Magneto-Driven Gradients of Diamagnetic Objects for Engineering Complex Tissues

Engineering complex tissues represents an extraordinary challenge and, to date, there have been few strategies developed that can easily recapitulate native‐like cell and biofactor gradients in 3D materials. This is true despite the fact that mimicry of these gradients may be essential for the functionality of engineered graft tissues. Here, a non‐traditional magnetics‐based approach is developed to predictably position naturally diamagnetic objects in 3D hydrogels. Rather than magnetizing the objects within the hydrogel, the magnetic susceptibility of the surrounding hydrogel precursor solution is enhanced. In this way, a range of diamagnetic objects (e.g., polystyrene beads, drug delivery microcapsules, and living cells) are patterned in response to a brief exposure to a magnetic field. Upon photo‐crosslinking the hydrogel precursor, object positioning is maintained, and the magnetic contrast agent diffuses out of the hydrogel, supporting long‐term construct viability. This approach is applied to engineer cartilage constructs with a depth‐dependent cellularity mirroring that of native tissue. These are thought to be the first results showing that magnetically unaltered cells can be magneto‐patterned in hydrogels and cultured to generate heterogeneous tissues. This work provides a foundation for the formation of opposing magnetic‐susceptibility‐based gradients within a single continuous material

Diagnostic accuracy of motor evoked potentials to detect neurological deficit during idiopathic scoliosis correction:a systematic review

OBJECTIVE The goal of this study was to evaluate the efficacy of intraoperative transcranial motor evoked potential (TcMEP) monitoring in predicting an impending neurological deficit during corrective spinal surgery for patients with idiopathic scoliosis (IS). METHODS The authors searched the PubMed and Web of Science database for relevant lists of retrieved reports and/or experiments published from January 1950 through October 2014 for studies on TcMEP monitoring use during IS surgery. The primary analysis of this review fit the operating characteristic into a hierarchical summary receiver operating characteristic curve model to determine the efficacy of intraoperative TcMEP-predicted change. RESULTS Twelve studies, with a total of 2102 patients with IS were included. Analysis found an observed incidence of neurological deficits of 1.38% (29/2102) in the sample population. Of the patients who sustained a neurological deficit, 82.8% (24/29) also had irreversible TcMEP change, whereas 17.2% (5/29) did not. The pooled analysis using the bivariate model showed TcMEP change with sensitivity (mean 91% [95% CI 34%-100%]) and specificity (mean 96% [95% CI 92-98%]). The diagnostic odds ratio indicated that it is 250 times more likely to observe significant TcMEP changes in patients who experience a new-onset motor deficit immediately after IS correction surgery (95% CI 11-5767). TcMEP monitoring showed high discriminant ability with an area under the curve of 0.98. CONCLUSIONS A patient with a new neurological deficit resulting from IS surgery was 250 times more likely to have changes in TcMEPs than a patient without new deficit. The authors' findings from 2102 operations in patients with IS show that TcMEP monitoring is a highly sensitive and specific test for detecting new spinal cord injuries in patients undergoing corrective spinal surgery for IS. They could not assess the value of TcMEP monitoring as a therapeutic adjunct owing to the limited data available and their study design

Strategies to Reduce Non-Ventilator-Associated Hospital-Acquired Pneumonia: A Systematic Review

Background Point prevalence studies identify that pneumonia is the most common healthcare associated infection. However, non-ventilator associated healthcare associated pneumonia (NV-HAP) is both underreported and understudied. Most research conducted to date, focuses on ventilator associated pneumonia. We conducted a systematic review, to provide the latest evidence for strategies to reduce NV-HAP and describe the methodological approaches used. Methods We performed a systematic search to identify research exploring and evaluating NV-HAP preventive measures in hospitals and aged-care facilities. The electronic database Medline was searched, for peer-reviewed articles published between 1st January 1998 and 31st August 2018. An assessment of the study quality and risk of bias of included articles was conducted using the Newcastle–Ottawa Scale. Results The literature search yielded 1551 articles, with 15 articles meeting the inclusion criteria. The majority of strategies for NV-HAP prevention focussed on oral care (n = 9). Three studies evaluated a form of physical activity, such as passive movements, two studies used dysphagia screening and management; and another study evaluated prophylactic antibiotics. Most studies (n = 12) were conducted in a hospital setting. Six of the fifteen studies were randomised controlled trials. Conclusion There was considerable heterogeneity in the included studies, including the type of intervention, study design, methods and definitions used to diagnose the NV-HAP. To date, interventions to reduce NV-HAP appear to be based broadly on the themes of improving oral care, increased mobility or movement and dysphagia management

