Characterizing the gut microbiota during plasmodium infection and antimalarial treatment.

Plasmodium, the parasitic cause of malaria, is a global pathogen, annually causing 216 million infections and 445,000 deaths. As drug resistance continues develop and no effective vaccine is available, it is critical to understand the factors underlying the severity of this disease. Plasmodium is an extra-gastrointestinal tract infection where the parasite infects red blood cells causing clinical malaria. However, recent publications have pointed to interactions between the gut microbiota and malaria. With this in mind, the role of the gut microbiota in malaria infection was studied. C57BL/6 mice from different vendors displayed differential resistance and susceptibility to severe malaria, and cecal contents transplanted from these mice to germ-free mice recapitulated the observed phenotypes. Similarly, resistant mice possessed a much more robust humoral immune response than susceptible mice, which is critical for Plasmodium clearance. When the cecal contents from resistant and susceptible mice were sequenced, Lactobacillus and Bifidobacterium genera were enriched in resistant mice. Moreover, treating susceptible mice with probiotics containing these bacterial genera after antibiotic administration led to a lower parasite burden. These observations point to a previously unknown role for the microbiota in modulating the severity of malaria. To further characterize the interactions between the host and gut microbiota in malaria, different components of gut homeostasis were investigated in both mild and severe disease. While intestinal permeability increased in both resistant and susceptible mice, there were no significant differences between the two groups. However, susceptible mice were shown to have greater numbers of lamina propria immune cells as well as greater abundances of cecal metabolites and bile acids during infection compared to resistant mice. Consistent with the decreased abundance of bile acids, histology showed much greater and prolonged damage and hemozoin deposition in the livers of susceptible mice compared to resistant mice. Despite these differences, the microbiota composition of resistant and susceptible mice became more similar during infection, although these changes were not associated with susceptibility or resistance when the altered cecal contents were transferred into germ-free mice. However, there were distinct differences in the functional capacity of the resistant and susceptible microbiota during infection. Susceptible mice showed significant increases in genes related to bacterial motility and flagellar assembly. Overall, there are profound differences in gut homeostasis during severe and mild Py infection. Finally, it was investigated whether antimalarial drugs, particularly clinically relevant artemisinin combination therapies (ACTs), could disrupt the gut microbiota. As previously shown, the composition of the gut microbiota alone can modulate the severity of Py infection; if ACTs change the microbiota composition, future infections could be more severe. To test this hypothesis, two common ACTs, artesunate plus amodiaquine and artemether plus lumefantrine, were used to orally treat mice while fecal pellets were collected to characterize the gut microbiota before and after treatment. After either ACT treatment, the overall species abundance in mice was similar to baseline. While alpha diversity remained unchanged by any treatment, there were minor, inconsistent changes in beta diversity that returned to baseline. With these findings, it does not appear that ACTs change the gut microbiota. This work has greatly increased the scientific knowledge concerning the three-fold interaction between host, gut microbiota, and Plasmodium. While much work still needs to be done, these findings can provide a contextual foundation on which future work can be built

Mobile Sensing Platform: Final Project Report

The Mobile Sensing Platform Team presents their final project report for the senior design project to create a mobile sensing platform for Dr. Nickels’ autonomy efforts. The sensing bed, or rover, is designed for mobility in extreme conditions in order to carry a payload of sensors and other equipment capable of collecting data into areas too dangerous for humans. The first step in achieving this goal was to create a prototype with functioning control and motor systems. As such, our design will operate using a control system that will be easily replaced for a more complicated computer. Our team has been tasked with creating a rover (or mobile sensing platform) with the ability to navigate 30 degree inclines, a step of 25 cm, and a payload of 50 kg, similar to the weight of the sensors that a typical rover might carry. To meet these requirements, the following subsystems were designed: chassis, legs, motor assembly, power distribution, and control system. Recent changes to the composition of the group and several other external setbacks such as the winter storm and COVID-19 restrictions have hindered progress, and thus, production of this prototype has been delayed, with the remaining work to be completed by a future team. The designed chassis and legs all withstood the required weight of the rover and payload of over 150 kg. The motor assembly was capable of supplying the necessary torque to ascend the hill, but struggled in dynamic tests under changing speeds and directions. While the power distribution system was delayed, the topology for the motor control was designed. Lastly the control system, which included the wireless controller, was manufactured and assembled, but never fully tested with the power distribution. Overall, the mobile sensing platform team successfully identified the necessary design specifications to complete the prototype, but was unfortunately unable to finish manufacturing all of these designed subsystems. We learned so much over the course of this project, and while we wish we had been able to complete the rover as designed, we are proud of what we accomplished given the changing circumstances. The final project report to follow will detail the completed design of the rover and the design solutions engineered to meet our project requirements

