15-Lipoxygenase-Mediated Lipid Peroxidation Regulates LRRK2 Kinase Activity.

Mutations in leucine-rich repeat kinase 2 (LRRK2) that increase its kinase activity are strongly linked to genetic forms of Parkinson's disease (PD). However, the regulation of endogenous wild-type (WT) LRRK2 kinase activity remains poorly understood, despite its frequent elevation in idiopathic PD (iPD) patients. Various stressors such as mitochondrial dysfunction, lysosomal dyshomeostasis, or vesicle trafficking deficits can activate WT LRRK2 kinase, but the specific molecular mechanisms are not fully understood. We found that the production of 4-hydroxynonenal (4-HNE), a lipid hydroperoxidation end-product, is a common biochemical response to these diverse stimuli. 4-HNE forms post-translational adducts with Cys2024 and Cys2025 in the kinase activation loop of WT LRRK2, significantly increasing its kinase activity. Additionally, we discovered that the 4-HNE responsible for regulating LRRK2 is generated by the action of 15-lipoxygenase (15-LO), making 15-LO an upstream regulator of the pathogenic hyperactivation of LRRK2 kinase activity. Pharmacological inhibition or genetic ablation of 15-LO prevents 4-HNE post-translational modification of LRRK2 kinase and its subsequent pathogenic hyperactivation. Therefore, 15-LO inhibitors, or methods to lower 4-HNE levels, or the targeting of Cys2024/2025 could provide new therapeutic strategies to modulate LRRK2 kinase activity and treat PD.

Qualité des soins dans les établissements de soins de longue durée canadiens accueillant différents groupes linguistiques.

OBJECTIVES: Canada has two official languages (English and French) that vary in usage by province/territory and other smaller geographic units. The objective of this study was to compare the characteristics of persons receiving care in long-term care homes serving different language groups and to examine the extent to which data quality and distributional properties of indicators vary between homes. METHODS: We used routinely collected interRAI Minimum Data Set (MDS) 2.0 assessment data from nine Canadian provinces and territories to classify 1,333 long-term care homes into predominately English, French, and mixed language groups. We compared resident characteristics, risk-adjusted quality indicator performance, and assessment data quality by facility language group. RESULTS: In these data, eighteen (1.35%) long-term care homes served predominately French-speaking residents. An additional 274 (20.54%) homes were classified as mixed language homes, where 20% or more residents spoke a language other than English or French. The remaining homes (1,042; 78.11%) were classified as English homes. We did not observe substantial differences between facility language groups in terms of resident characteristics, quality indicator performance, and data quality. CONCLUSIONS: Despite linguistic differences, long-term care homes in Canada serving residents that speak predominately French and other languages can be compared directly with homes serving predominantly English-speaking residents. These findings support language-agnostic benchmarking of quality of care among long-term care homes situated across Canada, particularly in officially bilingual provinces.

Prevalence and predictors of influenza vaccination in long-term care homes: a cross-national retrospective observational study.

OBJECTIVE: To compare facility-level influenza vaccination rates in long-term care (LTC) homes from four countries and to identify factors associated with influenza vaccination among residents. DESIGN AND SETTING: Retrospective cross-sectional study of individuals residing in LTC homes in New Brunswick (Canada), New Zealand, Switzerland, and the Netherlands between 2017 and 2020. PARTICIPANTS: LTC home residents assessed with interRAI assessment system instruments as part of routine practice in New Brunswick (n=7006) and New Zealand (n=34 518), and national pilot studies in Switzerland (n=2760) and the Netherlands (n=1508). End-of-life residents were excluded from all country cohorts. OUTCOMES: Influenza vaccination within the past year. RESULTS: Influenza vaccination rates among LTC home residents were highest in New Brunswick (84.9%) and lowest in Switzerland (63.5%). For all jurisdictions where facility-level data were available, substantial interfacility variance was observed. There was approximately a fourfold difference in the coefficient of variation for facility-level vaccination rates with the highest in Switzerland at 37.8 and lowest in New Brunswick at 9.7. Resident-level factors associated with vaccine receipt included older age, severe cognitive impairment, medical instability, health conditions affecting a greater number of organ systems and social engagement. Residents who displayed aggressive behaviours and smoke tobacco were less likely to be vaccinated. CONCLUSION: There are opportunities to increase influenza vaccine uptake at both overall country and individual facility levels. Enhanced vaccine administration monitoring programmes in LTC homes that leverage interRAI assessment systems should be widely adopted.

