Efficacy of calcium propionate against fungicide-resistant fungal plant pathogens and suppression of botrytis blight of ornamental flowers.

Conventional fungicides are used in IPM programs to manage fungal plant pathogens, but there are concerns about resistance development in target organisms, environmental contamination, and human health risks. This study explored the potential of calcium propionate (CaP), a common food preservative generally recognized as safe (GRAS) to control fungicide-resistant plant pathogens, mainly Botrytis cinerea, and botrytis blight in ornamentals. In-vitro experiments using mycelium growth inhibition indicated a mean EC50 value for CaP (pH 6.0) of 527 mg/L for six isolates of Botrytis cinerea as well as 618, 1354, and 1310 mg/L for six isolates each of Monilinia fructicola, Alternaria alternata, and Colletotrichum acutatum. In vitro efficacy tests indicated CaP equally inhibited mycelium growth of fungal isolates sensitive and resistant to FRAC codes 1, 2, 3, 7, 9, 11, 12, and 17 fungicides. CaP at 0.1% (pH 6.0-6.5) reduced infection cushion (IC) formation in vitro, botrytis blight on petunia flowers, and botrytis blight of cut flower roses with little to no visible phytotoxicity. Although higher concentrations strongly inhibited infection cushion formation, they did not improve efficacy and exhibited phytotoxicity. We hypothesize that high concentrations may create tissue damage that facilitates direct fungal penetration without the need for infection cushion and subsequent appressoria formation. This study indicates the potential usefulness of CaP for blossom blight disease management in ornamentals if applied at concentrations low enough to avoid phytotoxicity.

Characterization of Three Variants of SARS-CoV-2 In Vivo Shows Host-Dependent Pathogenicity in Hamsters, While Not in K18-hACE2 Mice.

Animal models are used in preclinical trials to test vaccines, antivirals, monoclonal antibodies, and immunomodulatory drug therapies against SARS-CoV-2. However, these drugs often do not produce equivalent results in human clinical trials. Here, we show how different animal models infected with some of the most clinically relevant SARS-CoV-2 variants, WA1/2020, B.1.617.2/Delta, B.1.1.529/Omicron, and BA5.2/Omicron, have independent outcomes. We show that in K18-hACE2 mice, B.1.617.2 is more pathogenic, followed by WA1, while B.1.1.529 showed an absence of clinical signs. Only B.1.1.529 was able to infect C57BL/6J mice, which lack the human ACE2 receptor. B.1.1.529-infected C57BL/6J mice had different T cell profiles compared to infected K18-hACE2 mice, while viral shedding profiles and viral titers in lungs were similar between the K18-hACE2 and the C57BL/6J mice. These data suggest B.1.1.529 virus adaptation to a new host and shows that asymptomatic carriers can accumulate and shed virus. Next, we show how B.1.617.2, WA1 and BA5.2/Omicron have similar viral replication kinetics, pathogenicity, and viral shedding profiles in hamsters, demonstrating that the increased pathogenicity of B.1.617.2 observed in mice is host-dependent. Overall, these findings suggest that small animal models are useful to parallel human clinical data, but the experimental design places an important role in interpreting the data. Importance: There is a need to investigate SARS-CoV-2 variant phenotypes in different animal models due to the lack of reproducible outcomes when translating experiments to the human population. Our findings highlight the correlation of clinically relevant SARS-CoV-2 variants in animal models with human infections. Experimental design and understanding of correct animal models are essential to interpreting data to develop antivirals, vaccines, and other therapeutic compounds against COVID-19.

Compounds co-targeting kinases in axon regulatory pathways promote regeneration and behavioral recovery after spinal cord injury in mice.

Recovery from spinal cord injury (SCI) and other central nervous system (CNS) trauma is hampered by limits on axonal regeneration in the CNS. Regeneration is restricted by the lack of neuron-intrinsic regenerative capacity and by the repressive microenvironment confronting damaged axons. To address this challenge, we have developed a therapeutic strategy that co-targets kinases involved in both extrinsic and intrinsic regulatory pathways. Prior work identified a kinase inhibitor (RO48) with advantageous polypharmacology (co-inhibition of targets including ROCK2 and S6K1), which promoted CNS axon growth in vitro and corticospinal tract (CST) sprouting in a mouse pyramidotomy model. We now show that RO48 promotes neurite growth from sensory neurons and a variety of CNS neurons in vitro, and promotes CST sprouting and/or regeneration in multiple mouse models of spinal cord injury. Notably, these in vivo effects of RO48 were seen in several independent experimental series performed in distinct laboratories at different times. Finally, in a cervical dorsal hemisection model, RO48 not only promoted growth of CST axons beyond the lesion, but also improved behavioral recovery in the rotarod, gridwalk, and pellet retrieval tasks. Our results provide strong evidence for RO48 as an effective compound to promote axon growth and regeneration. Further, they point to strategies for increasing robustness of interventions in pre-clinical models.

