Epidemiological associations between brachycephaly and upper respiratory tract disorders in dogs attending veterinary practices in England

Background: Brachycephalic dog breeds are increasingly common. Canine brachycephaly has been associated with upper respiratory tract (URT) disorders but reliable prevalence data remain lacking. Using primary-care veterinary clinical data, this study aimed to report the prevalence and breed-type risk factors for URT disorders in dogs. Results: The sampling frame included 170,812 dogs attending 96 primary-care veterinary clinics participating within the VetCompass Programme. Two hundred dogs were randomly selected from each of three extreme brachycephalic breed types (Bulldog, French Bulldog and Pug) and three common small-to medium sized breed types (moderate brachycephalic: Yorkshire Terrier and non-brachycephalic: Border Terrier and West Highland White Terrier). Information on all URT disorders recorded was extracted from individual patient records. Disorder prevalence was compared between groups using the chi-squared test or Fisher’s test, as appropriate. Risk factor analysis used multivariable logistic regression modelling. During the study, 83 (6.9 %) study dogs died. Extreme brachycephalic dogs (median longevity: 8.6 years, IQR: 2.4-10.8) were significantly younger at death than the moderate and non-brachycephalic group of dogs (median 12.7 years, IQR 11.1-15.0) (P \u3c 0.001). A higher proportion of deaths in extreme brachycephalic breed types were associated with URT disorders (4/24 deaths, 16.7 %) compared with the moderate and non-brachycephalic group (0/59 deaths, 0.0 %) (P = 0.001). The prevalence of having at least one URT disorder in the extreme brachycephalic group was higher (22.0 %, 95 % confidence interval (CI): 18.0-26.0) than in the moderate and non-brachycephalic group (9.7 %, 95 % CI: 7.1-12.3, P \u3c 0.001). The prevalence of URT disorders varied significantly by breed type: Bulldogs 19.5 %, French Bulldogs 20.0 %, Pugs 26.5 %, Border Terriers 9.0 %, West Highland White Terriers 7.0 % and Yorkshire Terriers 13.0 % (P \u3c 0.001). After accounting for the effects of age, bodyweight, sex, neutering and insurance, extreme brachycephalic dogs had 3.5 times (95 % CI: 2.4-5.0, P \u3c 0.001) the odds of at least one URT disorder compared with the moderate and non-brachycephalic group. Conclusions: In summary, this study reports that URT disorders are commonly diagnosed in Bulldog, French Bulldog, Pug, Border Terrier, WHWT and Yorkshire Terrier dogs attending primary-care veterinary practices in England. The three extreme brachycephalic breed types (Bulldog, French Bulldog and Pug) were relatively short-lived and predisposed to URT disorders compared with three other small-to-medium size breed types that are commonly owned (moderate brachycephalic Yorkshire Terrier and non-brachycephalic: Border Terrier and WHWT). Conclusions: In summary, this study reports that URT disorders are commonly diagnosed in Bulldog, French Bulldog, Pug, Border Terrier, WHWT and Yorkshire Terrier dogs attending primary-care veterinary practices in England. The three extreme brachycephalic breed types (Bulldog, French Bulldog and Pug) were relatively short-lived and predisposed to URT disorders compared with three other small-to-medium size breed types that are commonly owned (moderate brachycephalic Yorkshire Terrier and non-brachycephalic: Border Terrier and WHWT)

Self-Compassion, emotion regulation and stress among australian psychologists: Testing an emotion regulation model of self-compassion using structural equation modeling

Psychologists tend to report high levels of occupational stress, with serious implications for themselves, their clients, and the discipline as a whole. Recent research suggests that selfcompassion is a promising construct for psychologists in terms of its ability to promote psychological wellbeing and resilience to stress; however, the potential benefits of self-compassion are yet to be thoroughly explored amongst this occupational group. Additionally, while a growing body of research supports self-compassion as a key predictor of psychopathology, understanding of the processes by which self-compassion exerts effects on mental health outcomes is limited. Structural equation modelling (SEM) was used to test an emotion regulation model of self-compassion and stress among psychologists, including postgraduate trainees undertaking clinical work (n = 198). Self-compassion significantly negatively predicted emotion regulation difficulties and stress symptoms. Support was also found for our preliminary explanatory model of self-compassion, which demonstrates the mediating role of emotion regulation difficulties in the self-compassion-stress relationship. The final self-compassion model accounted for 26.2% of variance in stress symptoms. Implications of the findings and limitations of the study are discussed

Behavioral Modernity and the Cultural Transmission of Structured Information: The Semantic Axelrod Model

