Co-production and adaptation of a prison-based problem-solving workbook to support the mental health of patients housed within a medium- and low-secure forensic service.

INTRODUCTION: Problem-solving skills (PSS) help to provide a systematic approach to dealing with and managing complex problems. The overall aim of this study was to assess the acceptability and feasibility of developing and adapting a prison-based PSS  workbook for adults within a medium- and low-secure hospital. METHOD: We used the Medical Research Council framework in our participatory mixed methods study incorporating an adapted survey (to identify what types of problems people experience in secure hospitals), a series of three interactive workshops (to co-produce two case study examples for a workbook) and we gathered feedback from patients and hospital staff on the acceptability and feasibility of the workbook. Data from the survey were used to inform the case study examples, and the feedback from patients and hospital staff was descriptively summarised and the results consolidated. RESULTS: In total, 82 (51%) patients took part in the survey; 22 patients and 49 hospital staff provided feedback on the workbook. The survey results indicated that patients regularly experience problems while in the hospital. Patients reported problems relating to restrictions of freedom and boredom. The workshops produced two case studies for the workbooks, with mainly positive patient and staff feedback. More work is required to improve the visual representation of the characters in the case studies, the amount and content of the language and the mechanism of the intervention delivery. CONCLUSION: The adaptation process proved acceptable and feasible to both patients and staff. The co-production methodology for the workbook and feedback from patients and staff was an effective way of iteratively refining the materials to ensure that they were both meaningful and acceptable to staff and patients. Subsequent work is required to develop the workbook and evaluate the feasibility of the intervention delivery, recruitment rates, uptake and adherence to the PSS using a randomised controlled trial. PATIENT OR PUBLIC CONTRIBUTION: At each stage of the project consultation with patients and/or hospital staff was involved.

An examination of the effects of nucleus accumbens core nociceptin on appetitive and consummatory motivation for food.

The nucleus accumbens (NAc) is a critical region for regulating the appetitive and consummatory aspects of motivated behavior. Previous work has shown differential effects of NAc µ-, δ-, and κ- receptor stimulation on food intake and for shifting motivation within an effort-based choice (EBC) task. However, the motivational role of the nociceptin opioid peptide (NOP) receptor, a fourth member of the opioid receptor family, is less well understood. These experiments therefore characterized the effect of NAc injections of nociceptin, the endogenous ligand for the NOP receptor, on consummatory and appetitive motivation. Three groups of male Sprague-Dawley rats received nociceptin injections into the NAc core prior to testing in a progressive ratio lever pressing task, an EBC task, or a palatable feeding assay. In the feeding experiment, 10 nmol of nociceptin increased consumption in the first 30 min, but this increase was not sustained through the end of the 2-hr session. Additionally, nociceptin injections did not alter breakpoint in the progressive ratio task. However, in the EBC task, nociceptin significantly decreased breakpoint for sugar pellets without affecting consumption of rat chow. These data suggest that NAc NOP receptor stimulation transiently increases consummatory motivation toward palatable diets and inhibits appetitive motivation when alternate food options are freely available. This pattern of effects contrasts with those obtained following NAc stimulation of other opioid receptors, suggesting that the four opioid receptor classes each serve unique roles in modulating food-directed motivation within the NAc core.

CHD7 and SOX2 act in a common gene regulatory network during mammalian semicircular canal and cochlear development.