Telehealth cognitive behavioral therapy for insomnia in children with autism spectrum disorder: A pilot examining feasibility, satisfaction, and preliminary findings.

LAY ABSTRACT: Insomnia is common in children with autism. Cognitive behavioral treatment for childhood insomnia (CBT-CI) may improve sleep and functioning in children with autism and their parents, but typical delivery involving multiple office visits can make it difficult for some children to get this treatment. This pilot study tested telehealth delivery of CBT-CI using computers, which allowed children and their parents to get the treatment at home. This pilot shows therapists that parents and children were able to use telehealth CBT-CI to improve child and parent sleep, child behavior and arousal, and parent fatigue. Parents found telehealth CBT-CI helpful, age-appropriate, and autism-friendly. Telehealth CBT-CI holds promise for treating insomnia in school-aged children with autism and deserves further testing.

Cognitive behavioral treatment of insomnia in school-aged children with autism spectrum disorder: A pilot feasibility study.

Insomnia is common in autism and associated with challenging behavior and worse parent sleep. Cognitive behavioral treatment for childhood insomnia (CBT-CI) is efficacious in typically developing children, but not yet tested in school-aged children with autism. This single arm pilot tested 8-session CBT-CI in 17 children with autism and insomnia (M age = 8.76 years, SD = 1.99) and their parent(s) (M age = 39.50 years, SD = 4.83). Treatment integrity was assessed for each session [delivery (by therapist), receipt (participant understanding), and enactment (home practice)]. Children and parents wore actigraphs and completed electronic diaries for 2-weeks to obtain objective and subjective sleep onset latency (SOL), total sleep/wake times (TST/TWT), and sleep efficiency (SE) at pre/post/1-month follow-up. Parents also completed the Aberrant Behavior Checklist [irritability, lethargy, stereotypy, hyperactivity, inappropriate speech (e.g., excessive/repetitive, loud self-talk)] at pre/post/1-month. Fifteen children completed all sessions. Average integrity scores were high [90%-delivery/receipt, 87.5%-enactment]. Parents found CBT-CI helpful, age-appropriate, and autism-friendly. Paired samples t-tests (family-wise error controlled) found CBT-CI improved child sleep (objective SOL-18 min, TWT- 34 min, SE-5%; subjective SOL-29 min, TST-63 min, TWT-45 min, SE-8%), and decreased irritability, lethargy, stereotypy, and hyperactivity. At 1-month, objective TST improved, inappropriate speech decreased, but hyperactivity was no longer decreased. Other gains were maintained. Parent sleep (objective SOL-12 min, TST-35 min, TWT-21 min, SE-4%; subjective SOL-11 min, TWT- 31min, SE-11%) and fatigue also improved. At 1-month, gains were maintained. This pilot shows CBT-CI is a feasible treatment that holds promise for improving child and parent sleep and functioning and suggests a randomized controlled trial in school-aged children with autism is worth conducting. Autism Res 2020, 13: 167-176. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Insomnia is common in autism and associated with challenging behaviors and poor parent sleep and stress. Cognitive behavioral treatment for childhood insomnia (CBT-CI) has not been tested in school-aged children with autism. This pilot study shows therapists, parents, and children were able to use CBT-CI to improve child and parent sleep, child behavior, and parent fatigue. Parents found CBT-CI helpful, age-appropriate, and autism-friendly. CBT-CI holds promise for treating insomnia in school-aged children with autism and deserves further testing.

Surviving and thriving: Voices of Latina/o engineering students at a Hispanic serving institution.

