Mapping the Risk of Soil-Transmitted Helminthic Infections in the Philippines

BackgroundIn order to increase the efficient allocation of soil-transmitted helminth (STH) disease control resources in the Philippines, we aimed to describe for the first time the spatial variation in the prevalence of A. lumbricoides, T. trichiura and hookworm across the country, quantify the association between the physical environment and spatial variation of STH infection and develop predictive risk maps for each infection.Conclusions/SignificanceThis analysis revealed significant spatial variation in STH infection prevalence within provinces of the Philippines. This suggests that a spatially targeted approach to STH interventions, including mass drug administration, is warranted. When financially possible, additional STH surveys should be prioritized to high-risk areas identified by our study in Luzon.     

Detection of Innate Immune Response Modulating Impurities in Therapeutic Proteins

Therapeutic proteins can contain multiple impurities, some of which are variants of the product, while others are derived from the cell substrate and the manufacturing process. Such impurities, even when present at trace levels, have the potential to activate innate immune cells in peripheral blood or embedded in tissues causing expression of cytokines and chemokines, increasing antigen uptake, facilitating processing and presentation by antigen presenting cells, and fostering product immunogenicity. Currently, while products are tested for host cell protein content, assays to control innate immune response modulating impurities (IIRMIs) in products are focused mainly on endotoxin and nucleic acids, however, depending on the cell substrate and the manufacturing process, numerous other IIRMI could be present. In these studies we assess two approaches that allow for the detection of a broader subset of IIRMIs. In the first, we use commercial cell lines transfected with Toll like receptors (TLR) to detect receptor-specific agonists. This method is sensitive to trace levels of IIRMI and provides information of the type of IIRMIs present but is limited by the availability of stably transfected cell lines and requires pre-existing knowledge of the IIRMIs likely to be present in the product. Alternatively, the use of a combination of macrophage cell lines of human and mouse origin allows for the detection of a broader spectrum of impurities, but does not identify the source of the activation. Importantly, for either system the lower limit of detection (LLOD) of impurities was similar to that of PBMC and it was not modified by the therapeutic protein tested, even in settings where the product had inherent immune modulatory properties. Together these data indicate that a cell-based assay approach could be used to screen products for the presence of IIRMIs and inform immunogenicity risk assessments, particularly in the context of comparability exercises.     

Time-Dependent Increase in Network Response to Stimulation

In vitro neuronal cultures have become a popular method with which to probe network-level neuronal dynamics and phenomena in controlled laboratory settings. One of the key dynamics of interest in these in vitro studies has been the extent to which cultured networks display properties indicative of learning. Here we demonstrate the effects of a high frequency electrical stimulation signal in training cultured networks of cortical neurons. Networks receiving this training signal displayed a time-dependent increase in the response to a low frequency probing stimulation, particularly in the time window of 20–50 ms after stimulation. This increase was found to be statistically significant as compared to control networks that did not receive training. The timing of this increase suggests potentiation of synaptic mechanisms. To further investigate this possibility, we leveraged the powerful Cox statistical connectivity method as previously investigated by our group. This method was used to identify and track changes in network connectivity strength.     

Climate and Species Richness Predict the Phylogenetic Structure of African Mammal Communities

We have little knowledge of how climatic variation (and by proxy, habitat variation) influences the phylogenetic structure of tropical communities. Here, we quantified the phylogenetic structure of mammal communities in Africa to investigate how community structure varies with respect to climate and species richness variation across the continent. In addition, we investigated how phylogenetic patterns vary across carnivores, primates, and ungulates. We predicted that climate would differentially affect the structure of communities from different clades due to between-clade biological variation. We examined 203 communities using two metrics, the net relatedness (NRI) and nearest taxon (NTI) indices. We used simultaneous autoregressive models to predict community phylogenetic structure from climate variables and species richness. We found that most individual communities exhibited a phylogenetic structure consistent with a null model, but both climate and species richness significantly predicted variation in community phylogenetic metrics. Using NTI, species rich communities were composed of more distantly related taxa for all mammal communities, as well as for communities of carnivorans or ungulates. Temperature seasonality predicted the phylogenetic structure of mammal, carnivoran, and ungulate communities, and annual rainfall predicted primate community structure. Additional climate variables related to temperature and rainfall also predicted the phylogenetic structure of ungulate communities. We suggest that both past interspecific competition and habitat filtering have shaped variation in tropical mammal communities. The significant effect of climatic factors on community structure has important implications for the diversity of mammal communities given current models of future climate change.     