Inner ear morphogenesis requires tightly regulated epigenetic and transcriptional control of gene expression. CHD7, an ATP-dependent chromodomain helicase DNA-binding protein, and SOX2, an SRY-related HMG box pioneer transcription factor, are known to contribute to vestibular and auditory system development, but their genetic interactions in the ear have not been explored. Here, we analyzed inner ear development and the transcriptional regulatory landscapes in mice with variable dosages of Chd7 and/or Sox2. We show that combined haploinsufficiency for Chd7 and Sox2 results in reduced otic cell proliferation, severe malformations of semicircular canals, and shortened cochleae with ectopic hair cells. Examination of mice with conditional, inducible Chd7 loss by Sox2CreER reveals a critical period (~E9.5) of susceptibility in the inner ear to combined Chd7 and Sox2 loss. Data from genome-wide RNA-sequencing and CUT&Tag studies in the otocyst show that CHD7 regulates Sox2 expression and acts early in a gene regulatory network to control expression of key otic patterning genes, including Pax2 and Otx2. CHD7 and SOX2 directly bind independently and cooperatively at transcription start sites and enhancers to regulate otic progenitor cell gene expression. Together, our findings reveal essential roles for Chd7 and Sox2 in early inner ear development and may be applicable for syndromic and other forms of hearing or balance disorders.

Targeting BAM for Novel Therapeutics against Pathogenic Gram-Negative Bacteria.

The growing emergence of multidrug resistance in bacterial pathogens is an immediate threat to human health worldwide. Unfortunately, there has not been a matching increase in the discovery of new antibiotics to combat this alarming trend. Novel contemporary approaches aimed at antibiotic discovery against Gram-negative bacterial pathogens have expanded focus to also include essential surface-exposed receptors and protein complexes, which have classically been targeted for vaccine development. One surface-exposed protein complex that has gained recent attention is the ß-barrel assembly machinery (BAM), which is conserved and essential across all Gram-negative bacteria. BAM is responsible for the biogenesis of ß-barrel outer membrane proteins (ß-OMPs) into the outer membrane. These ß-OMPs serve essential roles for the cell including nutrient uptake, signaling, and adhesion, but can also serve as virulence factors mediating pathogenesis. The mechanism for how BAM mediates ß-OMP biogenesis is known to be dynamic and complex, offering multiple modes for inhibition by small molecules and targeting by larger biologics. In this review, we introduce BAM and establish why it is a promising and exciting new therapeutic target and present recent studies reporting novel compounds and vaccines targeting BAM across various bacteria. These reports have fueled ongoing and future research on BAM and have boosted interest in BAM for its therapeutic promise in combatting multidrug resistance in Gram-negative bacterial pathogens.

Specific Deoxyceramide Species Correlate with Expression of Macular Telangiectasia Type 2 (MacTel2) in a SPTLC2 Carrier HSAN1 Family.

Hereditary sensory and autonomic neuropathy type 1 (HSAN1/HSN1) is a peripheral neuropathy most commonly associated with pathogenic variants in the serine palmitoyltransferase complex (SPTLC1, SPTLC2) genes, which are responsible for sphingolipid biosynthesis. Recent reports have shown that some HSAN1 patients also develop macular telangiectasia type 2 (MacTel2), a retinal neurodegeneration with an enigmatic pathogenesis and complex heritability. Here, we report a novel association of a SPTLC2 c.529A>G p.(Asn177Asp) variant with MacTel2 in a single member of a family that otherwise has multiple members afflicted with HSAN1. We provide correlative data to suggest that the variable penetrance of the HSAN1/MacTel2-overlap phenotype in the proband may be explained by levels of certain deoxyceramide species, which are aberrant intermediates of sphingolipid metabolism. We provide detailed retinal imaging of the proband and his HSAN1+/MacTel2- brothers and suggest mechanisms by which deoxyceramide levels may induce retinal degeneration. This is the first report of HSAN1 vs. HSAN1/MacTel2 overlap patients to comprehensively profile sphingolipid intermediates. The biochemical data here may help shed light on the pathoetiology and molecular mechanisms of MacTel2.

A feasibility evaluation of Discovery Group: determining the acceptability and potential outcomes of a patient-led research group in a secure mental health inpatient setting.

