Neuropathogenesis of highly pathogenic avian influenza in ferrets following intranasal instillation or aerosol exposure to low doses

Highly pathogenic avian influenza (HPAI), subtype H5N1, has continued to infect humans every year since its initial outbreak in 1997. The overall mortality is approximately 60% and while the emergence of this avian influenza virus has yet to reach the Western Hemisphere, its high lethality and pandemic potential warrant attention from the research community to better understand HPAI disease. Neuroinvasiveness of H5N1 virus is poorly understood and using two HPAI strains of varying lethality in the ferret model provide a basis for comparing differences in neuropathogenesis and its contribution to lethality. The studies described herein used two methods of HPAI exposure in ferrets to elucidate the neuropathogenesis of the virus and its correlation between neurological signs of infection and lesions within the central nervous system (CNS). Following both methods of exposure to low doses of a lethal strain of H5N1, we observed 100% lethality in conjunction with the neurological signs of infection that correlated with lesions within the CNS. Furthermore, we showed that an H5N1 strain that does not cause neurological signs does not replicate in the brain and has attenuated lethality. We concluded that CNS involvement leads to a poor outcome following H5N1 infection. The increased understanding of the temporal-spatial kinetics of neuroinvasion and the correlation of neuroanatomical locations of lesions with the neurological signs observed during these studies could be useful for identifying routes of neuroinvasion and identifying targets for therapeutics to block CNS entry of HPAI. Finally, understanding the neurological sequelae of HPAI infection could aid clinicians in a more rapid diagnosis of influenza infection when patients present with atypical symptoms

Optimal Sampling of a Chemical Hazard Area

This thesis proposes a methodology for optimally sampling a chemical hazard area subsequent to a chemical weapons attack. The objective is to identify the maximum number of areas that no longer require protective gear for safe operations. We model the area as an undirected graph and employ network analysis techniques to provide a methodological framework for identifying an optimal sampling sequence within a fixed time limit. We propose four models that characterize the secondary vapor concentrations: i) static and deterministic, ii) static and stochastic, iii) dynamic and deterministic, and iv) dynamic and stochastic. Comparisons of the static cases and their dynamic counterparts demonstrate the impact of temporal evolution of vapor concentrations on the optimal sampling path. We conclude that the number of safe areas may be either under- or over-estimated depending on the assumed nature of the secondary vapors

Eicosapentaenoic acid decreases postprandial beta-hydroxybutyrate and free fatty acid responses in healthy young and elderly

Objectives: We investigated whether a dietary supplement rich in eicosapentaenoic acid (EPA) increases fasting plasma ketones or postprandial ketone responses in healthy young and elderly subjects. Methods: Ten young (22 ± 1 y old) and 10 elderly (75 ± 1 y old) subjects were recruited and participated in two identical study days, one before and one 6 wk after providing an EPA-enriched supplement (1.4 g/d of EPA and 0.2 g/d of docosahexaenoic acid). On the study days, blood samples were collected at fasting and every hour for 6 h after giving a breakfast. Fasting and postprandial plasma β-hydroxybutyrate (β-OHB), free fatty acid (FFA), triacylglycerol, glucose, and insulin responses were measured. Fatty acid profiles were assessed in fasting plasma samples before and after the EPA supplement. Results: After the EPA supplement, postprandial plasma β-OHB responses decreased by 44% in the young and by 24% in the elderly subjects, in addition to 20% and 34% lower FFA responses in the young and elderly adults, respectively. β-OHB and FFAs were positively and significantly correlated in young but not in elderly subjects before and after the EPA supplement. In both groups, postprandial plasma triacylglycerols, glucose, and insulin were not significantly different after the intake of the EPA supplement. Before and after the EPA supplement, fasting plasma EPA was 50% higher in the elderly but increased by about five times in both groups after intake of the EPA supplement. Conclusion: Contrary to our expectations, EPA supplementation lowered postprandial β-OHB response and, in the elderly subjects, the concentration of postprandial β-OHB was not lowered after intake of the EPA supplement

Symptoms of depression and anxiety increased marginally from before to during the COVID-19 pandemic among young adults in Canada

