Remote Monitoring of Sustained Low-Efficiency Dialysis (SLED) Machines in Intensive Care Unit

The Henry Ford Health System provides patients with a safe, improved system of continuous kidney replacement therapy using a proprietary, 24-hour sustained low-efficiency dialysis (SLED). The SLED system utilizes regional citrate anticoagulation (RCA) in conventional hemodialysis machines that have been configured to provide slow dialytic therapy. Within our hospital complex, SLED-RCA systems are deployed in intensive care units distributed over 4 floors in 2 buildings. This widespread footprint represents a spatial challenge for hemodialysis technicians. Fifteen SLED-RCA machines may be running at one time, and each deployed unit may signal an alarm for multiple reasons. Previously, audible alarms prompted intensive care unit nurses to identify the alarming machine and manually notify technicians by telephone. Technicians would then travel to resolve the alarm. To improve the process of addressing SLED-RCA machine alarms, we developed a remote alert alarm system that wirelessly notifies hemodialysis technicians of specific machine alarms. A quality improvement analysis of nearly 1,000 SLED-RCA alarms over a 1-week period revealed that the average time for alarm correction with a remote alert alarm system was approximately 5 minutes. Reducing alarm resolution time may free technicians and nurses for other critical duties

Detection of Hemodialysis Venous Needle Dislodgment Using Venous Access Pressure Measurements: A Simulation Study

BACKGROUND: In rare instances, hemodialysis venous needles may become dislodged, and when left undetected can lead to severe injury or death. Although dialysis machines have alarms to detect venous needle dislodgment, their range of detection is limited. An understanding of the clinical conditions that may lead to missed needle dislodgments is needed for development of more robust detection systems. METHODS: We created a sham dialysis circuit with a Fresenius 2008 K dialysis machine for in vitro simulation testing of machine alarm behavior under variable conditions. The circuit used a blood substitute and mimicked a patient\u27s venous access site. We varied blood flow rate, venous pressure, and upward drift in venous pressure and analyzed the time to alarm for the machine and an improved alarm algorithm. We also performed a cross-sectional retrospective study to identify the clinical occurrence of venous pressure upward drift between September 1, 2016, and November 1, 2016 in patients on hemodialysis with an arteriovenous fistula. RESULTS: Of 43,390 venous pressure readings for 147 patients on hemodialysis, 16,594 (38%) showed an upward drift in venous pressure (range 20-79 mmHg), with a mean ± SD increase of 11±18 mmHg within 20±14 minutes. A total of 19 venous needle dislodgment simulations under different venous pressure and blood flow parameters resulted in 19 (100%) algorithm alarm activations. Only 8 simulations (42%) activated a machine alarm, and machine alarm activation time was longer than the algorithm activation time for all 8 machine alarms (range 1-13 seconds). CONCLUSIONS: Patients can experience changes in venous pressure during hemodialysis which may not trigger a machine alarm in the case of a venous needle dislodgment. Our simulations showed that current dialysis machine alarm systems may not compensate for upward drift in venous pressure, and improved algorithms for detecting needle dislodgment during hemodialysis are needed

Bacillus anthracis genome organization in light of whole transcriptome sequencing

Emerging knowledge of whole prokaryotic transcriptomes could validate a number of theoretical concepts introduced in the early days of genomics. What are the rules connecting gene expression levels with sequence determinants such as quantitative scores of promoters and terminators? Are translation efficiency measures, e.g. codon adaptation index and RBS score related to gene expression? We used the whole transcriptome shotgun sequencing of a bacterial pathogen Bacillus anthracis to assess correlation of gene expression level with promoter, terminator and RBS scores, codon adaptation index, as well as with a new measure of gene translational efficiency, average translation speed. We compared computational predictions of operon topologies with the transcript borders inferred from RNA-Seq reads. Transcriptome mapping may also improve existing gene annotation. Upon assessment of accuracy of current annotation of protein-coding genes in the B. anthracis genome we have shown that the transcriptome data indicate existence of more than a hundred genes missing in the annotation though predicted by an ab initio gene finder. Interestingly, we observed that many pseudogenes possess not only a sequence with detectable coding potential but also promoters that maintain transcriptional activity

Egress of non-enveloped enteric RNA viruses

A long-standing paradigm in virology was that non-enveloped viruses induce cell lysis to release progeny virions. However, emerging evidence indicates that some non-enveloped viruses exit cells without inducing cell lysis, while others engage both lytic and non-lytic egress mechanisms. Enteric viruses are transmitted via the faecal-oral route and are important causes of a wide range of human infections, both gastrointestinal and extra-intestinal. Virus cellular egress, when fully understood, may be a relevant target for antiviral therapies, which could minimize the public health impact of these infections. In this review, we outline lytic and non-lytic cell egress mechanisms of non-enveloped enteric RNA viruses belonging to five families: Picornaviridae, Reoviridae, Caliciviridae, Astroviridae and Hepeviridae. We discuss factors that contribute to egress mechanisms and the relevance of these mechanisms to virion stability, infectivity and transmission. Since most data were obtained in traditional two-dimensional cell cultures, we will further attempt to place them into the context of polarized cultures and in vivo pathogenesis. Throughout the review, we highlight numerous knowledge gaps to stimulate future research into the egress mechanisms of these highly prevalent but largely understudied viruses

