A High-Methionine Diet for One-Week Induces a High Accumulation of Methionine in the Cerebrospinal Fluid and Confers Bipolar Disorder-like Behavior in Mice

Methionine (Met) is considered the most toxic amino acid in mammals. Here, we investigated biochemical and behavioral impacts of ad libitum one-week feeding of high-Met diets on mice. Adult male mice were fed the standard rodent diet that contained 0.44% Met (1×) or a diet containing 16 graded Met doses (1.2×–13×). High-Met diets for one-week induced a dose-dependent decrease in body weight and an increase in serum Met levels with a 2.55 mM peak (versus basal 53 µM) on the 12×Met diet. Total homocysteine (Hcy) levels were also upregulated while concentrations of other amino acids were almost maintained in serum. Similarly, levels of Met and Hcy (but not the other amino acids) were highly elevated in the cerebrospinal fluids of mice on the 10×Met diet; the Met levels were much higher than Hcy and the others. In a series of behavioral tests, mice on the 10×Met diet displayed increased anxiety and decreased traveled distances in an open-field test, increased activity to escape from water soaking and tail hanging, and normal learning/memory activity in a Y-maze test, which were reflections of negative/positive symptoms and normal cognitive function, respectively. These results indicate that high-Met ad libitum feeding even for a week can induce bipolar disorder-like disease models in mice.

A Longitudinal Study on the Mental Health of College Students in Jinan During the Peak Stage of the COVID-19 Epidemic and the Society Reopening

<b><i>Introduction:</i></b> COVID-19, a continuously emerging human-to-human infectious disease, has exerted a significant impact on the mental health of college students. However, little is known regarding the variations in the mental health issues experienced by college students during the peak versus reopening stages of the COVID-19 epidemic in China. <b><i>Methods:</i></b> To assess these issues, an online longitudinal survey was conducted via a WeChat applet. Undergraduates (<i>n</i> = 300) were recruited from 26 universities throughout Jinan in February 2020 (T1 – the epidemic peak stage) and in January 2021 (T2 – the society reopening stage). Their mental status was determined using the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7 item, and the Insomnia Severity Index. <b><i>Results:</i></b> Of the original 300 college students recruited for this survey, 294 responses at T1 and 285 at T2 were analyzed. Compared with responses obtained at T1, college students at T2 showed a greater prevalence of depression (65.3 vs. 51.0%; <i>p</i> = 0.001) and anxiety (47.7 vs. 38.1%, <i>p</i> = 0.019), and experienced more severe depression (<i>p</i> &#x3c; 0.001) and anxiety (<i>p</i> &#x3c; 0.001). Both males (<i>p</i> = 0.03) and females (<i>p</i> &#x3c; 0.01) showed higher levels of depression at T2 versus T1, while no differences were obtained with regard to anxiety and insomnia. At T1, Grade 4 students showed greater levels of depression (<i>p</i> = 0.005) and anxiety (<i>p</i> = 0.008) than that of Grade 1 students. While at T2, only greater levels of depression (<i>p</i> = 0.004) were present when compared with that of Grade 1 students. Additionally, Grade 4 college students demonstrated a greater prevalence of depression at T2 versus T1 (<i>p</i> = 0.03), but no statistically differences were present for anxiety and insomnia. No statistically significant differences were obtained among the 4 grades of college students for insomnia at either the T1 or T2. <b><i>Conclusion:</i></b> With progression of the COVID-19 epidemic, college students showed increasing levels of depression and anxiety, with Grade 4 college students being most seriously affected. It is imperative that intervention strategies be implemented to mitigate against these mental health issues resulting from the COVID-19 epidemic.

Wisdom of crowds detects COVID-19 severity ahead of officially available data

During the unfolding of a crisis, it is crucial to forecast its severity at an early stage , yet access to reliable data is often challenging early on. The wisdom of crowds has been effective at forecasting in similar scenarios. We investigated whether the initial regional social media reaction to the emerging COVID-19 pandemic in three critically affected countries has significant relations with their observed mortality a month later. We obtained COVID-19 related regionally geolocated tweets from Italian, Spanish, and United States regions. We quantified the predictive power of the wisdom of the crowds using correlations and regressions of geolocated Tweet Intensity (TI) during the initial social media attention peak versus the cumulative number of deaths a month ahead. We found that the intensity of initial COVID-19 related tweet attention at the beginning of the pandemic across Italian, Spanish, and United States regions is significantly related (p < 0.001) to the extent to which these regions had been affected by the pandemic a month later. This association is most striking in Italy as when at its peak of TI in late February 2020 only two of its regions had reported mortality. The collective wisdom of the crowds at early stages of the pandemic, when information on the number of infections was not broadly available, strikingly predicted the extent of mortality reflecting the regional severity of the pandemic almost a month later. Our findings could underpin the creation of real-time novelty detection systems aimed at early reporting of the severity of crises impacting a territory leading to early activation of control measures at a stage when available data is extremely limited.