BACKGROUND: Patient and public involvement and engagement (PPIE) is recognised as an essential part of health research. In addition to providing an opportunity for patients to shape health research and acquire research skills, in the inpatient mental health setting, PPIE may have additional value in providing meaningful activity and enhancing recovery, as defined using connectedness, hope, identity, meaning and empowerment (CHIME) principles. However, there have been challenges in applying PPIE principles in secure mental health inpatient settings. An eight -session PPIE programme ("Discovery Group") was designed to support patient-led research in a secure mental health hospital. This feasibility study aims to evaluate the acceptability of the programme from the perspective of patients and identify potential outcomes. METHODS: A retrospective single-arm post-programme evaluation of Discovery Group was undertaken. Participants attended an evaluation workshop where they were interviewed individually to complete an acceptability questionnaire designed using the domains of the Theoretical Framework of Acceptability. Participants also completed an outcomes questionnaire, which included CHIME-based recovery items, and were invited to share their ideas for programme improvement on posters. Quantitative data were analysed descriptively. Direct content analysis was applied to qualitative data. RESULTS: In our sample, eight participants attended at least one session of the discovery group with one patient attending all sessions. Most of the participants felt positive about taking part in the group and expressed interest in joining another group in future. All participants experienced some burden from the effort required during group sessions, but a low level of opportunity cost in terms of the extent to which they perceived they had to forfeit benefits to participate in the programme.. Some described the group as effective in helping them learn about research. Of the five CHIME recovery domains, only connectedness was reported as a benefit of the group. The participants valued the opportunity to use their time well and demonstrate that they were undertaking purposeful activity as part of their rehabilitation and recovery. CONCLUSIONS: Discovery Group is a tool to overcome barriers to effective PPIE in research in a secure inpatient mental health setting. The programme has a high level of acceptability among participants and offered several potential outcomes which require testing through further study.

Patients make an important contribution to research. However, it can be hard for patients in a secure mental health hospital to be involved in doing research. So we designed a programme called Discovery Group to give patients a chance to learn about research by doing it themselves with support. Then we did this study to answer three questions: 1. Did patients find Discovery Group acceptable? 2. What are the benefits of Discovery Group? 3. How can it be improved? Each patient completed two questionnaires about their experiences of Discovery Group. The first questionnaire asked about their level of satisfaction and how acceptable they found it. The second questionnaire asked about the benefits of Discovery Group. Patients also gave ideas for improving Discovery Group.Overall, the patients found Discovery Group acceptable and worthwhile. They would all recommend it to other patients. However, they felt that had to put in quite a bit of effort. Patients learned about research and felt valued as fellow researchers. Discovery Group also helped them feel more confident and connected but did not help them feel more hopeful or empowered. Patients suggested using the computer during Discovery Group for a better experience.The study showed that Discovery Group allows patients in a secure mental health hospital to be involved in research in an easy and acceptable way. There may be benefits for patients who join Discovery Group. We hope to improve Discovery Group and see if it can offer more benefits for more patients.

Experimental iron amendment suppresses toxic cyanobacteria in a hypereutrophic lake.

The effects of reducing nutrient inputs to lakes and reservoirs are often delayed by hysteresis resulting from internal phosphorus (P) loading from sediments. Consequently, controlling harmful algal blooms (HABs) in many eutrophic ecosystems requires additional management to improve water quality. We manipulated iron (Fe) concentrations in a hypereutrophic lake to determine if Fe amendment would suppress HABs by inhibiting P release from sediments. Our experiment consisted of 15 in situ mesocosms, 12 of which each received a different dose of Fe (ranging from 2 to 225 g/m2 ); the remaining three were unmanipulated to serve as controls. Iron amendment decreased P accumulation in porewaters and the flux of P from sediments, which significantly lowered P concentrations in the water column. Iron exerted significant dose-dependent negative effects on the biomass of phytoplankton and periphyton, and reduced the dominance of cyanobacteria. Even at the lowest doses, Fe appeared to reduce the toxicity of cyanobacterial blooms, as measured by concentrations of hepatotoxic microcystins. Overall, our findings highlight the potential for Fe treatment as an effective strategy for minimizing HABs in eutrophic lakes and reservoirs. More broadly, our study reinforces the importance of Fe in regulating the trophic state of freshwaters, and the sensitivity of certain ecosystems to changes in Fe supply. Finally, we hypothesize that decreases in natural Fe supplies to lakes associated with anthropogenic activities may worsen outbreaks of toxic cyanobacteria.

