Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic haematopoietic stem-cell transplantation (HSCT). In the last 3 years, there has been regulatory approval of new drugs and considerable change in clinical approaches to prophylaxis and management of GVHD. To standardise treatment approaches, the European Society for Blood and Marrow Transplantation (EBMT) has updated its clinical practice recommendations. We formed a panel of one methodologist and 22 experts in the field of GVHD management. The selection was made on the basis of their role in GVHD management in Europe and their contributions to the field, such as publications, presentations at conferences, and other research. We applied the GRADE process to ten PICO (patient, intervention, comparator, and outcome) questions: evidence was searched for by the panel and graded for each crucial outcome. In two consensus meetings, we discussed the evidence and voted on the wording and strengths of recommendations. Key updates to the recommendations include: (1) primary use of ruxolitinib in steroid-refractory acute GVHD and steroid-refractory chronic GVHD as the new standard of care, (2) use of rabbit anti-T-cell (thymocyte) globulin or post-transplantation cyclophosphamide as standard GVHD prophylaxis in peripheral blood stem-cell transplantations from unrelated donors, and (3) the addition of belumosudil to the available treatment options for steroid-refractory chronic GVHD. The EBMT proposes to use these recommendations as the basis for routine management of GVHD during allogenic HSCT. The current recommendations favour European practice and do not necessarily represent global preferences.

Rhinosinusitis is one of the most common diseases today. Among diseases requiring treatment with antibiotics, it is the fifth most common. Acute rhinosinusitis is a significant medical problem that can significantly lower quality of life and can cause a large economic impact on society. Herein, we collected and analyzed data from several published studies regarding sinusitis with the aim of creating a sinusitis model. We included data from 786 studies published between 1996 and 2016 that came up on Google, Pro Quest Central or PubMed using the following keywords (or combinations thereof): \"sinusitis\", \"rhinosinusitis\", \"experimental\", \"animal\", \"model\", \"rat\", \"rabbit\", \"guinea pig\" and \"mice\". An appropriate sinusitis model must be established using the correct animal. Thus far, sinusitis models have been published in rats, mice, and rabbits, with rabbits being the most frequently used animal. These animals are used because the anatomy and physiology of their sinuses are very similar to those of humans. While these animals can be used in surgical models, it must be noted that prolonged stress can cause them high mortality rates. Several studies have used strains of Streptococcus pneumoniae to induce rhinosinusitis; however, it has recently been shown that other pathogenic agents can be used for this purpose as well. In this review, we presented several experimental sinusitis models in rats, mice, and rabbits. We hope that by presenting these methods, researchers may be better able to design and perform more useful sinusitis studies.

There is a pressing need for new vaccines against alphaviruses, which can cause fatal encephalitis (Venezuelan equine encephalitis virus (VEEV) and others) and severe arthralgia (e.g. Chikungunya virus, CHIKV). These positive-strand RNA viruses are diverse and evolve rapidly, meaning that the sequence of any vaccine should cover multiple strains that may be quite different from any previous isolate. Here, consensus proteins were produced to represent the common physicochemical properties (PCPs) of the epitope rich, B domain of the E2 envelope protein. PCP-consensus proteins were based on multiple strains of VEEV (VEEVcon) and CHIKV (CHIKVcon) or the conserved PCPs of 24 different alphaviruses (AllAVcon). The AllAVcon was altered to include binding sites for neutralizing antibodies of both VEEV and CHIKV strains (Mosaikcon). All four designed proteins were produced solubly in E. coli and purified. They formed the β-strand core expected from experimental structures of this region of the wild type E2 proteins as indicated by circular dichroism (CD) spectra. Furthermore, the CHIKVcon protein bound to a structure dependent, CHIKV neutralizing monoclonal antibody. The AllAVcon and Mosaikcon proteins bound to polyclonal antibodies generated during natural infection with either VEEV or CHIKV, indicating they contained epitopes of both serotypes. The Mosaikcon antigen induced antibodies in rabbit sera that recognized both the VEEVcon and CHIKVcon spike proteins. These PCP-consensus antigens are promising starting points for novel, broad-spectrum alphavirus vaccines.

