Children’s immune system could hold the key to preventing sepsis

University of Sheffield | June 2018 | Children’s immune system could hold the key to preventing sepsis

An international team of scientists, including academics from the University of Sheffield and the public health graduate school at Harvard University,  have studied children and adults with sepsis or blood poisoning.  Their analysis and comparison of  child and adult blood profiles showed that children are naturally more resistant to lots of infectious diseases.  Importantly, this analysis enabled the research team to identify key differences in cell-pathway activity in the blood of septic adults and children.

Winston Hide, Professor of Computational Biology at Sheffield’s Institute of Translational Neuroscience (SITraN), said:

“During outbreaks like Spanish flu and Ebola we know that children survived much better than adults. By analysing the blood profiles of infected children and comparing them to adults with sepsis we were able to identify children whose natural resilience helped them to ward off infection (Source: University of Sheffield).

The study which is the first-of-its-kind has now been published in the journal Molecular Systems Biology  where it may be read or downloaded

Abstract

Attempts to develop drugs that address sepsis based on leads developed in animal models have failed. We sought to identify leads based on human data by exploiting a natural experiment: the relative resistance of children to mortality from severe infections and sepsis. Using public datasets, we identified key differences in pathway activity (Pathprint) in blood transcriptome profiles of septic adults and children. To find drugs that could promote beneficial (child) pathways or inhibit harmful (adult) ones, we built an in silico pathway drug network (PDN) using expression correlation between drug, disease, and pathway gene signatures across 58,475 microarrays. Specific pathway clusters from children or adults were assessed for correlation with drug‐based signatures. Validation by literature curation and by direct testing in an endotoxemia model of murine sepsis of the most correlated drug candidates demonstrated that the Pathprint‐PDN methodology is more effective at generating positive drug leads than gene‐level methods (e.g., CMap). Pathway‐centric Pathprint‐PDN is a powerful new way to identify drug candidates for intervention against sepsis and provides direct insight into pathways that may determine survival.

Full reference:  Joachim, R. B., Altschuler, G.M., Hutchinson, J. N., Wong,  H.R.,  Hide, W.A.,  Kobzik, L. | 2018| The relative resistance of children to sepsis mortality: from pathways to drug candidates |Molecular Systems Biology| Published online 17.05.2018|  14| e7998| DOI 10.15252/msb.20177998|

US study uses phone app to screen for autism

Science Daily | June 2018 | Mobile app for autism screening yields useful data

A new US study that uses a smartphone app to screen young children for signs of autism has found the application produces reliable data. It was also accessible for children and praised by caregivers (via Science Daily). 

During the year-long  there were over 10000 downloads of the app; parents completed more than 5000 surveys and uploaded 4441 videos. These data were collected, 88 per cent of the videos yielding useful data.  The app uses video footage of the adolescents filmed while watching films and designed to identify patterns of emotion and attention, autism risk factors, on the device.  The videos are then analysed by behavioural coding software which tracks the child’s response and quantifies their emotions and attention.

A member of the research team Geraldine Dawson, Director of the Duke Center for Autism and Brain Development, remarked “This demonstrates the feasibility of this approach.

“Many caregivers were willing to participate, the data were high quality and the video analysis algorithms produced results consistent with the scoring we produce in our autism program here at Duke.”

The full news article is available from Science Daily 
The study has now been published in the open access journal npj Digital Medicine. It can be accessed through Nature 

Full reference:

Egger, H. L. et al .| 2018| Automatic emotion and attention analysis of young children at home: a ResearchKit autism feasibility study |npj Digital Medicine| Vol. 1 |DOI: 10.1038/s41746-018-0024-6

How well do we recognise and detect facial expressions?

University of East Anglia | Study explores how emotions in facial expressions are understood | June 2018

Researchers at the University of East Anglia’s School of Psychology examined  the recognition and detection of six basic emotions, happiness, sadness, fear, disgust, anger and surprise,  changes when viewed centrally and up to 30 degrees in peripheral vision.
Participants (n=14)  were shown facial images expressing the six basic emotions and one neutral expression. For the recognition task, they had to decide which emotion was displayed, with the faces randomly presented centrally and to the left and right by 15 or 30 degrees. In the detection task, the participants had to decide whether the face displayed an emotion.

The team  found that fear was a better detected than recognised emotion, and that happiness and surprise are both recognised and detected well in peripheral vision, whereas others such as anger and sadness are not. Lead author Dr Fraser Smith said: “A key finding of our study is that while fear is indeed not a well-recognised emotion in peripheral or central vision, unlike happiness or surprise for instance, it is a very well detected emotion even in our visual periphery. This suggests that these special brain mechanisms may be more concerned with emotion detection than recognition per se (UEA).”


