A systematic review of the health effects of prenatal exposure to disaster.

OBJECTIVES: The aim of this study was to determine the health effects of prenatal exposure to disaster, based on a systematic review of existing research. METHODS: A literature search of scientific databases was conducted in February 2015 for articles on prenatal exposure to a natural or man-made disaster. Data was extracted from all articles that met the inclusion criteria, and we systematically analyzed contents based on type of disaster, health outcome, target group and time after birth. RESULTS: Prenatal exposure to famine or war was found to be associated with mental health, cardiovascular or metabolic outcomes, with varying degrees of significance. The majority of the studies showed limited or weak associations between exposures and outcomes. CONCLUSIONS: Due to the lack of variety in type of events studied, as well as large methodological variation, it is difficult to draw firm conclusions from existing literature. However, our systematic review highlights the potential of evaluating secondary data, both to accentuate research gaps in the field and to increase the understanding of what effects various types of disasters potentially have on the unborn child.

Foreign Medical Teams in the Philippines after Typhoon Haiyan 2013 - Who Were They, When Did They Arrive and What Did They Do?

BACKGROUND: Foreign medical teams (FMT) are international medical teams sent to provide assistance in the aftermath of a disaster. In the last decade, there has been an increase in FMTs deployed following disasters. Despite the potential benefit FMTs might have in substituting the collapsed health care and caring for excess morbidity after large-scale disasters, several studies have demonstrated the difficulties in determining the quality of the response, mainly due to lack of reliable data. In order to bridge the knowledge gap on functioning of FMTs, the aim of this study is to assess the timing, capacities and activities of FMTs deployed to the Philippines after typhoon Haiyan. METHODS: This is a retrospective, descriptive study. Data on characteristics of FMTs present in the Philippines after typhoon Haiyan was provided by the World Health Organization (WHO) and compiled into a single database. Additional data was collected through a web survey, email correspondence and internet searches. RESULTS: A total of 108 FMTs were identified as arriving to the Philippines within the first month following typhoon Haiyan. None of these were operational in the affected areas within the first 72 h and the average time between arriving and being on-site operational was three days. Of the 108 FMTs, 70% were FMT type 1, 11% were FMT type 2 and 3% were FMT type 3. 16% of FMTs had unknown status. The total number of staff within all these FMTs were 2121, of which 210 were medical doctors, 250 nurses and 6 midwifes. Compared to previous sudden onset disasters, this study found no improvement in data sharing.

Activation of mineralocorticoid receptors by exogenous glucocorticoids and the development of cardiovascular inflammatory responses in adrenalectomized rats.

Activation of the mineralocorticoid receptor (MR) in the context of a high salt intake produces cardiovascular inflammation plus cardiac fibrosis and failure. Inactivation of vascular 11beta-hydroxysteroid dehydrogenase type 2 activity in intact animals by carbenoxolone (CBX) produces a similar pathology, presumably reflecting coronary vascular MR activation by endogenous glucocorticoids. To test this hypothesis, we have used adrenalectomized rats, without endogenous corticosteroids, and examined the consequences of corticosterone (CORT) replacement on a series of cardiovascular disease parameters. Uninephrectomized adrenalectomized Sprague Dawley rats given 1% NaCl/0.3% KCl to drink were treated for 8 d as follows: control; 20 mg deoxycorticosterone (DOC); 2 mg/d CORT; 2.5 mg/d CBX; CORT plus CBX (CORT/CBX); and CORT/CBX plus 100 mg/kg.d eplerenone. Markers of cardiac oxidative stress (p22(phox) and NOX4 mRNA) were up-regulated in the DOC and CORT/CBX groups; in contrast, inflammatory cell infiltration was increased and endothelial nitric oxide synthase down-regulated by CORT as well as by DOC and CORT/CBX. In the kidney, connective tissue growth factor mRNA levels were increased by DOC and CORT/CBX; in contrast, DOC had no effect on mRNA levels for channel inducing factor or endothelin 3, which were elevated only by CORT/CBX. All changes noted were reversed by eplerenone. Rats given 10-fold lower CORT (0.2 mg/d) with or without CBX showed no change in any parameter. These results suggest that there exist distinct but overlapping ligand-specific MR-mediated tissue responses to a classic mineralocorticoid (DOC) and to the glucocorticoid CORT, in the presence and absence of CBX to block vascular 11beta-hydroxysteroid dehydrogenase type 2.

