Cognitive function, social integration and mortality in a U.S. national cohort study of older adults

<p>Abstract</p> <p>Background</p> <p>Prior research suggests an interaction between social networks and Alzheimer's disease pathology and cognitive function, all predictors of survival in the elderly. We test the hypotheses that both social integration and cognitive function are independently associated with subsequent mortality and there is an interaction between social integration and cognitive function as related to mortality in a national cohort of older persons.</p> <p>Methods</p> <p>Data were analyzed from a longitudinal follow-up study of 5,908 American men and women aged 60 years and over examined in 1988–1994 followed an average 8.5 yr. Measurements at baseline included self-reported social integration, socio-demographics, health, body mass index, C-reactive protein and a short index of cognitive function (SICF).</p> <p>Results</p> <p>Death during follow-up occurred in 2,431. In bivariate analyses indicators of greater social integration were associated with higher cognitive function. Among persons with SICF score of 17, 22% died compared to 54% of those with SICF score of 0–11 (p < 0.0001). After adjusting for confounding by baseline socio-demographics and health status, the hazards ratio (HR) (95% confidence limits) for low SICF score was 1.43 (1.13–1.80, p < 0.001). After controlling for health behaviors, blood pressure and body mass, C-reactive protein and social integration, the HR was 1.36 (1.06–1.76, p = 0.02). Further low compared to high social integration was also independently associated with increased risk of mortality: HR 1.24 (1.02–1.52, p = 0.02).</p> <p>Conclusion</p> <p>In a cohort of older Americans, analyses demonstrated a higher risk of death independent of confounders among those with low cognitive function and low social integration with no significant interaction between them.</p

Child and parent predictors of picky eating from preschool to school age

Background: Picky eating is prevalent in childhood. Because pickiness concerns parents and is associated with nutrient deficiency and psychological problems, the antecedents of pickiness need to be identified. We propose an etiological model of picky eating involving child temperament, sensory sensitivity and parent-child interaction. Methods: Two cohorts of 4-year olds (born 2003 or 2004) in Trondheim, Norway were invited to participate (97.2% attendance; 82.0% consent rate, n = 2475) and a screen-stratified subsample of 1250 children was recruited. We interviewed 997 parents about their child’s pickiness and sensory sensitivity using the Preschool Age Psychiatric Assessment (PAPA). Two years later, 795 of the parents completed the interview. The Children’s Behavior Questionnaire (CBQ) was used to assess children’s temperament. Parent- child interactions were videotaped and parental sensitivity (i.e., parental awareness and appropriate responsiveness to children’s verbal and nonverbal cues) and structuring were rated using the Emotional Availability Scales (EAS). Results: At both measurement times, 26% of the children were categorized as picky eaters. Pickiness was moderately stable from preschool to school age (OR = 5.92, CI = 3.95, 8.86), and about half of those who displayed pickiness at age 4 were also picky eaters two years later. While accounting for pickiness at age 4, sensory sensitivity at age 4 predicted pickiness at age 6 (OR = 1.25, CI = 1.08, 2.23), whereas temperamental surgency (OR = 0.88, CI = 0.64, 1.22) and negative affectivity (OR = 1.17, CI = 0.75, 1.84) did not. Parental structuring was found to reduce the risk of children’s picky eating two years later (OR = 0.90, CI = 0.82, 0.99), whereas parental sensitivity increased the odds for pickiness (OR = 1.10, CI = 1.00, 1.21). Conclusions: Although pickiness is stable from preschool to school age, children who are more sensory sensitive are at higher risk for pickiness two years later, as are children whose parents display relatively higher levels of sensitivity and lower levels of structuring. Our findings suggest that interventions targeting children’s sensory sensitivity, as well as parental sensitivity and structuring, might reduce the risk of childhood pickiness. Health care providers should support parents of picky eaters in repeatedly offering unfamiliar and rejected foods to their children without pressure and acknowledging child autonomy

High CO2 and Silicate Limitation Synergistically Increase the Toxicity of Pseudo-nitzschia fraudulenta

Anthropogenic CO2 is progressively acidifying the ocean, but the responses of harmful algal bloom species that produce toxins that can bioaccumulate remain virtually unknown. The neurotoxin domoic acid is produced by the globally-distributed diatom genus Pseudo-nitzschia. This toxin is responsible for amnesic shellfish poisoning, which can result in illness or death in humans and regularly causes mass mortalities of marine mammals and birds. Domoic acid production by Pseudo-nitzschia cells is known to be regulated by nutrient availability, but potential interactions with increasing seawater CO2 concentrations are poorly understood. Here we present experiments measuring domoic acid production by acclimatized cultures of Pseudo-nitzschia fraudulenta that demonstrate a strong synergism between projected future CO2 levels (765 ppm) and silicate-limited growth, which greatly increases cellular toxicity relative to growth under modern atmospheric (360 ppm) or pre-industrial (200 ppm) CO2 conditions. Cellular Si∶C ratios decrease with increasing CO2, in a trend opposite to that seen for domoic acid production. The coastal California upwelling system where this species was isolated currently exhibits rapidly increasing levels of anthropogenic acidification, as well as widespread episodic silicate limitation of diatom growth. Our results suggest that the current ecosystem and human health impacts of toxic Pseudo-nitzschia blooms could be greatly exacerbated by future ocean acidification and ‘carbon fertilization’ of the coastal ocean

