Quantitative Outcomes of a One Health approach to Study Global Health Challenges

Having gained momentum in the last decade, the One Health initiative promotes a holistic approach to address complex global health issues. Before recommending its adoption to stakeholders, however, it is paramount to first compile quantitative evidence of the benefit of such an approach. The aim of this scoping review was to identify and summarize primary research that describes monetary and non-monetary outcomes following adoption of a One Health approach. An extensive literature search yielded a total of 42,167 references, of which 85 were included in the final analysis. The top two biotic health issues addressed in these studies were rabies and malaria; the top abiotic health issue was air pollution. Most studies described collaborations between human and animal (n = 42), or human and environmental disciplines (n = 41); commonly reported interventions included vector control and animal vaccination. Monetary outcomes were commonly expressed as cost–benefit or cost–utility ratios; non-monetary outcomes were described using disease frequency or disease burden measurements. The majority of the studies reported positive or partially positive outcomes. This paper illustrates the variety of health challenges that can be addressed using a One Health approach, and provides tangible quantitative measures that can be used to evaluate future implementations of the One Health approach.     

The Marburgvirus-Neutralizing Human Monoclonal Antibody MR191 Targets a Conserved Site to Block Virus Receptor Binding

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Comparison of germination responses of Anigozanthos flavidus (Haemodoraceae), Gyrostemon racemiger and Gyrostemon ramulosus (Gyrostemonaceae) to smoke-water and the smoke-derived compounds karrikinolide (KAR1) and glyceronitrile

Background and Aims

A major germination-promoting chemical in smoke-water is 3-methyl-2H-furo[2,3-c]pyran-2-one (karrikinolide, KAR₁). However, not all species that germinate in response to smoke-water are responsive to KAR₁, such as Tersonia cyathiflora (Gyrostemonaceae). In this study, a test was made of whether two Gyrostemon species (Gyrostemonaceae) that have previously been shown to respond to smoke-water, respond to KAR₁. If not, then the smoke-derived chemical that stimulates germination of these species is currently unknown. Recently, glyceronitrile was isolated from smoke-water and promoted the germination of certain Anigozanthos species (Haemodoraceae). Whether this chemical promotes Gyrostemon racemiger germination is also examined. Furthermore, an investigation was carried out into whether these species germinate in response to smoke-water derived from burning cellulose alone.

Methods Gyrostemon racemiger

and G. ramulosus seeds were buried after collection and retrieved in autumn the following year when dormancy was alleviated and seeds had become responsive to smoke-water. Anigozanthos flavidus seeds were after-ripened at 35 °C to alleviate dormancy. Gyrostemon and Anigozanthos seeds were then tested with ‘Seed Starter’ smoke-water, KAR₁, glyceronitrile and cellulose-derived smoke-water.

Key Results

Although Gyrostemon racemiger, G. ramulosus and A. flavidus were all stimulated to germinate by ‘Seed Starter’ smoke-water, none of these species responded to KAR₁. Gyrostemon racemiger germination was not promoted by glyceronitrile. This is in contrast to A. flavidus, where glyceronitrile, at concentrations of 1–500 µm, promoted germination, although seedling growth was inhibited at ≥400 µm. Maximum A. flavidus germination occurred at glyceronitrile concentrations of 25–300 µm. Some Gyrostemon germination was promoted by cellulose-derived smoke-water.

Conclusions

KAR₁ and glyceronitrile, chemicals in smoke-water that are known to stimulate germination in other species, did not promote the germination of G. racemiger. This suggests that other chemical(s) which promote germination are present in smoke, and may be derived from burning cellulose alone.     

Pro-inflammatory cytokines from Kupffer cells downregulate hepatocyte expression of adrenomedullin binding protein-1

Polymicrobial sepsis is characterized by an early, hyperdynamic phase followed by a late hypodynamic phase. Adrenomedullin (AM), a vasodilatory peptide, inhibits this transition from the early phase to the late phase. Adrenomedullin binding protein-1 (AMBP-1) enhances AM-mediated activities. The decrease of AMBP-1 levels in late sepsis reduces the vascular response to AM and produces the hypodynamic phase. Studies have indicated that the administration of LPS downregulates AMBP-1 production in the liver. Since hepatocytes are the primary source of AMBP-1 biosynthesis in the liver, we employed a co-culture strategy using hepatocyte and Kupffer cells to determine whether LPS directly or by increasing pro-inflammatory cytokines from Kupffer cells downregulates AMBP-1 production. Hepatocytes and Kupffer cells isolated from rats were co-cultured and treated with LPS for 24 h. LPS significantly attenuated AMBP-1 protein expression in a dose-dependent manner. Since AMBP-1 is basically a secretory protein, cell supernatants from co-culture cells treated with LPS were examined for AMBP-1 protein levels. LPS treatment caused a dose related decrease in AMBP-1 protein secretion. Similarly, LPS treatment produced a significant decrease in AMBP-1 protein expression in hepatocytes and Kupffer cells cultured using transwell inserts. LPS had no direct effect on AMBP-1 levels in cultured hepatocytes or Kupffer cells alone. To confirm that the observed effects in co-culture were due to the cytokines released from Kupffer cells, hepatocytes were treated with IL-1beta or TNF-alpha for 24 h and AMBP-1 expression was examined. The results indicated that both cytokines significantly inhibited AMBP-1 protein levels. Thus, pro-inflammatory cytokines released from Kupffer cells are responsible for downregulation of AMBP-1.     

