The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt; is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a &lt;i&gt;T. b. brucei&lt;/i&gt; isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between &lt;i&gt;T. b. gambiense&lt;/i&gt; and the reference genome. We sought to identify features that were uniquely associated with &lt;i&gt;T. b. gambiense&lt;/i&gt; and its ability to infect humans.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and findings:&lt;/b&gt; An improved high-quality draft genome sequence for the group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with &lt;i&gt;T. b. brucei&lt;/i&gt; showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972. A comparison of the variant surface glycoproteins (VSG) in &lt;i&gt;T. b. brucei&lt;/i&gt; with all &lt;i&gt;T. b. gambiense&lt;/i&gt; sequence reads showed that the essential structural repertoire of VSG domains is conserved across &lt;i&gt;T. brucei&lt;/i&gt;.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This study provides the first estimate of intraspecific genomic variation within &lt;i&gt;T. brucei&lt;/i&gt;, and so has important consequences for future population genomics studies. We have shown that the &lt;i&gt;T. b. gambiense&lt;/i&gt; genome corresponds closely with the reference, which should therefore be an effective scaffold for any &lt;i&gt;T. brucei&lt;/i&gt; genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in &lt;i&gt;T. b. brucei&lt;/i&gt;, no &lt;i&gt;T. b. gambiense&lt;/i&gt;-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.&lt;/p&gt

Communicating Uncertainty During Public Health Emergency Events:A Systematic Review

To answer the question, "What are the best ways to communicate uncertainties to public audiences, at-risk communities, and stakeholders during public health emergency events?" we conducted a systematic review of published studies, grey literature, and media reports in English and other United Nations (UN) languages: Arabic, Chinese, French, Russian, and Spanish. Almost 11,500 titles and abstracts were scanned of which 46 data-based primary studies were selected, which were classified into four methodological streams: Quantitative-comparison groups; Quantitative-descriptive survey; Qualitative; and Mixed-method and case-study. Study characteristics (study method, country, emergency type, emergency phase, at-risk population) and study findings (in narrative form) were extracted from individual studies. The findings were synthesized within methodological streams and evaluated for certainty and confidence. These within-method findings were next synthesized across methodological streams to develop an overarching synthesis of findings. The findings showed that country coverage focused on high and middle-income countries in Asia, Europe, North America, and Oceania, and the event most covered was infectious disease followed by flood and earthquake. The findings also showed that uncertainty during public health emergency events is a multi-faceted concept with multiple components (e.g., event occurrence, personal and family safety, recovery efforts). There is universal agreement, with some exceptions, that communication to the public should include explicit information about event uncertainties, and this information must be consistent and presented in an easy to understand format. Additionally, uncertainty related to events requires a distinction between uncertainty information and uncertainty experience. At-risk populations experience event uncertainty in the context of many other uncertainties they are already experiencing in their lives due to poverty. Experts, policymakers, healthcare workers, and other stakeholders experience event uncertainty and misunderstand some uncertainty information (e.g., event probabilities) similar to the public. Media professionals provide event coverage under conditions of contradictory and inconsistent event information that can heighten uncertainty experience for all

Genetic and environmental (physical fitness and sedentary activity) interaction effects on cardiometabolic risk factors in Mexican American children and adolescents

Knowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited. The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6–17 years). The environments examined were sedentary activity (SA), assessed by recalls from “yesterday” (SAy) and “usually” (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS). CMRF data included body mass index (BMI), waist circumference (WC), fat mass (FM), fasting insulin (FI), homeostasis model of assessment—insulin resistance (HOMA‐IR), high‐density lipoprotein cholesterol (HDL‐C), triglycerides (TG), systolic (SBP) and diastolic (DBP) blood pressure, and number of metabolic syndrome components (MSC). We examined potential G × E interaction in the phenotypic expression of CMRFs using variance component models and likelihood‐based statistical inference. Significant G × SA interactions were identified for six CMRFs: BMI, WC, FI, HOMA‐IR, MSC, and HDL, and significant G × HPFS interactions were observed for four CMRFs: BMI, WC, FM, and HOMA‐IR. However, after correcting for multiple hypothesis testing, only WC × SAy, FM × SAy, and FI × SAu interactions became marginally significant. After correcting for multiple testing, most of CMRFs exhibited significant G × E interactions (Reduced G × E model vs. Constrained model). These findings provide evidence that genetic factors interact with SA and PF to influence variation in CMRFs, and underscore the need for better understanding of these relationships to develop strategies and interventions to effectively reduce or prevent cardiometabolic risk in children

Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and β-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and β-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and β-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10-18 and h2 = 0.58, P = 1 × 10-7]. We found significant (P ≤ 0.05) negative phenotypic correlations between β-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and β-carotenoids rather than that of β-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease

Biomarkers in adult asthma: a systematic review of 8-isoprostane in exhaled breath condensate

Objectives: We aimed to assess the evidence for the use of 8-isoprostane in exhaled breath condensate (EBC) as a biomarker in adult asthma. Design: A systematic review and meta-analysis of EBC 8-isoprostane. Methods: We searched a number of online databases (including PubMed, Embase and Scopus) in January 2016. We included studies of adult non-smokers with EBC collection and asthma diagnosis conducted according to recognised guidelines. We aimed to pool data using random effects meta-analysis and assess heterogeneity using I2. Results: We included twenty studies, the findings from which were inconsistent. Seven studies (n = 329) reported 8-isoprostane levels in asthma to be significantly higher than that of control groups, whilst six studies (n = 403) did not. Only four studies were appropriate for inclusion in a random effects meta-analysis of mean difference. This found a statistically significant between-groups difference of 22pg/ml. Confidence in the result is limited by the small number of studies and by substantial statistical heterogeneity (I2 = 94). Conclusion: The clinical value of EBC 8-isoprostane as a quantitative assessment of oxidative stress in asthma remains unclear due to variability in results and methodological heterogeneity. It is essential to develop a robust and standardised methodology if the use of EBC 8-isoprostane in asthma is to be properly evaluated