Flaxseed’s paradoxical role in extending lifespan and reproductive capacity in White Leghorn laying hens; and the effect of polyunsaturated fatty acids (PUFAs) on lipid metabolism, mitochondrial bioenergetics and E-cadherin expression in laying hen ovarian tumors

We are the first lab to report the occurrence of a diet-induced transsulfuration (TS) blockade associating with elevated S-adenosylmethionine (i.e. SAM) synthesis, enhanced lifespan and enhanced reproductive capacity, in a vertebrate animal model. In this paradoxical study, we used LC-MS/MS-derived metabolomics data to report the effects of flaxseed (Linum Usitatissimum) on one-carbon metabolism in White Leghorn laying hens (Gallus gallus). Flaxseed contains a vitamin B6-antagonizing molecule called ‘linatine’ that is particularly effective at reducing vitamin B6 levels in small rodents and poultry. Linatine reduces TS flux through its inhibition of the vitamin B6-dependent enzymes cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE). In this study, our flaxseed-fed hens displayed decreased 4-pyridoxic acid and decreased pyridoxamine, concomitant with 15-fold elevated cystathionine. Homocysteine levels were stable in flaxseed-fed hens despite such highly elevated cystathionine. This is an astonishing finding, because mammalian models would predict the induction of hyperhomocysteinemia (i.e. elevated homocysteine) when cystathionine is so highly elevated (1). We are therefore reporting a phenomenon that might be unique to birds. Our metabolomics data indicate increased consumption of one-carbon donor molecules (e.g. choline, betaine, dimethylglycine, serine, etc) in flaxseed-fed hens, probably as a means of fueling the betaine homocysteine methyltransferase (BHMT) and methionine synthase-B12 (MS-B12) reactions. This modeling approach provides a rationale that flaxseed-fed hens increase their rate of homocysteine remethylation via BHMT and MS-B12, and in turn this would maintain stable homocysteine levels in the animal. We observed that the culminating outcome is elevated synthesis of SAM and an elevated SAM:SAH ratio. The associated biological outcomes are extended lifespan and increased reproductive capacity (i.e. increased daily egg laying) in flaxseed-fed hens. Our data further indicate that flaxseed tremendously stimulates a glucagon-like phenotype in hens. Specifically, flaxseed-fed hens exhibit 3-fold elevated glycated hemoglobin (HbA1c), 2-fold elevated serum free fatty acids (FFAs), 10 to 14% reduced body weight, and slightly reduced plasma pyruvate. These phenotypic markers suggest that glucagon might also play a large role in extending lifespan and enhancing reproductive capacity in flaxseed-fed hens. We predict that the anti-vitamin B6 effects of flaxseed are responsible for stimulating this glucagon-like phenotype in hens. Therefore, we conclude that the vitamin B6-antagonizing effects of linatine (via flaxseed dieting) improve liver function, body leanness, egg laying and survival, in a manner associated with increased SAM synthesis, increased blood FFA levels and increased blood glucose levels, in laying hens. The second part of this dissertation is used to test the hypothesis that polyunsaturated fatty acids (PUFAs) regulate lipid metabolism, increase mitochondrial respiration and decrease E-cadherin expression, in laying hen ovarian tumors. Researchers are unaware of the mitochondrial effects of PUFAs within laying hen ovarian tumors, and only a few publications exist regarding the analysis of E-cadherin in laying hen ovarian cancer. The results of this present work suggest that dietary PUFAs accumulate within laying hen ovarian tumors, and these same tumors exhibit decreased gene transcripts that govern de novo lipogenesis (i.e. FASN). Simultaneously, these tumors exhibit elevated transcripts for oxidative phosphorylation (OXPHOS) and decreased transcripts for phase 2 antioxidant enzymes. These patterns associated with decreased transcript levels of CDH1 (the gene for E-cadherin) in ovarian tumors, but no effect on full length 120kDa protein was observed by PUFAs versus our control diet. Interestingly, the effect of PUFAs on E-cadherin occurred at the level of the cleaved 37kDa and 80kDa E-cadherin fragments, such that PUFAs reduced their levels in hen ovarian tumors. We therefore developed a system for depleting the 80kDa E-cadherin fragment from hen ascites fluid (i.e. fluid from a hen that had ovarian cancer), so that we could test our hypothesis that the 80kDa E-cadherin fragment is important for supporting mitochondrial respiration in normal ovarian surface epithelial cells (IOSE80s). Mitochondrial membrane potential was decreased in IOSE80s when the 80kDa fragment was removed from the ascites; however, there was no effect on basal oxygen consumption in subsequent tests using extracellular flux analysis with Seahorse XFp. During our analysis of microRNA-200a-3p (miR-200a) we did not observe any effect of diet on miR-200a within hen ovarian tumors; however, we did observe that miR-200a levels increased within the tumor when going from stage 2 to stage 4 disease. Overall, we observed reduced risk of ovarian cancer, stage 4 ovarian cancer, multiple peritoneal tumor involvement and cancer-associated mortality, in laying hens that consumed a diet that was supplemented with PUFAs

