A mathematical model of aging-related and cortisol induced hippocampal dysfunction

<p>Abstract</p> <p>Background</p> <p>The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silico<it/>model of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated.</p> <p>Results</p> <p>The in silico<it/>SBML model reflected the in vivo<it/>aging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation.</p> <p>Conclusion</p> <p>Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitro<it/>and in vivo<it/>studies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people.</p

The effect of long term combined yoga practice on the basal metabolic rate of healthy adults

BACKGROUND: Different procedures practiced in yoga have stimulatory or inhibitory effects on the basal metabolic rate when studied acutely. In daily life however, these procedures are usually practiced in combination. The purpose of the present study was to investigate the net change in the basal metabolic rate (BMR) of individuals actively engaging in a combination of yoga practices (asana or yogic postures, meditation and pranayama or breathing exercises) for a minimum period of six months, at a residential yoga education and research center at Bangalore. METHODS: The measured BMR of individuals practicing yoga through a combination of practices was compared with that of control subjects who did not practice yoga but led similar lifestyles. RESULTS: The BMR of the yoga practitioners was significantly lower than that of the non-yoga group, and was lower by about 13 % when adjusted for body weight (P < 0.001). This difference persisted when the groups were stratified by gender; however, the difference in BMR adjusted for body weight was greater in women than men (about 8 and 18% respectively). In addition, the mean BMR of the yoga group was significantly lower than their predicted values, while the mean BMR of non-yoga group was comparable with their predicted values derived from 1985 WHO/FAO/UNU predictive equations. CONCLUSION: This study shows that there is a significantly reduced BMR, probably linked to reduced arousal, with the long term practice of yoga using a combination of stimulatory and inhibitory yogic practices

Birth weight, hypertension and "white coat" hypertension: size at birth in relation to office and 24-h ambulatory blood pressure.

We investigated the association of size at birth with hypertensive status defined by office blood pressure (BP) and 24-h ambulatory BP monitoring in a historical cohort study of 736 men born 1920-1924 and examined at age 70 years. Office BP was measured after 10-min supine rest with a sphygmomanometer, ambulatory BP was recorded with Accutracker 2, and anthropometric and other measurements were taken at a clinic. Birth weight and gestational age were abstracted from the men's birth records. A total of 24% of the men were treated for hypertension at the time of the study. Among not treated subjects, there was a weak positive association of birth weight with daytime and 24-h diastolic ambulatory BP. In subjects treated for hypertension, both office and ambulatory BP were inversely related to birth weight, although these associations were not statistically significant. Birth weight did not show significant association with sustained hypertension (elevated office and daytime ambulatory BPs) but showed a strong and statistically significant inverse association with "white coat" hypertension (elevated office BP and normal daytime ambulatory BP) when adjusted for concurrent body mass index (odds ratios 1.91, 1.59, 1 and 1.21 from lowest to highest quartile of birth weight, P-value for trend 0.035). We conclude that BP measured by 24-h-ambulatory monitoring is not related to birth weight in a pattern previously reported for office BP and that factors related to growth in utero are particularly related to higher risk of "white coat" hypertension

Spiritual well-being and quality of life among Icelanders receiving palliative care: data from Icelandic pilot-testing of a provisional measure of spiritual well-being from the European Organisation for Research and Treatment of Cancer.

To access publisher's full text version of this article click on the hyperlink below.Palliative care focuses on improving quality of life (QoL). This study examined the feasibility of the Icelandic version of a provisional European Organisation for Research and Treatment of Cancer (EORTC) measure of spiritual well-being (SWB), and explored the relationship between SWB and QoL for palliative care patients in Iceland. Instruments from the EORTC were used: the provisional measure of SWB, which was undergoing pilot-testing in Iceland, and the EORTC QLQ C15-PAL. The correlation between scores was examined and descriptive statistics were used. Structured interviews explored feasibility. Thirty persons participated with average age 72 years. Belief in God or a higher power had the mean 3.33 on a 1-4 scale and the mean for overall SWB was 5.73 on a 1-7 scale. The mean score for global health/QoL was 59.4, physical functioning 48.5 and emotional functioning 78.9 on a 0-100 scale. Overall QoL was positively correlated with SWB showing r(30) = 0.386, P = 0.035. The participants found that answering the provisional EORTC QLQ-SWB prompted an emotional response and took the opportunity to discuss the subject. The provisional SWB measure was found relevant for the Icelandic context, and the study indicates that SWB and QoL are closely connected.Science Fund of Landspitali - The National University Hospital of Iceland Science Fund of The Icelandic Pastoral Associatio

High Atlastin 2-2 (ATL2-2) Expression Associates with Worse Prognosis in Estrogen-Receptor-Positive Breast Cancer

The disruption of endoplasmic reticulum (ER) homeostasis occurs in many human diseases. Atlastins (ATLs) maintain the branched network of the ER. The dysregulation of ATL2, located at ER network junctions, has been associated with cancer. ATL2 is necessary for lipid droplet formation in murine breast tissue. Thus, we analyzed whether ATL2 has a role in human breast cancer (BC) pathology. The expression of ATL2 variant ATL2-2 was analyzed in breast tumors from the BC cohorts of the TCGA, METABRIC, and two independent Icelandic cohorts, Cohort 1 and 2; its association with clinical, pathological, survival, and cellular pathways was explored. ATL2-2 mRNA and protein expression were higher in breast tumors than in normal tissue. ATL2-2 mRNA associated with tumor characteristics that indicate a worse prognosis. In METABRIC, high ATL2-2 mRNA levels were associated with shorter BC-specific survival (BCSS) in patients with estrogen-receptor-positive luminal breast tumors, which remained significant after correction for grade and tumor size (HR 1.334, CI 1.063–1.673). Tumors with high ATL2 mRNA showed an upregulation of hallmark pathways MYC targets v1, E2F targets, and G2M checkpoint genes. Taken together, the results suggest that high levels of ATL2-2 may support BC progression through key cancer driver pathways