The full, unabridged press release from University of East Anglia can be read at their website 

Abstract  

Facial expressions of emotion are signals of high biological value. Whilst recognition of facial expressions has been much studied in central vision, the ability to perceive these signals in peripheral vision has only seen limited research to date, despite the potential adaptive advantages of such perception. In the present experiment, we investigate facial expression recognition and detection performance for each of the basic emotions (plus neutral) at up to 30 degrees of eccentricity. We demonstrate, as expected, a decrease in recognition and detection performance with increasing eccentricity, with happiness and surprised being the best recognized expressions in peripheral vision. In detection however, while happiness and surprised are still well detected, fear is also a well detected expression. We show that fear is a better detected than recognized expression. Our results demonstrate that task constraints shape the perception of expression in peripheral vision and provide novel evidence that detection and recognition rely on partially separate underlying mechanisms, with the latter more dependent on the higher spatial frequency content of the face stimulus.

Full reference: Smith, F.W., Rossit, S. |2018 | Identifying and detecting facial expressions of emotion in peripheral vision|PLoS ONE| 13| Vol. 5|  e0197160| https://doi.org/10.1371/journal.pone.0197160

A paper based on the study has now been published in PLOS One, the article can be read in full here 

Hotter bodies fight infections and tumours better – researchers show how

Science Daily | May 2018 | Hotter bodies fight infections and tumors better — researchers show how

Researchers from the Universities  of Manchester and Warwick have shown how individuals with higher body temperatures are better equipped to fight infections and tumours.  A Multidisciplinary team were involved in the study, with mathematicians from Warwick calculating how temperature increases make the cycle accelerate.  The researchers have demonstrated that small rises in temperature (such as during a fever) speed up the speed of a cellular ‘clock’ that controls the response to infections — and this new understanding could lead to more effective and fast-working drugs which target a key protein involved in this process (Science Daily).

Higher body temperatures speed our bodies’ responses to infections, wounds and tumours – researchers at the Universities of Warwick and Manchester prove that a slight increase in body temperature and inflammation – such as a fever – speeds up cellular ‘clock’ in which proteins switch genes on and off to respond to infection.

• Slight rise in temperature and inflammation – such as a fever – speeds up cellular ‘clock’ in which proteins switch genes on and off to respond to infection
• New understanding could lead to more effective and fast-working drugs which target a key inflammation protein found to be critical for the temperature response
• Interdisciplinary team of Warwick mathematicians and Manchester biologists used modelling and lab experiments to jointly make discovery (University of Warwick)

The full news item from Science Daily can be read here 

University of Warwick Hotter bodies fight infections and tumours better – researchers show how

The research is published in the Proceedings of the National Academy of Sciences

The full article is available to read here

Full reference:

Harper, C. V. , et al | Temperature regulates NF-κB dynamics and function through timing of A20 transcription| Proceedings of the National Academy of Sciences | 2018; 201803609|  DOI: 10.1073/pnas.1803609115

 

Does healthy obesity exist?

BBC News | May 2018 | Study casts doubt on ‘healthy obesity’

A new longitudinal study that looked at women’s health in the US over a period of nearly 30 years reports that females who were overweight were more likely to have a stroke or heart attack, even if they had normal blood pressure and cholesterol and no diabetes. The US study followed over 90000 women for around 30 years. 

The study aimed to examine the association between metabolic health and its change over time and cardiovascular disease risk across BMI categories. The scientists found that most of the metabolically healthy women developed either high blood pressure, excess cholesterol or diabetes as they got older, even if they were normal weight. The risk was even higher for women who were overweight and obese.

Prof Matthias Schulze, from the German Institute of Human Nutrition Potsdam-Rehbruecke, who led the study said: “Our large cohort study confirms that metabolically healthy obesity is not a harmless condition, and even women who remain free of metabolic diseases for decades face an increased risk of cardiovascular events.” (via BBC News)

Summary

Background

Cardiovascular disease risk among individuals across different categories of BMI might depend on their metabolic health. It remains unclear to what extent metabolic health status changes over time and whether this affects cardiovascular disease risk. In this study, we aimed to examine the association between metabolic health and its change over time and cardiovascular disease risk across BMI categories.

Methods

Between June and December, 1976, 121 701 female nurses were recruited to the Nurses’ Health Study (NHS) of whom 103 298 returned a questionnaire in 1980 used as baseline in this study. After excluding women with a history of cardiovascular disease or cancer, with missing body weight and with underweight. 90 257 women were followed-up from 1980 to 2010 for incident cardiovascular disease. Participants were cross-classified by BMI categories, metabolic health (defined by absence of diabetes, hypertension and hypercholesterolaemia), and change in metabolic health status during follow-up.

