Anxiety: An overlooked confounder in the characterisation of chronic stress-related conditions?

Although anxiety disorders are among the most prevalent of psychiatric disorders, childhood trauma-related studies seldom consider anxiety proneness as distinct aetiological contributor. We aimed to distinguish between trauma- and anxiety-associated physiological profiles. South African adolescent volunteers were categorised for trauma exposure (CTQ, mean score 39±11) and anxiety proneness (AP)(CASI, mean score 37±7, STAI-T, mean score 41±8). Circulating hormone and leukocyte glucocorticoid receptor levels, as well as leukocyte functional capacity, were assessed. AP was associated with lower DHEAs (P<0.05) and higher leukocyte GR expression (P<0.05). DHEAs was also negatively correlated with anxiety sensitivity (CASI, P<0.05). In conclusion, AP may have more predictive power than trauma in terms of health profile. Increased glucocorticoid sensitivity previously reported after trauma, may be a unique function of anxiety and not trauma exposure per se. DHEAs concentration was identified as potentially useful marker for monitoring progressive changes in HPA-axis sensitivity and correlated with psychological measures of anxiety

Platelet activity and hypercoagulation in type 2 diabetes

CITATION: Pretorius, L., et al. 2018. Platelet activity and hypercoagulation in type 2 diabetes. Cardiovascular Diabetology, 17:141, doi:10.1186/s12933-018-0783-z.The original publication is available at https://cardiab.biomedcentral.comBackground: A strong correlation exists between type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), with CVD and the presence of atherosclerosis being the prevailing cause of morbidity and mortality in diabetic populations. T2DM is accompanied by various coagulopathies, including anomalous clot formation or amyloid fibrin(ogen), the presence of dysregulated inflammatory molecules. Platelets are intimately involved in thrombus formation and particularly vulnerable to inflammatory cytokines. Methods: The aim of this current study was therefore to assess whole blood (hyper)coagulability, platelet ultrastructure and receptor expression, as well as the levels of IL-1β, IL-6, IL-8 and sP-selectin in healthy and diabetic individuals. Platelet morphology was assessed through scanning electron microscopy (SEM), while assessment of GPIIb/IIIa receptor expression was performed with confocal microscopy and flow cytometry with the addition of FITC-PAC-1 and CD41-PE antibodies. IL-1β, IL-6 and IL-8 and sP-selectin levels were assessed using a multiplex assay. Results: In T2DM there is significant upregulation of circulating inflammatory markers, hypercoagulation and platelet activation, with increased GPIIb/IIIa receptor expression, as seen with flow cytometry and confocal microscopy. Analyses showed that these receptors were additionally shed onto microparticles, which was confirmed with SEM. Conclusions: Cumulatively, this provides mechanistic evidence that pathological states of platelets together with amyloid fibrin(ogen) in T2DM, might underpin an increased risk for cardiovascular events.https://cardiab.biomedcentral.com/articles/10.1186/s12933-018-0783-zPublisher's versio

Antibody responses to vaccination among South African HIV-exposed and unexposed uninfected infants during the first 2 years of life

CITATION: Reikie, B. A. et al. 2013. Antibody responses to vaccination among South African HIV-exposed and unexposed uninfected infants during the first 2 years of life. Clinical and Vaccine Immunology, 20(1):33–38, doi: 10.1128/CVI.00557-12.The original publication is available at http://cvi.asm.orgHIV-exposed but uninfected (HEU) infants born to HIV-infected mothers from areas in the world with a high burden of infectious disease suffer higher infectious morbidity and mortality than their HIV unexposed uninfected (HUU) peers. Vaccination provides protection from infection. The possibility exists that altered response to vaccination contributes to the higher rate of infection in HEU than in HUU infants. While short-term, cross-sectional studies support this notion, it is unclear whether or not HEU infants develop long-term protective immune responses following theWHOextended program on immunization (EPI). Vaccine-specific antibody responses were compared between HEU and HUU infants from 2 weeks until 2 years of age in a longitudinal South African cohort. Total IgG and antibodies specific for Bordetella pertussis, Haemophilus influenzae type b (Hib), tetanus toxoid, hepatitis B virus (HepB), and measles virus were measured at multiple time points throughout the first 2 years of life. Prevaccine antibodies (maternal antibodies passively acquired) specific for tetanus were lower in HEU than in HUU infants, while prevaccine antibodies to HepB were higher in HEU than in HUU infants. Both groups responded similarly to tetanus, Hib, and HepB vaccination. HEU demonstrated stronger pertussis vaccine responses, developing protective titers 1 year earlier than HUU patients, and maintained higher anti-tetanus titers at 24 months of age. Vaccine-induced antibodies to measles virus were similar in both groups at all time points. Our results suggest that the current EPI vaccination program as practiced in South Africa leads to the development of vaccine-specific antibody responses that are equivalent in HEU and HUU infants. However, our data also suggest that a large fraction of both HEU and HUU South African infants have antibody titers for several infectious threats that remain below the level of protection for much of their first 2 years of life.http://cvi.asm.org/content/20/1/33.abstract?sid=24f0e5f0-2fcf-4d33-a180-dc6acb659f99Publisher's versio

[en] SPORTS MARKETING: THE USE OF SPORTS AS AN ALTERNATIVE MEDIA FROM THE BEVERAGE INDUSTRY OF THE USA

The first year of life represents a time of marked susceptibility to infections; this is particularly true for regions in sub-Saharan Africa. As innate immunity directs the adaptive immune response, the observed increased risk for infection as well as a suboptimal response to vaccination in early life may be due to less effective innate immune function. In this study, we followed a longitudinal cohort of infants born and raised in South Africa over the first year of life, employing the most comprehensive analysis of innate immune response to stimulation published to date. Our findings reveal rapid changes in innate immune development over the first year of life. This is the first report depicting dramatic differences in innate immune ontogeny between different populations in the world, with important implications for global vaccination strategies

High level of cDC cytokine response to PAMPs decreased over the first year of life for all stimuli except LPS.