Evaluating the Effect of COVID-19 Pandemic Lockdown on Long-Term Care Residents' Mental Health: A Data-Driven Approach in New Brunswick.

Long-term care (LTC) residents, isolated because of the COVID-19 pandemic, are at increased risk for negative mental health outcomes. The purpose of our article is to demonstrate how the interRAI LTC facility (LTCF) assessment can inform clinical care and evaluate the effect of strategies to mitigate worsening mental health outcomes during the COVID-19 pandemic. We present a supporting analysis of the effects of lockdown in homes without COVID-19 outbreaks on depression, delirium, and behavior problems in a network of 7 LTC homes in New Brunswick, Canada, where mitigative strategies were deployed to minimize poor mental health outcomes (eg, virtual visits and increased student volunteers). This network meets regularly to review performance on risk-adjusted quality of care indicators from the interRAI LTCF and share learning through a community of practice model. We included 4209 assessments from 765 LTC residents between January 2017 to June 2020 and modeled the change within and between residents for depression, delirium, and behavioral problems over time with longitudinal generalized estimating equations. Though the number of residents who had in-person visits with family decreased from 73.2% before to 17.9% during lockdown (chi square, P < .001), the number of residents experiencing delirium (4.5%-3.5%, P = .51) and behavioral problems (35.5%-30.2%, P = .19) did not change. The proportion of residents with indications of depression decreased from 19.9% before to 11.5% during lockdown (P < .002). The final multivariate models indicate that the effect of lockdown was not statistically significant on depression, delirium, or behavioral problems. Our analyses demonstrate that poor mental health outcomes associated with lockdown can be mitigated with thoughtful intervention and ongoing evaluation with clinical information systems. Policy makers can use outputs to guide resource deployment, and researchers can examine the data to identify better management strategies for when pandemic strikes again.

Implications of interprofessional primary care team characteristics for health services and patient health outcomes: A systematic review with narrative synthesis.

Interprofessional primary care (IPPC) teams are promoted as an alternative to single profession physician practices in primary care with focus on preventive care and chronic disease management. Characteristics of teams can have an impact on their performance. We synthesized quantitative, qualitative or mixed-methods evidence addressing the design of IPPC teams. We searched Ovid MEDLINE, Embase, CINAHL, and PAIS using search terms focused on IPPC teams. Studies were included if they discussed the influence of team structure, organization, financial arrangements, or policies and procedures, or either health care processes or outputs, health outcomes, or costs, and were conducted in Australia, Canada, the United Kingdom or New Zealand between 2003 and 2016. We screened 11,707 titles, 5366 abstracts, and selected 77 full text articles (38 qualitative, 31 quantitative and 8 mixed-methods). Literature focused on the implications of team characteristics on team processes, such as teamwork, collaboration, or satisfaction of patients or providers. Despite heterogeneity of contexts, some trends are observable: shared space, common vision and goals, clear definitions of roles, and leadership as important to good teamwork. The impacts of these on health care outputs or patient health are not clear. To move the state of knowledge beyond perception of what works well for IPPC teams, researchers should focus on quantitative causal inference about the linkages between team characteristics and patient health.

Perceptions of the assistant theatre practitioner role: a view from my ivory tower.

At a recent AfPP event, during a debating session amongst fellow perioperative practitioners, the role and remit of assistant theatre practitioner (ATP) was raised. The debating panel's views were sought from several quarters and the subject seemed to spark discussion and much 'harrumphing' in the audience. A recently qualified ATP, who, having spent an intensive two years studying for a foundation degree, expressed his frustration about on-going role ambiguity and the struggle to have his newly acquired knowledge and skills recognised in practice. As a heated discussion went around the room, polarised views were emergent, in particular themed around concerns about delegation, accountability and scope of practice.

Is it blepharitis?

Blepharitis is a ubiquitous disease and arguably, among the most common conditions that eye care practitioners encounter. Usually, its diagnosis is straight forward. However, any deviation from its predicted clinical appearance should cause the practitioner to consider other possibilities. The patient described in this report was diagnosed with blepharitis and treated as such. However, the true cause of her difficulties was basal cell carcinoma. This condition is briefly reviewed.