Findings

During 2 127  391 person-years of follow-up with a median follow-up of 24 years, we documented 6306 cases of cardiovascular disease including 3304 myocardial infarction cases and 3080 strokes. Cardiovascular disease risk of women with metabolically healthy obesity was increased compared with women with metabolically healthy normal weight (HR 1·39, 95% CI 1·15–1·68), but risk was considerably higher in women with metabolically unhealthy normal weight (2·43, 2·19–2·68), overweight (2·61, 2·36–2·89) and obesity (3·15, 2·83–3·50). The majority of metabolically healthy women converted to unhealthy phenotypes (2555 [84%] of 3027 women with obesity, 22 215 [68%] of 32 882 women with normal-weight after 20 years). Women who maintained metabolically healthy obesity during follow-up were still at a higher cardiovascular disease risk compared with women with stable healthy normal weight (HR 1·57, 1·03–2·38), yet this risk was lower than for initially metabolically healthy women who converted to an unhealthy phenotype (normal-weight 1·90, 1·66–2·17 vs obesity 2·74, 2·30–3·27). Particularly incident diabetes and hypertension increased the risk among women with initial metabolic health.

Interpretation

Even when metabolic health is maintained during long periods of time, obesity remains a risk factor for cardiovascular disease. However, risks are highest for metabolically unhealthy women across all BMI categories. A large proportion of metabolically healthy women converted to an unhealthy phenotype over time across all BMI categories, which is associated with an increased cardiovascular disease risk.

Full reference:

Eckel, Nathalie et al.| Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses’ Health Study): 30 year follow-up from a prospective cohort study | The Lancet Diabetes & Endocrinology| Vol. 0 | 0 | DOI: https://doi.org/10.1016/S2213-8587(18)30137-2

The full article is available to Rotherham NHS staff to request here 

In the media: Study casts doubt on healthy obesity 

Successful weight loss maintainers have different behavioural and physiological responses to food, says study

University of Birmingham | May 2018 |Successful weight loss maintainers have different behavioural and physiological responses to food

Researchers at Birmingham University have discovered that leaner individuals have different responses to food compared to those with or those who have had obesity. The team compared the saliva production and heart rate (response) to pizza (stimuli) across the sample and found that obese individuals responded to the food, as their heart rate rose and saliva production increased. By contrast, the lean group who did not have a history of obesity were unresponsive.

In addition to the stimulus-response test, participants also completed cognitive tasks to gauge their motivation to gain, and avoid losing food and monetary rewards in a computerised task.  The sample had to decide whether a neutral symbol was associated with winning food, losing food, winning money or losing money. The ability of the lean group and the group with obesity to learn the task was affected by losing and winning food equally but the weight loss maintainers performance was less affected by food wins and more affected by food losses. Importantly, the three groups did not differ in their ability to learn the task in general as there was no difference in learning the task using monetary reward or losses (via University of Birmingham).

The full, undabridged details are available from the University of Birmingham

Taking supplements adds little benefit to health, finds Canadian study

May 2018|Supplemental Vitamins and Minerals for CVD Prevention and Treatment

A new systematic review has analysed the benefits of taking vitamins, using the findings of randomized controlled trials from earlier meta analyses on cardiovascular disease outcomes and all-cause mortality.  The researchers found that taking the most popular vitamin and mineral supplements afforded no consistent health benefit via (Science Daily). 

Abstract

The authors identified individual randomized controlled trials from previous meta-analyses and additional searches, and then performed meta-analyses on cardiovascular disease outcomes and all-cause mortality. The authors assessed publications from 2012, both before and including the U.S. Preventive Service Task Force review. Their systematic reviews and meta-analyses showed generally moderate- or low-quality evidence for preventive benefits (folic acid for total cardiovascular disease, folic acid and B-vitamins for stroke), no effect (multivitamins, vitamins C, D, β-carotene, calcium, and selenium), or increased risk (antioxidant mixtures and niacin [with a statin] for all-cause mortality). Conclusive evidence for the benefit of any supplement across all dietary backgrounds (including deficiency and sufficiency) was not demonstrated; therefore, any benefits seen must be balanced against possible risks.

Full reference:

Jenkins,David J.A. et al | Supplemental Vitamins and Minerals for CVD Prevention and Treatment |Journal of the American College of Cardiology | Vol. 71| 22 | 5 June 2018 |P. 2570–2584 |https://doi.org/10.1016/j.jacc.2018.04.020

The full article is available to download from Science Direct

 

Science Daily Most popular vitamin and mineral supplements provide no health benefit, study finds