Effects of chewing gum on nitric oxide metabolism, markers of cardiovascular health and neurocognitive performance after a nitrate-rich meal

Objectives: Cardiovascular and neurocognitive responses to chewing gum have been reported, but the mechanisms are not well understood. Chewing gum after a nitrate-rich meal may upregulate the reduction of oral nitrate to nitrite and increase nitric oxide (NO), a molecule important to cardiovascular and neurocognitive health. We aimed to explore effects of chewing gum after a nitrate-rich meal on nitrate metabolism (through the enterosalivary nitrate-nitrite-NO pathway), endothelial function, blood pressure (BP), neurocognitive performance, mood and anxiety. Methods: Twenty healthy men (n=6) and women (n=14) with a mean age of 48 years (range: 23-69) were recruited to a randomized controlled cross-over trial. After consumption of a nitrate-rich meal (180 mg of nitrate), we assessed the acute effects of chewing gum, compared to no gum chewing, on (i) salivary nitrate, nitrite and the nitrate reductase ratio (100 x [nitrite] / ([nitrate] + [nitrite]); (ii) plasma nitrite, S-nitrosothiols and other nitroso species (RXNO); (iii) endothelial function (measured by flow mediated dilatation); (iv) BP; (v) neurocognitive performance; (vi) mood; and (vii) anxiety. Results: Consumption of the nitrate-rich meal resulted in a significant increase in markers of nitrate metabolism. A significantly higher peak flow mediated dilatation was observed with chewing compared to no chewing (baseline adjusted mean difference: 1.10%, 95% CI: 0.06, 2.14; p=0.038) after the nitrate-rich meal. A significant small increase in systolic BP, diastolic BP and heart rate were observed with chewing compared to no chewing after the nitrate-rich meal. The study did not observe increased oral reduction of nitrate to nitrite and NO, or improvements in neurocognitive performance, mood or anxiety with chewing compared to no chewing. Conclusion: Chewing gum after a nitrate-rich meal resulted in an acute improvement in endothelial function and a small increase in BP but did not result in acute effects on neurocognitive function, mood or anxiety

A Mediterranean Diet and Walking Intervention to Reduce Cognitive Decline and Dementia Risk in Independently Living Older Australians:The MedWalk Randomized Controlled Trial Experimental Protocol, Including COVID-19 Related Modifications and Baseline Characteristics.

Background:Several clinical trials have examined diet and physical activity lifestyle changes as mitigation strategies for risk factors linked to cognitive decline and dementias such as Alzheimer’s disease. However, the ability to modify these behaviors longer term, to impact cognitive health has remained elusive.Objective:The MedWalk trial’s primary aim is to investigate whether longer-term adherence to a Mediterranean-style diet and regular walking, delivered through motivational interviewing and cognitive-behavioral therapy (MI-CBT), can reduce age-associated cognitive decline and other dementia risk factors in older, independently living individuals without cognitive impairment.Methods:MedWalk, a one-year cluster-randomized controlled trial across two Australian states, recruited 60–90-year-old people from independent living retirement villages and the wider community. Participants were assigned to either the MedWalk intervention or a control group (maintaining their usual diet and physical activity). The primary outcome is 12-month change in visual memory and learning assessed from errors on the Paired Associates Learning Task of the Cambridge Neuropsychological Test Automated Battery. Secondary outcomes include cognition, mood, cardiovascular function, biomarkers related to nutrient status and cognitive decline, MI-CBT effectiveness, Mediterranean diet adherence, physical activity, quality of life, cost-effectiveness, and health economic evaluation.Progress and Discussion:Although COVID-19 impacts over two years necessitated a reduced timeline and sample size, MedWalk retains sufficient power to address its aims and hypotheses. Baseline testing has been completed with 157 participants, who will be followed over 12 months. If successful, MedWalk will inform interventions that could substantially reduce dementia incidence and ameliorate cognitive decline in the community.<br/

Octupole correlations in the structure of O2 bands in the N=88 nuclei150Sm Gd

Knowledge of the exact microscopic structure of the 01 + ground state and first excited 02 + state in 150Sm is required to understand the branching of double β decay to these states from 150Nd. The detailed spectroscopy of 150Sm and 152Gd has been studied using (α,xn) reactions and the γ -ray arrays AFRODITE and JUROGAM II. Consistently strong E1 transitions are observed between the excited Kπ = 02 + bands and the lowest negative parity bands in both nuclei. These results are discussed in terms of the possible permanent octupole deformation in the first excited Kπ = 02 + band and also in terms of the “tidal wave” model of Frauendorf.Web of Scienc

