Current and Future Advances in the Detection and Surveillance of Biosecurity-Relevant Equine Bacterial Diseases Using Loop-Mediated Isothermal Amplification (LAMP).

Horses play an important role throughout the world, whether for work, culture, or leisure, providing an ever-growing significant contribution to the economy. The increase in importation and movement of horses, both nationally and internationally, has inevitably allowed for the global equine industry to grow. Subsequently, however, the potential for transmission of fatal equine bacterial diseases has also escalated, and devasting outbreaks continue to occur. To prevent such events, disease surveillance and diagnosis must be heightened throughout the industry. Current common, or "gold-standard" techniques, have shown to be inadequate at times, thus requiring newer technology to impede outbreaks. Loop-mediated isothermal amplification (LAMP) has proven to be a reliable, rapid, and accessible tool in both diagnostics and surveillance. This review will discuss equine bacterial diseases of biosecurity relevance and their current diagnostic approaches, as well as their respective LAMP assay developments. Additionally, we will provide insight regarding newer technology and advancements associated with this technique and their potential use for the outlined diseases.

How is resilience conceptualized and operationalized in occupational therapy and occupational science literature? Protocol for a scoping review / Como a resiliência é conceituada e operacionalizada na literatura de ciência ocupacional e terapia ocupacional? Protocolo para uma revisão de escopo

Abstract Introduction Resilience is a commonly discussed term describing the ability to overcome, adapt to, or cope with stressful/disruptive events. Although researchers and practitioners define resilience in diverse ways - e.g., psychological or disaster resilience - the concept fundamentally encompasses perseverance through adversity. As experts in the interplay between individuals, environments, and occupations, occupational therapists and occupational scientists have great potential to understand and enable resilience, with some similar concepts appearing in occupational theories (e.g., occupational adaptation). However, there are no published reviews of resilience in the occupation-focused literature. Objective We will explore how resilience is conceptualized and operationalized in the occupational therapy and occupational science research literature. Method Guided by the Joanna Briggs Institute scoping review methodology, we will search library databases and other sources for relevant records. Two team members will screen records for inclusion, with discrepancies settled by a third person. We will include English-language literature (including research papers, editorials, dissertations, etc.) published since 1990 which 1) contains the word root 'resilien*' and 2) is occupation focused, according to our criteria (occupational therapist/occupational scientist co-authors or research participants; and/or published in occupation-focused periodical). We will report key information of included literature, such as methodology and resilience theories discussed. Results Our study is ongoing at the time of publication; this manuscript reports its protocol without results. Conclusion Findings will be useful for clinicians and researchers looking for occupational conceptualizations of resilience. From a social justice perspective, our review may highlight evidence that occupational engagement can foster resilience among marginalized communities.

Resumo Introdução Resiliência é um termo que descreve a habilidade de superar, adaptar ou lidar com eventos estressantes ou perturbadores. Embora pesquisadores e profissionais definam resiliência de diversas maneiras - como resiliência psicológica ou a desastres - o conceito fundamentalmente engloba perseverança no enfrentamento de adversidades. Como especialistas na interação entre indivíduos, comunidades, ambientes e ocupações, terapeutas ocupacionais e cientistas ocupacionais têm potencial para compreender e propiciar a resiliência, com alguns conceitos semelhantes (como adaptação ocupacional). Entretanto, não há nenhuma revisão publicada sobre resiliência na área. Objetivo Explorar como a resiliência é conceituada e operacionalizada na literatura científica de terapia ocupacional e ciência ocupacional. Método Guiados pela metodologia para revisões de escopo proposta pelo Instituto Joanna Briggs, buscou-se por documentos em bases de dados científicas e outras fontes. Dois membros da equipe revisaram documentos para inclusão e as discrepâncias foram resolvidas por uma terceira pessoa. Utilizou-se literatura em inglês (artigos de pesquisa, editoriais, dissertações etc.) publicada desde 1990 que: (1) contenha 'resilien*' e (2) seja focada na ocupação, desde que: terapeutas ocupacionais ou cientistas ocupacionais fossem coautores ou participantes da pesquisa; e/ou publicada em periódico focado em terapia ocupacional/ciência ocupacional. Foram reportadas as principais informações dos documentos incluídos, como a metodologia e as teorias de resiliência. Resultados Este estudo está em andamento; foca-se aqui no protocolo de pesquisa, sem resultados. Conclusão As discussões serão úteis para profissionais na prática clínica e pesquisadores buscando por uma conceituação ocupacional de resiliência. De uma perspectiva de justiça social, essa revisão pode destacar evidências de que o engajamento com ocupações pode promover resiliência entre comunidades marginalizadas.

