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OBJECTIVE: To determine factors that predict disclosure of natural product use by patients to their primary care physicians. METHODS: An 18-item survey about health care use and communication was distributed to patients who presented to the Canadian College of Naturopathic Medicine in March 2003. We examined correlations between responses and created a multivariable logistic regression model to explore which factors were associated with patients' discussion of natural product use with their primary care physicians. RESULTS: The survey was given to 198 patients, 174 of whom responded (response rate, 87.9%). Most respondents (161 [92.5%] of 174) made use of natural products, and many (61 [41.5%] of 147) reported that they did not discuss natural product use with their primary care physician. The most significant factor predictive of patients having discussed natural product use with their primary care physician was having their primary care physician ask about natural product use (odds ratio, 18.77; 95% confidence interval, 5.06-69.62). Most respondents (107 [69.9%] of 153) indicated that their primary care physician did not ask about natural product use. CONCLUSIONS: An important number of patients who visit a naturopathic clinic do not disclose natural product use to their primary care physicians. Our findings suggest that disclosure rates could be improved by physicians taking a more active role in asking their patients about natural product use. [ABSTRACT FROM AUTHOR]

Background: Nonmelanoma skin cancer (NMSC) affects many Canadians. Although morbidity and mortality are rare, the burden to patients and the health-care system is significant. This study aims to evaluate current plastic surgery wait times and care pathways for patients with NMSC in Southwestern Ontario., Methods: A retrospective chart review of 225 patients treated in Ontario from 2015 to 2018 was conducted. Inclusion criteria included patients with an NMSC managed with surgical excision. Referral information was compared. Primary outcomes were wait times: from referral to consultation, referral to excision, and consultation to excision. Data were analyzed using Student t test with equal variance., Results: One-hundred forty-three patients were included from the academic cohort and 82 from the community cohort. Referrals to academic and community surgeons included lesion location (90% and 97.6%, respectively), but less frequently included size (18% and 29.2%, respectively). Most referrals to academic surgeons included biopsy results (78.6%), as opposed to community referrals (25.6%). Patients in the academic cohort waited 15.3 ± 12.7 weeks from referral to consultation, and 15.7 ± 13 weeks from referral to excision. Patients from the community cohort waited significantly shorter periods of 4.9 ± 3.1 ( P < .001) and 11.7 ± 9.9 weeks ( P = .016), respectively. However, patients of the academic cohort waited 2.4 ± 7.1 weeks from consultation to excision, while patients in the community cohort waited 6.7 ± 9.6 weeks ( P < .001). Rates of negative peripheral margins on pathology were similar between groups, at 89.5% of the academic cohort and 88.9% of the community cohort. Deep margins were positive 5.7% of the time at the academic sites and 6.2% of the time in the community., Conclusions: Patients referred to academic centres waited significantly longer periods of time in several parameters compared to those referred to a community surgeon. However, academic surgeons often had expedited consultation-to-excision time frame. This study provides important data for future quality improvement initiatives in NMSC care., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2019 The Author(s).)

Pathological mechanisms underlying Down syndrome (DS)/Trisomy 21, including dysregulation of essential signalling processes remain poorly understood. Combining bioinformatics with RNA and protein analysis, we identified downregulation of the Wnt/β-catenin pathway in the hippocampus of adult DS individuals with Alzheimer's disease and the 'Tc1' DS mouse model. Providing a potential underlying molecular pathway, we demonstrate that the chromosome 21 kinase DYRK1A regulates Wnt signalling via a novel bimodal mechanism. Under basal conditions, DYRK1A is a negative regulator of Wnt/β-catenin. Following pathway activation, however, DYRK1A exerts the opposite effect, increasing signalling activity. In summary, we identified downregulation of hippocampal Wnt/β-catenin signalling in DS, possibly mediated by a dose dependent effect of the chromosome 21-encoded kinase DYRK1A. Overall, we propose that dosage imbalance of the Hsa21 gene DYRK1A affects downstream Wnt target genes. Therefore, modulation of Wnt signalling may open unexplored avenues for DS and Alzheimer's disease treatment.

