Evaluating a natural horsemanship program in relation to the ISES first principles of horse training.

The ISES training principles provide an excellent starting point for professionals and horse owners. Currently, there does not seem to be an accepted protocol for evaluating horse training programs against the ISES principles. We suggest an approach to this, using Parelli Natural Horsemanship as our subject for evaluation. This initial pilot study (single-subject / n=1), trials two analytical methods, as applied to the current, video-based teaching materials from Parelli (latest DVD set, published and commercially available from 2015, supplied by Parelli for use in this study). The two methods used were: (i) ethology-based video observation / logging and (ii) discourse analysis of the language used to teach. The ethology-based approach uses an ethogram, which lists the behavioural characteristics of a human trainer adhering to the ISES principles. Computer-based ‘continuous sampling’ of Parelli video clips was used to log the frequencies of ISES principles. Inter Observer Reliability of the analysis to date was assessed using a two-way, mixed, absolute agreement, average-measures ICC (Intra Class Correlation). This evaluated observer agreement in the frequency count ratings for the ISES principles. Discourse analysis is a qualitative research methodology, applied across many domains including politics and health. Discourse analysis allows us to study transcripts of horse training materials, codifying the words, phrases and linguistic structures. Understanding the context within which training language is used, and its meaning to both the speaker and audience, makes it possible to evaluate compatibility with the ISES principles. Results for the ethology-based observations found all ISES principles present (1-10). High frequency counts for principles 2 & 10. Low counts for principles 5 & 7. Inter Observer Reliability (2 observers) was in the ‘excellent’ range (ICC=0.79). The high ICC value suggests that a minimal amount of measurement error was introduced by the independent observers, and therefore statistical power is not substantially reduced. At this stage (without an ICC value closer to 1.0 or further calibrating observers), increasing the evidence against random effects would require more extensive trials (p=0.16). The interim results from the discourse analysis shows consistent congruence between the Parelli materials and the ISES principles, particularly in the areas of: training according to the horse’s ethology and cognition, using learning theory appropriately, forming consistent habits, avoiding flight responses and ensuring that the horse should always be as calm as possible (1, 2, 7, 9 and 10)

Analysis of Smad nucleocytoplasmic shuttling in living cells

Transforming growth factor beta (TGF-beta) signalling leads to phosphorylation and activation of receptor-regulated Smad2 and Smad3, which form complexes with Smad4 and accumulate in the nucleus. The Smads, however, do not seem to reside statically in the cytoplasm in the absence of signalling or in the nucleus upon TGF-beta stimulation, but have been suggested to shuttle continuously between these cellular compartments in both the absence and presence of TGF-beta. Here we investigate this nucleocytoplasmic shuttling in detail in living cells using fusions of Smad2 and Smad4 with enhanced GFP. We first establish that the GFPSmad fusions behave like wild-type Smads in a variety of cellular assays. We go on to demonstrate directly, using photobleaching experiments, that Smad2 and Smad4 shuttle between the cytoplasm and nucleus in both TGF-beta-induced cells and in uninduced cells. In uninduced cells, GFPSmad2 is less mobile in the cytoplasm than is GFPSmad4, suggesting that it may be tethered there. In addition, we show that both GFPSmad2 and GFPSmad4 undergo a substantial decrease in mobility in the nucleus upon TGF-beta stimulation, suggesting that active complexes of Smads are tethered in the nucleus, whereas unactivated Smads are more freely diffusible. We propose that regulated cytoplasmic and nuclear retention may play a role in determining the distribution of Smads between the cytoplasm and the nucleus in both uninduced cells and upon TGF-beta induction

An improved Erk biosensor detects oscillatory Erk dynamics driven by mitotic erasure during early development

Extracellular signal-regulated kinase (Erk) signaling dynamics elicit distinct cellular responses in a variety of contexts. The early zebrafish embryo is an ideal model to explore the role of Erk signaling dynamics in vivo, as a gradient of activated diphosphorylated Erk (P-Erk) is induced by fibroblast growth factor (Fgf) signaling at the blastula margin. Here, we describe an improved Erk-specific biosensor, which we term modified Erk kinase translocation reporter (modErk-KTR). We demonstrate the utility of this biosensor in vitro and in developing zebrafish and Drosophila embryos. Moreover, we show that Fgf/Erk signaling is dynamic and coupled to tissue growth during both early zebrafish and Drosophila development. Erk activity is rapidly extinguished just prior to mitosis, which we refer to as mitotic erasure, inducing periods of inactivity, thus providing a source of heterogeneity in an asynchronously dividing tissue. Our modified reporter and transgenic lines represent an important resource for interrogating the role of Erk signaling dynamics in vivo

