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Severe falciparum malaria is a major cause of preventable child mortality in sub-Saharan Africa. Plasma concentrations of P. falciparum Histidine-Rich Protein 2 ( Pf HRP2) have diagnostic and prognostic value in severe malaria. We investigate the potential use of plasma Pf HRP2 and the sequestration index (the ratio of Pf HRP2 to parasite density) as quantitative traits for case-only genetic association studies of severe malaria. Data from 2198 Kenyan children diagnosed with severe malaria, genotyped for 14 major candidate genes, show that polymorphisms in four major red cell genes that lead to hemoglobin S, O blood group, α-thalassemia, and the Dantu blood group, are associated with substantially lower admission plasma Pf HRP2 concentrations, consistent with protective effects against extensive parasitized erythrocyte sequestration. In contrast the known protective ATP2B4 polymorphism is associated with higher plasma Pf HRP2 concentrations, lower parasite densities and a higher sequestration index. We provide testable hypotheses for the mechanism of protection of ATP2B4 . Numerous candidate malaria protective gene polymorphisms have been proposed. Here, Uyoga et al. investigate associations between malaria-protective red blood cell polymorphisms and total parasite biomass estimated from plasma concentrations of Pf HRP2, in a cohort of Kenyan children suffering from severe malaria. They suggest that plasma Pf HRP2 and the ratio of the plasma Pf HRP2 to the peripheral parasite density (sequestration index) as powerful quantitative phenotypic traits for severe malaria.

Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) are prevalent comorbidities related to a greater likelihood of poor treatment outcomes and prolonged treatment for Reward Deficiency Syndrome (RDS) behaviors. The current exploratory case study of a small cohort (n=3; f=2 m=1) used novel neurotechnology to treat co-occurring MDD and GAD with a multifaceted intervention that combines the novel bio-resonance neurotechnology (BRNT) referred to as NuCalm , to restore autonomic nervous system balance and dual hemispheric repetitive transcranial magnetic stimulation (rTMS) of the ipsilateral Dorsal Lateral Prefrontal Cortex (DLPFC) to treat the disrupted structural components of the brain. Neuroacoustic brainwave entrainment, electromagnetic frequency bio-resonance, and light-blocking combine to place patients into a parasympathetic dominant state. The paired -tests indicated a significant decrease in comparing before and after the intervention. The Patient Health Questionnaire PHQ-9 scores from the first to the last time-point (mean difference = 20, t(2) = 6.55, p = 0.0226), with a 95% confidence interval of mean difference ranging from 6.86 to 33.14. Similarly, there was a significant decrease in General Anxiety Disorder GAD-7 questionnaire scores from the first to the last time point (mean difference = 18.67, t(2) = 12.85, p = 0.0060), with a 95% confidence interval of the mean difference ranging from 12.42 to 24.92. After applying the Bonferroni correction, the corrected p-values for PHQ-9 and GAD-7 are 0.0452 and 0.0120, respectively. Cohen's d standardized effect size indicated that the main effect size was 5.47 and 13.8 times the noise (variability), respectively, for the initial versus final PHQ-9 and GAD-7. Further, more extensive, much larger sham-controlled and blinded studies are required to confirm these encouraging results and explore this multifaceted intervention.

Malaria has had a major effect on the human genome, with many protective polymorphisms—such as the sickle-cell trait—having been selected to high frequencies in malaria-endemic regions 1 , 2 . The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals 3 – 5 , a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC–parasite receptor–ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals. The rare blood group Dantu is known to protect against severe malaria, and a mechanism is proposed here: Dantu red blood cells have a high membrane tension that prevents invasion by malaria parasites.

Background Invasive alien species (IAS) cause significant economic losses in all parts of the world. Although IAS are widespread in Africa and cause serious negative impacts on livelihoods as a result of yield losses and increased labour costs associated with IAS management, few data on the impacts are available in the literature and the magnitude and extent of the costs are largely unknown. We estimated the cost of IAS to agriculture, the most important economic sector in Africa. Methods Data on the monetary costs of IAS to mainland Africa as well as information about the presence and abundance of the most important IAS were collected through literature review and an online survey among a wide variety of stakeholders. Using this and additional data from publicly available sources we estimated yield losses and management costs due to IAS in agriculture for individual countries and the entire continent. Where the data allowed, the costs for selected IAS or crops were estimated separately. The estimates were extrapolated using production and distribution data and/or matching of agro-ecological zones. Results The total estimated annual cost of IAS to agriculture in Africa is USD 65.58 Bn. Management costs (comprising mainly labour costs associated with weeding), crop yield losses and reductions in livestock derived income constitute the majority of the estimated cost (55.42, 44.31 and 0.26 percent, respectively). The IAS causing the highest yield losses was Spodoptera frugiperda (USD 9.4 Bn). Conclusions This study reveals the extent and scale of the economic impacts of IAS in the agricultural sector in one of the least studied continents. Although the cost estimate presented here is significant, IAS also cause major costs to other sectors which could not be assessed due to data deficit. The results highlight the need for pre-emptive management options, such as prevention and early detection and rapid response to reduce huge potential future costs, as well as measures that contribute to large-scale control of widely established IAS at little cost to farmers and other affected land users, to reduce losses and improve livelihoods.

