Body, ambient and felt temperature: An attempt to resolve a human and mice dilemma.

Mice thermoneutral zone lies at temperatures much higher than expected when considering the geographical extension of the species. Growing evidence shows that mouse-dependent thermogenesis experimentation needs to cope with temperatures below those at which the animals are most comfortable. The associated physiological changes interfere with experimental results, thereby highlighting the apparently trivial subject of room-temperature. Working at above 25 °C is difficult for researchers and animal care technicians. Herein, we explore alternative solutions related to living habits of wild mice that could improve translation of research on mice to humans. Standard murine environments are often colder than those in laboratory facilities and their behavior is mainly characterized by a gregarious, nesting and exploratory way of life. Optimization of their thermal environment can thus also be achieved by avoiding individual housing and providing high-quality nesting material and devices that would allow locomotor activity, hence muscle thermogenesis. These options have additional relevance in terms of animal welfare. When precise monitoring of the temperature is required, temperature-controlled cabinets can be used for the duration of the experiments. During the manipulation of mice, a heated laminar flow hood or tray could create an optimized microenvironment. The specification of temperature-related data in publications should contain information on the translatability of the described mouse models to humans. Furthermore, publications should describe the premises of the laboratory in relation to housing possibilities and murine behavior.

Creation and use of organoids in biomedical research and healthcare: the bioethical and metabioethical issues.

In the field of bioethics, scientific articles have already been published, and have highlighted relatively pluralist reflections concerning the creation and use of organoids. This plurality, rather than simply reflecting the complexity of the subject, may also be a consequence of the multiple theoretical and practical frameworks applied. Moreover, the creation and use of organoids in biomedical research and healthcare is probably in its infancy. This phenomenon is likely to increase in amplitude. Bioethics may be able to provide it with an effective and pertinent moral meaning, provided that a veritable metabioethical reflection is developed in parallel, that is, a reflection on bioethics itself, to provide scientists and clinicians with the best possible assistance in their everyday practice.

Assessment of ocular discomfort caused by 5 shampoos using the Slug Mucosal Irritation test.

Assessment of ocular discomfort caused by veterinary care products is less legitimately regulated than that caused by human care products. The Slug Mucosal Irritation (SMI) assay was adapted to evaluate canine hygiene shampoos to predict ocular discomfort. Experiments were performed using four commercial canine shampoos, a baby care product, and two controls (ArtTear® and BAC1%). Groups of 3 slugs were tested with 5% dilution of the 7 test substances. The negative control (ArtTear®) was the best tolerated. The baby care product Mixa bébé as well as Douxo Entretien Démêlant and Phlox Shampooing Entretien were classified to cause mild ocular discomfort. Together with the positive control (BAC 1%), Shampooing Physiologique Virbac and Physiovet Shampooing were considered to cause severe ocular discomfort. Different intensities of ocular discomfort were measured for veterinary care products. The SMI model was considered as a reproducible and adaptable evaluation method for screening veterinary care products causing ocular discomfort.

Canine atopic dermatitis diagnostic criteria: evaluation of four sets of published criteria among veterinary students.

Canine atopic dermatitis (cAD) is a major teaching point as its diagnosis and treatment are difficult. During 11 weeks, 140 dogs and students (third, fourth, and fifth years) were recruited and paired. One of the four lists of diagnostic criteria was randomly attributed to each student. Concordance results, calculated with Cohen's kappa, ranged from slight (κ=0.07) to moderate (κ=0.53). Favrot's diagnostic criteria received the best results. It has been observed that results are improved with clinical experience. We observed that students often forgot that Favrot's criteria apply only to pruritic dogs and that the fulfillment of the criteria allows only a suspicion, not a diagnosis, of cAD. Primary pruritus and corticosteroid-responsive pruritus were often misunderstood.

Skin fragility syndrome in a cat with multicentric follicular lymphoma.

An 11-year-old, spayed female domestic shorthair cat was presented for a right flank wound. On clinical examination, a single non-painful skin tear lesion with irregular edges was detected. During the examination, star-shaped cigarette paper-like skin lesions appeared spontaneously. An abdominal mass was also palpated. Feline skin fragility syndrome (FSFS) was suspected and a multicentric lymphoma was diagnosed by fine needle aspiration. The cat's condition declined and it died spontaneously. Post-mortem examination confirmed the diagnosis of lymphoma. Neoplastic lymphocytes were not observed in the skin. Histological analysis of the skin was consistent with the morphological aspects of FSFS. A possible direct link between the two conditions remains a matter of speculation, but this case report provides the first description of FSFS associated with multicentric follicular lymphoma. Thus, multicentric follicular lymphoma should be considered as a differential diagnosis in cats presenting with FSFS.

Establishment of diagnostic criteria for feline nonflea-induced hypersensitivity dermatitis.

Hypersensitivity dermatitides (HD) are commonly seen in cats, and they are usually caused by environmental, food and/or flea allergens. Affected cats normally present with one of the following clinical reaction patterns: head and neck excoriations, usually symmetrical self-induced alopecia, eosinophilic skin lesions or miliary dermatitis. Importantly, none of these clinical presentations is considered to be pathognomonic for HD skin diseases, and the diagnosis of HD is usually based on the exclusion of other pruritic diseases and on a positive response to therapy. The objectives of this study were to propose sets of criteria for the diagnosis of nonflea-induced HD (NFHD). We recruited 501 cats with pruritus and skin lesions and compared clinical parameters between cats with NFHD (encompassing those with nonflea, nonfood HD and those with food HD), flea HD and other pruritic conditions. Using simulated annealing techniques, we established two sets of proposed criteria for the following two different clinical situations: (i) the diagnosis of NFHD in a population of pruritic cats; and (ii) the diagnosis of NFHD after exclusion of cats with flea HD. These criteria sets were associated with good sensitivity and specificity and may be useful for homogeneity of enrolment in clinical trials and to evaluate the probability of diagnosis of NFHD in clinical practice. Finally, these criteria were not useful to differentiate cats with NFHD from those with food HD.

