Specific antibodies against vaccine-preventable infections: a mother-infant cohort study

OBJECTIVES: To determine maternal and neonatal specific antibody levels to selected vaccine-preventable infections (pertussis, Haemophilus influenzae type b (Hib), tetanus and pneumococcus). DESIGN: Prospective cohort study. SETTING: A UK secondary care maternity unit (March 2011-January 2012). PARTICIPANTS: Mothers and infants within 72 h of delivery were eligible. Unwell individuals, mothers less than 18 years of age, and infants born at less than 36 weeks gestation, or weighing less than 2500 g, were excluded. HIV-infected mothers were included. 112 mother-infant pairs were recruited. Samples from 111 mothers and 109 infants (108 pairs) were available for analysis. OUTCOME MEASURES: Specific antibody levels were determined using standard commercial ELISAs. Specific antibody to pertussis antigens (PT and FHA) of >50 IU/ml, defined as 'positive' by the test manufacturer, were interpreted as protective. Antitetanus antibody titres >0.1 IU/ml and anti-Hib antibody titres >1 mg/l were regarded as protective. RESULTS: Only 17% (19/111) of women exhibited a protective antibody response against pertussis. 50% (56/111) of women had levels of antibody protective against Hib and 79% (88/111) against tetanus. There was a strong positive correlation between maternal-specific and infant-specific antibodies' responses against pertussis (rs=0.71, p<0.001), Hib (rs=0.80, p<0.001), tetanus (rs=0.90, p<0.001) and pneumococcal capsular polysaccharide (rs=0.85, p<0.001). Only 30% (33/109) and 42% (46/109) of infants showed a protective antibody response to pertussis and Hib, respectively. Placental transfer (infant:mother ratio) of specific IgG to pertussis, Hib, pneumococcus and tetanus was significantly reduced from HIV-infected mothers to their HIV-exposed, uninfected infants (n=12 pairs) compared with HIV-uninfected mothers with HIV-unexposed infants (n=96 pairs) by 58% (<0.001), 61% (<0.001), 28% (p=0.034) and 32% (p=0.035), respectively. CONCLUSIONS: Low baseline antibody levels against pertussis in this cohort suggest the recently implemented UK maternal pertussis immunisation programme has potential to be effective

The influence of paediatric HIV infection on circulating B cell subsets and CXCR5+ T helper cells

Antiretroviral therapy (ART) only partially restores HIV-induced alterations in lymphocyte populations. We assessed B and T cell phenotypes in a cohort of children from a single centre in the United Kingdom with perinatally acquired HIV compared to healthy controls. The majority of HIV infected children (44 of 56) were on fully suppressive combination ART. Children with perinatally acquired HIV had significantly lower memory B and CD4(+) CD45RO(+) CXCR5(+) [follicular T helper cell (Tfh)-like] T cell percentages. Detectable viraemia was associated with higher CD21(-) (activated and exhausted/tissue-like memory) B cells. A greater proportion of life spent on suppressive ART was associated with higher memory B cell percentages. These results suggest that early and sustained suppressive ART may preserve B and T cell phenotypes in perinatally acquired HIV and limit deficits in humoral immunity. A lower proportion of circulating Tfh-like cells in HIV infected children appears to be independent of HIV treatment history and ongoing HIV viraemia and warrants further investigation

Recycling of plastic waste: Presence of phthalates in plastics from households and industry