A Sense of Control and Wellbeing in Older People Living with Frailty: A Scoping Review

A sense of control is important for supporting older people living with frailty to develop adaptive functioning to optimize wellbeing. This scoping review examined the literature on the sense of control and wellbeing in older people living with frailty within their everyday life and care service use. Nine databases were searched using the timeframe 2000 to 2021 to identify key ideas regarding control and wellbeing in older people with frailty. The review highlighted three major themes: a) Control as conveyed in bodily expressions and daily activities, b) Sense of control and influence of place of residence, and c) Control within health and social care relationships. Maintaining a sense of control is not only an internal feeling but is impacted by physical and social environments. Greater focus is needed on the nature of relationships between older people living with frailty and those who work alongside them, which support control and wellbein

‘I’d rather you didn’t come’: The impact of stigma on exercising with epilepsy

Epilepsy is a common but hidden disorder, leading to stigma in everyday life. Despite stigma being widely researched, little is known about the impact of stigma for people with epilepsy within a sports and exercise setting. Using constructionist grounded theory, we explored the barriers and adaptations to exercise for people with epilepsy. Three focus groups (2-3 participants per group) and three semi-structured interviews were conducted (11 participants total). Stigma negatively impacted joining team sports, running groups, and disclosure to others. The effect of stigma was reduced by educating others about epilepsy, thus creating more awareness and understanding

A New Class of Small Molecule Inhibitor of BMP Signaling

Growth factor signaling pathways are tightly regulated by phosphorylation and include many important kinase targets of interest for drug discovery. Small molecule inhibitors of the bone morphogenetic protein (BMP) receptor kinase ALK2 (ACVR1) are needed urgently to treat the progressively debilitating musculoskeletal disease fibrodysplasia ossificans progressiva (FOP). Dorsomorphin analogues, first identified in zebrafish, remain the only BMP inhibitor chemotype reported to date. By screening an assay panel of 250 recombinant human kinases we identified a highly selective 2-aminopyridine-based inhibitor K02288 with in vitro activity against ALK2 at low nanomolar concentrations similar to the current lead compound LDN-193189. K02288 specifically inhibited the BMP-induced Smad pathway without affecting TGF-β signaling and induced dorsalization of zebrafish embryos. Comparison of the crystal structures of ALK2 with K02288 and LDN-193189 revealed additional contacts in the K02288 complex affording improved shape complementarity and identified the exposed phenol group for further optimization of pharmacokinetics. The discovery of a new chemical series provides an independent pharmacological tool to investigate BMP signaling and offers multiple opportunities for pre-clinical development

Perinatal Cat and Dog Exposure and the Risk of Asthma and Allergy in the Urban Environment: A Systematic Review of Longitudinal Studies

Background. The literature is contradictory concerning pet exposure and the risk of development of asthma and other allergic diseases. Using longitudinal studies, we aimed to systematically review the impact of pet ownership in the critical perinatal period as a risk factor for allergies in childhood. Methods. Medline database was searched for urban cohort studies with perinatal exposure to cats and/or dogs and subsequent asthma or allergic disease. Results. Nine articles, comprising 6498 participants, met inclusion criteria. Six found a reduction in allergic disease associated with perinatal exposure to dogs or, cats or dogs. One study found no association. Two found increased risk only in high-risk groups. Conclusion. Longitudinal studies in urban populations suggest that perinatal pets, especially dogs, may reduce the development of allergic disease in those without a family history of allergy. Other unmeasured factors such as pet-keeping choices in allergic families may be confounding the association seen in these high-risk families, and further study is required

A systematic review of the qualitative literature on older individuals’ experiences of care and well-being during physical rehabilitation for acquired brain injury