Masitinib decreases signs of canine atopic dermatitis: a multicentre, randomized, double-blind, placebo-controlled phase 3 trial.

This study investigated the efficacy and safety of masitinib, a selective tyrosine kinase inhibitor capable of downregulating mast cell functions, for treatment of canine atopic dermatitis (CAD). Dogs with confirmed CAD received masitinib at 12.5 mg/kg/day (n = 202) or control (n = 104) for 12 weeks. A reduction in CAD Extent and Severity Index (CADESI-02) score of ≥ 50% at week 12 was observed in 61% of masitinib-treated dogs versus 35% of control dogs (P < 0.001), according to the modified intent-to-treat population. For dogs resistant to ciclosporin and/or corticosteroids (60% of the study population), CADESI-02 response rates were 60 versus 31%, respectively (P = 0.004). The mean reduction in pruritus score of severely pruritic dogs was 46 versus 29%, respectively (P = 0.045). Furthermore, 65% of owners with severely pruritic dogs assessed masitinib efficacy as good/excellent versus 35% control (P = 0.05). Overall, 63% of investigators assessed masitinib efficacy as good/excellent versus 35% control (P < 0.001). Premature discontinuations from the modified intent-to-treat population (28.2% masitinib versus 26.0% control) were mainly due to adverse events (13.4 versus 4.8%, respectively) or lack of efficacy (12.4 versus 18.3%, respectively). In total, 13.2% dogs presented with severe adverse events (16.0% masitinib versus 7.7% control). Masitinib showed a risk of reversible protein loss, although regular surveillance of blood albumin and proteinuria allowed for discontinuation of treatment while the dog was still clinically asymptomatic. Masitinib proved to be an effective and mostly well-tolerated treatment of CAD, including severe and refractory cases, with medically manageable adverse effects.

Clinical characteristics and causes of pruritus in cats: a multicentre study on feline hypersensitivity-associated dermatoses.

Hypersensitivity dermatitides (HD) are often suspected in cats. Cats with HD are reported to present with one or more of the following patterns: miliary dermatitis, eosinophilic dermatitis, self-induced symmetrical alopecia or head and/or neck excoriations. Previous reports on feline HD included small numbers of animals, took place in geographically restricted areas or did not compare these conditions with other causes of pruritus. The goal of the present study was to analyse 72 parameters covering signalment, clinical, laboratory and treatment characteristics from a large group of pruritic cats from different geographical areas. Of the 502 cats, the following diagnoses were made: flea HD (29% of cases), food HD (12%) nonflea/nonfood HD (20%) and other diseases in which pruritus was a feature (24%). Cats with signs consistent with a HD but which did not complete a food trial were not analysed further (15% of cases). Most cats with nonflea HD exhibited signs compatible with one or more of the four typical lesional patterns, but none of these patterns was found to be pathognomonic for any specific diagnosis. Food HD and nonflea/nonfood HD were found to be clinically undistinguishable. Young adult, purebred and female cats appeared predisposed to nonflea/nonfood HD. As many diagnoses presented with similar lesional patterns, a thorough clinical work-up is required for establishment of a specific diagnosis.

The Trw type IV secretion system of Bartonella mediates host-specific adhesion to erythrocytes.

Bacterial pathogens typically infect only a limited range of hosts; however, the genetic mechanisms governing host-specificity are poorly understood. The alpha-proteobacterial genus Bartonella comprises 21 species that cause host-specific intraerythrocytic bacteremia as hallmark of infection in their respective mammalian reservoirs, including the human-specific pathogens Bartonella quintana and Bartonella bacilliformis that cause trench fever and Oroya fever, respectively. Here, we have identified bacterial factors that mediate host-specific erythrocyte colonization in the mammalian reservoirs. Using mouse-specific Bartonella birtlesii, human-specific Bartonella quintana, cat-specific Bartonella henselae and rat-specific Bartonella tribocorum, we established in vitro adhesion and invasion assays with isolated erythrocytes that fully reproduce the host-specificity of erythrocyte infection as observed in vivo. By signature-tagged mutagenesis of B. birtlesii and mutant selection in a mouse infection model we identified mutants impaired in establishing intraerythrocytic bacteremia. Among 45 abacteremic mutants, five failed to adhere to and invade mouse erythrocytes in vitro. The corresponding genes encode components of the type IV secretion system (T4SS) Trw, demonstrating that this virulence factor laterally acquired by the Bartonella lineage is directly involved in adherence to erythrocytes. Strikingly, ectopic expression of Trw of rat-specific B. tribocorum in cat-specific B. henselae or human-specific B. quintana expanded their host range for erythrocyte infection to rat, demonstrating that Trw mediates host-specific erythrocyte infection. A molecular evolutionary analysis of the trw locus further indicated that the variable, surface-located TrwL and TrwJ might represent the T4SS components that determine host-specificity of erythrocyte parasitism. In conclusion, we show that the laterally acquired Trw T4SS diversified in the Bartonella lineage to facilitate host-restricted adhesion to erythrocytes in a wide range of mammals.