Mutual exclusivity of hyaluronan and hyaluronidase in invasive group A Streptococcus

A recent analysis of group A Streptococcus (GAS) invasive infections in Australia has shown a predominance of M4 GAS, a serotype recently reported to lack the antiphagocytic hyaluronic acid (HA) capsule. Here, we use molecular genetics and bioinformatics techniques to characterize 17 clinical M4 isolates associated with invasive disease in children during this recent epidemiology. All M4 isolates lacked HA capsule, and whole genome sequence analysis of two isolates revealed the complete absence of the hasABC capsule biosynthesis operon. Conversely, M4 isolates possess a functional HA-degrading hyaluronate lyase (HylA) enzyme that is rendered nonfunctional in other GAS through a point mutation. Transformation with a plasmid expressing hasABC restored partial encapsulation in wild-type (WT) M4 GAS, and full encapsulation in an isogenic M4 mutant lacking HylA. However, partial encapsulation reduced binding to human complement regulatory protein C4BP, did not enhance survival in whole human blood, and did not increase virulence of WT M4 GAS in a mouse model of systemic infection. Bioinformatics analysis found no hasABC homologs in closely related species, suggesting that this operon was a recent acquisition. These data showcase a mutually exclusive interaction of HA capsule and active HylA among strains of this leading human pathogen

The effect of maternal common mental disorders on infant undernutrition in Butajira, Ethiopia: The P-MaMiE study

BACKGROUND: Although maternal common mental disorder (CMD) appears to be a risk factor for infant undernutrition in South Asian countries, the position in sub-Saharan Africa (SSA) is unclear METHODS: A population-based cohort of 1065 women, in the third trimester of pregnancy, was identified from the demographic surveillance site (DSS) in Butajira, to investigate the effect of maternal CMD on infant undernutrition in a predominantly rural Ethiopian population. Participants were interviewed at recruitment and at two months post-partum. Maternal CMD was measured using the locally validated Self-Reported Questionnaire (score of > or = six indicating high levels of CMD). Infant anthropometry was recorded at six and twelve months of age. RESULT: The prevalence of CMD was 12% during pregnancy and 5% at the two month postnatal time-point. In bivariate analysis antenatal CMD which had resolved after delivery predicted underweight at twelve months (OR = 1.71; 95% CI: 1.05, 2.50). There were no other statistically significant differences in the prevalence of underweight or stunted infants in mothers with high levels of CMD compared to those with low levels. The associations between CMD and infant nutritional status were not significant after adjusting for pre-specified potential confounders. CONCLUSION: Our negative finding adds to the inconsistent picture emerging from SSA. The association between CMD and infant undernutrition might be modified by study methodology as well as degree of shared parenting among family members, making it difficult to extrapolate across low- and middle-income countries

The 12 Item Social and Economic Conservatism Scale (SECS)

Recent years have seen a surge in psychological research on the relationship between political ideology (particularly conservatism) and cognition, affect, behaviour, and even biology. Despite this flurry of investigation, however, there is as yet no accepted, validated, and widely used multi-item scale of conservatism that is concise, that is modern in its conceptualisation, and that includes both social and economic conservatism subscales. In this paper the 12-Item Social and Economic Conservatism Scale (SECS) is proposed and validated to help fill this gap. The SECS is suggested to be an important and useful tool for researchers working in political psychology

Global development and diffusion of outcome evaluation research for interpersonal and self-directed violence prevention from 2007 to 2013: A systematic review