Evaluating the Implementation of a National COVID-19 Hospital Guideline in Wales

BackgroundThe COVID-19 pandemic created a unique situation where a national clinical guideline would address uncertainty, and provide a trusted source for up-to-date information and advice. We developed a dynamic online infrastructure together with a dedicated implementation team to deliver this at scale and pace. The guideline was implemented through a digital implementation framework (SIMPSI framework) deploying facilitators to maximise guideline adoption, particularly targeting senior clinical decision makers (consultants) involved with the care of COVID-infected patients across six Health Boards (HB) in Wales. Methods We evaluated guideline implementation using the Taxonomy of Implementation Outcomes Model. The primary outcome was consultant engagement, with a target of 193 registrations. We assessed wider impact through analysis of guideline platform activity and a user survey, with additional sensitivity analysis to derive penetration ratios, catchment population, clinical staff, acute beds, and COVID-19 admissions. ResultsThe guideline platform had 4521 total registrants, with over 170,000 page views during the first wave. We exceeded the target nearly six-fold (1159 consultant registrants). This represented 45% of all medical consultants in Wales, and made up the highest proportion of guideline registrants of all professional groups (23%, 1159/4521). We observed significant variation in guideline penetration across the six HBs, ranging from 31% to 74% of consultants registered. The HB with highest penetration had the most active guideline facilitator. The HB with the lowest penetration was the region first impacted and most affected by COVID-19 at the time of guideline publication (37% inpatients of peak, versus 10% or less for the other HBs). ConclusionWe utilised a digital implementation framework to construct a system that could be rapidly applied throughout all hospitals in Wales. Whilst we exceeded the intended target demonstrating full implementation, we identified two key factors to account for differences in the penetration rates across the different HBs. First, an experienced and active facilitator with the capacity to undertake the role was associated with significantly better penetration. Second, timeliness of implementation was crucial as evidenced by lower penetrance is the one HB that was impacted earliest by COVID-19 at the time of guideline dissemination. Nevertheless, the rapid implementation of the guideline has coincided with Wales demonstrating more favourable intensive care survival rates and maintaining one of the lowest mortality rates when compared to the UK as a whole for the first wave of the COVID-19 pandemic.

Driver Response to a Dynamic Speed Feedback Sign on Freeway Exit Ramps Based on Sign Location, Interchange Type, and Time of Day

A series of field evaluations was performed at three freeway interchange ramps in Michigan that possessed significant horizontal curvature to assess the impacts of a dynamic speed feedback sign (DSFS) on driver speed selection and brake response while approaching and entering the ramp curve. A DSFS with a 15 in. full-matrix display was temporarily installed at each of the three exit ramp locations. The sign was programmed to display the same feedback message at each location, which included the speed number for all approaching vehicles, which alternated with a “Slow Down” message for vehicles approaching above 40 mph. The effectiveness of the feedback sign was tested across various sign locations (at the point of curvature versus 350 ft upstream), interchange types (system versus service), time of day (peak versus off-peak), light conditions (daylight versus darkness), and vehicle types (passenger vehicles versus trucks). Compared with the pre-DSFS site condition, the DSFS reduced curve entry speeds and improved brake response at two of the three ramp locations. In general, the greatest beneficial effects on driver behavior were achieved when the DSFS was positioned at the point of curvature, during which curve entry speeds were reduced by approximately 2 mph. These findings were consistent between the system interchanges and service interchanges, and across all vehicle types. The DSFS was also found to be most effective during daytime off-peak periods compared with peak periods and at night. Further evaluation of DSFS at additional ramp locations, and considering an expanded set of conditions, is recommended.

Evaluating The Implementation of A National COVID-19 Hospital Guideline In Wales

BackgroundThe COVID-19 pandemic created a unique situation where a national clinical guideline would address uncertainty, and provide a trusted source for up-to-date information and advice. We developed a dynamic online infrastructure together with a dedicated implementation team to deliver this at scale and pace. The guideline was implemented through a digital implementation framework (SIMPSI framework) deploying facilitators to maximise guideline adoption, particularly targeting senior clinical decision makers (consultants) involved with the care of COVID-infected patients across six Health Boards (HB) in Wales. Methods We evaluated guideline implementation using the Taxonomy of Implementation Outcomes Model. The primary outcome was consultant engagement, with a target of 193 registrations. We assessed wider impact through analysis of guideline platform activity and a user survey, with additional sensitivity analysis to derive penetration ratios, catchment population, clinical staff, acute beds, and COVID-19 admissions. ResultsThe guideline platform had 4521 total registrants, with over 170,000 page views during the first wave. We exceeded the target nearly six-fold (1159 consultant registrants). This represented 45% of all medical consultants in Wales, and made up the highest proportion of guideline registrants of all professional groups (23%, 1159/4521). We observed significant variation in guideline penetration across the six HBs, ranging from 31% to 74% of consultants registered. The HB with highest penetration had the most active guideline facilitator. The HB with the lowest penetration was the region first impacted and most affected by COVID-19 at the time of guideline publication (37% inpatients of peak, versus 10% or less for the other HBs). ConclusionWe utilised a digital implementation framework to construct a system that could be rapidly applied throughout all hospitals in Wales. Whilst we exceeded the intended target demonstrating full implementation, we identified two key factors to account for differences in the penetration rates across the different HBs. First, an experienced and active facilitator with the capacity to undertake the role was associated with significantly better penetration. Second, timeliness of implementation was crucial as evidenced by lower penetrance is the one HB that was impacted earliest by COVID-19 at the time of guideline dissemination. Nevertheless, the rapid implementation of the guideline has coincided with Wales demonstrating more favourable intensive care survival rates and maintaining one of the lowest mortality rates when compared to the UK as a whole for the first wave of the COVID-19 pandemic.