This study examined factors that played a role in Latina/o undergraduate students' persistence in engineering at a Hispanic serving institution (HSI; N = 10) using the consensual qualitative research method (CQR; Hill, Thompson, & Williams, 1997). Data analyses resulted in five domains: institutional conditions, additive intersectional burdens, personal and cultural wealth, coping skills, and engineering identity. Participants described how they persisted in the face of stressors, citing specific coping skills they developed over time as well as general personal and cultural strengths they carried with them into their pursuit of engineering. Although the structures of the students' institution were generally described as supportive, Latina participants reported experiences with gendered racism that created added barriers to their persistence in engineering. Supportive institutional conditions, personal and cultural assets, and adaptive coping strategies appeared to facilitate the development of a strong engineering identity, which helped to solidify students' sense of belonging, pride, and commitment to complete their degree. Results highlight the need to address intersecting experiences of privilege and oppression to promote access and equity for Latinas/os in engineering. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Principales hábitos de medicación por los propietarios de caninos que acuden a consulta veterinaria en Pasto, Nariño, Colombia / Main medication habits in dogs made by theirowners who come to veterinary consultation in Pasto, Nariño, Colombia

El objetivo de este trabajo es determinar los hábitos de medicación en caninos por parte de los propietarios, antes de la consulta médica, y clasificar los medicamentos utilizados por grupo farmacológico. Para ello se realizó un estudio de utilización de medicamentos por medio de un cuestionario dirigido a 196 propietarios en seis clínicas veterinarias. Se encontró que el 95% de los propietarios medicaban a sus mascotas antes de la consulta médica. En el 6,4 % de los casos no coincidió la medicación que administraron con el diagnóstico final emitido por el médico veterinario, ya que la patología derivaba de otro sistema. El 63% optó por utilizar la vía oral como medio para administrar medicamentos. Las dos formas farmacéuticas más utilizadas fueron la líquida (55,91%) y la sólida (32,8%). El grupo farmacológico más utilizado fue el de los analgésicos no esteroidales (24,73%). Según la correlación fármaco-dosis- frecuencia-patología, el 98% de los propietarios no administraron adecuadamente los medicamentos. Se concluye que los propietarios medican a sus mascotas sin recomendación del médico veterinario, la mayoría de ellos lo realizan con productos no aprobados para uso en caninos, y las dosis utilizadas son incorrectas y no tienen en cuenta la frecuencia de administración.

The main objective of this work is determining the habits of medication in dogs by the owners before the veterinary consultation, and to classify the drugs used by pharmacological group. A study of drug use was performed by means of a questionnaire sent to 196 owners in six veterinary clinics. In 95% of owners, medication habits were evidenced before medical consultation. In 6.4% of cases, administered medication to pets did not match with the final diagnosis issued by the veterinarian, since the pathology derived from another system. 63% opted for using mouth for giving medication. The two pharmaceutical forms most used were liquid (55.91%) and solid (32.8%). The most used pharmacological group was the non-steroidal analgesics (24.73%). According to the drug-dose-frequency-pathology correlation, 98% of owners did not administer medications properly. The findings are: the owners medicate their pets without veterinary doctor recommendation, most of them do it with products which are not approved for being used in dogs, and doses used are incorrect and do not take into account the frequency of administration.

Micropapillary urothelial carcinoma of the urinary bladder: a clinicopathological analysis of 24 cases.

OBJECTIVES: To stratify patients with micropapillary urothelial carcinoma of the urinary bladder based on the percentage of micropapillary component and to correlate tumor volume with other clinicopathological features. METHODS: Cases of micropapillary urothelial carcinoma of the urinary bladder from 2002 to 2009 were identified. Only patients with available follow-up information were included in the analysis. Tumor volumes were stratified based on the percentage of micropapillary component (<50%, >50% and 100%). RESULTS: Overall, 24 cases were analyzed. Mean patient age was 71 years (range 55-86 years), with a male to female ratio of 3:1. Six cases (6/24; 25%) were composed entirely of micropapillary component. A total of 12 cases (12/24; 50%) showed >50% micropapillary component. Six cases (6/24; 25%) showed <50% micropapillary component. A higher percentage of micropapillary urothelial carcinoma component was significantly associated with male sex, regional lymph node metastasis and pathological stage (P-values = 0.0005, 0.01 and 0.03, respectively). The percentage of the micropapillary component was, however, unrelated to patients' survival. CONCLUSIONS: The present study confirms that micropapillary urothelial bladder carcinoma is typically aggressive and presents with advanced stage disease in most cases. A quantification of the micropapillary component is to be recommended. An accurate diagnosis of this entity in relatively small biopsies or transurethral resection of bladder tumor specimens is especially critical to define the best treatment plan.