Trichophyton mentagrophytes complex: A retrospective study of 64 dogs from the Central United States (1997-2020).

BACKGROUND: There are limited clinical studies evaluating the Trichophyton mentagrophytes complex, with most reports confined to small case studies. Additionally, the studies are dated and provide limited information on response to newer or currently available therapies. HYPOTHESIS/OBJECTIVES: The aim of the study was to determine if there is a breed prevalence, lesion distribution and seasonality associated with the T. mentagrophytes complex for dogs evaluated in the central United States. An additional aim of the study was to evaluate response to therapies because there are minimal data available on clinical response with newer systemic antifungal drugs. ANIMALS: A total of 64 canine medical records were evaluated that had a previous diagnosis of T. mentagrophytes complex infection. MATERIALS AND METHODS: A retrospective study of medical records to evaluate signalment, time of onset of clinical signs, clinical presentation and therapeutic management. RESULTS: A higher incidence of T. mentagrophytes complex infection was observed in the American Kennel Club (AKC) Sporting group (43%) and Terrier group (20%). A seasonal influence was noted, with the onset of clinical signs being highest in October. Lesions most often affected the muzzle (48%), followed by the head excluding the pinnae (21%). Ketoconazole, itraconazole and terbinafine appeared equivalent as systemic therapeutic options to treat T. mentagrophytes complex infections. CONCLUSIONS AND CLINICAL RELEVANCE: This study identified patterns in breeds, seasonality and lesion distribution for the T. mentagrophytes complex in dogs from the central United States. Additionally, the study found several reasonable and reliable treatment options for systemic therapy.

Sensitive seismic sensors based on microwave frequency fiber interferometry in commercially deployed cables.

The use of fiber infrastructures for environmental sensing is attracting global interest, as optical fibers emerge as low cost and easily accessible platforms exhibiting a large terrestrial deployment. Moreover, optical fiber networks offer the unique advantage of providing observations of submarine areas, where the sparse existence of permanent seismic instrumentation due to cost and difficulties in deployment limits the availability of high-resolution subsea information on natural hazards in both time and space. The use of optical techniques that leverage pre-existing fiber infrastructure can efficiently provide higher resolution coverage and pave the way for the identification of the detailed structure of the Earth especially on seismogenic submarine faults. The prevailing optical technique for use in earthquake detection and structural analysis is distributed acoustic sensing (DAS) which offers high spatial resolution and sensitivity, however is limited in range (< 100 km). In this work, we present a novel technique which relies on the dissemination of a stable microwave frequency along optical fibers in a closed loop configuration, thereby forming an interferometer that is sensitive to deformation. We call the proposed technique Microwave Frequency Fiber Interferometer (MFFI) and demonstrate its sensitivity to deformation induced by moderate-to-large earthquakes from either local or regional epicenters. MFFI signals are compared to signals recorded by accelerometers of the National Observatory of Athens, Institute of Geodynamics National Seismic Network and by a commercially available DAS interrogator operating in parallel at the same location. Remarkable agreement in dynamical behavior and strain rate estimation is achieved and demonstrated. Thus, MFFI emerges as a novel technique in the field of fiber seismometers offering critical advantages with respect to implementation cost, maximum range and simplicity.

The effect of a mixed cannabidiol and cannabidiolic acid based oil on client-owned dogs with atopic dermatitis.

