanism of PP2A-mediated IKKβ dephosphorylation: a systems biological approach

BACKGROUND: Biological effects of nuclear factor-kappaB (NF kappaB) can differ tremendously depending on the cellular context. For example, NF kappaB induced by interleukin-1 (IL-1) is converted from an inhibitor of death receptor induced apoptosis into a promoter of ultraviolet-B radiation (UVB)-induced apoptosis. This conversion requires prolonged NF kappaB activation and is facilitated by IL-1 + UVB-induced abrogation of the negative feedback loop for NF kappaB, involving a lack of inhibitor of kappaB (I kappaB alpha) protein reappearance. Permanent activation of the upstream kinase IKK beta results from UVB-induced inhibition of the catalytic subunit of Ser-Thr phosphatase PP2A (PP2Ac), leading to immediate phosphorylation and degradation of newly synthesized I kappaB alpha. RESULTS: To investigate the mechanism underlying the general PP2A-mediated tuning of IKK beta phosphorylation upon IL-1 stimulation, we have developed a strictly reduced mathematical model based on ordinary differential equations which includes the essential processes concerning the IL-1 receptor, IKK beta and PP2A. Combining experimental and modelling approaches we demonstrate that constitutively active, but not post-stimulation activated PP2A, tunes out IKK beta phosphorylation thus allowing for I kappaB alpha resynthesis in response to IL-1. Identifiability analysis and determination of confidence intervals reveal that the model allows reliable predictions regarding the dynamics of PP2A deactivation and IKK beta phosphorylation. Additionally, scenario analysis is used to scrutinize several hypotheses regarding the mode of UVB-induced PP2Ac inhibition. The model suggests that down regulation of PP2Ac activity, which results in prevention of I kappaB alpha reappearance, is not a direct UVB action but requires instrumentality. CONCLUSION: The model developed here can be used as a reliable building block of larger NF kappa B models and offers comprehensive simplification potential for future modeling of NF kappa B signaling. It gives more insight into the newly discovered mechanisms for IKK deactivation and allows for substantiated predictions and investigation of different hypotheses. The evidence of constitutive activity of PP2Ac at the IKK complex provides new insights into the feedback regulation of NF kappa B, which is crucial for the development of new anti-cancer strategies

Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study

Background Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy. Methods A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. Results The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 – 57.7) for those that were HC2 positive and had a viral load of ≤ 181.1 RLU (the median HPV viral load), and 33.8 (95% CI 6.4 – 178.9) for those that were HC2 positive with a HPV viral load > 181.1 RLU. Conclusion Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer

Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer

<p>Abstract</p> <p>Background</p> <p>Mutational analysis of the <it>KRAS </it>gene has recently been established as a complementary <it>in vitro </it>diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of <it>KRAS </it>might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although <it>KRAS </it>is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of <it>KRAS </it>in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies.</p> <p>Methods</p> <p>Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. <it>KRAS </it>mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type <it>KRAS </it>or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp.</p> <p>Results</p> <p>We found no evidence of <it>KRAS </it>oncogenic mutations in all analyzed tumors.</p> <p>Conclusions</p> <p>This study indicates that <it>KRAS </it>mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases.</p

Despotism and Risk of Infanticide Influence Grizzly Bear Den-Site Selection

Given documented social dominance and intraspecific predation in bear populations, the ideal despotic distribution model and sex hypothesis of sexual segregation predict adult female grizzly bears (Ursus arctos) will avoid areas occupied by adult males to reduce risk of infanticide. Under ideal despotic distribution, juveniles should similarly avoid adult males to reduce predation risk. Den-site selection and use is an important component of grizzly bear ecology and may be influenced by multiple factors, including risk from conspecifics. To test the role of predation risk and the sex hypothesis of sexual segregation, we compared adult female (n = 142), adult male (n = 36), and juvenile (n = 35) den locations in Denali National Park and Preserve, Alaska, USA. We measured elevation, aspect, slope, and dominant land cover for each den site, and used maximum entropy modeling to determine which variables best predicted den sites. We identified the global model as the best-fitting model for adult female (area under curve (AUC) = 0.926) and elevation as the best predictive variable for adult male (AUC = 0.880) den sites. The model containing land cover and elevation best-predicted juvenile (AUC = 0.841) den sites. Adult females spatially segregated from adult males, with dens characterized by higher elevations ( = 1,412 m, SE = 52) and steeper slopes ( = 21.9°, SE = 1.1) than adult male (elevation:  = 1,209 m, SE = 76; slope:  = 15.6°, SE = 1.9) den sites. Juveniles used a broad range of landscape attributes but did not avoid adult male denning areas. Observed spatial segregation by adult females supports the sex hypothesis of sexual segregation and we suggest is a mechanism to reduce risk of infanticide. Den site selection of adult males is likely related to distribution of food resources during spring