A Curriculum for Enhancing Physician Teaching Skills: The Value of Physician-Educator Partnerships

Developing as a physician requires an enormous amount of complex training, and quality of instruction greatly affects training outcomes. But while physicians are expected to teach trainees within the clinic, they often do not receive formal training in effective instructional practices. Providing faculty development programs is one way that institutions can help physicians develop teaching skills, but these programs often are developed without the input of educational specialists and not based in educational theory. In this methodology paper, we describe a 5-module curriculum that was developed in a cross-disciplinary collaboration between instructional designers and physician faculty. By merging educational and medical expertise and using adult learning theory with the Charlotte-Danielson educational framework, an essentials for clinical teaching educational endorsement program (ECTEEP) was created as a feature of the institutional curriculum within a large, urban teaching hospital. Here we describe how the program was developed through a physician-educator partnership, outline the program\u27s key content, and highlight essential aspects of successful implementation. The ECTEEP incorporates active learning approaches within an abbreviated format, distilling 5 critical aspects of effective teaching that are relevant to the clinical environment: cultural humility and safe learning environments, instruction practices for engaging learners, instruction and assessment strategies, receiving and giving feedback, and mentorship and coaching. A central feature of the program is that facilitators actively model the teaching behaviors they are conveying, which underscores the critical importance of facilitator preparation and skill. Our curriculum is offered here as a basic template for institutions that may want to establish a program for enhancing physician teaching skill

Regulation of Petrobactin and Bacillibactin Biosynthesis in Bacillus anthracis under Iron and Oxygen Variation

siderophore biosynthetic operons that are responsible for synthesis of petrobactin and bacillibactin, during variable growth conditions., a member of the bacillibactin biosynthetic operon, was only transcribed under conditions of iron-depletion, regardless of growth aeration.

Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape.

Human astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type and VA-type have been reported in humans. One limitation towards a better understanding of these viruses has been the lack of a physiologically relevant cell culture model that supports growth of all clades of HAstV. Herein, we demonstrate infection of HAstV strains belonging to all three clades in epithelium-only human intestinal enteroids (HIE) isolated from biopsy-derived intestinal crypts. A detailed investigation of infection of VA1, a member of the non-canonical HAstV-VA/HMO clade, showed robust replication in HIE derived from different patients and from different intestinal regions independent of the cellular differentiation status. Flow cytometry and immunofluorescence analysis revealed that VA1 infects several cell types, including intestinal progenitor cells and mature enterocytes, in HIE cultures. RNA profiling of VA1-infected HIE uncovered that the host response to infection is dominated by interferon (IFN)-mediated innate immune responses. A comparison of the antiviral host response in non-transformed HIE and transformed human colon carcinoma Caco-2 cells highlighted significant differences between these cells, including an increased magnitude of the response in HIE. Additional studies confirmed the sensitivity of VA1 to exogenous IFNs, and indicated that the endogenous IFN response of HIE to curtail the growth of strains from all three clades. Genotypic variation in the permissiveness of different HIE lines to HAstV could be overcome by pharmacologic inhibition of JAK/STAT signaling. Collectively, our data identify HIE as a universal infection model for HAstV and an improved model of the intestinal epithelium to investigate enteric virus-host interactions

Comparative Transcriptional Profiling of Bacillus cereus Sensu Lato Strains during Growth in CO2-Bicarbonate and Aerobic Atmospheres

Bacillus species are spore-forming bacteria that are ubiquitous in the environment and display a range of virulent and avirulent phenotypes. This range is particularly evident in the Bacillus cereus sensu lato group; where closely related strains cause anthrax, food-borne illnesses, and pneumonia, but can also be non-pathogenic. Although much of this phenotypic range can be attributed to the presence or absence of a few key virulence factors, there are other virulence-associated loci that are conserved throughout the B. cereus group, and we hypothesized that these genes may be regulated differently in pathogenic and non-pathogenic strains.Here we report transcriptional profiles of three closely related but phenotypically unique members of the Bacillus cereus group--a pneumonia-causing B. cereus strain (G9241), an attenuated strain of B. anthracis (Sterne 34F(2)), and an avirulent B. cereus strain (10987)--during exponential growth in two distinct atmospheric environments: 14% CO(2)/bicarbonate and ambient air. We show that the disease-causing Bacillus strains undergo more distinctive transcriptional changes between the two environments, and that the expression of plasmid-encoded virulence genes was increased exclusively in the CO(2) environment. We observed a core of conserved metabolic genes that were differentially expressed in all three strains in both conditions. Additionally, the expression profiles of putative virulence genes in G9241 suggest that this strain, unlike Bacillus anthracis, may regulate gene expression with both PlcR and AtxA transcriptional regulators, each acting in a different environment.We have shown that homologous and even identical genes within the genomes of three closely related members of the B. cereus sensu lato group are in some instances regulated very differently, and that these differences can have important implications for virulence. This study provides insights into the evolution of the B. cereus group, and highlights the importance of looking beyond differences in gene content in comparative genomics studies