Plastics recycling has the potential to substitute virgin plastics partially as a source of raw materials in plastic product manufacturing. Plastic as a material may contain a variety of chemicals, some potentially hazardous. Phthalates, for instance, are a group of chemicals produced in large volumes and are commonly used as plasticisers in plastics manufacturing. Potential impacts on human health require restricted use in selected applications and a need for the closer monitoring of potential sources of human exposure. Although the presence of phthalates in a variety of plastics has been recognised, the influence of plastic recycling on phthalate content has been hypothesised but not well documented. In the present work we analysed selected phthalates (DMP, DEP, DPP, DiBP, DBP, BBzP, DEHP, DCHP and DnOP) in samples of waste plastics as well as recycled and virgin plastics. DBP, DiBP and DEHP had the highest frequency of detection in the samples analysed, with 360 μg/g, 460 μg/g and 2700 μg/g as the maximum measured concentrations, respectively. Among other, statistical analysis of the analytical results suggested that phthalates were potentially added in the later stages of plastic product manufacturing (labelling, gluing, etc.) and were not removed following recycling of household waste plastics. Furthermore, DEHP was identified as a potential indicator for phthalate contamination of plastics. Close monitoring of plastics intended for phthalates-sensitive applications is recommended if recycled plastics are to be used as raw material in productionThe help provided by Mikael E. Olsson and Satomi Matsuura (DTU Environment) in the analytical part of the work is greatly appreciated. Vincent M.E. Edjabou (DTU Environment) is acknowledged for his valuable help in statistical data analysis. The authors would like to acknowledge the financial support of the Danish Research Council through the 3R Research School and the IRMAR project (grant no. 11-116775)

Effects of different leukocyte subpopulations and flow conditions on leukocyte accumulation during reperfusion

Background/Aims: The study examined the interdependent effects of shear stress and different leukocyte subpopulations on endothelial cell activation and cell interactions during low flow and reperfusion. Methods: Human umbilical venous endothelial cells were perfused with either neutrophils or monocytes at different shear stress (2-0.25 dyn/cm 2) and adhesion was quantified by microscopy. Effects of adherent neutrophils and monocytes on endothelial cell adhesion molecule expression were analyzed by flow cytometry after 4-hour static coincubation. After coincubation, the cocultures were reperfused with labeled neutrophils at 2 dyn/cm 2 and their adhesion was quantified selectively. For the control, endothelium monocultures with and without lipopolysaccharide activation were used. Results: At 2 dyn/cm 2, adhesion did not exceed baseline levels on nonactivated endothelium. Decreasing shear stress to 0.25 dyn/cm 2 largely increased the adhesion of both leukocyte subpopulations, similar to the effect of lipopolysaccharide at 2 dyn/cm 2. However, only adherent monocytes increased adhesion molecule expression, whereas neutrophils had no effect. As a functional consequence, adherent monocytes largely increased neutrophil adhesion during reperfusion, whereas adherent neutrophils did not. Conclusion: Compromised shear stress is an autonomous trigger of leukocyte adhesion even in the absence of additional activators. Exceeding this immediate effect, adherent monocytes induce further endothelial activation and enhance further neutrophil adhesion during reperfusion. Copyrigh

Dual gene activation and knockout screen reveals directional dependencies in genetic networks.

Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair. Based on the results from over 100,000 perturbed gene pairs, we reconstruct a directional dependency network for human K562 leukemia cells and demonstrate how our approach allows the determination of directionality in activating genetic interactions. Our interaction network connects previously uncharacterized genes to well-studied pathways and identifies targets relevant for therapeutic intervention

Serological response to 13-valent pneumococcal conjugate vaccine in children and adolescents with perinatally acquired HIV infection

BACKGROUND: Children with perinatally acquired HIV (paHIV) remain at an increased risk of pneumococcal infection despite highly active antiretroviral therapy (HAART). Beyond infancy, responses to pneumococcal conjugate vaccine (PCV) remain under-investigated. There are currently no published data on serological response to 13-valent PCV (PCV13) in the HIV-infected populations. METHODS: We measured pneumococcal serotype-specific IgG in 48 paHIV-infected child patients (CP), 27 young adult healthy controls (AHC) and 30 child healthy controls (CHC). Opsonophagocytic assay (OPA) titres for three PCV13-exclusive serotypes were measured in a subset of children. Serotype-specific IgG was repeated 1 and 6 months following PCV13 vaccination of CP and AHC groups. OPA titres for four serotypes were measured at the 1-month time-point. RESULTS: The majority of CP, CHC and AHC had serotype-specific IgG above 0.35 μg/ml at baseline, although OPA activity was undetectable for two of the three serotypes studied. Baseline IgG concentrations were significantly lower in CP than AHC for a proportion of serotypes and were strongly predictive of responses to vaccine. After adjusting for baseline, postvaccination IgG concentrations were comparable, although responses to some serotypes were impaired for CP. OPA correlated well with IgG after vaccination. Detectable HIV viral load was associated with significantly lower IgG concentration and OPA titre. CONCLUSION: Children with paHIV mount a robust serological response to PCV13 for most but not all vaccine serotypes. Viral load suppression with HAART and higher baseline IgG concentration are associated with higher postvaccination antibody levels. This has implications for HAART treatment and vaccination practices