BACKGROUND: Cannabidiol (CBD) and cannabidiolic acid (CBDA) are reported to have antinociceptive, immunomodulatory and anti-inflammatory actions. OBJECTIVES: To determine if CBD/CBDA is an effective therapy for canine atopic dermatitis (cAD). ANIMALS: Thirty-two privately owned dogs with cAD. MATERIALS AND METHODS: Prospective, randomised, double-blinded, placebo-controlled study. Concurrent therapies were allowed if remained unchanged. Dogs were randomly assigned to receive either 2 mg/kg of an equal mix of CBD/CBDA (n = 17) or placebo for 4 weeks. On Day (D)0, D14 and D28, Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and pruritus Visual Analog Scale (pVAS) scores were determined by investigators and owners, respectively. Complete blood count, serum biochemistry profiles and cytokine bioassays were performed on serum collected on D0 and D28. RESULTS: There was no significant difference in CADESI-04 from D0 to D14 (p  = 0.42) or D28 (p  = 0.51) in either group. pVAS scores were significantly lower for the treatment group at D14 (p  = 0.04) and D28 (p  = 0.01) and a significant change in pVAS from baseline was seen at D14 (p  = 0.04) and not D28 (p  = 0.054) between groups. There was no significant difference in serum levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein - 1, IL-31 or IL-34 between groups at D0 or D28. Elevated alkaline phosphatase was observed in four of 17 treatment group dogs. CONCLUSIONS AND CLINICAL RELEVANCE: CBD/CBDA as an adjunct therapy decreased pruritus, and not skin lesions associated with cAD in dogs.

Contexte - Le cannabidiol (CBD) et l'acide cannabidiolique (CBDA) auraient des actions antinociceptives, immunomodulatrices et anti-inflammatoires. Objectifs - Déterminer si le CBD/CBDA est une thérapie efficace pour la dermatite atopique canine (cAD). Animaux - Trente-deux chiens de propriétaires privés atteints de cAD Matériels et méthodes - Étude prospective, randomisée, en double aveugle, contrôlée versus placebo. Les thérapies concomitantes étaient autorisées si elles restaient inchangées. Les chiens ont été répartis au hasard pour recevoir soit 2 mg/kg d'un mélange égal de CBD/CBDA (n = 17) soit un placebo pendant quatre semaines. Aux jours (J)0, J14 et J28, les scores Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) et prurit Visual Analog Scale (pVAS) ont été déterminés respectivement par les investigateurs et les propriétaires. Une formule sanguine complète, des profils biochimiques sériques et des dosages biologiques des cytokines ont été réalisés sur le sérum prélevé à J0 et J28. Résultats - Il n'y avait pas de différence significative au CADESI-04 de J0 à J14 (P = 0,42) ou J28 (P = 0,51) dans les deux groupes. Les scores pVAS étaient significativement inférieurs pour le groupe de traitement à J14 (P = 0,04) et J28 (P = 0,01) et un changement significatif de la pVAS par rapport à l'inclusion a été observé à J14 (P = 0,04) et non à J28 (P = 0,054) entre les groupes. Il n'y avait pas de différence significative dans les taux sériques d'interleukine (IL)-6, IL-8, protéine chimiotactique des monocytes-1, IL-31 ou IL-34 entre les groupes à J0 ou J28. Une phosphatase alcaline élevée a été observée chez quatre des 17 chiens du groupe de traitement. Conclusions et pertinence clinique - Le CBD/CBDA en tant que traitement d'appoint a diminué le prurit, et non les lésions cutanées associées à la DAC chez les chiens.

Introducción- se ha descrito que el cannabidiol (CBD) y el ácido cannabidiólico (CBDA) tienen acciones antinociceptivas, inmunomoduladoras y antiinflamatorias. Objetivos- determinar si el CBD/CBDA es una terapia eficaz para la dermatitis atópica canina (CAD). Animales - Treinta y dos perros de propietarios privados con cAD Materiales y métodos - Estudio prospectivo, aleatorio, doble ciego, controlado con placebo. Se permitieron terapias concurrentes si permanecían sin cambios. Los perros fueron asignados al azar para recibir 2 mg/kg de una mezcla igual de CBD/CBDA (n = 17) o placebo durante cuatro semanas. En el día (D)0, D14 y D28, los investigadores y los propietarios determinaron las puntuaciones del índice de extensión y gravedad de la dermatitis atópica canina, cuarta revisión (CADESI-04) y la escala análoga visual de prurito (pVAS), respectivamente. Se realizaron hemogramas completos, perfiles bioquímicos séricos y bioensayos de citoquinas en suero obtenido en D0 y D28. Resultados- no hubo diferencias significativas en CADESI-04 de D0 a D14 (P = 0,42) o D28 (P = 0,51) en ninguno de los grupos. Las puntuaciones de pVAS fueron significativamente más bajas para el grupo de tratamiento en D14 (P = 0.04) y D28 (P = 0.01) y se observó un cambio significativo en pVAS desde el inicio en D14 (P = 0.04) y no en D28 (P = 0.054) entre grupos . No hubo diferencias significativas en los niveles séricos de interleuquina (IL)-6, IL-8, proteína quimioatrayente de monocitos-1, IL-31 o IL-34 entre los grupos en D0 o D28. Se observó fosfatasa alcalina elevada en cuatro de los 17 perros del grupo de tratamiento. Conclusiones y relevancia clínica- CBD/CBDA como terapia adjunta disminuyó el prurito y no las lesiones cutáneas asociadas con la CAD en perros.

