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The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia.
As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years.
Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status.
Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.
Head impact exposure (HIE) in youth football is a public health concern. The objective of this study was to determine if one season of HIE in youth football was related to cognitive changes.
Over 200 participants (ages 9–13) wore instrumented helmets for practices and games to measure the amount of HIE sustained over one season. Pre- and post-season neuropsychological tests were completed. Test score changes were calculated adjusting for practice effects and regression to the mean and used as the dependent variables. Regression models were calculated with HIE variables predicting neuropsychological test score changes.
For the full sample, a small effect was found with season average rotational values predicting changes in list-learning such that HIE was related to negative score change: standardized beta (β) = -.147, t(205) = -2.12, and p = .035. When analyzed by age clusters (9–10, 11–13) and adding participant weight to models, the R2 values increased. Splitting groups by weight (median split), found heavier members of the 9–10 cohort with significantly greater change than lighter members. Additionaly, significantly more participants had clinically meaningful negative changes: X2 = 10.343, p = .001.
These findings suggest that in the 9–10 age cluster, the average seasonal level of HIE had inverse, negative relationships with cognitive change over one season that was not found in the older group. The mediation effects of age and weight have not been explored previously and appear to contribute to the effects of HIE on cognition in youth football players.
Poor postprandial glucose control is a risk factor for multiple health conditions. The second-meal effect refers to the progressively improved glycaemic control with repeated feedings, an effect which is achievable with protein ingestion at the initial eating occasion. The most pronounced glycaemic response each day therefore typically occurs following breakfast, so this study investigated whether ingesting protein during the night could improve glucose control at the first meal of the day. In a randomised cross-over design, fifteen adults (7 males, 8 females; age, 22 ± 3 years; BMI, 24.0 ± 2.8 kg·m−2; fasting blood glucose, 4.9 ± 0.5 mmol·L−1) woke at 0400 ± 1 h to ingest 300 ml water with or without 63 g whey protein. Participants then completed a mixed-macronutrient meal tolerance test (1 g carbohydrate·kg body mass−1, 563 ± 104 kcal,) 5 h 39 min following the nocturnal feeding. Nocturnal protein ingestion increased the glycaemic response (incremental area under curve) to breakfast by 43.5 ± 55.5 mmol•120 min•L-1 (p=0.009, d=0.94). Consistent with this effect, individual peak blood glucose concentrations were 0.6 ± 1.0 mmol·L-1 higher following breakfast when protein had been ingested (p=0.049, d=0.50). Immediately prior to breakfast, rates of lipid oxidation were 0.02 ± 0.03 g·min-1 higher (p=0.045) in the protein condition, followed by an elevated postprandial energy expenditure (0.09 ± 0.12 kcal·min-1, p=0.018). Postprandial appetite and energy intake were similar between conditions. This study reveals a paradoxical second-meal phenomenon whereby nocturnal whey protein feeding impaired subsequent glucose tolerance, whilst increasing postprandial energy expenditure.
The Ross Sea is known for showing the greatest sea-ice increase, as observed globally, particularly from 1979 to 2015. However, corresponding changes in sea-ice thickness and production in the Ross Sea are not known, nor how these changes have impacted water masses, carbon fluxes, biogeochemical processes and availability of micronutrients. The PIPERS project sought to address these questions during an autumn ship campaign in 2017 and two spring airborne campaigns in 2016 and 2017. PIPERS used a multidisciplinary approach of manned and autonomous platforms to study the coupled air/ice/ocean/biogeochemical interactions during autumn and related those to spring conditions. Unexpectedly, the Ross Sea experienced record low sea ice in spring 2016 and autumn 2017. The delayed ice advance in 2017 contributed to (1) increased ice production and export in coastal polynyas, (2) thinner snow and ice cover in the central pack, (3) lower sea-ice Chl-a burdens and differences in sympagic communities, (4) sustained ocean heat flux delaying ice thickening and (5) a melting, anomalously southward ice edge persisting into winter. Despite these impacts, airborne observations in spring 2017 suggest that winter ice production over the continental shelf was likely not anomalous.