We documented changes in depressive and anxiety symptoms from before to during the COVID-19 pandemic among young adults and investigated whether changes differed across participant characteristics. Data were available in an investigation of 1294 grade 7 students recruited in 1999–2000. For this analysis, we used data collected pre-pandemically in 2017–20 (mean (SD) age = 30.6 (1.0)) and during the pandemic in 2020–21 (mean (SD) age = 33.6 (0.6)). 673 participants with data in both cycles were retained for analysis. Symptoms were measured using the Major Depression Inventory (MDI) and the Generalized Anxiety Disorder-7 (GAD-7) scale. Standardized mean differences (SMD) of changes in MDI and GAD-7 values between cycles were calculated across participant characteristics. On average, MDI scores increased by 2.1 (95%CI 1.4, 2.8) points during the pandemic from mean 10.5; GAD-7 scores increased by 1.2 (0.8, 1.5) points from mean 4.7. The SMD was 0.24 (0.14, 0.33) for MDI, and 0.24 (0.13, 0.34) for GAD-7. No differences in MDI change scores were observed across participant characteristics. Differences in GAD-7 change scores were observed by mood/anxiety disorder (SMD − 0.31 (− 0.58, − 0.05)), household income (0.24 (0.02, 48)), living with young children (− 0.56 (− 1.23,− 0.05)), and adherence to public health recommendations 0.58 (0.19, 1.03)). Increases in depressive and anxiety symptoms were observed 10–16 months into the COVID-19 pandemic among adults age 32–36

Linking low docosahexaenoic acid intake to Alzheimer's disease : caution recommended

Prospective cohort studies and animal models support the concept that low docosahexaenoic acid intake is implicated in the etiology or progression of Alzheimer’s disease. However, other studies crucial to this relationship are less encouraging. To date, the few trials using docosahexaenoic acid to treat declining cognition in the elderly have either been very small or, in the largest trial, the beneficial effect was mild and limited to a sub-group of patients. The supplements used in each of these clinical trials contained at least one polyunsaturated fatty acid other than docosahexaenoic acid, so the active ingredient remains unclear. One widely cited study reported markedly lower brain docosahexaenoic acid in Alzheimer’s disease but at least five other much less commonly cited reports have not corroborated this effect. There are numerous inconsistencies or confounders in the data and several challenges to overcome before definitively attributing a specific role to docosahexaenoic acid in the protection of cognitive function in the elderl

Plasma response to fish oil in the elderly

Little information is available concerning whether incorporation of dietary omega-3 fatty acids into plasma lipids changes during healthy aging. Elderly (74 ± 4 years old) and young (24 ± 2 years old) adults were given a fish oil supplement for 3 weeks that provided 680 mg/day of docosahexaenoic acid and 320 mg/day of eicosapentaenoic acid, followed by a 2 week wash-out period. Compliance was monitored by spiking the capsules with carbon-13 glucose, the excretion of which was measured in breath CO2. In response to the supplement, plasma docosahexaenoic acid rose 42% more in the elderly but eicosapentaenoic responded similarly in both groups. Despite raising docosahexaenoic acid intake by five to tenfold, the supplement did not raise plasma free docosahexaenoic acid (% or mg/dL) in either group. We conclude that healthy aging is accompanied by subtle but significant changes in DHA incorporation into plasma lipids

Plasma n-3 fatty acids in the elderly

The elderly reportedly have a significantly higher % of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma and red cell lipids. However, these observations are from a few small studies and the health status of the elderly in these studies is for the most part unclear. Since the elderly are susceptible to cardiovascular and neurological illnesses that seem to be related in part to lower intake of n-3 fatty acids it seems paradoxical that their blood levels of EPA and DHA would be higher than in young adults. We report here plasma fatty acid profiles and their response to supplementation with two types of fish oils from several of our recent studies in the moderately healthy elderly. We define the moderately healthy elderly as those who were in good physical condition, had no cognitive decline and, if present, in whom hypothyroidism, hyperlipidemia and/or hypertension were well-controlled. As shown previously, we confirm the higher % EPA and % total n-3 fatty acids (but not DHA) in fasting plasma and extend these findings to include higher plasma concentrations (mg/L) of n-3 fatty acids as well. The EPA-predominant supplement raised DHA only in the young, whereas the DHA-predominant supplement raised EPA more in the young than in the elderly. The moderately healthy elderly clearly have higher plasma n-3 fatty acids but whether this reflects differences in intake versus aging-related changes in n-3 fatty acid metabolism remains to be elucidated