Contexto - O canabidiol (CBD) e ácido canabidiólico (CBDA) são relatados como tendo ações antinociceptivas, imunomoduladoras e anti-inflamatórias. Objetivos - Determinar se CBD/CBDA é eficaz no tratamento da dermatite atópica canina (CAD) Animais - Trinta e dois cães de propriedade privada com DAC. Materiais e métodos - Estudo prospectivo, randomizado, duplo-cego, placebo-controle. As terapias concomitantes foram permitidas se permanecessem inalteradas. Os cães foram divididos aleatoriamente em dois grupos, o que receberia 2 mg/kg de uma mistura igual de CBD/CBDA (n = 17) ou placebo durante quatro semanas. No Dia (D) 0, D14 e D28, o Índice de Extensão e Gravidade da Dermatite Atópica Canina, 4ª iteração (CADESI-04) e os escores da Escala Visual Analógica de Prurido (pVAS) foram determinados pelos investigadores e proprietários, respectivamente. Hemograma completo, perfis bioquímicos séricos e ensaios de citocinas foram realizados no soro coletado em D0 e D28. Resultados - Não houve diferença significativa no CADESI-04 de D0 a D14 (P = 0,42) ou D28 (P = 0,51) em nenhum dos grupos. Os escores de pVAS foram significativamente menores para o grupo de tratamento no D14 (P = 0,04) e D28 (P = 0,01) e observou-se uma alteração significativa no pVAS do D0 comparado ao D14 (P = 0,04) e não ao D28 (P = 0,054) entre os grupos. Não houve diferença significativa nos níveis séricos de interleucina (IL)-6, IL-8, proteína quimiotática de monócitos-1, IL-31 ou IL-34 entre os grupos em D0 ou D28. Elevação na fosfatase alcalina foi observada em quatro dos 17 cães do grupo de tratamento. Conclusões e relevância clínica - CBD e CBDA como uma terapia adjuvante é capaz de reduzir prurido, mas não lesões cutâneas associadas à DAC em cães.

A blockchain empowered and privacy preserving digital contact tracing platform.

The spread of the COVID-19 virus continues to increase fatality rates and exhaust the capacity of healthcare providers. Efforts to prevent transmission of the virus among humans remains a high priority. The current efforts to quarantine involve social distancing, monitoring and tracking the infected patients. However, the spread of the virus is too rapid to be contained only by manual and inefficient human contact tracing activities. To address this challenge, we have developed Connect, a blockchain empowered digital contact tracing platform that can leverage information on positive cases and notify people in their immediate proximity which would thereby reduce the rate at which the infection could spread. This would particularly be effective if sufficient people use the platform and benefit from the targeted recommendations. The recommendations would be made in a privacy-preserving fashion and contain the spread of the virus without the need for an extended period of potential lockdown. Connect is an identity wallet platform which will keep user digital identities and user activity trace data on a blockchain platform using Self-Sovereign Identity(SSI) proofs. User activities include the places he/she has travelled, the country of origin he/she came from, travel and dispatch updates from the airport etc. With these activity trace records, Connect platform can easily identify suspected patients who may be infected with the COVID-19 virus and take precautions before spreading it. By storing digital identities and activity trace records on blockchain-based SSI platform, Connect addresses the common issues in centralized cloud-based storage platforms (e.g. lack of data immutability, lack of traceability).

Effective and efficient characterization of Chinese hamster ovary production cell lines using automated intracellular staining and statistical modeling.

