Modeling of human cytomegalovirus maternal-fetal transmission in a novel decidual organ culture

Human cytomegalovirus (HCMV) is the leading cause of congenital infection, associated with severe birth defects and intrauterine growth retardation. The mechanism of HCMV transmission via the maternal-fetal interface is largely unknown, and there are no animal models for HCMV. The initial stages of infection are believed to occur in the maternal decidua. Here we employed a novel decidual organ culture, using both clinically derived and laboratory-derived viral strains, for the ex vivo modeling of HCMV transmission in the maternal-fetal interface. Viral spread in the tissue was demonstrated by the progression of infected-cell foci, with a 1.3- to 2-log increase in HCMV DNA and RNA levels between days 2 and 9 postinfection, the expression of immediate-early and late proteins, the appearance of typical histopathological features of natural infection, and dose-dependent inhibition of infection by ganciclovir and acyclovir. HCMV infected a wide range of cells in the decidua, including invasive cytotrophoblasts, macrophages, and endothelial, decidual, and dendritic cells. Cell-to-cell viral spread was revealed by focal extension of infected-cell clusters, inability to recover infectious extracellular virus, and high relative proportions (88 to 93%) of cell-associated viral DNA. Intriguingly, neutralizing HCMV hyperimmune globulins exhibited inhibitory activity against viral spread in the decidua even when added at 24 h postinfection-providing a mechanistic basis for their clinical use in prenatal prevention. The ex vivo-infected decidual cultures offer unique insight into patterns of viral tropism and spread, defining initial stages of congenital HCMV transmission, and can facilitate evaluation of the effects of new antiviral interventions within the maternal-fetal interface milieu.     

Development of Non-Profit Organisations Providing Health and Social Services in Rural South Africa: A Three-Year Longitudinal Study

Introduction

In an effort to increase understanding of formation of the community and home-based care economy in South Africa, we investigated the origin and development of non-profit organisations (NPOs) providing home- and community-based care for health and social services in a remote rural area of South Africa.

Methods

Over a three-year period (2010-12), we identified and tracked all NPOs providing health care and social services in Bushbuckridge sub-district through the use of local government records, snowballing techniques, and attendance at NPO networking meetings—recording both existing and new NPOs. NPO founders and managers were interviewed in face-to-face in-depth interviews, and their organisational records were reviewed.

Results

Forty-seven NPOs were formed prior to the study period, and 14 during the study period – six in 2010, six in 2011 and two in 2012, while four ceased operation, representing a 22% growth in the number of NPOs during the study period. Histories of NPOs showed a steady rise in the NPO formation over a 20-year period, from one (1991-1995) to 12 (1996-2000), 16 (2001-2005) and 24 (2006-2010) new organisations formed in each period. Furthermore, the histories of formation revealed three predominant milestones – loose association, formal formation and finally registration. Just over one quarter (28%) of NPOs emerged from a long-standing community based programme of ‘care groups’ of women. Founders of NPOs were mostly women (62%), with either a religious motivation or a nursing background, but occasionally had an entrepreneurial profile.

Conclusion

We observed rapid growth of the NPO sector providing community based health and social services. Women dominated the rural NPO sector, which is being seen as creating occupation and employment opportunities. The implications of this growth in the NPO sector providing community based health and social services needs to be further explored and suggests the need for greater coordination and possibly regulation.     

AVPR1A variant associated with preschoolers' lower altruistic behavior

The genetic origins of altruism, defined here as a costly act aimed to benefit non-kin individuals, have not been examined in young children. However, previous findings concerning adults pointed at the arginine vasopressin receptor 1A (AVPR1A) gene as a possible candidate. AVPR1A has been associated with a range of behaviors including aggressive, affiliative and altruistic phenotypes, and recently a specific allele (327 bp) of one of its promoter region polymorphisms (RS3) has been singled out in particular. We modeled altruistic behavior in preschoolers using a laboratory-based economic paradigm, a modified dictator game (DG), and tested for association between DG allocations and the RS3 "target allele." Using both population and family-based analyses we show a significant link between lower allocations and the RS3 "target allele," associating it, for the first time, with a lower proclivity toward altruistic behavior in children. This finding helps further the understanding of the intricate mechanisms underlying early altruistic behavior.     

