We previously showed that folic acid prescriptions for any indication were associated with lower rates of suicidal behaviour. Given that future randomised clinical trials are likely to focus on psychiatric disorders carrying elevated risk for suicide, we now report on the moderating effects of prior suicidal behaviour, psychiatric diagnoses and psychotropic medications on potential antisuicidal effects of folic acid. Data were obtained from the MarketScan Commercial Claims and Encounters databases that cover 164 million insured persons from 2005–2017, from which a cohort of 866 586 patients was derived. Analysis revealed no significant moderation effects on the antisuicidal effect of folic acid. These findings indicate that the potential benefit of folic acid for preventing suicidal behaviour is comparable in psychiatric populations at higher risk of suicide and that it may be additive to any benefit from psychotropic medications.

Background: Saccade and pupil responses are potential neurodegenerative disease biomarkers due to overlap between oculomotor circuitry and disease-affected areas. Instruction-based tasks have previously been examined as biomarker sources, but are arduous for patients with limited cognitive abilities; additionally, few studies have evaluated multiple neurodegenerative pathologies concurrently. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with Alzheimer’s disease (AD), mild cognitive impairment (MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, progressive supranuclear palsy, or Parkinson’s disease (PD). Patients (n=274, age 40-86) and healthy controls (n=101, age 55-86) viewed 10 minutes of frequently changing video clips without instruction while their eyes were tracked. We evaluated differences in saccade and pupil parameters (e.g. saccade frequency and amplitude, pupil size, responses to clip changes) between groups. Results: Preliminary data indicates low-level behavioural alterations in multiple disease cohorts: increased centre bias, lower overall saccade rate and reduced saccade amplitude. After clip changes, patient groups generally demonstrated lower saccade rate but higher microsaccade rate following clip change to varying degrees. Additionally, pupil responses were blunted (AD, MCI, ALS) or exaggerated (PD). Conclusions: This task may generate behavioural biomarkers even in cognitively impaired populations. Future work should explore the possible effects of factors such as medication and disease stage.

Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic-inflammatory disease associated with poor outcomes and decreased quality of life. NAFLD is overrepresented in patients with psychiatric disorders like depression, bipolar disorder, and schizophrenia; however, a comprehensive review on NAFLD and psychiatric disorders remains to be delineated. This review endeavors to investigate the association of NAFLD with psychiatric disorders, including shared pathogenesis and future clinical derivatives. Extant literature suggests that patients with psychiatric disorders (in particular, mood disorders) are more susceptible to the development of NAFLD due to multiple reasons, including but not limited to hypothalamic–pituitary–adrenal axis dysregulation, metabolic syndrome, and chronic perceived stress. Moreover, the clinical manifestations of mood disorders (e.g., anhedonia, psychomotor retardation, lifestyle modification, etc.), and potentially long-term treatment with weight-gaining agents, differentially affect these patients, making them more prone to NAFLD. Considering the increased morbidity associated with both mood disorders and NAFLD, our review recommends regular screenings for NAFLD in select patients with mood disorders exhibiting signs of increased risk (i.e., obesity, metabolic syndrome, diabetes, or family history of NAFLD) for better diagnosis and holistic care of both potentially interrelated conditions.

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Background: Assessment of patients for temporal lobe epilepsy (TLE) surgery requires multimodality input, including EEG to ensure optimal surgical planning. Often EEG demonstrates abnormal foci not detected on clinical MRI. 7T MRI provides improved resolution and we investigated its utility to detect potential abnormalities associated with EEG. Methods: Images were acquired on 7T MRI scanner (N=13) in oatients with TLE. Evaluation of 7T imaging for focal abnormalities was performed. Correlation of 7T MRI findings with EEG of focal slowing or interictal epileptic spikes (IEDs) and seizures was performed. Results: Assessment of 7T MRI demonstrated concordance with TLE in 8/13 cases. Three cases exhibited abnormal 7T MRI abnormalities not detected by 1.5 T MRI. Eleven out of 13 cases had EEG findings without anatomic correlates on MRI, with IEDs localizing to contralateral temporal, frontal, and parieto-occipital lobes. 7T images did not reveal focal anatomical abnormalities to account for the EEG findings in these patients. Conclusions: To our knowledge, this is the first study to investigate the role of 7T MRI in relation to EEG abnormalities. 7T RI findings show concordance with clinical data. 7T MRI did not reveal anatomical findings to account for EEG abnormalities, suggesting that such changes may be functional rather than anatomical.

Background: While the use of neural stem/progenitor cells has been reported as a promising therapeutic approach for spinal cord injury, direct comparison of adult primary animal spinal cord NSPCs have not been compared to human NSPCs under the same conditions to characterize intrinsic differences between human/animal NSPC response to inflammatory/regenerative factors. Methods: To mimic post-injury inflammation, primary-derived NSPCs from adult humans, pigs, and rats were treated with pro-inflammatory factors.To direct regeneration, NSPCs were treated with retinoic acid, platelet-derived growth factor or bone morphogenic protein-(BMP4) to induce neurons, oligodendrocytes or astrocytes, respectively.Cultures were treated for 7 or 14 days and characterized by immunocytochemistry. Results: Pro-inflammatory factors promoted more astrogenesis in rat and pig NSPCs compared to human NSPCs and induced neuronal differentiation in human NSPCs. RA increased neurogenesis of human and rat NSPCs, PDGFα increased oligodendrocyte differentiation of rat NSPCs, and BMP4 increased astrogenesis of human and rat NSPCs Conclusions: For the first time, differences in response of human, pig and rat primary NSPCs to inflammatory and regenerative factors have been identified. Better understanding of these differences is essential to improving the successful translation of regenerative therapies to humans.

