Cognitive reserve is associated with the functional organization of brain networks in healthy aging: a MEG study

The proportion of elderly people in the population has increased rapidly in the last century and consequently "healthy aging" is expected to become a critical area of research in neuroscience. Evidence reveals how healthy aging depends on three main behavioral factors: social lifestyle, cognitive activity and physical activity. In this study, we focused on the role of cognitive activity, concentrating specifically on educational and occupational attainment factors, which were considered two of the main pillars of cognitive reserve. 21 subjects with similar rates of social lifestyle, physical and cognitive activity were selected from a sample of 55 healthy adults. These subjects were divided into two groups according to their level of cognitive reserve; one group comprised subjects with high cognitive reserve (9 members) and the other contained those with low cognitive reserve (12 members). To evaluate the cortical brain connectivity network, all participants were recorded by Magnetoencephalography (MEG) while they performed a memory task (modified version of the Sternberg¿s Task). We then applied two algorithms (Phase Locking Value & Phase-Lag Index) to study the dynamics of functional connectivity. In response to the same task, the subjects with lower cognitive reserve presented higher functional connectivity than those with higher cognitive reserve. These results may indicate that participants with low cognitive reserve needed a greater 'effort' than those with high cognitive reserve to achieve the same level of cognitive performance. Therefore, we conclude that cognitive reserve contributes to the modulation of the functional connectivity patterns of the aging brain.

Expansion of a recurrent V beta 5.3+ T-cell population in newly diagnosed and untreated HLA-DR2 multiple sclerosis patients.

We have used a PCR-based technology to study the V beta 5 and V beta 17 repertoire of T-cell populations in HLA-DR2 multiple sclerosis (MS) patients. We have found that the five MS DR2 patients studied present, at the moment of diagnosis and prior to any treatment, a marked expansion of a CD4+ T-cell population bearing V beta 5-J beta 1.4 beta chains. The sequences of the complementarity-determining region 3 of the expanded T cells are highly homologous. One shares structural features with that of the T cells infiltrating the central nervous system and of myelin basic protein-reactive T cells found in HLA-DR2 MS patients. An homologous sequence was not detectable in MS patients expressing DR alleles other than DR2. However, it is detectable but not expanded in healthy DR2 individuals. The possible mechanisms leading to its in vivo proliferation at the onset of MS are discussed.

Isolation and molecular characterization of a human T-cell lymphotropic virus type II (HTLV-II), subtype B, from a healthy Pygmy living in a remote area of Cameroon: an ancient origin for HTLV-II in Africa.

We report characterization of a human T-cell lymphotropic virus type II (HTLV-II) isolated from an interleukin 2-dependent CD8 T-cell line derived from peripheral blood mononuclear cells of a healthy, HTLV-II-seropositive female Bakola Pygmy, aged 59, living in a remote equatorial forest area in south Cameroon. This HTLLV-II isolate, designated PYGCAM-1, reacted in an indirect immunofluorescence assay with HTLV-II and HTLV-I polyclonal antibodies and with an HTLV-I/II gp46 monoclonal antibody but not with HTLV-I gag p19 or p24 monoclonal antibodies. The cell line produced HTLV-I/II p24 core antigen and retroviral particles. The entire env gene (1462 bp) and most of the long terminal repeat (715 bp) of the PYGCAM-1 provirus were amplified by the polymerase chain reaction using HTLV-II-specific primers. Comparison with the long terminal repeat and envelope sequences of prototype HTLV-II strains indicated that PYGCAM-1 belongs to the subtype B group, as it has only 0.5-2% nucleotide divergence from HTLV-II B strains. The finding of antibodies to HTLV-II in sera taken from the father of the woman in 1984 and from three unrelated members of the same population strongly suggests that PYGCAM-1 is a genuine HTLV-II that has been present in this isolated population for a long time. The low genetic divergence of this African isolate from American isolates raises questions about the genetic variability over time and the origin and dissemination of HTLV-II, hitherto considered to be predominantly a New World virus.

