Whole-genome sequencing of trypanosoma brucei reveals introgression between subspecies that is associated with virulence

Human African trypanosomiasis is caused by two subspecies of Trypanosoma brucei. Trypanosoma brucei rhodesiense is found in East Africa and frequently causes acute disease, while Trypanosoma brucei gambiense is found in West Africa and is associated with chronic disease. Samples taken from a single focus of a Ugandan outbreak of T. b. rhodesiense in the 1980s were associated with either chronic or acute disease. We sequenced the whole genomes of two of these isolates, which showed that they are genetically distinct from each other. Analysis of single nucleotide polymorphism markers in a panel of 31 Ugandan isolates plus 32 controls revealed a mixture of East African and West African haplotypes, and some of these haplotypes were associated with the different virulence phenotypes. It has been shown recently that T. b. brucei and T. b. rhodesiense populations undergo genetic exchange in natural populations. Our analysis showed that these strains from the Ugandan epidemic were intermediate between the reference genome sequences of T. b. gambiense and T. b. brucei and contained haplotypes that were present in both subspecies. This suggests that the human-infective subspecies of T. brucei are not genetically isolated, and our data are consistent with genomic introgression between East African and West African T. b. brucei subspecies. This has implications for the control of the parasite, the spread of drug resistance, and understanding the variation in virulence and the emergence of human infectivity.<p></p> IMPORTANCE We present a genetic study of the acute form of “sleeping sickness” caused by the protozoan parasite Trypanosoma brucei rhodesiense from a single outbreak in Uganda. This represents an advance in our understanding of the relationship between the T. b. rhodesiense and Trypanosoma brucei gambiense subspecies that have previously been considered geographically distinct. Our data suggest that introgression of West African-derived T. brucei haplotypes may be associated with differences in disease presentation in the East African disease. These findings are not only of scientific interest but also important for parasite control, as they suggest that the human-infective T. brucei subspecies are not genetically isolated.<p></p&gt

21st Century Cures Act: Patient Perceptions on Open Information Sharing in Vermont Primary Care Clinics

Introduction: The 21st Century Cures Act federally mandated the release of progress notes, laboratory test results, and radiology/pathology reports to the patient’s electronic health record (EHR) portal. This study investigates patient perspectives on shared notes and addresses provider concerns about patient uptake due to potential factors like worry, confusion, and distress at the University of Vermont Medical Center. Materials and Methods: An electronic cross-sectional survey was designed and distributed to 7,240 eligible patients, adults who logged into MyChart on Epic and had an outpatient/telemedical visit at either the Colchester Family Medicine and South Burlington Primary Care locations in Vermont within one year prior to the study. Results: The survey response rate was 4.6%. Of the respondents, 90% agreed that the use of shared notes is a good idea, 76% found accessing notes easy, and 2% felt more worried about their health because of shared notes. 89%, 85%, and 82% of respondents found visit notes important for understanding their health, remembering their care plan, and feeling in control of their care, respectively. Conclusions: Based on this survey, provider concerns about patient stress may be overstated, as patients appear to benefit from shared notes through increased engagement with their health, communication with providers, and adherence to care plans

Fluorescence detection of hydroxyl radicals in water produced by atmospheric pulsed discharges

It has been proven that hydroxyl (OH) radicals can be generated by streamer discharges across water surfaces under ambient atmospheric conditions. Hydroxyl radicals have the highest oxidation capability amongst all oxygen-based reactive species, thus OH play an important role in oxidation of organic molecules and the bactericidal effects of plasma discharges. In this study, generation of hydroxyl radicals in water by pulsed streamer discharges was investigated. Terephthalic acid was used as a chemical probe as this acid is converted into 2-hydroxyterephthalic acid (HTA) by chemical reaction with OH radicals. The concentration of OH radicals was quantified by measuring the fluorescence light intensity generated by HTA molecules in water solutions. Both positive and negative pulsed discharges with different voltage levels were tested. Two different types of sample holder – non-conductive plastic dishes, and dishes lined with conductive aluminum foil – were used in order to investigate the effect of the discharge propagation path on the efficiency of OH production. The efficiency of OH production was measured as a function of: the distance between the needle electrode and the water surface; the magnitude and polarity of HV energization; and the total delivered charge. The obtained results will help in optimization of non-thermal plasma systems for chemical and biological decontamination

Oxidation and bio-decontamination effects of impulsive discharges in atmospheric air

Chemical oxidation and the bactericidal capabilities of non-thermal plasma discharges can be used in different practical applications such as bio-decontamination, sterilisation of medical equipment, waste water treatment, syn-gas treatment and others. In this paper, the oxidation and bio-decontamination effects of impulsive plasma discharges which propagate across a liquid sample/air interface (surface discharges), and through the bulk of a liquid sample (direct discharges), have been investigated. The oxidising capability was analysed by measuring the degree of decolourisation of indigo carmine dye in water solutions. Gram-negative and Gram-positive bacteria, E. coli and S. aureus, respectively, were used as model microorganisms in the investigation of the biocidal effects of plasma discharges. Surface and direct plasma discharges were generated by high-voltage impulses of both polarities, with magnitudes of 20 kV, 24 kV and 28 kV, the chemical oxidation and bio-decontamination capabilities of such discharges have been obtained and analysed. It has been established that the defining factor in the chemical and biological effects of plasma discharges is the normalised delivered charge (dose). The results obtained in this study show that surface discharges have greater bio-decontamination capability as compared with direct transient plasma discharges. Also, it was shown that the decontamination rate of E.coli is more than double than that of S. aureus

