Microarray Analysis of PBMC after Plasmodium falciparum Infection: Molecular Insights into Disease Pathogenesis

Our laboratory’s previous microarray analysis of subjects with Plasmodium falciparum revealed up-regulation of Toll-like receptor, NF-kB, TNF-α, IFN-γ, IL-1β, p38 MAPK, and MHC molecules. We performed further time-course microarray analysis focusing on malaria pathogenesis by using peripheral leukocytes as a cellular model. We found up-regulation of coagulation-related genes (SERPINB2, thrombomodulin, thrombospondin), heat shock proteins, glycolytic enzymes, glucose transporters, and vacuolar H+-ATPases in acute febrile malaria. In early malaria, prior to detectable parasitemia, CD36 and ICAM1 were up-regulated. During acute malaria, a correlation was observed between IL-1ß and heat shock proteins, suggesting heat shock protein response may be in the febrile response induced by IL-1ß. CD163, a hemoglobin scavenger receptor, was up-regulated in acute malaria to potentially facilitate free hemoglobin up-take by peripheral leukocytes. In acute malaria, high MafB gene expression was negatively correlated with down-regulation of hemoglobin and platelet counts. Consistent with a down-regulation of hemoglobin expression, peripheral RBC counts tended to increase during the acute malaria. In our model, up-regulations of RBC and/or leucocyte binding mediators like CD36, ICAM1, thrombospondin, and thrombomodulin may contribute to the pathogenesis of cerebral malaria. Similarly, up-regulation of genes coding for glycolytic enzymes, glucose transporter and H+-ATPases may contribute to the hypoglycemia and metabolic acidosis frequently observed in seriously ill malaria patients. Overall gender effects on gene expression profiles between male and female subjects were not apparent, except that some hemoglobins were significantly down-regulated in male versus female; suggesting males may be more prone to the development of malaria associate anemia

The origin and prevention of pandemics.

Despite the fact that most emerging diseases stem from the transmission of pathogenic agents from animals to humans, the factors that mediate this process are still ill defined. What is known, however, is that the interface between humans and animals is of paramount importance in the process. This review will discuss the importance of the human-animal interface to the disease emergence process. We also provide an overview of factors that are believed to contribute to the origin and global spread of emerging infectious diseases and offer suggestions that may serve as future prevention strategies, such as social mobilization, public health education, behavioral change, and communication strategies. Because there exists no comprehensive global surveillance system to monitor zoonotic disease emergence, the intervention measures discussed herein may prove effective temporary alternatives

Utilizing the Boston Syncope Observation Management Pathway to Reduce Hospital Admission and Decrease Adverse Outcomes

Introduction: In an age of increasing scrutiny of each hospital admission, emergency department (ED) observation has been identified as a low-cost alternative. Prior studies have shown admission rates for syncope in the United States to be as high as 70%. However, the safety and utility of substituting ED observation unit (EDOU) syncope management has not been well studied. The objective of this study was to evaluate the safety of EDOU for the management of patients presenting to the ED with syncope and its efficacy in reducing hospital admissions. Methods: This was a prospective before-and-after cohort study of consecutive patients presenting with syncope who were seen in an urban ED and were either admitted to the hospital, discharged, or placed in the EDOU. We first performed an observation study of syncope management and then implemented an ED observation-based management pathway. We identified critical interventions and 30-day outcomes. We compared proportions of admissions and adverse events rates with a chisquared or Fisher’s exact test. Results: In the “before” phase, 570 patients were enrolled, with 334 (59%) admitted and 27 (5%) placed in the EDOU; 3% of patients discharged from the ED had critical interventions within 30 days and 10% returned. After the management pathway was introduced, 489 patients were enrolled; 34% (p\u3c0.001) of pathway patients were admitted while 20% were placed in the EDOU; 3% (p=0.99) of discharged patients had critical interventions at 30 days and 3% returned (p=0.001). Conclusion: A focused syncope management pathway effectively reduces hospital admissions and adverse events following discharge and returns to the ED. [West J Emerg Med. 2019;20(2)250–255.

Bushmeat Hunting, Deforestation, and Prediction of Zoonotic Disease

Integrating virology, ecology, and other disciplines enhances prediction of new emerging zoonoses

Recent Trends and Results for Organ Donation and Transplantation in the United States, 2005

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72853/1/j.1600-6143.2006.01268.x.pd

Reinforcement learning in large, structured action spaces: A simulation study of decision support for spinal cord injury rehabilitation

Reinforcement learning (RL) has helped improve decision-making in several applications. However, applying traditional RL is challenging in some applications, such as rehabilitation of people with a spinal cord injury (SCI). Among other factors, using RL in this domain is difficult because there are many possible treatments (i.e., large action space) and few patients (i.e., limited training data). Treatments for SCIs have natural groupings, so we propose two approaches to grouping treatments so that an RL agent can learn effectively from limited data. One relies on domain knowledge of SCI rehabilitation and the other learns similarities among treatments using an embedding technique. We then use Fitted Q Iteration to train an agent that learns optimal treatments. Through a simulation study designed to reflect the properties of SCI rehabilitation, we find that both methods can help improve the treatment decisions of physiotherapists, but the approach based on domain knowledge offers better performance. Our findings provide a "proof of concept" that RL can be used to help improve the treatment of those with an SCI and indicates that continued efforts to gather data and apply RL to this domain are worthwhile.Comment: 31 pages, 7 figure

Genotypic Diversity and Host-Specificity of Frankia Bacteria Associated with Sympatric Populations of Alnus rubra and Alnus rhombifolia in Oregon

Biological nitrogen fixation is one of the most critical processes contributing to ecosystem productivity and stability on a global scale. In temperate climates of the northern hemisphere, plant-root associated bacteria of the genus Frankia are the major nitrogen fixers in forest environments. Trees belonging to the genus Alnus are the most widespread hosts of Frankia in the Pacific Northwest, and a myriad of biotic and abiotic factors can influence the robustness of this symbiosis. Host identity and bacterial strain are important features that can impact Alnus-Frankia association, but little is known about the interplay of intrageneric hosts that co-occur in natural settings. In this study we investigated the genetic diversity and host specificity of Frankia bacteria associated with sympatrically occurring populations of Alnus rubra (red alder) and Alnus rhombifolia (white alder) in Oregon. Based on sequence analysis of the nifH gene recovered from root nodules we found low overall bacterial diversity. One dominant Frankia genotype was associated with both host species, indicating a lack of strong host specificity in this system. Our results suggest that certain intrageneric plant hosts with overlapping distributions show cross-compatibility with symbiotic actinorhizal bacteria, and that low strain diversity of these bacteria can persist across mixed host populations

Wild Primate Populations in Emerging Infectious Disease Research: The Missing Link?

Wild primate populations, an unexplored source of information regarding emerging infectious disease, may hold valuable clues to the origins and evolution of some important pathogens. Primates can act as reservoirs for human pathogens. As members of biologically diverse habitats, they serve as sentinels for surveillance of emerging pathogens and provide models for basic research on natural transmission dynamics. Since emerging infectious diseases also pose serious threats to endangered and threatened primate species, studies of these diseases in primate populations can benefit conservation efforts and may provide the missing link between laboratory studies and the well-recognized needs of early disease detection, identification, and surveillance