1H HR-MAS NMR Based Metabolic Profiling of Cells in Response to Treatment with a Hexacationic Ruthenium Metallaprism as Potential Anticancer Drug

¹H high resolution magic angle spinning (HR-MAS) NMR spectroscopy was applied in combination with multivariate statistical analyses to study the metabolic response of whole cells to the treatment with a hexacationic ruthenium metallaprism [1]⁶⁺ as potential anticancer drug. Human ovarian cancer cells (A2780), the corresponding cisplatin resistant cells (A2780cisR), and human embryonic kidney cells (HEK-293) were each incubated for 24 h and 72 h with [1]⁶⁺ and compared to untreated cells. Different responses were obtained depending on the cell type and incubation time. Most pronounced changes were found for lipids, choline containing compounds, glutamate and glutathione, nucleotide sugars, lactate, and some amino acids. Possible contributions of these metabolites to physiologic processes are discussed. The time-dependent metabolic response patterns suggest that A2780 cells on one hand and HEK-293 cells and A2780cisR cells on the other hand may follow different cell death pathways and exist in different temporal stages thereof.     

A Social-Ecological View of Barriers and Facilitators for HIV Treatment Adherence: Interviews with Puerto Rican HIV Patients

Purpose

To identify perceived barriers and facilitators for HAART adherence among people living with HIV/AIDS in Southern Puerto Rico using a Social Ecological framework.

Patients and Methods

Individual in-depths interviews were conducted with 12 HIV patients with a history of HAART non-adherence. Interviews were audio-taped and transcribed. Content analysis was performed for each transcribed interview by three independent coders using a codebook. Using Atlas TI, super-codes and families were generated to facilitate the categorization tree as well as grounded analyses and density estimates

Results

Most participants reported a monthly income of $500 or less (n = 7), a high school education level (n = 7), being unemployed (n = 9) and being recipients of government health insurance (n = 11). Three out of six women reported living alone with their children and most men informed living with their parents or other relatives (n = 4). For the grounded analyses, the top four sub-categories linked to high number of quotations were mental health barriers (G = 32) followed by treatment regimen (G = 28), health system (G = 24) and interpersonal relations (G = 16). The top four sub-categories linked to high number of codes are treatment regimen (D = 4), health status perception (D = 3), interpersonal relations (D = 3) and health system (D = 3).

Conclusion

The results of this study suggest the interconnection of HIV treatment adherence barriers at various system levels. Future studies on HIV treatment barriers should explore these interactions and investigate the possible synergistic effect on non-adherent behavior     

Genetic Analysis for the Lack of Expression of the O157 Antigen in an O Rough:H7 Escherichia coli Strain

The O-antigen (rfb) operon and related genes of MA6, an O rough:H7 Shiga-toxigenic Escherichia coli strain, were examined to determine the cause of the lack of O157 expression. A 1,310-bp insertion, homologous to IS629, was observed within its gne gene. trans complementation with a functional gne gene from O157:H7 restored O157 antigen expression in MA6.Shiga-toxigenic Escherichia coli (STEC) serotype O157:H7 carries O157 and H7 antigens, so these traits are extensively used in identification (1). Strain MA6, isolated from beef in Malaysia (8), carries the O157:H7 virulence factor genes, including the Shiga toxin 2 gene (stx₂), the γ intimin allele (γ-eae), the enterohemolysin gene (ehxA), and the +93 uidA single nucleotide polymorphism (SNP) found only in O157:H7 strains (1). Multilocus sequence typing also showed MA6 to have the most common sequence type (ST-66) for O157:H7 strains. However, and in spite the fact that MA6 had per gene sequences essential for O157 antigen synthesis (2), no O157 antigen is expressed (O rough), and therefore, it is undetectable with serological assays used in O157:H7 analysis.The biosynthesis and assembly of E. coli O antigen are highly complex (9). The rfb operon (12 genes) (16), along with 3 ancillary genes outside of the rfb, is required for the biosynthesis of the 4 sugar nucleotide precursors and the assembly of the O unit (11). This is then linked to the core antigen, comprising an inner and an outer component, which require 3 other operons for biosynthesis and assembly (9). As defects in any of these genes could produce the O-null phenotype (13), we systematically examined these genes (Table ​(Table1)1) to elucidate the cause of the absence of O157 expression in MA6.

TABLE 1.

rfb operon genes, ancillary genes, and waa cluster genes examined in this study