It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
Commercialization of 2,4-D–tolerant crops is a major concern for sweetpotato producers because of potential 2,4-D drift that can cause severe crop injury and yield reduction. A field study was initiated in 2014 and repeated in 2015 to assess impacts of reduced rates of 2,4-D, glyphosate, or a combination of 2,4-D with glyphosate on sweetpotato. In one study, 2,4-D and glyphosate were applied alone and in combination at 1/10, 1/100, 1/250, 1/500, 1/750, and 1/1,000 of anticipated field use rates (1.05 kg ha−1 for 2,4-D and 1.12 kg ha−1 for glyphosate) to ‘Beauregard’ sweetpotato at storage root formation (10 days after transplanting [DAP]). In a separate study, all these treatments were applied to ‘Beauregard’ sweetpotato at storage root development (30 DAP). Injury with 2,4-D alone or in combination with glyphosate was generally equal or greater than with glyphosate applied alone at equivalent herbicide rates, indicating that injury is attributable mostly to 2,4-D in the combination. There was a quadratic increase in crop injury and quadratic decrease in crop yield (with respect to most yield grades) with increased rate of 2,4-D applied alone or in combination with glyphosate applied at storage root development. However, neither the results of this relationship nor of the significance of herbicide rate were observed on crop injury or sweetpotato yield when herbicide application occurred at storage root formation, with a few exceptions. In general, crop injury and yield reduction were greatest at the highest rate (1/10×) of 2,4-D applied alone or in combination with glyphosate, although injury observed at lower rates was also a concern after initial observation by sweetpotato producers. However, in some cases, yield reduction of U.S. no.1 and marketable grades was also observed after application of 1/250×, 1/100×, or 1/10× rates of 2,4-D alone or with glyphosate when applied at storage root development.
OBJECTIVES/GOALS: Initiation of JUUL use by young adults is one of the most significant issues of concern within the debate on vaping. Despite the proliferation of products and the surge in prevalence, no studies have investigated individual-level interventions or prevention strategies for pod-mod use. METHODS/STUDY POPULATION: Participants (N = 947) were young adults (<30 years old) recruited from Amazon’s Mechanical Turk based on smoking (never, former, and current smokers) and JUUL use status (never and current users), resulting in 6 use groups. In a pre-post design, participants completed baseline assessments, were presented with a brief JUUL-specific educational intervention, and completed post-assessment measures. The one-page intervention provided basic information about JUUL and stated that JUUL is harmful to non-smokers but could be beneficial to smokers if they completely switch. Primary outcomes were changes in JUUL knowledge, perceived harmfulness, intentions for future use, and motivation to change. RESULTS/ANTICIPATED RESULTS: Participants (Mage = 26.1) were male (57%) and White (75%). Overall, the intervention increased JUUL-related knowledge, risk perceptions, commitment to quitting, and readiness to quit JUUL (ps<.01). Similarly, participants showed decreased interest in future JUUL use, interest in purchasing JUUL, and interest in future regular use (ps<.01). Non-JUUL users showed decreased interest in initiating JUUL use after viewing the intervention (p<.01). There were significant Time X Group interactions for JUUL-related knowledge (p<.001), with never JUUL/never smokers showing the greatest increase in product knowledge following the intervention. However, no other interaction effects were significant. DISCUSSION/SIGNIFICANCE OF IMPACT: The intervention was effective in increasing knowledge and risk perceptions while reducing intentions for future use. The intervention was most effective in increasing knowledge among non-users, suggesting that brief educational interventions may be useful tools for preventing pod-mod initiation. CONFLICT OF INTEREST DESCRIPTION: Dr. Carpenter has received consulting honoraria from Pfizer. All other authors have no conflicts to disclose.
Morning coffee is a common remedy following disrupted sleep yet each factor can independently impair glucose tolerance and insulin sensitivity in healthy adults. Remarkably, the combined effects of sleep fragmentation and coffee on glucose control upon waking per se have never been investigated.
In a randomised cross-over design, 29 adults (Mean ± SD; age: 21 ± 1 years, BMI: 24.4 ± 3.3 kg·m-2) underwent three oral glucose tolerance tests (OGTT). One following a habitual night of sleep (Control; in bed, lights-off trying to sleep ~2300-0700 h) the others following a night of sleep fragmentation (as Control but waking hourly for 5 min), once with and once without morning coffee ~1 h after waking (~300 mg caffeine as black coffee 30 min prior to OGTT).