Loneliness, an established risk factor for both, mental and physical morbidity, is a mounting public health concern. However, the neurobiological mechanisms underlying loneliness-related morbidity are not yet well defined. Here we examined the role of genes and associated DNA risk polymorphic variants that are implicated in loneliness via genetic and epigenetic mechanisms and may thus point to specific therapeutic targets. Searches were conducted on PubMed, Medline, and EMBASE databases using specific Medical Subject Headings terms such as loneliness and genes, neuro- and epigenetics, addiction, affective disorders, alcohol, anti-reward, anxiety, depression, dopamine, cancer, cardiovascular, cognitive, hypodopaminergia, medical, motivation, (neuro)psychopathology, social isolation, and reward deficiency. The narrative literature review yielded recursive collections of scientific and clinical evidence, which were subsequently condensed and summarized in the following key areas: (1) Genetic Antecedents: Exploration of multiple genes mediating reward, stress, immunity and other important vital functions; (2) Genes and Mental Health: Examination of genes linked to personality traits and mental illnesses providing insights into the intricate network of interaction converging on the experience of loneliness; (3) Epigenetic Effects: Inquiry into instances of loneliness and social isolation that are driven by epigenetic methylations associated with negative childhood experiences; and (4) Neural Correlates: Analysis of loneliness-related affective states and cognitions with a focus on hypodopaminergic reward deficiency arising in the context of early life stress, eg, maternal separation, underscoring the importance of parental support early in life. Identification of the individual contributions by various (epi)genetic factors presents opportunities for the creation of innovative preventive, diagnostic, and therapeutic approaches for individuals who cope with persistent feelings of loneliness. The clinical facets and therapeutic prospects associated with the current understanding of loneliness, are discussed emphasizing the relevance of genes and DNA risk polymorphic variants in the context of loneliness-related morbidity.

Malaria has had a major effect on the human genome, with many protective polymorphisms--such as the sickle-cell trait--having been selected to high frequencies in malaria-endemic regions.sup.1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals.sup.3-5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC-parasite receptor-ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals.

Malaria has had a major effect on the human genome, with many protective polymorphisms--such as the sickle-cell trait--having been selected to high frequencies in malaria-endemic regions.sup.1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals.sup.3-5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC-parasite receptor-ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals.

Malaria has had a major effect on the human genome, with many protective polymorphisms--such as the sickle-cell trait--having been selected to high frequencies in malaria-endemic regions.sup.1,2. The blood group variant Dantu provides 74% protection against all forms of severe malaria in homozygous individuals.sup.3-5, a similar degree of protection to that afforded by the sickle-cell trait and considerably greater than that offered by the best malaria vaccine. Until now, however, the protective mechanism has been unknown. Here we demonstrate the effect of Dantu on the ability of the merozoite form of the malaria parasite Plasmodium falciparum to invade red blood cells (RBCs). We find that Dantu is associated with extensive changes to the repertoire of proteins found on the RBC surface, but, unexpectedly, inhibition of invasion does not correlate with specific RBC-parasite receptor-ligand interactions. By following invasion using video microscopy, we find a strong link between RBC tension and merozoite invasion, and identify a tension threshold above which invasion rarely occurs, even in non-Dantu RBCs. Dantu RBCs have higher average tension than non-Dantu RBCs, meaning that a greater proportion resist invasion. These findings provide both an explanation for the protective effect of Dantu, and fresh insight into why the efficiency of P. falciparum invasion might vary across the heterogenous populations of RBCs found both within and between individuals.

Gilchrist et al discuss an identification of a trait-associated SNP, rs8060947 in VAC14. rs8060947 is an expression quantitative trait locus for VAC14 RNA expression and carriage of the A allele is associated with reduced VAC14 RNA and protein expression and increased invasion of S. Typhi. VAC14-associated inhibition of S. Typhi invasion is mediated by a reduction in host cell membrane cholesterol.