Abstract Aims: To acquire an in-depth understanding of how older individuals diagnosed with acquired brain injury (ABI) experience their well-being and care when undergoing physical rehabilitation. Design: Systematic literature review. Data sources: The electronic databases of PubMed, CINAHL, APA PsycInfo, ASSIA and SCOPUS were searched from 2005 to 2020. Extensive reference checking was also conducted. Review methods: A systematic review was conducted following PRISMA guidelines, including predominantly qualitative studies. Studies’ quality was appraised using the critical apraisal skills programme (CASP) tool. Results: Seventeen studies met the inclusion criteria. Following methods of thematic synthesis, four overarching interpretive themes were identified: (a) Rehabilitation processes and their impact on older individuals’ well-being; (b) Identity and embodiment concerns of older individuals during rehabilitation; (c) Institutional factors affecting older individuals’ care and well-being experiences; and (d) Older individuals’ participation in creative activities as part of rehabilitation. Conclusion: Organizational and structural care deficiencies as well as health disparities can adversely impact older individuals’ autonomous decision-making and goal-setting potentials. The discrepancy between older individuals’ expectations and the reality of returning home along with the illusionary wish to return to a perceived normality, can further negatively affect older individuals’ sense of well-being. Constructive communication, emotional support, family involvement in rehabilitation and creating a stimulating, enriching social environment can humanize and facilitate older individuals’ adjustment to their new reality following ABI. Impact: There is a lack of qualitative research on older individuals’ ABI rehabilitation experiences, especially traumatic brain injury incidents. Further study should consider patients concerns over their involvement in decision-making and goal setting about their care. Overall, this review reveals the need to examine further the significance of humanizing care and the factors that affect older individuals’sense of well-being

Backbone resonance assignments of the monomeric DUF59 domain of human Fam96a

Proteins containing a domain of unknown function 59 (DUF59) appear to have a variety of physiological functions, ranging from iron-sulfur cluster assembly to DNA repair. DUF59 proteins have been found in bacteria, archaea and eukaryotes, however Fam96a and Fam96b are the only mammalian proteins predicted to contain a DUF59 domain. Fam96a is an 18 kDa protein comprised primarily of a DUF59 domain (residues 31-157) and an N-terminal signal peptide (residues 1-27). Interestingly, the DUF59 domain of Fam96a exists as monomeric and dimeric forms in solution, and X-ray crystallography studies of both forms unexpectedly revealed two different domain-swapped dimer structures. Here we report the backbone resonance assignments and secondary structure of the monomeric form of the 127 residue DUF59 domain of human Fam96a. This study provides the basis for further understanding the structural variability exhibited by Fam96a and the mechanism for domain swapping

Venous injection of a triphasic calcium-based implant in a sheep model of pulmonary embolism demonstrates minimal acute systemic effects.

PURPOSE Implant leakage is the most common complication of vertebral augmentation. Alternative injectable materials must demonstrate intravascular safety comparable to or better than polymethyl methacrylate (PMMA). This study assessed the systemic effects of a triphasic calcium-based implant or PMMA injected directly into the femoral vein in a large animal model designed to mimic severe intravascular implant leakage. METHODS Six skeletally mature female sheep were randomly assigned (n = 3) to either the PMMA or the triphasic implant (AGN1, composition: calcium sulfate, β-tricalcium phosphate, brushite) treatment group. Femoral veins of each sheep were directly injected with 0.5 mL of implant material to mimic leakage volumes reported during PMMA vertebroplasty. To compare acute systemic effects of the materials, cardiovascular parameters, laboratory coagulation markers, and calcium and sulfate serum levels were monitored for 60 min after implant injection. Thrombotic and embolic events were evaluated by radiologic imaging, necropsy, and histopathology. RESULTS Heart rate, systemic arterial blood pressure, arterial oxygenation, arterial carbon dioxide content, and coagulation markers remained within physiological range after either AGN1 or PMMA injection. No blood flow interruption in the larger pulmonary vessels was observed in either group. Lung histopathology revealed that the severity of thrombotic changes after AGN1 injection was minimal to slight, while changes after PMMA injection were minimal to massive. CONCLUSION Acute systemic effects of intravascular AGN1 appeared to be comparable to or less than that of intravascular PMMA. Furthermore, in this preliminary study, the severity and incidence of pulmonary histological changes were lower for AGN1 compared to PMMA