Cultural transmission models are coming to the fore in explaining increases in the Paleolithic toolkit richness and diversity. During the later Paleolithic, technologies increase not only in terms of diversity but also in their complexity and interdependence. As Mesoudi and O'Brien (2008) have shown, selection broadly favors social learning of information that is hierarchical and structured, and multiple studies have demonstrated that teaching within a social learning environment can increase fitness. We believe that teaching also provides the scaffolding for transmission of more complex cultural traits. Here, we introduce an extension of the Axelrod (1997} model of cultural differentiation in which traits have prerequisite relationships, and where social learning is dependent upon the ordering of those prerequisites. We examine the resulting structure of cultural repertoires as learning environments range from largely unstructured imitation, to structured teaching of necessary prerequisites, and we find that in combination with individual learning and innovation, high probabilities of teaching prerequisites leads to richer cultural repertoires. Our results point to ways in which we can build more comprehensive explanations of the archaeological record of the Paleolithic as well as other cases of technological change.Comment: 24 pages, 7 figures. Submitted to "Learning Strategies and Cultural Evolution during the Paleolithic", edited by Kenichi Aoki and Alex Mesoudi, and presented at the 79th Annual Meeting of the Society for American Archaeology, Austin TX. Revised 5/14/1

A Topical Microbicide Gel Formulation of CCR5 Antagonist Maraviroc Prevents HIV-1 Vaginal Transmission in Humanized RAG-hu Mice

For prevention of HIV infection many currently licensed anti-HIV drugs and new ones in the pipeline show potential as topically applied microbicides. While macaque models have been the gold standard for in vivo microbicide testing, they are expensive and sufficient numbers are not available. Therefore, a small animal model that facilitates rapid evaluation of potential candidates for their preliminary efficacy is urgently needed in the microbicide field. We previously demonstrated that RAG-hu humanized mouse model permits HIV-1 mucosal transmission via both vaginal and rectal routes and that oral pre-exposure chemo-prophylactic strategies could be tested in this system. Here in these proof-of-concept studies, we extended this system for topical microbicide testing using HIV-1 as the challenge virus. Maraviroc, a clinically approved CCR5 inhibitor drug for HIV treatment, was formulated as a microbicide gel at 5 mM concentration in 2.2% hydroxyl ethyl cellulose. Female RAG-hu mice were challenged vaginally with HIV-1 an hour after intravaginal application of the maraviroc gel. Our results showed that maraviroc gel treated mice were fully protected against vaginal HIV-1 challenge in contrast to placebo gel treated mice which all became infected. These findings highlight the utility of the humanized mouse models for microbicide testing and, together with the recent data from macaque studies, suggest that maraviroc is a promising candidate for future microbicide clinical trials in the field

Ethyl pyruvate reduces mortality in an endotoxin-induced severe acute lung injury mouse model

<p>Abstract</p> <p>Background</p> <p>Ethyl pyruvate (EP) was recently identified as an experimental therapeutic agent in a wide variety of model systems for inflammation-mediated tissue and cellular injury.</p> <p>Objective</p> <p>To evaluate the effect of ethyl EP on improving the survival in mice with LPS-induced acute lung injury (ALI).</p> <p>Methods</p> <p>ALI was induced by administering lipopolysaccharide (LPS) intratracheally. The mice were treated intraperitoneally (i.p.) with 100, 50 and 10 mg/kg EP immediately before intratracheal instillation of LPS, and 100 mg/kg EP was administered 0, 12, 24 and 48 hours after induction of ALI. The mortality rate was recorded and analyzed by the Kaplan-Meier method. Serum tumor necrosis factor (TNF)-α, interleukin (IL) -6 and IL-1 β were measured in bronchial alveolar lavage fluid using an enzyme-linked immunosorbent assay. High-mobility group box 1 levels were measured by Western immunoblotting.</p> <p>Results</p> <p>Treatment with EP significantly inhibited the release of HMGB1, TNF-α, IL-6 and IL-1β into bronchoalveolar lavage (BAL) fluids of ALI mice, and reduced the permeability index of the injured lung. High EP doses reduced the mortality from ALI and the permeability index (100 mg/kg and 50 mg/kg EP versus control; P < 0.0001). Early administration of high-dose EP significantly increased survival rate (0, 12 and 24 h versus control; P < 0.0001, P < 0.0001 and P = 0.01 respectively by log-rank test). There was no survival advantage when EP was initiated at 48 h.</p> <p>Conclusion</p> <p>Ethyl pyruvate improves survival and reduces the lung permeability index in mice with LPS-induced ALI.</p

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein

Enhanced self-renewal of hematopoietic stem/progenitor cells mediated by the stem cell gene Sall4