Mammalian cell line development is critical to bioproduct manufacturing. Success requires selecting a line with desirable performance characteristics, including consistent expression throughout the proposed manufacturing window. Given the genetic and phenotypic flux inherent to immortalized lines such as Chinese hamster ovary cells, clonally-derived cell line characterization is vital. We describe here the development and implementation of a novel addition to our characterization approach to ensure production cell line suitability: automated intracellular staining with statistical modeling. Case studies are presented which highlight this method's sensitivity to epigenetic expression effects, closing a gap left by our historically-leveraged genetic suitability characterization. Additionally, we demonstrate how an orthogonal, complimentary assay can help identify opportunities for improvement in even a well-established methodology such as our genetic suitability assessment. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:570-583, 2018.

Canine demodicosis: a retrospective study of a veterinary hospital population in California, USA (2000-2016).

BACKGROUND: Demodex spp. are cutaneous mites that cause clinical disease when present in increased numbers. There is an association in some dogs with underlying systemic disease or immunosuppressive medications. HYPOTHESIS/OBJECTIVES: Retrospective study to document breed predisposition, identify any concurrent diseases or underlying immunosuppressive conditions, and to determine the frequency of demodicosis recurrence after treatment completion. ANIMALS: There were 431 dogs with demodicosis presented to a veterinary teaching hospital in California, USA, from 2000 to 2016. METHODS: Inclusion in this study required a diagnosis of demodicosis based on direct demonstration of the mite. Records were reviewed for signalment, disease history, potential underlying aetiologies, diagnosed concurrent diseases, medications and demodicosis treatment. Analyses were performed to evaluate for potential breed predispositions and because of the large number of dogs with allergic dermatoses, analyses for this diagnosis as a disease associated with demodicosis was also performed. E-mailed surveys and follow-up telephone calls were used to assess for information about disease recurrence. RESULTS: The pit bull terrier group and West Highland white terrier, based on calculated odds ratio, were breeds predisposed to developing demodicosis. For dogs with demodicosis, allergic dermatoses was an associated disease. Relapse or recurrence of disease after treatment was uncommon, affecting 11% of the dogs with long-term follow-up. CONCLUSIONS/CLINICAL IMPORTANCE: This study identified, in dogs attending the institution based in California, USA, breed predilections for canine demodicosis and associated concomitant diseases. It also revealed a low occurrence of disease relapse, recurrence or persistence.

Development of a highly-efficient CHO cell line generation system with engineered SV40E promoter.

Chinese hamster ovary (CHO) cells have been one of the most widely used host cells for the manufacture of therapeutic recombinant proteins. An effective and efficient clinical cell line development process, which could quickly identify those rare, high-producing cell lines among a large population of low and non-productive cells, is of considerable interest to speed up biological drug development. In the glutamine synthetase (GS)-CHO expression system, selection of top-producing cell lines is based on controlling the balance between the expression level of GS and the concentration of its specific inhibitor, l-methionine sulfoximine (MSX). The combined amount of GS expressed from plasmids that have been introduced through transfection and the endogenous CHO GS gene determine the stringency and efficiency of selection. Previous studies have shown significant improvement in selection stringency by using GS-knockout CHO cells, which eliminate background GS expression from the endogenous GS gene in CHOK1SV cells. To further improve selection stringency, a series of weakened SV40E promoters have been generated and used to modulate plasmid-based GS expression with the intent of manipulating GS-CHO selection, finely adjusting the balance between GS expression and GS inhibitor (MSX) levels. The reduction of SV40E promoter activities have been confirmed by TaqMan RT-PCR and GFP expression profiling. Significant productivity improvements in both bulk culture and individual clonal cell line have been achieved with the combined use of GS-knockout CHOK1SV cells and weakened SV40E promoters driving GS expression in the current cell line generation process. The selection stringency was significantly increased, as indicated by the shift towards higher distribution of producing-cell populations, even with no MSX added into cell culture medium. The potential applications of weakened SV40E promoter and GS-knockout cells in development of targeted integration and transient CHO expression systems are also discussed.