Protocol for randomized controlled trial of electric stimulation with high-volt twin peak versus placebo for facial functional recovery from acute Bell’s palsy in patients with poor prognostic factors

Background Electric stimulation (ES) can prevent muscle atrophy and promote tissue healing and therefore may help prevent sequelae of Bell’s palsy but due to lack of high-quality studies, the effectiveness of ES in Bell’s palsy remains controversial. Here we describe a protocol to evaluate the effects of monophasic high volt ES in patients with Bell’s palsy and poor prognosis for recovery. Results This is a protocol for a prospective, double-blinded, randomized, placebo-controlled study. Participants include adults with acute Bell’s palsy with poor prognosis for full recovery due to complete paralysis or being over age 60. ES will be a monophasic, high-volt pulsed waveform, 100μsec pulse duration, 35 hertz, motor-level intensity. Follow up will be at months 1, 2, 3 and 6. The primary outcome will be the proportion of patients with complete recovery using the eFACES tool. Secondary outcomes include patient reported quality of life measured by FaCE and the synkinesis assessment questionnaires, objective photographs, time to complete recovery, adverse effects, and tolerability. Conclusion This protocol has the potential to provide high quality evidence regarding the effects, up to 6 months after onset, of pulsed monophasic high-volt ES for patients with acute Bell’s palsy and poor prognosis for complete recovery.

Diurnal Patterns for Cortisol, Cortisone and Agouti-Related Protein in Human Cerebrospinal Fluid and Blood

Context Cortisol in blood has a robust circadian rhythm and exerts potent effects on energy balance that are mediated in part by central mechanisms. These interactions involve orexigenic agouti-related protein (AgRP) neurons that are stimulated by glucocorticoids. However, diurnal changes in brain or cerebrospinal fluid (CSF) cortisol and cortisone, which are interconverted by 11ß-HSD1, have not been characterized in humans. Objective To conduct a secondary analysis of existing samples to characterize diurnal changes in cortisol and cortisone in CSF and examine their relationships to changes in AgRP. Methods Stored CSF and plasma samples were obtained from 8 healthy subjects who served as controls for a sleep study. CSF was collected every 2h for 36h via indwelling lumbar catheter; plasma was collected every 2h. Results There was a diurnal rhythm for cortisol and cortisone in CSF that closely followed the plasma rhythm by 2 h with peak and nadir levels at 0900h and 0100h. The ratio of cortisol (active) to cortisone (inactive) in CSF was 48% higher at the peak versus nadir. There was a diurnal rhythm for AgRP in plasma that was out of phase with the cortisol rhythm. There was a less distinct diurnal rhythm for AgRP in CSF that oscillated with a similar phase as cortisol. Conclusions There is a robust diurnal rhythm for cortisol and cortisone in CSF. Diurnal changes were noted for AgRP that are related to the cortisol changes. It remains to be determined if AgRP mediates adverse metabolic effects associated with disruption of the cortisol circadian rhythm.

Exploring sales data during a healthy corner store intervention in Toronto: the Food Retail Environments Shaping Health (FRESH) project

Introduction Population health interventions in the retail food environment, such as corner store interventions, aim to influence the kind of cues consumers receive so that they are more often directed toward healthier options. Research that addresses financial aspects of retail interventions, particularly using outcome measures such as store sales that are central to retail decision making, is limited. This study explored store sales over time and across product categories during a healthy corner store intervention in a lowincome neighbourhood in Toronto, Ontario. Methods Sales data (from August 2014 to April 2015) were aggregated by product category and by day. We used Microsoft Excel pivot tables to summarize and visually present sales data. We conducted t-tests to examine differences in product category sales by “peak” versus “nonpeak” sales days. Results Overall store sales peaked on the days at the end of each month, aligned with the issuing of social assistance payments. Revenue spikes on peak sales days were driven predominantly by transit pass sales. On peak sales days, mean sales of nonnutritious snacks and cigarettes were marginally higher than on other days of the month. Finally, creative strategies to increase sales of fresh vegetables and fruits seemed to substantially increase revenue from these product categories. Conclusion Store sales data is an important store-level metric of food environment intervention success. Furthermore, data-driven decision making by retailers can be important for tailoring interventions. Future interventions and research should consider partnerships and additional success metrics for retail food environment interventions in diverse Canadian contexts.