<p>Abstract</p> <p>Background</p> <p>Sall4 is a key factor for the maintenance of pluripotency and self-renewal of embryonic stem cells (ESCs). Our previous studies have shown that Sall4 is a robust stimulator for human hematopoietic stem and progenitor cell (HSC/HPC) expansion. The purpose of the current study is to further evaluate how Sall4 may affect HSC/HPC activities in a murine system.</p> <p>Methods</p> <p>Lentiviral vectors expressing Sall4A or Sall4B isoform were used to transduce mouse bone marrow Lin-/Sca1+/c-Kit+ (LSK) cells and HSC/HPC self-renewal and differentiation were evaluated.</p> <p>Results</p> <p>Forced expression of Sall4 isoforms led to sustained <it>ex vivo </it>proliferation of LSK cells. In addition, Sall4 expanded HSC/HPCs exhibited increased <it>in vivo </it>repopulating abilities after bone marrow transplantation. These activities were associated with dramatic upregulation of multiple HSC/HPC regulatory genes including HoxB4, Notch1, Bmi1, Runx1, Meis1 and Nf-ya. Consistently, downregulation of endogenous Sall4 expression led to reduced LSK cell proliferation and accelerated cell differentiation. Moreover, in myeloid progenitor cells (32D), overexpression of Sall4 isoforms inhibited granulocytic differentiation and permitted expansion of undifferentiated cells with defined cytokines, consistent with the known functions of Sall4 in the ES cell system.</p> <p>Conclusion</p> <p>Sall4 is a potent regulator for HSC/HPC self-renewal, likely by increasing self-renewal activity and inhibiting differentiation. Our work provides further support that Sall4 manipulation may be a new model for expanding clinically transplantable stem cells.</p

Humanized Rag1−/−γc−/− Mice Support Multilineage Hematopoiesis and Are Susceptible to HIV-1 Infection via Systemic and Vaginal Routes

Several new immunodeficient mouse models for human cell engraftment have recently been introduced that include the Rag2−/−γc−/−, NOD/SCID, NOD/SCIDγc−/− and NOD/SCIDβ2m−/− strains. Transplantation of these mice with CD34+ human hematopoietic stem cells leads to prolonged engraftment, multilineage hematopoiesis and the capacity to generate human immune responses against a variety of antigens. However, the various mouse strains used and different methods of engrafting human cells are beginning to illustrate strain specific variations in engraftment levels, duration and longevity of mouse life span. In these proof-of-concept studies we evaluated the Balb/c-Rag1−/−γ−/− strain for engraftment by human fetal liver derived CD34+ hematopoietic cells using the same protocol found to be effective for Balb/c-Rag2−/−γc−/− mice. We demonstrate that these mice can be efficiently engrafted and show multilineage human hematopoiesis with human cells populating different lymphoid organs. Generation of human cells continues beyond a year and production of human immunoglobulins is noted. Infection with HIV-1 leads to chronic viremia with a resultant CD4 T cell loss. To mimic the predominant sexual viral transmission, we challenged humanized Rag1−/−γc−/− mice with HIV-1 via vaginal route which also resulted in chronic viremia and helper T cell loss. Thus these mice can be further exploited for studying human pathogens that infect the human hematopoietic system in an in vivo setting

An empirical examination of the factor structure of compassion

Compassion has long been regarded as a core part of our humanity by contemplative traditions, and in recent years, it has received growing research interest. Following a recent review of existing conceptualisations, compassion has been defined as consisting of the following five elements: 1) recognising suffering, 2) understanding the universality of suffering in human experience, 3) feeling moved by the person suffering and emotionally connecting with their distress, 4) tolerating uncomfortable feelings aroused (e.g., fear, distress) so that we remain open to and accepting of the person suffering, and 5) acting or being motivated to act to alleviate suffering. As a prerequisite to developing a high quality compassion measure and furthering research in this field, the current study empirically investigated the factor structure of the five-element definition using a combination of existing and newly generated self-report items. This study consisted of three stages: a systematic consultation with experts to review items from existing self-report measures of compassion and generate additional items (Stage 1), exploratory factor analysis of items gathered from Stage 1 to identify the underlying structure of compassion (Stage 2), and confirmatory factor analysis to validate the identified factor structure (Stage 3). Findings showed preliminary empirical support for a five-factor structure of compassion consistent with the five-element definition. However, findings indicated that the ‘tolerating’ factor may be problematic and not a core aspect of compassion. This possibility requires further empirical testing. Limitations with items from included measures lead us to recommend against using these items collectively to assess compassion. Instead, we call for the development of a new self-report measure of compassion, using the five-element definition to guide item generation. We recommend including newly generated ‘tolerating’ items in the initial item pool, to determine whether or not factor-level issues are resolved once item-level issues are addressed