Peak plasma glucose and insulin concentrations were unaffected by sleep quality but were higher following coffee consumption (Mean [normalised confidence interval] for Control, Fragmented, and Fragmented+Coffee, respectively; Glucose: 8.20 [7.93-8.47] mmol∙L-1versus 8.23 [7.96-8.50] mmol∙L-1versus 8.96 [8.70-9.22] mmol.L-1; Insulin: 265 [247-283] pmol∙L-1; and 235 [218-253] pmol∙L-1; and 310 [284-337] pmol∙L-1). Likewise, iAUC for plasma glucose was higher in the Fragmented+Coffee trial compared to Fragmented.
Whilst sleep fragmentation did not alter glycaemic or insulinaemic responses to morning glucose ingestion, if a strong caffeinated coffee is consumed then a reduction in glucose tolerance can be expected.
Classical stewardship efforts have targeted immunocompetent patients; however, appropriate use of antimicrobials in the immunocompromised host has become a target of interest. Cytomegalovirus (CMV) infection is one of the most common and significant complications after solid-organ transplant (SOT). The treatment of CMV requires a dual approach of antiviral drug therapy and reduction of immunosuppression for optimal outcomes. This dual approach to CMV management increases complexity and requires individualization of therapy to balance antiviral efficacy with the risk of allograft rejection. In this review, we focus on the development and implementation of CMV stewardship initiatives, as a component of antimicrobial stewardship in the immunocompromised host, to optimize the management of prevention and treatment of CMV in SOT recipients. These initiatives have the potential not only to improve judicious use of antivirals and prevent resistance but also to improve patient and graft survival given the interconnection between CMV infection and allograft function.
A major concern of sweetpotato producers is the potential negative effects from herbicide drift or sprayer contamination events when dicamba is applied to nearby dicamba-resistant crops. A field study was initiated in 2014 and repeated in 2015 to assess the effects of reduced rates of N,N-Bis-(3-aminopropyl)methylamine (BAPMA) or diglycloamine (DGA) salt of dicamba, glyphosate, or a combination of these individually in separate trials with glyphosate on sweetpotato. Reduced rates of 1/10, 1/100, 1/250, 1/500, 1/750, and 1/1,000 of the 1× use rate of each dicamba formulation at 0.56 kg ha−1, glyphosate at 1.12 kg ha−1, and a combination of the two at aforementioned rates were applied to ‘Beauregard’ sweetpotato at storage root formation (10 d after transplanting) in one trial and storage root development (30 d after transplanting) in a separate trial. Injury with each salt of dicamba (BAPMA or DGA) applied alone or with glyphosate was generally equal to or greater than glyphosate applied alone at equivalent rates, indicating that injury is most attributable to the dicamba in the combination. There was a quadratic increase in crop injury and a quadratic decrease in crop yield (with respect to most yield grades) observed with an increased herbicide rate of dicamba applied alone or in combination with glyphosate applied at storage root development. However, with a few exceptions, neither this relationship nor the significance of herbicide rate was observed on crop injury or sweetpotato yield when herbicide application occurred at the storage root formation stage. In general, crop injury and yield reduction were greatest at the highest rate (1/10×) of either salt of dicamba applied alone or in combination with glyphosate, although injury observed at lower rates would be cause for concern after initial observation by sweetpotato producers. However, in some cases yield reduction of No.1 and marketable grades was observed following 1/250×, 1/100×, or 1/10× application rates of dicamba alone or with glyphosate when applied at storage root development.
