α-Synuclein Pathology and Reduced Neurogenesis in the Olfactory System Affect Olfaction in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathologic changes in the olfactory pathway of transgenic (Tg) mice of both sexes expressing the human A30P mutant α-synuclein (α-syn; α-syn-Tg mice) at 6-7 and 12-14 months of age, representing early and late-stages of motor progression, respectively. α-Syn-Tg mice at late stages exhibited olfactory behavioral deficits, which correlated with severe α-syn pathology in projection neurons (PNs) of the olfactory pathway. In parallel, olfactory bulb (OB) neurogenesis in α-syn-Tg mice was reduced in the OB granule cells at six to seven months and OB periglomerular cells at 12-14 months, respectively, both of which could contribute to olfactory dysfunction. Proteomic analyses showed a disruption in endocytic and exocytic pathways in the OB during the early stages which appeared exacerbated at the synaptic terminals when the mice developed olfactory deficits at 12-14 months. Our data suggest that (1) the α-syn-Tg mice recapitulate the olfactory functional deficits seen in PD; (2) olfactory structures exhibit spatiotemporal disparities for vulnerability to α-syn pathology; (3) α-syn pathology is restricted to projection neurons in the olfactory pathway; (4) neurogenesis in adult α-syn-Tg mice is reduced in the OB; and (5) synaptic endocytosis and exocytosis defects in the OB may further explain olfactory deficits.SIGNIFICANCE STATEMENT Olfactory dysfunction is a characteristic symptom of Parkinson's disease (PD). Using the human A30P mutant α-synuclein (α-syn)-expressing mouse model, we demonstrated the appearance of olfactory deficits at late stages of the disease, which was accompanied by the accumulation of α-syn pathology in projection neurons (PNs) of the olfactory system. This dysfunction included a reduction in olfactory bulb (OB) neurogenesis as well as changes in synaptic vesicular transport affecting synaptic function, both of which are likely contributing to olfactory behavioral deficits.

Inflammatory Response and Defects on Myelin Integrity in the Olfactory System of K18hACE2 Mice Infected with SARS-CoV-2.

Viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), use respiratory epithelial cells as an entry point for infection. Within the nasal cavity, the olfactory epithelium (OE) is particularly sensitive to infections which may lead to olfactory dysfunction. In patients suffering from coronavirus disease 2019, deficits in olfaction have been characterized as a distinctive symptom. Here, we used the K18hACE2 mice to study the spread of SARS-CoV-2 infection and inflammation in the olfactory system (OS) after 7 d of infection. In the OE, we found that SARS-CoV-2 selectively targeted the supporting/sustentacular cells (SCs) and macrophages from the lamina propria. In the brain, SARS-CoV-2 infected some microglial cells in the olfactory bulb (OB), and there was a widespread infection of projection neurons in the OB, piriform cortex (PC), and tubular striatum (TuS). Inflammation, indicated by both elevated numbers and morphologically activated IBA1+ cells (monocyte/macrophage lineages), was preferentially increased in the OE septum, while it was homogeneously distributed throughout the layers of the OB, PC, and TuS. Myelinated OS axonal tracts, the lateral olfactory tract, and the anterior commissure, exhibited decreased levels of 2',3'-cyclic-nucleotide 3'-phosphodiesterase, indicative of myelin defects. Collectively, our work supports the hypothesis that SARS-CoV-2 infected SC and macrophages in the OE and, centrally, microglia and subpopulations of OS neurons. The observed inflammation throughout the OS areas and central myelin defects may account for the long-lasting olfactory deficit.

Delivering Trauma-Informed Care in a Hospital Ward for Older Adults With Dementia: An Illustrative Case Series.

Introduction: Up to 70% of older adults have experienced a psychologically traumatic event in their life. Traumatic events can have lifelong effects on functioning and emotion regulation and can affect behavior and experiences in care settings. Common healthcare practices and environments can be re-traumatizing for trauma survivors. These features may trigger behavior change (e.g., aggression and agitation) particularly after the onset of dementia. However, very little research exists to understand how the effects of traumatic events manifest in aged care settings. Trauma-informed care is a framework in which the potential impact of trauma is acknowledged, and practices and procedures are adapted to maximize feelings of control and safety for the patient. Trauma-informed care is an innovative approach with little published evidence in acute geriatric settings. Methods: We present a series of cases to demonstrate how psychological trauma can affect the experience of inpatient care for older people. The cases detail the patients' relevant background, triggers and behaviors followed by the steps taken by staff to support the patient and respond to their trauma-related needs. These cases describe how the principles of trauma-informed care can be applied to recognize when past psychologically traumatic events are impacting the older adult in hospital. The outcomes of these interventions are reported on in terms of their impact on challenging behavior, patient experiences and satisfaction with care, and/or staff confidence and skill. Findings: A range of past events negatively impacted the patients during their time in hospital, including childhood abuse, military service, and domestic violence. Staff implemented strategies to accommodate trauma-related needs while providing care that improved safety and reduced patient distress. Principles of trauma-informed care were applied where able, including providing choices and enabling autonomy. However, organizational and environmental features of inpatient wards continued to pose risks for re-traumatisation. Conclusions: Trauma-informed care is an under-utilized yet potentially beneficial approach to care for older adults in the hospital setting. The cases detailed here demonstrated that the impact of psychological trauma requires an individualized response from staff which when effectively implemented can promote staff and patient safety, reduce the risk of re-traumatisation, and minimize adverse events.

A collaborative process for a program redesign for education in evidence-based health care.

OBJECTIVE:: We outline the framework of a collaborative process to redesign an existing 5-year health education program, which may prove useful to other similar institutions. The aim was to strengthen evidence-based practice and curriculum alignment. METHODS:: A whole-of-program approach was used to restructure the existing courses into 3 "streams": professional practice, clinical research, and clinical science. The process incorporated a series of facilitated workshops organized by the department director of learning and teaching and the faculty facilitation team, and it was inclusive of all available members of the department, a clinic supervisor, a sessional (casual teaching) staff member, and a recent graduate of the program. RESULTS:: Unit content and assessments were restructured to progress the program learning outcomes from year to year. The undergraduate program was redesigned to create a more logical learning pathway for students. Consolidation of subject topics in the postgraduate program allowed for the development of stand-alone research-only units. CONCLUSION:: The mechanism of curriculum mapping allowed for discussion about the flow of information from year to year and how evidenced knowledge and understanding can be developed. It is necessary that everyone participates and understands the importance of program goals as developed by the process. Because drift in curriculum can occur incrementally over the years, to be effective, the program requires ongoing monitoring and regular collaboration to continue improvements.