Differences in physical activity domains, guideline adherence, and weight history between metabolically healthy and metabolically abnormal obese adults: a cross-sectional study

BACKGROUND: Despite the accepted health consequences of obesity, emerging research suggests that a significant segment of adults with obesity are metabolically healthy (MHO). To date, MHO individuals have been shown to have higher levels of physical activity (PA), but little is known about the importance of PA domains or the influence of weight history compared to their metabolically abnormal (MAO) counterpart. OBJECTIVE: To evaluate the relationship between PA domains, PA guideline adherence, and weight history on MHO. METHODS: Pooled cycles of the National Health and Nutritional Examination Survey (NHANES) 1999–2006 (≥20 y; BMI ≥ 30 kg/m(2); N = 2,753) and harmonized criteria for metabolic syndrome (MetS) were used. Participants were categorized as “inactive” (no reported PA), “somewhat active” (>0 to < 500 metabolic equivalent (MET) min/week), and “active” (PA guideline adherence, ≥ 500 MET min/week) according to each domain of PA (total, recreational, transportation and household). Logistic and multinomial regressions were modelled for MHO and analyses were adjusted for age, sex, education, ethnicity, income, smoking and alcohol intake. RESULTS: Compared to MAO, MHO participants were younger, had lower BMI, and were more likely to be classified as active according to their total and recreational PA level. Based on total PA levels, individuals who were active had a 70 % greater likelihood of having the MHO phenotype (OR = 1.70, 95 % CI: 1.19–2.43); however, once stratified by age (20–44 y; 45–59 y; and; ≥60 y), the association remained significant only amongst those aged 45–59 y. Although moderate and vigorous PA were inconsistently related to MHO following adjustment for covariates, losing ≥30 kg in the last 10 y and not gaining ≥10 kg since age 25 y were significant predictors of MHO phenotype for all PA domains, even if adherence to the PA guidelines were not met. CONCLUSION: Although PA is associated with MHO, the beneficial effects of PA may be moderated by longer-term changes in weight. Longitudinal analysis of physical activity and weight change trajectories are necessary to isolate the contribution of duration of obesity, PA behaviours, and longer-term outcomes amongst MHO individuals

Kinetics of 13C-DHA before and during fish-oil supplementation in healthy older individuals

Background: Docosahexaenoic acid (DHA) kinetics appear to change with intake, which is an effect that we studied in an older population by using uniformly carbon-13–labeled DHA (13C-DHA). Objective: We evaluated the influence of a fish-oil supplement over 5 mo on the kinetics of 13C-DHA in older persons. Design: Thirty-four healthy, cognitively normal participants (12 men, 22 women) aged between 52 and 90 y were recruited. Two identical kinetic studies were performed, each with the use of a single oral dose of 40 mg 13C-DHA. The first kinetic study was performed before participants started taking a 5-mo supplementation that provided 1.4 g DHA/d plus 1.8 g eicosapentaenoic acid (EPA)/d (baseline); the second study was performed during the final month of supplementation (supplement). In both kinetic studies, blood and breath samples were collected ≤8 h and weekly over 4 wk to analyze 13C enrichment. Results: The time × supplement interaction for 13C-DHA in the plasma was not significant, but there were separate time and supplement effects (P < 0.0001). The area under the curve for plasma 13C-DHA was 60% lower while subjects were taking the supplement than at baseline (P < 0.0001). The uniformly carbon-13–labeled EPA concentration was 2.6 times as high 1 d posttracer while patients were taking the supplement as it was at baseline. The mean (±SEM) plasma 13C-DHA half-life was 4.5 ± 0.4 d at baseline compared with 3.0 ± 0.2 d while taking the supplement (P < 0.0001). Compared with baseline, the mean whole-body half-life was 61% lower while subjects were taking the supplement. The loss of 13C-DHA through β-oxidation to carbon dioxide labeled with carbon-13 increased from 0.085% of dose/h at baseline to 0.208% of dose/h while subjects were taking the supplement. Conclusions: In older persons, a supplement of 3.2 g EPA + DHA/d increased β-oxidation of 13C-DHA and shortened the plasma 13C-DHA half-life. Therefore, when circulating concentrations of EPA and DHA are increased, more DHA is available for β-oxidation. This trial was registered at clinicaltrials.gov as NCT01577004