Functional Characteristics of the Gut Microbiome in C57BL/6 Mice Differentially Susceptible to Plasmodium yoelii

C57BL/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. In a previous study, it was observed that when C57BL/6 mice purchased from different vendors were infected with Plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. To gain insight into the mechanism of resistance, we removed whole ceca from mice purchased from two vendors, Taconic Biosciences (low parasitemia) and Charles River Laboratories (high parasitemia), to determine the combined host and microflora metabolome and metatranscriptome. With the exception of two Charles River samples, we observed 90% similarity in overall bacterial gene expression within vendors and 80% similarity between vendors. In total 33 bacterial genes were differentially expressed in Charles River mice (p-value \u3c 0.05) relative to the mice purchased from Taconic. Included among these, fliC, ureABC, and six members of the nuo gene family were overrepresented in microbiomes susceptible to more severe malaria. Moreover, 38 mouse genes were differentially expressed in these purported genetically identical mice. Differentially expressed genes included basigin, a cell surface receptor required for P. falciparum invasion of red blood cells. Differences in metabolite pools were detected, though their relevance to malaria infection, microbial community activity, or host response is not yet understood. Our data have provided new targets that may connect gut microbial activity to malaria resistance and susceptibility phenotypes in the C57BL/6 model organism

Phenome-wide association study identifies marked increased in burden of comorbidities in African Americans with systemic lupus erythematosus.

BACKGROUND: African Americans with systemic lupus erythematosus (SLE) have increased renal disease compared to Caucasians, but differences in other comorbidities have not been well-described. We used an electronic health record (EHR) technique to test for differences in comorbidities in African Americans compared to Caucasians with SLE. METHODS: We used a de-identified EHR with 2.8 million subjects to identify SLE cases using a validated algorithm. We performed phenome-wide association studies (PheWAS) comparing African American to Caucasian SLE cases and African American SLE cases to matched non-SLE controls. Controls were age, sex, and race matched to SLE cases. For multiple testing, a false discovery rate (FDR) p value of 0.05 was used. RESULTS: We identified 270 African Americans and 715 Caucasians with SLE and 1425 matched African American controls. Compared to Caucasians with SLE adjusting for age and sex, African Americans with SLE had more comorbidities in every organ system. The most striking included hypertension odds ratio (OR) = 4.25, FDR p = 5.49 × 10 CONCLUSIONS: African Americans with SLE have an increased comorbidity burden compared to Caucasians with SLE and matched controls. This increase in comorbidities in African Americans with SLE highlights the need to monitor for cardiovascular and infectious complications