A Phase I cardiac safety and pharmacokinetic study of tivozanib hydrochloride in patients with advanced solid tumors.

Tivozanib hydrochloride (tivozanib) is a potent, selective tyrosine kinase inhibitor of all three vascular endothelial growth factor receptors, with a long half-life. Tivozanib's effects on the QTc interval in patients with advanced solid tumors were assessed. Patients received 1.5 mg of tivozanib orally, once daily, for 21 days. Safety evaluations, serial blood samples for pharmacokinetic measurements, and time-matched, triplicate, 12-lead electrocardiograms (ECG) were collected. Fifty patients were evaluable. The maximum change in QTcF was 9.3 milliseconds (90% confidence interval [CI] 5-13.6), occurring 2.5 hours after dosing on Day 21. The central tendency change across all time points was +2.2 milliseconds. The slope of the exposure-ΔQTcF relationship was 0.08464 ms/ng/mL, with a predicted QTcF change of 8.27 milliseconds at the average tivozanib Tmax of 118.1 ng/mL (upper CI 12.6 milliseconds). There were no QTcF values >500 milliseconds or significant changes from baseline observed in heart rate, PR interval, and QRS complex. These data, evaluated along with other tivozanib preclinical and clinical study results, suggest that administration of 1.5 mg tivozanib for 21 days has a minimal effect on cardiac repolarization or ECG morphology in oncology subjects.

Developing low-literacy health education materials for women.

Research has consistently shown that people absorb information significantly better when written information is provided in conjunction with verbal explanations. Despite this, studies also show that many written health education materials do not have readability levels that are appropriate for women who have low literacy skills. This article summarizes the process and essential considerations, such as content of the material, readability, layout, design, culture, language, and medium of delivery in the development of low-literacy health education materials.

Understanding the management of electronic test result notifications in the outpatient setting.

BACKGROUND: Notifying clinicians about abnormal test results through electronic health record (EHR) -based "alert" notifications may not always lead to timely follow-up of patients. We sought to understand barriers, facilitators, and potential interventions for safe and effective management of abnormal test result delivery via electronic alerts. METHODS: We conducted a qualitative study consisting of six 6-8 member focus groups (N = 44) at two large, geographically dispersed Veterans Affairs facilities. Participants included full-time primary care providers, and personnel representing diagnostic services (radiology, laboratory) and information technology. We asked participants to discuss barriers, facilitators, and suggestions for improving timely management and follow-up of abnormal test result notifications and encouraged them to consider technological issues, as well as broader, human-factor-related aspects of EHR use such as organizational, personnel, and workflow. RESULTS: Providers reported receiving a large number of alerts containing information unrelated to abnormal test results, many of which were believed to be unnecessary. Some providers also reported lacking proficiency in use of certain EHR features that would enable them to manage alerts more efficiently. Suggestions for improvement included improving display and tracking processes for critical alerts in the EHR, redesigning clinical workflow, and streamlining policies and procedures related to test result notification. CONCLUSION: Providers perceive several challenges for fail-safe electronic communication and tracking of abnormal test results. A multi-dimensional approach that addresses technology as well as the many non-technological factors we elicited is essential to design interventions to reduce missed test results in EHRs.

Errors of diagnosis in pediatric practice: a multisite survey.