Background: To measure trends in child growth and combat rising levels of obesity, Manchester University NHS Foundation Trust and the University of Manchester have developed Children's Health and Monitoring Programme (CHAMP). CHAMP collects an annual measurement for primary school children (aged 4 to 11) in Manchester, England, and offers feedback of Body Mass Index (BMI) results to parents via a secure website. No similar digital tool exists that both provides high resolution data on the trajectory of child growth and acts as a feedback and monitoring system. This study investigates how effectively this intervention engaged with parents and supported the reduction of childhood obesity., Methods: Anonymised CHAMP registration and BMI data (UK1990) were collected between September 2013 and March 2017 from a total of 63,337 children. BMI change over time was compared in matched cohorts of 24,551 children, whose parents had and had not registered with the CHAMP website. Qualitative focus groups and interviews were used to explore perspectives among 29 key informants (parents, school and healthcare professionals) from six schools in Manchester., Results: Overweight children whose parents had not registered with the CHAMP website gained a median of 0.14 BMI centile between measurements, whilst children of CHAMP-registered parents reduced their BMI by a median of 0.4 centile per year (P = 0.02). Normal weight children of registered parents decreased their BMI by 0.3 centile each year, whilst those not registered increased their BMI by 0.8 centile per year (P = 0.001). There was no significant association between registration and BMI centile change in children already classified as obese (P = 0.34). A qualitative, thematic analysis revealed that the annual measurement programme was widely supported by parents and staff. A range of psychological and behavioural impacts on families were reported as a result of the monitoring and feedback processes, in some cases prompting reflection and monitoring of health and lifestyle choices., Conclusion: These early findings indicate that CHAMP, as both a monitoring system and a digital intervention, could encourage positive lifestyle change and support healthier child growth trajectories.

Mutations in leucine-rich repeat kinase 2 (LRRK2) segregate with familial Parkinson's disease (PD) and genetic variation around LRRK2 contributes to risk of sporadic disease. Although knockout (KO) of Lrrk2 or knock-in of pathogenic mutations into the mouse germline does not result in a PD phenotype, several defects have been reported in the kidneys of Lrrk2 KO mice. To understand LRRK2 function in vivo, we used an unbiased approach to determine which protein pathways are affected in LRRK2 KO kidneys. We nominated changes in cytoskeletal-associated proteins, lysosomal proteases, proteins involved in vesicular trafficking and in control of protein translation. Changes were not seen in mice expressing the pathogenic G2019S LRRK2 mutation. Using cultured epithelial kidney cells, we replicated the accumulation of lysosomal proteases and demonstrated changes in subcellular distribution of the cation-independent mannose-6-phosphate receptor. These results show that loss of LRRK2 leads to co-ordinated responses in protein translation and trafficking and argue against a dominant negative role for the G2019S mutation.

Cytoskeletal homeostasis is essential for the development, survival and maintenance of an efficient nervous system. Microtubules are highly dynamic polymers important for neuronal growth, morphology, migration and polarity. In cooperation with several classes of binding proteins, microtubules regulate long-distance intracellular cargo trafficking along axons and dendrites. The importance of a delicate interplay between cytoskeletal components is reflected in several human neurodegenerative disorders linked to abnormal microtubule dynamics, including Parkinson's disease (PD). Mounting evidence now suggests PD pathogenesis might be underlined by early cytoskeletal dysfunction. Advances in genetics have identified PD-associated mutations and variants in genes encoding various proteins affecting microtubule function including the microtubule-associated protein tau. In this review, we highlight the role of microtubules, their major posttranslational modifications and microtubule associated proteins in neuronal function. We then present key evidence on the contribution of microtubule dysfunction to PD. Finally, we discuss how regulation of microtubule dynamics with microtubule-targeting agents and deacetylase inhibitors represents a promising strategy for innovative therapeutic development.

Background: This article describes the testing of a new nursing home food delivery system that empowers elders to choose the foods they want to eat and gives them an active voice in menu development., Methods: Using a 2-group, repeated measures design, 61 elderly residents from 2 eastern Washington nursing homes were recruited to participate in a 6-month study. Outcome measures included food and meal service satisfaction, body weight, serum prealbumin, and food intake., Results: Serum prealbumin levels and body weight increased post intervention for treatment group residents. Mini-Mental Status Examination (MMSE) scores were not associated with the changes in serum prealbumin, body weight, or food intake., Discussion: The MMSE scores did not influence the resident's ability to actively participate in the rate the food process or choose the foods they liked and preferred to eat. Cognitive impaired older adults experienced weight gain similarly to higher functioning elderly individuals., (© The Author(s) 2012.)