Congenital cytomegalovirus mortality in the United States, 1990-2006

Background

Congenital cytomegalovirus (CMV) infection is the most common intrauterine infection in the United States disproportionately affecting minority races and those of lower socio-economic class. Despite its importance there is little information on the burden of congenital CMV-related mortality in the US. To measure congenital CMV-associated mortality in the US and assess possible racial/ethnic disparities, we reviewed national death certificate data for a 17-year period.

Methods

Congenital CMV-associated deaths from 1990 through 2006 were identified from multiple-cause-coded death records and were combined with US census data to calculate mortality rates.

Results

A total of 777 congenital CMV-associated deaths occurred over the 17-year study period resulting in 56,355 years of age-adjusted years of potential life lost. 71.7% (557) of congenital CMV-associated deaths occurred in infants (age less than 1 year). Age-adjusted mortality rates stratified by race/ethnicity revealed mortality disparities. Age-adjusted rate ratios were calculated for each racial/ethnic group using whites as the reference. Native Americans and African Americans were 2.34 (95% CI, 2.11–2.59) and 1.89 (95% CI, 1.70–2.11) times respectively, more likely to die from congenital CMV than whites. Asians and Hispanics were 0.54 (95% CI, 0.44–0.66) and 0.96 (95% CI, 0.83–1.10) times respectively, less likely to die from congenital CMV than whites.

Conclusions/Significance

Congenital CMV infection causes appreciable mortality in the US exacting a particular burden among African Americans and Native Americans. Enhanced surveillance and increased screening are necessary to better understand the epidemiology of congenital CMV infection in addition to acceleration of vaccine development efforts.     

Human maternal behaviour is associated with arginine vasopressin receptor 1A gene

Parenting is one of the main influences on children's early development, and yet its underlying genetic mechanisms have only recently begun to be explored, with many studies neglecting to control for possible child effects. This study focuses on maternal behaviour and on an allele at the RS3 promoter region of the arginine vasopressin receptor 1A (AVPR1A) gene, previously associated with autism and with higher amygdala activation in a face-matching task. Mothers were observed during a free-play session with each of their 3.5-year-old twins. Multilevel regression analyses revealed that mothers who are carriers of the AVPR1A RS3 allele tend to show less structuring and support throughout the interaction independent of the child's sex and RS3 genotype. This finding advances our understanding of the genetic influences on human maternal behaviour.     

Human echinococcosis mortality in the United States, 1990-2007

Background

Despite the endemic nature of Echinococcus granulosus and Echinococcus multilocularis infection in regions of the United States (US), there is a lack of data on echinococcosis-related mortality. To measure echinococcosis-associated mortality in the US and assess possible racial/ethnic disparities, we reviewed national-death certificate data for an 18-year period.

Methodology/Principal Findings

Echinococcosis-associated deaths from 1990 through 2007 were identified from multiple-cause-coded death records and were combined with US census data to calculate mortality rates. A total of 41 echinococcosis-associated deaths occurred over the 18-year study period. Mortality rates were highest in males, Native Americans, Asians/Pacific Islanders, Hispanics and persons 75 years of age and older. Almost a quarter of fatal echinococcosis-related cases occurred in residents of California. Foreign-born persons accounted for the majority of echinococcosis-related deaths; however, both of the fatalities in Native Americans and almost half of the deaths in whites were among US-born individuals.

Conclusions/Significance

Although uncommon, echinococcosis-related deaths occur in the US. Clinicians should be aware of the diagnosis, particularly in foreign-born patients from Echinococcus endemic areas, and should consider tropical infectious disease consultation early.     

High-resolution crystal structure of activated Cyt2Ba monomer from Bacillus thuringiensis subsp. israelensis

The Cyt family of proteins consists of δ-endotoxins expressed during sporulation of several subspecies of Bacillus thuringiensis. Its members possess insecticidal, hemolytic, and cytolytic activities through pore formation and attract attention due to their potential use as vehicles for targeted membrane destruction. The δ-endotoxins of subsp. israelensis include three Cyt species: a major Cyt1Aa and two minor proteins, Cyt2Ba and Cyt1Ca. A cleaved Cyt protein that lacks the N- and C-terminal segments forms a toxic monomer. Here, we describe the crystal structure of Cyt2Ba, cleaved at its amino and carboxy termini by bacterial endogenous protease(s). Overall, its fold resembles that of the previously described volvatoxin A2 and the nontoxic form of Cyt2Aa. The structural similarity between these three proteins may provide information regarding the mechanism(s) of membrane-perforating toxins.