OBJECTIVE: We surveyed pediatricians to elicit their perceptions regarding frequency, contributing factors, and potential system- and provider-based solutions to address diagnostic errors. METHODS: Academic, community, and trainee pediatricians (N = 1362) at 3 tertiary care institutions and 109 affiliated clinics were invited to complete the survey anonymously through an Internet survey administration service between November 2008 and May 2009. RESULTS: The overall response rate was 53% (N = 726). More than one-half (54%) of respondents reported that they made a diagnostic error at least once or twice per month; this frequency was markedly higher (77%) among trainees. Almost one-half (45%) of respondents reported diagnostic errors that harmed patients at least once or twice per year. Failure to gather information through history, physical examination, or chart review was the most-commonly reported process breakdown, whereas inadequate care coordination and teamwork was the most-commonly reported system factor. Viral illnesses being diagnosed as bacterial illnesses was the most-commonly reported diagnostic error, followed by misdiagnosis of medication side effects, psychiatric disorders, and appendicitis. Physicians ranked access to electronic health records and close follow-up of patients as strategies most likely to be effective in preventing diagnostic errors. CONCLUSION: Pediatricians reported making diagnostic errors relatively frequently, and patient harm from these errors was not uncommon.

Notification of abnormal lab test results in an electronic medical record: do any safety concerns remain?

BACKGROUND: Follow-up of abnormal outpatient laboratory test results is a major patient safety concern. Electronic medical records can potentially address this concern through automated notification. We examined whether automated notifications of abnormal laboratory results (alerts) in an integrated electronic medical record resulted in timely follow-up actions. METHODS: We studied 4 alerts: hemoglobin A1c > or =15%, positive hepatitis C antibody, prostate-specific antigen > or =15 ng/mL, and thyroid-stimulating hormone > or =15 mIU/L. An alert tracking system determined whether the alert was acknowledged (ie, provider clicked on and opened the message) within 2 weeks of transmission; acknowledged alerts were considered read. Within 30 days of result transmission, record review and provider contact determined follow-up actions (eg, patient contact, treatment). Multivariable logistic regression models analyzed predictors for lack of timely follow-up. RESULTS: Between May and December 2008, 78,158 tests (hemoglobin A1c, hepatitis C antibody, thyroid-stimulating hormone, and prostate-specific antigen) were performed, of which 1163 (1.48%) were transmitted as alerts; 10.2% of these (119/1163) were unacknowledged. Timely follow-up was lacking in 79 (6.8%), and was statistically not different for acknowledged and unacknowledged alerts (6.4% vs 10.1%; P =.13). Of 1163 alerts, 202 (17.4%) arose from unnecessarily ordered (redundant) tests. Alerts for a new versus known diagnosis were more likely to lack timely follow-up (odds ratio 7.35; 95% confidence interval, 4.16-12.97), whereas alerts related to redundant tests were less likely to lack timely follow-up (odds ratio 0.24; 95% confidence interval, 0.07-0.84). CONCLUSIONS: Safety concerns related to timely patient follow-up remain despite automated notification of non-life-threatening abnormal laboratory results in the outpatient setting.

Improving follow-up of abnormal cancer screens using electronic health records: trust but verify test result communication.

BACKGROUND: Early detection of colorectal cancer through timely follow-up of positive Fecal Occult Blood Tests (FOBTs) remains a challenge. In our previous work, we found 40% of positive FOBT results eligible for colonoscopy had no documented response by a treating clinician at two weeks despite procedures for electronic result notification. We determined if technical and/or workflow-related aspects of automated communication in the electronic health record could lead to the lack of response. METHODS: Using both qualitative and quantitative methods, we evaluated positive FOBT communication in the electronic health record of a large, urban facility between May 2008 and March 2009. We identified the source of test result communication breakdown, and developed an intervention to fix the problem. Explicit medical record reviews measured timely follow-up (defined as response within 30 days of positive FOBT) pre- and post-intervention. RESULTS: Data from 11 interviews and tracking information from 490 FOBT alerts revealed that the software intended to alert primary care practitioners (PCPs) of positive FOBT results was not configured correctly and over a third of positive FOBTs were not transmitted to PCPs. Upon correction of the technical problem, lack of timely follow-up decreased immediately from 29.9% to 5.4% (p<0.01) and was sustained at month 4 following the intervention. CONCLUSION: Electronic communication of positive FOBT results should be monitored to avoid limiting colorectal cancer screening benefits. Robust quality assurance and oversight systems are needed to achieve this. Our methods may be useful for others seeking to improve follow-up of FOBTs in their systems.