Resistance gene enrichment sequencing (RenSeq) enables reannotation of the NB-LRR gene family from sequenced plant genomes and rapid mapping of resistance loci in segregating populations

RenSeq is a NB-LRR (nucleotide binding-site leucine-rich repeat) gene-targeted, Resistance gene enrichment and sequencing method that enables discovery and annotation of pathogen resistance gene family members in plant genome sequences. We successfully applied RenSeq to the sequenced potato Solanum tuberosum clone DM, and increased the number of identified NB-LRRs from 438 to 755. The majority of these identified R gene loci reside in poorly or previously unannotated regions of the genome. Sequence and positional details on the 12 chromosomes have been established for 704 NB-LRRs and can be accessed through a genome browser that we provide. We compared these NB-LRR genes and the corresponding oligonucleotide baits with the highest sequence similarity and demonstrated that ~80% sequence identity is sufficient for enrichment. Analysis of the sequenced tomato S. lycopersicum ‘Heinz 1706’ extended the NB-LRR complement to 394 loci. We further describe a methodology that applies RenSeq to rapidly identify molecular markers that co-segregate with a pathogen resistance trait of interest. In two independent segregating populations involving the wild Solanum species S. berthaultii (Rpi-ber2) and S. ruiz-ceballosii (Rpi-rzc1), we were able to apply RenSeq successfully to identify markers that co-segregate with resistance towards the late blight pathogen Phytophthora infestans. These SNP identification workflows were designed as easy-to-adapt Galaxy pipelines

The Intrinsic Origin of Spin Echoes in Dipolar Solids Generated by Strong Pi Pulses

In spectroscopy, it is conventional to treat pulses much stronger than the linewidth as delta-functions. In NMR, this assumption leads to the prediction that pi pulses do not refocus the dipolar coupling. However, NMR spin echo measurements in dipolar solids defy these conventional expectations when more than one pi pulse is used. Observed effects include a long tail in the CPMG echo train for short delays between pi pulses, an even-odd asymmetry in the echo amplitudes for long delays, an unusual fingerprint pattern for intermediate delays, and a strong sensitivity to pi-pulse phase. Experiments that set limits on possible extrinsic causes for the phenomena are reported. We find that the action of the system's internal Hamiltonian during any real pulse is sufficient to cause the effects. Exact numerical calculations, combined with average Hamiltonian theory, identify novel terms that are sensitive to parameters such as pulse phase, dipolar coupling, and system size. Visualization of the entire density matrix shows a unique flow of quantum coherence from non-observable to observable channels when applying repeated pi pulses.Comment: 24 pages, 27 figures. Revised from helpful referee comments. Added new Table IV, new paragraphs on pages 3 and 1

Transport poverty meets the digital divide : accessibility and connectivity in rural communities

Peer reviewedPublisher PD

Utilization of ambulatory physician encounters, emergency room visits, and hospitalizations by systemic lupus erythematosus patients: A 13-year population health study

Objective: To determine total physician encounters, emergency room (ER) visits and hospitalizations in an incident cohort of systemic lupus erythematosus (SLE) cases and matched control patients over 13 years. Methods: A retrospective cohort study was performed utilizing administrative health care data from approximately 1 million people with access to universal healthcare. Using ICD-9 and ICD-10 diagnostic codes, 7 SLE case definitions were used. Each case was matched by age and gender to 4 randomly selected controls. Data included physician billings, ER visits and hospital discharges over 13 years. Results: The number of incident SLE cases varied from 564 to 4,494 depending up the case definition. The mean age varied from 47.7 to 50.6 years and the proportion of females from 78.0 to 85.1%. SLE utilization of physicians was highest in the index year, declining significantly thereafter for all case definitions. By the fourth year, encounters with subspecialty physicians fell by 60% (Rheumatologists), 50% (Internal medicine) and 31% (other physicians). In contrast, visits to family physicians fell by only 9%. Visits to the ER and hospital admissions for SLE cases were also more frequent early in the disease and fell significantly over the study for both ER visits (all case definitions) and hospitalizations (2 of 7 case definitions). Conclusion: In SLE patients, health care utilization is highest in the first few years following the diagnosis which is also the time of maximal involvement by rheumatologists. Utilization declines over time and encounters with patient's family physicians predominate over other physician groups. This article is protected by copyright. All rights reserved

Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones

The emergence of mobile colistin resistance (mcr) threatens to undermine the clinical efficacy of the last antibiotic that can be used to treat serious infections caused by Gram-negative pathogens. Here we measure the fitness cost of a newly discovered MCR-3 using in vitro growth and competition assays. mcr-3 expression confers a lower fitness cost than mcr-1, as determined by competitive ability and cell viability. Consistent with these findings, plasmids carrying mcr-3 have higher stability than mcr-1 plasmids across a range of Escherichia coli strains. Crucially, mcr-3 plasmids can stably persist, even in the absence of colistin. Recent compensatory evolution has helped to offset the cost of mcr-3 expression, as demonstrated by the high fitness of mcr-3.5 as opposed to mcr-3.1. Reconstructing all of the possible evolutionary trajectories from mcr-3.1 to mcr-3.5 reveals a complex fitness landscape shaped by negative epistasis between compensatory and neutral mutations. Our findings highlight the importance of fitness costs and compensatory evolution in driving the dynamics and stability of mobile colistin resistance in bacterial populations, and they highlight the need to understand how processes (other than colistin use) impact mcr dynamics