Paraneoplastic leukocytosis in a dog following liposarcoma resection

A 10-year-old, female, neutered cocker spaniel presented for surgical debulking of an axillary and cranial thoracic wall liposarcoma. Pre-surgical blood analysis demonstrated anaemia (packed cell volume 17%), leukocytosis (white blood cell count 43.95 × 10 9/L) and thrombocytopenia (15 × 10 9/L), with platelet loss secondary to chronic intra-lesional haemorrhage or immune-mediated destruction, and concomitant Staphylococcus pseudintermedius urinary tract infection. A blood transfusion and antibiotics were administered before surgery. Within 48 hours after surgery, an extreme leukocytosis (white blood cell count 170 × 10 9/L), involving a severe left shift neutrophilia (95 × 10 9/L) was observed; this resolved within 10 days. Serum granulocyte-colony stimulating factor levels were similar to controls. The extreme leukocytosis was suspected to be related to a paraneoplastic leukaemoid reaction combined with an expected postoperative mild leukocytosis. Further investigation into the pathophysiology underlying similar cases is required. One month after surgery, all haematological abnormalities had normalised, and metronomic chemotherapy with chlorambucil commenced.</p

Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity

Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever

Human Complement Regulators C4b-Binding Protein and C1 Esterase Inhibitor Interact with a Novel Outer Surface Protein of Borrelia recurrentis

The spirochete Borrelia recurrentis is the causal agent of louse-borne relapsing fever and is transmitted to humans by the infected body louse Pediculus humanus. We have recently demonstrated that the B. recurrentis surface receptor, HcpA, specifically binds factor H, the regulator of the alternative pathway of complement activation, thereby inhibiting complement mediated bacteriolysis. Here, we show that B. recurrentis spirochetes express another potential outer membrane lipoprotein, termed CihC, and acquire C4b-binding protein (C4bp) and human C1 esterase inhibitor (C1-Inh), the major inhibitors of the classical and lectin pathway of complement activation. A highly homologous receptor for C4bp was also found in the African tick-borne relapsing fever spirochete B. duttonii. Upon its binding to B. recurrentis or recombinant CihC, C4bp retains its functional potential, i.e. facilitating the factor I-mediated degradation of C4b. The additional finding that ectopic expression of CihC in serum sensitive B. burgdorferi significantly increased spirochetal resistance against human complement suggests this receptor to substantially contribute, together with other known strategies, to immune evasion of B. recurrentis

Unknotting night-time muscle cramp: a survey of patient experience, help-seeking behaviour and perceived treatment effectiveness

Background: Night-time calf cramping affects approximately 1 in 3 adults. The aim of this study was to explore the experience of night-time calf cramp; if and where people seek treatment advice; and perceived treatment effectiveness. Methods: 80 adults who experienced night-time calf cramp at least once per week were recruited from the Hunter region, NSW, Australia through newspaper, radio and television advertisements. All participants completed a pilot-tested survey about muscle cramp. Quantitative data were analysed with independent-sample t-tests, Chi square tests and Fisher’s tests. Qualitative data were transcribed and sorted into categories to identify themes. Results: Median recalled age of first night-time calf cramp was 50 years. Most participants recalled being awoken from sleep by cramping, and experiencing cramping of either calf muscle, calf-muscle soreness in the days following cramp and cramping during day-time. Despite current therapies, mean usual pain intensity was 66 mm on a 100 mm visual analogue scale. Participants described their cramps as being ‘unbearable’, ‘unmanageable’ and ‘cruel’. One participant stated that ‘sometimes I just wish I could cut my legs open’ and another reported ‘getting about 2h sleep a night due to cramps’. Most participants had sought advice about their night-time calf cramps from a health professional. Participants identified 49 different interventions used to prevent night-time calf cramp. Of all treatment ratings, 68% described the intervention used to prevent cramp as being ‘useless’ or of ‘a little help’. Of 14 participants who provided additional information regarding their use of quinine, eight had a current prescription of quinine for muscle cramp at the time of the survey. None had been asked by their prescribing doctor to stop using quinine. Conclusion: Night time calf cramps typically woke sufferers from sleep, affected either leg and caused ongoing pain. Most participants experienced little or no relief with current therapies used to prevent muscle cramp. Most people who were taking quinine for muscle cramp were unaware that the Australian Therapeutic Goods Administration withdrew support of quinine for muscle cramp in 2004 due to the risk of thrombocytopaenia. Case-control studies are required to identify therapeutic targets so that clinical trials can evaluate safe interventions to prevent recurrent cramp

