Stop and Think: A Case Study Illustrating the Implementation of Bright IDEAS-YA Being Delivered via Telehealth to a Young Adult Cancer Patient.

Bright IDEAS-Young Adults (Bright IDEAS-YA) is a problem-solving skills training intervention that has been adapted for young adults with cancer. Presently, a multisite randomized control trial is being conducted to determine Bright IDEAS-YA's efficacy in supporting a young adult population. This case study demonstrates the young adult adaptation of Bright IDEAS - Bright IDEAS-YA - being delivered to a young adult cancer patient via telehealth. Telehealth is a novel delivery method for Bright IDEAS and Bright IDEAS-YA that was established due to COVID-19 safety precautions. The patient, who reported challenges in several life domains, was taught how to apply the Bright IDEAS-YA framework over six telehealth sessions. After completing the Bright IDEAS-YA framework, the patient reported increased feelings of confidence in managing new stressors, which was corroborated through outcome measures delivered during and following intervention. This case illustrates how early psychosocial intervention following a cancer diagnosis, delivered via telehealth, can help patients develop and implement personal strategies to reduce stress levels.

Factors Associated with COVID­19 Vaccine Uptake Among Adolescents and Young Adults Recently Diagnosed with Cancer.

Adolescents and young adults (AYAs) recently diagnosed with cancer are medically vulnerable but little is known about vaccine uptake/intent in this group. AYAs reported on their COVID-19 vaccine uptake/intent. Logistic regression models examined factors associated with vaccine uptake. Higher education (adjusted odds ratio [aOR] = 1.9, 95% confidence interval [CI]: 1.0-3.5) and knowing someone diagnosed with COVID-19 (aOR = 7.2, 95% CI: 1.6-33.5) were associated with increased vaccine uptake. Prior personal diagnosis of COVID-19 (aOR = 0.1, 95% CI: 0.1-0.7) was associated with lower odds of uptake. Targeted interventions may be needed to improve uptake among this group. (ClinicalTrials.gov Identifier: NCT04585269).

Aspergillus nidulans Septa Are Indispensable for Surviving Cell Wall Stress.

Septation in filamentous fungi is a normal part of development, which involves the formation of cross-hyphal bulkheads, typically containing pores, allowing cytoplasmic streaming between compartments. Based on previous findings regarding septa and cell wall stress, we hypothesized that septa are critical for survival during cell wall stress. To test this hypothesis, we used known Aspergillus nidulans septation-deficient mutants (ΔsepH, Δbud3, Δbud4, and Δrho4) and six antifungal compounds. Three of these compounds (micafungin, Congo red, and calcofluor white) are known cell wall stressors which activate the cell wall integrity signaling pathway (CWIS), while the three others (cycloheximide, miconazole, and 2,3-butanedione monoxime) perturb specific cellular processes not explicitly related to the cell wall. Our results show that deficiencies in septation lead to fungi which are more susceptible to cell wall-perturbing compounds but are no more susceptible to other antifungal compounds than a control. This implies that septa play a critical role in surviving cell wall stress. IMPORTANCE The ability to compartmentalize potentially lethal damage via septation appears to provide filamentous fungi with a facile means to tolerate diverse forms of stress. However, it remains unknown whether this mechanism is deployed in response to all forms of stress or is limited to specific perturbations. Our results support the latter possibility by showing that presence of septa promotes survival in response to cell wall damage but plays no apparent role in coping with other unrelated forms of stress. Given that cell wall damage is a primary effect caused by exposure to the echinocandin class of antifungal agents, our results emphasize the important role that septa might play in enabling resistance to these drugs. Accordingly, the inhibition of septum formation could conceivably represent an attractive approach to potentiating the effects of echinocandins and mitigating resistance in human fungal pathogens.

Micafungin-Induced Cell Wall Damage Stimulates Morphological Changes Consistent with Microcycle Conidiation in Aspergillus nidulans.

Fungal cell wall receptors relay messages about the state of the cell wall to the nucleus through the Cell Wall Integrity Signaling (CWIS) pathway. The ultimate role of the CWIS pathway is to coordinate repair of cell wall damage and to restore normal hyphal growth. Echinocandins such as micafungin represent a class of antifungals that trigger cell wall damage by affecting synthesis of ß-glucans. To obtain a better understanding of the dynamics of the CWIS response and its multiple effects, we have coupled dynamic transcriptome analysis with morphological studies of Aspergillus nidulans hyphae in responds to micafungin. Our results reveal that expression of the master regulator of asexual development, BrlA, is induced by micafungin exposure. Further study showed that micafungin elicits morphological changes consistent with microcycle conidiation and that this effect is abolished in the absence of MpkA. Our results suggest that microcycle conidiation may be a general response to cell wall perturbation which in some cases would enable fungi to tolerate or survive otherwise lethal damage.

Dynamic Transcriptomic and Phosphoproteomic Analysis During Cell Wall Stress in Aspergillus nidulans.

The fungal cell-wall integrity signaling (CWIS) pathway regulates cellular response to environmental stress to enable wall repair and resumption of normal growth. This complex, interconnected, pathway has been only partially characterized in filamentous fungi. To better understand the dynamic cellular response to wall perturbation, a ß-glucan synthase inhibitor (micafungin) was added to a growing A. nidulans shake-flask culture. From this flask, transcriptomic and phosphoproteomic data were acquired over 10 and 120 min, respectively. To differentiate statistically-significant dynamic behavior from noise, a multivariate adaptive regression splines (MARS) model was applied to both data sets. Over 1800 genes were dynamically expressed and over 700 phosphorylation sites had changing phosphorylation levels upon micafungin exposure. Twelve kinases had altered phosphorylation and phenotypic profiling of all non-essential kinase deletion mutants revealed putative connections between PrkA, Hk-8-4, and Stk19 and the CWIS pathway. Our collective data implicate actin regulation, endocytosis, and septum formation as critical cellular processes responding to activation of the CWIS pathway, and connections between CWIS and calcium, HOG, and SIN signaling pathways.