Multiple genes for essential-hypertension susceptibility on chromosome 1q

Essential hypertension, defined as elevated levels of blood pressure (BP) without any obvious cause, is a major risk factor for coronary heart disease, stroke, and renal disease. BP levels and susceptibility to development of essential hypertension are partially determined by genetic factors that are poorly understood. Similar to other efforts to understand complex, non-Mendelian phenotypes, genetic dissection of hypertension-related traits employs genomewide linkage analyses of families and association studies of patient cohorts, to uncover rare and common disease alleles, respectively. Family-based mapping studies of elevated BP cover the large intermediate ground for identification of genes with common variants of significant effect. Our genomewide linkage and candidate-gene-based association studies demonstrate that a replicated linkage peak for BP regulation on human chromosome 1q, homologous to mouse and rat quantitative trait loci for BP, contains at least three genes associated with BP levels in multiple samples: ATP1B1, RGS5, and SELE. Individual variants in these three genes account for 2-5-mm Hg differences in mean systolic BP levels, and the cumulative effect reaches 8-10 mm Hg. Because the associated alleles in these genes are relatively common (frequency >5%), these three genes are important contributors to elevated BP in the population at large.     

Culturable and VBNC <Emphasis Type="Italic">Vibrio cholerae</Emphasis>: Interactions with Chironomid Egg Masses and Their Bacterial Population

Vibrio cholerae, the etiologic agent of cholera, is autochthonous to various aquatic environments. Recently, it was found that chironomid (nonbiting midges) egg masses serve as a reservoir for the cholera bacterium and that flying chironomid adults are possible windborne carriers of V. cholerae non-O1 non-O139. Chironomids are the most widely distributed insect in freshwater. Females deposit egg masses at the water's edge, and each egg mass contains eggs embedded in a gelatinous matrix. Hemagglutinin/protease, an extracellular enzyme of V. cholerae, was found to degrade chironomid egg masses and to prevent them from hatching. In a yearly survey, chironomid populations and the V. cholerae in their egg masses followed phenological succession and interaction of host–pathogen population dynamics. In this report, it is shown via FISH technique that most of the V. cholerae inhabiting the egg mass are in the viable but nonculturable (VBNC) state. The diversity of culturable bacteria from chironomid egg masses collected from two freshwater habitats was determined. In addition to V. cholerae, representatives of the following genera were isolated: Acinetobacter, Aeromonas, Klebsiella, Shewanella, Pseudomonas, Paracoccus, Exiguobacterium, and unidentified bacteria. Three important human pathogens, Aeromonas veronii, A. caviae, and A. hydrophila, were isolated from chironomid egg masses, indicating that chironomid egg masses may be a natural reservoir for pathogenic Aeromonas species in addition to V. cholerae. All isolates of V. cholerae were capable of degrading chironomid egg masses. This may help explain their host–pathogen relationship with chironomids. In contrast, almost none of the other bacteria that were isolated from the egg masses possessed this ability. Studying the interaction between chironomid egg masses, the bacteria inhabiting them, and V. cholerae could contribute to our understanding of the nature of the V. cholerae–egg mass interactions.     

Monosaccharides promote flowering in <Emphasis Type="Italic">Kniphofia leucocephala</Emphasis> in vitro

An investigation into the role of carbohydrates in flowering of the endangered species Kniphofia leucocephala Baijnath. (Asphodelaceae) in vitro revealed that a carbohydrate source is essential for the induction of inflorescences. Both the concentration and type of sugar influenced the percentage of flowering, with 60 g l⁻¹ fructose and 10 μM N⁶-benzyladenine (BA) inducing the best flowering response. A high percentage of flowering was also observed with 60 g l⁻¹ glucose and 10 μM BA. The optimal concentration of sucrose for flower induction was 30 g l⁻¹, beyond which the flowering percentage declined, but could be partially restored by increasing the BA concentration. Although overall plant growth declined at high sugar concentrations, there does not appear to be any significant correlations between various growth parameters and flowering percentage, suggesting that sugars play a direct role in floral transition in vitro.     