Innovation Concept: Research training programs for students, especially in emergency medicine (EM), may be difficult to initiate due to lack of protected time, resources, and mentors (Chang Y, Ramnanan CJ. Academic Medicine 2015). We developed a ten-week summer program for medical students aimed at cultivating research skills through mentorship, clinical enrichment, and immersion in EM research culture through shadowing and project support. Methods: Five second year Ontario medical students were recruited to participate in the Summer Training and Research in Emergency Medicine (STAR-EM) program at University Health Network, Toronto, from June - Aug, 2019. Program design followed review of existing summer research programs and literature regarding challenges to EM research (McRae, Perry, Brehaut et al. CJEM 2018). The program had broad emergency physician (EP) engagement, with five EP research project mentors, and over ten EPs delivering academic sessions. Curriculum development was collaborative and iterative. All projects were approved by the hospital Research Ethics Board (REB). Curriculum, Tool or Material: Each weekly academic morning comprised small group teaching (topics including research methodology, manuscript preparation, health equity, quality improvement, and wellness), followed by EP-led group progress review of each student's project. Each student spent one half day per week in the emergency department (ED), shadowing an EP and identifying patients for recruitment for ongoing mentor-initiated ED research projects. Remaining time was spent on independent student project work. Presentation to faculty and program evaluation occurred in week 10. Scholarly output included one abstract submitted for publication per student. Program evaluation by students reflected a uniform impression that course material and mentorship were each excellent (100%, n = 5). Interest in pursuing academic EM as a career was identified by all students. Faculty researchers rated the program as very effective (80%, n = 4) or somewhat effective (20%, n = 1) in terms of enhancing productivity and scholarly output. Conclusion: The STAR-EM program provides a transferable model for other academic departments seeking to foster the development of future clinician investigators and enhance ED research culture. Program challenges included delays in REB approval for student projects and engaging recalcitrant staff to participate in research.
Psychiatric morbidity was measured in a prospective follow-up study of 51 patients admitted to hospital after minor head injury. By means of self report questionnaires (eg General Health Questionnaire (SHQ) and Impact of Event Scale), semistructured interviews and symptom-checklists, it was found that nearly half of the patients suffered considerable discomfort after 1 week. Improvement during the 3 months follow-up was generally poor. Both concussional symptoms and stress response contributed to the compromised well-being as measured by the GHQ, but outcome did not correlate to severity of injury. The GHQ-60 score of 1 week showed a strong positive correlation with outcome after 3 months. The incidence of post-traumatic stress disorder was low.
Psychological stress is associated with accelerated cellular aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear.
We examined the effect of stress on a DNA methylation age predictor that was shown to correlate strongly with chronological age across human tissues (Horvath 2013). Genome-wide DNA methylation was measured in peripheral blood using the 450K Illumina array in three independent cohorts: the Grady Trauma Project/GTP (N=366); a panic disorder case/control sample recruited at the Max Planck Institute of Psychiatry/MPI-P (N=318); and the Conte Center for the Psychobiology of Early-Life Trauma/Conte (N=42). Age acceleration was calculated by subtracting chronological age from age predicted by DNA methylation. Psychiatric symptomatology and stressors were assessed using standard questionnaires.
DNA methylation age strongly correlated with chronological age in all samples (r=0.9, p=2.5x10<sup>-133</sup>). Cumulative lifetime stress but not childhood or current stress predicted age acceleration in GTP (p=0.012) and MPI-P (p=0.021). Moreover, epigenetic age acceleration predicted depression (GTP: p=0.002; Conte: p=0.014) and panic disorder (p=0.007). In secondary analyses, we examined the effect of lifetime stress on individual CpGs of the DNA methylation age predictor. After correcting for multiple comparisons, we identified in both GTP and MPI-P a stress-regulated CpG near MCAM, a gene implicated in aging-related diseases, including cardiovascular disease and cancers.
Cumulative lifetime stress, but not childhood or current stress, and psychiatric phenotypes are associated with accelerated epigenetic aging. Our findings may explain the accelerated cellular aging and increased disease risk associated with chronic stress and psychiatric disorders.
Against a backdrop of poor mental health education in UK schools a group of students from Norwich Medical School have formed a student society called ‘Headucate’ in order to create, deliver and evaluate an educational intervention for adolescents, initially to be delivered in Norfolk schools.
To create an educational intervention that:
Is the length of a standard lesson
Is age appropriate and acceptable
Contains appropriate signposting
Contains content that challenges common myths and replaces them with knowledge
Contains content that encourages empathy and understanding towards those with mental illnesses
Is easily delivered in the same way each time so that its effectiveness can be evaluated
To create an intervention effective at tackling stigma and empowering adolescents to recognise signs of poor mental health and access services appropriately.
