Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults.

A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development

Climate impacts on human livelihoods: Where uncertainty matters in projections of water availability

Climate change will have adverse impacts on many different sectors of society, with manifold consequences for human livelihoods and well-being. However, a systematic method to quantify human well-being and livelihoods across sectors is so far unavailable, making it difficult to determine the extent of such impacts. Climate impact analyses are often limited to individual sectors (e.g. food or water) and employ sector-specific target measures, while systematic linkages to general livelihood conditions remain unexplored. Further, recent multi-model assessments have shown that uncertainties in projections of climate impacts deriving from climate and impact models, as well as greenhouse gas scenarios, are substantial, posing an additional challenge in linking climate impacts with livelihood conditions. This article first presents a methodology to consistently measure what is referred to here as AHEAD (Adequate Human livelihood conditions for wEll-being And Development). Based on a trans-disciplinary sample of concepts addressing human well-being and livelihoods, the approach measures the adequacy of conditions of 16 elements. We implement the method at global scale, using results from the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) to show how changes in water availability affect the fulfilment of AHEAD at national resolution. In addition, AHEAD allows for the uncertainty of climate and impact model projections to be identified and differentiated. We show how the approach can help to put the substantial inter-model spread into the context of country-specific livelihood conditions by differentiating where the uncertainty about water scarcity is relevant with regard to livelihood conditions – and where it is not. The results indicate that livelihood conditions are compromised by water scarcity in 34 countries. However, more often, AHEAD fulfilment is limited through other elements. The analysis shows that the water-specific uncertainty ranges of the model output are outside relevant thresholds for AHEAD for 65 out of 111 countries, and therefore do not contribute to the overall uncertainty about climate change impacts on livelihoods. In 46 of the countries in the analysis, water-specific uncertainty is relevant to AHEAD. The AHEAD method presented here, together with first results, forms an important step towards making scientific results more applicable for policy decisions

Sarcoidosis of the hypothalamus and pituitary stalk

We report a rare case of sarcoidosis of the hypothalamic and suprasellar region, with clinical course and the magnetic resonance imaging follow-up

Interactions between dietary patterns and genetic factors in relation to incident dementia among 70-year-olds

PURPOSE: To investigate potential interactions between dietary patterns and genetic factors modulating risk for Alzheimer's disease (AD) in relation to incident dementia. METHODS: Data were derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden, including 602 dementia-free 70-year-olds (examined 1992-93, or 2000-02; 64% women) followed for incident dementia until 2016. Two factors from a reduced rank regression analysis were translated into dietary patterns, one healthy (e.g., vegetables, fruit, and fish) and one western (e.g., red meat, refined cereals, and full-fat dairy products). Genetic risk was determined by APOE ε4 status and non-APOE AD-polygenic risk scores (AD-PRSs). Gene-diet interactions in relation to incident dementia were analysed with Cox regression models. The interaction p value threshold was < 0.1. RESULTS: There were interactions between the dietary patterns and APOE ε4 status in relation to incident dementia (interaction p value threshold of < 0.1), while no evidence of interactions were found between the dietary patterns and the AD-PRSs. Those with higher adherence to a healthy dietary pattern had a reduced risk of dementia among ε4 non-carriers (HR: 0.77; 95% CI: 0.61; 0.98), but not among ε4 carriers (HR: 0.86; CI: 0.63; 1.18). Those with a higher adherence to the western dietary pattern had an increased risk of dementia among ε4 carriers (HR: 1.37; 95% CI: 1.05; 1.78), while no association was observed among ε4 non-carriers (HR: 0.99; CI: 0.81; 1.21). CONCLUSIONS: The results of this study suggest that there is an interplay between dietary patterns and APOE ε4 status in relation to incident dementia

High-intensity activity is more strongly associated with metabolic health in children compared to sedentary time: a cross-sectional study of the I.Family cohort

Background: Physical activity (PA) during childhood is important for preventing future metabolic syndrome (MetS). To examine the relationship between PA and MetS in more detail, accurate measures of PA are needed. Previous studies have only utilized a small part of the information available from accelerometer measured PA. This study investigated the association between measured PA and MetS in children with a new method for data processing and analyses that enable more detailed interpretation of PA intensity level. Methods: The association between PA pattern and risk factors related to MetS was investigated in a cross- sectional sample of children (n = 2592, mean age 10.9 years, 49.4% male) participating in the European multicenter I. Family study. The risk factors examined include body mass index, blood pressure, high-density lipoprotein cholesterol, insulin resistance and a combined risk factor score (MetS score). PA was measured by triaxial accelerometers and raw data was processed using the 10 Hz frequency extended method (FEM). The PA output was divided into an intensity spectrum and the association with MetS risk factors was analyzed by partial least squares regression. Results: PA patterns differed between the European countries investigated, with Swedish children being most active and Italian children least active. Moderate intensity physical activity was associated with lower insulin resistance (R2 = 2.8%), while vigorous intensity physical activity was associated with lower body mass index (R2 = 3.6%), MetS score (R2 = 3.1%) and higher high-density lipoprotein cholesterol (R2 = 2.3%). PA of all intensities was associated with lower systolic- and diastolic blood pressure, although the associations were weaker than for the other risk factors (R2 = 1.5% and R2 = 1.4%). However, the multivariate analysis implies that the entire PA pattern must be considered. The main difference in PA was observed between normal weight and overweight children. Conclusions: The present study suggests a greater importance of more PA corresponding to an intensity of at least brisk walking with inclusion of high-intense exercise, rather than a limited time spent sedentary, in the association to metabolic health in children. The methods of data processing and statistical analysis enabled accurate analysis and interpretation of the health benefits of high intensity PA that have not been shown previously. © 2021, The Author(s)

Membranes and synaptosomes used to investigate synaptic GABAergic currents in epileptic patients

Among the most prevalent neurological disorders, epilepsy affects about 1% of the population worldwide. We previously found, using human epileptic tissues, that GABAergic neurotransmission impairment is a key mechanism that drives the pathological phenomena that ultimately lead to generation and recurrence of seizures. Using both a "microtransplantation technique" and synaptosomes preparations from drug-resistant temporal lobe epilepsies (TLEs), we used the technique of two-electrode voltage clamp to record GABA-evoked currents, focusing selectively on the synaptic "fast inhibition" mediated by low-affinity GABA(A) receptors. Here, we report that the use-dependent GABA current desensitization (i.e., GABA rundown, which is evoked by applying to the cells consecutive pulses of GABA, at high concentration), which is a distinguishing mark of TLE, is mainly dependent on a dysfunction that affects synaptic GABA(A) receptors. In addition, using the same approaches, we recorded a depolarized GABA reversal potential in synaptosomes samples from the human epileptic subicula of TLE patients. These results, which confirm previous experiments using total membranes, suggest an altered chloride homeostasis in the synaptic area. Finally, the lack of a Zn2+ block of GABA-evoked currents using the synaptosomes supports the enrichment of "synaptic fast inhibitory" GABA(A) receptors in this preparation. Altogether, our findings suggest a pathophysiological role of low-affinity GABA(A) receptors at the synapse, especially during the fast and repetitive GABA release underlying recurrent seizures

Overcoming gender inequality for climate resilient development

Gender inequalities are reflected in differential vulnerability, and exposure to the hazards posed by climate change and addressing them is key to increase the adaptive capacities of societies. We provide trajectories of the Gender Inequality Index (GII) alongside the Shared-Socioeconomic Pathways (SSPs), a scenario framework widely used in climate science. Here we find that rapid improvements in gender inequality are possible under a sustainable development scenario already in the near-term. The share of girls growing up in countries with the highest gender inequality could be reduced to about 24% in 2030 compared to about 70% today. Largely overcoming gender inequality as assessed in the GII would be within reach by mid-century. Under less optimistic scenarios, gender inequality may persist throughout the 21st century. Our results highlight the importance of incorporating gender in scenarios assessing future climate impacts and underscore the relevance of addressing gender inequalities in policies aiming to foster climate resilient development

Variations in the Prevalence of Obesity Among European Countries, and a Consideration of Possible Causes

Over the last 10 years the prevalence of obesity across the European continent has in general been rising. With the exception of a few countries where a levelling-off can be perceived, albeit at a high level, this upward trend seems likely to continue. However, considerable country to country variation is noticeable, with the proportion of people with obesity varying by 10% or more. This variation is intriguing and suggests the existence of different profiles of risk or protection factors operating in different countries. The identification of such protection factors could indicate suitable targets for interventions to help manage the obesity epidemic in Europe. This report is the output of a 2-day workshop on the ‘Diversity of Obesity in Europe'. The workshop included 14 delegates from 12 different European countries. This report contains the contributions and discussions of the materials and viewpoints provided by these 14 experts; it is not the output of a single mind. However, such is the nature of scientific analysis regarding obesity that it is possible that a different set of 14 experts may have come to a different set of conclusions. Therefore the report should not be seen as a definitive statement of a stable situation. Rather it is a focus for discussion and comment, and a vehicle to drive forward further understanding and management of obesity in Europe