Fungal Planet description sheets : 951–1041

Novel species of fungi described in this study include those from various countries as follows: Antarctica,Apenidiella antarctica from permafrost, Cladosporium fildesense from an unidentified marine sponge. Argentina,Geastrum wrightii on humus in mixed forest. Australia, Golovinomyces glandulariae on Glandularia aristigera,Neoanungitea eucalyptorum on leaves of Eucalyptus grandis, Teratosphaeria corymbiicola on leaves of Corymbiaficifolia, Xylaria eucalypti on leaves of Eucalyptus radiata. Brazil, Bovista psammophila on soil, Fusarium awaxy onrotten stalks of Zea mays, Geastrum lanuginosum on leaf litter covered soil, Hermetothecium mikaniae-micranthae(incl. Hermetothecium gen. nov.) on Mikania micrantha, Penicillium reconvexovelosoi in soil, Stagonosporopsis vannacciifrom pod of Glycine max. British Virgin Isles, Lactifluus guanensis on soil. Canada, Sorocybe oblongisporaon resin of Picea rubens. Chile, Colletotrichum roseum on leaves of Lapageria rosea. China, Setophoma cavernafrom carbonatite in Karst cave. Colombia, Lareunionomyces eucalypticola on leaves of Eucalyptus grandis. CostaRica, Psathyrella pivae on wood. Cyprus, Clavulina iris on calcareous substrate. France, Chromosera ambiguaand Clavulina iris var. occidentalis on soil. French West Indies, Helminthosphaeria hispidissima on dead wood.Guatemala, Talaromyces guatemalensis in soil. Malaysia, Neotracylla pini (incl. Tracyllales ord. nov. and Neotracyllagen. nov.) and Vermiculariopsiella pini on needles of Pinus tecunumanii. New Zealand, Neoconiothyriumviticola on stems of Vitis vinifera, Parafenestella pittospori on Pittosporum tenuifolium, Pilidium novae-zelandiaeon Phoenix sp. Pakistan, Russula quercus-floribundae on forest floor. Portugal, Trichoderma aestuarinum fromsaline water. Russia, Pluteus liliputianus on fallen branch of deciduous tree, Pluteus spurius on decaying deciduous wood or soil. South Africa, Alloconiothyrium encephalarti, Phyllosticta encephalarticola and Neothyrostromaencephalarti (incl. Neothyrostroma gen. nov.) on leaves of Encephalartos sp., Chalara eucalypticola on leaf spots ofEucalyptus grandis x urophylla, Clypeosphaeria oleae on leaves of Olea capensis, Cylindrocladiella postalofficiumon leaf litter of Sideroxylon inerme, Cylindromonium eugeniicola (incl. Cylindromonium gen. nov.) on leaf litter ofEugenia capensis, Cyphellophora goniomatis on leaves of Gonioma kamassi, Nothodactylaria nephrolepidis (incl.Nothodactylaria gen. nov. and Nothodactylariaceae fam. nov.) on leaves of Nephrolepis exaltata, Falcocladiumeucalypti and Gyrothrix eucalypti on leaves of Eucalyptus sp., Gyrothrix oleae on leaves of Olea capensis subsp.macrocarpa, Harzia metro-sideri on leaf litter of Metrosideros sp., Hippopotamyces phragmitis (incl. Hippopotamycesgen. nov.) on leaves of Phragmites australis, Lectera philenopterae on Philenoptera violacea, Leptosilliamayteni on leaves of Maytenus heterophylla, Lithohypha aloicola and Neoplatysporoides aloes on leaves of Aloesp., Millesimomyces rhoicissi (incl. Millesimomyces gen. nov.) on leaves of Rhoicissus digitata, Neodevriesiastrelitziicola on leaf litter of Strelitzia nicolai, Neokirramyces syzygii (incl. Neokirramyces gen. nov.) on leaf spots of Syzygium sp., Nothoramichloridium perseae (incl. Nothoramichloridium gen. nov. and Anungitiomycetaceae fam.nov.) on leaves of Persea americana, Paramycosphaerella watsoniae on leaf spots of Watsonia sp., Penicilliumcuddlyae from dog food, Podocarpomyces knysnanus (incl. Podocarpomyces gen. nov.) on leaves of Podocarpusfalcatus, Pseudocercospora heteropyxidicola on leaf spots of Heteropyxis natalensis, Pseudopenidiella podocarpi,Scolecobasidium podocarpi and Ceramothyrium podocarpicola on leaves of Podocarpus latifolius, Scolecobasidiumblechni on leaves of Blechnum capense, Stomiopeltis syzygii on leaves of Syzygium chordatum, Strelitziomycesknysnanus (incl. Strelitziomyces gen. nov.) on leaves of Strelitzia alba, Talaromyces clemensii from rotting wood ingoldmine, Verrucocladosporium visseri on Carpobrotus edulis. Spain, Boletopsis mediterraneensis on soil, Calycinacortegadensisi on a living twig of Castanea sativa, Emmonsiellopsis tuberculata in fluvial sediments, Mollisia cortegadensison dead attached twig of Quercus robur, Psathyrella ovispora on soil, Pseudobeltrania lauri on leaf litterof Laurus azorica, Terfezia dunensis in soil, Tuber lucentum in soil, Venturia submersa on submerged plant debris.Thailand, Cordyceps jakajanicola on cicada nymph, Cordyceps kuiburiensis on spider, Distoseptispora caricis onleaves of Carex sp., Ophiocordyceps khonkaenensis on cicada nymph. USA, Cytosporella juncicola and Davidiellomycesjuncicola on culms of Juncus effusus, Monochaetia massachusettsianum from air sample, Neohelicomycesmelaleucae and Periconia neobrittanica on leaves of Melaleuca styphelioides x lanceolata, Pseudocamarosporiumeucalypti on leaves of Eucalyptus sp., Pseudogymnoascus lindneri from sediment in a mine, Pseudogymnoascusturneri from sediment in a railroad tunnel, Pulchroboletus sclerotiorum on soil, Zygosporium pseudomasonii onleaf of Serenoa repens. Vietnam, Boletus candidissimus and Veloporphyrellus vulpinus on soil. Morphological andculture characteristics are supported by DNA barcodes