Isothermal Nucleic Acid Amplification Technologies for the Detection of Equine Viral Pathogens.

The global equine industry provides significant economic contributions worldwide, producing approximately USD $300 billion annually. However, with the continuous national and international movement and importation of horses, there is an ongoing threat of a viral outbreak causing large epidemics and subsequent significant economic losses. Additionally, horses serve as a host for several zoonotic diseases that could cause significant human health problems. The ability to rapidly diagnose equine viral diseases early could lead to better management, treatment, and biosecurity strategies. Current serological and molecular methods cannot be field-deployable and are not suitable for resource-poor laboratories due to the requirement of expensive equipment and trained personnel. Recently, isothermal nucleic acid amplification technologies, such as loop-mediated isothermal amplification (LAMP) and insulated isothermal polymerase chain reaction (iiPCR), have been developed to be utilized in-field, and provide rapid results within an hour. We will review current isothermal diagnostic techniques available to diagnose equine viruses of biosecurity and zoonotic concern and provide insight into their potential for in-field deployment.

Heterodimeric GW7604 Derivatives: Modification of the Pharmacological Profile by Additional Interactions at the Coactivator Binding Site.

(E/Z)-3-(4-((E)-1-(4-Hydroxyphenyl)-2-phenylbut-1-enyl)phenyl)acrylic acid (GW7604) as a derivative of (Z)-4-hydroxytamoxifen (4-OHT) was linked by diaminoalkane spacers to molecules that are known binders to the coactivator binding site (benzimidazole or thioxo-quinazolinone scaffolds). With this modification, an optimization of the pharmacological profile was achieved. The most active thioxo-quinazolinone derivative 16 showed extraordinarily high affinity to the estrogen receptor (ER) ß (RBA = 110%), inhibited effectively the coactivator recruitment (IC50 = 20.88 nM (ERα) and 28.34 nM (ERß)), acted as a pure estradiol (E2) antagonist in a transactivation assay (IC50 = 18.5 nM (ERα) and 7.5 nM (ERß)), and downregulated the ERα content in MCF-7 cells with an efficacy of 60% at 1 µM. The cytotoxicity was restricted to hormone-dependent MCF-7 (IC50 = 4.2 nM) and tamoxifen-resistant MCF-7TamR cells (IC50 = 476.6 nM). The compounds bearing a thioxo-quinazolinone moiety can therefore be assigned as pure E2-antagonistic selective ER degraders/downregulators. By contrast, the benzimidazole derivatives acted solely as pure antagonists without degradation of the ER.

Development of bivalent triarylalkene- and cyclofenil-derived dual estrogen receptor antagonists and downregulators.

Up to 80% of mammary carcinoma initially exhibit estrogen-dependent growth, which can be treated by aromatase inhibitors or SERMs/SERDs. To increase the options after failure of the hormonal therapy with these drugs, the search for alternatives with a different mode of action to prevent estrogen action is of high relevance. Therefore, this study focused on the inhibition of coactivator recruitment at the estrogen receptor (ER) by targeted attachment of bivalent compounds at the coactivator binding site besides the primary binding at the ligand binding domain. Eight homodimeric 4-[1-(4-hydroxyphenyl)-2-phenyl-1-butenyl]cinnamic acid (GW7604)- or cyclofenilacrylic acid-based ER ligands with diaminoalkane linkers (C2-C5) were synthesized and their effects on the ER subtypes were assessed in vitro. All compounds possessed full antagonistic potency at ERα/ß as determined in a transactivation assay. Furthermore, they exerted medium downregulatory effects dependent on the spacer length and did not stimulate the ER expression as observed for 4-hydroxytamoxifen. The cyclofenil-derived dimer with C4 spacer (15b) showed the highest binding affinity to ERα (RBA = 79.2%) and downregulated the ER content in MCF-7 cells with an efficiency of 38% at 1 µM.