Health inequality between immigrants and natives in Spain: the loss of the healthy immigrant effect in times of economic crisis

Background: The immigrant population living in Spain grew exponentially in the early 2000s but has been particularly affected by the economic crisis. This study aims to analyse health inequalities between immigrants born in middle- or low-income countries and natives in Spain, in 2006 and 2012, taking into account gender, year of arrival and socioeconomic exposures. Methods: Study of trends using two cross-sections, the 2006 and 2012 editions of the Spanish National Health Survey, including residents in Spain aged 15–64 years (20 810 natives and 2950 immigrants in 2006, 14 291 natives and 2448 immigrants in 2012). Fair/poor self-rated health, poor mental health (GHQ-12 > 2), chronic activity limitation and use of psychotropic drugs were compared between natives and immigrants who arrived in Spain before 2006, adjusting robust Poisson regression models for age and socioeconomic variables to obtain prevalence ratios (PR) and 95% confidence interval (CI). Results: Inequalities in poor self-rated health between immigrants and natives tend to increase among women (age-adjusted PR2006 = 1.39; 95% CI: 1.24–1.56, PR2012 = 1.56; 95% CI: 1.33–1.82). Among men, there is a new onset of inequalities in poor mental health (PR2006 = 1.10; 95% CI: 0.86–1.40, PR2012 = 1.34; 95% CI: 1.06–1.69) and an equalization of the previously lower use of psychotropic drugs (PR2006 = 0.22; 95% CI: 0.11–0.43, PR2012 = 1.20; 95% CI: 0.73–2.01). Conclusions: Between 2006 and 2012, immigrants who arrived in Spain before 2006 appeared to worsen their health status when compared with natives. The loss of the healthy immigrant effect in the context of a worse impact of the economic crisis on immigrants appears as potential explanation. Employment, social protection and re-universalization of healthcare would prevent further deterioration of immigrants’ health status.

The Portuguese National Programme for the Promotion of Healthy Eating: 2012–2015

This paper describes the first 4-year period (2012–2015) of implementation of the Portuguese National Programme for the Promotion of Healthy Eating (PNPAS). PNPAS was approved in 2012 and emerged as a preventive programme for noncommunicable diseases, aiming to improve the nutritional status of the population; it represents the first national strategy in Portugal for the promotion of healthy eating. To accomplish its mission, and taking into account its overall principles, PNPAS has five main goals: (i) to increase knowledge about the food intake of the Portuguese population and about its determinants and consequences; (ii) to modify the availability of certain foods (high in sugar, salt and fat), in schools, workplaces and public spaces; (iii) to inform and empower the population for the purchase, preparation and storage of healthy food, especially the most vulnerable groups; (iv) to identify and promote crosssectoral actions that encourage the consumption of foods of good nutritional quality in an articulate and integrated way with other sectors, namely agriculture, sport, environment, education, social security and local authorities; and (v) to improve the qualifications and conduct of the different professionals who, owing to their roles, may influence nutritional knowledge, attitudes and behaviours. The design of PNPAS followed the latest strategic lines suggested by WHO and the European Commission, proposing a crosssectoral mix of interventions to ensure physical and economic access to healthy eating by creating healthy environments and empowering individuals and communities. Several actions were implemented at different levels during the first 4-year period of implementation of PNPAS; two were especially relevant. The first concerned the empowerment of citizens regarding healthy eating, where the most important aspect was introduction of a digital strategy through development of a website and a blog dedicated to healthy eating. The second concerned the development of documents for health care and other professionals, including several guidelines in new areas, such as anthropometric measures and intervention in preobesity. Process and output indicators were defined to monitor and evaluate the programme. Among those considered as output indicators were the evaluation of childhood obesity, salt consumption and intake of breakfast by school-aged children.

The High Frequency Component of Heart Rate Variability and Delta EEG Power during Sleep in Healthy Women and Women with Irritable Bowel Syndrome

Thesis (Ph.D.)--University of Washington, 2016-06

Effects of chronic exposure to low-level cadmium on renal tubular function and CYP2A6-mediated coumarin metabolism in healthy human subjects

Relationships between cadmium (Cd) body burden, kidney function and coumarin metabolism were investigated using two groups of 197 and 200 healthy Thais with men and women in nearly equal numbers. A mean age of one group was 30.5 years and it was 39.3 years for the other group. Of 397, 20 subjects (5%) excreted urine Cd between 1.4 mug/g and 3.8 mug/g creatinine and these subjects faced 10-15% increase in the probability of having abnormal urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG-uria). The prevalence of NAG-uria varied with Cd body burden in a dose-dependent manner (chi(2) = 22, P < 0.008). Also NAG-nuria was one of the three kidney effect markers tested that showed the greatest strength of correlation with urine Cd in both men and women (r = 0.48 P < 0.001). In addition, urine Cd excretion of men and women showed a positive correlation (r = 0.46 to 0.54. P < 0.001) with urine 7-hydroxycoumarin (7-OHC) excretion which was used as a marker of liver cytochrome P450 2A6 (CYP2A6) enzyme activity. Urinary CA excretion accounted for 25% of the total variation in urine 7-OHC excretion (P < 0.001). These data suggest that Cd may increase the expression of CYP2A6 in liver, resulting in enhanced coumarin metabolism in subjects with high Cd body burden. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Influence of body iron store status and cigarette smoking on cadmium body burden of healthy Thai women and men