The Government of Kenya's Cash Transfer Program Reduces the Risk of Sexual Debut among Young People Age 15-25

The aim of this study is to assess whether the Government of Kenya''s Cash Transfer for Orphans and Vulnerable Children (Kenya CT-OVC) can reduce the risk of HIV among young people by postponing sexual debut. The program provides an unconditional transfer of US$20 per month directly to the main caregiver in the household. An evaluation of the program was implemented in 2007–2009 in seven districts. Fourteen Locations were randomly assigned to receive the program and fourteen were assigned to a control arm. A sample of households was enrolled in the evaluation in 2007. We revisited these households in 2011 and collected information on sexual activity among individuals between 15–25 years of age. We used logistic regression, adjusted for the respondent''s age, sex and relationship to caregiver, the age, sex and schooling of the caregiver and whether or not the household lived in Nairobi at baseline, to compare rates of sexual debut among young people living in program households with those living in control households who had not yet entered the program. Our results, adjusted for these covariates, show that the program reduced the odds of sexual debut by 31 percent. There were no statistically significant effects on secondary outcomes of behavioral risk such as condom use, number of partners and transactional sex. Since the CT-OVC provides cash to the caregiver and not to the child, and there are no explicit conditions associated with receipt, these impacts are indirect, and may have been achieved by keeping young people in school. Our results suggest that large-scale national social cash transfer programs with poverty alleviation objectives may have potential positive spillover benefits in terms of reducing HIV risk among young people in Eastern and Southern Africa.     

PSD95 Suppresses Dendritic Arbor Development in Mature Hippocampal Neurons by Occluding the Clustering of NR2B-NMDA Receptors

Considerable evidence indicates that the NMDA receptor (NMDAR) subunits NR2A and NR2B are critical mediators of synaptic plasticity and dendritogenesis; however, how they differentially regulate these processes is unclear. Here we investigate the roles of the NR2A and NR2B subunits, and of their scaffolding proteins PSD-95 and SAP102, in remodeling the dendritic architecture of developing hippocampal neurons (2–25 DIV). Analysis of the dendritic architecture and the temporal and spatial expression patterns of the NMDARs and anchoring proteins in immature cultures revealed a strong positive correlation between synaptic expression of the NR2B subunit and dendritogenesis. With maturation, the pruning of dendritic branches was paralleled by a strong reduction in overall and synaptic expression of NR2B, and a significant elevation in synaptic expression of NR2A and PSD95. Using constructs that alter the synaptic composition, we found that either over-expression of NR2B or knock-down of PSD95 by shRNA-PSD95 augmented dendritogenesis in immature neurons. Reactivation of dendritogenesis could also be achieved in mature cultured neurons, but required both manipulations simultaneously, and was accompanied by increased dendritic clustering of NR2B. Our results indicate that the developmental increase in synaptic expression of PSD95 obstructs the synaptic clustering of NR2B-NMDARs, and thereby restricts reactivation of dendritic branching. Experiments with shRNA-PSD95 and chimeric NR2A/NR2B constructs further revealed that C-terminus of the NR2B subunit (tail) was sufficient to induce robust dendritic branching in mature hippocampal neurons, and suggest that the NR2B tail is important in recruiting calcium-dependent signaling proteins and scaffolding proteins necessary for dendritogenesis.     

A Regional-Scale Ocean Health Index for Brazil

Brazil has one of the largest and fastest growing economies and one of the largest coastlines in the world, making human use and enjoyment of coastal and marine resources of fundamental importance to the country. Integrated assessments of ocean health are needed to understand the condition of a range of benefits that humans derive from marine systems and to evaluate where attention should be focused to improve the health of these systems. Here we describe the first such assessment for Brazil at both national and state levels. We applied the Ocean Health Index framework, which evaluates ten public goals for healthy oceans. Despite refinements of input data and model formulations, the national score of 60 (out of 100) was highly congruent with the previous global assessment for Brazil of 62. Variability in scores among coastal states was most striking for goals related to mariculture, protected areas, tourism, and clean waters. Extractive goals, including Food Provision, received low scores relative to habitat-related goals, such as Biodiversity. This study demonstrates the applicability of the Ocean Health Index at a regional scale, and its usefulness in highlighting existing data and knowledge gaps and identifying key policy and management recommendations. To improve Brazil''s ocean health, this study suggests that future actions should focus on: enhancing fisheries management, expanding marine protected areas, and monitoring coastal habitats.