MDMA, cortisol and heightened stress in recreational Ecstasy users

Stress develops when an organism requires additional metabolic resources to cope with demanding situations. This review will debate how recreational 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') can increase some aspects of acute and chronic stress in humans. Laboratory studies on the acute effects of MDMA on cortisol release and neurohormone levels in drug-free regular ecstasy/MDMA users have been reviewed, and the role of the hypothalamic-pituitary-adrenal (HPA) axis in chronic changes in anxiety, stress, and cognitive coping is debated. In the laboratory, acute ecstasy/MDMA use can increase cortisol levels by 100-200%, whereas ecstasy/MDMA-using dance clubbers experience an 800% increase in cortisol levels, because of the combined effects of the stimulant drug and dancing. Three-month hair samples of abstinent users revealed cortisol levels 400% higher than those in controls. Chronic users show heightened cortisol release in stressful environments and deficits in complex neurocognitive tasks. Event-related evoked response potential studies show altered patterns of brain activation, suggestive of increased mental effort, during basic information processing. Chronic mood deficits include more daily stress and higher depression in susceptible individuals. We conclude that ecstasy/MDMA increases cortisol levels acutely and subchronically and that changes in the HPA axis may explain why recreational ecstasy/MDMA users show various aspects of neuropsychobiological stress

Evaluating the Hounsfield unit assignment and dose differences between CT-based standard and deep learning-based synthetic CT images for MRI-only radiation therapy of the head and neck.

BACKGROUND: Magnetic resonance image only (MRI-only) simulation for head and neck (H&amp;N) radiotherapy (RT) could allow for single-image modality planning with excellent soft tissue contrast. In the MRI-only simulation workflow, synthetic computed tomography (sCT) is generated from MRI to provide electron density information for dose calculation. Bone/air regions produce little MRI signal which could lead to electron density misclassification in sCT. Establishing the dosimetric impact of this error could inform quality assurance (QA) procedures using MRI-only RT planning or compensatory methods for accurate dosimetric calculation. PURPOSE: The aim of this study was to investigate if Hounsfield unit (HU) voxel misassignments from sCT images result in dosimetric errors in clinical treatment plans. METHODS: Fourteen H&amp;N cancer patients undergoing same-day CT and 3T MRI simulation were retrospectively identified. MRI was deformed to the CT using multimodal deformable image registration. sCTs were generated from T1w DIXON MRIs using a commercially available deep learning-based generator (MRIplanner, Spectronic Medical AB, Helsingborg, Sweden). Tissue voxel assignment was quantified by creating a CT-derived HU threshold contour. CT/sCT HU differences for anatomical/target contours and tissue classification regions including air (&lt;250 HU), adipose tissue (-250 HU to -51 HU), soft tissue (-50 HU to 199 HU), spongy (200 HU to 499 HU) and cortical bone&nbsp;(&gt;500 HU) were quantified. t-test was used to determine if sCT/CT HU differences were significant. The frequency of structures that had a HU difference&nbsp;&gt;&nbsp;80 HU (the CT window-width setting for intra-cranial structures) was computed to establish structure classification accuracy. Clinical intensity modulated radiation therapy (IMRT) treatment plans created on CT were retrospectively recalculated on sCT images and compared using the gamma metric. RESULTS: The mean ratio of sCT HUs relative to CT for air, adipose tissue, soft tissue, spongy and cortical bone were 1.7&nbsp;±&nbsp;0.3, 1.1&nbsp;±&nbsp;0.1, 1.0&nbsp;±&nbsp;0.1, 0.9&nbsp;±&nbsp;0.1 and 0.8&nbsp;±&nbsp;0.1 (value of 1 indicates perfect agreement). T-tests (significance set at t&nbsp;=&nbsp;0.05) identified differences in HU values for air, spongy and cortical bone in sCT images compared to CT. The structures with sCT/CT HU differences&nbsp;&gt;&nbsp;80 HU of note were the left and right (L/R) cochlea and mandible (&gt;79% of the tested cohort), the oral cavity (for 57% of the tested cohort), the epiglottis (for 43% of the tested cohort) and the L/R TM joints (occurring&nbsp;&gt;&nbsp;29% of the cohort). In the case of the cochlea and TM joints, these structures contain dense bone/air interfaces. In the case of the oral cavity and mandible, these structures suffer the additional challenge of being positionally altered in CT versus MRI simulation (due to a non-MR safe immobilizing bite block requiring absence of bite block in MR). Finally, the epiglottis HU assignment suffers from its small size and unstable positionality. Plans recalculated on sCT yielded global/local gamma pass rates of 95.5%&nbsp;±&nbsp;2% (3&nbsp;mm, 3%) and 92.7%&nbsp;±&nbsp;2.1% (2&nbsp;mm, 2%). The largest mean differences in D95, Dmean , D50 dose volume histogram (DVH) metrics for organ-at-risk (OAR) and planning tumor volumes (PTVs) were 2.3%&nbsp;±&nbsp;3.0% and 0.7%&nbsp;±&nbsp;1.9% respectively. CONCLUSIONS: In this cohort, HU differences of CT and sCT were observed but did not translate into a reduction in gamma pass rates or differences in average PTV/OAR dose metrics greater than 3%. For sites such as the H&amp;N where there are many tissue interfaces we did not observe large scale dose deviations but further studies using larger retrospective cohorts are merited to establish the variation in sCT dosimetric accuracy which could help to inform QA limits on clinical sCT usage