The influence of cigarette smoking, body iron store status and gender on cadmium (Cd) body burden was examined in a group of 197 healthy Thais with overall mean age of 30.5 year (19-47 year). The lowest, geometric mean, and the highest urinary Cd excretion rate was 0.04, 0.46 and 3.84 mug/g creatinine, respectively. The prevalence of low iron stores (serum ferritin

Family average income and body mass index above the healthy weight range among urban and rural residents in regional Mainland China

Objective: To explore the relationship between family average income (FAI; an index of socio-economic status) and body mass index (BMI; a widely used, inexpensive indicator of weight status) above the healthy weight range in a region of Mainland China. Design: Population-based cross-sectional study, conducted between October 1999 and March 2000 on a sample of regular local residents aged 35 years or older who were selected by random cluster sampling. Setting: Forty-five administrative villages selected from three urban districts and two rural counties of Nanjing municipality, Mainland China, with a regional population of 5.6 million. Subjects: In total, 29 340 subjects participated; 67.7% from urban and 32.3% from rural areas; 49.8% male and 50.2% female. The response rate among eligible participants was 90.1%. Results: The proportion of participants classified as overweight was 30.5%, while 7.8% were identified as obese. After adjusting for possible confounding variables (age, gender, area of residence, educational level, occupational and leisure-time physical activity, daily vegetable consumption and frequency of red meat intake), urban participants were more likely to be overweight or obese relative to their rural counterparts, more women than men were obese, and participants in the lowest FAI tertile were the least likely to be above the healthy weight range. Conclusions: The proportion of adults with BMI above the healthy weight range was positively related to having a higher socio-economic status (indexed by FAI) in a regional Chinese population.

Area-under-the-curve monitoring of prednisolone for dose optimization in a stable renal transplant population

Background: Renal transplant recipients were noted to appear cushingoid while on low doses of steroid as part of a triple therapy immunosuppression of cyclosporin A (CsA), prednisolone, and azathioprine. Methods: The study group comprised adult renal transplant recipients with stable graft function who had received their renal allograft a minimum of 1 year previously (43 studies undertaken in 22 men and 20 women) with median daily prednisone dose of 7 mg (range 3-10). The control group was healthy nontransplant subjects [median dose 10 mg (10-30)]. Prednisolone bioavailability was measured using a limited 6-hour area under the curve (AUC), with prednisolone measured using specific HPLC assay. Results: The median prednisolone AUC/mg dose for all transplant recipients was significantly greater than the control group by approximately 50% (316 nmol(.)h/L/mg prednisolone versus 218). AUC was significantly higher in female recipients (median 415 versus 297 for men) and in recipients receiving cyclospotin (348 versus 285). The highest AUC was in women on estrogen supplements who were receiving cyclosporin (median 595). A significantly higher proportion of patients on triple therapy had steroid side effects compared with those on steroid and azathioprine (17/27 versus 4/15), more women than men had side effects (14/16 versus 7/22), and the AUC/mg prednisone was greater in those with side effects than without (median 377 versus 288 nmol-h/L/mg). Discussion: The results are consistent with the hypothesis that CsA increases the bioavailability of prednisolone, most likely through inhibition of beta-glycoprotein. The increased exposure to steroid increased the side-effect profile of steroids in the majority of patients. Because the major contributor to AUC is the maximum postdose concentration, it may be possible to use single-point monitoring (2 hours postdose) for routine clinical studies.

A simple lifestyle score predicts survival in healthy elderly men

Background. Although improvements in life expectancy have been attributed in part to the adoption or a more prudent lifestyle, few studies have examined the association of lifestyle with survival, using several lifestyle factors simultaneously, in a healthy elderly population. Methods. We investigated the association of health related behaviors with mortality in 7989 men aged 65 to 83 years participating in a population-based trial in Perth, Western Australia, by calculating a lifestyle score as a simple tally of flow many or eight prudent behaviors each individual followed. Results. Invitations to screening produced a corrected response of 70.5%. Out of a possible score of 8.46% of men had a score of less than 5. Within 5 years, a total of 703 men (9%) had died from any cause. The hazard ratio in men with a low lifestyle score was 1.3 [95% confidence interval (CI): 1.1-1.5] compared with men with a score of 5 or more. Conclusions. Lifestyle remains an important predictor of mortality even in old age. Survival in older men without a history of cardiovascular disease can potentially be enhanced by promoting a healthy lifestyle. © 2004 Elsevier Inc, All rights reserved.