Precision health and big data approaches have great potential, yet such benefits will be realized only when social and behavioral determinants of health and patient preferences are combined with genomic information. Literature review and co-author experiences informed this commentary. Validated health behavior, mental health, and patient preference measures were collected and summarized in real time. Integration of such data into existing data sets will advance precision health, patient-centered care, research, and policy.

Introduction: Palliative care is a broad approach to care for patients with serious or life-threatening illnesses. This includes relief of symptoms, such as pain, that interfere with a patient’s quality of life. It therefore falls firmly within the realm of emergency medicine (EM). 94% of emergency physicians report a need for education in dealing with death and dying. Nevertheless, there are no generally agreed upon competencies for Canadian EM residents with regard to palliative care and end of life care in the emergency department (ED). We performed a cross-sectional study of Canadian EM residency programs to measure the existing curricula in palliative and end of life care. Our primary outcome was the prevalence of structured educational programs for palliative and end of life care. Methods: An e-survey was e-mailed to all program directors of both CCFP(EM) and EM post-graduate training programs countrywide, using FluidSurveysTM. It included questions regarding current palliative and end of life care curricula from formal rotations to seminars and online modules. The survey was developed in consultation with the author group including specialists in education, palliative care medicine, emergency medicine, and medical education. Hired translators were employed to include French speaking programs in Canada. This study had ethical approval: Interior Health REB and UBC CREB certificate 2016-17-026-H. Results: The survey was open from October 12th to December 19th, 2016. During that time, we received 26 responses including 5 French speaking programs, for a response rate of 72.2%. The primary outcome was present in 38.5% of programs. There was no difference between FRCP and CCFP(EM) programs in the occurrence of the primary outcome (p=1; Fisher’s Exact Text). However, CCFP(EM) program directors commented that many of their residents had completed palliative care rotations in their family medicine training. The largest barriers to education included time (84.6%), curriculum development (80.8%), and availability of instructors (50.0%). Conclusion: Our preliminary analysis shows that few Canadian post-graduate EM programs have a structured educational program pertaining to palliative and end of life care. Current barriers to education that can be addressed in future curricular initiatives include lack of time, curriculum development, and instructor availability.

Factors contributing to academic achievement among recently arrived Chinese adolescents in Australia remain relatively underexplored. Previous studies focused on Asian migrants, including Chinese, but did not distinguish Chinese from other Asian migrants. The current study specifically looks at Chinese migrants who have recently arrived, as opposed to Asian migrants. This study aims to explore the role of social support, school belonging, and acculturative stress on academic achievement of recently arrived Chinese adolescents (n = 55). Questionnaires were administered to this sample. The results indicated that school belonging, interestingly, was negatively associated with academic achievement. Perceived social support and acculturative stress were not significantly associated with academic achievement. The findings provide insights into risk and protective factors influencing academic achievement of Chinese migrants. Implications of the findings are discussed.

In June 2011, a cluster of suspected cases of Guillain–Barré syndrome (GBS), which can follow Campylobacter jejuni infection, was identified in San Luis Río Colorado (SLRC), Sonora, Mexico and Yuma County, Arizona, USA. An outbreak investigation identified 26 patients (18 from Sonora, eight from Arizona) with onset of GBS 4 May–21 July 2011, exceeding the expected number of cases (n = 1–2). Twenty-one (81%) patients reported antecedent diarrhoea, and 61% of 18 patients tested were seropositive for C. jejuni IgM antibodies. In a case-control study matched on age group, sex, ethnicity, and neighbourhood of residence, all Arizona GBS patients travelled to SLRC during the exposure period vs. 45% of matched controls (matched odds ratio 8·1, 95% confidence interval 1·5–∞). Exposure information and an environmental assessment suggested that GBS cases resulted from a large outbreak of C. jejuni infection from inadequately disinfected tap water in SLRC. Binational collaboration was essential in investigating this cross-border GBS outbreak, the first in mainland North America since 1976.

Background: Highly educated participants with normal cognition show lower incidence of Alzheimer's disease (AD) than poorly educated participants, whereas longitudinal studies involving AD have reported that higher education is associated with more rapid cognitive decline. We aimed to evaluate whether highly educated amnestic mild cognitive impairment (aMCI) participants show more rapid cognitive decline than those with lower levels of education.

Methods: A total of 249 aMCI patients enrolled from 31 memory clinics using the standard assessment and diagnostic processes were followed with neuropsychological evaluation (duration 17.2 ± 8.8 months). According to baseline performances on memory tests, participants were divided into early-stage aMCI (−1.5 to −1.0 standard deviation (SD)) and late-stage aMCI (below −1.5 SD) groups. Risk of AD conversion and changes in neuropsychological performances according to the level of education were evaluated.

Results: Sixty-two patients converted to AD over a mean follow-up of 1.43 years. The risk of AD conversion was higher in late-stage aMCI than early-stage aMCI. Cox proportional hazard models showed that aMCI participants, and late-stage aMCI participants in particular, with higher levels of education had a higher risk of AD conversion than those with lower levels of education. Late-stage aMCI participants with higher education showed faster cognitive decline in language, memory, and Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores. On the contrary, early-stage aMCI participants with higher education showed slower cognitive decline in MMSE and CDR-SOB scores.

Conclusions: Our findings suggest that the protective effects of education against cognitive decline remain in early-stage aMCI and disappear in late-stage aMCI.