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Identification of novel Coxiella burnetii genotypes from Ethiopian ticks

Background: Coxiella burnetii , the etiologic agent of Q fever, is a highly infectious zoonotic bacterium. Genetic information about the strains of this worldwide distributed agent circulating on the African continent is limited. The aim of the present study was the genetic characterization of C. burnetii DNA samples detected in ticks collected from Ethiopian cattle and their comparison with other genotypes found previously in other parts of the world. Methodology/Principal Findings: A total of 296 tick samples were screened by real-time PCR targeting the IS 1111 region of C. burnetii genome and from the 32 positive samples, 8 cases with sufficient C. burnetii DNA load ( Amblyomma cohaerens ,n 5 6; A. variegatum ,n 5 2) were characterized by multispacer sequence typing (MST) and multiple-locus variable-number tandem repeat analysis (MLVA). One novel sequence type (ST), the proposed ST52, was identified by MST. The MLVA-6 discriminated the proposed ST52 into two newly identified MLVA genotypes: type 24 or AH was detected in both Amblyomma species while type 26 or AI was found only in A. cohaerens . Conclusions/Significance: Both the MST and MLVA genotypes of the present work are closely related to previously described genotypes found primarily in cattle samples from different parts of the globe. This finding is congruent with the source hosts of the analyzed Ethiopian ticks, as these were also collected from cattle. The present study provides genotype information of C. burnetii from this seldom studied East-African region as well as further evidence for the presumed host-specific adaptation of this agent

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Financing of U.S. Biomedical Research and New Drug Approvals across Therapeutic Areas

We estimated U.S. biomedical research funding across therapeutic areas, determined the association with disease burden, and evaluated new drug approvals that resulted from this investment.We calculated funding from 1995 to 2005 and totaled Food and Drug Administration approvals in eight therapeutic areas (cardiovascular, endocrine, gastrointestinal, genitourinary, HIV/AIDS, infectious disease excluding HIV, oncology, and respiratory) primarily using public data. We then calculated correlations between funding, published estimates of disease burden, and drug approvals. Financial support for biomedical research from 1995 to 2005 increased across all therapeutic areas between 43% and 369%. Industry was the principal funder of all areas except HIV/AIDS, infectious disease, and oncology, which were chiefly sponsored by the National Institutes of Health (NIH). Total (rho = 0.70; P = .03) and industry funding (rho = 0.69; P = .04) were correlated with projected disease burden in high income countries while NIH support (rho = 0.80; P = .01) was correlated with projected disease burden globally. From 1995 to 2005 the number of new approvals was flat or declined across therapeutic areas, and over an 8-year lag period, neither total nor industry funding was correlated with future approvals.Across therapeutic areas, biomedical research funding increased substantially, appears aligned with disease burden in high income countries, but is not linked to new drug approvals. The translational gap between funding and new therapies is affecting all of medicine, and remedies must include changes beyond additional financial investment

Mapping Migratory Bird Prevalence Using Remote Sensing Data Fusion

This is the publisher’s final pdf. The published article is copyrighted by the Public Library of Science and can be found at: http://www.plosone.org/home.action.Background: Improved maps of species distributions are important for effective management of wildlife under increasing anthropogenic pressures. Recent advances in lidar and radar remote sensing have shown considerable potential for mapping forest structure and habitat characteristics across landscapes. However, their relative efficacies and integrated use in habitat mapping remain largely unexplored. We evaluated the use of lidar, radar and multispectral remote sensing data in predicting multi-year bird detections or prevalence for 8 migratory songbird species in the unfragmented temperate deciduous forests of New Hampshire, USA. \ud \ud Methodology and Principal Findings: A set of 104 predictor variables describing vegetation vertical structure and variability from lidar, phenology from multispectral data and backscatter properties from radar data were derived. We tested the accuracies of these variables in predicting prevalence using Random Forests regression models. All data sets showed more than 30% predictive power with radar models having the lowest and multi-sensor synergy ("fusion") models having highest accuracies. Fusion explained between 54% and 75% variance in prevalence for all the birds considered. Stem density from discrete return lidar and phenology from multispectral data were among the best predictors. Further analysis revealed different relationships between the remote sensing metrics and bird prevalence. Spatial maps of prevalence were consistent with known habitat preferences for the bird species. \ud \ud Conclusion and Significance: Our results highlight the potential of integrating multiple remote sensing data sets using machine-learning methods to improve habitat mapping. Multi-dimensional habitat structure maps such as those generated from this study can significantly advance forest management and ecological research by facilitating fine-scale studies at both stand and landscape level