Relative validity of a web-based food frequency questionnaire for Danish adolescents

Background: With increased focus on dietary intake among youth and risk of diseases later in life, it is of importance, prior to assessing diet-disease relationships, to examine the validity of the dietary assessment tool. This study’s objective was to evaluate the relative validity of a self-administered web-based FFQ among Danish children aged 12 to 15 years. Methods: From a nested sub-cohort within the Danish National Birth Cohort, 124 adolescents participated. Four weeks after completion of the FFQ, adolescents were invited to complete three telephone-based 24HRs; administered 4 weeks apart. Mean or median intakes of nutrients and food groups estimated from the FFQ were compared with the mean of 3x24HRs. To assess the level of ranking we calculated the proportion of correctly classified into the same quartile, and the proportion of misclassified (into the opposite quartile). Spearman’s correlation coefficients and de-attenuated coefficients were calculated to assess agreement between the FFQ and 24HRs. Results: The mean percentage of all food groups, for adolescents classified into the same and opposite quartile was 35 and 7.5%, respectively. Mean Spearman’s correlation was 0.28 for food groups and 0.35 for nutrients, respectively. Adjustment for energy and within-person variation in the 24HRs had little effect on the magnitude of the correlations for food groups and nutrients. We found overestimation by the FFQ compared with the 24HRs for fish, fruits, vegetables, oils and dressing and underestimation by the FFQ for meat/poultry and sweets. Median intake of beverages, dairy, bread, cereals, the mean total energy and carbohydrate intake did not differ significantly between the two methods. Conclusion: The relative validity of the FFQ compared with the 3x24HRs showed that the ranking ability differed across food groups and nutrients with best ranking for estimated intake of dairy, fruits, and oils and dressing. Larger variation was observed for fish, sweets and vegetables. For nutrients, the ranking ability was acceptable for fatty acids and iron. When evaluating estimates from the FFQ among Danish adolescents these findings should be considered.The study was supported by grants from The Danish Research Council 09–067124 (Center for Fetal Programming), 09–075611; and the Intramural Research Program of The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract # HHSN275201000020C). The funding bodies had no role in the design of the study, collection, analysis, interpretation of data or in writing the manuscript.Peer Reviewe

p16 expression in oropharyngeal cancer: its impact on staging and prognosis compared with the conventional clinical staging parameters

Background: Currently, staging of head neck squamous cell carcinoma (HNSCC) is on the basis of primary tumor extension (cT), lymph node involvement (cN) and distant metastasis (cM). The aim of cancer staging was to improve diagnosis, prognosis and to compare outcome results. A new subgroup of oropharyngeal squamous cell carcinoma (OPSCC) induced by human papillomavirus (HPV) infection is reported to show an increasing incidence. These HPV-positive OPSCC show distinct molecular differences, specific p16 overexpression and a significantly better prognosis. Therefore, the aim of this study was to evaluate the prognostic influence of p16 expression in OPSCC and compare its relevance with the established prognostic markers cT and cN classification and the clinical stages I-IV. Patients and methods: Immunohistochemistry for p16 was carried out on the basis of a tissue microarray including 102 OPSCC patients with corresponding retrospective clinicopathological and follow-up data. Results: p16 is the strongest independent prognostic marker in OPSCC, surpassing the significance of cT and cN classification as well as the clinical stages I-IV. Prognosis of p16-positive OPSCC of an advanced stage reached or even exceeded prognosis of the next clinically smaller conventionally staged group of tumors. Conclusion: p16 is the most relevant prognostic marker in OPSCC and should be considered for inclusion into the official staging system of HNSC