<p>Whole blood samples from ∼30 neonate-infant subjects were followed longitudinally from 2 weeks (2 wk; n = 28), 6 weeks (6 wk; n = 26), 6 months (6 mo; n = 23) and 12 months (12 mo; n = 20) of life, and 10 adults (Ad) were stimulated with the indicated TLR ligands for 6 h, and intracellular cytokine levels were measured by flow cytometry for TNF-α, IL-6 and IL-12/23p40 gated on cDC. For each cell type, the total percentage of cytokine-producing cells is represented by the overall height of bar graphs; color-coded segments constituting the bar allow differentiation of cells producing various cytokine combinations. Unstimulated samples displayed cytokine production at near 0% and were subtracted from the stimulated samples. (<b>A</b>) Overall stacked bar graph height; statistically significant differences in percent responders are indicated by p-value *<0.05, **<0.01, ***<0.001. Cytokine profile – color combinations indicated in inset in identical order as in bar graphs from top to bottom. (<b>B</b>) Line graphs indicate polyfunctionality degree (PFD) for cDC, summarizing the percentage of cells producing 1 (PFD1), 2 (PFD2), or 3 (PFD3) cytokines for each age group.</p

Decline in secretion of cytokines promoting either Th1 or Th17 development in South African infants' whole blood within the first year of life.

<p>Whole blood from subjects enrolled in our longitudinal cohort and sampled at 2 weeks (2 wk; n = 28), 6 weeks (6 wk; n = 26), 6 months (6 mo; n = 23) and 12 months (12 mo; n = 20) of life, and 10 adults (Ad) was stimulated with the indicated TLR ligands and cytokine secretion into the culture supernatant was measured by Luminex xMAP cytokine assay or by ELISA (IL-23 only). Mean cytokine concentration (pg/ml) is indicated on the y-axis; error bars indicate SEM. Unstimulated samples displayed cytokine production at very low levels and were subtracted from the stimulated samples. Cytokines were grouped based on their major known functions, i.e. those promoting either Th1 (IFN-α, IFN-γ and IL-12p70 as well as the IFN-γ-induced-protein IP-10), or Th17 development of CD4 T cells (IL-12p40, IL-23, and IL-6).</p

Decline of secretion of pro- as well as anti-inflammatory cytokines following PRR stimulation in South African infants' whole blood within the first year of life.

<p>The same samples analyzed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044763#pone-0044763-g001" target="_blank">Figure 1</a> were also analyzed for production of cytokines considered to be general pro-inflammatory or chemoattractant (TNF-α, IL1-β, IL-8, MCP-1, MIP-1α, MIP-1β) vs. anti-inflammatory (IL-10).</p

Mean fluorescence intensities (MFI) of monocyte or cDC cytokine production drastically fell over the first year of life for all cytokines except TNF-α and IL-6 in response to LPS stimulation.

<p>Whole blood samples from ∼30 neonate-infant subjects were followed longitudinally from 2 weeks (2 wk; n = 28), 6 weeks (6 wk; n = 26), 6 months (6 mo; n = 23) and 12 months (12 mo; n = 20) of life, and 10 adults (Ad) were stimulated with the indicated TLR ligands for 6 h, and intracellular cytokine levels were measured by flow cytometry for TNF-α, IL-6 and IL-12/23p40 gated on monocytes (blue line) and cDC (red line). The MFI values from all samples of each age group were averaged after first excluding the samples that had cytokine-positive percentage <4% of the APC subtype. Means for each population were derived from the FlowJo software; error bars indicate SEM.</p

The fraction of pDC producing cytokines in response to PAMPs remained high throughout the first year of life, but the MFI for INF-α decreased.

<p>Whole blood samples from ∼30 neonate-infant subjects were followed longitudinally from 2 weeks (2 wk; n = 28), 6 weeks (6 wk; n = 26), 6 months (6 mo; n = 23) and 12 months (12 mo; n = 20) of life, and 10 adults (Ad) were stimulated with the TLR7/8 agonist R848 for 6 h, and intracellular cytokine levels were measured by flow cytometry for TNF-α, IL-6 and INF-α gated on pDC. Unstimulated samples displayed cytokine production at near 0% and were subtracted from the stimulated samples. (<b>A</b>) Overall stacked bar graph height indicates the total percentage of pDC producing one of the measured cytokines. Overall responses were broken down by cytokine expression profile and were coded by color (cytokine profile – color combinations indicated in inset in identical order as in bar graphs from top to bottom). (<b>B</b>) Line graphs indicate polyfunctionality degree (PFD) for cDC, summarizing the percentage of cells producing 1 (PFD1), 2 (PFD2), or 3 (PFD3) cytokines for each age group. (<b>C</b>) Line graphs indicate the mean fluorescent intensity (MFI) in the respective sample for INFα and TNF-α. The MFI values from all samples were averaged after first excluding the samples that have cytokine-positive percentage <4%. Means for each population are derived from the FlowJo software; error bars indicate SEM.</p