The effect of 12 weeks of combined upper- and lower-body high-intensity interval training on muscular and cardiorespiratory fitness in older adults

Background: High-intensity interval training (HIT) can impact cardiorespiratory and muscular fitness simultaneously, yet protocols typically focus on lower-body exercise. For older adults however, performing activities of daily living requires upper- and lower-body fitness. Aims: To assess the effects of combined upper- and lower-body HIT on fitness in adults aged > 50 years. Methods: Thirty-six adults (50–81 years; 21 male) were assigned via minimisation to either HIT (n = 18) or a no-exercise control group (CON, n = 18) following baseline assessment of leg extensor muscle power, handgrip strength, cardiorespiratory fitness (predicted VO2max) and health-related quality of life (HRQoL). The HIT group completed two training sessions per week for 12-weeks, performing a combination of upper-, lower- and full-body exercises using a novel hydraulic resistance ergometer. Data were analysed via ANCOVA with probabilistic inferences made about the clinical relevance of observed effects. Results: All participants completed the intervention with mean (82 ± 6%HRmax) and peak (89 ± 6%HRmax) exercise heart rates confirming a high-intensity training stimulus. Compared with CON, HIT showed possibly small beneficial effects for dominant leg power (10.5%; 90% confidence interval 2.4–19.4%), non-dominant leg power (9.4%; 3.3–16.0%) and non-dominant handgrip strength (6.3%; 1.2–11.5%) while the intervention effect was likely trivial (5.9%; 0.5–11.5%) for dominant handgrip strength. There was a likely small beneficial effect for predicted VO2max (8.4%; 1.8–15.4%) and small-moderate improvements across several domains of HRQoL. Conclusion: Combined upper- and lower-body HIT has small clinically relevant beneficial effects on muscular and cardiorespiratory fitness in older adults

International trade and the stability of food supplies in the Global South

Many countries in the Global South depend increasingly on imports to provide food for their rising populations. Trade is a key mechanism to address distributional issues, especially in countries with limited biophysical resources. In theory, by pooling the risk of crop failures via global trade, trade should stabilize food supplies. In practice, however, an over-reliance on imported food may be detrimental to domestic food stability. Here, we disentangle the role of imports from that of domestic production in countries in the Global South for three staple crops: maize, rice, and wheat. First, we use FAO data to differentiate between exposure to production variance in exporting countries, domestic production variance, and total supply variance. Next, we analyze trade relationships and assess the biophysical capacities of countries to investigate why some countries have more unstable supplies than others. We find that food imports have been a source of food supply instability—in particular for maize in Southern Africa, wheat in Central Asia, and rice more generally. But the reason that imports lead to instability is not the same across regions or crops and imports are at times necessary due to limited available water and land resources. Furthermore, the source of imports may be important in the case of co-occurring crop failures in both importing and exporting countries, or exporters with high export variance. Finally, we find that the increasing prevalence of global trade from 1985–2010 has increased exposure to food supply variance in some regions, although it has not increased exposure to supply variance in all regions. These results provide guidance for future analyses to focus on regions that are vulnerable to imported food supply disruptions of important staple crops, and inform debates about the risks associated with food trade in the Global South.EC/FP7/605728 /EU/Postdoctoral Researchers International Mobility Experience/ P.R.I.M.E.DFG, 414044773, Open Access Publizieren 2019 - 2020 / Technische Universität Berli

Performance of diagnostic tests to detect respiratory viruses in older adults.

The performance of 4 laboratory methods for diagnosis of viral respiratory tract infections (RTI) in older adults was evaluated. Seventy-four nasopharyngeal (NP) swab specimens were obtained from 60 patients with RTI at a long-term care facility over 2 respiratory seasons. Sixteen specimens were positive for a respiratory virus by at least 1 method. Multiplex reverse transcriptase polymerase chain reaction (RT-PCR) by the Luminex xTAG Respiratory Viral Panel (RVP) detected 16 (100%) of the positive specimens, RVP of 24-h culture supernatant detected 8 (50%), direct fluorescent antibody testing detected 4 (25%), rapid culture detected 2 (12.5%), and rapid antigen testing detected none. For a comparison group, RVP was performed on NP swabs from 20 outpatient children with RTI. The mean fluorescence intensity by RVP was significantly lower for positive adult patients than pediatric patients (P = 0.0373). Our data suggest that older adult patients shed lower titers of viruses, necessitating a highly sensitive assay such as RT-PCR to reliably detect respiratory viral pathogens

Outcomes Considered Most Important by Emergency Physicians When Determining Disposition of Patients with Pulmonary Embolism