Lesson plan created after consultation with psychiatrists, a psychologist, a GP, a university outreach professional, a teacher and secondary school age children, then trialled and revised.
Interactive workshop produced with 5 sections.
1) Myth vs Fact activity that dispels prevalent myths
2) Scenario based activity to demonstrate that mental health is a spectrum
3) An interactive presentation covering the most common mental illnesses and their symptoms
4) An activity focusing on talking to those with mental illnesses, furthering the scenario from the previous activity
5) A question and answer session. Every student leaves with a leaflet containing appropriate signposting.
We have created an educational intervention ready to be delivered and evaluated.
Mental health education is not compulsory in the UK therefore adolescents have very varied experiences despite half of people with mental health illnesses reporting having experienced symptoms by 14 years old. University students are ideal for delivering a relaxed, educational intervention aimed at this age group, providing an opportunity to for them to learn necessary tools for recognising signs of poor mental health and tackle associated stigma.
To expand Headucate's membership, including other disciplines within the University of East Anglia (UEA) and provide core training enabling members to deliver a school-based educational intervention
Recruitment of members has been a multifaceted approach utilising social media sites such as Facebook and the Headucate website, and oncampus events and ‘awareness campaigns’ including several successful evening talks and lectures.
Three training sessions, which include ‘Introduction to Mental Health’, ‘Workshop run-through’ and ‘Child Protection’, have been developed for all members wishing to partake in the delivery of workshops.
We have recruited approximately 300 members since summer 2012; 70 fully paid members in 2012/13 academic year and currently 45 paid members for 2013/14.
A total of 18 members are fully trained and ready to deliver workshops within schools and 17 other members have just one training session remaining.
We are looking forward to delivering our first workshops in October and building on a successful first year. We are confident we can provide workshops for approximately 600 children per year.
The symptoms of many mental illnesses often begin during high school. Interventions to improve mental health awareness amongst adolescents may lead to improved outcomes. in the UK unfortunately many schools do not fulfil this need and mental health education is not a compulsory part of the curriculum.
To develop and measure the effectiveness of and educational intervention designed to raise awareness and empower adolescents to recognise signs of poor mental health and access services appropriately.
Evaluate the effectiveness of the intervention through baseline and follow up surveys.
Students at Norwich Medical School collaborated with teachers, psychiatrists and general practitioners to design an educational intervention that aims to tackle stigma and raise awareness of mental health conditions among 13-14 year olds in the hope that they can access services when needed, support those around them and look after their mental health. To evaluate effectiveness of the intervention, a knowledge, attitudes and practices survey that utilises a social distance scale that has been adapted for this age group and will be used to gather baseline and follow up data after six months.
We have developed a one-hour educational intervention delivered by medical students, that uses a variety of teaching techniques to raise awareness of mental health issues. We will start implementation in January 2013 so will have baseline effectiveness results shortly after.
Headucate has the potential to fill an important gap in effectively raising awareness of mental health issues in schools.
The Department of Health in the UK wants the National Health Service to make £20 Billion worth of efficiency savings by 2015 to reinvest.
In the UK the General Hospitals use paper records which are then scanned to create electronic records while Psychiatric Hospitals require that information to be typed on to their electronic records and these electronic records are not available to each other.
Therefore liaison psychiatry assessments require a written entry to be made in the Medical notes and a second entry typed on to the psychiatric electronic patient record which requires a full psychiatric history.
This duplication in typing information was consuming a considerable amount of this Teams time and resources which could have instead been spent with patients.
To identify how much time is spent by Staff typing information on to the psychiatric electronic patient records.
We electronically checked for the preceding three months the amount of time spent typing information on to the electronic records after every liaison psychiatry assessment.
We were then able to obtain the average for every week.
On average about 36 to 40 hours were spent every week typing information on to the electronic records.
Liaison Psychiatry should dispense with the requirement for information to be duplicated on to the electronic patient records and should instead scan the written entry made in the Medical notes.
This should lead to a saving of about £50,000, enough to employ an additional member of Staff every week.