Optimal design for model discrimination and parameter estimation for itraconazole population pharmacokinetics in cystic fibrosis patients

Optimal sampling times are found for a study in which one of the primary purposes is to develop a model of the pharmacokinetics of itraconazole in patients with cystic fibrosis for both capsule and solution doses. The optimal design is expected to produce reliable estimates of population parameters for two different structural PK models. Data collected at these sampling times are also expected to provide the researchers with sufficient information to reasonably discriminate between the two competing structural models.

The population pharmacokinetics of citalopram after deliberate self-poisoning: A Bayesian approach

Defining the pharmacokinetics of drugs in overdose is complicated. Deliberate self-poisoning is generally impulsive and associated with poor accuracy in dose history. In addition, early blood samples are rarely collected to characterize the whole plasma-concentration time profile and the effect of decontamination on the pharmacokinetics is uncertain. The aim of this study was to explore a fully Bayesian methodology for population pharmacokinetic analysis of data that arose from deliberate self-poisoning with citalopram. Prior information on the pharmacokinetic parameters was elicited from 14 published studies on citalopram when taken in therapeutic doses. The data set included concentration-time data from 53 patients studied after 63 citalopram overdose events (dose range: 20-1700 mg). Activated charcoal was administered between 0.5 and 4 h after 17 overdose events. The clinical investigator graded the veracity of the patients' dosing history on a 5-point ordinal scale. Inclusion of informative priors stabilised the pharmacokinetic model and the population mean values could be estimated well. There were no indications of non-linear clearance after excessive doses. The final model included an estimated uncertainty of the dose amount which in a simulation study was shown to not affect the model's ability to characterise the effects of activated charcoal. The effect of activated charcoal on clearance and bioavailability was pronounced and resulted in a 72% increase and 22% decrease, respectively. These findings suggest charcoal administration is potentially beneficial after citalopram overdose. The methodology explored seems promising for exploring the dose-exposure relationship in the toxicological settings.

Behavioral determinants of healthy aging

With global trends in population aging, many nations are developing and implementing healthy aging policies to promote quality as well as years of healthy life. To broaden the evidence base for such policy development, a review of the literature was conducted to summarize the existing evidence regarding the behavioral determinants of health), aging. Such research is needed so that the efficacy of modes of intervention can be better understood. The Outcome of: healthy or successful aging was selected for this review since this nomenclature dominates the literature describing a global measure of multidimensional functioning at the positive end of the health continuum in older age. Studies published between 1985 and 2003 that reported statistical associations between baseline determinants and healthy aging Outcome were identified from a systematic search of medical, psychological, sociological, and gerontological databases. Eight studies satisfied the search criteria. Modifiable risk factors among the behavioral determinants included smoking status, physical activity level, body mass index, diet, alcohol use, and health practices. On the basis of these findings, effective healthy aging policies need to enhance opportunities across the life span for modification of lifestyle risk factors. Efforts to standardize concepts and terminology will facilitate further research activity in this important area. (Am J Prev Med 2005;28(3):298-304) (c) 2005 American Journal of Preventive Medicine.

Health-protective behaviours and risk of fall-related hip fractures: a population-based case-control study

Background: fall-related hip fractures are one of the most common causes of disability and mortality in older age. The study aimed to quantify the relationship between lifestyle behaviours and the risk of fall-related hip fracture in community-dwelling older people. The purpose was to contribute evidence for the promotion of healthy ageing as a population-based intervention for falls injury prevention. Methods: a case-control study was conducted with 387 participants, with a case-control ratio of 1:2. Incident cases of fall-related hip fracture in people aged 65 and over were recruited from six hospital sites in Brisbane, Australia, in 2003-04. Community-based controls, matched by age, sex and postcode, were recruited via electoral roll sampling. A questionnaire designed to assess lifestyle risk factors, identified as determinants of healthy ageing, was administered at face-to-face interviews. Results: behavioural factors which had a significant independent protective effect on the risk of hip fracture included never smoking [adjusted odds ratio (AOR): 0.33 (0.12-0.88)], moderate alcohol consumption in mid- and older age [AOR: 0.49 (0.25-0.95)], not losing weight between mid- and older age [AOR: 0.36 (0.20-0.65)], playing sport in older age [AOR: 0.49 (0.29-0.83)] and practising a greater number of preventive medical care [AOR: 0.54 (0.32-0.94)] and self-health behaviours [AOR: 0.56 (0.33-0.94)]. Conclusion: with universal exposures, clear associations and modifiable behavioural factors, this study has contributed evidence to reduce the major public health burden of fall-related hip fractures using readily implemented population-based healthy ageing strategies.