ABSTRACT
Parkinson's disease (PD) is a complex diagnosis commonly associated with motor dysfunction, but known to comprise cognitive, psychiatric, and mood disturbances as well. Music has been successfully used to address motor and non-motor symptoms of PD. Still, little is known about the nature of an individual with PD's experience and relationship with music on conceptual and emotional levels, which may factor into their engagement in music-based techniques to ameliorate impairments. Two surveys were administered to 19 individuals with PD and 15 individuals without PD in order to gauge their subjective impressions and valuations of music. Participants completed The Brief Music Experience Questionnaire (BMEQ), a standard self-report measure pertaining to the role of music in one's life, prior to performing a perception task which involved listening to and making sound adjustments to three music recordings. Following the perception task, a custom Exit Survey was administered to evaluate the experience of listening to and engaging with the music in the perception task. In all six dimensions of the BMEQ, examining aspects of music experience including commitment to music, self-reported musical aptitude, social uplift, affective reactions, positive psychotropic effects, and reactive musical behavior (RMB, pertaining to actions or behaviors in response to music), the mean and the median were greater for the control group than for the PD group, but the difference was only statistically significant in the RMB dimension. On the Exit Survey, both groups assessed recent, specific, and interactive music listening more positively than the imagined, hypothetical or general music experiences addressed on the BMEQ. Additionally, familiarity had a greater effect on listening pleasure for participants with PD than those without PD. We conclude that people with PD may perceive less of an automatic connection between music and activity than their healthy peers. Additionally, they may receive more pleasure and value from music than they anticipate. Taken together, our results suggest that people with PD may require encouragement to participate as well as empowerment to choose familiar selections in order to better access music-based interventions and the benefits they can offer.
ABSTRACT
Invasive aspergillosis (IA) remains the primary cause of morbidity and mortality in chronic granulomatous disease (CGD) patients, often due to infection by Aspergillus species refractory to antifungals. This motivates the search for alternative treatments, including immunotherapy. We investigated the effect of exogenous type I interferon (IFN) activation on the outcome of IA caused by three Aspergillus species, A. fumigatus, A. nidulans, and A. tanneri, in CGD mice. The animals were treated with poly(I):poly(C) carboxymethyl cellulose poly-l-lysine (PICLC), a mimetic of double-stranded RNA, 24 h preinfection and postinfection. The survival rates and lung fungal burdens were markedly improved by PICLC immunotherapy in animals infected with any one of the three Aspergillus species. While protection from IA was remarkable, PICLC induction of type I IFN in the lungs surged 24 h posttreatment and returned to baseline levels by 48 h, suggesting that PICLC altered early events in protection against IA. Immunophenotyping of recruited leukocytes and histopathological examination of tissue sections showed that PICLC induced similar cellular infiltrates as those in untreated-infected mice, in both cases dominated by monocytic cells and neutrophils. However, the PICLC immunotherapy resulted in a marked earlier recruitment of the leukocytes. Unlike with conidia, infection with A. nidulans germlings reduced the protective effect of PICLC immunotherapy. Additionally, antibody depletion of neutrophils totally reversed the protection, suggesting that neutrophils are crucial for PICLC-mediated protection. Together, these data show that prophylactic PICLC immunotherapy prerecruits these cells, enabling them to attack the conidia and thus resulting in a profound protection from IA.IMPORTANCE Patients with chronic granulomatous disease (CGD) are highly susceptible to invasive aspergillosis (IA). While Aspergillus fumigatus is the most-studied Aspergillus species, CGD patients often suffer IA caused by A. nidulans, A. tanneri, and other rare species. These non-fumigatus Aspergillus species are more resistant to antifungal drugs and cause higher fatality rates than A. fumigatus Therefore, alternative therapies are needed to protect CGD patients. We report an effective immunotherapy of mice infected with three Aspergillus species via PICLC dosing. While protection from IA was long lasting, PICLC induction of type I IFN surged but quickly returned to baseline levels, suggesting that PICLC was altering early events in IA. Interestingly, we found responding immune cells to be similar between PICLC-treated and untreated-infected mice. However, PICLC immunotherapy resulted in an earlier recruitment of the leukocytes and suppressed fungal growth. This study highlights the value of type I IFN induction in CGD patients.