PERANCANGAN DAN PENGEMBANGAN APLIKASI HOSPITAL MOBILE BERBASIS ANDROID

Mobile applications are computer programs that have many benefits, such as making it easier forusers to obtain and disseminate information. The mobile application can also be used to help patientsconnect with hospitals. Some of the problems faced by patients are the difficulty of contactinghospitals to register for treatment or consultation, also the difficulty of patients finding informationabout doctor's practice schedules and information about polyclinic and existing facilities so patientsmust come to the hospital to find out that information. Based on the analysis of the problem, it isproposed making a mobile application with some features needed by patients. The design andmanufacture of this application is divided into three parts, namely database using MySQL, webapplications using PHP and mobile applications using Android. Based on respondent data, it can beconcluded that this application has several uses for respondents.Aplikasi mobile merupakan suatu program komputer yang memiliki banyak manfaat, sepertimempermudah pengguna untuk memperoleh dan menyebarluaskan informasi. Aplikasi mobile jugadapat digunakan untuk membantu pasien berhubungan dengan rumah sakit. Beberapa masalah yangdihadapi oleh pasien adalah sulitnya menghubungi rumah sakit untuk melakukan pendaftaran berobatatau konsultasi, juga sulitnya pasien mencari informasi mengenai jadwal praktek dokter dan informasimengenai poli dan fasilitas yang ada sehingga pasien harus datang ke rumah sakit untuk mengetahuiinformasi tersebut. Berdasarkan analisis masalah maka diusulkan pembuatan aplikasi mobile denganbeberapa fitur yang dibutuhkan pasien.Perancangan dan pembuatan aplikasi ini dibagi menjadi tigabagian yaitu basisdata menggunakan MySQL, aplikasi web menggunakan PHP dan aplikasi mobilemenggunakan Android. Berdasarkan data responden maka dapat disimpulkan bahwa aplikasi inimemiliki beberapa kegunaan bagi responden

Understanding patient-provider communication entered via a patient portal system

ABSTRACT Our study examines patient-provider communication via a patient portal in a large medical center. Our study is based on 1172 interactions made among stakeholders concerning 100 patients who are randomly selected from the 2009 MyHealthAtVanderbilt.com (a patient portal at the Vanderbilt Medical Center) patient pool; among which, 35 use the patient portal for messages. The findings show a wide range of topics discussed and ways in which patients provide and seek information as well as express psychosocial and emotional needs. In addition, while the patient portal has advantages over traditional communication technologies, it was not the primary communication media for our study sample. More research is needed to better elucidate barriers to the use of patient portals and the optimal methods of communication in differing contexts

An integrative functional genomics framework for effective identification of novel regulatory variants in genome–phenome studies

Background: Genome–phenome studies have identified thousands of variants that are statistically associated with disease or traits; however, their functional roles are largely unclear. A comprehensive investigation of regulatory mechanisms and the gene regulatory networks between phenome-wide association study (PheWAS) and genome-wide association study (GWAS) is needed to identify novel regulatory variants contributing to risk for human diseases. Methods: In this study, we developed an integrative functional genomics framework that maps 215,107 significant single nucleotide polymorphism (SNP) traits generated from the PheWAS Catalog and 28,870 genome-wide significant SNP traits collected from the GWAS Catalog into a global human genome regulatory map via incorporating various functional annotation data, including transcription factor (TF)-based motifs, promoters, enhancers, and expression quantitative trait loci (eQTLs) generated from four major functional genomics databases: FANTOM5, ENCODE, NIH Roadmap, and Genotype-Tissue Expression (GTEx). In addition, we performed a tissue-specific regulatory circuit analysis through the integration of the identified regulatory variants and tissue-specific gene expression profiles in 7051 samples across 32 tissues from GTEx. Results: We found that the disease-associated loci in both the PheWAS and GWAS Catalogs were significantly enriched with functional SNPs. The integration of functional annotations significantly improved the power of detecting novel associations in PheWAS, through which we found a number of functional associations with strong regulatory evidence in the PheWAS Catalog. Finally, we constructed tissue-specific regulatory circuits for several complex traits: mental diseases, autoimmune diseases, and cancer, via exploring tissue-specific TF-promoter/enhancer-target gene interaction networks. We uncovered several promising tissue-specific regulatory TFs or genes for Alzheimer’s disease (e.g. ZIC1 and STX1B) and asthma (e.g. CSF3 and IL1RL1). Conclusions: This study offers powerful tools for exploring the functional consequences of variants generated from genome–phenome association studies in terms of their mechanisms on affecting multiple complex diseases and traits. Electronic supplementary material The online version of this article (10.1186/s13073-018-0513-x) contains supplementary material, which is available to authorized users