Clamp loader ATPases and the evolution of DNA replication machinery

Clamp loaders are pentameric ATPases of the AAA+ family that operate to ensure processive DNA replication. They do so by loading onto DNA the ring-shaped sliding clamps that tether the polymerase to the DNA. Structural and biochemical analysis of clamp loaders has shown how, despite differences in composition across different branches of life, all clamp loaders undergo the same concerted conformational transformations, which generate a binding surface for the open clamp and an internal spiral chamber into which the DNA at the replication fork can slide, triggering ATP hydrolysis, release of the clamp loader, and closure of the clamp round the DNA. We review here the current understanding of the clamp loader mechanism and discuss the implications of the differences between clamp loaders from the different branches of life

Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles

<div><p>Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in <i>Trypanosoma brucei</i>. We describe an oxidative enzymatic pathway composed of host semicarbazide-sensitive amine oxidase and a trypanosomal aldehyde dehydrogenase TbALDH3. Two sequential reactions through this pathway serve as the key underlying mechanism for activating a series of 4-aminomethylphenoxy-benzoxaboroles as potent trypanocides; the methylamine parental compounds as pro-drugs are transformed first into intermediate aldehyde metabolites, and further into the carboxylate metabolites as effective forms. Moreover, comparative biochemical and crystallographic analyses elucidated the catalytic specificity of TbALDH3 towards the benzaldehyde benzoxaborole metabolites as xenogeneic substrates. Overall, this work proposes a novel drug activation mechanism dependent on both host and parasite metabolism of primary amine containing molecules, which contributes a new perspective to our understanding of the benzoxaborole MoA, and could be further exploited to improve the therapeutic index of antimicrobial compounds.</p></div

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

Wetlands for wastewater treatment and subsequent recycling of treated effluent : a review

Due to water scarcity challenges around the world, it is essential to think about non-conventional water resources to address the increased demand in clean freshwater. Environmental and public health problems may result from insufficient provision of sanitation and wastewater disposal facilities. Because of this, wastewater treatment and recycling methods will be vital to provide sufficient freshwater in the coming decades, since water resources are limited and more than 70% of water are consumed for irrigation purposes. Therefore, the application of treated wastewater for agricultural irrigation has much potential, especially when incorporating the reuse of nutrients like nitrogen and phosphorous, which are essential for plant production. Among the current treatment technologies applied in urban wastewater reuse for irrigation, wetlands were concluded to be the one of the most suitable ones in terms of pollutant removal and have advantages due to both low maintenance costs and required energy. Wetland behavior and efficiency concerning wastewater treatment is mainly linked to macrophyte composition, substrate, hydrology, surface loading rate, influent feeding mode, microorganism availability, and temperature. Constructed wetlands are very effective in removing organics and suspended solids, whereas the removal of nitrogen is relatively low, but could be improved by using a combination of various types of constructed wetlands meeting the irrigation reuse standards. The removal of phosphorus is usually low, unless special media with high sorption capacity are used. Pathogen removal from wetland effluent to meet irrigation reuse standards is a challenge unless supplementary lagoons or hybrid wetland systems are used

Glycosylation of plasma IgG in colorectal cancer prognosis

In this study we demonstrate the potential value of Immunoglobulin G (IgG) glycosylation as a novel prognostic biomarker of colorectal cancer (CRC). We analysed plasma IgG glycans in 1229 CRC patients and correlated with survival outcomes. We assessed the predictive value of clinical algorithms and compared this to algorithms that also included glycan predictors. Decreased galactosylation, decreased sialylation (of fucosylated IgG glycan structures) and increased bisecting GlcNAc in IgG glycan structures were strongly associated with all-cause (q < 0.01) and CRC mortality (q = 0.04 for galactosylation and sialylation). Clinical algorithms showed good prediction of all-cause and CRC mortality (Harrell’s C: 0.73, 0.77; AUC: 0.75, 0.79, IDI: 0.02, 0.04 respectively). The inclusion of IgG glycan data did not lead to any statistically significant improvements overall, but it improved the prediction over clinical models for stage 4 patients with the shortest follow-up time until death, with the median gain in the test AUC of 0.08. These glycan differences are consistent with significantly increased IgG pro-inflammatory activity being associated with poorer CRC prognosis, especially in late stage CRC. In the absence of validated biomarkers to improve upon prognostic information from existing clinicopathological factors, the potential of these novel IgG glycan biomarkers merits further investigation

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion