Growth to early adulthood following extremely preterm birth: the EPICure study.

OBJECTIVE: To investigate growth trajectories from age 2.5 to 19 years in individuals born before 26 weeks of gestation (extremely preterm; EP) compared with term-born controls. METHODS: Multilevel modelling of growth data from the EPICure study, a prospective 1995 birth cohort of 315 EP participants born in the UK and Ireland and 160 term-born controls recruited at school age. Height, weight, head circumference and body mass index (BMI) z-scores were derived from UK standards at ages 2.5, 6, 11 and 19 years. RESULTS: 129 (42%) EP children were assessed at 19 years. EP individuals were on average 4.0 cm shorter and 6.8 kg lighter with a 1.5 cm smaller head circumference relative to controls at 19 years. Relative to controls, EP participants grew faster in weight by 0.06 SD per year (95% CI 0.05 to 0.07), in head circumference by 0.04 SD (95% CI 0.03 to 0.05), but with no catch-up in height. For the EP group, because of weight catch-up between 6 and 19 years, BMI was significantly elevated at 19 years to +0.32 SD; 23.4% had BMI >25 kg/m2 and 6.3% >30 kg/m2 but these proportions were similar to those in control subjects. EP and control participants showed similar pubertal development in early adolescence, which was not associated with height at 19 years in either study group. Growth through childhood was related to birth characteristics and to neonatal feeding practices. CONCLUSIONS: EP participants remained shorter and lighter and had smaller head circumferences than reference data or controls in adulthood but had elevated BMI

Developing a Molecular Roadmap of Drug-Food Interactions

Recent research has demonstrated that consumption of food -especially fruits and vegetables- can alter the effects of drugs by interfering either with their pharmacokinetic or pharmacodynamic processes. Despite the recognition of such drug-food associations as an important element for successful therapeutic interventions, a systematic approach for identifying, predicting and preventing potential interactions between food and marketed or novel drugs is not yet available. The overall objective of this work was to sketch a comprehensive picture of the interference of ∼ 4,000 dietary components present in ∼1800 plant-based foods with the pharmacokinetics and pharmacodynamics processes of medicine, with the purpose of elucidating the molecular mechanisms involved. By employing a systems chemical biology approach that integrates data from the scientific literature and online databases, we gained a global view of the associations between diet and dietary molecules with drug targets, metabolic enzymes, drug transporters and carriers currently deposited in DrugBank. Moreover, we identified disease areas and drug targets that are most prone to the negative effects of drug-food interactions, showcasing a platform for making recommendations in relation to foods that should be avoided under certain medications. Lastly, by investigating the correlation of gene expression signatures of foods and drugs we were able to generate a completely novel drug-diet interactome map.published_or_final_versio

Accelarated immune ageing is associated with COVID-19 disease severity

BackgroundThe striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls.ResultsWe performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p &lt; 0.0001); increased frequency of EMRA CD4 (p &lt; 0.003) and CD8 T cells (p &lt; 0.001); a higher frequency (p &lt; 0.0001) and absolute numbers (p &lt; 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p &lt; 0.003) and absolute numbers (p &lt; 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p &lt; 0.0001); higher frequency of memory B cells (p &lt; 0.001) and increased frequency (p &lt; 0.0001) and numbers (p &lt; 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p &lt; 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( = 0.174, p = 0.043), with a major influence being disease severity ( = 0.188, p = 0.01).ConclusionsOur analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease.<br/

Brazilin Isolated from Caesalpinia sappan Suppresses Nuclear Envelope Reassembly by Inhibiting Barrier-to-Autointegration Factor Phosphorylation

To date, many anticancer drugs have been developed by directly or indirectly targeting microtubules, which are involved in cell division. Although this approach has yielded many anticancer drugs, these drugs produce undesirable side effects. An alternative strategy is needed, and targeting mitotic exit may be one alternative approach. Localization of phosphorylated barrier-to-autointegration factor (BAF) to the chromosomal core region is essential for nuclear envelope compartment relocalization. In this study, we isolated brazilin from Caesalpinia sappan Leguminosae and demonstrated that it inhibited BAF phosphorylation in vitro and in vivo. Moreover, we demonstrated direct binding between brazilin and BAF. The inhibition of BAF phosphorylation induced abnormal nuclear envelope reassembly and cell death, indicating that perturbation of nuclear envelope reassembly could be a novel approach to anticancer therapy. We propose that brazilin isolated from C. sappan may be a new anticancer drug candidate that induces cell death by inhibiting vaccinia-related kinase 1-mediated BAF phosphorylation.X1153Ysciescopu

A demonstration of 'broken' visual space

It has long been assumed that there is a distorted mapping between real and ‘perceived’ space, based on demonstrations of systematic errors in judgements of slant, curvature, direction and separation. Here, we have applied a direct test to the notion of a coherent visual space. In an immersive virtual environment, participants judged the relative distance of two squares displayed in separate intervals. On some trials, the virtual scene expanded by a factor of four between intervals although, in line with recent results, participants did not report any noticeable change in the scene. We found that there was no consistent depth ordering of objects that can explain the distance matches participants made in this environment (e.g. A > B > D yet also A < C < D) and hence no single one-to-one mapping between participants’ perceived space and any real 3D environment. Instead, factors that affect pairwise comparisons of distances dictate participants’ performance. These data contradict, more directly than previous experiments, the idea that the visual system builds and uses a coherent 3D internal representation of a scene

A 3D Human Posture Approach for Activity Recognition Based on Depth Camera

Human activity recognition plays an important role in the context of Ambient Assisted Living (AAL), providing useful tools to improve people quality of life. This work presents an activity recognition algorithm based on the extraction of skeleton joints from a depth camera. The system describes an activity using a set of few and basic postures extracted by means of the X-means clustering algorithm. A multi-class Support Vector Machine, trained with the Sequential Minimal Optimization is employed to perform the classification. The system is evaluated on two public datasets for activity recognition which have different skeleton models, the CAD-60 with 15 joints and the TST with 25 joints. The proposed approach achieves precision/recall performances of 99.8 % on CAD-60 and 97.2 %/91.7 % on TST. The results are promising for an applied use in the context of AAL

Adsorption and reduction of palladium (Pd2+) by Bacillus licheniformis R08

Preliminary study on the mechanism of Pd2+ biosorption by resting cells of Bacillus licheniformis R08 biomass has been carried out by means of chemical kinetics and AAS, TEM, XRD and FTIR methods. The results showed that at 30degreesC and PH 3.5, when dry R08 biomass powder (800 mg/L) was mixed with Pd2+ (100 mg/L) for 45 min, the rate constant k of biosorption of Pd2+ attained a maximum of 5.97 x 10(-2) min(-1) and the half life period of the reaction reached 12 min. The part of Pd2+ adsorbed by R08 biomass was reduced to elemental, cell-bound Pd-0 at the same condition. The cell wall of R08 biomass was the primary location for accumulating Pd2+, and aldoses, i. e. hydrolysate of a part of polysaccharides on the peptidoglycan layer in the acidic medium, serving as the electron donor, in situ reduced the Pd2+ to Pd-0

Methodological considerations in the analysis of fecal glucocorticoid metabolites in tufted capuchins (Cebus apella)

Analysis of fecal glucocorticoid (GC) metabolites has recently become the standard method to monitor adrenocortical activity in primates noninvasively. However, given variation in the production, metabolism, and excretion of GCs across species and even between sexes, there are no standard methods that are universally applicable. In particular, it is important to validate assays intended to measure GC production, test extraction and storage procedures, and consider the time course of GC metabolite excretion relative to the production and circulation of the native hormones. This study examines these four methodological aspects of fecal GC metabolite analysis in tufted capuchins (Cebus apella). Specifically, we conducted an adrenocorticotrophic hormone (ACTH) challenge on one male and one female capuchin to test the validity of four GC enzyme immunoassays (EIAs) and document the time course characterizing GC me- tabolite excretion in this species. In addition, we compare a common field-friendly technique for extracting fecal GC metabolites to an established laboratory extraction methodology and test for effects of storing “field extracts” for up to 1 yr. Results suggest that a corticosterone EIA is most sensitive to changes in GC production, provides reliable measures when extracted according to the field method, and measures GC metabolites which remain highly stable after even 12 mo of storage. Further, the time course of GC metabolite excretion is shorter than that described yet for any primate taxa. These results provide guidelines for studies of GCs in tufted capuchins, and underscore the importance of validating methods for fecal hormone analysis for each species of interest