High-Quality Draft Genome Sequence of Desulfovibrio carbinoliphilus FW-101-2B, an Organic Acid-Oxidizing Sulfate-Reducing Bacterium Isolated from Uranium(VI)-Contaminated Groundwater.

Desulfovibrio carbinoliphilus subsp. oakridgensis FW-101-2B is an anaerobic, organic acid/alcohol-oxidizing, sulfate-reducing δ-proteobacterium. FW-101-2B was isolated from contaminated groundwater at The Field Research Center at Oak Ridge National Lab after in situ stimulation for heavy metal-reducing conditions. The genome will help elucidate the metabolic potential of sulfate-reducing bacteria during uranium reduction

Reducing urinary catheter use: a protocol for a mixed methods evaluation of an electronic reminder system in hospitalised patients in Australia

Introduction Despite advances in infection prevention and control, catheter-associated urinary tract infections (CAUTIs) are common and remain problematic. Prolonged urinary catheterisation is the main risk factor for development of CAUTIs; hence, interventions that target early catheter removal warrant investigation. The study’s objectives are to examine the efficacy of an electronic reminder system, the CATH TAG, in reducing urinary catheter use (device utilisation ratio) and to determine the effect of the CATH TAG on nurses’ ability to deliver patient care.Methods and analysis This study uses a mixed methods approach in which both quantitative and qualitative data will be collected. A stepped wedge randomised controlled design in which wards provide before and after observations will be undertaken in one large Australian hospital over 24 weeks. The intervention is the use of the CATH TAG. Eligible hospital wards will receive the intervention and act as their own control, with analysis undertaken of the change within each ward using data collected in control and intervention periods. An online survey will be administered to nurses on study completion, and a focus group for nurses will be conducted 2 months after study completion. The primary outcomes are the urinary catheter device utilisation ratio and perceptions of nurses about ease of use of the CATH TAG. Secondary outcomes include a reduced number of cases of catheter-associated asymptomatic bacteriuria, a reduced number of urinary catheters inserted per 100 patient admissions, perceptions of nurses regarding effectiveness of the CATH TAG, changes in ownership/interest by patients in catheter management, as well as possible barriers to successful implementation of the CATH TAG.Ethics and dissemination Approval has been obtained from the Human Research Ethics Committees of Avondale College of Higher Education (2017:15) and Queensland Health (HREC17QTHS19). Results will be disseminated via peer-reviewed journals and conference presentations

Particlization in hybrid models

In hybrid models, which combine hydrodynamical and transport approaches to describe different stages of heavy-ion collisions, conversion of fluid to individual particles, particlization, is a non-trivial technical problem. We describe in detail how to find the particlization hypersurface in a 3+1 dimensional model, and how to sample the particle distributions evaluated using the Cooper-Frye procedure to create an ensemble of particles as an initial state for the transport stage. We also discuss the role and magnitude of the negative contributions in the Cooper-Frye procedure.Comment: 18 pages, 28 figures, EPJA: Topical issue on "Relativistic Hydro- and Thermodynamics"; version accepted for publication, typos and error in Eq.(1) corrected, the purpose of sampling and change from UrQMD to fluid clarified, added discussion why attempts to cancel negative contributions of Cooper-Frye are not applicable her

Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants

Cys2-His2 zinc finger proteins (ZFPs) are the largest group of transcription factors in higher metazoans. A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes. As a first step in this process, we have characterized the DNA-binding specificities of 129 zinc finger sets from Drosophila using a bacterial one-hybrid system. This data set contains the DNA-binding specificities for at least one encoded ZFP from 70 unique genes and 23 alternate splice isoforms representing the largest set of characterized ZFPs from any organism described to date. These recognition motifs can be used to predict genomic binding sites for these factors within the fruit fly genome. Subsets of fingers from these ZFPs were characterized to define their orientation and register on their recognition sequences, thereby allowing us to define the recognition diversity within this finger set. We find that the characterized fingers can specify 47 of the 64 possible DNA triplets. To confirm the utility of our finger recognition models, we employed subsets of Drosophila fingers in combination with an existing archive of artificial zinc finger modules to create ZFPs with novel DNA-binding specificity. These hybrids of natural and artificial fingers can be used to create functional zinc finger nucleases for editing vertebrate genomes

APOL1 Kidney-Risk Variants Induce Mitochondrial Fission

IntroductionAPOL1 G1 and G2 nephropathy-risk variants cause mitochondrial dysfunction and contribute to kidney disease. Analyses were performed to determine the genetic regulation of APOL1 and elucidate potential mechanisms in APOL1-nephropathy.MethodsA global gene expression analysis was performed in human primary renal tubule cell lines derived from 50 African American individuals. Follow-up gene knock out, cell-based rescue, and microscopy experiments were performed.ResultsAPOL1 genotypes did not alter APOL1 expression levels in the global gene expression analysis. Expression quantitative trait locus (eQTL) analysis in polyinosinic-polycytidylic acid (poly IC)-stimulated renal tubule cells revealed that single nucleotide polymorphism (SNP) rs513349 adjacent to BAK1 was a trans eQTL for APOL1 and a cis eQTL for BAK1; APOL1 and BAK1 were co-expressed in cells. BAK1 knockout in a human podocyte cell line resulted in diminished APOL1 protein, supporting a pivotal effect for BAK1 on APOL1 expression. Because BAK1 is involved in mitochondrial dynamics, mitochondrial morphology was examined in primary renal tubule cells and HEK293 Tet-on cells of various APOL1 genotypes. Mitochondria in APOL1 wild-type (G0G0) tubule cells maintained elongated morphology when stimulated by low-dose poly IC, whereas those with G1G1, G2G2, and G1G2 genotypes appeared to fragment. HEK293 Tet-on cells overexpressing APOL1 G0, G1, and G2 were created; G0 cells appeared to promote mitochondrial fusion, whereas G1 and G2 induced mitochondrial fission. The mitochondrial dynamic regulator Mdivi-1 significantly preserved cell viability and mitochondrial cristae structure and reversed mitochondrial fission induced by overexpression of G1 and G2.ConclusionResults suggest the mitochondrial fusion/fission pathway may be a therapeutic target in APOL1-nephropathy

Tumor immune infiltration estimated from gene expression profiles predicts colorectal cancer relapse

A substantial fraction of patients with stage I-III colorectal adenocarcinoma (CRC) experience disease relapse after surgery with curative intent. However, biomarkers for predicting the likelihood of CRC relapse have not been fully explored. Therefore, we assessed the association between tumor infiltration by a broad array of innate and adaptive immune cell types and CRC relapse risk. We implemented a discovery-validation design including a discovery dataset from Moffitt Cancer Center (MCC; Tampa, FL) and three independent validation datasets: (1) GSE41258 (2) the Molecular Epidemiology of Colorectal Cancer (MECC) study, and (3) GSE39582. Infiltration by 22 immune cell types was inferred from tumor gene expression data, and the association between immune infiltration by each cell type and relapse-free survival was assessed using Cox proportional hazards regression. Within each of the four independent cohorts, CD4+ memory activated T cell (HR: 0.93, 95% CI: 0.90-0.96; FDR = 0.0001) infiltration was associated with longer time to disease relapse, independent of stage, microsatellite instability, and adjuvant therapy. Based on our meta-analysis across the four datasets, 10 innate and adaptive immune cell types associated with disease relapse of which 2 were internally validated using multiplex immunofluorescence. Moreover, immune cell type infiltration was a better predictors of disease relapse than Consensus Molecular Subtype (CMS) and other expression-based biomarkers (Immune-AICMCC:238.1-238.9; CMS-AICMCC: 241.0). These data suggest that transcriptome-derived immune profiles are prognostic indicators of CRC relapse and quantification of both innate and adaptive immune cell types may serve as candidate biomarkers for predicting prognosis and guiding frequency and modality of disease surveillance