Effect of a 12-Week Almond-Enriched Diet on Biomarkers of Cognitive Performance, Mood, and Cardiometabolic Health in Older Overweight Adults

Long term nut consumption is associated with reduced risk of coronary heart disease and better cognitive function. This study examined supplementing habitual diets with almonds or carbohydrate-rich snack foods (providing 15% energy) on biomarkers of cardiovascular and metabolic health, mood and cognitive performance. Participants (overweight/obese, 50&ndash;80 years) were randomised to an almond-enriched diet (AED) or isocaloric nut-free diet (NFD) for 12 weeks. Body weight, blood lipids, glucose, insulin, blood pressure (BP), arterial stiffness, cell adhesions molecules, C reactive protein (CRP), mood, and cognitive performance (working memory primary outcome), dietary profiles and energy intake/expenditure were measured at baseline and Week 12 in 128 participants (n = 63 AED, n = 65 NFD). Compared with NFD, AED was associated with altered macro and micronutrient profiles, but no differences in energy intake or expenditure. The AED significantly reduced triglycerides and SBP but there were no other changes in cardiometabolic biomarkers, mood, or cognitive performance. The inclusion of almonds in the diet improves aspects of cardiometabolic health without affecting cognitive performance or mood in overweight/obese adults

Influence of glucosamine on glomerular mesangial cell turnover: implications for hyperglycemia and hexosamine pathway flux

Cells exposed to high glucose may undergo hypertrophy, proliferation, and apoptosis, but the role of hexosamine flux in mediating these effects has not been fully elucidated. Accordingly, we studied the effects of glucose and glucosamine on rat glomerular mesangial cells (MC) turnover. Compared with physiological glucose (5.6 mM), treatment with high glucose (25 mM) for 24 h stimulated MC proliferation, an effect that was mimicked by exposure to low concentrations of glucosamine (0.05 mM). The percentage of cells in G0/G1 phase of the cell cycle was reduced with a concomitant increase of the number of cells in G2/M phase. Proliferating cell nuclear antigen, phosphorylated mammalian target of rapamycin [phospho-mTOR (Ser2448)], and total regulatory-associated protein of mTOR were increased by high glucose and glucosamine treatment. Inhibition of glutamine:fructose-6-phosphate amidotransferase (GFAT), the rate-limiting enzyme for hexosamine flux, with 6-diazo-5-oxonorleucine (10 μM) and of mTOR with rapamycin both attenuated glucose-mediated MC proliferation. Higher glucosamine concentrations (0.25–10 mM) caused MC apoptosis after 48 h, and, in addition, GFAT overexpression also increased MC apoptosis (TdT-dUTP nick end-labeling-positive cells: 3.8 ± 0.3 vs. 1.1 ± 0.2% for empty vector; P < 0.05). Hence, hexosamine flux is an important determinant of MC proliferation and apoptosis. The proliferative response to high glucose and hexosamine flux is rapamycin-sensitive, suggesting that this effect is associated with signaling through rapamycin-sensitive mTOR complex 1 (mTORC1)

In-beam γ-ray spectroscopy of low- and medium-spin levels in 211Po

The structure of the low- and medium-spin levels of the 211Po nucleus have been studied with in-beam γ-ray spectroscopy with the 208Pb(α,n)211Po fusion-evaporation reaction. The level scheme was further extended with levels of the configurations π(h9/2)22+−4+⊗νg9/2, π(h9/2)28+⊗νg9/2, π(h9/2)22+−4+⊗νi11/2, π(h9/2)22+−4+⊗νj15/2, π(h9/2f7/2)8+⊗νg9/2, and π(h9/2)20+⊗ν(g9/2)20+(s1/2)−1. The single-particle neutron states νd5/2 and νs1/2 were also identified. Furthermore, a number of states feeding the low-spin structures were added.peerReviewe

Recoil-decay tagging study of 205Fr

The nucleus 205Fr has been studied through γ -ray and electron spectroscopy using the recoil-decay tagging technique. The resulting level scheme presents a spherical structure built on the 9/2− ground state and a rotational structure on top of a short-lived isomer. The isomer, with a spin and parity of 13/2+ and a half-life of 80(20) ns, de-excites by an M2 transition directly to the 9/2− ground state. Another, longer-lived, isomer, with a half-life of 1.15(4) ms, has also been found and assigned a spin and parity of 1/2+. Transitions populating and de-exciting this isomer have been observed as well.peerReviewe

Spectroscopy of the proton drip-line nucleus 203Fr

The nucleus 203Fr has been studied through γ -ray and electron spectroscopy, using the recoil-decay tagging technique. A 13/2+ state, with a half-life of 0.37(5) μs, has been observed in 203Fr. Both the α-decay branch and the internal de-excitation of the 1/2+ isomer in 203Fr have been studied. Furthermore, the corresponding 1/2+ state, with a half-life of 0.31(8) s, has been found in 199At. In addition, transitions feeding the 9/2− ground state of 203Fr have been identified. The observed level pattern suggests that the ground state is still spherical.peerReviewe