Intergenerational conversations on death and dying during the COVID-19 pandemic: A pedagogical approach.

This exploratory study examined how twenty-two undergraduate students and fifty-six older adults experienced discussing dying, death, and the COVID-19 pandemic with one another, using the book Tuesdays with Morrie as a conversational guide. The timing of these conversations is significant as discussions took place in March 2021, one year into the COVID-19 pandemic. Thematic analysis of students' and older adult's reflections on the discussion was employed and three themes were identified: the inevitability of death, gaining and giving perspective, and the importance of relationships. The pandemic was especially influential within two of the three themes. The findings highlight the benefits of bringing previously unknown people together to engage in conversations about dying and death during the pandemic using contemporary literature. This study also presents a pedagogical technique for educators to use to help students engage in discussions about death and dying.

Anti-cancer potential of cannabis terpenes in a Taxol-resistant model of breast cancer.

Chemotherapeutic resistance can limit breast cancer outcomes; therefore, the exploration of novel therapeutic options is warranted. Isolated compounds found in cannabis have previously been shown to exhibit anti-cancer effects, but little is known about their effects in resistant breast cancer. Our study aimed to evaluate the effects of terpenes found in cannabis in in vitro chemotherapy-resistant model of breast cancer. We aimed to identify whether five terpenes found in cannabis produced anti-cancer effects, and whether their effects were improved upon co-treatment with cannabinoids and flavonoids also found in cannabis. Nerolidol and ß-caryophyllene produced the greatest cytotoxic effects, activated the apoptotic cascade, and reduced cellular invasion. Combinations with the flavonoid kaempferol potentiated the cytotoxic effects of ocimene, terpinolene, and ß-myrcene. Combinations of nerolidol and Δ9-tetrahydrocannabinol or cannabidiol produced variable responses ranging from antagonism and additivity to synergy, depending on concentrations used. Our results indicate that cannabis terpenes, alone or combined with cannabinoids and flavonoids, produced anti-cancer effects in chemotherapy-resistant breast cancer cell lines. This study is a first step in the identification of compounds that could have therapeutic potential in the treatment of resistant breast cancer.

Polarity scaffolds signaling in epithelial cell permeability.

As an integral part of the innate immune system, the epithelial membrane is exposed to an array of insults that may trigger an immune response. One of the immune system's main functions is to regulate the level of communications between the mucosa and the lumen of various tissues. While it is clear that inhaled or ingested substances, or microorganisms may induce changes that affect the epithelial barrier in various ways, the proteins involved in the signaling cascades and physiological events leading to the regulation and maintenance of the barrier are not always well characterized. We review here some of the signaling components involved in regulating the barrier's paracellular permeability, and their potential effects on the activation of an immune response. While an effective immune response must be launched against pathogenic insults, tolerance must also be maintained for non-pathogenic antigens such as those in the commensal flora or for endogenous metabolites. Along with other members of the innate and adaptive immunity, the endocannabinoid system also plays an instrumental role in maintaining the balance between inflammation and tolerance. We discuss the potential effects of endo- and phytocannabinoids on epithelial permeability and how the dysregulation of this system could be involved in diseases and targeted for therapy.

Retrospective analysis of oblique and straight distal sesamoidean ligament desmitis in 52 horses.

BACKGROUND: Injuries to the oblique (ODSL) or straight (SDSL) distal sesamoidean ligaments are a recognised cause of distal limb lameness in the horse. However, there are only limited publications addressing common diagnostic features and prognosis. OBJECTIVES: (a) Report findings on ultrasonography and standing low-field magnetic resonance imaging (sMRI) in horses with ODSL or SDSL injury; (b) Identify clinical variables associated with lesion type and (c) Identify factors associated with return to soundness in horses with ODSL or SDSL injury. STUDY DESIGN: Retrospective case series. METHODS: Horses with a primary diagnosis of ODSL or SDSL injury confirmed with a combination of diagnostic analgesia and detection of a lesion on imaging (ultrasonographic ± advanced imaging) were included. Return to soundness and performance follow-up data were obtained. RESULTS: Fifty-one horses were included. SDSL injuries were more common in the forelimb (13/21, 62%), while ODSL injuries had equal frequency in fore- (15/30, 50%) and hindlimbs (15/30, 50%). ODSL injuries were more likely than SDSL injuries to affect the proximal third of the ligament (OR =13; 95% CI 2.3-74.3; p = 0.004) and often presented with periligamentar swelling (20/30;67%) and focal pain (22/28;79%). Lesions were frequently detected using ultrasonography (35/42;83%) and sMRI examination (18/25;72%). Only 27/49 cases (55%) returned to soundness, with only 15/49 (31%) returning to intended use. There were no significant associations between outcome and clinical features or treatment. MAIN LIMITATIONS: There was no comparative "gold standard" to validate lesions such as high-field MRI or histopathology. CONCLUSIONS: In contrast to previous studies, ODSL and SDSL injuries were readily identified ultrasonographically using appropriate views, and with sMRI. Given the limited availability, cost and general anaesthetic risks associated with high-field MRI, more focus should be placed on optimising the ultrasonographic examination. Owners of affected horses should be informed of the guarded prognosis for return to full use.

Antitumor Activity of Abnormal Cannabidiol and Its Analog O-1602 in Taxol-Resistant Preclinical Models of Breast Cancer.

Cannabinoids exhibit anti-inflammatory and antitumorigenic properties. Contrary to most cannabinoids present in the Cannabis plant, some, such as O-1602 and abnormal cannabidiol, have no or only little affinity to the CB1 or CB2 cannabinoid receptors and instead exert their effects through other receptors. Here, we investigated whether the synthetic regioisomers of cannabidiol, abnormal cannabidiol, and a closely related compound, O-1602, display antitumorigenic effects in cellular models of breast cancer and whether it could reduce tumorigenesis in vivo. Several studies have shown the effects of cannabinoids on chemotherapy-sensitive breast cancer cell lines, but less is known about the antitumorigenic effects of cannabinoids in chemotherapy-resistant cell lines. Paclitaxel-resistant MDA-MB-231 and MCF-7 breast cancer cell lines were used to study the effect of O-1602 and abnormal cannabidiol on viability, apoptosis, and migration. The effects of O-1602 and abnormal cannabidiol on cell viability were completely blocked by the combination of GPR55 and GPR18-specific siRNAs. Both O-1602 and abnormal cannabidiol decreased viability in paclitaxel-resistant breast cancer cells in a concentration-dependent manner through induction of apoptosis. The effect of these cannabinoids on tumor growth in vivo was studied in a zebrafish xenograft model. In this model, treatment with O-1602 and abnormal cannabidiol (2 µM) significantly reduced tumor growth. Our results suggest that atypical cannabinoids, like O-1602 and abnormal cannabidiol, exert antitumorigenic effects on paclitaxel-resistant breast cancer cells. Due to their lack of central sedation and psychoactive effects, these atypical cannabinoids could represent new leads for the development of additional anticancer treatments when resistance to conventional chemotherapy occurs during the treatment of breast and possibly other cancers.