Purpose: Clinical decision rules for the disposition of patients with pulmonary embolism (PE) are typically validated against an outcome of 30-day mortality or disease recurrence. There is little justification for this time frame, nor is it clear whether this outcome reflects emergency department (ED) decision making. Aims: To determine which outcomes emergency physicians (EP) consider most relevant to disposition decisions. Methods: Survey of attending EPs in geographically diverse US states using acute PE as the diagnostic framework. Responses required single-answer multiple choice, a numerical percentage, rank-ordered responses, or a five-point Likert scale. We distributed the survey via e-mail to 608 EPs. Results: We received responses from 292 (48%) EPs: 88% board certified, 91% trained in emergency medicine, and 70% work in academics. Respondents reported discharging 1% of patients with PE from the ED, but 21% reported being asked to do so by an admitting service. EPs were more interested in knowing 5-day (in hospital) outcomes [192/265, 72% (95% exact CI=66%–78%)] than 30-day outcomes [39/261, 15% (95% exact CI=11%–20%)] or 90-day outcomes [29/263, 11% (95% exact CI=8%–15%)]. On a Likert scale, 212/241 (88%, 95% exact CI=83%–92%) agreed or strongly agreed that they considered 5-day (in hospital) clinical deterioration when making a decision to admit or discharge a patient from the ED compared to 184/242 (76%, 95% exact CI=70%–81%) and 73/242 (30%, 95% exact CI=24%–36%) for 30 and 90 days, respectively. A wide variety of clinical outcomes beyond death or recurrent PE were considered indicative of clinical deterioration. Conclusions: Five-day (in hospital) outcomes that incorporate a variety of clinical deterioration events are of interest to EPs when determining the disposition of ED patients with PE. Researchers should consider this when developing and validating clinical decision rules

Autophagy: A cyto-protective mechanism which prevents primary human hepatocyte apoptosis during oxidative stress

The role of autophagy in the response of human hepatocytes to oxidative stress remains unknown. Understanding this process may have important implications for the understanding of basic liver epithelial cell biology and the responses of hepatocytes during liver disease. To address this we isolated primary hepatocytes from human liver tissue and exposed them ex vivo to hypoxia and hypoxia-reoxygenation (H-R). We showed that oxidative stress increased hepatocyte autophagy in a reactive oxygen species (ROS) and class III PtdIns3K-dependent manner. Specifically, mitochondrial ROS and NADPH oxidase were found to be key regulators of autophagy. Autophagy involved the upregulation of BECN1, LC3A, Atg7, Atg5 and Atg 12 during hypoxia and H-R. Autophagy was seen to occur within the mitochondria of the hepatocyte and inhibition of autophagy resulted in the lowering a mitochondrial membrane potential and onset of cell death. Autophagic responses were primarily observed in the large peri-venular (PV) hepatocyte subpopulation. Inhibition of autophagy, using 3-methyladenine, increased apoptosis during H-R. Specifically, PV human hepatocytes were more susceptible to apoptosis after inhibition of autophagy. These findings show for the first time that during oxidative stress autophagy serves as a cell survival mechanism for primary human hepatocytes

The effects of same-session combined exercise training on cardiorespiratory and functional fitness in older adults: a systematic review and meta-analysis

Endurance and strength training are effective strategies for counteracting age-associated reductions in physical performance in older adults, with a combination of both exercise modes recommended to maximise potential fitness benefits. This meta-analysis sought to quantify the effects of same-session combined endurance and strength training on fitness in adults aged over 50 years. Five electronic databases were searched with studies required to include one of the following outcome measures: VO2peak, 6-min walk test (6MWT), 8-ft timed up-and-go (TUG), and 30-s chair stand. Separate random-effects meta-analyses compared combined training with (1) no-exercise control, (2) endurance training, and (3) strength training with probabilistic magnitude-based inferences subsequently applied. Twenty-seven studies involving 1346 subjects with a mean age of 68.8 years (range 54–85 years) were included in the analysis. The meta-analysed effect on VO2peak was a moderately beneficial effect for the combined training compared to no-exercise controls (3.6 mL kg−1 min−1; ± 95% confidence limits 0.8 mL kg−1 min−1) with additional increases for studies with greater proportions of female participants and shorter training interventions. Combined training also had small-to-moderately beneficial effects on VO2peak when compared to endurance training (0.8 mL kg−1 min−1; ± 1.0 mL kg−1 min−1), 30-s chair stand when compared with strength training (1.1 repetitions; ± 0.5 repetitions) and on TUG (0.8 s; ± 0.7 s), 30-s chair stand (2.8 repetitions; ± 1.7 repetitions), and 6MWT (31.5 m; ± 22.4 m) when compared to no-exercise controls. All other comparisons were unclear. Same-session combined training can induce clinically relevant fitness improvements in older adults