Improving outpatient safety through effective electronic communication: a study protocol.

BACKGROUND: Health information technology and electronic medical records (EMRs) are potentially powerful systems-based interventions to facilitate diagnosis and treatment because they ensure the delivery of key new findings and other health related information to the practitioner. However, effective communication involves more than just information transfer; despite a state of the art EMR system, communication breakdowns can still occur. [1-3] In this project, we will adapt a model developed by the Systems Engineering Initiative for Patient Safety (SEIPS) to understand and improve the relationship between work systems and processes of care involved with electronic communication in EMRs. We plan to study three communication activities in the Veterans Health Administration's (VA) EMR: electronic communication of abnormal imaging and laboratory test results via automated notifications (i.e., alerts); electronic referral requests; and provider-to-pharmacy communication via computerized provider order entry (CPOE). AIM: Our specific aim is to propose a protocol to evaluate the systems and processes affecting outcomes of electronic communication in the computerized patient record system (related to diagnostic test results, electronic referral requests, and CPOE prescriptions) using a human factors engineering approach, and hence guide the development of interventions for work system redesign. DESIGN: This research will consist of multiple qualitative methods of task analysis to identify potential sources of error related to diagnostic test result alerts, electronic referral requests, and CPOE; this will be followed by a series of focus groups to identify barriers, facilitators, and suggestions for improving the electronic communication system. Transcripts from all task analyses and focus groups will be analyzed using methods adapted from grounded theory and content analysis.

Genome sequences of three agrobacterium biovars help elucidate the evolution of multichromosome genomes in bacteria.

The family Rhizobiaceae contains plant-associated bacteria with critical roles in ecology and agriculture. Within this family, many Rhizobium and Sinorhizobium strains are nitrogen-fixing plant mutualists, while many strains designated as Agrobacterium are plant pathogens. These contrasting lifestyles are primarily dependent on the transmissible plasmids each strain harbors. Members of the Rhizobiaceae also have diverse genome architectures that include single chromosomes, multiple chromosomes, and plasmids of various sizes. Agrobacterium strains have been divided into three biovars, based on physiological and biochemical properties. The genome of a biovar I strain, A. tumefaciens C58, has been previously sequenced. In this study, the genomes of the biovar II strain A. radiobacter K84, a commercially available biological control strain that inhibits certain pathogenic agrobacteria, and the biovar III strain A. vitis S4, a narrow-host-range strain that infects grapes and invokes a hypersensitive response on nonhost plants, were fully sequenced and annotated. Comparison with other sequenced members of the Alphaproteobacteria provides new data on the evolution of multipartite bacterial genomes. Primary chromosomes show extensive conservation of both gene content and order. In contrast, secondary chromosomes share smaller percentages of genes, and conserved gene order is restricted to short blocks. We propose that secondary chromosomes originated from an ancestral plasmid to which genes have been transferred from a progenitor primary chromosome. Similar patterns are observed in select Beta- and Gammaproteobacteria species. Together, these results define the evolution of chromosome architecture and gene content among the Rhizobiaceae and support a generalized mechanism for second-chromosome formation among bacteria.

A model of lysosomal metabolism of dextran coated superparamagnetic iron oxide (SPIO) nanoparticles: implications for cellular magnetic resonance imaging.