© 2014 The Authors. Published by Elsevier Ltd. Through a global review, we identified gaps in the geographical distribution of violence prevention evidence outcome evaluation studies and the types of violence addressed. Systematic literature searches identified 355 articles published between 2007 and 2013 that evaluated programs to prevent interpersonal or self-directed violence; focused on universal or selected populations; and reported outcomes measuring violence or closely related risk factors. The number of studies identified increased annually from 2008 (n = 37), reaching 64 in 2013. Over half (n = 203) of all studies focused on youth violence yet only one on elder maltreatment. Study characteristics varied by year and violence type. Only 9.3% of all studies had been conducted in LMICs. These studies were less likely than those in high income countries (HICs) to have tested established interventions yet more likely to involve international collaboration. Evaluation studies successfully established in LMIC had often capitalized on other major regional priorities (e.g. HIV). Relationships between violence and social determinants, communicable and non-communicable diseases, and even economic prosperity should be explored as mechanisms to increase the global reach of violence prevention research. Results should inform future research strategies and provide a baseline for measuring progress in developing the violence prevention evidence-base, especially in LMICs

Improving early childhood care and development, HIV testing, treatment and support, and nutrition in Mokhotlong, Lesotho: study protocol for a cluster randomized controlled trial

Background Since 1990, the lives of 48 million children under the age of 5 have been saved because of increased investments in reducing child mortality. However, despite these unprecedented gains, more than 200 million children in low and middle income countries (LMIC) cannot meet their developmental potential due to poverty, poor health and nutrition, and lack of necessary stimulation and care. Lesotho has high levels of poverty, HIV and malnutrition, all of which affect child development outcomes. There is a unique opportunity to address these complex issues through the widespread network of informal preschools in rural villages in the country, which provide a setting for inclusive, integrated Early Childhood Care and Development (ECCD), HIV and nutrition interventions. Methods We are conducting a cluster randomised controlled trial in Mokhotlong district, Lesotho, to evaluate a newly developed community-based intervention programme to integrate HIV testing and treatment services, ECCD, and nutrition education for caregivers with children aged 1-5 years living in rural villages. Caregivers and their children are randomly assigned by village to intervention or control condition. We select, train, and supervise community health workers recruited to implement the intervention, which consists of nine group-based sessions with caregivers and children over 12 weeks (eight weekly sessions, and a ninth top up session one month later), followed by a locally hosted community health outreach day event. Group-based sessions focus on using early dialogic booksharing to promote cognitive development and caregiver-child interaction, health-related messages, including motivation for HIV-testing and treatment uptake for young children, and locally appropriate nutrition education. All children aged 1-5 years and their primary caregivers living in study villages are eligible for participation. Caregivers and their children will be interviewed and assessed at baseline, immediately after completion of the intervention, and 12 months post intervention. Discussion This study provides a unique opportunity to assess the potential of an integrated early childhood development intervention to prevent or mitigate developmental delays in children living in a context of extreme poverty and high HIV rates in rural Lesotho. This paper presents the intervention content and research protocol for the study

Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors

Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and consequent phagocytosis. Several strains of GAS bind to human-specific complement inhibitors, C4b-binding protein (C4BP) and/or Factor H (FH), to curtail complement C3 (a critical opsonin) deposition. This results in diminished activation of phagocytes and clearance of GAS that may lead to the host being unable to limit the infection. Herein we describe the course of GAS infection in three human complement inhibitor transgenic (tg) mouse models that examined each inhibitor (human C4BP or FH) alone, or the two inhibitors together (C4BPxFH or 'double' tg). GAS infection with strains that bound C4BP and FH resulted in enhanced mortality in each of the three transgenic mouse models compared to infection in wild type mice. In addition, GAS manifested increased virulence in C4BPxFH mice: higher organism burdens and greater elevations of pro-inflammatory cytokines and they died earlier than single transgenic or wt controls. The effects of hu-C4BP and hu-FH were specific for GAS strains that bound these inhibitors because strains that did not bind the inhibitors showed reduced virulence in the 'double' tg mice compared to strains that did bind; mortality was also similar in wild-type and C4BPxFH mice infected by non-binding GAS. Our findings emphasize the importance of binding of complement inhibitors to GAS that results in impaired opsonization and phagocytic killing, which translates to enhanced virulence in a humanized whole animal model. This novel hu-C4BPxFH tg model may prove invaluable in studies of GAS pathogenesis and for developing vaccines and therapeutics that rely on human complement activation for efficacy