Differential recognition of P. falciparum VAR2CSA domains by naturally acquired antibodies in pregnant women from a malaria endemic area.

BACKGROUND: Plasmodium falciparum infected red blood cells (iRBC) express variant surface antigens (VSA) of which VAR2CSA is involved in placental sequestration and causes pregnancy-associated malaria (PAM). Primigravidae are most susceptible to PAM whereas antibodies associated with protection are often present at higher levels in multigravid women. However, HIV co-infection with malaria has been shown to alter this parity-dependent acquisition of immunity, with more severe symptoms as well as more malaria episodes in HIV positive women versus HIV negative women of a similar parity. METHODS: Using VAR2CSA DBL-domains expressed on the surface of CHO-745 cells we quantified levels of DBL-domain specific IgG in sera from pregnant Malawian women by flow cytometry. Dissociations constants of DBL5epsilon specific antibodies were determined using a surface plasmon resonance technique, as an indication of antibody affinities. RESULTS: VAR2CSA DBL5epsilon was recognized in a gender and parity-dependent manner with anti-DBL5epsilon IgG correlating significantly with IgG levels to VSA-PAM on the iRBC surface. HIV positive women had lower levels of anti-DBL5epsilon IgG than HIV negative women of similar parity. In primigravidae, antibodies in HIV positive women also showed significantly lower affinity to VAR2CSA DBL5epsilon. CONCLUSIONS: Pregnant women from a malaria-endemic area had increased levels of anti-DBL5epsilon IgG by parity, indicating this domain of VAR2CSA to be a promising vaccine candidate against PAM. However, it is important to consider co-infection with HIV, as this seems to change the properties of antibody response against malaria. Understanding the characteristics of antibody response against VAR2CSA is undoubtedly imperative in order to design a functional and efficient vaccine against PAM.

Simultaneous transcription of duplicated var2csa gene copies in individual Plasmodium falciparum parasites.

BACKGROUND: Single nucleotide polymorphisms are common in duplicated genes, causing functional preservation, alteration or silencing. The Plasmodium falciparum genes var2csa and Pf332 are duplicated in the haploid genome of the HB3 parasite line. Whereas the molecular function of Pf332 remains to be elucidated, VAR2CSA is known to be the main adhesin in placental parasite sequestration. Sequence variations introduced upon duplication of these genes provide discriminative possibilities to analyze allele-specific transcription with a bearing towards understanding gene dosage impact on parasite biology. RESULTS: We demonstrate an approach combining real-time PCR allelic discrimination and discriminative RNA-FISH to distinguish between highly similar gene copies in P. falciparum parasites. The duplicated var2csa variants are simultaneously transcribed, both on a population level and intriguingly also in individual cells, with nuclear co-localization of the active genes and corresponding transcripts. This indicates transcriptional functionality of duplicated genes, challenges the dogma of mutually exclusive var gene transcription and suggests mechanisms behind antigenic variation, at least in respect to the duplicated and highly similar var2csa genes. CONCLUSIONS: Allelic discrimination assays have traditionally been applied to study zygosity in diploid genomes. The assays presented here are instead successfully applied to the identification and evaluation of transcriptional activity of duplicated genes in the haploid genome of the P. falciparum parasite. Allelic discrimination and gene or transcript localization by FISH not only provide insights into transcriptional regulation of genes such as the virulence associated var genes, but also suggest that this sensitive and precise approach could be used for further investigation of genome dynamics and gene regulation.