The welfare of all animals under human management is an area of consistent public concern, but strategies to improve welfare may vary across species. In this study, expert consensus, using a modified Delphi approach, was used to prioritise welfare issues of farmed and companion animals in the UK.
The study involved 117 experts, divided between eight species groups. Experts were recruited from a broad range of disciplines. Two rounds of online surveys were conducted using the online survey tool, and the final round was an in-person workshop with a subsection of experts (n=21). The experts agreed that welfare issues should be ranked considering three categories: (1) severity, (2) duration and (3) perceived prevalence.
A comprehensive list of welfare issues was generated for each species by discussion boards (cats, rabbits and horses) or by literature review (dogs, pigs, poultry, cattle and small ruminants). In the first online survey, the experts scored each welfare issue using the three categories (severity, duration and prevalence) on a 6-point Likert scale, where 1=never/none and 6=always/high. Lists of welfare issues were reduced to 25 per cent-59 per cent of the total number, by determining mean ranks from expert ratings. In round 2, experts were asked whether they agreed or disagreed with the rankings. In the final stage, during the workshop, the top-ranking welfare issues for animals were determined for individual animals (considering the greatest severity and duration, in the expert\'s opinion) and for perceived prevalence.
Overall, prioritised welfare issues included lack of knowledge of welfare needs, social behaviour issues, problem behaviours, inappropriate diet and environment, lack of veterinary care, consequences from breeding decisions, poor pain management, delayed euthanasia and chronic ill health. The Delphi process resulted in consensus on the most significant welfare challenges of animals in the UK and can help to guide future research and education priority decisions.

This collaborative initiative aimed to provide recommendations on the use of polyclonal antithymocyte globulin (ATG) or anti-T lymphocyte globulin (ATLG) for the prevention of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). A comprehensive review of articles released up to October, 2018 was performed as a source of scientific evidence. Fourteen clinically relevant key questions to the domains indication, administration, and post-transplant management were developed and recommendations were produced using the Delphi technique involving a Panel of 14 experts. ATG/ATLG was strongly recommended as part of myeloablative conditioning regimen prior to matched or mismatched unrelated bone marrow or peripheral blood allogeneic HSCT in malignant diseases to prevent severe acute and chronic GvHD. ATG/ATLG was also recommended prior to HLA-identical sibling peripheral HSCT with good but lesser bulk of evidence. In reduced intensity or nonmyeloablative conditioning regimens, ATG/ATLG was deemed appropriate to reduce the incidence of acute and chronic GvHD, but a higher risk of relapse should be taken into account. Recommendations regarding dose, application, and premedication were also provided as well as post-transplant infectious prophylaxis and vaccination. Overall, these recommendations can be used for a proper and safe application of polyclonal ATG/ATLG to prevent GvHD after allogeneic HSCT.

BACKGROUND: In recent years, animal models of bone infections have been used with increased frequency in order to evaluate novel diagnostic and anti-infective technologies, like antibacterial coating of bone implants or local antibiotic carrier products. Therefore, it is highly relevant to evaluate the scientific quality of existing bone infection models.
METHODS: We conducted a systematic review of 316 studies of large non-rodent animal models of bone infection (254 rabbit, 16 pig, 23 dog, 11 goat, and 12 sheep) and extracted data on study design, methodological quality, and postmortem evaluation of infection with respect to reporting and quantification of pathology and microbiology.
RESULTS: The review demonstrated a substantial lack of study-design information, which hampers reproducibility and continuation of the established work. Furthermore, the methodological study quality was found to be low, as the definition of infection, randomization, power analysis, and blinding were only seldomly reported. The use of histology increased in recent years, but a semi-quantitative scoring of the lesions was often missing, i.e. no objective quantification of outcome. Most of the studies focused on whether the inoculated bacteria were present within the bone tissue post mortem or not. However, very often the bacterial burden was not quantified. In many of the models, different antimicrobial interventions were examined and, although antimicrobial effects were commonly described, a lack of complete sterile outcome was observed in many models. On the basis of the systematic review, we established a study template providing a guideline for the standard reporting of animal models of bone infections, including details related to the animal, pathogen, infected animal, and postmortem analysis that are of crucial importance for validation of results and reproducibility.
CONCLUSIONS: As the aim of many bone infection models is to examine the effect of an intervention, the guideline emphasizes the importance of objective quantification of outcome, e.g., blinded quantitative scoring of histological findings and quantification of bacterial burden within tissue and on inserted implants. Less than 5% of the analyzed studies adhered completely to the ideal form presented in the study template.
CONCLUSIONS: Anti-infective interventions must be tested in preclinical animal models before implementation in human patients, and optimal design and validation is essential for a high translational value.

Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus sequence of all HIV-1 group M isolates (ConM). The ConM trimer displays the epitopes of most known bNAbs and several germline bNAb precursors. The crystal structure of the ConM trimer at 3.9 Å resolution resembles that of the native Env trimer and its antigenic surface displays few rare residues. The ConM trimer elicits strong NAb responses against the autologous virus in rabbits and macaques that are significantly enhanced when it is presented on ferritin nanoparticles. The dominant NAb specificity is directed against an epitope at or close to the trimer apex. Immunogens based on consensus sequences might have utility in engineering vaccines against HIV-1 and other viruses.

OBJECTIVE: Allergic rhinitis (AR) is a symptomatic disorder of the nose induced by allergen exposure, which triggers immunoglobulin E (IgE)-mediated inflammation of the nasal membranes. Allergic rhinitis is one of the most common health problems and has a major effect on the quality of life.
METHODS: In this review, we aimed to provide a consensus for experimental studies on allergic rhinitis in terms of allergic rhinitis models. For this purpose, we searched for experimental studies in the PubMed, Proquest Central, and Google electronic databases over a 20-year period from the current time (1996-2016). The literature survey was performed using keywords including \"allergic rhinitis\", \"experimental\", \"animal\", \"model\", \"rat\", \"rabbit\", \"guinea pig\", and \"mice\" alone or in various combinations. The search identified a total of 285 papers, which were included in this review.
RESULTS: It is vital to select a suitable animal for an allergic model. Rodents like rats, guinea pigs, and mice can produce allergen-specific antibodies with the use of adjuvants. Rats are cheap and the vast majority of the allergen-specific antibodies are immunoglobulin E (IgE). Still, intraperitoneal sensitization is inescapable and adjuvants are required for sensitization. Rats, mice, rabbits, and guinea pigs can be utilized for this reason.
CONCLUSIONS: This review presented allergic rhinitis models in rats, mice, guinea pigs, and rabbits. Using these methods, researchers may perform well-designed studies.

The Organisation for Economic Co-operation and Development (OECD) Test Guideline (TG) 439 is an in vitro test method of reconstructed human epidermis (RhE), which was developed for hazard identification of irritating chemicals in accordance with a primary skin irritation test using rabbits with 4-hr exposure. A regulation for quasi-drugs in Japan requires data from primary skin irritation tests using rabbits to undergo 24-hr exposure, and this is used as an evidence for 24-hr closed patch tests in humans. In this study with the same chemicals, primary skin irritation test data using rabbits undergoing 24-hr exposure and a 24-hr occlusive human patch test data were analyzed by comparing the results obtained with four test methods adopted in OECD TG 439. The performances of in vitro test methods showed a positive predictive value of 72.7-85.7% to predict the results of 24-hr primary rabbit skin irritation test knowing that its positive predictive value was 57.1% against humans only. The prediction factors of in vitro test methods were higher for the human patch test data with a sensitivity reaching 60 to 80%. Three surfactants gave false negatives in some of the RhE methods evaluated with the human patch test, but in each case, they were correctly classified as positive when evaluated at double concentration. Therefore, the approach of setting the margin to 2 was effective in eliminating false negatives. This suggests that in vitro test methods are useful for assessing skin irritation potential without animal testing for the application of quasi-drugs in Japan.

Neuropathic pain has a substantial effect on quality of life (QOL). The Japanese Society of Pain Clinicians (JSPC) has developed clinical guidelines of pharmacotherapy for neuropathic pain. These guidelines offer clarity on recommendations based on both the most recent scientific evidence and expert opinions. Understanding the concept, disease entity, and burden of neuropathic pain, as well as its screening and diagnosis are important steps before starting pharmacotherapy. As well as other guidelines, the guidelines propose several lines of pharmacotherapies in a step-wise manner. To name a few different points, our guidelines propose an extract from inflamed cutaneous tissue of rabbits inoculated with vaccinia virus, which has been found to be effective for post-herpetic neuralgia in Japan, as one of the second-line drugs. When prescribing opioid analgesics, proposed as the third-line drugs, for neuropathic pain, the guidelines recommend physicians continue evaluations on either abuse or addiction. The guidelines do not recommend concomitant use of nonsteroidal anti-inflammatory drugs and acetaminophen because of lack of clinical evidence of their efficacy. If patients do not respond well to pharmacotherapy, which is prescribed in a step-wise manner, other treatment strategies should be considered to improve patients\' activities of daily living and QOL.