Intestinal infection with Echinococcus multilocularis in a dog.

OBJECTIVE To raise veterinary awareness of a newly recognized parasitic threat to canine and human health, highlight the increasing availability of molecular parasitological diagnostics and the need to implement best practices of cestocidal use in high-risk dogs. ANIMAL A young Boxer dog with vomiting and bloody diarrhea, suspected diagnosis of inflammatory bowel disease. CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES Bloodwork revealed inflammation, dehydration, and protein loss, addressed with supportive therapy. Fecal culture revealed only Escherichia coli. On centrifugal flotation, tapeworm eggs (which could be Taenia or Echinococcus spp) and, unusually, adult cestodes of Echinococcus were observed. The referring veterinarian was contacted to initiate immediate treatment with a cestocide due to zoonotic potential. Diagnosis was confirmed with a coproPCR which has higher sensitivity for Echinococcus spp than fecal flotation alone. DNA was identical to an introduced European strain of E multilocularis currently emerging in dogs, people, and wildlife. Since dogs can also self-infect and develop hepatic alveolar echinococcosis (severe and often fatal), this was ruled out using serology and abdominal ultrasound. TREATMENT AND OUTCOME Following cestocidal treatment, fecal flotation and coproPCR were negative for eggs and DNA of E multilocularis; however, coccidia were detected and diarrhea resolved following treatment with sulfa-based antibiotics. CLINICAL RELEVANCE This dog was serendipitously diagnosed with E multilocularis, acquired through ingestion of a rodent intermediate host likely infected from foxes and coyotes. Therefore, as a dog at high risk of reexposure from eating rodents, regular (ideally monthly) treatment with a labeled cestocide is indicated going forward

First Person Experience of Body Transfer in Virtual Reality

Background: Altering the normal association between touch and its visual correlate can result in the illusory perception of a fake limb as part of our own body. Thus, when touch is seen to be applied to a rubber hand while felt synchronously on the corresponding hidden real hand, an illusion of ownership of the rubber hand usually occurs. The illusion has also been demonstrated using visuomotor correlation between the movements of the hidden real hand and the seen fake hand. This type of paradigm has been used with respect to the whole body generating out-of-the-body and body substitution illusions. However, such studies have only ever manipulated a single factor and although they used a form of virtual reality have not exploited the power of immersive virtual reality (IVR) to produce radical transformations in body ownership.Principal Findings: Here we show that a first person perspective of a life-sized virtual human female body that appears to substitute the male subjects' own bodies was sufficient to generate a body transfer illusion. This was demonstrated subjectively by questionnaire and physiologically through heart-rate deceleration in response to a threat to the virtual body. This finding is in contrast to earlier experimental studies that assume visuotactile synchrony to be the critical contributory factor in ownership illusions. Our finding was possible because IVR allowed us to use a novel experimental design for this type of problem with three independent binary factors: (i) perspective position (first or third), (ii) synchronous or asynchronous mirror reflections and (iii) synchrony or asynchrony between felt and seen touch.Conclusions: The results support the notion that bottom-up perceptual mechanisms can temporarily override top down knowledge resulting in a radical illusion of transfer of body ownership. The research also illustrates immersive virtual reality as a powerful tool in the study of body representation and experience, since it supports experimental manipulations that would otherwise be infeasible, with the technology being mature enough to represent human bodies and their motion

Parameter instability, superexogeneity, and the monetary model of the exchange rate

C22, C32, F30, F41,

A novel bioluminescent NanoLuc yeast-estrogen screen biosensor (nanoYES) with a compact wireless camera for effect-based detection of endocrine-disrupting chemicals

The presence of chemicals with estrogenic activity in surface, groundwater, and drinking water poses serious concerns for potential threats to human health and aquatic life. At present, no sensitive portable devices are available for the rapid monitoring of such contamination. Here, we propose a cell-based mobile platform that exploits a newly developed bioluminescent yeast-estrogen screen (nanoYES) and a low-cost compact camera as light detector. Saccharomyces cerevisiae cells were genetically engineered with a yeast codon-optimized variant of NanoLuc luciferase (yNLucP) under the regulation of human estrogen receptor α activation. Ready-to-use 3D-printed cartridges with immobilized cells were prepared by optimizing a new procedure that enables to produce alginate slices with good reproducibility. A portable device was obtained exploiting a compact camera and wireless connectivity enabling a rapid and quantitative evaluation (1-h incubation at room temperature) of total estrogenic activity in small sample volumes (50 Î1⁄4L) with a LOD of 0.08 nM for 17Î2-estradiol. The developed portable analytical platform was applied for the evaluation of water samples spiked with different chemicals known to have estrogen-like activity. Thanks to the high sensitivity of the newly developed yeast biosensor and the possibility to wireless connect the camera with any smartphone model, the developed configuration is more versatile than previously reported smartphone-based devices, and could find application for on-site analysis of endocrine disruptors. [Figure not available: see fulltext.]

Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia

BACKGROUND A single-group, phase 1–2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months. RESULTS Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P=0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome. CONCLUSIONS The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects

Current preventive strategies and management of Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplantation in Europe. Results of the ESGICH Questionnaire-based Cross-sectional Survey

There is limited clinical evidence on the utility of the monitoring of Epstein-Barr virus (EBV) DNAemia in the pre-emptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programmes in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programmes from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centres (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programmes and 77.4% reported performing pre-emptive treatment for patients with significant EBV DNAemia levels. Pre-emptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to mammalian target of rapamycin inhibitors in 30.9%, and use of rituximab in 14.5% of programmes. Imaging by whole-body 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) is used in 60.9% of centres to rule out PTLD and complemented computer tomography is used in 50%. In 10.9% of centres, FDG-PET is included in the first-line diagnostic workup in patients with high-risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic workup and pre-emptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients

Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial

Background Recipients of autologous haemopoietic stem-cell transplants (auto-HSCT) have an increased risk of herpes zoster and herpes zoster-related complications. The aim of this study was to establish the efficacy and safety of an inactivated varicella zoster vaccine for the prevention of herpes zoster after auto-HSCT. Methods In this randomised, double-blind, placebo-controlled phase 3 trial, participants were recruited from 135 medical centres (ie, stem-cell transplant centres and hospitals) in North America, South America, Europe, and Asia. Patients were eligible if they were aged 18 years or older, scheduled to receive an auto-HSCT within 60 days of enrolment, and had a history of varicella infection or were seropositive for antibodies to varicella zoster virus, or both. Exclusion criteria included a history of herpes zoster within the previous year of enrolment, and intended antiviral prophylaxis for longer than 6 months after transplantation. Participants were randomly assigned according to a central randomisation schedule generated by the trial statistician, to receive either the inactivated-virus vaccine from one of three consistency lots, a high-antigen lot, or placebo, stratified by age (= 50 years) and intended duration of antiviral prophylaxis after transplantation ( 3 to <= 6 months). Participants, investigators, trial staff, and the funder's clinical and laboratory personnel were masked to group assignment. Participants were given four doses of inactivated vaccine or placebo, with the first dose 5-60 days before auto-HSCT, and the second, third, and fourth doses at about 30, 60, and 90 days after transplantation. The primary efficacy endpoint was the incidence of herpes zoster, confirmed by PCR or adjudication by a masked clinical committee, or both, assessed in all participants randomly assigned to the vaccine consistency lot group or placebo group who received at least one dose of vaccine and had auto-HSCT. Safety was assessed in all randomised participants who received at least one dose of vaccine and had follow-up data. A prespecified vaccine efficacy success criterion required the lower bound of the 95% CI be higher than 25% for the relative reduction of the hazard ratio of herpes zoster infection in participants given the vaccine from one of the consistency lots compared with those given placebo. This trial is registered on ClinicalTrials. gov (NCT01229267) and EudraCT (2010-020150-34). Findings Between Dec 7, 2010, and April 25, 2013, 560 participants were randomly assigned to the vaccine consistency lot group, 106 to the high-antigen lot group, and 564 to the placebo group. 249 (44%) of patients in the vaccine consistency lot group, 35 (33%) in the high-antigen lot group, and 220 (39%) in the placebo group discontinued before study end, mostly because of death or withdrawal. 51 participants were excluded from the primary efficacy endpoint analyses because they did not undergo auto-HSCT or were not vaccinated, or both (22 [4%] in the vaccine consistency lot group, and 29 [5%] in the placebo group). Mean follow-up for efficacy was 2 . 4 years (SD 1.3) in the vaccine consistency lot group and 2.3 years (SD 1.3) in the placebo group. 42 (8%) of 538 participants in the vaccine consistency lot group (32.9 per 1000 person-years) and 113 (21%) of 535 in the placebo group (91.9 per 1000 person-years) had a confirmed case of herpes zoster. The estimated vaccine efficacy was 63.8% (95% CI 48.4-74.6), meeting the pre-specified success criterion. For the combined vaccine groups versus the placebo group, the proportion of patients with serious adverse events (216 [33%] of 657 vs 181 [33%] of 554; risk difference 0.2%, 95% CI -5.1 to 5.5) and serious vaccine-related adverse events (five [1%] vs five [1%]; risk difference 0.1%, -1.4 to 1.1) were similar. Vaccine-related injection-site adverse events occurred more frequently in participants given vaccine than those given placebo (191 [29%] vs 36 [7%]; risk difference 22.6%, 95% CI 18.5-26.6; p<0.0001). Interpretation This study shows for the first time in a large phase 3 trial that early vaccination of auto-HSCT recipients during the peri-transplant period can be effective for the prevention of an opportunistic infection like herpes zoster and that the vaccine is well tolerated. Funding Merck & Co., Inc. Copyright (C) 2018 Elsevier Ltd. All rights reserved