Ferumoxides, dextran-coated superparamagnetic iron oxide (SPIO) particles, form ferumoxide-transfection agent (FE-TA) complexes that are internalized into endosomes/lysosomes and have been used to label cells for in vivo MRI tracking and localization studies. A better understanding of the physical state of the FE-TA complexes during endocytosis could improve their use. The purpose of this study was to measure the rate of the degradation of iron particles under varying physiological conditions. FE-TA complexes were incubated in seven different buffers containing different chelates with different pH. Reducible iron concentrations, T2 relaxation rates and gradient echo (GRE) magnetic resonance images (MRI) were obtained from each condition immediately after incubation and at 6, 24, 48, 72 and 96 h and days 7, 14 and 21. The dynamics of FE-TA in the endosome/lysosomes within the cells were visualized with electron microscopy. Sodium citrate buffer at pH 4.5 rapidly dissolved FE-TA complexes. However, FE-TA complexes were less soluble in the same buffer at pH 5.5. Similarly, FE-TA complexes were not readily soluble in any of the other buffers with or without chelates, regardless of pH. Electron microscopic images showed degraded FE-TA in some intracellular endosome/lysosomes between days 3 and 5. In the cellular environment, some of the FE-TA-containing endosomes were found to fuse with lysosomes, causing rapid dissociation at low pH and exposing the iron core to chelates that resulted in soluble Fe(III) within the lysosomes. The studies presented represent a first step in identifying the important cellular environmental parameters affecting the integrity of FE-TA complexes.

Effect of human stem cells labeled with ferumoxides-poly-L-lysine on hematologic and biochemical measurements in rats.

PURPOSE: To determine whether ferumoxides-poly-l-lysine (PLL) complex-labeled mesenchymal stem cells (MSCs) or ferumoxides-PLL complex alone alters hematologic, blood chemistry, renal function, and/or liver function measurements after being intravenously infused into rats. MATERIALS AND METHODS: Twenty-five rats (group 1) received intravenous injections of labeled MSCs, and 25 additional rats (group 2) received intravenous injections of ferumoxides-PLL complex only. Complete blood counts, liver and renal function test results, and serum electrolyte and iron concentrations were measured for 42 days after the injections and compared with those measured in five control rats (group 3). To determine the duration of labeled MSCs in the circulation, venous blood was serially drawn from five additional rats (group 4) that were injected with labeled MSCs. Analyses of variance (ANOVA) followed by Fisher protected least significant difference post hoc tests were used to statistically analyze results. P < .05 was considered to indicate significance in all analyses. RESULTS: Administration of neither labeled MSCs nor ferumoxides-PLL complex had a significant effect on hematologic or blood chemistry indicators of organ function. Of the parameters measured, only hemoglobin concentration and mean corpuscular volume (MCV) in the rats injected with labeled MSCs, as well as MCV and hemoglobin, alkaline phosphatase, aspartate aminotransferase, and direct bilirubin concentrations in the rats injected with ferumoxides-PLL complex, varied significantly during the 42-day postinjection period (P < .05, ANOVA). No other measurements, including serum electrolyte and iron concentrations, changed significantly during the test period (P > .05). Furthermore, injected labeled MSCs had cleared from the peripheral circulation by 15 minutes after injection. CONCLUSION: Results indicate that infusing cells that are magnetically labeled with ferumoxides-PLL complex into rats does not alter biochemical or hematologic measures of organ function in a clinically relevant or preclusive manner.

Comparison of transfection agents in forming complexes with ferumoxides, cell labeling efficiency, and cellular viability.

By complexing ferumoxides or superparamagnetic iron oxide (SPIO) to transfection agents (TAs), it is possible to magnetically label mammalian cells. There has been no systematic study comparing TAs complexed to SPIO as far as cell labeling efficiency and viability. This study investigates the toxicity and labeling efficiency at various doses of FEs complexed to different TAs in mammalian cells. Different classes of TAs were used, such as polycationic amines, dendrimers, and lipid-based agents. Cellular toxicity was measured using doses of TAs from 1 to 50 microg/mL in incubation media. Iron incorporation efficiency was measured by combining various amounts of FEs and different doses of TAs. Lipofectamine2000 showed toxicity at lowest dose (1 microg/mL), whereas FuGENE6 and low molecular weight poly-L-lysine (PLL) showed the least toxicity. SPIO labeling efficiency was similar with high-molecular-weight PLL (388.1 kDa) and superfect, whereas FuGENE6 and low-molecular-weight PLL were inefficient in labeling cells. Concentrations of 25 to 50 microg/mL of FEs complexed to TAs in media resulted in sufficient endocytosis of the SPIO into endosomes to detect cells on cellular magnetic resonance imaging.