Different Domains of the RNA Polymerase of Infectious Bursal Disease Virus Contribute to Virulence

BACKGROUND: Infectious bursal disease virus (IBDV) is a pathogen of worldwide significance to the poultry industry. IBDV has a bi-segmented double-stranded RNA genome. Segments A and B encode the capsid, ribonucleoprotein and non-structural proteins, or the virus polymerase (RdRp), respectively. Since the late eighties, very virulent (vv) IBDV strains have emerged in Europe inducing up to 60% mortality. Although some progress has been made in understanding the molecular biology of IBDV, the molecular basis for the pathogenicity of vvIBDV is still not fully understood. METHODOLOGY, PRINCIPAL FINDINGS: Strain 88180 belongs to a lineage of pathogenic IBDV phylogenetically related to vvIBDV. By reverse genetics, we rescued a molecular clone (mc88180), as pathogenic as its parent strain. To study the molecular basis for 88180 pathogenicity, we constructed and characterized in vivo reassortant or mosaic recombinant viruses derived from the 88180 and the attenuated Cu-1 IBDV strains. The reassortant virus rescued from segments A of 88180 (A88) and B of Cu-1 (BCU1) was milder than mc88180 showing that segment B is involved in 88180 pathogenicity. Next, the exchange of different regions of BCU1 with their counterparts in B88 in association with A88 did not fully restore a virulence equivalent to mc88180. This demonstrated that several regions if not the whole B88 are essential for the in vivo pathogenicity of 88180. CONCLUSION, SIGNIFICANCE: The present results show that different domains of the RdRp, are essential for the in vivo pathogenicity of IBDV, independently of the replication efficiency of the mosaic viruses